Venous Surgery EMR: SonoSoft Chooses Practice Management Solution MPMsoft As Its Medical Billing Software

Written By: Sam Savage

Published Date: September 1, 2008 Last Edited: September 1, 2008

SAN FRANCISCO, Sept. 1 /PRNewswire/ — As baby boomers age, varicose veins can signal health concerns of not merely unsightly veins, but sometimes painful ulcers that can be a harbinger of a potential for stroke. Fortunately, a fairly simple procedure of laser surgery exists that can reduce the risk of serious complications.

As doctors retool in response to the rising demand for vein corrective procedures, an innovative software technology company, Empower Technologies is helping surgeons treat, consult, and chart their patient’s condition and post surgery progress.

Empower’s flagship product, SonoSoft is a comprehensive EMR (electronic medical record) specifically designed for Phlebology and Venous Surgery. SonoSoft’s Vein Specialist module produces detailed reports of every procedure including a complete initial workup, endovenous ablation procedures (laser or radiofrequency), follow-up visits for sclerotherapy, and can automatically generate a comprehensive CEAP classification.

SonoSoft has recently chosen MPMsoft as its front office patient scheduling and back office electronic medical billing software solution. “Practices today require an integrated solution that can meet all their needs from charting a patient’s treatment to the electronic billing of medical insurance,” says Dr. John Stagl, president of Empower. “MPM provides the important link of ‘getting paid’ by insurances.”

“We believe that our partnership with MPMsoft gives us a state of the art product that meets the specialized needs of vein surgery practices, providing a simple, seamless operation between the two programs. The doctor has everything he needs to chart the patient, and the office staff has exactly what they need to take care of the patient billing and claim adjudication.

“It’s an ideal situation,” says Stagl. “MPM supplies the ongoing day to day support related to our client’s electronic billing needs, which allows us to focus all our energy on meeting our physician’s charting and medical record needs.”

About MPMsoft

MPMsoft is a national provider of electronic billing software solutions for the health care industry whose standardized solutions empower a growing number of electronic medical record and practice management systems with the electronic billing capacity to ‘get paid.’

About Empower Technologies, Inc.

Empower Technologies is a pioneer of specialty specific electronic medical record software systems. Its flagship product, SonoSoft Vein Specialist helps doctors treat, consult, and chart their patient’s condition, surgery, and post surgery progress.

MPMsoft

CONTACT: Michael Sculley of MPMsoft, +1-707-226-1155, ext. 14,[email protected]

Web site: http://www.mpmsoft.com/

Science

Wetlands Pioneer, Unlikely Steward

Written By: Sam Savage

Published Date: September 1, 2008 Last Edited: September 1, 2008

By MIKE SAEWITZ

Chesapeake

Emil Viola used to think wetlands were nothing but trouble . Swamps, bogs and wet fields spread over the region have cost him money and given him headaches.

They also have proven lucrative for Viola, the developer who has emerged as the region’s leader in a little-known industry that sprang out of environmental protection laws: wetlands restoration.

Viola and his partners have invested millions to buy more than 5,000 acres of farmland and forest in South Hampton Roads and North Carolina. They have planted thousands of trees found in swamps and filled man-made ditches that once drained soils.

Viola’s ventures have reaped at least $14 million in revenue by selling “credits” to government agencies and land developers, who in turn use these restored wetlands to offset those they destroy on a construction project elsewhere.

Viola would seem an unlikely wetlands steward. His construction company has been cited for illegally digging drainage ditches, for filling large tracts of wetlands with wood chips and for clearing soggy forests regulated by the federal government. The company has been slapped with at least 10 Clean Water Act violations.

Despite flaps with regulators, governments come to him for wetlands credits so they can build. The North Carolina Department of Transportation and the city of Chesapeake have been among his biggest customers.

His wetlands-restoration operations also have generated a series of deals with the family of former Chesapeake Mayor Dalton Edge. Edge and his relatives sold part of the family’s sprawling farm to Viola’s companies for about $3 million, and the former mayor later bought back more than a third of the property for $5,000 after it was turned into wetlands.

As Viola pursued what’s known as “wetland mitigation banking,” the federal government continued to accuse his construction company of major wetlands violations. He has used his wetlands-restoration operation to settle problems with the Environmental Protection Agency and the Department of Justice, according to federal officials.

When the federal government has used the Clean Water Act to stop his firm from building on wetlands – with threats of up to $25,000 in fines per day – Viola sees that as an unfair taking of land without compensation. Politicians should go to bat to get some of Chesapeake’s wetlands released for development, he said.

“All of that infrastructure and yet it’s going to waste,” he said. “The whole Clean Water Act is not right.”

Like other longtime contractors and developers, Viola saw Chesapeake’s vast tracts of nontidal wetlands – anything from deep swamps to seasonally wet fields or forests – as suitable to meet the city’s growth needs.

That was before federal agencies began, in 1989, to enforce a policy of “no net loss” of the nation’s wetlands. Essentially, many developers and landowners were now asked to create or restore at least an acre of wetlands for every acre they were allowed to destroy.

For Viola, the new enforcement hit him in the late 1980s while his company was clearing lots to build the Jolliff Woods subdivision in Chesapeake’s Western Branch.

Viola was stunned when he was told he might have cleared chunks of federally regulated wetlands, which are considered important because they help control flooding – an especially crucial purpose for an area with so many drainage issues. They also provide animal habitat and filter pollutants.

Around the same time, the EPA ordered Viola’s company, Vico Construction Corp., to stop filling wetlands on nearly 300 acres off Military Highway. He fought the action in court and is still upset that the EPA prevented him from developing that land.

If the EPA and other environmentalists were around when this area was settled, a lot of South Hampton Roads would never have been developed, Viola said during a recent interview.

Those experiences gave him an idea allowable under the law: Buy forests and farmlands that were once wetlands, and then convert them back to their natural state. Developers who needed to fill in or disrupt wetlands for a project could offset those losses by buying credits for restored wetlands.

In some cases, it’s a one-for-one trade-off: buy and bank 1 acre of restored wetlands for every 1 acre destroyed. Sometimes it’s 2 restored acres for every natural 1 acre taken.

In the watershed that serves much of South Hampton Roads, the going rate for 1 acre of restored wetlands – known as a “credit” – eventually hovered between $35,000 and $55,000.

Viola had some prospective clients in mind when he set out on this new business.

What he needed first was land that could be cheaply and reliably converted into wetlands.

Viola read up on wetlands. Looking at aerial photographs of Chesapeake, a consultant told him about a piece of farmland that jutted like a thumb into the Great Dismal Swamp.

It was owned by the family of Dalton Edge, the Chesapeake businessman who later would enter city politics.

At first, Edge was reluctant to sell. But Viola said Edge told him that pieces of the farm were wet most of the year and did not make for good farmland. “Some years he couldn’t plant it because it was so wet,” Viola said.

Edge sold about 150 acres to Viola’s company in January 1995, months before Edge joined the Chesapeake City Council.

Viola and other investors used that first chunk of land to set up White Cedar LLC, the first private wetlands bank in Hampton Roads.

The Edge Farm had perfect soils for wetlands restoration, experts said. All it needed was the type of trees and shrubs that typically grow in the swamp. To bring the water back, Viola’s company filled a network of ditches.

“It was and is clearly one of the best sites around,” said Doug Davis, a Virginia Beach environmental consultant who specializes in wetlands restoration.

White Cedar bought nearly 140 acres more from Edge in 1996.

Viola’s goal was to cover the land with rows of Atlantic white cedar.

For a while, the bank had problems getting the trees and vegetation to grow enough. But in the end, it met federal criteria for wetness and plant growth.

“Is it the 300 acres of white cedar they were shooting for? No,” said Steve Martin, an Army Corps of Engineers environmental planner who monitored the site. “But portions of it are now forested wetlands, with a substantial component of white cedar.”

To expand, Viola bought more property from the Edge family. The councilman decided to sell another 215 acres in 2003. Edge, who was elected mayor in 2004, agreed to sell the bank 92 acres later that year, another 92 acres in 2005, and 93 acres in 2006, real estate records show.

Viola’s companies ultimately would buy a total of 785 acres from Edge and his relatives, who made about $3 million off the sales.

Edge, who finished his mayoral term in June and decided not to run again, has had nothing to do with the operation of these wetlands banks. In 2001, Edge requested an opinion from the commonwealth’s attorney on whether his land sales would result in a conflict of interest on council matters related to Viola’s bank or other wetlands issues. The attorney said there would be no conflict.

Edge still abstained on at least two dozen votes that involved Viola or his companies.

After White Cedar finished restoring wetlands on the first pieces of land bought from Edge, Viola’s company sold nearly 300 of those acres back to Edge’s company for $5,000.

By making the sale, White Cedar violated an agreement that required the company to first shop the land to a government agency and then try to donate it to a nonprofit conservation group, federal records show. The Corps of Engineers agreed to for go any action against the company as long as the former mayor protected the property forever. Edge could gain federal and state tax advantages by signing a conservation easement on the land, and he also plans to charge others to hunt there.

“That’s a nice deal,” said Skip Stiles, executive director of Wetlands Watch, a Norfolk-based advocacy group.

Viola said he hopes Edge gets credits to offset real estate taxes on property that now has a greatly reduced value because it is wetlands.

Edge said the deals were not about the money, pointing out that he had gotten other offers from businesspeople interested in turning the family farm into a golf course or airport. Now, he’s agreeing to conserve the land.

He said he wanted the property back because it reminds him of days spent farming with his father. He has options to buy back more of the family farm after it’s converted to wetlands.

“If I was in this for the money, I wouldn’t be doing what I’m doing,” he said. “I’d have sold the property, got myself a condo, and I wouldn’t have looked back.”

In 2007, Edge purchased 232 acres of cut-over timber land in Greensville County, which surrounds Emporia. After much of it was declared swampland , he successfully petitioned the county this year to lower his tax assessment from $345,800 to $172,500. Edge said he has no plans to create a wetlands bank.

As Viola’s first wetlands-restoration company took off, his building company continued to have run-ins with environmental regulators.

EPA spokeswoman Donna Heron said Vico Construction was one of the companies that took advantage of a loophole by using a method called Tulloch ditching, which involves cutting trenches across wetlands but trucking material away to avoid federal regulations for filling wetlands.

Between 1999 and 2003 on sites across Chesapeake, records show the EPA accused Vico of:

* Filling wetlands with wood chips on land intended for a Western Branch school.

* Filling wetlands on construction sites for the Willow Lakes, Mill Creek Harbor and Emerald Woods subdivisions.

* Draining wetlands at the Smith and Lewis farms.

In one of the biggest wetlands cases at the time, Vico was one of several firms accused by the Department of Justice in 2001 of destroying wetlands to clear the way for Edinburgh, a golf course and residential community in southern Chesapeake.

Viola said he was under the impression that Tulloch ditching was completely legal and had been upheld by the courts. He said he notified federal officials before doing each job, and he noted that Corps of Engineers workers were present while his company did the work in some cases.

The EPA visits and violations came without warning, he said.

To Stiles of Wetlands Watch, Vico Construction started to stick out as one of several local companies that were repeatedly accused of wetlands violations. “When you see someone’s name time after time on a violation sheet, you can assume that good environmental stewardship is not on the top of their business plan,” Stiles said.

As the EPA sought thousands of dollars in fines, Viola was putting the finishing touches on starting a much larger wetlands- restoration bank. John C. Holland Jr., a private landfill owner whose business has had previous federal wetlands violations, signed on as a partner.

The original plan for the Great Dismal Swamp Restoration Bank called for doing wetlands restoration and preservation on 10,000 acres of farmland and forest in Chesapeake and North Carolina.

The sheer size drew letters from critics. The Southeastern Association for Virginia’s Environment worried about expanding an industry “which makes a profit from the destruction of wetland resources,” according to the group’s letter to the Corps of Engineers.

The Great Dismal Swamp Restoration Bank made its first credit sale in June 2003, just six months after White Cedar sold out.

A number of big projects ended up buying credits from the Great Dismal Swamp Restoration Bank. The city of Chesapeake spent more than $450,000 with the bank to offset wetlands losses created by building Moses Grandy Trail.

Some of the bank’s biggest customers were Viola’s companies, which in some cases withdrew credits to help settle the EPA cases.

Viola felt settling was the prudent thing to do. “I still believe what they did was not right,” he said.

To make up for destroying wetlands on the Edinburgh site, Vico and other firms were allowed to break off 160 acres from the land that Viola’s wetlands company bought from Edge.

The Corps of Engineers is “generally not concerned” that Viola’s construction and development companies are frequent users of his wetlands bank, said Martin, a corps environmental planner. The government just wants the restoration work to be done.

The Great Dismal Swamp Restoration Bank has done a fair amount of restoration work.

On a tract in North Carolina, the group plugged or filled 33 miles of ditches, said consultant Robert “Bud” Needham, a former corps worker .

In 2005 alone, the bank planted 1.5 million trees on its sites, Needham said. On a recent tour of one of them, Needham pointed out bald cypress trees that were the size of lead pencils when they were planted. Now, they are more than 8 feet tall.

Viola cautions that wetlands restoration is not easy money. “It sounds simple, but it’s an expensive proposition,” he said.

He pointed to about 4,000 acres the bank purchased in North Carolina. The North Carolina Department of Transportation paid at least $3 million for wetlands credits from the site. But the money he took in wasn’t enough to pay off his land and restoration costs, he said. Now credits are not selling well in North Carolina.

And the real estate market has hampered credit sales in Hampton Roads.

“It’s a risky business,” Viola said. “It’s not set in stone you’re going to make money. When the dust all settles, I think we’ll be all right.”

When asked about his profits, he said: “We’re not losing money.”

The market hasn’t completely dried out. The Hampton Roads Executive Airport plans to expand a runway and has proposed buying $2.5 million worth of wetlands credits from Viola’s bank, records show.

Viola may get even more active in the wetlands-restoration arena. The Great Dismal Swamp Restoration Bank has options to buy more land in Chesapeake.

Last year, Viola donated more than $130,000 and $45,000 worth of equipment to environmental research efforts at Duke University and the University of North Carolina. He plans to give more money this year.

Through all of his experiences with wetlands banking and the EPA, Viola said wetlands laws need to be changed to free up more land in Hampton Roads – and especially in Chesapeake, which is covered with nontidal wetlands that prevent development. “That’s the shame of it,” he said.

“I am strong on being able to develop property that has the backbone for improvements,” he said.

His idea is that wetlands in places such as Western Branch should be allowed to be developed, while land in southern Chesapeake should be devoted to wetlands restoration.

“I’m not against the environment,” he said. “For all the taxes we pay, the government should give us some guidance.”

Mike Saewitz, (757) 222-5207, [email protected]

Part 2 of 2

To read the first part in the series, go to Pilot Online.com. a local player

Developer Emil Viola, left, has made millions by restoring thousands of acres of wetlands and selling the credits to those who need the offsets, but his building company has been charged with at least 10 Clean Water Act violations. – online

Take an interactive quiz on wetlands restoration and see video of the process at PilotOnline. com. council voting

During his time on Chesapeake City Council, Mayor Dalton Edge abstained on at least two dozen votes that involved Emil Viola or his companies. After White Cedar finished restoring wetlands on the first pieces of land bought from Edge, Viola sold nearly 300 of those acres back to him for $5,000.

Originally published by BY MIKE SAEWITZ | THE VIRGINIAN-PILOT.

Health

STAYING ON TRACK ; Norwell Company Offers System to Encourage Patients to Take Their Medicines

Written By: Sam Savage

Published Date: September 1, 2008 Last Edited: September 1, 2008

By A.J. BAUER

NORWELL – It’s a question as old as medicine itself: How can doctors get their patients to actually take the drugs prescribed to them?

HealthHonors, a three-year-old company in Norwell, claims to have found the answer in a technology it’s calling Dynamic Intermittent Reinforcement. The program has already earned the small company three major clients – including British pharmaceutical company AstraZeneca, which reported last week that it would employ DIR.

The DIR program has also positioned the company, which is hunting for a larger office, for rapid growth.

The program is an interactive system that allows patients to call or log in via a computer to confirm they’ve taken their medicine.

Once a patient types in his or her pin number, an automated system congratulates the patient, provides educational information pertinent to the medicine they’re taking and rewards them with a number of “points.” These points, which increase or decrease based on the patient’s adherence history, are accumulated and may be redeemed for health-related discounts or other rewards.

“Different people need different types of reinforcement to get them to change their behavior,” said HealthHonors co-founder Dr. Murat Kalayoglu.

He said the DIR system uses algorithms to customize the program to each user: “We activate the fundamental reward circuits that get people to choose the healthy behavior day after day.”

Kalayoglu, a resident of Boston, co-founded the company with Dr. Michael Singer of Newton in January 2006, about a year and a half after the two met while they served as residents in the emergency room of Massachusetts Eye and Ear Infirmary in Boston.

The two found that their individual research specialties – Singer in neuroinformatics and human behavior and Kalayoglu in chronic disease – were complementary in developing a solution to the problem of making sure patients take their medicine correctly.

After a year and a half of development and clinical trials, HealthHonors commercialized the DIR program last fall and has seen strong revenue growth since that time, according to CEO John Sheehan, a Cohasset resident.

Last month, the National Institutes of Health’s National Institute on Aging granted HealthHonors $300,000 to perform a clinical trial of the DIR platform. The study, which is expected to begin in October and last about a year, will be conducted with patients over the age of 55 at Yale University School of Medicine’s primary care clinic in New Haven, Conn.

If the study goes as well as previous ones – which found patients who used DIR were 33 percent more likely to adhere to their prescriptions – it could help further establish the company as the place to go to make sure patients take their medicine.

“Between now and the fourth quarter next year, we’ll probably double in size,” Sheehan said.

HealthHonors employs seven people in about 2,400 square feet of space at Norwell Executive Center on Washington Street (Route 53). But Sheehan said the company plans to establish a more permanent headquarters, either in Boston or along the Route 128 corridor between Braintree and Woburn, by year’s end.

“The ultimate end game is to provide access to every patient to this platform so they can live longer, healthier lives,” Kalayoglu said.

A.J. Bauer may be reached at [email protected].

Originally published by By A.J. BAUER, The Patriot Ledger.

Health

Shionogi & Co., Ltd. To Acquire Sciele Pharma, Inc.

Written By: Sam Savage

Published Date: September 1, 2008 Last Edited: September 1, 2008

Shionogi & Co., Ltd. and Sciele Pharma, Inc. (NASDAQ:SCRX) today announced that they have entered into a definitive agreement under which Shionogi & Co., Ltd. will acquire Sciele Pharma, Inc.

Under the terms of agreement and pursuant to a tender offer, Shionogi will acquire all the outstanding shares of Sciele’s common stock at a price of $31 per share, for a total equity purchase price of approximately $1.1 billion. Upon completion of the acquisition, Sciele will become a wholly-owned subsidiary of Shionogi and will continue operations in Atlanta, GA, USA as a standalone business unit. The Board of Directors of Shionogi and Sciele have approved this transaction. This acquisition is subject to clearance under the Hart-Scott-Rodino Antitrust Improvement Act and other customary conditions.

This acquisition of Sciele provides Shionogi with an immediate expansion in the U.S. market, significantly increasing Shionogi’s commercial presence and product pipeline in the United States. This transaction will not result in any reduction of Sciele employees.

Dr. Isao Teshirogi, President & Representative Director, Shionogi, said, “Sciele has a well-established sales and marketing team with a proven track record in the United States. Sciele also has expertise in several other key areas, including clinical, regulatory and business development. This acquisition will give us a strong platform in the United States to launch products that are currently in the Shionogi and Sciele pipelines. Our therapeutic areas complement each other and broaden our product portfolio and R&D pipeline. This transaction is expected to generate additional growth for Shionogi in the near-term and long-term.”

Mr. Patrick Fourteau, Chief Executive Officer of Sciele, said, “Sciele will be a stronger company as part of Shionogi, which is one of the leading pharmaceutical companies in Japan, with an extensive product pipeline. Shionogi will rely on Sciele to continue to operate on the business platform that has made our company successful: Speed of Execution, an Entrepreneurial Spirit, Innovation, Simplicity, and Teamwork. The Sciele management team will remain in place, and we look forward to contributing to the continued growth and profitability of Shionogi in the United States.”

Financial

There is no financing condition to the tender offer or subsequent merger.

Shionogi expects that the acquisition will enhance Shionogi’s earnings starting in the fiscal year ending March 2010.

Transaction Terms

The acquisition is structured as an all cash tender offer for all of the outstanding shares of Sciele common stock, followed by a merger in which the remaining shares would be converted into the right to receive the same $31 cash per share price paid in the tender offer.

The transaction is subject to the tender of a majority of Sciele common stock on a fully diluted basis on the date of purchase as well as other customary closing conditions, including expiration of the applicable waiting period under Hart-Scott-Rodino Antitrust Improvements Act of 1976 and the antitrust laws of applicable foreign jurisdictions. The transaction is expected to close in the fourth quarter of 2008.

To effect the transaction, Shionogi will establish a wholly-owned subsidiary known as Tall Bridge, Inc. In the merger that follows completion of the tender offer, this subsidiary will be merged with and into Sciele, and the surviving entity, Sciele Pharma, Inc., will be an indirect wholly-owned subsidiary of Shionogi.

Goldman Sachs served as financial advisors to Shionogi and UBS Investment Bank served as financial advisors to Sciele.

Davis Polk & Wardwell served as legal advisors to Shionogi and Paul, Hastings, Janofsky & Walker LLP served as legal advisors to Sciele Pharma, Inc.

Shionogi Press Conference Information

Shionogi will host a press conference in Tokyo, Japan on September 1, 2008, at 4:00 p.m. (JST) at the Imperial Hotel, Tokyo.

Sciele Conference Call Information

Sciele will host a conference call on Tuesday, September 2, 2008, beginning at 12:00 p.m. Eastern Time to discuss this announcement. Analysts, investors, and other interested parties are invited to participate by visiting the Company’s website, www.sciele.com, and entering the Investor Relations page. A replay of the webcast will be available using the same link.

You may also dial in to listen to the conference call. The dial-in numbers are (877) 675-4752 for U.S. domestic callers and (719) 325-4874 for callers outside the U.S. and Canada. All callers should use passcode 2465327 to gain access to the conference call. Please plan to dial-in or log on at least ten minutes prior to the designated start time so management can begin the call promptly.

About Shionogi & Co., Ltd.

Shionogi & Co., Ltd. is a major research-driven Japanese pharmaceutical manufacturer. The company’s primary businesses are research and development, manufacturing, marketing, and import and export sales of pharmaceuticals and diagnostics. Shionogi follows a basic policy of continually providing the superior medicines essential to people’s health. For more details, please visit www.shionogi.co.jp.

About Sciele Pharma, Inc.

Sciele Pharma, Inc. is a pharmaceutical company specializing in sales, marketing and development of branded prescription products focused on the therapeutic areas of Cardiovascular, Diabetes, Women’s Health and Pediatrics. The Company’s Cardiovascular and Diabetes products treat patients with high cholesterol, hypertension, high triglycerides, unstable angina and Type 2 diabetes; its Women’s Health products are designed to improve the health and well-being of women and mothers and their babies; and its Pediatrics products treat allergies, asthma, coughs and colds, and attention deficit and hyperactivity disorder (ADHD). The Company was founded in 1992 and is headquartered in Atlanta, Georgia. The Company employs more than 1,000 people. The Company’s success is based on placing the needs of patients first, improving health and quality of life, and implementing its business platform – an Entrepreneurial Spirit, Innovation, Execution Excellence, Simplicity, and Teamwork. For more information on Sciele, please visit www.sciele.com.

Additional Information

The tender offer for the outstanding common stock of Sciele referred to in this press release has not yet commenced. This press release is neither an offer to purchase nor a solicitation of an offer to sell any securities. The solicitation and the offer to buy shares of Sciele common stock will be made pursuant to an offer to purchase and related materials that Tall Bridge, Inc. intends to file with the U.S. Securities and Exchange Commission. At the time the tender offer is commenced, Tall Bridge, Inc. will file a Tender Offer Statement on Schedule TO with the U.S. Securities and Exchange Commission, and thereafter Sciele will file a Solicitation/Recommendation Statement on Schedule 14D-9 with respect to the tender offer. THE TENDER OFFER STATEMENT (INCLUDING AN OFFER TO PURCHASE, A RELATED LETTER OF TRANSMITTAL AND OTHER OFFER DOCUMENTS) AND THE SOLICITATION /RECOMMENDATION STATEMENT WILL CONTAIN IMPORTANT INFORMATION THAT SHOULD BE READ CAREFULLY AND CONSIDERED BEFORE ANY DECISION IS MADE WITH RESPECT TO THE TENDER OFFER. These materials will be sent free of charge to all stockholders of Sciele. In addition, all of these materials (and all other materials filed by Sciele with the U.S. Securities and Exchange Commission) will be available at no charge from the U.S. Securities and Exchange Commission through its website at http://www.sec.gov. Investors and security holders may also obtain free copies of the documents filed with the U.S. Securities and Exchange Commission by Sciele at http://www.sciele.com.

Safe Harbor Statement

This press release contains forward-looking statements that are subject to risks and uncertainties that could cause actual results to materially differ from those described. Although Sciele believes the expectations expressed in these statements are reasonable, it cannot promise that these expectations will turn out to be correct. Actual results could be materially different from and worse than expectations.

This press release contains “forward-looking statements” that involve significant risks and uncertainties. All statements other than statements of historical fact are statements that could be deemed forward-looking statements. Investors and security holders are cautioned not to place undue reliance on these forward-looking statements. Actual results could differ materially from those currently anticipated due to a number of risks and uncertainties. Risks and uncertainties that could cause results to differ form expectations include; uncertainties as to the timing of the tender offer and merger; uncertainties as to how many of the Sciele stockholders will tender their stock in the offer; the risk that competing offers will be made; the possibility that various closing conditions for the transaction may not be satisfied or waived, including that a governmental entity may prohibit, delay or refuse to grant approval for the consummation of the transaction; the effects of disruption from the transaction making it more difficult to maintain relationships with employees, licensees, other business partners or governmental entities; other business effects, including the effects of industry, economic or political conditions outside of Sciele or Shionogi’s control; transaction costs; actual or contingent liabilities; and other risks and uncertainties discussed in documents filed with the SEC. Neither Shionogi nor Sciele undertakes any obligation to update any forward-looking statements as a result of new information, future developments or otherwise.

Health

Urgent Care Center for Veterans to Open in New Orleans

Written By: Sam Savage

Published Date: September 1, 2008 Last Edited: September 1, 2008

By Anonymous

The Department Of Veterans Affairs said the Southeast Louisiana Veterans Health Care System is opening an Urgent Care Center in New Orleans at 1601 Perdido St. on Tuesday.

The center will accept veteran patients. No appointments are necessary.

The center will offer care for illnesses that are not life- threatening. Services include diagnosis and treatment of mild to moderate illnesses and minor injuries. Mental health staff and a social worker will also be available to assist with evaluations, treatment and referral of urgent mental health needs.

Ambulances will not be accepted at the center.

“Until now, our veterans were referred to emergency rooms for conditions that were urgent but not life-threatening,” said SLVHCS Director Julie Catellier. “The Urgent Care Center will provide veterans with an additional level of service that we have not been able to offer since the hurricane. Now veterans can receive VA care from VA providers which will also help to reduce the wait in community emergency rooms.”

The main entrance to the center is on Gravier Street. Patient parking is available, and a parking attendant and VA police will be on the site.

The center will have access for walk-in patients from 8 a.m. to 5 p.m. Mondays through Fridays.

Credit: CityBusiness Staff Report

Health

Valley Health Expecting to Deliver Hospitals

Written By: Sam Savage

Published Date: September 1, 2008 Last Edited: September 1, 2008

By Heerwagen, Peter

Valley Health is going into the hospital building business.

The Winchester health-care organization recently purchased land in Warren County for a new hospital, and its West Virginia subsidiary, East Mountain Health Advantage, has purchased land near Romney for a new hospital. A proposed merger announced last month with Page Memorial Hospital in Luray, Va., 45 miles from Winchester, includes a new hospital.

And Valley Health is in the hunt to purchase War Memorial Hospital in Berkeley Springs, whose owner, the Morgan County Commission, is looking to build a new facility. It already manages the hospital, has loaned the county $1.2 million for a land purchase and has agreed to guarantee any loans taken out for the build.

Except for Warren Memorial, the other three hospitals are designated as “critical care” facilities, with 25 or fewer beds, located in rural areas. As such, they are entitled to higher Medicare and Medicaid reimbursement than other hospitals.

But many smaller and older non-profit hospitals, although reporting excess revenue over expenses, need to replace outdated and inefficient facilities that are not geared to today’s medical technologies. Because they cannot afford to service the added debt incurred to build a new facility, they join hospital systems with stronger cash flows and balance sheets.

Enter the financial resources of Valley Health. Led by its large tertiary care hospital, Winchester Medical Center, it has consistently generated large excesses of revenues over expenses, including $63 million in calendar year 2007. Adding in depreciation of $34 million, the healthcare system threw off $97 million of cash flow last year.

Although Valley Health carried $218 million in long-term debt on its balance sheet at December 31, 2007, Valley Health and its subsidiaries had cash and investments of $160 million on that date. During last calendar year it invested $85 million in plant and equipment.

Mike Halseth, president and CEO of Valley Health, estimated the costs to build each of the three critical care hospitals would fall in the $25 million to $28 million range. “We would finance them with long-term debt of our own or one of our subsidiaries.

“I can’t say for sure if it [the mergers] will all pan out, but it potentially could make sense for us because Winchester Medical Center is a referral hospital that supports rural hospitals, and they will partner with us over time. It is very much part of our strategic plan to be that regional center.”

Valley Health’s Warren Memorial Hospital recently paid $2.6 million for 150 acres in southeastern Warren County, between John Marshall Highway and Happy Creek Road, located west of Front Royal. The state’s planned upgrade of the low-water Morgan Ford Bridge over the Shenandoah River would improve access to a new hospital for people living in the northern part of the county.

No plans have been developed for a new facility that would replace the 67-bed hospital on Shenandoah Avenue, nor has a price tag been estimated. “We wanted to purchase the land while it was available, but no site planning is contemplated at this point,” said Tom Urtz, director of marketing and public relations at Valley Health. “They need a more modernized facility.”

Halseth said a new build is about a decade away. “We have no short term plans. The [37,000-square-foot] outpatient facility on Commerce Street has taken the pressure off the main campus.

Last month Valley Health purchased 50 acres for a new Hampshire Memorial Hospital, replacing the current critical access, 25-bed facility owned by Hampshire County. On January 1, the health-care system purchased the certificate of need and certain operational assets of the hospital from a private party for about $6 million.

“The property is located behind the Hampshire Wellness and Fitness Center,” said Urtz, who estimated the construction cost at $30 million. The wellness facility is owned by the county, but managed by Valley Health.

“A certificate of need will be submitted to the West Virginia Health Care Authority in July, and if approval is received by the fall, we’ll -break ground before the end of the year,” said Urtz. “The new 65,000-square-foot hospital will have 14 critical-care, beds and 31 long-term care beds.”

With the signing of a letter of intent on July 10, Valley Health has a tentative agreement to merge the nonprofit Page Memorial Hospital into its health-care system. As with its mergers of Warren Memorial and Shenandoah Memorial hospitals, no money would change hands.

“Valley Health has a very good reputation for clinical quality and a positive approach to patient care,” said Travis Clark, president and CEO of Page Memorial.

Two years ago, Page Memorial conducted a strategic planning study, and concluded that it needed a new facility, but could not afford to build it. The $ 17 million revenue hospital had excess revenues over expenses of $330,000 in 2007, and with depreciation added, had a cash flow of $ 1.1 million.

“We determined that as an independent rural hospital, it would be difficult to get $25 million needed to build a new one,” said Clark. “After Valley Health does its due diligence, we will do a more formal plan. The actual cost of the hospital is way down the road.

“We’ve been able to do a fairly good job of buying new equipment for the hospital, spending about $1 million a year on it. But when you add in another $1 million [debt to pay for new] for bricks and mortar, that’s more difficult.

“Of the seven critical care hospitals in Virginia, only two are not part of larger organizations, ourselves and Bath County in hot Springs, and they have a large endowment.”

Clark said the hospital sent out six or seven requests for proposals “to regional hospitals and health-care organizations,” but for privacy purposes, would not reveal the names.

Halseth said two of them were Rockingham Memorial Hospital in Harrisonburg and the University of Virginia Health System in Charlottesville. They and Winchester Medical Center each get one- third of the Page County patients going to referral hospitals, he said.

Rockingham, although closer to Luray than Winchester, does not own other hospitals and is in the midst of building its own new facility, at a total cost of $300 million, to replace one built in 1912. And UVA is in the process of taking over Culpeper Regional Hospital to the east of Page County.

“We border Rockingham County, and folks here have doctors over there, but quite a few also go to Winchester,” said Clark. “Valley Health’s Warren Memorial and Shenandoah Memorial hospitals are fairly close, so they go to them for certain services.” With 2007 revenues of $85 and $68 million, respectively, for Warren and Shenandoah, they do a considerably larger business than Page Memorial.

But Todd Way, vice president of corporate services at Valley Health, said the goal is to beef up medical services at Page Memorial. “Our main strategy is to develop more services there, because a lot of patients are leaving the county.”

Using borrowed funds to build a new hospital might put Valley Health in the same loss position as Page Memorial, even if its interest costs were lower. But Halseth said, “We think we can operate it better than they can. We do back-office work for all our hospitals, including human resources and purchasing systems. There are economies of scale; we can do it for much less expense then they can.”

As for getting more referrals to Winchester Medical Center from Page County patients, Halseth said, “We have to earn it, and we expect to earn it.”

After exploring the idea of financing a new hospital itself, the Morgan County Commission has put War Memorial Hospital in Berkeley Springs up for sale. Likely buyers would be Valley Health, which has managed the hospital for a number of years, and West Virginia United Health System, which through its WVU Hospitals, owns both City Hospital in Martinsburg and Jefferson Memorial Hospital in Ranson.

“They [Morgan County Commission] have made a decision to sell it because they don’t know how to run it,’ said Halseth. “I expect the sale will be similar to that of Hampshire Memorial.”

Todd Way is on the War Memorial Board. ? don’t know who will be competing, but they are going to publish an RFP in newspapers in D.C., Pittsburgh and Richmond. We intend to participate.”

According to Halseth, that would be a different scenario from the way the merger of City Hospital and Jefferson Memorial Hospital into WVU Hospitals was handled. “That was a very closed deal, and we never had the opportunity to openly participate,” he said.

Health

Cutting-Edge Research Continues at Methodist Rehab Center

Written By: Sam Savage

Published Date: September 1, 2008 Last Edited: September 1, 2008

By Lofton, Lynn

There’s plenty going on at the Wilson Research Foundation, the fundraising arm of Methodist Rehabilitation Center in Jackson. Along with the latest research and innovative rehabilitative services that the foundation supports, the organization has a new executive director and three new board members.

Chris Blount, 44, became the executive director in January after a career in public relations and marketing. For the past nine years, the Louisiana native was director of communications for L-3 Vertex Aerospace in Madison. Prior to that, he served on the staff of the Greater Jackson Chamber Partnership.

“This is a humbling but fascinating place to work,” he said. “The Wilson Research Foundation is funding cutting-edge research in rehabilitation medicine to help those who have suffered a stroke, spinal or brain injury or neurological disease. It’s a great mission that’s helping people right now, while contributing to the worldwide pursuit of cures to disabling illnesses and injuries.”

New foundation board members include Sam Lane Sr., John D. Robinson and Dick Molpus. They join fellow board members the Honorable Judge Virginia Wilson Mounger, Richard M. Fountain, Sharon Woodfield, Sally Carmichael, Faser Triplett, M.D., Matt Holleman, Martha Lyles Wilson, Ed Kossman, Marion Wofford, M.D., Mary Ann McCarty, Dean Miller, Nat Rogers, Steve Sansom and Robert Smith, M.D.

Exciting research being done at the center ranges from studies on improved physical motion and control, improving cognitive function such as reducing confusion after a stroke and therapeutic interventions for control of spasticity.

Applied studies in technology advances are being conducted that allow disabled persons to have a high quality of life such as better ways for those with paralysis to access the computer. An adaptive computing lab that serves research and direct patient care was recently opened. It focuses on adaptive technologies and education to help spinal cord injured and other patients.

“Having the research performed here from our main hospital is a huge advantage,” Blount said. “Our current patients benefit as they are able to participate in research trials, and they receive better diagnostics, treatment and evaluation because of the research labs.”

That means there’s no line between research and patient care at Methodist where research is integrated into most everything that’s done. It’s part of an interdisciplinary approach that includes research investigators, medical directors over each specialty area that’s treated and an army of therapists and nurses specialized and experienced in helping each patient overcome disabling events.

“This comprehensive approach is why we are the premiere neurological rehab center, not just in Mississippi but regionally,” Blount said. “We are among a handful of centers in the nation providing such comprehensive services and achieving the outcomes you see here daily.”

Lisa Michie-Kamp, director of operations of the East Campus, explains the significance of the rehabilitation center’s treatment of chronic pain management.

“We utilize a multi-disciplinary, holistic approach to quickly alleviating pain,” she said. Our goal is to provide excellent quality care and the most favorable outcomes possible for our patients. The key factor in doing so requires a thorough patient evaluation to consider what options are appropriate and best for each patient.”

Blount doesn’t believe the state of the economy will affect fundraising efforts.

“People want to give and will give to things they believe in; causes that truly help people,” he said. “A miserly person is typi (text missing)

Business

Reach for Profits Challenges Utilities

Written By: Sam Savage

Published Date: September 1, 2008 Last Edited: September 1, 2008

By Friedman, Mark

IN AN ERA OF SOARING ENERGY COSTS, Arkansas’ investor-owned utilities are facing many of the same price pressures as their customers, causing some to encourage consumer conservation.

The utilities, however, must balance efforts to conserve with their duty to shareholders, which is to make a profit.

At the heart of the struggle is their business model, one that generally rewards utilities for selling more energy and, again generally, provides few incentives for selling less. The challenge is how to give for-profit utilities reasons to sell less.

Although the Arkansas Public Service Commission late last year approved a series of initial programs to encourage the conservation of electricity and natural gas, critics are skeptical that investor- owned utilities – IOUs – will push hard to persuade their customers to use less energy.

“It is somewhat like asking them to shoot themselves in the foot,” said Bill Ball, chairman of the Arkansas Renewable Energy Association of Little Rock. “They very carefully aim between each toe…. It is counter to their business model.”

Kevin Smith, co-chair of the Arkansas Governor’s Commission on Global Warming, also has some concerns about IOUs, whose goals are to represent the company and shareholders.

“A lot of times, the public’s goals arc not the same as the utilities’ goals,” Smith said.

Arkansas Western Gas Co. of Fayetteville has even said that promoting conservation could financially hurt the company because it receives lower revenue.

Entergy Arkansas Inc. of Little Rock, however, points out that it’s now supporting programs that encourage its customers to use less energy. That’s because the electric utility must have sufficient generating capacity to meet what’s called “peak” demand, when almost every air conditioner, every fan, every TV in Arkansas is operating.

“You’ve got to have enough generation capability to meet the customers’ peak demand for electricity,” said Kurt Castleberry, Entergy’s director of resource planning. “That peak demand may only occur for one hour a year, but we’ve got to have enough generation capability to meet that peak demand.”

If the utility doesn’t have the capacity to meet peak demand, then it has to start looking to buy energy or produce energy from other, higher-cost sources. Or the utility eventually would have to build an expensive power plant to meet the demand, said John Bethel, a spokesman for the PSC.

If utilities can help customers reduce their use and demand for electricity and natural gas, that would reduce the amount of electricity or natural gas the utility has to deliver, Bethel said.

One example is investor-owned Southwestern Electric Power Co. of Shreveport. It serves nearly 500,000 customers in three states, including more than 110,000 in Arkansas. On Aug. 4, Swepco set an all-time high for customer demand for energy.

Swepco couldn’t produce enough energy, so it had to buy electricity from a third party at a higher cost, spokesman Scott McCloud said.

To recover the higher energy costs, Swepco has to appeal to the Arkansas Public Service Commission for a rate increase, but there’s no guarantee that the increase will be approved. And a rate increase can be permitted only twice a year.

And as a result of the climbing peak demand, Swepco is trying to build a $1.5 billion coal-fired power plant in Hempstead County, but the controversial project has been delayed by more than a year. McCloud said the project is awaiting approval from the Arkansas Department of Environmental Quality.

Entergy Arkansas, however, said keeping a lid on peak use would financially help the company, which saw its assessable revenue drop 2.7 percent between 2006 and 2007 to $1.6 billion. The company’s net income was $139.1 million in 2007, off nearly 20 percent from 2006.

Entergy has several sources to tap to get electricity for its customers, including its own nuclear-, coal- or natural gas-fueled plants. And if it gets into a bind, it could also buy electricity from the wholesale market.

Each fuel source, though, has a different cost associated with generating the energy, from a half-penny per kilowatt-hour at a nuclear power plant to 10 cents – or more – on the open market.

“So we like our customers to use energy wisely,” Castleberry said. “When they do that, that helps us avoid the highest-cost energy out there.”

Changing Energy Policy

In 2006, the Arkansas Public Service Commission issued an order that encourages utilities to focus on energy efficiency and conservation programs to improve Arkansas’ dismal energy record. The order said Arkansas ranked in the lowest tier among the states in terms of spending on energy efficiency, whether measured on a per- capita basis, as a percentage of total retail energy sales or as a percent of total revenue.

“Due to the current high energy prices and the minimal level of energy efficiency programs in Arkansas, Commission action regarding energy efficiency is necessary,” the order said.

In November 2007, the PSC approved a series of initial programs designed to encourage the conservation of electricity and natural gas, PSC spokesman Bethel said.

But critics say investor-owed utilities are rewarded for selling more energy.

“They’re unenthusiastic about energy efficiency that hurts their shareholders,” Amory Lovins, CEO of the Rocky Mountain Institute at Snowmass, Colo., wrote in a September 2005 report. “Nearly all architects and engineers, too, are paid for what they spend, not for what they save; ‘performance-based fees’ have been shown to yield superior design, but are rarely used.”

Ball, of the Arkansas Renewable Energy Association of Little Rock, said utilities have their own incentive to cut peak demand though.

“Peak demand electricity is very expensive,” he said.

And he said utilities typically don’t charge residential customers different rates based on the time of day of their energy use.

“They have to charge the same for that cheap kilowatt-hour that they can make at 2 o’clock in the morning as they do for that very expensive kilowatt-hour that they’re making at 2 o’clock in the afternoon,” Ball said “It’s in their interest to lower that peak.”

He thinks there will be a bigger push in the 2009 legislative session to reduce energy use.

Ball also is working on legislation for a Renewable Energy Feed- In Tariff, which would allow customers producing excess solar power or any other renewable energy – to feed it directly into the power grid and get paid for it.

Ball said he was working with legislators – he wouldn’t say who – to have the legislation considered in the upcoming session.

Natural Gas

To lower energy use, one program the PSC approved allows gas utilities to adjust their rates to compensate for lost revenue from customers using less gas.

The natural gas industry in Arkansas had watched as customers used less gas over the last couple of years. (See list, Page 23.) Customers weren’t using as much gas because of the higher price of natural gas, more efficient appliances and conservation measures, said Arkansas Western Gas spokesman Marshall Moody.

Arkansas Western, like all gas utilities, passes the cost of the gas itself directly to its customers.

“We get paid for moving natural gas and the vehicle that we use is pipelines,” Moody said.

Moody said Arkansas Western has helped customers with energy- saving tips.

“It’s the right thing to do,” he said.

But when customers use less natural gas, it hurts the company financially.

In 2007, only Arkansas Western among the gas utilities operating in Arkansas saw its assessable revenue rise from 2006. And its revenue increased only 1.3 percent to $174.5 million.

CenterPoint Energy’s assessable revenue was off 5.6 percent in 2007 from the previous year, and Arkansas Oklahoma Gas Co. of Fort Smith saw its revenue slip 0.7 percent during the same period.

Arkansas Western proposed that it could recover lost revenue resulting from the reduced use of natural gas by being allowed by the PSC to raise rates if revenue for non-natural gas charges falls below $57.7 million.

The shortfall, however, has to be as a result of the lower revenue from its residential and small-business sectors, said Ricky Gunter, vice president of rates and regulation for Arkansas Western. Otherwise, to adjust the rate, Arkansas Western would have to go before the state PSC, a process that could take up to 14 months with no guarantee of getting the rate increased, he said.

The first year of the three-year program, which is called Trial Billing Determinate Adjustment, started Aug. 1, 2007, and ended July 31. Arkansas Western Gas is now analyzing the natural gas use numbers to determine if the rates will need to be adjusted. If the rates do rise, they will go into effect in January 2009, Gunter said.

“This is designed to allow utility companies to promote energy efficiency and not be harmed by the reduction in the volume,” Gunter said.

Gunter said the residential and small-business customers still should see a lower bill even if the rates have to rise to cover the revenue shortfall.

“The customer still benefits, because they use less gas, which is the largest component of their bill,” he said. “The customers still could benefit and the utilities would not be harmed.”Entergy Arkansas

Entergy Arkansas, meanwhile, has ripped a page out of Woodruff Electric Cooperative Corp.’s playbook on how to reduce energy costs.

Woodruff County, which is one of Arkansas’ 17 nonprofit electric cooperatives, found that if it monitors demand for energy and places automatic controls to reduce energy use during those peak demand times, both it and the customer save money.

For the cooperatives, wholesale rates for the year are based on peak demand. When the utilities can control the demand during the summer – when demand is at its highest – they can save money throughout the year.

The electric cooperatives are owned by their customers, so it’s always in the cooperatives’ interest to keep a lid on the rates, said Doug White, vice president of system services for the Electric Cooperatives of Arkansas.

“We’ve got a built-in incentive to operate as efficiently as we can versus just saying spin the meter so we can make money,” White said. “We don’t do that.”

Entergy Arkansas’ Castleberry said the utility talked to Woodruff Electric about its demand-side management program, which is when the utility, rather than the customer, reduces demand during the peak periods.

In June, Entergy Arkansas signed up about 60 farmers in Hazen who have irrigation systems for a pilot program to control energy use. Entergy now has the ability to turn the irrigation systems for the farmers on and off for up three hours a day every weekday.

The start-up cost for the program was $81,000.

In exchange for controlling the systems, Entergy will give the farmers a discount of up to 30 percent on their electric bills.

“We’re testing the program now with hopes of learning how to deploy it on a greater scale in the near future,” Castleberry said. He said Entergy would analyze the results this fall and then decide if it will expand the program.

So far the results have been promising, he said. “We’re hopeful that we’re able to expand it to a greater number of meters next summer,” Castleberry said.

Entergy Arkansas has 2,000 irrigation wells in its service area.

“It’s a big opportunity,” Castleberry said. “And we think a big benefit for our customers.”

Castleberry said both sides benefit because Entergy avoids having to acquire high-cost energy during the peak times and it sidesteps the possibility of having to build or buy a new power plant as a result of the high demands.

In April, Entergy Arkansas expects to file with the PSC more plans to reduce energy use.

Global Warming Commission

The Global Warming Commission was created during the 2007 meeting of the General Assembly to set a “global warming pollution reduction goal,” according to the commission’s Web site.

Smith, the co-chair of the commission, said the commission is studying ways to persuade utilities to offer alternative sources of renewable energy to customers.

Other study areas include tax incentives for utilities to cuts costs; however, the question then becomes how to pay for those, he said.

The utilities also don’t want to be strapped with unfunded mandates from the commission.

“They want to have cost recovery on anything they’re required to do,” Smith said. “They are open to a lot of suggestions, and they are open to incentive-based programs, provided that it doesn’t cost them anything.”

He said the report is due to Gov. Mike Beebe on Oct. 31 and will go to the General Assembly next year for action.

“We haven’t settled on anything yet,” Smith said.

Education

A Salute to NEPA’s Outstanding Educators

Written By: Sam Savage

Published Date: September 1, 2008 Last Edited: September 1, 2008

By Anonymous

The pursuit of happiness of which America’s forefathers bespoke means different things to different people. For some it may involve building great stores of wealth in a visible and lofty position, for others it may mean working in an interesting career, no matter the compensation. The really lucky ones find their place in a well- paying business that allows them to wake up in the morning raring to go.

The 15 outstanding educators we profile here are involved in the business of business. Said simply, they teach America future business practitioners, entrepreneurs and (dare we say it?) tycoons in the theory, practice and ethics of what it means to be a great business person in America.

We salute these top educators and the fortunate students they teach.

Bloomsburg University

A. Blair Staley, CPA MST, DBA, brings a wealth of executive and practical accounting experience to the classroom as professor of accounting at Bloomsburg University. From his services as accounting officer for the U.S. Patent and Trademark Office, to elected auditor, to tax preparing CPA, he brings accounting theory and the tax code to life helping students to truly learn and understand the material.

“I care deeply whether my students learn accounting, so I use many hands-on projects and involve students by calling on them (in a non-threatening way) during every class thus learning every students’ name,” he explained.

Staley likes to apply four of the more universal Generally Accepted Auditing Principles (there are a total of 10) in describing what it takes to be outstanding in business.

First, it takes technical training and technical proficiency in the functional areas of business: accounting, economics, finance, marketing, management, information systems, statistical analysis, entrepreneurship and business law.

Second, it takes planning, supervision, and leadership. This means that business leaders must learn how to forecast revenue and expenses; learn how to get things done through others, learn how to command, control and lead organizations.

Third, it takes continuous, adequate data collection and analysis so that decisions are based on facts, and fourth, it takes professional care. “This means not only possessing adequate technical training and technical proficiency, but also being diligent and thorough in one’s work.

In addition, due professional care means behaving in an ethical manner and making ethical decisions,” he said.

Staley has published 18 works and his research has been recently cited by the Third Circuit Court of Appeals for a precedential decision, a very rare occurrence and a true honor, he said.

He is also the Volunteer Income Tax Assistance (VITA) program coordinator for Columbia and Montour counties and serves as faculty advisor for the Bloomsburg University Student Accounting Association.

Staley holds a doctorate in business administration from Nova Southeastern University, Fla., in management; an master of science in taxation from American University; a master’s in public affairs from the LBJ School of Public Affairs, University of Texas; and a BA in history from Western Connecticut State University

East Stroudsburg University

S. Elaine Rogers, Ed.D., department chairperson of Recreation and Leisure Services Management, at East Stroudsburg University, has always felt that teaching and learning is a process – a journey that both teacher and student make together. “The teacher and student learn together as the journey unfolds,” she said.

Most teachers have favorite quotes that express their teaching philosophy, one of Rogers’ is from Christa McAuliffe, the teacher who died in the 1986 Challenger Space Shuttle explosion, ‘I touch the future. I teach,’ ” she said.

Everyday Rogers works with her students, she says she must think of not only who they are now, but who they will become – who do they want to become and how can she help to get them there.

“When any of us look back on teachers who made a difference for us, I believe the first thing we remember is that they cared about us, made us feel worthwhile and all the dreams, needs, and even struggles were important. “I try to pass on that caring approach more than anything. My students may not always remember the facts and ideas I’ve taught them, but they will remember whether I cared about them. I want our future professionals to be caring people themselves and the best way to learn how is to experience being cared about,” she added.

Every teacher looks forward to recognition fora job well done. It is part of what keeps them going. For Rogers the greatest reward is when a former student says to her, “I am glad that you were my teacher.” Whenever she hears those words she says she thinks about how they took their journey together.

Rogers has been teaching at East Stroudsburg University for the pace 30 years, and five years prior to that as a graduate teaching assistant at two universities and a science teacher in a public high school. She has taught all of the nearly 750 graduates of the program. “Most of our graduates are now pursuing very successful careers in our professional field all over the United States. I feel privileged to have had an opportunity to know these people and to have made some small difference for them with their success,” she said.

She holds a doctorate of education in park and recreation management from the University of Oregon; a master of science degree from East Stroudsburg University in biology; a master of science in education from Northern Illinois University; and a bachelor of science degree in physical education from North Georgia College.

Johnson College

According to Michael K. Novak, department chairperson of the Johnson College Diesel Truck Technology program, career opportunities for graduates of the diesel trucking program are excellent business opportunities.

“Given our location in the northeast corridor of interstate highways and the top-quality hands-on education of the students, this career field has seen a boom at Johnson,” he explained

During his career, Novak has seen terrific changes in the diesel trucking industry as it made the transition from mechanical to electronic components. His industry experience enables him to be an effective liaison with regional trucking companies who send representatives to campus to make classroom presentations and often donate technical equipment for students to use.

Novak joined Johnson College in 2003 after working at Kenworth of Pennsylvania for 14 years.

Between his industry experience and his formal education Novak is noted as one of the most popular and effective instructors at Johnson College.

His education in diesel technology began at home where many members of his family are involved in various aspects of the trucking business.

He completed the diesel technology program at the Lackawanna County Lamer Technology Center, then went on to earn an associate’s degree from Penn College of Technology. He is currently maintaining a 3.9 GPA in his baccalaureate studies at Temple University. He is also certified by the Council of Educators as a technical instructor, and a certified Original Equipment Manufacturer Technician.

The backbone of a Johnson College education is a “hands-on” approach to learning and diesel truck engines have become very sophisticated so Novak’s strength is in relating the conceptual knowledge of the classroom to the experiential knowledge of the workplace.

As a former technician himself, he can understand and anticipate the kinds of questions a student will have and guide them through the learning process.

He also teaches his students the skills that are critically necessary for preventive maintenance and the importance of customer service. In industries such as distribution and logistics, a disabled vehicle can cause delays in delivering goods which may, in turn, have an impact on a manufacturers production schedule. He instills in them the understanding that they are always representatives of their employer and their technical ability must be combined with “people skills” in order to the successful.

Keystone College

Sonji Lee, Ph.D. believes that by being a teacher she is also a steward entrusted with responsibility for the academic and intellectual growth of her students. She is an assistant professor at Keystone College in the division of business, management and technology.

“I believe that, as a leader, l must lead by example, for this is the most enduring way to achieve the leadership abilities in others,” she explained.”In order to maintain effective stewardship and leadership, I must practice ongoing self-reflection exploring my values and beliefs because by knowing myself it enables me to effectively teach others.”

She abides by Ralph Waldo Emerson’s quote, “Do not follow where the path may lead. Go instead where there is no path and leave a trail.”

Lee brings enthusiasm and intellectual excitement to the classroom; maintains an ongoing focus on scholarship in her field of study; sets high standards for achieving excellence; and tries to empower her students to identify and achieve their dreams.

She embraces change, especially since she expects her students to readily adapt to the dynamic, rapidly changing world around them. She tries to create a community of learners that focuses on the application of their knowledge.

As a teacher she maintains a sincere and meaningful rapport with her students, and is totally committed to her teaching on every level.

Lee not only demands accountability from her students, but she also challenges them as well to help develop critical thinking skills and innovative solutions.

Lee obtained her BA in sociology and certificate in gerontology from College Misericordia; her master’s of public administration from Marywood University; and her doctorate in philosophy in business from Capella University, Minn.

King’s College

The fact that Rev. Jack Ryan, C.S.C., Ph.D., a professor of business and management at the William G. McGowan School of Business and Management at Kings College, has both real world (13 years in an international engineering consulting firm) and academic experience allows him to present the subject of business to his students from the prospective of both practitioner and academic.

He feels it very important to begin each class or student encounter by addressing the “so what?” question. That is, why should the class consider the subject mat-ter and why is it significant to the student and to others? “My practitioner experience aids me in setting the hook as to why the subject matter of the class is significant and useful, while my training as an academic can then help de-bunk some of the widely held views of business practitioners that really don’t have very much evidence to support them,” he explained.

In addition, Ryan has been a Roman Catholic priest the last 13 years, and uses this experience to demonstrate, by example, how management theory applies in the not-for-profit world

The underlying principle that guides his instruction is management as a profession. “I continually remind students that the professional is the person who stands between a complex body of knowledge and the general public. They are working to master that knowledge so as to provide a valued service to the public. They may very well have a financially rewarding career, but they are equally called to serve the public good by their competence and moral leadership.”

During the course of their college career he challenges them to review the “tool box” they are developing and answer the questions:” Why is your future employer going to offer you amount of money? and What value are you bringing to your employer and society?”

“Formal studies can often lose track of the big picture and the reasons why you want to give your life to a certain career Students are making a big investment of time and money, it is important that they do it for the right reasons and in the right fashion.”

Lackawanna College

Professor Joseph F. Gilroy says you cannot rush experience even though experience is what every business person needs. “What I try to do is give them the foundation they will need in order to have a successful career. No one gets a Ph.D. without going through a 101 class first. Fundamentals don’t change, just philosophies, explained Gilroy, business chairman at Lackawanna College.

He encourages each student to ask the question, “Why?” The more they question, the more they learn and hopefully retain.”

“Business people must have a total understanding of business from accounting to marketing to management and especially to economics. They must also he able to communicate effectively either through writing or public speaking.”

To be successful in the 21st Century, Gilroy said a person must have a complete knowledge of business – not only hard skills, but more importantly soft skills. “If you don’t like people, don’t go into business. If you can’t write or speak to people you just can’t do business,” he said.

Gilroy returned to Lackawanna after a successful 35-year career in upper management positions for several major corporations. During this time he was vice-president of a regional company, and

then CEO of his own corporation.

Gilroy graduated from Lackawanna College in 1967, and after completing his military service, continued his education at the University of Scranton and at Marywood. He graduated in 1975 with a degree in business management.

He has taught at Lackawanna’s main campus and satellite centers since the late 1970’s. Mr. Gilroy says, “I love the opportunity to return to Lackawanna on a more permanent basis to share my knowledge and experience with my students, and am grateful that at the same time I continue to learn from them as well.”

Luzerne County Community College

Lori Major, CPA, associate professor of business at Luzerne County Community College. loves to teach. She wakes up every morning looking forward to going to work.

When she first graduated from King’s College with a bachelor of science degree in accounting, she immediately began a career in business, working in public accounting and as a controller at private and public companies.

She took to the classroom in 1997, “I feel a real need to educate people about business. I not only have an excellent educational background, but also the experience of the “real world,” she explained.

She said students of today need to hear about practical real world decision making in order to produce excellent business-minded leaders for tomorrow.

“The most important aspect of educating our future business leaders is practical experience,” she said. Theory is important in the classroom, but engaging the student to apply the theory is what we must do to prepare them for their future. “Students stay engaged and learn so much more when they are taking the information that is talked about and work on realistic projects and/or internships in their field,” she added.

She always has students work in teams to solve problems because that is how they will be working in the future.

Major agrees that there are many challenges facing business leaders today as the business world becomes more complex. For many years, she says, it was the company who called the shots without regard for customer service. With the dawn of the Internet age the customer has many more outlets to purchase their products; a large database of information to work from; and an easy way to perform research,” she added.

Another challenge is attracting and retaining superior talent in organizations. “Employees expect to work with one another, have empowerment, be educated, and of course, be compensated according to their abilities. Businesses must know their employees wants and needs, and then be prepared to accommodate them,” she explains.

Finally, she believes that business leaders in any size company must be prepared for “disaster,” which can come from the economy, laws, and even terrorist attacks. “A business leader must be able to overcome and adapt their company to these potential disasters,” concludes Major.

She also holds a master’s degree in taxation from King’s College and has been a CPA since 2002.

Marywood University

At Marywood University, professors expound upon three “pillars of excellence” to build success in the world of business, according to Arthur Comstock, Ph.D., associate professor and chair of the business programs at the university.

The first pillar consists of “industry-relevant and technically- driven skills.” He explains, “Business students must attain curtain skills and be technically competent within their discipline. These skills go beyond the classroom setting and require real-world experience.” For this reason, students are encouraged to participate in an internship program where they receive hands-on training in a variety of local and regional organizations with whom the department has developed relationships and alumni connections.

The second pillar is based on “ethical leadership.” He noted, “Marywood has had a strong reputation for ethics, and this is something that our business pm-grams hold near and dear as well. Training is received in business ethics and industry leaders from around the country are invited to speak here.

The third and most important pillar is “entrepreneurship.”

“Even if a student is not interested in starting his or her own business, taking an entrepreneurial perspective will pave the way to career success, and we consistently challenge our students to think creatively and to seek innovative solutions to problems,” said Comstock.

The department his also sponsored several student teams in the Great Valley Technology Alliance (GVTA) Business Plan Competition, in which students develop a business plan for their own “companies:

The Pacer Investment Fund, a student-managed portfolio that uses Marywood endowment money brings these three “pillars of excellence” in an all-encapsulating experience for students. Comstock is the founding director of the fund.

Comstock has been at Marywood University for eight years, where he has served as chair of the Business and Managerial Science programs for the past five years. He obtained his Ph.D. in business and economics from Lehigh University.

He has published numerous articles; has been selected to “Who’s Who Among America’s Teachers” each year from 2004; has served as a financial consultant for organizations throughout the northeast region and as a board member for several local organizations, and currently serve as treasurer of the board for the Electric Theatre Company.

Misericordia University

Personal business experience, keeping up with current events, business research and best business practices are some of the teaching tools Corina N. Mihai, Ph.D. uses.

Mihai is assistant professor of business and director of the Master of Business Administration and Organizational Management programs, as well as faculty liaison for business majors enrolled in the Expressway program at Misericordia University in Dallas.

“I believe that in business education, especially at the graduate level, students need to know how to apply what they learn in class for it to be of any use to them. Therefore, my strategy is to make my classes worthy of my students’ time. Theory is great but application is the key to success,” Mihai said.

In her classes, discussion of theory is first, then applying it to real situations and real companies is the next step.

She said, “There are also two key aspects of leadership that I continuously emphasize in all my classes: that leaders need to have people skills and lead companies where people matter and that they need to be ethically and socially responsible – the essence of our MBA program.”

She urges students to practice, practice, practice as it is key to a successful business education program. “If my students cannot use what they’ve learned in class immediately, then I did not do my job right. Nothing makes me happier than when a student proudly announces in class how he/she used what was learned in class to successfully complete a task at work,” she said.

Mihai earned her bachelor’s degree and MBA from Wilkes University and her Ph.D. in organizational management, with a specialization in leadership, from Capella University, Minneapolis, Minn. Her dissertation was titled: “Emotional Intelligence and Academic Leadership: An Exploratory Study of College and University Presidents.”

Some of her professional memberships include the Luzerne County Council on Adult Higher Education and the Academy of Management. She has more than 10 years academic administration experience mainly at the graduate level, and more than eight years of business teaching experience at graduate and under-graduate levels. Her research interests include emotional intelligence, leadership, organizational behavior and development, strategic management, and higher education administration.

In 2001 she became the first female president of the Wilkes- Barre Rotary Club.

Northampton Community College

The new director of hotel and restaurant programs at Northampton Community College is bringing experience and enthusiasm to the region. David Schweiger recently moved from San Diego to Pennsylvania, to head up the hotel and restaurant management prograins at Northampton Community College. He is excited about overseeing the expansion of degree programs and noncredit training programs to support the growth of tourism in the Poconos and in the Lehigh Valley.

Schweiger earned a bachelor of science degree in human resources at the University of Idaho and a bachelor of arts degree in hotel/ restaurant administration and a master’s in hotel/restaurant administration from Washington State University. He has extensive experience in hotel and restaurant managing and consulting, as well as in teaching, having held managerial positions with major hotel chains such as Hilton and Starwood, and served as department coordinator for hospitality management programs at Cypress and Mira Costa colleges.

In announcing his appointment, Dr. Paul Pierpoint, vice president for community education at Northampton Community College said, “David has the right combination of academic credentials, industry experience, college teaching and administrative experience, and professionalism to work with all of the various constituencies of the program and to serve them all very well.”

Northampton offers an associate in applied science degree in hotel/restaurant management with specialization either in restaurants or hotels. Northampton Community College also provides customized training programs for employers in the industry.

Schweiger’s enthusiasm for the hospitality industry dates back to when he was a kid. As a child, he took countless-mini vacations” with his family, enjoying the thrill of staying in new places. Through that work he hopes to pass on that pleasure to other travelers and to diners. It’s a welcoming thought.

Penn State Hazleton

Sherry K. Robinson, Ph.D., associate professor of business administration at Penn State Hazleton, always tries to focus on the practical, making theories relevant to real life.

“In many cases, this means pointing out to students that there are often many theories regarding the same topic, and the choice of which one is best is frequently a matter of the situation and personal preferences. It depends is usually the most accurate answer to many questions. Therefore, being able to absorb relevant information, analyze situations, make decisions based on the situation, and communicate those decisions are important skills that are useful in a variety of circumstances,” she said.

Robinson has been awarded a Fulbright Scholar grant to lecture and perform research at Buskerud University College, Honefoss, Norway, during the 2008-2009 academic year.

From Aug. 2008 to July 2009, Robinson will teach business counts at graduate and undergraduate levels and perform joint management research projects with Buskerud faculty She is one of approximately 800 U.S. faculty and professionals who will travel abroad through the Fulbright Scholar Program.

At Penn State, Robinson has taught a variety of business administration, management, international business, marketing and economics courses. Her research topics include entrepreneurship, particularly rural women small business owners, as well as a project on business incubators. Her pedagogical research has focused on the use of interactive technologies, such as “clickers” (student response systems) and podcasting.

She has helped to develop a new student exchange program between Penn State Hazleton and Buskerud University College, making Hazleton the first campus in Penn State to offer a study abroad session in Norway, other than student teaching experience. Two students from Penn State Hazleton successfully completed International Management and International Marketing during this summer’s session at Buskerud. This reciprocal program will bring Norwegian students to Penn State Hazleton for a semester of study.

While at Buskerud, Robinson will teach organization and management, consumer behavior, travel and tourism marketing, and negotiating. Additionally, she will assist the Fulbright office in Oslo with podcasting.

A native of New Albany, Robinson earned her bachelor’s degree from Messiah College in 1990, master of science in Business Administration from Bucknell University in 1994, and doctoral degree in Applied Management and Decision Sciences from Walden University in 2000. She has taught at Penn State since 1995 and was granted tenure and promoted to associate professor of business at Penn State Hazleton in July 2007.

Penn State Wilkes-Barre

Even though Theresa Clemente, MBA has been teaching for 29 years, she is still passionate about her profession. “My motivation is to help students become respectful, responsible, and knowledgeable employees that have high standards of performance and recognize the value of lifelong learning. I want to help students grow and find passion in their lives that will be enriching,” said Clemente, Penn State Wilkes-Barre faculty and internship coordinator.

In teaching a variety of business courses in the marketing and management she teaches her students to be comfortable in their own shoes, and be proud of their accomplishments; he passionate about what they do, and everything will fall in place; get excited about the power behind knowledge; be willing to take the steps to grow after careful self reflection; take on difficult personal challenges; step out of one’s comfort zone; and embrace continuous learning by enhancing strengths, discovering what needs to be learned, and make necessary changes.

In enforcing these philosophies, Clemente introduces her passion for learning through special interest projects, student-centered discussion and a great deal of teamwork. “I also bring my excitement for learning by finding new ways to teach through new technologies offered by the university and involving students in community based service learning initiatives.”

Clemente assists students in finding suitable internships in their senior year that will lead them on their chosen career path. “In this role, I am the last one to advise students before they graduate, and will continue to be available for consultation in the job search. Most of the time, I suggest that students continue their education by pursuing a master’s degree,” she said.

“Companies of today need to be informed organizations that possess good communications, internally and externally, and to utilize the right technologies as a tool to make informed decisions,” she said. Companies need to develop a plan for change and to embrace change as well as to provide inspirational leadership and a new type of team work.

Clemente holds a master’s in business administration from St. Joseph’s University. She is the business club advisor and gets involved with students outside the classroom in this capacity. “I want to link them to the community through the Joint Urban Studies Center, Great Valley Technology Alliance, Business Plan Competition and Entrepreneur Institute, and other community businesses,” she notes. She is also a board member of the Visiting Nurse Association.

Penn State Worthington

Ronald J. Yevitz works brings the theories and definitions introduced in a business curriculum “to life” on a daily basis.

“My passion is to help students appreciate how the theory can apply to our current business climate,” said Yevitz, business instructor, curriculum coordinator and internship coordinator at Penn State Worthington Scranton Campus since 1999.

Having spent more than 30 years in the corporate world, he believes he is fortunate to be able to “connect the dots” between theory and reality in the courses he teaches. “I am afforded the opportunity to bring current business world experiences, along with my own experiences, into each class. There is much to be learned in my courses and I attempt to inject humor where appropriate to keep students on their toes,” he said.

His goal is simple: to help them reach their full potential, whatever level that may be. “I tell them all the time that by attending Penn State they have raised the bar for themselves in terms of what responsibilities and compensation they want to be considered for after graduation. It is my job to make whatever concepts we are discussing have enough of a connection that they might store it in their memory bank for future reference. The business world is not a perfect road map, and I constantly remind them of that all the time,” Yevitz explained.

His business internship experience affords him the opportunity to help students build their resume and to use the experience as a “trial balloon” for the efforts required to secure employment after graduation.

Students are encouraged to “pick his brain” on any subject and he tries to assist them in any way he can. “Between the students I advise, those in my classes, and those who seek me as business curriculum coordinator, my days can be quite interesting to say the least,” he said.

Yevitz is also involved in many faculty related efforts to further the growth of the campus, and enjoys assisting wherever possible helping young people.

He holds a bachelor of science in marketing from Susquehanna University and a master’s degree in finance from the University of Scranton.

He owned an advertising agency in Scranton and provided marketing for various companies including three financial institutions.

University of Scranton

The philosophy of Murli Rajan, Ph.D. is quite simple. He “keeps it relevant” for students in the Kania School of Management (KSOM) at the University of Scranton.

“Our students need to know that what they are learning in class can be used in the real world,” he said. A combination of solid academics and practical experience helps this associate professor relate to students.

“MBA students really need to know how the theory applies and I am responsible for teaching them just that,” he added.

Today’s business leader needs a wide range of skills to succeed, according to the professor. Also, a solid understanding of finance and accounting is essential and one needs to recognize the global nature of business.

“A successful business leader must have a good grasp of political and cultural issues; understanding local business customs and social mores is a must,” he explained. Finally, one cannot underestimate the importance of always conducting business in an ethical manner – in the end it always pays off, he said.

Rajan is currently associate professor of finance at the Kania School of Management at the University of Scranton, and is also the director of the MBA program at the institution. He teaches courses in corporate finance, investments, portfolio management and fixed income securities.

Rajan received the “Finance Teacher of theYear Award” in 2008 and 2006. He also received the “Student Choice Award for Excellence in Teaching” in 2000. In addition to his academic duties, Rajan also works as a consultant serving as an expert witness in the area of economic damages. He also serves as a consultant to the Chartered Financial Analyst (CFA) Institute in matters relating to curriculum.

He received his PhD., in finance from Temple University, Philadelphia, and he holds an MBA from the University of Scranton, an MCOM from the Delhi School of Economics, and a BCA from the Victoria University of Wellington, New Zealand. Rajan is also a Chartered Financial Analyst (CM).

His research interests are in equities and asset allocation. His research has been published in several noted business journals. He has lived in a number of countries including, the United Kingdom, Sri Lanka, New Zealand, and Yugoslavia.

Wilkes-University

Justin C. Maros, Ph.D., assistant professor and academic chair of the business division of the Jay S. Sidhu School of Business and Leadership at Wilkes University believes that no matter what size the organization, it must have a strong leader who knows very clearly what the business is trying to be and how to take it there.

“Any successful business very likely has a leader with laser- like focus on things like great products, low-cost structure and efficient operations, or a powerful organizational culture. And interestingly, many successful companies truly don’t do everything at 100 percent efficiency, but the things on which they do focus, they almost never, never slip.”

Another important focus of a successful business is adaptability; all great businesses know how to read and anticipate changes in the marketplace and then they adapt and change with that movement. “Successful companies do not continue to try and sell typewriters when everyone wants a PC.

He believes in investing in great customer service. “Too many companies think that in order to achieve low cost you must skimp on customer service, yet it need not he that way Southwest Airlines is the perfect example of a company that offers low-cost airfares with great customer service. The reality is that investing in great customer service will always pay for itself and then some through improved image, customer loyalty, customer satisfaction and repeat busness,” he said.

Another important aspect of a successful business is execution. “Quite simply this means doing what you say you want to do. If a business promises to do something they do it, whether it’s a plumber who shows up when scheduled or a product that works the way its advertised, a business must keep its promises…otherwise the customer will ruthlessly fire that business and go someplace else,” he notes.

Matus, who is well-published has a Ph.D. in health services/ management from Old Dominion University, Norfolk, Va.; his MBA in business administration from Golden Gate University, San Francisco; and a B.S. in business administration from King’s College.

Education

60% of Modern Jobs Require a 2-Year Degree: What It Takes to Fill This Niche

Written By: Sam Savage

Published Date: September 1, 2008 Last Edited: September 1, 2008

By Gardner, Dave

Melissa Casper is on track to become a professional diesel girl.

The Waymart resident is beginning her senior year at Johnson college, where she is enrolled in the school’s diesel truck technology program. She explains that she tried various jobs after her graduation from Forest City High School, including real estate sales, but always wound up a “bored” member of the northeastern Pemsylvania (NEPA) workforce.

“My grandfather and father were mechanics, and I have always liked tinkering with machines,” says Casper “This educational major was a natural for me. I’m also working at Kenworth Truck, half of the time as a service advisor and the other half as a mechanic.

Melissa Ide, director of enrollment management at Johnson, says the technical college now serves 371 students who study for two- year degrees in 12 separate programs. The school will soon launch a new curriculum in HVAC Technology, which will he the third new program introduced since 2000.

“The other new curriculums we added are distribution and supply logistics technology and radiologic technology,” says Ide. “Programs that are popular include electrical and construction maintenance, electronic technology that’s offered in conjunction with Tobyhanna Army Depot and computer information technology.”

Johnson employs more than 60 people, with student tuition for 2008 totaling $13,500 plus fees, books and housing. During 2007 the school’s students were 74 percent male, while veterinary sciences and radiology featured larger female enrollments.

Math, reading and writing skills are tested for each freshman, and remedial classes are offered if necessary. There are no undecided majors at Johnson.

“As continued immigration unfolds, we could see a big influx of diversity from the immigrants’ children, if they have good math skills,” says Ide.

One of the reasons Johnson is adding the HVAC major is that the Bureau of Labor Statistics forecasts a 9 percent national increase in HVAC employment over the next ten years. A regional survey also indicated that a skills gap exists for HVAC specialists.

The best students at Johnson, according to Ide, match a technical interest with strong mathematics abilities. She says public school instruction in math is still lacking, with student awareness of the problem below the level that industry desires.

She also explains that the technical trades have evolved. Originally, math was not needed as it is today, but the math mindsets of many industrial workers haven’t evolved with the ongoing needs of employers.

“Unfortunately, we just haven’t seen the necessary improvement in math skills,” says Ide. “This is the No. 1 area of deficiency, and it needs a major revolution.”

As with virtually all schools, student obstacles can appear within the Johnson student body. Ide says that these problems usually involve issues the school can’t control, such as finance and mental health issues.

To help with potential problems, Johnson requires all new students to complete a Freshman Experience program. This curriculum discusses areas such as life skills, time management and monetary issues.

She also comnents that the school’s staff is witnessing an increased level of parental involvement and awareness.

“We need to get across to prospective students that this type of schooling provides a quick return on a two-year educational investment,” says Ide.

Dominick Carachilo, vice president of academic affairs says that in many ways a national public disconnect is occurring regarding how fast technology is moving and the subsequent needs for knowledge in the workplace. However, he also comments that a market revolution is occurring in NEPA with increased recognition of the need for professional training.

He comments that the ongoing workforce needs at Tobyhanna Army Depot have been a blessing to NEPA, and that enrollment in Johnson’s related electronic programs is growing. There also have been a few surprises that have confronted the Johnson College planners.

“Enrollment in our distribution and supply logistics associate degree program has not been as strong as we expected,” explains Carachilo. “Perhaps there’s a stigma with this type of work, pushing people away from the highly skilled technical jobs that are available. A big factor in future logistics will be the explosive fuel costs, making efficiency in the industry more important than ever before, and there will be some very good job opportunities.”

According to Carachilo, it is vital to target middle school students before career choices are made, and to educate teachers about today’s specific needs.

“Matching entrepreneur abilities with technical educations can be a great mix,” says Carachilo. “We are offering an entrepreneur elective, and the kids love it.”

Regarding society’s lost kids Carachilo says that there is only so much any school system can do.

“Parental follow through for workforce education is vital, but its missing in many families,” says Carachilo. “Our NEPA schools are aware of this, and they are doing a better job than in many other parts of the state. We must communicate the availability of jobs and the necessary educations.”

Marie Allison, coordinator of continuing education at Johnson, explains that contract training for industry is growing. Companies frequently call Johnson with educational needs, starting a process that may include an on-site analysis.

“We then develop curriculums and costs, which can be offered on- site at the employer or here at Johnson,” says Allison. “Sometimes we partner classes for multiple employers, and as a rule our regular staff teaches the classes. If needed, we will use additional instructors.”

During the first half of 2008, in addition to the school’s students studying for electronic degrees, 150 total students have taken advantage of Johnson’s continuing educational programs in classes of eight to 80 people. Allison comments that similar specialized continuing education programs arc also offered by Penn State University and Luzern County Community College.

One of Johnson’s successful continuing educational programs involves numerous employees of the former McKinney Manufacturing. Allison says Johnson developed a partnership with Pennsylvania’s Careerlink office and Lackawanna College to deliver a Computerized Numeric Controls (CNC) machine trade program.

The 575-hour course earns graduates a certificate, with Johnson providing the curriculum’s technical segment. Allison comments that adult learners such as these participants are often highly motivated, and to succeed only need a program that matches their needs.

This may include cross training in areas such as hydraulics or pneumatics. Math skills are watched carefully with continuing educational students, and a basic module in math is available.

“I’ve had my eyes opened concerning the need for this math instruction,” says Allison. “In the old days employers could hire entry level people and there was no need for additional math instruction, but that’s no longer the case.”

Health

Rescuers Carry Girl By Stretcher

Written By: Sam Savage

Published Date: September 1, 2008 Last Edited: September 1, 2008

By Vail Daily

A search-and- rescue team carried a 14-year-old girl with neck injuries down a steep and rocky hiking trail in the Holy Cross Wilderness near Carter Lake late Thursday night and early Friday morning.Rescuers had first planned on flying the girl out by helicopter but couldn’t get her safely to the landing zone by nightfall, and there were no helicopter pilots trained to fly with night vision technology available.The girl was instead carried by stretcher on the difficult 21/2-mile hike on the trail connecting Henderson Park and Frying Pan Road. The girl was treated at Aspen Valley Hospital and released.The girl had been hiking with a church group when she fell near the bottom of a scree field and complained of severe neck pain and a sprained ankle, Smith said. A Flight for Life helicopter from Summit County landed on Savage Peak at 3:53 p.m., about a mile from the victim.

Originally published by Vail Daily.

Health

Car Park MRI Scans Slated

Written By: Sam Savage

Published Date: August 31, 2008 Last Edited: August 31, 2008

A HOSPITAL is to carry out MRI scans in its CAR PARK in a desperate bid to wade through a backlog of 1,040 patients.

The Princess Royal University Hospital in Farnborough, Kent, came up with the drastic solution after being named as the second-worst hospital in England for meeting national targets of seeing patients within six weeks.

Boss Mike Marchment said: “We can’t squeeze more in so we have to go outside.” But patient Cindy Barnes, 32, raged: “It’s like a Third World health service. It’s a disgrace.”

Health

TRANSCEND(TM) Trial Results Presented at European Society of Cardiology Congress and Published in The Lancet

Written By: Sam Savage

Published Date: August 31, 2008 Last Edited: August 31, 2008

RIDGEFIELD, Conn., Aug. 31 /PRNewswire/ — The primary results of the TRANSCEND(TM)* trial demonstrated that treatment with MICARDIS(R) (telmisartan) 80mg in patients receiving current standard of care resulted in an 8% reduction in the composite endpoint of cardiovascular death, myocardial infarction, stroke and hospitalization for congestive heart failure. This reduction was not statistically significant (p=0.216; HR 0.92) compared to patients receiving placebo in addition to current standard of care.(1) Results of the main secondary endpoint of TRANSCEND as pre-specified in the statistical plan demonstrated that telmisartan significantly reduced the risk of cardiovascular death, myocardial infarction and stroke in high-risk cardiovascular patients by 13% compared with those patients already receiving current standard of care (p=0.048).(1) This risk reduction was achieved despite a high proportion of patients receiving proven therapies such as statins, anti-platelet agents or beta blockers. The main secondary endpoint of TRANSCEND mirrors the primary endpoint of the landmark HOPE trial.(2) A post-hoc analysis to adjust for multiplicity and overlap with primary endpoint showed a p-value of 0.068.(1) The results were presented today at the annual meeting of the European Society of Cardiology in Munich, Germany and published online in The Lancet.

In high-risk patients who cannot tolerate an angiotensin-converting enzyme (ACE) inhibitor, the TRANSCEND trial was designed to investigate potential cardiovascular risk reduction benefits using the second-generation angiotensin II receptor blocker (ARB) telmisartan. Telmisartan was compared to placebo on top of standard therapy (including anti-hypertensives, anti-platelet therapy and statins).

The TRANSCEND trial was part of the ONTARGET(TM) Trial Program, the largest clinical trial ever undertaken with an ARB, involving more than 31,000 high-risk cardiovascular patients with either normal or controlled blood pressure. The ONTARGET Trial Program was based on the design of the landmark HOPE trial and encompassed two randomized, double-blind, multi-center international outcome trials: ONTARGET**, the main trial with results reported in March 2008,(3) and TRANSCEND, the parallel trial.

“Previously, the ONTARGET trial showed that telmisartan was as effective as the ACE inhibitor ramipril in reducing the risk of cardio- and cerebrovascular events, but with a lower rate of discontinuations. For high- risk patients who cannot tolerate an ACE inhibitor, the TRANSCEND results could represent an important step forward,” said Michael Weber, M.D., professor of medicine at the State University of New York, Downstate College of Medicine.

It was also published that all cardiovascular hospitalizations were significantly reduced with telmisartan (894 vs. 980; p=0.025). Therapy with telmisartan was well tolerated and showed a trend toward a lower rate of discontinuation (640 patients discontinued taking telmisartan vs. 707 taking placebo, p=0.051). The most frequently reported reasons for discontinuation were hypotensive symptoms, syncope, cough, diarrhea, angioedema and renal abnormalities.(1)

TRANSCEND included 5,926 patients from 40 countries who were at high risk for cardiovascular disease (patients older than 55 years, who have had myocardial infarction, peripheral arterial occlusive disease, stroke or transient ischaemic attacks or suffer from diabetes mellitus and additional risk factors) and intolerant to widely-prescribed ACE inhibitors. Patients in the trial were randomized to treatment with telmisartan 80mg/day or placebo.

It has been reported in medical literature that the incidence of patients with hypertension who are intolerant to ACE inhibitors ranges between 10-39%,(4-6) which often leads to discontinuation of treatment leaving patients unprotected. Side effects associated with ACE inhibitors include intolerable cough and rare, but potentially life threatening, angioedema.(4-6)

“The landmark ONTARGET and TRANSCEND trials have contributed significant and important clinical information to the cardiovascular community and could help uncover new treatment strategies to improve patient outcomes and care,” said Thor Voigt, M.D., senior vice president, Medicine and Drug Regulatory Affairs, Boehringer Ingelheim Pharmaceuticals, Inc.

About the ONTARGET Trial Program

The ONTARGET Trial Program was the largest clinical trial ever undertaken with an ARB, involving more than 31,000 high-risk cardiovascular patients with either normal or controlled blood pressure. The ONTARGET Trial Program encompassed two randomized, double-blind, multi-center international outcome trials: ONTARGET, the main trial, and TRANSCEND, the parallel trial.

ONTARGET evaluated more than 25,600 high-risk cardiovascular patients with normal blood pressure or controlled high blood pressure and a history of a broad range of cardiovascular diseases. The study found that telmisartan is equally effective as the current standard, ramipril, in reducing the risk of cardiovascular death, myocardial infarction, stroke and hospitalization for congestive heart failure, and resulted in fewer discontinuations. Telmisartan is now the only ARB to have demonstrated cardio and vascular risk reduction benefits beyond lowering blood pressure in this high-risk population; these benefits may be attributed to the specific pharmacological properties and mode of action of the drug.(2)

The combined primary endpoint in both the TRANSCEND and ONTARGET trials included cardiovascular death, non-fatal myocardial infarction, non-fatal stroke and hospitalization for congestive heart failure. The secondary endpoint in the TRANSCEND trial was the effect of telmisartan treatment on the incidence of newly diagnosed congestive heart failure, revascularization procedures, newly diagnosed diabetes mellitus, cognitive decline and dementia and new onset of atrial fibrillation.

More than 700 sites throughout Asia, Australia, New Zealand, Europe, North/South America and South Africa participated in the ONTARGET Trial Program. The ONTARGET Steering Committee consisted of scientists from McMaster University in Ontario, Canada; Oxford University in Oxford, England; the University of Auckland in Auckland, New Zealand; and Boehringer Ingelheim.

The ONTARGET Trial Program was investigational and was conducted to expand scientific knowledge of telmisartan. Note that the trial included treatment for conditions outside the approved indication for telmisartan.

About Cardiovascular Disease

Cardiovascular disease (CVD) is the number one cause of death and disability globally(7) and is responsible for one of every three deaths worldwide — an estimated 17 million people per year.(8) CVD causes more deaths than cancer, chronic respiratory disease and diabetes combined.(9) By 2020, it is predicted that CVD will surpass infectious diseases to become the largest cause of death and disability worldwide.(10) It is also contributes significantly to the escalating costs of health care. In 2006, the cost of CVD in the U.S. was estimated at $403.1 billion.(11)

About Boehringer Ingelheim Pharmaceuticals, Inc.

Boehringer Ingelheim Pharmaceuticals, Inc., based in Ridgefield, CT, is the largest U.S. subsidiary of Boehringer Ingelheim Corporation (Ridgefield, CT) and a member of the Boehringer Ingelheim group of companies.

The Boehringer Ingelheim group is one of the world’s 20 leading pharmaceutical companies. Headquartered in Ingelheim, Germany, it operates globally with 135 affiliates in 47 countries and approximately 39,800 employees. Since it was founded in 1885, the family-owned company has been committed to researching, developing, manufacturing and marketing novel products of high therapeutic value for human and veterinary medicine.

In 2007, Boehringer Ingelheim posted net sales of US $15.0 billion (euro 10.9 billion) while spending approximately one-fifth of net sales in its largest business segment, Prescription Medicines, on research and development.

   For more information, please visit http://us.boehringer-ingelheim.com/.    About Micardis(R) (telmisartan)

Telmisartan is marketed in the United States by Boehringer Ingelheim as MICARDIS(R) tablets. MICARDIS is indicated for the treatment of hypertension.

USE IN PREGNANCY

When used in pregnancy during the second and third trimesters, drugs that act directly on the renin-angiotensin system can cause injury and even death to the developing fetus. When pregnancy is detected, MICARDIS tablets should be discontinued as soon as possible (see WARNINGS, Fetal/Neonatal Morbidity and Mortality).

Thiazides cross the placental barrier and appear in cord blood. There is a risk of fetal or neonatal jaundice, thrombocytopenia, and possibly other adverse reactions that have occurred in adults.

MICARDIS is contraindicated in patients who are hypersensitive to any of their components.

In patients with an activated renin-angiotensin system, such as volume- and/or salt-depleted patients (e.g., those receiving high doses of diuretics), symptomatic hypotension may occur after initiation of MICARDIS therapy. This condition should be corrected prior to administration of MICARDIS tablets, and treatment should start under close medical supervision.

The most common adverse events occurring with MICARDIS tablets monotherapy at a rate of 1% and greater than placebo, respectively, were: upper respiratory tract infection (URTI) (7%, 6%), back pain (3%, 1%), sinusitis (3%, 2%), diarrhea (3%, 2%), and pharyngitis (1%, 0%).

Please visit http://www.micardis.com/ for full Prescribing Information for MICARDIS.

*Telmisartan Randomized AssessmeNt Study in ACE-iNtolerant subjects with cardiovascular Disease

**ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial

References

(1) Yusuf, S et al. Effects of the angiotensin-receptor blocker telmisartan on cardiovascular events in high-risk patients intolerant to angiotensin-converting enzyme inhibitors: a randomized controlled trial. The Lancet. Published Online, August 31, 2008; DOI:10.1016/S0140-6736(08)61242-8.

(2) The Heart Outcomes Prevention Evaluation Study Investigators. Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. N Engl J Med 2000; 342:145-53.

(3) The ONTARGET investigators. Telmisartan, ramipril, or both in patients at high risk for vascular events. N Eng J Med 2008; 358(15):1547-59.

(4) Israili ZH, Hall WD. Cough and angioedema associated with angiotensin-converting enzyme inhibitor therapy. A review of the literature and pathophysiology. Ann Intern Med 1992; 117(3):234-42.

(5) Matchar DB, et al. Systematic Review: Comparative effectiveness of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers for treating essential hypertension. Ann Intern Med 2008; 148:16-29.

(6) Macaulay TE, Dunn SP. Cross-reactivity of ACE-inhibitor-induced angioedema with ARBs. US Pharmacist 2007; 32 (2).

(7) Facts and Figures: World Health Report 2003. World Health Organization

(8) The Atlas of Heart Disease and Stroke 2004 World Health Organization http://www.who.int/cardiovascular_diseases/resources/atlas/en/index.html

(9) World Health Organization, Cardiovascular Disease http://www.who.int/cardiovascular_diseases/en/

(10) Levenson J. et al. Reducing the global burden of cardiovascular disease: the role of risk factors. Preventative Cardiology, 2002; 5: 188-189.

(11) Thom T et al. Heart disease and stroke statistics – 2006 update. Circulation 2006; 113:e85-e151.

Boehringer Ingelheim Pharmaceuticals, Inc.

CONTACT: Anna Moses, Boehringer Ingelheim, +1-203-417-7327

Web site: http://us.boehringer-ingelheim.com/http://www.micardis.com/

Health

Necrotizing Candida Infection After Percutaneous Endoscopic Gastrostomy

Written By: Sam Savage

Published Date: August 31, 2008 Last Edited: August 31, 2008

By Wirth, Rainer Bauer, Jurgen; Sieber, Cornel

Gastrostomy site infections following percutaneous endoscopic gastrostomy (PEG) are the most common complication after PEG placement. Recent meta-analyses were able to show that PEG site infections can be reduced significantly with a systemic antimicrobial prophylaxis. This mostly cephalosporin- or penicillin- based prophylaxis does not cover fungal infections. Although Candida skin infections after PEG placement are rarely described, a mucosal colonization or infection of the upper GI tract with Candida species is very common, especially in severely ill patients such as those requiring artificial nutrition. The authors report a rare and lethal case of a necrotizing PEG site infection with Candida albicans in a patient with diabetes with multiple comorbidities, presenting like gas gangrene. In patients with probable immunodeficiency or visible candidiasis of the skin, oropharynx, or esophagus, a Candida infection should be considered in case of a gastrostomy site infection. (JPENJ Parenter Enteral Nutr. 2008;32:285-287) Keywords: Candida; elderly; infection; necrotizing; PEG; percutaneous endoscopic gastrostomy

Case Report

A 77-year-old woman was referred from the department of vascular surgery to our geriatric department. She was diabetic, was nearly blind, and had permanent atrial fibrillation. Before the primary hospital admission, she had normal orientation and was walking without aid. In previous hospital reports, she was diagnosed as obese. Because of severe arteriosclerosis with necrosis of the left fifth toe, a revascularization procedure with venous bypass and amputation of the fifth toe was performed. After the operation, the inguinal wound did not heal. Even a split-thickness skin graft and a cutaneous flap failed. In addition, the patient became delirious with confusion and agitation.

At the time of admission in the geriatric department, we saw a delirious patient, unable to drink or eat reasonable amounts of food, with a body mass index of 22 kg/m^sup 2^. It was unrecognized that she had lost about 10 kg of body weight in the past weeks in the hospital and another 10 kg in the months before hospital admission. Because of her agitation and restlessness, she pulled out every catheter, even though she was treated with neuroleptics. Hence, we were unable to give her sufficient enteral feeding through a nasogastric tube. That is why we performed a percutaneous endoscopic gastrostomy on the fifth day of stay in our department. The esophagus and stomach were without any endoscopic pathological findings. The uneventful procedure was done with an 18 Fr catheter using the pull-through method. The abdominal wall was disinfected carefully and draped with sterile towels. The oral pharynx was not disinfected. No antibiotics were given prior to the procedure. Enteral nutrition was initiated 3 hours after percutaneous endoscopic gastrostomy (PEG) placement with fluid, and after another 3 hours, small amounts of a standard formula were given. The amount of enteral nutrition was increased over the following days and was well tolerated.

The patient first complained of abdominal pain on the fifth day after PEG placement, but the abdominal examination and PEG site appeared normal. Because of probable food intolerance, the amount of enteral feeding was reduced. The next day, the patient complained of increasing abdominal pain, and abdominal examination revealed a cold, black-grey area of 7-cm diameter within a huge red area next to the PEG (see Figure 1). The external bolster was positioned 1 cm off the abdominal wall without any pressure on the skin. Palpation showed a soft abdominal wall with a localized subcutaneous emphysema within the necrotic area at the PEG site. Bowel sounds were normal. The patient had a low-grade fever and was hypotensive. An abdominal ultrasound was performed to look for signs of acute cholecystitis and to exclude intra-abdominal or subcutaneous abscess or fluid collection. The ultrasound examination was normal except for gas bubbles in the subcutaneous adipose tissue and a reticular fluid formation in the areas of the discolored skin.

Figure 1. Necrotizing percutaneous endoscopic gastrostomy site infection with Candida.

The PEG site was cultured, and antibiotic treatment with intravenous penicillin was started. Because gas gangrene was suspected, an emergent extensive wound debridement was performed. An area of 50 X 30 cm with skin, subcutaneous fat, and anterior rectus sheath was resected. The muscle below the fascia showed no typical signs of gas gangrene. The PEG tube was removed, and the gastric fistula was surgically closed. A wound closure with sponge and vacuum treatment was performed. The patient was mechanically ventilated, the antibiotic regimen was continued, and nutrition was given parenterally. Two days later, the patient died in a septic state, despite continued and extended parenteral antibiotic treatment. Postmortem, the PEG site and tissue cultures grew large amounts of Candida albicans while the blood cultures remained sterile. All anaerobic cultures from peristomal swab, resection material, and blood remained sterile as well.

Discussion

Gastrostomy site infections following PEG are the most common complication after PEG placement and are reported in 3% -36% of the procedures.1-3 Although antimicrobial prophylaxis before PEG insertion is performed in many hospitals in Europe, routine systemic antimicrobial prophylaxis is not recommended as mandatory in present European PEG guidelines.4 Antibiotic prophylaxis before PEG insertion is the standard of care in the United States and is recommended by corresponding guidelines.5 In accordance with European guidelines, antimicrobial prophylaxis was not performed in this patient. Recent meta-analyses, however, were able to show that PEG site infections can be reduced significantly with a systemic antimicrobial prophylaxis.6,7 Based on this information, our current departmental policy is now to routinely administer prophylactic antibiotics before PEG.

Here, we experienced a very unusual case of PEG site infection. First, we never experienced a visible skin necrosis after PEG placement before, and no previous cases have been reported in the literature. Second, an infection with gas-producing microbes following PEG placement has not been described before, although PEG site infections with Candida species have been reported.8-10 Theoretically, the emphysema of the abdominal wall could be a consequence of the pneumoperitoneum, which is regularly seen after PEG insertion. But in this patient, the emphysema could be detected only within the necrotic skin area. In view of the fact that Candida belongs to the yeast group of fungal microbes, which produce carbon dioxide from glucose,” we presume that the Candida infection itself might be the cause of the skin emphysema in the necrotic area. Although emphysematous skin infections due to Candida are rarely discribed,12 there are several case reports of other emphysematous infections caused by Candida, such as emphysematous pyelonephritis.13 Several studies have suggested that transfer of oral microbial colonization into the puncture wound is a common source of PEG site infections.14,15 Especially diabetics and patients with poor oral hygiene show higher rates of Candida colonization and infections.16 In our case, no obvious infection of the oral and esophageal mucosa or the skin of the trunk was detected, even though diabetes and heavy weight loss might have induced immunosuppression with an increased likelihood of a mycotic colonization or infection. Nevertheless, in our case, either transfer of oral microbial colonization or local skin microbial colonization at the PEG site are the most likely etiologies of the infection. Another potential contributing factor to PEG site infections and skin necrosis is excessive compression of the abdominal wall skin with the external bolster.17 The standard of care in our department is the fixation of the external bolster without pressure and at a distance of 0.5 to 1.0 cm from the abdominal wall. In addition, the compression would hardly explain a necrosis developing on the sixth day after PEG placement. Thus, tissue compression is not a probable cause of skin necrosis in this patient. As some other studies reported necrotizing infections in connection Candida in different regions of the body,18,19 we suspect a necrotizing candidiasis also in this case.

In conclusion, we learned from this case that PEG site infections can be lethal and that in the case of a PEG site infection not responding to current antimicrobial treatment, a Candida infection should also be considered.

References

1. Wijdicks EF, McMahon MM. Percutaneous endoscopic gastrostomy after acute stroke: complications and outcome. Cerebrovasc Dis. 1999;9:109-111

2. Dormann AJ, Wigginghaus B, Risius H, et al. Antibiotic prophylaxis in percutaneous endoscopic gastrostomy (PEG)-results from a prospective randomized multicenter trial. Z Gastroenterol. 2000;38:229-234.

3. Zalar AE, Guedon C, Piskorz EL, Sanchez Basso A, Ducrotte P. Percutaneous endoscopic gastrostomy in patients with neurological diseases: results of a prospective multicenter and international study. Acta Gastroenterol Latinoam. 2004;34:127-132. 4. Loser C, Aschl G, Hebuterne X, et al. ESPEN guidelines on artificial enteral nutrition – percutaneous endoscopic gastrostomy (PEG). Clin Nutr. 2005;24:848-861.

5. Hirota WK, Petersen K, Baron TH, et al. Guidelines for antibiotic prophylaxis for GI endoscopy. Gastrointest Endose. 2003;58:475-482.

6. Lipp A, Lusardi G. Systemic antimicrobial prophylaxis for percutaneous endoscopic gastrostomy. Cochrane Database Syst Rev. 2006;4:CD005571.

7. Jafri NS, Mahid SS, Minor KS, Idstein SR, Hornung CA, Galandiuk S. Meta-analysis: antibiotic prophylaxis to prevent peristomal infection following percutaneous endoscopic gastrostomy. Aliment Pharmacol Ther. 2007;25:647-656.

8. Patel AS, DeRidder PH, Alexander TJ, Veneri RJ, Lauter CB. Candida cellulitis: a complication of percutaneous endoscopic gastrostomy. Gastrointest Endosc. 1989;35:571-572.

9. Murugasu B, Conley SB, Lemire JM, Portman RJ. Fungal peritonitis in children treated with peritoneal dialysis and gastrostomy feeding. Pediatr Nephrol. 1991;5:620-621.

10. Gillanders IA, Davda NS, Danesh BJ. Candida albicans infection complicating percutaneous endoscopic gastrostomy. Endoscopy. 1992;24:733.

11. Land GA, McDonald WC, Stjernhol RL, Friedamnn L. Factors affecting filamentation in Candida albicans: changes in respiratory activity of Candida albicans during filamentation. Infect Immun. 1975;12:119-127.

12. Hamayun H, Maliwan N. Emphysematous genital infection caused by Candida albicans. J Urol. 1982;128:1049-1050.

13. Hildebrand TS, Nibbe L, Frei U, Schindler R. Bilateral emphysematous pyelonephritis caused by Candida infection. Am J Kidney Dis. I999;33:E10.

14. Faias S, Cravo M, Claro I, Lage P, Nobre-Leitao C. High rate of percutaneous endoscopic gastrostomy site infections due to oropharyngeal colonization. Dig Dis Sci. 2006;51:2384-2388.

15. Thomas S, Cantrill S, Waghorn DJ, Mclntyre A. The role of screening and antibiotic prophylaxis in the prevention of percutaneous gastrostomy site infection caused by methicillin- resistant Staphylococcus aureus. Aliment Pharmacol Ther. 2007;25:593- 597.

16. Belazi M, Velegraki A, Fleva A, et al. Candidal overgrowth in diabetic patients: potential predisposing factors. Mycoses. 2005;48:192-196.

17. DeLegge M, DeLeggeR, Brady C. External bolster placement alter percutaneous endoscopic gastrostomy tube insertion: is looser better? JPEN J Parenter Enteral Nutr. 2006;30:16-20.

18. Cabrera H, Skoczdopole L, Marini M, Giovanna PD, Saponaro A, Echeverria C. Necrotizing gangrene of the genitalia and perineum. Int J Dematol. 2002;41:847-851.

19. Grudell AB, Mueller PS, Viggiano TR. Black esophagus: report of six cases and review of the literature, 1963-2003. Dis Esophagus. 2006;19:105-110.

Rainer Wirth, MD1; Jurgen Bauer, MD2; and Cornel Sieber, MD2

Financial disclosure: none declared.

From the 1 Clinic for Internal Medicine and Geriatrics, St MarienHospital Borken, Borken, Germany, and 2 Friedrich-AJexander- Universitat Erlangen-Nuremberg, Clinic for Internal Medicine II, Nuremberg Hospital, Nuremberg, Germany. Rainer Wirth provided the case treatment and preparation of the article; Jurgen Bauer and Cornel Sieber provided the critical review.

Received for publication May 30, 2007; accepted for publication January 9, 2008.

Address correspondance to: Rainer Wirth, MD, Klinik fur Innere Medizin-Geriatrie, St Marien-Hospital Borken, D-46322 Borken, Germany; e-mail: [email protected].

Health

Hospital Opens New Facilities

Written By: Sam Savage

Published Date: August 31, 2008 Last Edited: August 31, 2008

By Sharon Baker

The first phase of a pounds5-million refurbishment to Grimsby’s Accident and Emergency department is now complete.

From Monday, patients will be able to make use of the brand new facilities as part of a massive overhaul to Diana, Princess of Wales Hospital’s emergency care centre.

The new centre boasts ten treatment rooms filled with state-of- the-art equipment and will soon play host to an array of additional primary care services as part of an integrated model for the department.

The latest refurbishment is the first of three phases in the development, which will also see a new major injuries area, reception and resuscitation room up and running by April next year.

Hazel Coley, assistant director of services development and modernisation for Northern Lincolnshire and Goole Hospitals Trust, said: “There is still work going on and there will still be some disruption for which we would apologise to the patients.

“But I’m sure once we are at the end of the scheme they will see that it’s been worthwhile.”

For more, see today’s Grimsby Telegraph.

Health

Actors Tread the Wards on Hospital Set

Written By: Sam Savage

Published Date: August 31, 2008 Last Edited: August 31, 2008

Hospital patients are to appear as extras in a film after actors transformed a hospital ward into a film set.

Actors Brian Blessed and Susan Skipper visited Stafford General Hospital together with a film crew from the British Youth Film Academy (BYFA) in tow.

They used the self-contained Anson Suite in the hospital’s Shugborough Ward as a set for their latest production – Re- Evolution.

Hospital patients and staff got themselves in on the act by appearing as extras.

Youngsters James Gill, aged 17, of Hednesford, Emily Austin, 14, and Joe Barnes, 11, both of Stafford, all appear as patients in the 12A film, which will be screened at Odeon cinemas next year.

And matron Tess Mobberley, plays therapist Julie Milestone, while paediatric psychology nurse specialist Rona Borland and project support officer Lisa Stokes will also be in the film.

Brian Blessed said: “I think the young patients upstaged the lot of us with their performances.

“We have been made to feel very welcome by everyone at the hospital and it was marvellous to be here with the staff and these patients – a real privilege.

“The subject matter of the film is very important and it deals with a lot of current issues.

“The scenes we have done at the hospital were really very challenging and the staff and patients were all great.”

Matron Mobberley said: “We worked closely with the film crew to ensure there was no disruption to our normal ward routine and they were all brilliant at following our hand washing and infection control procedures.

“It was great to see the actors and crew at work and I’m really looking forward to seeing the finished production.”

Health

Benny Hill Girl Digs Up Home’s History

Written By: Sam Savage

Published Date: August 31, 2008 Last Edited: August 31, 2008

Kerryanne Clancy

Looks back 15 years in The Sentinel’s files and revisits a landmark hospital which was the birthplace of thousands of Staffordshire children

MANY a bouncing baby began life at Groundslow in Tittensor.

Once a 117-bed maternity hospital, the Winghouse Lane site shut its doors in 1983 following the opening of the new district general hospital in Stafford.

A Sentinel headline in August that year declared that the complex had been sold for an undisclosed sum.

And brushing the dust off Sentinel cuttings dating back to 1936 reveals that Groundslow had been a sanatorium for more than 70 female patients with tuberculosis, following reports of a high death rate among women between the ages of 15 and 25.

Yet before this it had a very different life. Before 1913, when the Staffordshire, Wolverhampton and Dudley Joint Committee for Tuberculosis purchased Groundslow, a house was built in 1832 as a hunting lodge for the Duke of Sutherland when he lived at Trentham Park.

As it turned out, Groundslow was to have many more lives over the years.

Following the closure of the hospital, the site was divided. By October 1983, The Sentinel reported that major development plans were on the drawing board, including a hotel, private nursing home and a computer centre. At this stage it was proposed that the old nurses’ home would be the nursing home, the main building would be a hotel and the wards at the back of the site would be a computer company headquarters.

Camelot Court nursing home later opened in the administrative block of the former hospital in September 1985, while Groundslow Grange care home opened in October 1984 in the former nurses’ accommodation, which had been built in 1949. It was run by Peter Ratchford and former Benny Hill girl Anne Bruzac.

The residential care home closed in 1997, and by 2002 the adjacent former hospital was redeveloped into detached homes and terraces, while the Duke’s former home was converted into 25 flats.

But Anne and Peter remain on site in one of the few remaining parts, which are testament to the former life of this once grand estate.

Anne says: “I have done some homework into the site as I’m fascinated with history and old buildings. Groundslow is a hamlet and used to be an Elizabethan village so it’s steeped in history.

“The surroundings are really beautiful here with lots of old trees. They are identical to those found at Trentham Gardens, because the Duke of Sutherland also owned that, so planted the same trees on both sites.

“The houses on the old site came after it was bulldozed in 2000, though the lodge which we live in was built in 1832. When they started building work they found a medieval wall deep underground, so then it became an archaeological site.”

Anne and Peter remain owners of the nurses’ accommodation building, and having initially thought about turning it into a hotel, last year they got permission to turn it into executive apartments.

But she says: “We won’t demolish the nurses block, though we’ve been approached by a lot of developers wanting to do just that. We will keep the gardens and everything intact.”

And perhaps surprisingly, Anne says she and Peter still get a knock on their door almost every week from former Groundslow babies and staff making a special visit.

“Three years ago it was quite exciting,” she says. “There was a knock on the door and it was the former superintendent of the hospital who had come back to visit. He worked there in the 1970s and was now living in the Central Park area of New York. He was very nostalgic when I showed him around and it was quite emotional.

“I become a tour guide for people as the nurses building hasn’t changed so much, and a lot of people still call in and want to have their pictures taken where they were born.”

Were you a Groundslow baby or do you have memories of the former hospital? Write to Colette Warbrook, including a telephone number and address, at Features Desk, The Sentinel, Forge Lane, Etruria, Stoke-on-Trent, ST1 5SS. Alternatively, email [email protected]

Health

Trans Fats Linked To Increased Risk For Colon Cancer

Written By: Sam Savage

Published Date: August 30, 2008 Last Edited: August 30, 2008

According to a new study in the American Journal of Epidemiology, consuming a large amount of trans fats could increase the risk of colon cancer.

Dr. Lisa C. Vinikoor of the University of North Carolina, found that people who had a high intake of trans fatty acids were more likely to have pre-cancerous polyps in their colon than those with a low trans fat intake.

“These results provide further support for recommendations to limit consumption of trans-fatty acids,” said Vinikoor.

Trans fats are created by processing vegetable oils so they can last longer, and are found in many baked and packaged snacks. Eating products with trans fats increases “bad” LDL-cholesterol levels and can bring about increased risk for heart disease. US food manufacturers are now required to label their foods with the amount of trans fat contained in the product.

According to Vinikoor, consuming trans fats can change the normal balance of bile acids in the colon, therefore increasing the risk for colon cancer.

Vinikoor and her team studied 622 people who had colonoscopies in 2001 and 2002. Participants in the study were questioned about their physical activity, and diet during the 12 weeks of testing.

Those who consumed the most trans fat were 86 percent more likely to have colon polyps than those who consumed the least. The top fourth of the study, with the increased risk, consumed 6.54 grams of trans fat per day. Those outside of the top group averaged 4.42 grams of trans fat per day.

Vinikoor and her team added that the findings back current recommendations to limit trans fat consumption.

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Health

Exercise Increases Breast Cancer Survival Rates

Written By: Sam Savage

Published Date: August 30, 2008 Last Edited: August 30, 2008

Researchers at Yale University report that women who exercise after receiving a breast cancer diagnosis increase their chance of surviving the disease by over 30 percent.

The survival advantage applies even to women who began exercising for the first time after their diagnosis, the researchers found.

“Anything is better than nothing,” said Dr. Melinda L. Irwin of the Yale School of Medicine during an interview with Reuters.

“We actually observed benefits with just doing a little bit of exercise,” said Irwin, one of the researchers involved in the study.

Previous studies over the past 20 years have shown that exercise can cut the risk of breast cancer by up to 40 percent. However, recent research indicates that exercise has an equal or greater impact on survival rates among women with breast cancer.

In the current study, Irwin and her team examined 933 women who had been diagnosed with breast cancer between 1995 and 1998. The women were followed through 2004 to help researchers better understand the amount and timing of physical activity required to improve survival.

They discovered that women who exercised the equivalent of two to three hours of brisk walking per week in the year prior to their breast cancer diagnosis were 31 percent less likely to die of the disease than those who were sedentary before their diagnosis.

Two years after diagnosis, those who engaged in any amount of exercise had a 64 percent lower risk of dying than women who were inactive at that time. Women who got at least two to three hours of brisk walking each week reduced their risk of death by 67 percent, the researchers found.

The results further showed that women who decreased their physical activity after diagnosis increased their risk of dying from breast cancer by a factor of four compared with those who were sedentary and remained so. And inactive who began exercising after diagnosis reduced their risk of death by 45 percent.

Irwin said that women undergoing treatment for breast cancer treatment should view exercise as part of their therapy, even if it means beginning with only a 15-minute walk every other day.

“Hopefully this study shows what a major benefit exercise can be,” Irwin said.

In addition to its survival benefits, exercise may also help with the increased risk of cardiovascular disease that may accompany treatment, Irwin said, along with improving a woman’s quality of life.

The research was published in the August 20, 2008 Journal of Clinical Oncology.

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Technology

FAA Outage Highlights Need For Modernization

Written By: Sam Savage

Published Date: August 30, 2008 Last Edited: August 30, 2008

The turmoil caused by a software glitch at the Federal Aviation Administration (FAA) on Tuesday, which caused widespread flight disruptions, shed light on the antiquated system used by the agency, and its urgent need for modernization.

Through its use of practices that would be considered inadequate in other critical sectors, the FAA allowed its systems to be vulnerable to the glitch, which occurred as new software was loaded at a flight plan distribution center in Atlanta.

Since the agency depends on just two such centers, one each in Salt Lake City and Atlanta, to manage flight plans for the country, the software glitch all but shut down the entire system. And although the Salt Lake center remained operational and served as a backup, it became overloaded, resulting in more than 600 flights being delayed throughout the eastern United States.

A failure at the same facility in June 2007 also caused significant flight delays across the East Coast.

Glitches such as the one that occurred this week can often be avoided with sufficient system redundancy, meaning alternate systems and communication channels are in place to handle the workload should one system fail.

In fact, proper redundancy is so critical for utility companies that those found insufficiently prepared can be penalized with daily fines of up to thousands of dollars, and $1 million per day if they are found deliberately negligent.

“In the industries I work in, if you have something that critical, you generally build more redundancy,” Jason Larsen, a security researcher with consultancy IOActive Inc., told the Associated Press.

Larson had spent five previous years at the Idaho National Laboratory monitoring the control systems of electrical plants.

“If this (FAA outage) happened at a power plant, I’d be telling them to open up their checkbook and expect to be fined.”

Tammy Jones, an FAA spokeswoman, emphasized that these types of issues “don’t happen on a mass scale or a regular basis”, pointing out that the agency manages 50,000 to 60,000 daily fights and that flying on U.S. airlines has never been safer.

“The system is working.”

“We are making sure people are getting from one place to another,” she said.

Basil Barimo, vice president of operations and safety for the Air Transport Association of America, said the basic problem is the FAA’s dependence on older technology, such as a radar-based control system designed in the 1940s and ’50s. But he is nevertheless optimistic that the agency’s NextGen modernization program will make more efficient use of the nation’s airspace while safely allowing more planes to fly. The program includes a $15 billion upgrade to satellite-based technology that will take nearly two decades years to complete.

The National Airspace Data Interchange Network computer, located at the Atlanta facility where this week’s glitch occurred, has been owned and operated by the FAA since the 1980s, after the Netherlands-based firm that developed it went out of business. The network is being upgraded to include additional memory, faster data processing and to be more “fault-tolerant.”

“We should see significant improvements by the end of September…which should prevent the type of problem we had on Tuesday,” said FAA spokeswoman Laura Brown.

The FAA is also looking at installing a third backup system at a technology center in New Jersey, however final decisions have yet to be made, she said.

National Air Traffic Controllers Association spokesman Doug Church claims the FAA has tried to focus on future technology to detract from its deficiency in maintaining current systems. Church claimed the FAA lacks a “safety net of redundancy”, and cited the agency’s “fix-on-fail” policy of addressing an issue only after it has become a problem.

To Church’s point, in December the agency exempted its computer maintenance staff from having to perform some periodic certification checks as mandated by government handbooks for technical equipment.

The FAA defended their decision, saying it would eliminate needless certifications that had little or no effect on safety or system performance. A 2006 Government Accountability Office (GAO) report supported the practice in some instances. However, industry experts say they often advise against such an approach.

“It’s common, you see it in retail too – it’s the whole ‘don’t fix it if it ain’t broke’ thing,” Branden Williams, director of a unit of VeriSign Inc. that reviews the security of retailers’ payment systems, told the AP.

“It’s unfortunate because it’s very reactive, and it typically winds up costing you more. If you do fix-on-fail, it usually costs you more.”

However, an outage occurring at a private company that may delay a retail order is much different than one that happens at the nation’s Federal Aviation Administration. And outages such as Tuesday’s have happened multiple times with the FAA.

For instance, earlier this month communications an unknown number of planes and a Memphis, TN, air traffic control center that directs planes passing through a 250-mile radius from the city were disrupted after a car hit a utility pole and cut a fiber-optic cable.

And last fall, the same center lost all its communications, requiring some air traffic controllers to use their personal cell phones to route planes out of the area. The FAA said the outage was a result of a failure of one of AT&T’s major communications links.

In May, the FAA system that distributes preflight notices to pilots about equipment, runway and security issues shut down for about a day when a server failed and the backup was ineffective. Although the database was unable to issue updates or new notices, pilots continued to receive information from local air traffic controllers and through alternate systems.

Referring to this week’s outage, Paul Proctor, a Gartner Inc. analyst focused on security and regulatory compliance for large companies, said it seemed the FAA didn’t install the flight-plan systems with the same amount of redundancy as big companies generally have in their critical systems.

“You need to do a good analysis about whether this is acceptable risk,” Proctor told the AP.

“One of the things the government is betting on is the fact that if there’s…a failure, it’s not a safety issue.”

Sid McGuirk, associate professor and coordinator of the air traffic management program at Embry-Riddle Aeronautical University, and a former air traffic controller and FAA manager for 35 years, said the agency has maintained a good balance given their budget constraints.

“It keeps the system running efficiently without compromising safety,” he said.

“From time to time, we are going to have a glitch, but it’s a tradeoff.”

“Would I like to see more modern equipment in the system? Sure. But most folks would not want to see their taxes tripled to pay for new technology every two years.”

Health

Matrons to Make Their Mark at Musgrove Park

Written By: Sam Savage

Published Date: August 30, 2008 Last Edited: August 30, 2008

Three new matrons will bring more than 50 years of combined experience to the nursing staff of a Somerset hospital.

Paul Jagger, Andrea Mostyn-Jones and Katy Evans have joined the team at Musgrove Park Hospital in Taunton, which serves 340,000 local people.

The three matrons will head up the general theatres, cancer and maternity nursing teams in the hospital.

Mr Jagger, who lives in Stoke St Michael, has been appointed as matron in general theatres after nine years of nursing.

He has spent the last three years as a senior nurse in The Alfred in Melbourne, Australia – the largest trauma centre in the southern hemisphere.

He said: “It’s great to have started at Musgrove in such a challenging and interesting role. I loved Australia, but it was time to come home. My ambition is for all our patients to be treated the way I would want my family to be treated. That’s why I went into nursing and that’s what keeps me in nursing.”

Ms Mostyn-Jones recently moved to Clevedon from Yorkshire to head the cancer team. She has spent 21 years as a nurse, 16 in cancer care, and is excited about working in the new cancer centre, due to open in May.

Ms Evans, who has more than 20 years of NHS experience, was already a member of the ante-natal department of Musgrove. She has recently been shortlisted for the national Nursing Times Award (Midwifery) for improvements to patient care.

The hospital will now have a team of 11 matrons managing the nursing staff of the hospital.

Martine Price, director of nursing and governance at Musgrove, said: “We are delighted to welcome these three new matrons on to the team. They are all committed to leading their nursing teams to provide the best possible care for our patients.”

Health

San Leandro Hospital May Be Sold

Written By: Sam Savage

Published Date: August 30, 2008 Last Edited: August 30, 2008

By Karen Holzmeister

SAN LEANDRO — San Leandro Hospital’s days as a community-owned facility — providing short-term patient care, surgeries and an emergency room — may be coming to an end.

A scenario is unfolding in which Sutter Health affiliate Eden Medical Center of Castro Valley may buy the 122-bed San Leandro Hospital for little or no cash over the next two years.

Eden could leave San Leandro Hospital as a full-service hospital, scale back its operations or convert the East 14th Street complex for other medical programs, such as psychiatric or rehabilitation services.

“The citizens of San Leandro use that hospital, and the ER is very busy,” said anesthesiologist Frank Rico, a director of the Eden Township Healthcare District, which owns San Leandro Hospital.

If San Leandro’s emergency room is closed, Rico said during a directors’ meeting Wednesday, “it’s going to be a significant burden” on Eden’s emergency room.

The district can’t afford to independently subsidize and operate San Leandro Hospital, Rico added.

So, directors voted to spend $40,000 on a consultant. Healthcare Financial Solutions of Oakland will evaluate whether San Leandro Hospital can operate as an independent general hospital.

If a negative report comes back in September or October, directors are likely to move toward an Eden-Sutter purchase of San Leandro Hospital.

San Leandro Hospital continues to lose $250,000 to $500,000 a month, Rico said.

Nearly two-thirds of its admissions are Medicare or Medi-Cal patients, he added, and government reimbursements either don’t cover care costs or are break-even.

San Leandro Hospital loses income-producing outpatient medical procedures to surgery centers. George Bischalaney, Eden’s chief executive officer, also said San Leandro Hospital’s in-patient cases average between 35 and 70 people a day.

Contractually, Eden and Sutter can stop providing emergency medical, surgical and intensive care services at San Leandro Hospital next year. The district paid $35 million for San Leandro Hospital in 2004. Since then, it has leased the hospital to Eden and Sutter.

As part of a long-term agreement approved by district directors last November, Eden and Sutter have infused cash into the financially strapped San Leandro Hospital. Eden and Sutter also hold the state licenses for San Leandro Hospital patient beds.

Eden and Sutter have an exclusive option to buy the hospital in 2009-10, transferring this district asset at a price to be determined.

Dev Mahadevan, the district’s chief executive officer, said Eden and Sutter could choose to buy San Leandro Hospital for what they have invested up to that point and no actual cash.

“The (operating ) losses will equal the value of the (San Leandro) hospital,” he explained.

San Leandro Hospital, known in the past as Doctors and Humana hospitals, opened in 1960.

Originally published by Karen Holzmeister, The Daily Review.

Health

Thousands Remain on Waiting List for NHS Dental Care in North Lincs

Written By: Sam Savage

Published Date: August 30, 2008 Last Edited: August 30, 2008

More Than 5,000 patients in North Lincolnshire remain on a waiting list for dental services.

But local health officials claim they are making headway in clearing the backlog.

Since March the North Lincolnshire Primary Care Trust has been allocating permanent places at dental practices at the rate of more than 300 a month.

Of the 5,003 people on the current waiting list, a total of 1,250 have also been offered some temporary relief.

A spokeswoman for the trust explained the relief consisted of a course of dental treatment, offering a check-up and any subsequent treatment required.

The spokeswoman added: “It is anticipated the majority of patients on the list will either be offered a place at a practice or a course of treatment within the forthcoming months.”

Dental health in North Lincolnshire has been a contentious issue since the new contract system came into being in April 2006. Some dental practices became private with patients then having to sign up for dental plan care.

A shortage of dentists in the region also led to difficulties and in April 2007 two dentists left the area, leaving gaps in the local services.

In August last year there were 6,000 people on the waiting list, and two new dentists were recruited to fill the crucial posts.

The majority of dental surgeries in North Lincolnshire have currently closed their books to National Health Service patients.

Private patients can expect to pay on average pounds30 for an X- ray, pounds97 for a large tooth filling, pounds289 for teeth whitening and pounds175 for a wisdom tooth extraction.

For the full story, buy today’s Scunthorpe Telegraph.

Health

Hospitals’ Surgery Chief Resigns From Post

Written By: Sam Savage

Published Date: August 30, 2008 Last Edited: August 30, 2008

Dr. Mark Roh, the interim chairman of surgery at Allegheny General Hospital in the North Side and West Penn Hospital in Bloomfield, has resigned from the post, hospital officials said Thursday.

Roh, who will remain on staff at the hospitals, cited personal matters for the resignation, according to a letter sent to hospital employees. He could not be reached for comment.

Both hospitals are part of the West Penn Allegheny Health System, where officials in recent months have been consolidating several clinical departments such as surgery. Spokesman Tom Chakurda declined comment.

Dr. Daniel Gagne has been appointed interim chair of surgery at West Penn and Dr. John Raves has been appointed interim chair at Allegheny General.

Originally published by The Tribune-Review.

Science

The Cognitive and Attitudinal Effects of a Conservation Educational Module on Elementary School Students

Written By: Sam Savage

Published Date: August 30, 2008 Last Edited: August 30, 2008

By Dimopoulos, Dimitrios Paraskevopoulos, Stefanos; Pantis, John D

ABSTRACT: The ability of the National Marine Park of Zakynthos (NMPZ) in Greece to protect an important sea turtle rookery will ultimately depend on the level of local support and involvement that it receives. Therefore, it is essential for environmental educators to generate among local inhabitants, starting at early ages, positive attitudes concerning the NMPZ. The authors designed a conservation educational module, with 15 activities, to affect knowledge and attitudes of elementary school students. The authors used a quasi-experimental design for summative evaluation with a pretest-posttest control and experimental group to measure the effects on 4 dependent variables: (a) knowledge, (b) understanding and concern, (c) locus of control, and (d) verbal commitment. The survey instrument comprised 32 items that the authors divided into 4 subscales that measured the dependent variables. In total, 332 elementary school students-162 girls and 170 boys, 11-13 years of age-from 21 classes and 15 schools participated. The results indicated a significant effect on knowledge (low pretest scores), but not on attitudes (high pretest scores). However, posttest correlations in the experimental group indicated that as knowledge level increased, students’ (a) locus of control and (b) understanding and concern for the sea turtle issue became more defensible. The study thus provides a model for environmental educators to design conservation education modules to foster positive attitudes in managing endangered species in protected areas. KEYWORDS: Caretta caretta, conservation, environmental education, evaluation, protected areas, sea turtles, Zakynthos

The National Marine Park of Zakynthos (NMPZ) was established in Greece in 1999 (Dimopoulos, 2001) with the prime objective of managing the major sea turtle (Caretta caretta) rookery in the Mediterranean Sea. As with all protected areas (Pyrovetsi & Daoutopoulos, 1997; Schuett & Ostergren, 2003), the viability and success of the NMPZ will ultimately depend on the level of local support and involvement that it receives. Public involvement has become increasingly important in implementing wildlife management measures (Bright & Tarrant, 2002; International Union for Conservation of Nature [IUCN] Commission on National Parks and Protected Areas, 1994).

Therefore, it is essential that, through organized educational interventions, knowledge and attitudes of local inhabitants regarding wildlife conservation be influenced by the National Park Authority to generate positive behavior toward sea turtle conservation. Educational interventions can effectively improve environmental behavior (Zelezny, 1999). Environmental education (EE) is now widely acknowledged as an important tool in promoting nature conservation (Fien, 2001; Loughland, Reid, Walker, & Petocz, 2003), and extension programs for populations living in or near the protected areas are a common management activity (Ham, Sutherland, & Meganck, 1993).

The results vary, but it appears that exposure to EE in the classroom has at least a minimal effect on knowledge and attitudes. Researchers have reported significant gains of knowledge after 1- day and 5-day programs (Bogner, 1998) and positive changes in attitudes after 2-10 hr of classroom instructions (Leeming, Dwyer, Porter, & Cobern, 1993). Aivazidis, Lazaridou, and Hellden (2006) reported significant positive changes in knowledge and attitudes among 13-14-year-old students following 7.5 hr of classroom interventions.

Children acquire knowledge and develop attitudes toward the environment as early as kindergarten (Leeming, Dwyer, & Bracken, 1995). Children are also more open to innovations than are previous generations; children have a creative potential and can become involved in practical action to protect the environment (Trudel, 1995). Therefore, it would be advantageous that educational interventions start at an early stage before children establish complex conceptual frameworks concerning environmental and social issues (Francis, Boyes, Qualter, & Stanisstreet, 1993).

To assess the effectiveness of EE programs, it is vital for researchers and educators to resort to evaluation (Bennett, 1988- 1989; Marcinkowski, 1997). Evaluation provides feedback loops that are critical to the ongoing design of better programs (McLoughlin & Young, 2005).

Purpose

The purpose of this study was to construct a conservation educational module for elementary school students and to evaluate whether the independent-variable application of an EE module caused a real change to four dependent variables that we selected for this study: (a) knowledge of basic sea turtle biology and existing conservation measures (entry-level variable), (b) understanding and concern for the Zakynthos sea turtle issue (ownership variable), (c) locus of control (empowerment variable), and (d) verbal commitment to sea turtle conservation (empowerment variable).

We adapted the variables from the Hungerford and Volk (1990) Behavior Flow Chart as predictors of responsible environmental behavior (Emmons, 1997): (a) entry-level variables-knowledge of ecology, environmental sensitivity, androgyny, attitudes toward pollution, technology, and economics; (b) ownership variables-in- depth knowledge about issues, personal investment in issues and the environment, knowledge of consequences of both positive and negative behavior, and a personal commitment to issue resolution; and (c) empowerment variables-knowledge of and skill in using environmental action strategies, locus of control, intention to act, and in-depth knowledge about issues.

Furthermore, Chawla and Flanders Cushing (2007) drew a parallel between Hungerford’s (Hungerford & Volk, 1990) predictor variables and the more recent value-belief-norm theory summarized by Stern (2000), thus providing additional validity to the model that we used in the construction of the conservation educational module that we applied for the purpose of this study.

The null hypotheses guiding this study were that in the control and experimental groups, the scores of the four dependent variables will remain the same between first administration and second administration of the questionnaire. In reality, this hypothesis means that the implementation of the conservation educational module in the experimental group will have no significant effect on the four dependent variables and that the control group scores will not change significantly between the two administrations of the questionnaire.

Method

Evaluation Design

For the purpose of this study, we used a quasi-experimental design for summative evaluation with a pretest-posttest control group and an experimental group (Kruse & Card, 2004; Lindemann- Matthies, 2005). This design is recommended by researchers when they cannot randomly assign students to programs, but must work with whole classes. Some classes that are not getting the experimental program can form nonequivalent control (nonrandomized) groups (Aivazidis et al., 2006; Fitz-Gibbon & Morris, 1987).

Evaluation Instrument

The evaluation instrument consisted of a questionnaire that we designed for the purpose of the study (Dimopoulos & Pantis, 2003). Questionnaires are particularly well suited to measuring knowledge, understanding, and thinking skills (Bennett, 1984).

After close consultation with two elementary school teachers and two professors of education, we chose the questions to suit the intellectual and environmental background of the children (Williams & McCrorie, 1990). All items included an “I do not know/I am not sure” option (Cox, 1996). The questionnaire was anonymous to avoid social desirability in answering questions (Streiner & Norman, 1989). Certain questions were keyed in a negative direction to minimize response set (Iarossi, 2006; Oppenheim, 1993).

The questionnaire contained 32 items divided into four subscales. Each subscale measured one of the four dependent variables that we selected for the purpose of this study. The first subscale measured the dependent variable of knowledge on basic sea turtle biology and existing protection measures. It consisted of 13 closed multiple- choice questions with five response options, including one “I do not know/I am not sure” option. A sample of questions follows, with the correct reply in italics:

1. How many days do the eggs remain in the nest before the baby turtles come out? Response options: 10, 30, 60, 90

2. Where do sea turtles nest? Response options: on all beaches with fine sand, only on the beaches they were born on, on beaches that are on islands, on beaches with coarse sand

3. Out of a thousand baby turtles that reach the sea, how many survive to adulthood? Response options: 1-2, 50, 100, 500

4. Are sun umbrellas allowed on the nesting beaches of the National Park? Response options: everywhere, nowhere, only on certain parts, only on the wet sand

The second subscale measured the dependent variable of understanding and concern for the survival of sea turtles on Zakynthos. The subscale consisted of nine 5-point Likert-type questions ranging from 1 (not at all or very negative) to 5 (very much or very positive) and one closed multiple-choice question with five response options. These responses reflected meaningful insight into children’s attitudes (Van Es, Lorence, Morgan, & Church, 1996). A sample of the Likert-type questions follows: 1. Do you believe it is bad for us humans if sea turtles become extinct?

2. Do you think that sea turtles are really threatened with extinction?

3. Do you think that protecting sea turtles is good for the economy of Zakynthos?

The third subscale measured locus of control and consisted of three 5-point Likert-type questions ranging from 1 (not at all or very negative) to 5 (very much or very positive) and one closed multiplechoice question with six response options. A sample of the Likert-type questions follows:

1. Do you think you have a role in protecting sea turtles?

2. Do you think that you could better protect sea turtles if you worked together with others?

The fourth subscale measured the level of verbal commitment to sea turtle conservation and consisted of five 5-point Likert-type questions ranging from 1 (not at all or very negative) to 5 (very much or very positive). A sample of the questions follows:

1. Would you wake up at 6 o’clock in the morning to protect the sea turtle nests?

2. Would you write a letter to the Minister of Environment to ask for more protection of sea turtles?

We scored the 13 knowledge questions so that 1 reflected a correct answer and 0 reflected a wrong answer. We considered the “I do not know/I am not sure” option as a wrong answer. Scores were summed so that the total score reflected the number of correct answers for each student (e.g., a score of 13 indicated that all questions were answered correctly). The score per subscale was calculated as a percentage of the total score for each student.

Reliability and Validity of Survey Instrument

We completed the survey instrument twice in a class of 24 fourth and fifth graders at an interval of 14 days to determine stability (test-retest reliability) (Streiner & Norman, 1989). The sample size was similar to that used by Sia, Hungerford, and Tomera (1986) to determine stability. The test-retest reliability value was .67 (n = 23, significant at the .01 alpha level). The value for test-retest reliability was acceptably high, because-according to Streiner and Norman (1989)-stability measure must be over .50. The test-retest reliability was also consistent with the r values accepted by other researchers (Culen & Volk, 2000; Musser & Diamond, 1999). A panel of teachers and experts reviewed and accepted the instrument for content validity (Litwin, 1995; Ozgul & Andersen, 2004).

The Cronbach’s alpha correlation coefficient for internal consistency was .72 (n = 257) for the whole instrument. Cronbach’s alpha correlation coefficients for each of the four dependent variables were .40 for knowledge, .51 for understanding and concern, .49 for locus of control, and .71 for verbal commitment. Low Cronbach values (.40) for knowledge variable suggest that random guessing occurred (Leeming et al., 1995). This inference is further supported by a study conducted among fifth and sixth graders in Greece that showed limited knowledge about plants and animals in general (Paraskevopoulos, Padeliadou, & Zafiropoulos, 1998). Similarly, Korfiatis, Stamou, and Paraskevopoulos (2004) pointed out that there are no courses that specialize in EE and ecology in the curriculum of Greek primary schools. Similarly, a Cronbach’s alpha value of .46 was accepted for a subscale of seven items in a questionnaire measuring environmental literacy among 8-9-year-old students (Chu et al., 2007).

Furthermore, Smith-Sebasto and Semrau (2004) considered a questionnaire with Cronbach’s alpha coefficient .70 as having a highly internal consistency. Hence, the survey instrument consisting of 32 items had a relatively good internal consistency because of the age group for which it was intended and the fact that it was deemed by the authors more important to include certain items at the expense of internal consistency (Litwin, 1995; McDowell & Newell, 1996; Musser & Diamond, 1999).

Participants

The sample frame was all the schools on the island of Zakynthos, Greece. We defined the sample unit at the class level.

Participants were 332 students (162 girls, 170 boys from 21 whole classes and 15 schools). Ages ranged from 11 to 13 years. In this age group, children shift to more realistic thinking and develop an awareness of conservation needs for animals (Myers, Saunders, & Garrett, 2004).

Experimental and Control Groups

We assigned 16 whole classes from eight schools (178 students in sum) to the experimental group, which received the treatment (application of conservation education module). We chose 14 whole classes from seven different schools (154 students in sum) for the control group, and for this purpose we did not give the 14 classes any treatment. Similarly, other researchers (Aivazidis et al., 2006; Ramsey, 1993) have used a control group from schools other than those used for the experimental group.

The Conservation Educational Module

The construction approach. We based the module on the case study format, also referred to as extended case study, for the investigation of issues (Hungerford & Volk, 1990). The case study format was selected for the design of the module because it provides the instructor with a substantial amount of flexibility and control. The instructor can choose the issue, determine methods to be used, and make decisions concerning the depth to which the issue will be analyzed. It is an instructional method that can be used for learners in fifth and sixth grades too (Hungerford & Volk, 1998).

We based the planning of the instructional module on Hungerford, Volk, Dixon, Marcinkowski, and Sia’s (1988) General Teaching Model (GTM). The model is presented in Figure 1. The GTM schematic diagram illustrates components of the instructional process that those researchers recommended for preparing for instruction. Parts A, B2, and C represent the critical components of instruction (i.e., the instructional [learner] objectives, the content and methods to be used, and posttesting). Pretesting (B1) must also be considered as a critical component when needed in the instructional process. All components are interrelated.

The module aimed at affecting the four selected dependent variables (knowledge, understanding/ concern, locus of control, and verbal commitment). There were 7 activities that addressed the knowledge variable, 12 activities that addressed the understanding and concern variable, 11 activities that addressed the locus of control variable, and 11 activities that addressed the verbal commitment variable. The correspondence of each activity to the four selected dependent variables is presented in Table 1.

We designed the 15 activities in accordance with the four instructional subgoals of EE (Hungerford & Volk, 1990): (a) Goal Level I-the Ecological Foundations Level, which aims to provide learners with that knowledge that can help them make ecologically sound environmental decisions; (b) Goal Level II-the Conceptual Awareness Level, which aims to develop a conceptual awareness of how human behavior can influence the environment; (c) Goal Level III- the Investigation and Evaluation Level, which provides for the development of knowledge and skills needed for issue investigation, evaluation, and values clarification; and (d) Goal Level IV-Action Skills Level Training and Application, which aims to develop those skills important to citizenship action. Of the 15 activities, 7 address EE Goal Level I; 11 address EE Goal Levels II and III; and 8 address EE Goal Level IV (see Table 1).

All activities were active-learning oriented, and such orientation is essential in EE (Cohen, 1994) and is more efficient than traditional learning methods (Kjellin, Naslund, & Stenfors, 2003). Studies reveal that learning experience is enhanced with the active participation and cooperation of the students (Devine- Wright, Devine-Wright, & Fleming, 2004).

The specific teaching or learning strategies that we used in this study were the following: instructions, reading, text writing, lectures, questions, discussion, slide presentations, artwork or drawing, observation and comparison, field survey, critical thinking, belief or value analysis, and simulation and gaming (Askell-Williams & Lawson, 2005; Bailey, 2002; Cheng & Stimpson, 2004; Engleson & Yockers, 1994; Ernst & Monre, 2004; Hewitt, 1997; Lijmbach, Margadant-Van Arcken, Van Koppen, & Wals, 2002; Malone, 2004).

Description of activities. The conservation educational module included 15 activities, which students in the experimental group completed either during class or outside school, and either individually or in groups. A short description of the activities applied to the experimental group follows. Activity 1 involved a slide presentation on basic ecological principles (i.e., environment, food web, biodiversity, endangered species, extinction). By using old postcards and family stories, students in Activity 2 researched how nesting beaches were 20-30 years ago and compared them with how they are today. Activity 3 involved a slide presentation on basic sea turtle biology and ecology, natural and human-induced threats, the role of nongovernmental organizations (NGOs) in sea turtle conservation, and the purpose of the NMPZ and local participation. In Activity 4, students ranked photographs of a pristine and a developed nesting beach and drew conclusions about which beach the turtles preferred. In Activity 5, students drew onto paper pictures of how the nesting beaches look today and how they visualized them to be in 20 years. For Activity 6, students wrote letters from the point of view of a turtle that had returned after many years to her natal beach and found it unsuitable for nesting. They described her disappointment and what she needed to be able to nest. Activity 7 involved a slide presentation on basic conservation measures and the purpose of the NMPZ. In Activity 8, students identified and analyzed the beliefs and values of players or stakeholders involved in the sea turtle issue (e.g., landowners, speedboat owners, local authorities, conservationists). In Activity 9, students wrote a letter to a local newspaper and to the Minister of Environment requesting effective measures for sea turtles and alternative solutions for landowners who had been affected by protection measures. Activity 10 involved a slide presentation on the concept of zoning within the NMPZ. In Activity 11, students picked out items (e.g., seashells, fishing nets, fishing hooks) from a box and explained how they related to the sea turtle issue. Activity 12 was a game in which students in a circle impersonated items that were related to sea turtles (i.e., sand, seashell, fisherman, lights, speedboat). The students on the circumference of the circle were connected by a ribbon to a student in the center of the circle identified as the sea turtle. The students on the circumference then explained their relationships to the turtle. In Activity 13, a questionnaire with five items was prepared by the students and completed by their families to record their opinions on the sea turtle issue. In Activity 14, students assumed the roles of stakeholders or players (i.e., landowners, conservationists) involved in the sea turtle issue and supported their interests in a debate held in the classroom. In Activity 15, students discussed and drafted the objectives of an NGO that they planned to establish with the aim of protecting sea turtles. Data collection and implementation of educational module. We obtained a permit from the Institute of Pedagogy and the Department of Education of the Ministry of Education to visit the schools. Normally, teachers were not present during the completion of questionnaires and the implementation of the activities (Richardson, Politikou, Terzidou, Maka, & Kokkevi, 2006).

Students within the experimental and control groups completed the same questionnaire for both the pretest and posttest measurements. Dimopoulos delivered the questionnaire to all classes. All participants completed the pretest questionnaire on average 18 days before we applied treatment to the experimental group. Our timing was similar to that of other researchers (Dettmann-Easler & Pease, 1999). On average, it took students 27.2 min to complete the pretest questionnaire.

Dimopoulos implemented 13 of the 15 activities during seven visits to every class (13 teaching hr in sum) of the experimental group. Following instructions that he gave in class, students conducted the two remaining activities (Activity 2 and Activity 13) at home. However, they discussed results at school with Dimopoulos. Homework is known to stimulate interactions, interest, and knowledge transfer between parents and students (Vaughan, Gack, Solorazano, & Ray, 1999).

The students of both groups completed the posttest questionnaire an average of 63 days after we applied treatment to the experimental group. On average, it took students 24.2 min to complete the posttest questionnaire. Although many researchers have selected smaller periods of time that range from 3 days to 1 month for completion of posttest questionnaires (Ballantyne, Connell, & Fien, 1998; Powell & Wells, 2002; Randler, Ilg, & Kern, 2005), in the present study we preferred a longer period to assess the effects of the module, as other researchers have done (Dettmann-Easler & Pease, 1999; Hsu, 2004). Looy and Wood (2006) delivered a posttest questionnaire 8-12 weeks later to account for the possibility that simply completing a questionnaire on attitudes may trigger thought and discussion over time, thus affecting a participant’s attitudes.

Data Analysis

The unit of statistical analysis was the class because we applied the treatment to whole classes. Individual children in a class do not constitute independent experimental units because they are all taught by the same teacher and interact in various ways with each other (Leeming et al., 1993; Lindemann-Matthies, 2002, 2005). Similarly, other researchers have used class means as a unit of analysis (Culen & Volk, 2000; Powell & Wells, 2002; Smith-Sebasto, 2001).

Because the sample sizes were smaller than 20, and because three of the four dependent variables were skewed to the upper end, we used nonparametric statistics because they require fewer assumptions about population distribution (Agresti & Finlay, 1997; Foster, 2001). We used the Wilcoxon Signed Ranks test for within-subject comparisons and the Mann-Whitney U test for between-subjects comparisons. Other researchers have used nonparametric statistical tests to analyze sample sizes smaller than 20 (Gerakis, 1998; Randler et al., 2005).

We used Pearson correlation coefficient r to determine test- retest reliability of evaluation instrument. To express the extent to which the dependent variables varied together, the Spearman rank (rho) correlation, as a nonparametric statistical analysis, was used. It must be noted that correlation does not imply causation (Foster, 2001). The SPSS statistical package was used for data analysis (Howard, 2002; Randler et al., 2005), and a priori alpha of .05 was established for statistical significance (Bright & Tarrant, 2002; Hsu, 2004).

Results

Pretest Descriptive Statistics for Experimental and Control Groups

Because the Mann-Whitney test indicated that statistically significant differences did not exist on a pretest basis (Mann- Whitney U = 84.00, p = .244, for knowledge; Mann-Whitney U = 91.50, p = .394, for understanding and concern; Mann-Whitney U = 109.00, p = .901, for locus of control; and Mann-Whitney U = 90.50, p = .371, for verbal commitment), we considered the experimental and control groups to be equal.

Pretest and Posttest Measurements for Experimental and Control Groups

The mean scores and standard deviations for each of the four dependent variables, before and after the treatment, for both the experimental and control groups are shown in Table 2. Pretest scores for both control and treatment groups were low on knowledge (M = 33.28, SD = 7.06 for the experimental group, and M = 29.55, SD = 7.99 for the control group) but were relatively high on the other three dependent variables (ranging from M = 77.08, SD = 7.91 to M = 85.29, SD = 6.13). All posttest mean scores for both groups were higher on all variables except the variable of verbal commitment.

On the knowledge score, the experimental group showed a 90.87% increase (pretest M = 33.28, SD = 7.06 and posttest M = 63.52, SD = 8.78), whereas the control group showed only a 9.68% increase (pretest M = 29.55, SD = 7.99 and posttest M = 32.41, SD = 8.61). On the variable of understanding and concern, the experimental classes showed a 1.06% increase, whereas the control group showed a 3.23% increase. On the variable of locus of control, the experimental group showed an increase of .98%, whereas the control group showed an increase of 1.15%. In contrast, the verbal commitment scores showed a decrease of 1.22% in the experimental group and one of 1.49% in the control group.

The Wilcoxon Signed Ranks Test indicated that only the knowledge variable differed significantly between the pretest and posttest measurements both within the control group (Z = .2.009, p = .045) and the experimental group (Z = .3.516, p = .0005; Table 2). However, a Mann-Whitney test between posttest scores of both groups showed that the class mean scores for knowledge (Mann- Whitney U = .000, p = .0005) were significantly higher in the experimental group than in the control group (Table 3). Consequently, only the null hypotheses that knowledge scores would not change in the control and experimental groups were rejected. Hence, from the preceding data, the authors can infer that, overall, the educational intervention had a significant effect on the knowledge score and no statistically significant effect on the three other variables of the experimental group.

Correlations Between Dependent Variables Before and After Treatment

Correlations between scores on the four dependent variables during the first administration of the questionnaire were not statistically significant in both the control and experimental groups. Correlations remained statistically nonsignificant for the control group also after second administration of the questionnaire. However, for the experimental group, significant and positive correlations emerged between the variable of knowledge and that of understanding and concern (r = .638, p = .008, significant at the .01 level, two-tailed), and between the variable of understanding and concern and that of locus of control (r = .540 and p = .031, significant at the .05 level, two-tailed).

In other words, in the experimental group, after treatment, as the score of knowledge increased, so did the score of understanding and concern. Similarly, as the score of understanding and concern increased, so did the score of locus of control.

Discussion

Knowledge

The results indicate that the conservation education module had a significant effect on the knowledge of fifth and sixth graders in Zakynthos concerning basic sea turtle biology and existing protection measures within the NMPZ. Knowledge scores of the experimental group rose by 90.8%. This finding is consistent with those of other researchers who have evidenced significant gains of knowledge following 1-5-day programs among 12-13-year-old students (Bogner, 1998); a 1.5-hr program on endangered species for elementary school students (Ballantyne et al., 1998); and a 4- day visit to a bird sanctuary for 6-15-year-old students (Blanchard, 1995). In counterpoint, other researchers have not observed significant gains in knowledge after educational programs (cf. Edwards et al. as cited in Leeming et al., 1993). Unexpectedly, students of the control group scored significantly higher (increase by 9.68%, p = .045) on knowledge during posttest administration of questionnaire. However, this is congruent with the results from Randler et al. (2005). Students are known to perform better on posttest simply because they are more familiar with the test the second time (Bogner, 1998; Gerakis, 1998). It is also possible that some teachers discussed the answers to the questions in class after the first administration.

Attitudes

The treatment did not yield a significant change in the scores of the attitude variables in the experimental group. Similarly, we observed nonsignificant changes in the control group. This finding may be attributable to the fact that pretest attitude scores were already high (Gerakis, 1998; Leeming et al., 1993). The overall result of this study is congruent with the findings of other studies with high pretest attitude scores (Ballantyne et al., 1998; Smith- Sebasto & Semrau, 2004). Significant changes in attitude scores after educational programs are observable only in cases in which the level of positive attitude in the pretest is generally low (Blanchard, 1995; Hsu & Roth, 1999; Wilson & Tomera, 1980).

The decrease in the posttest scores of the variable of verbal commitment is attributable to the facts that knowledge is likely to lead to moderate positions rather than extreme positions (Ramsey & Rickson, 1976) and that awareness of personal impacts may be empowering but can be overwhelming too (Meyer & Munson, 2005). It is possible that a high cognitive level may lead to a better understanding of the social implications surrounding the conservation of sea turtles in the NMPZ; therefore, it may make students more realistic in how they formulate and express their positions.

Correlations between the four variables before and after treatment indicate a pretest pattern in how the experimental group’s students replied. It seems that while students, after treatment, acquired more knowledge, they became more defensible in their understanding and concern for the sea turtle issue and in their belief that their personal actions can influence sea turtle conservation. This explanation by no means denotes causality. It simply implies a simultaneous change in three dependent variables. In the present study, the reinforcement of students’ understanding and concern and their locus of control were consistent with those of other studies (e.g., Newhouse, 1990) in which participants’ completion of an environmental study course did not lead to significant changes in attitudes; it did, however, lead to a defensible attitude.

The point that we make in this study is that when attitude scores are already high, the application of an educational program that may lead to a significant increase in knowledge level may strengthen and further reinforce the students’ attitudes. In other words, students may better support and explain their existing positive attitudes regarding an environmental issue as their level of knowledge improves.

Conclusion

The conservation educational module, designed according to the extended case study approach and in accordance with the General Teaching Model, proved to be successful in increasing knowledge among elementary students on Zakynthos and in reinforcing their locus of control and their understanding and concern regarding the sea turtle issue. Because these are considered to be behavior predictor variables (Hungerford & Volk, 1990), they may in turn contribute to positive behavior toward the sea turtles and the NMPZ.

Therefore, the NMPZ Management Agency can use the module on a long-term basis to create future citizenry that will be knowledgeable and motivated to support the purposes of the National Park. Long-term and systematic implementation of EE modules is a prerequisite for effective learning results (Bogner, 1998) and in fostering pro-environmental attitudes (Lindemann-Matthies, 2005). Further, Chawla and Flanders Cushing (2007) claimed that educational programs for elementary school students should focus on local environmental issues and have an extended duration. Children, as present and future citizens, have concerns for the current and future environments: They are affected by environmental decision making and have a right to be involved in it (Barratt Hacking, Barratt, & Scott, 2007).

Of course, EE alone does not suffice to ensure the achievement of the purposes of the NMPZ. However, when combined with comprehensive governmental policies, EE may prove to be a significant contributing factor. The results can be better achieved if the Management Agency creates a partnership with local society, teachers (Bainer, Cantrell, & Barron, 2000), and NGOs (Cardwell & Mata, 2002; Fien, Scott, & Tilbury, 2002). In the long run, EE can influence local attitudes and behaviors and create a new social structure with either simple or more complex models of governance, local participation, and local involvement for managing protected areas sustainably.

Environmental researchers and educators should consider the following constraints: (a) The present study focused on only four of the Hungerford and Volk (1990) predictor variables, and this limitation may affect generalizability of results, and (b) the evaluation was based solely on the quantitative approach.

Notwithstanding the positive results of this study, additional research is necessary to address the above constraints. Such research may include the following: (a) investigating the remaining predictor variables of the Hungerford and Volk (1990) behavior model to get the full picture of the students’ emotional and cognitive world; (b) further testing the questionnaire to improve its capacity to record the knowledge and attitudes of students, because questionnaires improve through constant trials and changes (Stokking, van Aert, Meijberg, & Kaskens, 1999); (c) combining qualitative and quantitative evaluation approaches for complementary outcomes (Bamberger, Rugh, Church, & Fort, 2004); and (d) constantly evaluating the module, because educational programs should always evolve and improve (Fien, 2001; McDuff, 2002).

The present study provides for environmental educators the methodology for designing and evaluating an effective conservation educational module for students. The module can be used as a model for designing and evaluating EE programs for endangered species in protected areas. This use is of utmost importance because protected areas have just recently been established in Greece, and local community support is much needed for their success. EE programs starting at an elementary school level may not only be a long-term investment in creating pro-environmental citizens but may also have immediate results, because children are known to directly affect behaviors of their parents (Ballantyne, Fien, & Packer, 2001). Therefore, when implemented by the NMPZ systematically and over a long period in all elementary schools of Zakynthos, the conservation educational module may eventually contribute to supporting better environmental governance by broadening stakeholder acceptance and involvement at a local level.

ACKNOWLEDGMENTS

The authors thank the Sea Turtle Protection Society of Greece for inspiring and supporting this study; the Institute of Pedagogy and the Department of Education of the Ministry of Education for issuing the permit to conduct the study in the elementary schools of Zakynthos; Mrs. Chatzisavas, Department of Elementary Education of Zakynthos; and Mr. D. Visvardis, Environmental Education, Department of Elementary Education of Zakynthos, for their wholehearted support. The authors also thank the teachers of the schools that cooperated for the purpose of this study.

NOTES

This article was written as part of the doctoral dissertation of Dimitrios Dimopoulos at the Aristotle University of Thessaloniki in Greece.

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Dimitrios Dimopoulos is a biologist and an active member of a nongovernmental organization involved in sea turtle conservation in Greece. Stefanos Paraskevopoulos is an associate professor of environmental education in the Department of Special Education at the University of Thessaly, Greece. John D. Pantis is an associate professor in the Department of Ecology at the Aristotle University of Thessaloniki, Greece.

Health

Hereditary Benign Intraepithelial Dyskeratosis: An Evaluation of Diagnostic Cytology

Written By: Sam Savage

Published Date: August 30, 2008 Last Edited: August 30, 2008

By Cummings, Thomas J Dodd, Leslie G; Eedes, Christopher R; Klintworth, Gordon K

Context.-Hereditary benign intraepithelial dyskeratosis (HBID) is a rare autosomal dominant disorder characterized by elevated epibulbar and oral plaques and hyperemic conjunctival blood vessels. The condition is predominantly seen in Native Americans belonging to the Haliwa-Saponi tribe located in northeastern North Carolina. Objective.-To determine whether HBID can be diagnosed using cytologic preparations of the conjunctiva, and whether the cytologic findings correlated with the genetic linkage involving a duplication in chromosome 4 (4q35).

Design.-Cytologic preparations from conjunctival brushings in patients afflicted with HBID and from unaffected blood relatives with normal conjunctivas were compared in a masked fashion. Cytologic observations were correlated with molecular genetic analyses.

Results.-Papanicolaou-stained preparations from the conjunctiva showed the typical cytologic features of HBID, including rounded squamous epithelial cells with dense homogenous orange cytoplasm and hyperchromatic, pyknotic, or crenated nuclei. All cases with the diagnostic cytologic findings of HBID had a duplication in chromosome 4 (4q35).

Conclusion.-HBID is an entity with distinct clinical, histopathologic, and genetic features. The results of this study indicate the diagnosis can also be supported in an appropriate clinical setting when adequate epibulbar cytology preparations are obtained and the characteristic genetic attributes are present.

(Arch Pathol Lab Med. 2008;132:1325-1328)

Hereditary benign intraepithelial dyskeratosis (HBID) (Mendelial Inheritance of Man [MIM] identification 127600) is a rare autosomal dominant disorder characterized by elevated epithelial plaques located on the ocular and oral mucous membranes. The condition, which was first documented by von Sallmann and Paton,1,2 occurs almost exclusively in individuals who reside in the northeastern section of North Carolina. Most affected persons are members of the Native American Haliwa-Saponi tribe (formerly referred to as Haliwa Indians) or are descendents of them. The ethnic group takes the Haliwa portion of its name from Halifax and Warren counties in North Carolina, where most of the population live. Saponi denotes the “Red Earth People,” one of the original ancestral tribes from which the people descended. Currently, approximately 3000 members are enrolled in the clan. Rare cases of HBID have been described outside of North Carolina. One such individual lived in Philadelphia her entire life but was of Haliwa-Saponi ancestry.3,4 Two individuals from Texas were diagnosed with HBID, but their ancestry remains uncertain.5

HBID is characterized by bilateral elevated white to grayish epithelial plaques on the exposed perilimbal conjunctiva, sometimes with encroachment of the cornea (Figure 1). The conjunctival leukoplakic lesions are readily moveable over the underlying tissue, and the remainder of the ocular examination is typically unremarkable. The epibulbar blood vessels are commonly hyperemic and have given rise to the common colloquial term for HBID: red eye disease. This bloodshot appearance has caused discrimination against some affected individuals in job employment and in social interactions. Persons not familiar with HBID frequently assume from the appearance of the eyes that alcohol, drug use, or an ocular infection is responsible for the affliction. Clinically, ocular involvement ranges from mild asymptomatic lesions to extensive plaques that involve much of the cornea and bulbar conjunctiva and impaired vision.6

HBID has an apparent seasonal variation, becoming worse in the spring and summer and subsiding in the cooler weather of autumn. According to affected individuals and their family members, the plaques can shed spontaneously, but this has never been documented photographically. Although the ocular lesions of HBID can resemble malignant neoplasms clinically, and they invariably recur following surgical excision, they do not invade the underlying tissue and remain localized to the conjunctiva and cornea. Furthermore, malignant transformation has never been documented.

The histologic features of surgically excised lesions of HBID include hyperplastic stratified squamous epithelium with an overlying multilayered parakeratotic mantle containing rounded cells with dense cytoplasm and pyknotic nuclei. A mild to moderate lymphoplasmacytic infiltrate within the subepithelial stroma beneath the affected epithelium is typical (Figure 2, A).1-9 Scattered throughout the hyperplastic epithelium from the basal layer to the surface are rounded isolated cells with pyknotic or crenated nuclei surrounded by dense eosinophilic cytoplasm, lending the appearance defined as intraepithelial dyskeratosis in the term HBID (Figure 2, B). The adjacent conjunctival epithelium may vary from normal to a thickened stratified squamous epithelium with or without goblet cells. An ultrastructural study documented the presence of vesicular bodies and cytoplasmic tonofilaments and an absence of cellular interdigitations and desmosomes in dyskeratotic cells.10

MATERIALS AND METHODS

Field trips to the Haliwa-Saponi Native American tribe and to another large family in northeast North Carolina with allegedly no Native American ancestry were undertaken. During these field trips, all family members were examined after providing written informed consent according to a Duke University Institutional Review Board- approved protocol. The conjunctiva was briefly brushed with a CytoSoft Brush (1 CP-5B, Medical Packaging Corp, Camarillo, Calif) for cytologic examination in consenting participants after instilling 1% xylocaine topical local anesthetic. The specimens were smeared on glass slides, fixed with Shannon Cell Fixx Spray Fixative (Thermo Electron Corp, Watham, Mass), and stained with the Papanicolaou method.

Cytologic preparations were obtained from the conjunctiva of 40 individuals (Table), and 123 slides were prepared from this material for microscopic evaluation. A total of 26 individuals were female, 14 were male, and their ages ranged from 5 to 67 years. As previously described, patients were clinically classified by a board- certified ophthalmologist as “definite” HBID (conjunctival erythema in both eyes and plaque

RESULTS

The cytologic preparations from 15 patients with a clinical impression of definite HBID disclosed rounded squamous epithelial cells with dense homogenous orange cytoplasm and hyperchromatic oval or crenated nuclei (Figure 3, A and B). Cellular halos or cytoplasmic inclusions were not identified. Small lymphocytes were occasionally seen (Figure 3, C). All 15 patients with clinically definite HBID demonstrated 3 alleles for chromosome 4q35 markers.

Three of 4 subjects with a clinical impression of probable HBID manifested the aforementioned cytologic features of HBID, and 1 was cytologically normal. The 3 with the cytologic features of HBID also demonstrated 3 alleles for chromosome 4q35, and the cytologically normal individual did not.

Of 5 patients with unknown but suspected HBID, 3 had cytologic features of HBID, and 2 were cytologically normal. Those with the cytologic features of HBID exhibited 3 alleles for chromosome 4q35 markers, and the 2 with normal cytology did not.

Cytologic brushes of the conjunctiva of the 16 individuals with a clinically normal conjunctiva disclosed squamous cells with round to oval nuclei with a delicate chromatin pattern and lightly eosinophilic or transparent cytoplasm. These normal cells were generally polygonal or elongated, unlike the rounded cells seen in HBID. Unlike the malignant cells of squamous cell carcinoma, the ratios of nuclear to cytoplasmic areas in the cells of HBID were low, and the cells did not have the atypical nuclei of malignant neoplasms with irregular membranes or prominent nucleoli. All clinically normal patients were negative for the chromosome 4q35 markers. Thus, the correlation was 100% between the cytology and genetic findings.

COMMENT

HBID is a clinicopathologic entity that exhibits characteristic clinical, histopathologic, and genetic features. The typical clinical features are confirmed histologically in severe cases that affect vision and whereby the lesions are surgically excised. Although at the current time there are no recommended indications to use cytology and genetic studies for diagnostic purposes, hypothetically they might serve as possible alternatives if there were to be individuals in the future with either an uncertain diagnosis or in whom an excisional biopsy might not be indicated. Our findings indicate that HBID can be diagnosed in an appropriate clinical setting when the characteristic cytologic abnormalities are present, and confirmation of the characteristic cytology was supported in all cases by the presence of the genetic abnormality involving duplication in chromosome 4q35. The HBID gene has been mapped to the telomeric region of chromosome 4 (4q35) with a peak logarithm of the odds (LOD) score of (z) = 8.97. All affected individuals have had 3 alleles for 2 tightly linked markers, D4S1652 and D4S2390, suggesting that HBID is caused by a genetic duplication at this locus.11 A candidate gene in the region of the duplication is the large (15-kb) human homolog of the Drosophila fat gene, an epithelial gene that can promote abnormal epithelial cell proliferation in Drosophila12,13 and which is thought to function in mammalian cell communication. Even though affected members of the Haliwa-Saponi tribe and persons with no apparent Native American ancestry with HBID do not share a known common ancestor, the finding of an identical duplicated haplotype in these individuals strongly suggests a common ancestral founder.

The hereditary, benign, and intraepithelial components of HBID are well established, and although the responsible gene has yet to be identified, the disorder appears to involve the process of dyskeratosis, which is the abnormal or premature keratinization of individual keratinocytes that results in the formation of cells with a dense hypereosinophilic cytoplasm. Dyskeratocytes can be seen in a variety of benign and malignant processes, including condylomas and squamous cell carcinoma.

HBID shares some cytologic similarities with the genetically unrelated, autosomal dominant Darier-White disease (MIM 124200) and the white sponge nevus of Cannon (MIM 193900), which may also manifest dyskeratotic cells in benign oral mucosa. In contrast to HBID, however, Darier-White disease and the white sponge nevus of Cannon both spare the conjunctiva. Darier-White disease is characterized by suprabasal acantholysis of the epidermis, with the formation of suprabasal clefts. The dyskeratotic cells display central, homogenous, basophilic, pyknotic nuclei surrounded by a clear halo, with a shell of basophilic dyskeratotic material adjacent to the halo.2,8,14-16 The dyskeratocytes are referred to as corps ronds when they are localized within the stratum spinosum, and as grains when they are located within the stratum corneum. Although one report described the occasional finding of perinuclear halos in HBID,2 we have not observed them in any of our cytologic preparations from affected persons. The white sponge nevus of Cannon is characterized by surface parakeratosis and hydropic swelling of the epithelial cells that extends into the rete ridges but spares the basal layer.17,18 The white sponge nevus cells exhibit perinuclear and paranuclear dense eosinophilic intracytoplasmic inclusions composed of disorganized aggregates of cytokeratin filaments and clearing of peripheral cytoplasm. 19

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11. Allingham RR, Seo B, Rampersaud E, et al. A duplication in chromosome 4q35 is associated with hereditary benign intraepithelial dyskeratosis. Am J Hum Genet. 2001;68:491-494.

12. Dunne J, Hanby AM, Poulsom R, et al. Molecular cloning and tissue expression of FAT, the human homologue of the Drosophila fat gene that is located on chromosome 4q34-q35 and encodes a putative adhesion molecule. Genomics. 1995;30:207-223.

13. Mahoney PA,Weber U, Onofrechuk P, et al. The fat tumor suppressor gene in Drosophila encodes a novel member of the cadherin gene superfamily. Cell. 1991;67:853-868.

14. Gorlin RJ, Chaudry AP. The oral manifestation of keratosis follicularis. Oral Surg Oral Med Oral Pathol. 1959;12:1468-1470.

15. Sehgal VN, Srivastava G. Darier’s (Darier-White) disease/ keratosis follicularis. Int J Dermatol. 2005;44:184-192.

16. Cooper SM, Burge SM. Darier’s disease: epidemiology, pathophysiology, and management. Am J Clin Dermatol. 2003;4:97-105.

17. Cannon AB. White sponge nevus of the oral mucosa (naevus spongiosus albus mucosae). Arch Dermat Syph. 1935;31:365.

18. Simpson HE. White sponge nevus: report of three cases. J Oral Surg. 1966; 24:463-466.

19. Morris R, Gansler TS, Rudisill MT, Neville B. White sponge nevus: diagnosis by light microscopic and ultrastructural cytology. Acta Cytol. 1988;32:357-361.

Thomas J. Cummings, MD; Leslie G. Dodd, MD; Christopher R. Eedes, MB,ChB; Gordon K. Klintworth, MD, PhD

Accepted for publication January 10, 2008.

From the Departments of Pathology (Drs Cummings, Dodd, and Klintworth) and Ophthalmology (Drs Cummings and Klintworth), Duke University Medical Center, Durham, NC; and PathCare, Cape Town, South Africa (Dr Eedes).

The authors have no relevant financial interest in the products or companies described in this article.

Reprints: Gordon K. Klintworth, MD, PhD, Duke University Eye Center, Durham, NC 27710 (e-mail: [email protected]).

Health

Adverse Event Detection in Drug Development: Recommendations and Obligations Beyond Phase 3

Written By: Sam Savage

Published Date: August 30, 2008 Last Edited: August 30, 2008

By Berlin, Jesse A Glasser, Susan C; Ellenberg, Susan S

Premarketing studies of drugs, although large enough to demonstrate efficacy and detect common adverse events, cannot reliably detect an increased incidence of rare adverse events or events with significant latency. For most drugs, only about 500 to 3000 participants are studied, for relatively short durations, before a drug is marketed. Systems for assessment of postmarketing adverse events include spontaneous reports, computerized claims or medical record databases, and formal postmarketing studies. We briefly review the strengths and limitations of each. Postmarketing surveillance is essential for developing a full understanding of the balance between benefits and adverse effects. More work is needed in analysis of data from spontaneous reports of adverse effects and automated databases, design of ad hoc studies, and design of economically feasible large randomized studies. (Am J Public Health. 2008; 98:1366-1371. doi:10.2105/AJPH.2007.124537)

REPORTS OF DEVASTATING adverse events suffered by patients create public doubt about whether drugs are safe. Developing “safe” drugs presents a high hurdle, because every drug carries potential for harm (“risk”). Drug safety cannot be considered an absolute; it can only be assessed relative to the drug’s benefits. At the time of marketing, however, the amount of information on benefits and risks, especially long term, is relatively small, and often based on highly selected populations with respect to age, comorbidities, use of concomitant medications, and other factors.

We discuss drug development and assessment of adverse events and offer recommendations for continued evaluation of benefits and harms after a medicinal product becomes marketed.

DRUG DEVELOPMENT PROCESS

The drug development process, from discovery to market, is long and costly.1,2 Rigorous processes are in place during clinical trials that protect the safety of study participants and also ensure that collection of adverse event data is complete. This completeness, coupled with the randomized design, also helps develop an understanding of the benefits and side effects of a new medicine by strengthening the validity of the comparisons between the new drug and the comparator, which could be a placebo or an active therapy for the condition under study.

Preclinical Testing

Prior to being studied in humans, a drug candidate undergoes an extensive series of laboratory and animal tests to study possible therapeutic and adverse effects. Preclinical studies are also used to characterize the pharmacokinetics and pharmacodynamics of the drug, including absorption, distribution, metabolism, excretion, and persistence of pharmacological effects.

A preclinical evaluation of safety includes in vitro and in vivo studies in animals to search for unintended pharmacological and toxic effects at the wholeanimal level and on specific organs and tissues. In addition, carcinogenicity and mutagenicity studies are conducted, along with specific tests of effects on cardiac rhythms. If results suggest the product can be used safely and may produce the desired beneficial effects, the stage is set for testing in humans. There is generally a low threshold for rejecting drugs for safety reasons; the assumption is that unfavorable preclinical results are predictive of human safety problems (although the validity of this assumption may be questionable). Most drug candidates, whether for safety concerns or insufficient potential for efficacy, will never complete the development process; only 1 of every 5000 to 10 000 compounds that enter preclinical testing will become approved for marketing.3

Application for Study and Clinical Testing

US law requires manufacturers to petition the US Food and Drug Administration (FDA) to allow the study of investigational drugs or of new indications or dosages for approved drugs. This process ensures that the FDA can make sponsors and investigators aware of potentially unsafe uses of drugs before studies in humans are initiated.

Traditionally, clinical testing of investigational drugs proceeds in a phased fashion. We describe the research program and refer to human participants in a clinical trial as participants and users of medicines outside of a research setting as patients.

Phase-1 studies evaluate the safety and pharmacology of a compound to determine a range of tolerable doses; preliminary pharmacodynamic data, involving small numbers of participants (20- 100), are sometimes obtained. Phase 2 looks for initial indications of efficacy and more data on safety among somewhat larger numbers of participants (typically 100-500), as well as optimal dosage and method of drug delivery. Phase-3 studies are the final step in obtaining the primary evidence of efficacy and safety prior to seeking drug approval. These studies range widely in size (dozens to thousands of participants), depending on the prevalence of the condition being treated and the rate of the event of primary interest, and usually involve random assignment of participants to new treatment or “control” treatment in a blinded manner, to allow an unbiased comparison of both the efficacy outcome and the adverse event profiles in the treatment and control groups. These studies may test one or several doses of the compound.

Approval to market a drug often involves commitments by the sponsor to perform additional studies. These may include randomized or cohort studies that examine the benefits and potential harms of the new drug in a different population or under somewhat different conditions from those originally studied, or special monitoring in a high-risk population-often by establishing a registry of such patients. These studies are sometimes designed to define more carefully an identified signal not adequately quantitated in the premarketing setting.

One such example involves a postmarketing commitment to conduct a prospective, multicenter registry of 4000 adult patients with psoriasis treated with infliximab in the United States. In some of the clinical trials of drugs in this class, including infliximab, increased incidences of some cancers and serious infections have been observed in other populations, such as individuals with rheumatoid arthritis. Given these prior observations, a registry was initiated to characterize and assess the incidence of malignancies and serious infections as well as other adverse events of interest in individuals treated for psoriasis.4,5 In addition to these measures, health authorities often require the submission of a risk management plan with the marketing application to improve detection or to mitigate potential harms for new medicinal products.

LIMITATIONS ON DETECTING RISK

In phase-3 programs that enroll 3000 participants or more, even for adverse events occurring at a frequency of 1 in 1000, at least one such event will probably be observed. However, observing an adverse event is not equivalent to identifying that event as an adverse reaction to the drug. To do the latter, one needs to show that the rate of the event in those treated with the drug is greater than the rate in the control group.

An elementary principle in the design of studies is that the number of participants needed to detect an increased rate of an adverse event depends on how confident one wants to be of identifying a risk of a given magnitude (i.e., the desired statistical power). For example, with 1000 participants, we have a greater than 80% chance of detecting a true doubling in the rate of an adverse event from 5% to 10%, but we have far less confidence (only a 17% chance) in detecting a doubling from 1% to 2%. We would need to study at least 50000 participants to achieve 80% power of detecting a doubling of a 0.1% event rate (Table 1). Although such an event rate seems very small, if the treatment is used by millions of individuals, the number of excess adverse events resulting from an increase to 0.2% will be substantial.

Thus, premarketing studies of new pharmaceuticals cannot reliably detect rare, but potentially important, adverse events. Moreover, events that take time to be observed (i.e., that have a latency period) may not be seen in trials of relatively short duration, which are typical in a development program. Drugs are therefore, as a rule, made available for public use before rare but potentially serious reactions have been identified and their probability quantified. Moreover, the adverse event profile of the drug, which is usually well defined in relatively small, carefully controlled, premarketing studies, may not adequately reflect the profile that will emerge with widespread use after approval, for several reasons: (1) study participants may represent a somewhat healthier and select subset of all participants, (2) they may receive better care than “real-life” patients, (3) study drugs will (of necessity) be given for shorter durations in studies than in postmarketing use, and (4) neither concomitant medications administered in clinical trials nor comorbidities of study participants will represent all those possible outside the trial setting.

ADVERSE EVENTS AFTER MARKETING

Data on adverse events after marketing of the drug include spontaneous case reports, computerized claims or medical record databases, and data collected in prospective postmarketing studies.7 Such systems have been extensively reviewed.8-16 Clearly, a comprehensive drug safety program also includes evaluation of other relevant clinical findings (e.g., laboratory test results, vital signs, cardiac or other specialized testing) that we do not address. Spontaneous Reporting

Spontaneous reports refer to unsolicited reports of clinical observations originating outside of a formal clinical study that are submitted to drug manufacturers or regulatory agencies.16 Some of the events will represent true adverse effects of treatment; many will be symptoms of the disease being treated, or coincidental events that are unrelated to disease or treatment.

The most important reports are either new (i.e., not included in the product label), rare, serious events associated with the drug’s use, or recognized adverse events occurring at a higher than anticipated rate. Other reports may reflect medical errors, inappropriate dosing or other misuse of the drug, and product defects. 17 Spontaneous reporting systems can “signal” emerging problems and thereby have the potential for uncovering previously unknown adverse reactions. Because these reports are written by health care professionals whose clinical judgment is valued, the companies spend a great deal of time analyzing individual reports and any patterns underlying these reports.

The limitations of spontaneous reports include substantial and unquantifiable underreporting (thus, such systems do not produce accurate estimates of incidence for a given adverse event) as well as lack of verification of important clinical details.

Adverse events may be spontaneously reported at disproportionately high rates at various times in the drug’s marketing life cycle. For example, health care professionals and patients are more inclined to report adverse reactions when a drug is newly introduced (Weber effect),18 when the events are medically very significant, when the event occurs very close in time to the administration of treatment, or when negative publicity emerges, such as the increased number of cases of rotavirus vaccine- associated intussusception reported after the Centers for Disease Control and Prevention recommended suspension of the rotavirus vaccination program.19

Sophisticated statistical approaches to formalize the “signal generation” aspect of spontaneous reports, aimed at determining when a particular type of adverse event is reported disproportionately relative to other adverse events associated with a given drug, have been developed. Such systems, often using Bayesian statistical methods, are used and evaluated by safety reviewers employed by regulatory authorities and pharmaceutical companies, as well as by an increasing number of academic investigators. 20,21 These methods may be useful as automated searching tools, especially as the number of spontaneous reports increases.

Once a signal is detected, the correct course of action is usually not obvious. If the signal is compelling-that is, if the increase in risk seems very large and is consistent with the known mechanism of action of the drug, the attribution to the drug is certain, and the event in question is clinically significant-there may be a need to initiate action immediately. (For very severe events, immediate action may be warranted even if they are not obviously related to the drug’s mechanism of action.) If the signal is suggestive but too preliminary for immediate action, a more rigorous follow-up investigation may be needed to support taking any action. The dilemma is that if action comes too late, more people may suffer harm; if too early, people may stop taking beneficial medications unnecessarily.

In some cases, preliminary analysis of adverse event rates may suggest an apparent risk, although ultimately that risk could be dismissed as artifactual. For example, preliminary review of data from the Vaccine Adverse Event Report System showed that higher rates of serious adverse events were reported for children who received a specific brand of recombinant hepatitis B vaccine; subsequent analysis from a retrospective cohort study showed that there was no difference in rates of adverse events for the 2 vaccines.22 Signals from spontaneous reporting therefore need to be interpreted very cautiously.

Electronic Databases

Electronic databases are broadly classified as based on claims or on medical records. Claims-based databases, such as Medicaid- Medicare in the United States, are usually set up by health maintenance or other health insurance organizations, or by government programs, and contain useful information on reimbursable expenses (prescriptions, hospitalizations), often with diagnoses from a definable population of patients. Their use is limited by lack of clinical detail, necessitating the access of other sources of information, such as hospital charts, to obtain further information.23 Such databases often provide little information on outpatient events, including deaths. Studies using these databases can take substantial time to complete if they involve obtaining information from the supplemental sources described, and therefore cannot usually provide a rapid “check” on a worrisome (but very possibly false) signal.8

Medical practice databases contain patient medical records and prospectively recorded information on medical events, such as prescriptions, previous history, diagnoses, and test results. One widely used database for pharmacoepidemiological research is the General Practices Research Database in the United Kingdom.11 This database is a unique resource because it includes very detailed medical information, symptoms, and signs in a well-defined, representative, and stable population, and it is also validated (i.e., information on diagnoses and on prescriptions has been found to agree with that recorded on paper charts or provided by physicians). It is, however, limited with respect to exposures to recently marketed drugs and may be therefore better suited to studying older, well-established drugs or drug classes. Another limitation is the duration of patient follow-up, which tends to be only a few years.23

Medical practice data sets are not designed to collect specific safety information with clear definitions. For example, differences among physicians in how a particular clinical presentation is coded in an insurance claim can make it difficult to identify all cases of a particular end point without also identifying spurious cases. In many databases, only the fact that a prescription was written and filled may be recorded. Whether the patient was actually taking the medication in the clinically relevant time period preceding the event cannot always be reliably determined; thus, assumptions about timing and adherence generally need to be made to infer a given patient’s exposure status.

The recently enacted Food and Drug Administration Amendment Act (or FDAAA; Public Law 110-85, signed into law September 27, 2007) calls for the establishment, under the auspices of an independent foundation, of a database of health insurance claims data for 100 million people by July 2012. This database is to be used to generate signals for further investigation.

Ultimately, a comprehensive health care database, including all interactions between an individual and the health care system (outpatient and inpatient visits, laboratory and other diagnostic results, and prescriptions), could provide the necessary breadth and depth for assessing safety and effectiveness in actual clinical practice. Conceivably, specific additional measures of effectiveness (e.g., patient- or physician-reported measures of symptoms) might be included as supplemental items in the electronic data capture systems that would give rise to a truly comprehensive database.

Observational Studies

Observational studies (typically, cohort or case-control designs), which do not include an intervention, can provide considerable information on the probability of specific adverse events.

Cohort studies. Cohort studies evaluate individuals who have a certain condition (e.g., epilepsy) or receive a particular treatment (e.g., anti-epileptic drug) over time. Their experience may be compared with that of others who are not affected by the condition under investigation, or are exposed to medications other than the one of interest. Registry is another name for a cohort study, which may be disease based (e.g., epilepsy) or product based (e.g., individuals with any condition who are prescribed a particular anti- epileptic medication).

Cohort studies may or may not include a comparison group. For example, one could estimate the incidence of cancer in participants with rheumatoid arthritis, with or without comparing that incidence to the rate of cancer among those without rheumatoid arthritis. Similarly, one could estimate the risk of cancer in a cohort of participants with rheumatoid arthritis who are exposed to a particular rheumatoid arthritis medication, with or without studying participants who are exposed to other rheumatoid arthritis medications. Omitting a comparison group, however, can make it difficult to interpret rates observed in a single group, because there is no set reference rate determined by using similar methods of data collection for different groups.

Even when there is a comparison group, cohort studies are not as reliable for making comparisons as randomized controlled studies, because the 2 groups of participants in a cohort study may differ in ways other than in the variable under study. For example, if more severely ill rheumatoid arthritis participants are selectively prescribed a particular medication, their cancer risk may differ because of the medication or some other factor related to the severity of the underlying illness. Statistical “adjustment” for those differences may not be sufficient, because there may be important unknown or unmeasured selection factors that contribute to the observed outcomes. When adverse events, such as cancer, occur infrequently or develop slowly, large numbers of participants, long- term follow-up, or both are required. Case-control studies. In case- control studies, information is collected retrospectively from “cases” (participants who already have a certain condition) and “controls” (those who do not have the condition). This design can assess whether certain characteristics are associated with the specific condition or adverse event being studied.

Case-control studies are most appropriate when the event rate is low,23 because the number of participants required is far smaller than would be needed for a cohort study. This efficiency stems from identifying the cases after they occur and needing to study only a relatively small sample of noncases, rather than having to follow a large number of participants to observe development of cases in “real time.” The most important limitation of case-control studies is that a statistical relationship between an exposure and an outcome does not necessarily mean that the exposure caused the event. For example, participants with gastrointestinal bleeding may tend to have received H2-receptor blocker drugs more commonly than controls without gastrointestinal bleeding. Because these drugs are used for the prevention of such bleeding, an explanation could be that participants exhibiting early, subtle signs of bleeding are preferentially prescribed these medications. Other types of biases in these studies can also arise.24 Still, case-control studies are often the only feasible way to study the relationship between an exposure and a rare adverse outcome, and have been used to establish several important relationships, including those between use of diethylstilbestrol in mothers and vaginal cancer in their daughters, use of aspirin and Reye’s syndrome, and use of oral contraceptives and thromboembolic events.8

Large Simple Safety Trials

Large simple safety trials are conducted in larger numbers of participants than registration studies (typically, many thousands). They are considered when a product is to be used widely and when it is important to ensure that the risks of severe adverse events (usually not assessable in typically sized registration trials) are sufficiently low. Study conduct is facilitated by use of broad eligibility criteria consistent with the expected target population. Streamlined trial entry procedures and minimal data collection are essential to permit large studies without placing unacceptable burdens on investigators.12

A trial that compared ibuprofen with acetaminophen for treatment of fever in children is an interesting example of how a large trial can be done simply. The study was conducted when ibuprofen, a nonsteroidal anti-inflammatory drug, was proposed for over-the- counter use in children; this was at a time when there was relatively little pediatric experience with ibuprofen and concerns about the safety of antipyretics had been heightened by the association of aspirin with Reye’s syndrome. Primary outcomes were hospitalization for events known to be associated with use of nonsteroidal antiinflammatory drugs in adults (e.g., acute gastrointestinal bleeding, kidney failure, anaphylaxis) as well as Reye’s syndrome. Results from this large controlled trial of more than 84000 children showed no differences in the outcomes of interest25 and provided sufficient reassurance to support the move to over-thecounter status.

RECOMMENDATIONS

The solutions to the challenges of postmarketing evaluation of drug safety are complex and will require highly collaborative interactions among the FDA, other health authorities, and industry regarding new product labels and the development of epidemiological and statistical methodology for detecting and interpreting adverse event signals.26-30 Methods and resources for rapid collection of adverse event data and further study when necessary should be considered and specified before marketing.

To attain this goal, we recommend a variety of approaches that may need to be tailored to specific situations. For example, although all new drugs require careful monitoring, a drug that is the first to be used for a particular therapeutic purpose, that has a unique mechanism of action, or about which a safety question was raised during the development stage may need closer scrutiny. One approach involves more-systematic ascertainment of adverse events, which may include prospective follow-up of a defined cohort-either disease based or product based-such as is used in an observational study registry. This improved ascertainment could be complemented by use of claims databases, but that use should be accompanied by refinement of methodology for monitoring data and detecting signals and enhancement of availability of electronic data to facilitate rapid study, with careful attention to ethical and legal considerations. For products that are widely used in fundamentally healthy populations, even low rates of serious adverse events may affect large numbers of people. In such cases, if the adverse events are clinically important, expanded simple trials, preferably involving randomization, might be considered; all adverse events, or a specific set of adverse events of concern, would then be the primary or coprimary outcome measures.

All of the aforementioned measures will come at a price. The additional financial and staff resources at the FDA that the Institute of Medicine has recommended31 will be difficult to achieve in the current government fiscal environment. The Food and Drug Administration Amendment Act provides additional funding to the FDA, but the resources proposed-for example, for the creation of the very large claims database-are likely to be inadequate and may require public-private partnerships. Such partnerships should fully engage all stakeholders-especially industry, academic, and regulatory scientists-in methodological discussions.

Greater drug company expenditures for more and larger studies may mean higher drug prices or possibly a declining rate of new drug development. Lastly, greater concern about the balance of a drug’s benefits and potential harms may mean longer delays until new drugs become available, unless there is public acceptance of more-limited information at the time of approval coupled with commitments to expanding information and understanding about the drug’s safety profile throughout its life cycle.

Balancing a drug’s benefits against its potential harms is a complex task. Improved statistical methods are needed for automated signal detection and the ability to rapidly perform followup studies to confirm or refute signals. Such improvements will require expansion-and expanded availability-of databases containing information on exposures and outcomes of large numbers of individuals. More work is needed in (1) the analysis of data from spontaneous reports of adverse effects and claims databases; (2) the design of ad hoc studies to assess favorable and unfavorable drug effects in actual practice in an unbiased manner, with appropriate measures to reduce false positive findings; and (3) the design of economically feasible, large, randomized studies to identify small but serious risks that may have public health significance. Appropriate interpretation and communication of findings are also important. As the amount of information available increases in the media and on the Internet, the average person-even the average physician-may need help in understanding the practical implications of that information.

In conclusion, quantification of the potential for harm is a critical goal before and after marketing. The objective of drug development and subsequent postmarketing evaluation must be to provide information that allows physicians and patients to make educated decisions about the potential benefits and harms of a drug. It is also important to identify products whose benefits are outweighed by their harms; they should be used only for specific indications or in populations likely to benefit from them, or they should be removed from the market. It is also important to identify products with an unfavorable overall balance between benefits and harms: such products should be used only for specific indications or populations in which the benefits do not outweigh the harms or they should be removed from the market.

References

1. DiMasi JA, Hansen RW, Grabowski HG. The price of innovation: new estimates of drug development costs. J Health Econ. 2003;22:151- 185.

2. DiMasi JA. New drug development in the United States from 1963 to 1999. Clin Pharmacol Ther. 2001;69: 286-296.

3. Pharmaceutical Industry Profile 2006. Washington, DC: Pharmaceutical Research and Manufacturers of America; March 2006.

4. Remicade [package insert]. Malvern, PA: Centocor Inc; 2007.

5. Department of Health and Human Services, Food and Drug Administration Remicade (infliximab) psoriasis approval letter 2006, BL 103772/5129. Available at: http://www.fda.gov/cder/foi/appletter/ 2007/103772s5129LTR.pdf. Accessed June 28, 2007.

6. Ellenberg SS. Safety considerations for new vaccine development. Pharmacoepidemiol Drug Saf. 2001;10: 411-415.

7. Strom BL. How the US drug safety system should be changed. JAMA. 2006;295:2072-2075.

8. Strom B, ed. Pharmacoepidemiology. 4th ed. Chichester, England: John Wiley & Sons Ltd; 2005.

9. Yusuf S, Collins R, Peto R. Why do we need some large, simple randomized trials? Stat Med. 1984;3:409-422.

10. Hasford J. Drug risk assessment: a case for large trials with lean protocols. Pharmacoepidemiol Drug Saf. 1994;3: 321-327.

11. Rodriguez L, Gutthann S. Use of the UK General Practice Research Database for pharmacoepidemiology. Br J Clin Pharmacol. 1998;45:415-425.

12. Ellenberg SS, Foulkes MA, Midthun K, Goldenthal KL. Evaluating the safety of new vaccines: summary of a workshop. Am J Public Health. 2005; 95:800-807. 13. Mitchell AA, Lesko SM. When a randomised controlled trial is needed to assess drug safety. The case of paediatric ibuprofen. Drug Saf. 1995;13: 15-24.

14. Wood L, Coulson R. Revitalizing the General Practice Research Database: plans, challenges, and opportunities. Pharmacoepidemiol Drug Saf. 2001; 10:379-383.

15. Jick SS, Kaye JA, Vasilakis-Scaramozza C, et al. Validity of the general practice research database. Pharmacotherapy. 2003;23:686- 689.

16. Ahmad SR. Adverse drug event monitoring at the Food and Drug Administration. J Gen Intern Med. 2003;18: 57-60.

17. Edwards R, Faich G, Tilson H. Points to consider: the roles of surveillance and epidemiology in advancing drug safety. Pharmacoepidemiol Drug Saf. 2005;14:665-667.

18. Weber JCP. Epidemiology of Adverse Reactions to Nonsteroidal Antiinflammatory Drugs. New York, NY: Raven Press; 1984:1-7. Rainsford KD, Velo GP, eds. Advances in Inflammation Research; vol 6.

19. Niu MT, Erwin DE, Braun MM. Data mining in the US Vaccine Adverse Event Reporting System (VAERS): early detection of intussusception and other events after rotavirus vaccination. Vaccine. 2001;19:4627-4634.

20. Almenoff JS, DuMouchel W, Kindman LA, Yang X, Fram D. Disproportionality analysis using empirical Bayes data mining: a tool for the evaluation of drug interactions in the post-marketing setting. Pharmacoepidemiol Drug Saf. 2003;12:517-521.

21. DuMouchel W. Bayesian data mining in large frequency tables, with an application to the FDA Spontaneous Reporting System. Am Stat. 1999;53: 177-202.

22. Niu MT, Rhodes P, Salive M, et al. Comparative safety of two recombinant hepatitis B vaccines in children: data from the Vaccine Adverse Event Reporting System (VAERS) and Vaccine Safety Datalink (VSD). J Clin Epidemiol. 1998; 51:503-510.

23. Abenhaim L, Moore N, Begaud B. The role of pharmacoepidemiology in pharmacovigilance: a conference at the 6th ESOP Meeting, Budapest, 28 September 1998. Pharmacoepidemiol Drug Saf. 1999;8:S1-S7.

24. Csizmadi I, Collet J-P, Boivin J-F. Bias and confounding in pharmacoepidemiology. In: Strom B, ed. Pharmacoepidemiology. 4th ed. Chichester, England: John Wiley & Sons Ltd; 2005: 791-810.

25. Lesko SM, Mitchell AA. An assessment of the safety of pediatric ibuprofen. A practitioner-based randomized clinical trial. JAMA. 1995;273: 929-933.

26. Wood AJ, Stein CM, Woosley R. Making medicines safer-the need for an independent drug safety board. N Engl J Med. 1998;339:1851- 1854.

27. Ray WA, Stein CM. Reform of drug regulation-beyond an independent drug-safety board. N Engl J Med. 2006;354:194-201.

28. Taylor MR. Protecting FDA’s ability to protect public health. Food Drug Law J. 2006;61:805-808.

29. Curfman GD, Morrissey S, Drazen JM. Blueprint for a stronger Food and Drug Administration. N Engl J Med. 2006;355:1821.

30. Furberg CD, Levin AA, Gross PA, Shapiro RS, Strom BL. The FDA and drug safety: a proposal for sweeping changes. Arch Intern Med. 2006;166: 1938-1942.

31. Committee on the Assessment of the US Drug Safety System, Baciu A, Stratton K, Burke SP, eds. The Future of Drug Safety: Promoting and Protecting the Health of the Public. Washington, DC: National Academies Press; 2006. Available at: http://www.iom.edu/ CMS/3793/26341/37329.aspx. Accessed June 26, 2007.

Jesse A. Berlin, ScD, Susan C. Glasser, PhD, and Susan S. Ellenberg, PhD

About the Authors

Jesse A. Berlin and Susan C. Glasser are with Johnson & Johnson Pharmaceutical Research & Development, LLC, Raritan, NJ. Susan S. Ellenberg is with the University of Pennsylvania School of Medicine Center for Clinical Epidemiology and Biostatistics, Philadelphia, PA.

Requests for reprints should be sent to Jesse A. Berlin, ScD, Johnson & Johnson Pharmaceutical Research & Development, 1125 Trenton-Harbourton Rd, PO Box 200, Mail Stop K-304, Titusville, NJ 08560 (e-mail: [email protected]).

This essay was accepted December 21, 2007.

Contributors

J. A. Berlin and S. C. Glasser prepared the initial draft, with major substantive additions and revisions provided by all authors. All authors contributed equally to the conceptual development of the essay before any drafts were prepared.

Acknowledgments

We thank Patricia Molino and Audrey Phillips of Johnson & Johnson for their advice and counsel and Wendy Battisti of Johnson & Johnson Pharmaceutical Research & Development, LLC, for assistance in the preparation of this essay.

Health

Latino Disparities in Child Mental Health Services

Written By: Sam Savage

Published Date: August 30, 2008 Last Edited: August 30, 2008

By Lopez, Cintia Bergren, Martha Dewey; Painter, Susan G

TOPIC: Access and utilization of mental health services for Latino children. PURPOSE: As Latino children may experience higher rates of unmet needs, this article examines the current literature for the reasons for the disparity and the barriers to the utilization of mental health services for Latino children.

SOURCES: An integrative literature review was undertaken from child psychiatry and nursing.

CONCLUSIONS: The literature confirmed a pattern of underutilization of mental health services by Latino children, but did not completely address the reasons for the disparity. Suggested barriers were language and cultural issues. Gaps in the literature include a lack of agreement for definition of a mental health problem and the tools to identify these, insufficient studies into the barriers for Latino children in the access and utilization of mental health services, and cultural and language issues related to Latino research.

Search terms: Latino child mental health access, Latino child mental health disparities, Latino child mental health, Latino child mental health utilization

Health Disparities Among Latinos for Child Mental Health Services

The prevention and treatment of mental health problems in children in this country has received national attention in recent years. Mental health in children includes social, developmental, emotional, and behavioral issues and is an essential component of overall health (American Academy of Pediatrics [AAP], 2001). Factors such as physical impairments, cognitive disabilities, low birth weight, a family history of mental or additive disorders or poverty, parental separation, or child abuse or neglect place children at risk for mental health problems (U.S. Public Health Service [U.S. PHS], 2000). According to the U.S. Department of Health and Human Services (U.S. DHHS, 1999), although 1 in 10 children in the United States are estimated to have a mental health problem severe enough to cause impairment, only 1 in 5 of these children receive services.

Considering the morbidities associated with mental health problems and the possible consequences of inadequate or nonexistent treatment, it is little wonder the problem of mental illness in children has been called a national public health crisis by former Surgeon General David Satcher (U.S. DHHS, 1999). While mental health problems in children can lead to problems in school, such as learning or attention difficulties, these problems can, in turn, lead to mental health problems (DeSocio & Hootman, 2004). These problems can also develop into an increase in violence, such as suicide and homicide (AAP, 2001). In fact, the Illinois Children’s Mental Health Task Force (2003) stated that almost 70% of youths detained in the juvenile justice system suffer from a mental health problem. Mental health problems can also increase the likelihood of risky behaviors of adolescents, such as smoking and unsafe sexual practices, that can negatively impact physical health (AAP).

Utilization of mental health services remains low among all children (U.S. DHHS, 1999). Children are a particularly vulnerable group as they completely rely on adult caregivers for their healthcare needs during the early childhood and school-age years. Even as they grow older and become more independent, children still depend on their parents or guardians to a large extent to access needed services. Barriers common to children of all backgrounds in accessing mental health services include stigma, cost, insufficient coverage for services from private health insurances, and inadequately trained mental health providers (Illinois Children’s Mental Health Task Force, 2003). However, there are certain groups who have even higher rates of unmet needs. The Illinois Children’s Mental Health Task Force reports that mental health disparities exist for Hispanic and African American children. According to the U.S. PHS (2000), the difficulties in accessing mental health services can be exacerbated by cultural differences.

The elimination or reduction of racial and socioeconomic disparities by providing culturally competent care has been stressed in several reports (Illinois Children’s Mental Health Partnership, 2005; U.S. DHHS, 1999; U.S. PHS, 2000). One way to begin to eliminate health disparities is to examine affected groups and to identify and address any cultural barriers or challenges. The focus of this investigation is Latino children.

The terms Latino and Hispanic are often used interchangeably and include people of any race with a Spanish-speaking background. Latinos make up 12% of the population of the United States at 39.9 million, and are one of the fastest growing groups in the United States (U.S. Census Bureau, 2004). As with any cultural group, it is important to avoid stereotyping or assume its people are homogeneous. For instance, there are dozens of Hispanic countries and they are quite different from each other. In the United States, the largest Latino groups are Mexican Americans (58.8%), followed by Puerto Ricans (9.6%) and Cuban Americans (3.5%) (U.S. Census Bureau). However, there are similarities among cultures that can help in understanding its individual members.

In efforts to reduce the health disparity in Latino child mental health utilization, an integrative literature review was undertaken using the standards and guidelines set forth by Ganong (1987) to ensure a rigorous review that can contribute to nursing knowledge. The first step is to establish the purpose of the review and related questions to be answered. Next is to establish tentative selection criteria for the inclusion of studies. Third is to conduct a literature review. In order to gather information from the research, a questionnaire or survey tool should be developed. Next, rules of inference should be established for use in data analysis and interpretation. Inclusion criteria should be revised as necessary. Studies should be read using the tool to gather data. Then, data should be analyzed, followed by discussion and interpretation. The last step is to report the review.

The purpose of this paper is to examine past research on Latino child mental health access and utilization in an effort to expand the current knowledge base and determine areas for further research. The following questions-“Why is there a greater rate of unmet need among Latinos for mental health services?” and “What are the barriers facing Latinos in accessing and utilizing services for child mental health problems?”-were used to focus this investigation.

Method

In efforts to begin to understand these issues, a literature search was undertaken. The computerized databases CINAHL (1982 to August 2005), Ovid MEDLINE (1964 to August 2005), and PsycINFO (1872 to August 2005) were searched using the keywords “children mental health” and “child mental health” combined with “Latino” and “Hispanic.” Titles were screened and all relevant abstracts reviewed. Additionally, citations in relevant articles led to more articles to review. A total of 43 articles were reviewed. All research articles having to do with access and utilization of mental health services for children were selected for inclusion if Latinos were included. An exclusion criterion was not including Latinos or not specifying whether Latinos were included under the categories of White or Black. Articles that excluded children or that focused on specific treatment interventions were excluded. A total of 5 research articles were selected for review in the first search wave.

Due to the scarcity of available research in the initial search, Ovid MEDLINE (1966 to third week of September 2005), CINAHL (1982 to fourth week of September 2005), and PsychINFO (1806 to fourth week of September 2005) were again utilized in a second search wave. This time the search words “Latino mental health,””Hispanic mental health,””pathways into mental health services,””help-seeking for child mental health,””access to mental health care,””barriers to mental health services,” as well as the combination of “child mental health” and “access to care” were used for a yield of 228 research articles to review. Using the link “find similar” in the University of Illinois online library for the most relevant of these articles resulted in an additional 360 articles. Additionally, the online journal Psychiatric Services (http:// psychservices.psychiatryonline.org/cgi/content/full/ 54/1/60) was searched using the term “access to service” for a result of 121 articles. The titles of all these articles were screened for relevance to the topic with the most relevant ones selected for abstract review. Once again the inclusion criterion was to select all articles pertaining to the access and utilization of mental health services for children if Latino children were included. Articles on specific treatment interventions were excluded, as were those that focused on mental health access and utilization for adults in general or that did not specify Latino ethnicity. In the second search wave, 3 articles were selected for review.

Results

In all, a total of 8 research articles were selected for review. To aid in analyzing the research, the suggestion by Ganong (1987) to develop a survey tool was followed. See Appendix A for the survey tool, which was used to gather key elements of the studies and to take notes on their strengths and weaknesses. The 8 articles selected were examined for relevance to the topic of Latino child mental health access and utilization of services. Specifically, answers as to whether a health disparity exists and, if so, why it exists and what are the factors leading to this disparity were sought by reviewing the literature.

All of the studies reviewed were quantitative in nature and none were experimental. To aid in evaluating the current knowledge base on access and utilization of child mental health services for Latinos in the United States, the studies are examined by themes beginning with the studies relating to mental health service needs and utilization of services, followed by those examining service entry points and pathways, and ending with studies that focused on access issues and barriers.

National Surveys: Mental Health Service Needs and Utilization

Two studies analyzed data from national surveys with large samples representative of the U.S. population (Kataoka, Zhang, & Wells, 2002; Simpson, Bloom, Cohen, Blumberg, & Bourdon, 2005). In the Kataoka et al. study, secondary analysis of 3 national data sets- the National Health Interview Survey, the National Survey of American Families, and the Community Tracking Survey-from 1996 to 1998 was done for a total sample size of 48,736 randomly selected children. Parents were questioned about their children’s mental health. Unmet need was defined as not having been seen by a mental health professional in the past for those children in need of a mental health evaluation based on a screening tool that used selected items from the Child Behavior Checklist. The Simpson et al. study was based on the 2001, 2002, and 2003 National Health Interview Surveys, with a total of 29,278 randomly selected children. Parents or a knowledgeable adult were questioned using the Strengths and Difficulties Questionnaire to determine parental perception of having a definite or severe difficulty in emotions, concentration, behavior, or in getting along with others. The Kataoka et al. study found the need for mental health services to be much higher at 15.2-20.8% for 6- to 17-year-olds, with nearly 80% not receiving services compared to the Simpson et al. study, which estimated the need to be 5% for 4-to 17-year-olds with 55-60% not having contact with a mental health professional. Furthermore, Kataoka et al. found a significantly greater unmet need among Latinos as compared to White children, but did not explore the possible reasons for this disparity. On the other hand, the Simpson et al. study actually found that Hispanic children had a lower percentage of mental health issues compared to African Americans and Caucasians but does not speculate the rate of unmet need for specific groups. One possible reason for the discrepancy in findings is the manner in which mental health needs are measured. The Kataoka et al. study used selected items from the Child Behavior Checklist to determine need and had a much larger sample size than the Simpson et al. study. Furthermore, the Simpson et al. study was based on 3 years of a single survey and, despite being a later version of one of the surveys used by Kataoka et al., used a different tool, the Strengths and Difficulties Questionnaire, to determine need.

Latino Children: Mental Health Service Needs and Utilization

Other studies reviewed were not based on a national representative sample but specifically looked at Latino children and mental service utilization. Similar to the findings of Kataoka et al. (2002), Latino children were found to have significantly less utilization of mental health services as compared to White children (Hough et al., 2002; Snowden, Evans Cuellar, & Libby, 2003; Yeh, McCabe, Hough, Dupuis, & Hazen, 2003). Two of these studies were based on the same data set of over 1,000 randomly selected high- risk Latino, White, and African American children receiving services from 1 or more of 5 public sectors of care (mental health services, alcohol and drug programs, public school programs for the emotionally disturbed, child welfare programs, and the juvenile justice system) from San Diego County, California (Hough et al.; Yeh et al.). Both share the same limitation of excluding most primarily Spanish speakers due to a lack of instruments in Spanish. The study by Snowden et al. examined Medicaid claims for foster children and compared utilization of services among African American, Hispanic, and White children in areas starting Medicaid capitated managed care from September 1994 to June 1997 in 2 managed care sites and 1 fee- for-service site in Colorado. While all groups had a decline in services under managed care, Hispanic children had the lowest level of use under both models. Again, the reasons for this disparity were not explored.

Additionally, Alegria et al. (2004) found a high rate of unmet need, which limits the investigation of children in Puerto Rico in terms of their need, utilization of services, and the location of services. Here, need was assessed for the randomly selected sample of 1,890 children with the use of the Computerized Diagnostic Interview for Children (Version IV) to determine psychiatric disorders, while impairment was assessed by interviewing the parents using the Parent Interviewer Children Global Assessment Scale. This study found that 22% of children had significant mental health impairment and a majority of these children (87.8%) did not receive services in the previous year. These findings are striking since there would be no language barriers or incongruity in culture in Puerto Rico among parents, their children, and the mental health providers.

Service Entry Points and Pathways

A crucial aspect of accessing mental health services is the process of seeking help and the actual initiation of services. One study compared Latinos with African Americans and Caucasians in their sources of help leading to utilization of mental health services for children (McMiller & Weisz, 1996). The sample consisted of 192 families conveniently chosen from seven community mental health clinics in central and southern California. Latinos and African Americans were found to differ from Caucasians in that initial help tended to come from nonprofessional sources such as family and community members versus sources such medical or school personnel. Another study looked at the court system as an entry point for mental health services for foster children, a group expected to have a greater need (Garland & Besinger, 1997). Here the sample size was 142 children aged 2-16 years randomly selected from a larger study of children placed in foster care. While there were no differences among ethnicities for court recommendations for services, Whites were found to have a significantly higher rate of court-mandated services as compared to Latinos and African Americans. Although the sample size is small at 142, this finding is important as a court mandate is likely to elicit compliance for initiation of mental health services and also carries a financial responsibility for coverage.

Parental Perceptions: Access Issues and Barriers

When examining access issues, some researchers have highlighted parental perception of a possible problem or concern over the child’s mental health. The study by Alegria et al. (2004) was based only on parents and children in Puerto Rico, and found that 30% of the caregivers were concerned about their child’s mental health but only 12.2% of the children had received services in the previous year. Generalizability is limited as Latinos in the U.S. mainland were not included.

The study by Yeh et al. (2003) specifically looked at the barriers, or rather the endorsement of barriers, faced by ethnic minority parents in accessing mental health care for their children. Parents were not asked to name barriers but instead were asked to rate a total of 54 questions representing different possible barriers, including content of services, helpfulness of services, provider characteristics, effects of service, economic/ financial constraints, accessibility, language problems, and a lack of need for services. The questions were comprised of 15 items adapted from the Service Assessment of Children and Adolescents, 14 items adapted from other research deemed appropriate for children’s mental health services (namely, that of Alegria et al.), and 25 items created by two of the investigators. Surprisingly enough, the parents of the ethnic minorities, including Latinos, surveyed reported significantly fewer barriers in accessing care despite a significantly greater rate of unmet needs when compared to Whites. A notable exception for Latinos was language issues, which was endorsed as a barrier. Another intriguing finding was that greater acculturation was positively associated with barrier endorsement, even after controlling for symptoms severity. Since this study looked at an at-risk group already receiving services in a public health sector, the findings are not generalizable to the general population for whom barriers may have prevented receiving care altogether. Another consideration is whether the 54 items representing barriers captured all the possible barriers Latino parents may face in seeking mental health services for their children.

Aside from language and cultural issues, a frequently mentioned barrier for Latinos in healthcare access includes insurance issues. However, only one study included ethnicity when investigating the impact of insurance in the mental health access for children (Snowden et al., 2003). As described earlier, this study compared Medicaid-managed care to the traditional fee-for-service model and did find a decline in utilization under the fee-for-service model for Hispanic children. In addition, while Hispanics were found to have the lowest utilization rates as compared to African Americans and Whites, there was an increase in the use of residential treatment centers in managed care for both Hispanics and African Americans. Discussion

Clearly, there are gaps in the literature to date. The problem of underutilization of mental health services among all children with mental health problems has been documented (Kataoka et al., 2002; Simpson et al., 2005; U.S. DHHS, 1999). Furthermore, most of the studies examining issues of disparities in utilization of mental health services found that Latino children have a lower rate of utilization as compared to White children (Hough et al., 2002; Kataoka et al; Snowden et al., 2003; Yeh et al., 2003). However, it should be noted that the two national studies differed in terms of the prevalence of mental health issues among Latino children. While Kataoka et al. suggest that there is an increased prevalence of mental health problems among Latino youth as compared to Whites, another national study by Simpson et al. had the conflicting finding of a lower percentage of mental health issues among Hispanic children as compared to African Americans and Caucasians but does not differentiate the rate of unmet needs for specific groups.

The crucial questions as to why there is an unmet need and what barriers exist among Latino children for mental health service access and utilization remain only partially answered. During the literature search, most of the studies on Latino barriers to healthcare access centered on adults, with only a few investigations exclusive to Latino children and only one focusing specifically on mental healthcare access for Latino children (Yeh et al., 2003). This single study looked at children already receiving services when assessing parental perceptions of barriers. The puzzling findings that Latino parents do not report as many barriers as White parents do and yet Latino children have a lower rate of utilization suggest that there may be some cultural factors influencing parental perceptions of what constitutes a barrier or of recognizing that their child may require mental health services or even in voicing complaints about accessing services.

Aside from the issue of quantity or, rather, the insufficient number of studies investigating barriers specifically for Latino children and mental health services, other serious problems are apparent in the literature.

Perhaps the most critical problems are related to cultural issues in research. One such issue is the lack of validated Spanish language instruments. Due to the lack of an instrument, Spanish speakers were excluded from some studies on Latino child mental health access and utilization (Hough et al., 2002; Yeh et al., 2003). This is a major omission as it effectively excludes from the study Latinos who are likely among the most vulnerable and most at risk for health disparities due to language barriers. Another problem, which led to the exclusion of many articles in the literature search, is not including or specifying whether Latinos are included in the sample. Since Latinos can be of any race, simply categorizing the sample as White or Black does not clarify whether Latinos are being included. Since Latinos are not only of different races, but also originate from various Spanish-speaking countries and are in differing degrees of acculturation to the United States, they should not be treated or grouped as a homogeneous group. To be fair, it may be difficult, if not impossible, to have a large enough sample of Latinos to distinguish findings by country of origin, including U.S. born, or by degree of acculturation. However, indicating these differences among the Latinos in a sample can assist one in generalizing the findings.

Another basic issue is the lack of consensus as to what defines a mental health need, impairment, or actual diagnosis and how these are determined. Across the studies, various instruments were utilized to determine mental health need or impairment. For instance, one study used the Strengths and Difficulties Questionnaire (Simpson et al., 2005) while another used selected items from the Child Behavior Checklist to determine impairment (Kataoka et al., 2002). Yet another study used the Parent Interviewer Children Global Assessment Scale and the Computerized Diagnostic Interview for Children (Version IV) (Alegria et al., 2004). With such a wide variety among researchers as to what constitutes an impairment or a diagnosis, it is difficult to compare findings from study to study.

Implications

Advanced practice nurses in child mental health services have little empirical evidence to direct them to explain the phenomenon of low utilization of services or to assist in developing appropriate interventions for increasing access to care for Latino children. The current literature highlights the need for further studies to investigate barriers in Latino child mental health service access and utilization. Areas in need of further study for Latino children include the investigation into the impact of poverty and insurance issues, such as managed care versus public aid, and versus no insurance. The perception of barriers to mental health care must be evaluated from both the parent and child perspective and assessed as to whether any differences exist. Another necessity is the consensus among mental health experts as to what constitutes a mental health need and what instruments determine impairment, problems, or diagnosis.

It is essential that research into child mental health issues include Latino children and reflect the diversity within the Latino community, identifying Latinos from all countries of origin and regardless of English language skills. To investigate access to child mental health services between the various Latino subgroups, national studies should oversample Latinos to allow the measurement of differences between subgroups. Spanish language measurement tools must be developed and validated for Latino children and their parents. Based on previously identified barriers of language and cultural issues, research teams should include bilingual and bicultural members. Addressing these issues will result in research that can guide advanced practice nursing priorities and intervention efforts.

While community, poverty, and insurance issues have been examined in healthcare access for Latino adults and occasionally for children, these possible barriers have yet to be fully explored in the access and utilization for child mental health services. Future studies should include community samples for a complete picture of the barriers that may be preventing Latino children from initial entry into the mental health system. It is also imperative that advance practice nurses become politically involved in bringing these issues to the forefront in support of funding mental health issues for our nation’s children.

Until the gaps in the literature are narrowed, mental health providers in both private and public arenas must investigate strategies to reduce health disparities for Latino children in mental health service access and utilization. Careful consideration of the evidence indicating that all children, in particular minority groups, such as Latinos, underutilize mental health services is a first step. Advanced practice nurses must examine language and cultural sensitivity in their own settings and decrease possible bias in their own practice. For instance, providers can take steps to reduce the language barrier by ensuring that materials are available in Spanish and English, that at least some staff members are bilingual or that qualified translators are available at all times, and to provide services in the language of choice (keeping in mind that this may be different for parent and child). Certainly, ongoing education of staff on issues of cultural competency can alleviate cultural barriers, as would the inclusion of bilingual and bicultural staff. To increase the numbers of culturally competent mental health advanced practice nurses, Latino nurses should be actively recruited and supported to enter the mental health advanced practice specialties. Advance practice nurses must continue to support minorities who practice and who receive services in the mental healthcare system.

Advanced practice nurses can also improve the sensitivity of those who refer clients to mental health services to the health disparities among Latino children. Community and school providers can be alerted to the criteria for referring child clients for services, and be given strategies for ensuring that Latino families can locate and avail themselves of mental health care for their children. Providing services where the children are, either as a school-based service or in their neighborhoods, will decrease some of the barriers faced.

Conclusion

This integrative literature review found that Latino children experience a higher rate of unmet needs and mental health underutilization compared to White children. The current literature does not fully explore the reasons for the disparity, although suggested barriers include language and cultural issues. Further study is clearly needed to close the current gaps in the literature and must continue in order to support minorities in the mental healthcare system. Research into how mental health issues are addressed within the Latino culture would also benefit the advance practice nurse in practice. Advance practice nurses need to understand and support how mental illness impacts children’s lives within the Latino community, in order to build a foundation to narrow the gaps within a community.

Answers as to whether a health disparity exists and, if so, why it exists and what are the factors leading to this disparity were sought.

Aside from language and cultural issues, a frequently mentioned barrier for Latinos in healthcare access includes insurance issues. This integrative literature review found that Latino children experience a higher rate of unmet needs and mental health underutilization compared to White children.

References

Alegria, M., Canino, G., Lai, S., Ramirez, R., Chavez, L., Rusch, D., et al. (2004). Understanding caregivers’ help seeking for Latino children’s mental health care use. Medical Care, 42(5), 447-455.

American Academy of Pediatrics, Committee on Psychosocial Aspects of Child and Family Health. (2001). The new morbidity revisited: A renewed commitment to the psychosocial aspects of pediatric care. Pediatrics, 108(5), 1227-1230.

DeSocio, J., & Hootman, J. (2004). Children’s mental health and school success. Journal of School Nursing, 20(4), 189-196.

Ganong, L. H. (1987). Integrative reviews of nursing research. Research in Nursing and Health, W, 1-11.

Garland, A. F., & Besinger, B. A. (1997). Racial/ethnic differences in court referred pathways to mental health services for children in foster care. Children and Youth Services Review, 19(8), 651-666.

Hough, R. L., Hazen, A. L., Soriano, R I., Wood, P., McCabe, K., & Yeh, M. (2002). Mental health services for Latino adolescents with psychiatric disorders. Psychiatric Services, 53(12), 1556-1562. Retrieved October 29, 2005, from http:// psychservices.psychiatryordine.org/cgi/content/full/54/1/60

Illinois Children’s Mental Health Partnership. (2005). Draft PLAN recommendations and strategies for building a comprehensive children’s mental health system in Illinois. Chicago: Author.

Illinois Children’s Mental Health Task Force (2003). Children’s mental health: An urgent priority for Illinois. Chicago: Author.

Kataoka, S. H., Zhang, L., & Wells, K. B. (2002). Unmet need for mental health care among U.S. children: Variation by ethnicity and insurance status. American Journal of Psychiatry, 159(9), 1548- 1555.

McMiller, W. P., & Weisz, J. R. (1996). Help-seeking preceding mental health clinic intake among African-American, Latino, and Caucasian youths. Journal of the American Academy of Child & Adolescent Psychiatry, 35(8), 1086-1094.

Simpson, G. A., Bloom, B., Cohen, R. A., Blumberg, S., & Bourdon, K. H. (2005). U.S. children with emotional and behavioral difficulties: Data from the 2001, 2002, and 2003 National Health Interview Surveys. Advance Data from Vital and Health Statistics, No. 360, 1-13.

Snowden, L. R., Evans Cuellar, A., & Libby, A. M. (2003). Minority youth in foster care: Managed care and access to mental health treatment. Medical Care, 41(2), 264-274.

U.S. Census Bureau. (2004). American factfinder. Retrieved September 10, 2005, from http://www.census.gov/.

U.S. Department of Health and Human Services. (1999). Mental health: Areport of the surgeon general. Rockville, MD: U.S. Department of Health and Human Services, Substance Abuse & Mental Health Services Administration, Center for Mental Health Services.

U.S. Public Health Service. (2000). Report of the surgeon general’s conference on children’s mental health: A national agenda. Washington, DC: Department of Health and Human Services. Retrieved July 23, 2005, from http://www.surgeongeneral.gov/cmh/default.htm

Yeh, M., McCabe, K., Hough, R. L., Dupuis, D., & Hazen, A. (2003). Racial/ethnic differences in parental endorsement of barriers to mental health services for youth. Mental Health Services Research, 5(2), 65-77

Cintia Lopez, RN, MS, ILCSN, is a School Nurse, Chicago Public Schools, Chicago, IL; Martha Dewey Bergren, DNS, RN, NCSN, ILCSN, FNASN, is Clinical Assistant Professor, College of Nursing, University of Illinois at Chicago, Chicago, IL; and Susan G. Painter, APRN, BC, is a Clinical Instructor, College of Nursing, University of Illinois at Chicago, Chicago, IL. This article was written as part of the requirements for Master’s in Nursing at the University of Illinois at Chicago.

Author contact: [email protected], with a copy to the Editor: [email protected]

(ProQuest: Please refer to full text PDF for images of the Appendix)

Health

Acupuncture for Psychiatric Illness: A Literature Review

Written By: Sam Savage

Published Date: August 30, 2008 Last Edited: August 30, 2008

By Samuels, Noah Gropp, Cornelius; Singer, Shepherd Roee; Oberbaum, Menachem

The use of complementary and alternative medicine (CAM) is on the rise, especially among psychiatric patients. Acupuncture is considered a safe and effective treatment modality, and traditional Chinese medicine teaches that acupuncture harmonizes the body’s energies. Scientific research has found that acupuncture increases a number of central nervous system hormones (ACTH, beta-endorphins, serotonin, and noradrenaline) and urinary levels of MHPG-sulfate, an adrenergic metabolite inversely related to the severity of illness in schizophrenics. Acupuncture can have positive effects on depression and anxiety, although evidence is still lacking as to its true efficacy for these conditions. To the authors’ knowledge, no trials have been conducted for schizophrenia, and researchers evaluating acupuncture in cases of substance abuse have found conflicting results. Further research is warranted. Index Terms: acupuncture, anxiety, depression, schizophrenia, substance abuse

The use of complementary and alternative medicine (CAM) is on the rise,1,2 with psychiatric patients, especially those diagnosed with disorders such as anxiety or depression, more likely to use CAM than are patients with nonpsychiatric illness.3,4 The ancient Chinese treatment of acupuncture incorporates the use of ultra-fine needles (diameter 0.15-0.30 mm), which are inserted into specific points on the skin (acupoints). Acupuncture is central to the treatment regimen of traditional Chinese medicine (TCM), along with other manual therapies (eg, Tui Na, Chi Gong), herbal remedies, and nutritional and lifestyle changes. TCM promotes a holistic, energy- based approach to well-being, as opposed to the disease-oriented approach of Western (scientific) medicine. Both the US National Institutes of Health and British Medical Association recognize acupuncture as an effective treatment for many medical conditions,5,6 although for many in the medical profession, acupuncture and other CAM treatments remain enigmatic.

According to TCM, the body’s energy, or Qi (pronounced chee), flows along series of points called meridians. Each of the internal organs has a corresponding meridian, and applying pressure (acupressure, Shiatsu), heat (Moxibustion), or needles (acupuncture) to relevant acupoints is believed to influence each of the internal organs and harmonize the body’s Qi. There are many schools of acupuncture (eg, Chinese, Japanese, Korean, Indian), each with its own approach to diagnosis and allocation of acupoints. Modern acupuncture has branched out into related fields, such as electroacupuncture (low-voltage stimulation of needles) and laser acupuncture. Auricular acupuncture is a related field in which needles are inserted into points located on and around the earlobe that correspond to internal organs.

TCM teaches that Qi exists in many forms in the human body. For example, Jing-considered the most concrete form of Qi-is housed in the kidneys. Levels of Jing increase and decrease in 7-year cycles in women in a circadian fashion that is similar to levels of estradiol in the fertility cycle. Shen (meaning “of the mind”) is the most spiritual form of energy and is housed in the heart. Shen is responsible for the various mental activities required for day- to-day functioning. Mental illness can result when there is disharmony or imbalance in the body’s energy system, especially when the Shen is affected. A number of etiological factors-such as constitutional makeup, fetal trauma, improper diet, overwork, excessive sexual activity, and narcotic drugs-can create such an imbalance.

The exact mechanism by which acupuncture induces physiological changes, relieves pain, and alleviates illness is still unclear. Research has shown that treatment with acupuncture results in local and systemic effects, such as an increased release of pituitary beta- endorphins and ACTH.7 The release of endorphins may partly explain the analgesic effects of this treatment, whereas increased ACTH secretion-which leads to elevated serum cortisol levels-may account for its antiinflammatory effects. Acupuncture can also lead to accelerated synthesis and release of serotonin and noradrenaline in the central nervous system,8 with activation of descending antinociceptive pathways and deactivation of multiple limbic areas subserving pain association.9 Clinical studies of the efficacy of acupuncture for psychiatric illness are often convincing but still inconclusive in many areas. Thus, we present a literature review (using Medline, 1966-2007) on the effectiveness of acupuncture for 4 Axis I disorders: depression, anxiety disorders, schizophrenia, and substance abuse.

Depression

Depression is the most common psychiatric illness in the United States, with a prevalence as high as 18.9% in the primary care setting.10 Many who suffer from depression may remain undiagnosed or inadequately treated because of a failure to recognize symptoms, underestimation of severity, limited access to health care, reluctance to see a mental healthcare specialist, noncompliance with treatment, or lack of health insurance.11 Conventional medical treatment is problematic for several reasons. First, as many as 35% of patients do not respond to conventional treatment, perhaps more so among those with chronic illness.12 Second, although compliance with next-generation selective serotonin reuptake inhibitor medications has improved, the dropout rate is as high as 15%.13 Last, a number of clinical trials have failed to demonstrate a significant difference between active treatment and placebo groups,14 undermining the public’s confidence in these drugs. Women may be hesitant to initiate treatment during childbearing years, and elderly patients may have comorbid medical conditions that warrant specialist expertise or contraindicate the use of these drugs.

TCM teaches that depressive symptoms result from disharmony between the physical Qi and the spiritual Shen energies of the body. According to the Five-Element school of TCM, 3 distinct forms of depression exist, each with its own predominant emotional imbalance: Earth type (worry), Water type (fear), and Wood type (anger). Each of these forms of depression correspond to an imbalance in one of 3 internal organ systems: the spleen/stomach (Earth), the kidneys (Water), and the liver (Wood). In most instances, the depressed patient may suffer from more than 1. The imbalance can be caused by internal organ deficiencies (eg, innate deficiency of kidney Qi), excesses (eg, stagnation of liver Qi caused by repressed anger), or both. As with many other ailments, TCM recommends an integrated approach to treatment, using herbal remedies and acupuncture in addition to nutrition and other lifestyle changes.

Depression is among the top 10 diagnoses for which patients turn to CAM treatment, often as a result of dissatisfaction with conventional treatments, the feeling of personal autonomy and empowerment offered by CAM therapies, and compatibility with personal values and beliefs.15 Acupuncture may alleviate symptoms of depression through central effects, such as the release of noradrenaline and serotonin,8 or as a result of patient expectations. Although many researchers who have examined the efficacy of acupuncture treatment for depression were limited by study size and methodology, enough evidence exists to support a role for this treatment modality. In their double-blind, placebo- controlled, multicenter study of first 29 and then 241 depressed inpatients, Luo et al16 found electroacupuncture to be as effective as amitriptyline for depressive symptoms. Patients in this study who were treated with acupuncture had better outcomes with respect to somatization and cognitive process disturbances than did those treated with medication, an effect that Yang et al17 also observed. Acupuncture is also a promising treatment for depression during pregnancy.18 Table 1 summarizes clinical study findings regarding the efficacy of acupuncture for depression.

Anxiety Disorders

Anxiety disorders are the second most prevalent psychiatric condition in the United States, with a lifetime prevalence of 5%.24 Anxiety is also a common complaint in any medical environment, especially in prehospital and inhospital settings. Because preoperative anxiety has a negative effect on postoperative outcomes,25 physicians use sedative medications and preparation programs to treat preoperative anxiety, which is a practice that incurs increased operational costs for the healthcare system. According to TCM, anxiety results from an innate deficiency of the heart and kidney energies, excess of liver Qi, and a lack of communication between the heart and the kidneys, among other imbalances.

Acupuncture may alleviate anxiety through a number of mechanisms. Acupuncture results in a “stillness,” with prominent alpha rhythm in electroencephalography readings, deep general relaxation, and a high degree of unresponsiveness to ordinarily painful stimuli.26 Acupuncture also can modulate the neuropeptide Y system in the basolateral amygdale of rats,27 increase nocturnal endogenic melatonin secretion in humans,28 and increase the release of previously mentioned endogenous endorphins. Investigators studying acupuncture as a treatment for anxiety have observed beneficial responses. In a prospective, randomized, placebo-controlled trial of 30 patients scheduled to undergo colonoscopy, Fanti et al29 found that treatment with acupuncture decreased patients’ demand for sedative drugs, reducing both discomfort and anxiety during the procedure. In another randomized, blinded, controlled trial of 91 ambulatory surgery patients, Wang et al30 found that patients treated with auricular acupuncture at relaxation points reported significantly lower levels of anxiety than did controls. Table 2 summarizes results from clinical studies of the efficacy of acupuncture on anxiety-related conditions. Schizophrenia

Schizophrenia is a psychiatric illness characterized by thought disturbances, bizarre behavior, and cognitive impairment that may diminish a person’s social relations, school, work, and self-care. Because of the distorted thought process, treatment is difficult and conventional treatments are of limited benefit. Antipsychotic medication has limited efficacy and many potential side effects, with second-generation agents such as Clozapine more effective but requiring frequent monitoring of the leukocyte count. Newer agents such as Risperidone have a relatively safer profile and result in lower recurrence rates.37

TCM categorizes schizophrenia as 2 types: depressive psychosis and manic psychosis. The onset of the depressive form is gradual and accompanied by reduced mental clarity, followed by incoherent speech, mood swings, anorexia, and insomnia. Depressive psychosis requires regulating Qi, alleviating mental depression, and calming Shen. The onset of manic psychosis is sudden and accompanied by irritability, excessive motor activity, and abusive and violent behavior. This form of schizophrenia must be treated by cooling and calming methods that tranquilize the mind and calm the Shen. Few clinical studies in the field of acupuncture treatment address schizophrenia, with only 1 comparative study38 and a few case reports39- 41 published. However, electroacupuncture may increase the urinary secretion of 3-methoxy-4-hydroxypheylglycol sulphate,42 a metabolite of noradrenaline that is inversely related to the severity of illness in schizophrenics.43 The clinical significance of this finding has yet to be correlated with clinically significant findings.

Substance Abuse

Substance abuse is prevalent in Western society, with as many as 15% of patients who present to a primary care practice exhibiting an at-risk pattern of alcohol use or an alcohol-related health problem, and 5% a history of illicit drug use.44 Treatment of addiction is limited by poor compliance and toxic effects of long-acting agents that are substituted for the abused drug and then tapered gradually. In TCM, drugs such as cannabis, cocaine, heroine, and LSD deeply affect Shen, with prolonged use leading to confusion, memory loss, and decreased concentration.45

Although many clinical studies of auricular acupuncture treatment for substance abuse have been published, the results are far from conclusive. In a randomized controlled trial of 82 cocaine- dependent methadone-maintained patients, Avants et al46 found that those assigned to acupuncture treatment were significantly more likely to provide cocaine-negative urine samples than were controls. Margolin et al47 repeated the study protocol (N = 620) but found no difference between the groups. The latter authors posited that the discrepancy in outcome may have resulted from factors such as differences between counseling protocols. Also, a participation payment in the second study may have fostered retention of more severely addicted and unmotivated patients. Table 3 provides a substance-specific list of clinical studies.

COMMENT

Psychiatric illness is both common and complex, with conventional therapeutic options limited by partial efficacy, toxicity, and poor patient compliance. Acupuncture is a safe and effective treatment option that, along with other CAM treatments, patients with psychiatric illness choose far more often than do nonpsychiatric patients. When used in conjunction with conventional therapies, CAM treatment modalities such as acupuncture do not decrease adherence to conventional medical treatment.62-65 Although patient compliance is high for acupuncture treatment of chronic pain,66 it remains to be shown that psychiatric patients would be as compliant.

Many of the studies cited regarding the Axis 1 psychiatric diagnoses presented are either not yet convincing (as with schizophrenia) or show conflicting results (as with substance abuse). Better studies of disorders such as depression have been conducted, although it is still not possible to recommend routine use of acupuncture for this disorder.67 The Cochrane Corporation, via its Cochrane Database of Systematic Reviews, has investigated the efficacy of acupuncture treatment for depression,68 schizophrenia,69 and cocaine dependence.70 Each review reached the same conclusion: because of poor design and a limited number of studies, there is no evidence that acupuncture is effective for any of these conditions.

A recent Institute of Medicine committee was formed at the request of the National Center for Complementary and Integrative Medicine of the US National Institutes of Health to define principles that will guide the research agenda for CAM. The committee recommendation was that “the same principles and standards of evidence of treatment effectiveness apply to all treatments, whether currently labeled as conventional medicine or CAM.”71(p149) At the same time, however, the world of conventional medicine is expected to take CAM seriously. For this to happen, future researchers must conduct large and controlled studies, unlike most of the studies presented here, which are small and, at best, exhibit limited statistical power. Such studies would allow mental health professionals to consider acupuncture a complementary treatment with the potential to augment current therapy and increase the frequency of positive outcomes without increasing the risk for potentially harmful effects.

REFERENCES

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10. Olfson M, Shea S, Feder A, et al. Prevalence of anxiety, depression and substance use disorders in an urban general medicine practice. Arch Fam Med. 2000;9:876-883.

11. Hirschfeld RM, Keller MB, Panio S, et al. The National Depressive and Manic-Depressive Association consensus statement on the undertreatment of depression. JAMA. 1997;277:333-340.

12. Manber R, Allen JJB, Morris MM. Alternative treatments for depression: empirical support and relevance to women. J Clin Psychiatry. 2002;63:628-640.

13. Keller MB, McCullough JP, Klein DN, et al. A comparison of nefazodone, the Cognitive Behavioral Analysis System of Psychotherapy, and their combination for the treatment of chronic depression. N Engl J Med. 2000;342:1462-1470.

14. Lieberman JA, Greenhouse J, Hamer RM, et al. Comparing the effects of antidepressants: consensus guidelines for evaluating quantitative reviews of antidepressant efficacy. Neuropsychopharmacology. 2005;30:445-460.

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16. Luo H, Meng F, Jia Y, Zhao X. Clinical research on the therapeutic effect of the electroacupuncture treatment in patients with depression. Psychiatry Clin Neurosci. 1998;52:S338-S340.

17. Yang X, Liu X, Luo H, Jia Y. Clinical observation on needling extra-channel points in treating mental depression. J Tradit Chin Med. 1994;14:14-18.

18. Manber R, Schnyer RN, Allen JJB, Rush AJ, Blasey CM. Acupuncture: a promising treatment for depression during pregnancy. J Affect Disord. 2004;83:89-95.

19. Allen JJB, Schnyer RN, Hitt SK. The efficacy of acupuncture in the treatment of major depression in women. Psychol Sci. 1998;9:397-401.

20. Gallagher SM, Allen JJB, Hitt SK, Schnyer RN, Manber R. Six- month depression relapse rates among women treated with acupuncture. Complement Ther Med. 2001;9:216-218.

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22. Macpherson H, Thorpe L, Thomas K, Geddes D. Acupuncture for depression: first steps toward a clinical evaluation. J Altern Complement Med. 2004;10:1083-1091.

23. Roschke J, Wolf C, Muller MJ, et al. The benefit of whole body acupuncture in major depression. J Affect Disord. 2000;57:73- 81.

24. Fricchione G. Generalized anxiety disorder. N Engl J Med. 2004;351:675-682.

25. Johnston M. Pre-operative emotional states and post- operative recovery. Adv Psychosom Med. 1986;15:1-22. 26. Freed S. Acupuncture as therapy of traumatic affective disorders and of phantom limb pain syndrome. Acupunct Electrother Res. 1989;14:121- 129.

27. Park HJ, Chae Y, Jang J, Shim I, Lee H, Lim S. The effect of acupuncture on anxiety and neuropeptide Y expression in the basolateral amygdala of maternally separated rats. Neurosci Lett. 2005;4:179-184.

28. Spence DW, Kayumov L, Chen A, et al. Acupuncture increases nocturnal melatonin secretion and reduces insomnia and anxiety: a preliminary report. J Neuropsychiatry Clin Neurosci. 2004;16:19-28.

29. Fanti L, Gemma M, Passaretti S, et al. Electroacupuncture analgesia for colonoscopy: a prospective, randomized, placebocontrolled study. Am J Gastroenterol. 2003;98:312-316.

30. Wang SM, Peloquin C, Kain ZN. The use of auricular acupuncture to reduce preoperative anxiety. Anesth Analg. 2001;93:1178-1180.

31. Kober A, Scheck T, Schubert B, et al. Auricular acupuncture as a treatment for anxiety in prehospital transport settings. Anesthesiology. 2003;98:1328-1332.

32. Liu GZ, Zang YJ, Guo LX, Liu AZ. Comparative study on acupuncture combined with behavioral desensitization for treatment of anxiety neuroses. Am J Acupuncture. 1998;26:220-223.

33. Lo CW, Chung QY. The sedative effect of acupuncture. Am J Chin Med. 1979;7:253-258.

34. Paraskeva A, Melemei A, Petropoulos G, Siafaka I, Fassoulaki A. Needling of the extra 1-point decreases BIS values and preoperative anxiety. Am J Chin Med. 2004;32:789-794.

35. Shuaib BM, Haq MF. Electro-acupuncture in psychiatry. Am J Chin Med. 1977;5:85-90.

36. Wang SM, Kain ZN. Auricular acupuncture: a potential treatment for anxiety. Anesth Analg. 2001;92:548-553.

37. Freedman R. Schizophrenia. N Engl J Med. 2003;349:1738-1749.

38. Zhang LD, Tang YH, Zhu WB, Xu SH. Comparative study of schizophrenia treatment with electroacupuncture, herbs, and chlorpromazine. Chin Med J (Engl). 1987;100:152-157.

39. Kane J, Di Scipio WJ. Acupuncture treatment of schizophrenia. Report on 3 cases. Am J Psychiatry. 1979;136:297-302.

40. Shi ZX, Tan MZ. An analysis of the therapeutic effects of acupuncture treatment in 500 cases of schizophrenia. J Trad Chin Med. 1986;6:99-104.

41. Wu F. Treatment of schizophrenia with acu-moxibustion and Chinese medicine. J Tradit Chin Med. 1995;15:106-109.

42. Wenhe Z, Hechun L, Yucun S. The effect of electric acupuncture treatment on urinary MHPG-sulphate excretion in unmedicated schizophrenics. Int J Neurosci. 1981;14:179-182.

43. Joseph MH, Baker HF, Johnstone EC, Crow TJ. Determination of 3-methoxy-4-hydroxyphenylglycol conjugates in urine. Application to the study of central noradrenaline metabolism in unmedicated chronic schizophrenic patients. Psychopharmacology (Berl). 1976;51:47-51.

44. Manwell LB, Fleming MF, Johnson K, Barry KL. Tobacco, alcohol and dug use in a primary care sample: 90-day prevalence and associated factors. J Addict Dis. 1998;17:67-81.

45. Macciocia G. The Practice of Chinese Medicine. New York: Churchill Livingstone; 1994:449-460.

46. Avants SK, Margolin A, Holford TR, Kosten TR. A randomized controlled trial of auricular acupuncture for cocaine dependence. Arch Intern Med. 2000;160:2305-2312.

47. Margolin A, Kleber HD, Avants SK, et al. Acupuncture for the treatment of cocaine addiction: a randomized controlled trial. JAMA. 2002;287:55-63.

48. Bullock ML, Umen AJ, Culliton PD, Olander RT. Acupuncture treatment of alcoholic recidivism: a pilot study. Alcohol Clin Exp Res. 1987;11:292-295.

49. Bullock ML, Cullington PD, Olander RT. Controlled trial of acupuncture for severe recidivist alcoholism. Lancet. 1989;1:1435- 1439.

50. Bullock ML, Kiresuk TJ, Sherman FE, et al. A large randomized placebo controlled study of auricular acupuncture for alcohol dependence. J Subst Abuse Treat. 2002;22:71-77.

51. Karst M, Passie T, Friedrich S, Wiese B, Schneider U. Acupuncture in the treatment of alcohol withdrawal symptoms: a randomized, placebo-controlled inpatient study. Addict Biol. 2002;7:415-419.

52. Sapir-Weise R, Berglund M, Frank A, Kristenson H. Acupuncture in alcoholism treatment: a randomized out-patient study. Alcohol Alcohol. 1999;34:629-635.

53. Trumpler F, Oez S, Stahli P, Brenner HD, Juni P. Acupuncture for alcohol withdrawal: a randomized controlled trial. Alcohol Alcohol. 2003;38:369-375.

54. Zalewska-Kaszubska J, Obzejta D. Use of low-energy laser as adjunct treatment of alcohol addiction. Laser Med Sci. 2004;19:100- 104.

55. Avants SK, Margolin A, Chang P, Kosten TR, Birch S. Acupuncture for the treatment of cocaine addiction. Investigation of a needle-puncture control. J Subst Abuse Treat. 1995;12:195-205.

56. Bullock ML, Kiresuk TJ, Pheley AM, Culliton PD, Lenz SK. Auricular acupuncture in the treatment of cocaine abuse. A study of efficacy and dosing. J Subst Abuse Treat. 1999;16:31-38.

57. Lipton DS, Brewington V, Smith M. Acupuncture for crack cocaine detoxification: experimental evaluation of efficacy. J Subst Abuse Treat. 1994;11:205-215.

58. Margolin A, Chang P, Avants SK, Kosten TR. Effects of sham and real auricular needling: implications for trials of acupuncture for cocaine addiction. Am J Chin Med. 1993;21:103-111.

59. Otto KC, Quinn C, Sung YF. Auricular acupuncture as an adjunctive treatment for cocaine addiction. A pilot study. Am J Addict. 1998;7:164-170.

60. Schwartz M, Saitz R, Mulvey K, Brannigan P. The value of acupuncture detoxification programs in a substance abuse treatment system. J Subst Abuse Treat. 1999;17:305-312.

61. Washburn AM, Fullilove RE, Fullilove MT, et al. Acupuncture heroin detoxification: a single-blind clinical trial. J Subst Abuse Treat. 1993;10:345-351.

62. Feldman DE, Duffy C, De Civita M, et al. Factors associated with the use of complementary and alternative medicine in juvenile idiopathic arthritis. Arthritis Rheum. 2004;51:527-532.

63. Matthees BJ, Anantachoti P, Kreitzer MJ, Savik K, Hertz MI, Gross CR. Use of complementary therapies, adherence, and quality of life in lung transplant recipients. Heart Lung. 2001;30:258-268.

64. Pucci E, Cartechini E, Taus C, Giuliani G. Why physicians need to look more closely at the use of complementary and alternative medicine by multiple sclerosis patients. Eur J Neurol. 2004;11:263-267.

65. Sollner W, Maislinger S, DeVries A, Steixner E, Rumpold G, Lukas P. Use of complementary and alternative medicine by cancer patients is not associated with perceived distress or poor compliance with standard treatment but with active coping behavior: a survey. Cancer. 2000;89:873-880.

66. Moroz A, Spivack S, Lee MH. Adherence to acupuncture treatment for chronic pain. J Altern Complement Med. 2004;10:739- 740.

67. Mukaino Y, Park J, White A, Ernst E. The effectiveness of acupuncture for depression-a systematic review of randomized controlled trials. Acupunct Med. 2005;23:70-76.

68. Smith CA, Hay PP. Acupuncture for depression. Cochrane Database Syst Rev. 2005;4:CD004046.

69. Rathbone J, Xia J. Acupuncture for schizophrenia. Cochrane Database Syst Rev. 2005;4:CD005475.

70. Gates S, Smith LA, Foxcroft DR. Auricular acupuncture for cocaine dependence. Cochrane Database Syst Rev. 2006;1: CD005192.

71. Bondurant S, Sox HC. Mainstream and alternative medicine: converging paths require common standards. Ann Intern Med. 2005;142:149-151.

Noah Samuels, MD; Cornelius Gropp, MD; Shepherd Roee Singer, MD; Menachem Oberbaum, MD

Drs Samuels, Singer, and Oberbaum are with the The Center for Integrative Complementary Medicine in Jerusalem, Israel. Dr Gropp is with Psychiatric Consultation and Liaison Service at Shaare Zedek Medical Center in Jerusalem.

NOTE

For comments and further information, address correspondence to Dr Noah Samuels, The Center for Integrative Complementary Medicine, Shaare Zedek Medical Center, P.O.B. 3235, Jerusalem 91031, Israel (e- mail: [email protected]).

Health

Lesions of the Adrenal Cortex

Written By: Sam Savage

Published Date: August 30, 2008 Last Edited: August 30, 2008

By McNicol, Anne Marie

* Context.-In surgical pathology practice adrenal cortical tumors are rare. However, in autopsy series adrenal cortical nodules are found frequently. These are now being identified more commonly in life when the abdomen is scanned for other disease. It is important to differentiate between benign and malignant lesions as adrenal cortical carcinoma is an aggressive tumor. Molecular genetic investigations are providing new information on both pathogenesis of adrenal tumors and basic adrenal development and physiology. Objective.-To provide an overview of current knowledge on adrenal cortical development and structure that informs our understanding of genetic diseases of the adrenal cortex and adrenal cortical tumors.

Data Sources.-Literature review using PubMed via the Endnote bibliography tool.

Conclusions.-The understanding of basic developmental and physiologic processes permits a better understanding of diseases of the adrenal cortex. The information coming from investigation of the molecular pathology of adrenal cortical tumors is beginning to provide additional tests for the assessment of malignant potential in diagnosis but the mainstay remains traditional histologic analysis.

(Arch Pathol Lab Med. 2008;132:1263-1271)

Recent advances have significantly informed our understanding of the structure and function of the normal adrenal cortex and of the diseases that affect it. This review highlights some of the findings in relation to the human gland and their relevance to nonneoplastic disease. It also discusses the pathogenesis and diagnosis of adrenal cortical tumors.

NORMAL ADRENAL CORTEX

Structure and Function

The normal adult adrenal gland weighs 4 g at surgical excision or in cases of sudden death. At hospital autopsy the average is 6 g, reflecting the stimulation by adrenocorticotrophic hormone (ACTH) in the stress of terminal illness. It is divided into head, body, and tail with alae extending laterally. The medulla comprises approximately 10% of the total weight and is present in the head and body and focally in the alae. The cortex comprises 3 zones with characteristic histologic features. The zona glomerulosa (ZG) is composed of small angular cells with a high nuclear-cytoplasmic ratio, dispersed focally under the capsule. It synthesizes the main mineralocorticoid, aldosterone. The major part is the zona fasciculata (ZF) with large clear lipid-laden cells arranged in columns from the capsule or ZG to the inner zona reticularis (ZR). It is now thought to be the major source of glucocorticoids (cortisol in the human gland). The ZR comprises eosinophilic (compact) cells with little lipid storage arranged in cords around vascular sinusoids. This zone appears to be the source of androgens. All steroids are derived from cholesterol and the enzymes involved in synthesis are 4 of the members of the cytochrome P-450 family, mainly with hydroxylase activities, and a 3beta-hydroxysteroid dehydrogenase. These are distributed between the smooth endoplasmic reticulum and the mitochondria and precursors move between these loci during steroid synthesis. The first stage is the transport of cholesterol to the inner mitochondrial membrane by a key protein, steroid acute response protein. 1 Cortisol production is mainly controlled by the hypothalamic- pituitary-adrenal axis, by the actions of ACTH. Aldosterone secretion is under the control of the renin-angiotensin system. The control of androgen secretion is still poorly understood. Adrenocorticotropic hormone can have an effect, but other factors are also involved as levels may rise without any change in ACTH (eg, at adrenarche). Other signaling molecules that may play a role in steroidogenesis include insulin-like growth factors (IGFs), IGF-1 and IGF-2,2 vasopressin, adrenomedullin, 3 transforming growth factor beta, and activin A.4 Catecholamines may also be involved.5

There is a complex vascular supply that may help regulate growth and function by altering blood flow to various compartments. This may be controlled by local release of neurotransmitters from nerve fibers within the cortical plexus.6-8 Interestingly, ACTH appears to be important in the development and maintenance of adrenal vasculature, possibly by regulating the secretion of vascular endothelial growth factor by the endocrine cells.9

Development and Growth

Extended reviews of this subject are available elsewhere. 10,11 The adrenal cortex arises from the adrenogonadal primordium that develops from the urogenital ridge.11 The Wilms tumor gene (WT1) and wingless-type mouse mammary tumor virus integration site family, member 4 (WNT4) play an early role. Important regulators of development include transcription factors such as steroidogenic factor 1 and a nuclear hormone receptor, dosage sensitive sex reversal-adrenal hypoplasia congenita gene on the X chromosome, gene 1 (DAX1).12 The inner fetal zone develops first, followed by the outer definitive (or adult) zone. After birth, the fetal zone undergoes apoptosis and disappears by the third month. The definitive zone grows and migrates inward to form the adult cortex, forming the ZG, ZF, and inner ZR. Zonation is completed by the end of the second decade.

There are 2 theories as to how adrenal cell mass is maintained. The migration theory proposes that proliferation occurs at the junction of the ZG and ZF with cells differentiating into ZG, then migrating in a centripetal manner to the ZF and ZR before undergoing programmed cell death. This is supported by a number of experimental approaches. 13-15 In the rat, more recent immunohistochemical studies have demonstrated an undifferentiated zone between the ZG and ZF that is proposed as a stem cell zone.16 This theory also fits with the observation of apoptosis in the inner zones.17,18 The zonal theory, in contrast, suggests that each zone proliferates to maintain itself. Although the bulk of evidence supports the migration theory, cells in cycle, as demonstrated by immunopositivity for Ki-67, can be seen in the inner zones suggesting that both mechanisms may coexist.19

Hypophysectomy and exogenous glucocorticoids result in atrophy of ZF and ZR, implicating ACTH and related factors in control of growth. Adrenocorticotrophic hormone induces hypertrophy of ZF and ZR in vivo20 followed by increased mitotic activity.21 However, ACTH is not directly mitogenic in vitro,22 so the in vivo effects may represent interaction with other factors. Peptides from the N- terminal region of the ACTH precursor, proopiomelanocortin, can cause hypertrophy and hyperplasia.23 In addition, ACTH stimulates the release of intra-adrenal growth factors including IGF-I and IGF- II, which have trophic and steroidogenic2 effects. Other factors thought to be involved include epidermal growth factor, basic fibroblast growth factor, and cytokines including interleukin 1. Angiotensin II, vasopressin, vasoactive intestinal peptide, and endothelin 1 may also be important, particularly with reference to the ZG. The actions of ACTH are mediated via immediate early genes Jun and Fos.24 Transforming growth factor beta and activin25 may have inhibitory roles, the latter by increasing apoptosis.4

ASPECTS OF GENETIC DISEASES OF THE ADRENAL CORTEX

Congenital adrenal hyperplasia is a group of autosomal recessive diseases affecting cortisol synthesis.26,27 In most forms, mutations or translocations of genes encoding the steroidogenic enzymes lead to inefficient steroidogenesis with decreased negative feedback to the pituitary. This results in increased secretion of ACTH, with adrenocortical hyperplasia. The glands have a characteristic cerebriform appearance. The cortex is lipid depleted, because all cholesterol stores are used for steroidogenesis in an attempt to achieve normal cortisol levels. Each enzyme defect is associated with a characteristic profile of steroid secretion and clinical findings. The most common form is 21-hydroxylase deficiency. In the salt-losing variant of this disease there is abnormal development of the adrenal medulla, with chromaffin cells extending neurites between cortical cells.26 This is in keeping with the proposed role for cortisol in the development and maintenance of the medulla. There is also a higher frequency of adrenal cortical tumors in patients with congenital adrenal hyperplasia than in the general population, suggesting that chronic stimulation by ACTH may have a role in tumorigenesis. 28 Myelolipomas have also been reported.29,30 Congenital lipoid hyperplasia is a very rare cause of congenital adrenal hyperplasia and the histologic appearance of the gland differs from the other variants in that there is significant accumulation of lipid within the cells. Until recently, this was thought to be due to an abnormality in the side-chain cleavage enzyme that starts the process of steroidogenesis. It is now known to be associated with mutations in steroid acute response protein,31 thus preventing transport of cholesterol to the mitochondrion for steroid synthesis. The accumulation of cholesterol in the cytoplasm adequately explains the unusual histologic appearance.

Primary congenital hypoplasia shows an X-linked pattern of inheritance and is due to mutations or deletions in the DAX1 gene on Xp21,32 important in the development of steroidogenic tissues. The condition is often fatal and the adrenals are small and difficult to find at autopsy. Secondary hypoplasia may result from lack of ACTH, either as a genetic disease33,34 or secondary to acquired hypopituitarism. In isolated familial glucocorticoid insuffi- ciency, glucocorticoid synthesis is impaired, whereas aldosterone is unaffected. This is explained in some cases by the detection of mutations in the ACTH receptor.35,36 The pathology is poorly documented. ADRENAL CORTICAL HYPERFUNCTION

Response to Stress

Chronic stress causes increased output of ACTH and increased stimulation of the adrenal cortex. Adrenal weight increases with enlargement of ZF and ZR. This is probably a combination of hypertrophy, hyperplasia, and reduced apoptosis.37,38 Lipid depletion occurs in the ZF in a centrifugal manner. Degenerative changes may be seen in the outer ZF with cords of cells converted into tubular structures.39 Lipid reversion is characterized by reaccumulation of lipid, also in a centrifugal manner. These changes are often seen in hospital autopsies. Care should be taken not to misinterpret outer lipid depleted cells as hyperplastic ZG.

Chronic Hypersecretion of Hormones

Three classical clinical syndromes are associated with hypersecretion of adrenal cortical steroids: primary hyperaldosteronism (including Conn syndrome), Cushing syndrome (hypercortisolism), and adrenogenital syndrome (hypersecretion of sex steroids).

Primary Hyperaldosteronism. Historically this has been thought to be a rare cause of hypertension, accounting for less than 1% of patients attending clinics although some would say it is more common, responsible for up to 10% of cases.40,41 High aldosterone levels are coupled with low renin and hypokalemia. About two thirds of patients have classical Conn syndrome with an adrenal adenoma. Carcinomas are extremely rare. The tumors are usually small, often less than 2 cm in diameter, and half weigh less than 4 g. Women are affected more commonly than men, with a peak incidence in the third to fifth decades.42 The cut surface has a golden-yellow color. Histologic examination shows various cell types. Most resemble ZF cells with only a minority of ZG morphology. Hybrid cells show mixed features, containing lipid but with a higher nuclear-cytoplasmic ratio than ZF cells. Compact cells are also found. It has been reported that tumors with ZG morphology respond to angiotensin, whereas those with ZF appearances do not43; this requires further study. The para-adenomatous gland may contain micronodules. The adjacent ZG may be normal but may be hyperplastic. Whether this relates to the pathogenesis of the disease or indicates effects of treatment is not clear. Where spironolactone has been given, small whorled globular intracellular inclusions, known as spironolactone bodies, may be seen in the ZG and outer ZF and, in some cases in the tumor itself. These are probably derived from smooth endoplasmic reticulum.

Bilateral hyperplasia of the ZG, so-called idiopathic hyperaldosteronism, is now more commonly recognized. Instead of the normal focal distribution, the ZG usually forms a continuous subcapsular band and may extend into the ZF, but unless nodules are present, the glands are of normal weight. Other cases may be associated with unilateral nodular hyperplasia.44 A number of these occur in a familial setting, both with and without tumors45,46 and ongoing research aims to elucidate the correlations between genetic changes and pathology.

In glucocorticoid-suppressible aldosteronism the aldosterone levels can be suppressed by the administration of exogenous glucocorticoids.45,47 This is an autosomal dominant disorder, the result of a chimeric gene formed by a cross-over of genetic material between the ACTH-responsive regulatory portion of the 11beta- hydroxylase (CYP11B1) gene responsible for cortisol synthesis and the coding region of the aldosterone synthase (CYP11B2) gene. The ZF is reported as hyperplastic.43

Cushing Syndrome. The clinical features associated with hypercortisolism are well known. Two thirds of cases are due to hypersecretion of ACTH by the anterior pituitary gland-Cushing disease-with 80% to 90% of these patients having a pituitary corticotroph adenoma. In 80% to 90% of cases, the adrenals show bilateral diffuse cortical hyperplasia, each gland weighing 6 to 12 g. The cortex is broadened with a relative increase in the width of the ZR. Microscopic nodules are not uncommon, usually in the outer ZF. Ten percent to 20% of patients have bilateral nodular (or macronodular) hyperplasia (Figure 1). In the past, this diagnosis was restricted to glands with nodules visible to the naked eye and was usually made by the pathologist. It is now applied when nodules are seen on computed tomography scan, which can currently detect nodules of 6 mm or more in diameter. The intervening cortex is diffusely hyperplastic and the nodules merge with it. Diffuse and nodular hyperplasia may be a continuum, nodules developing in longstanding disease. The emergence of adrenal autonomy in occasional cases suggests that neoplastic transformation can occur on a background of hyperplasia.48

Ectopic ACTH syndrome accounts for 15% of cases, about half caused by secretion of ACTH from a bronchial carcinoid or small cell lung carcinoma. Other tumors associated with the syndrome are thymic carcinoids, islet cell tumors of pancreas, medullary carcinoma of thyroid, and pheochromocytoma. The adrenals show marked bilateral symmetrical enlargement weighing on average 15 g each and rarely contain nodules. Compact cells extend close to the capsule, mitotic figures may occasionally be found and pleomorphism is common. Metastases are often present in the gland in patients with bronchial carcinoma.

Fifteen percent to 20% of adults with Cushing syndrome have an adrenal tumor, equally divided between benign and malignant and most common in the fourth and fifth decades. In contrast, more than half of children with the disease have a tumor, and the majority are malignant. Females are affected 4 times as often as males at all ages. Coexistent virilization is more common in carcinomas. Because the high levels of cortisol suppress ACTH secretion from the pituitary, the ZF and ZR of the adjacent cortex and the contralateral gland are atrophic. The ZG may appear more prominent than in the normal gland, due to the relative loss of the other 2 zones.

A rare variant is macronodular hyperplasia without ACTH hypersecretion.49,50 The glands are markedly enlarged and distorted. The nodules are composed mainly of lipidladen cells and the intervening cortex can be difficult to recognize but has been reported atrophic. Adrenocorticotrophic hormone levels are suppressed. It has now been shown that some of these cases are due to the aberrant or ectopic expression of receptors not normally present in the adrenal cortex51 and the stimulation of cortisol release is due to a peptide that does not usually play a role. A range of receptors have been identified including beta-adrenergic and those for gastric inhibitory polypeptide, vasopressin, luteinizing hormone,52 and serotonin.53 In patients with gastric inhibitory polypeptide receptor expression, the hypersecretion of cortisol is in relation to intake of food.54 Occasional adenomas also express aberrant receptors.55

Primary pigmented nodular adrenocortical disease is a rare familial condition of children and young adults. Patients have typical features of Cushing syndrome but osteopenia is more severe. Both glands usually consist of multiple small brown to black nodules and the combined weights range from 4 to 21 g. The intervening cortex may be difficult to identify but comprises small regular cells with clear cytoplasm consistent with functional suppression. Plasma ACTH levels are low consistent with adrenal autonomy. In some patients this forms part of the Carney complex,56 with myxomas, spotty skin pigmentation, schwannomas, and tumors of the pituitary, testis, and thyroid, frequently caused by mutations in the PRKAR1A gene, which encodes the 1alpha regulatory subunit of protein kinase A.

Adrenogenital Syndrome (Sex Steroid Excess). Excess production of sex steroids causes virilization, feminization, or precocious puberty, depending on the steroids secreted and the age and sex of the patient. The pathology of congenital adrenal hyperplasia has already been discussed. Adrenocortical tumors may also produce sex steroids, usually androgens, either as the predominant hormone or, more commonly, in combination with cortisol (mixed Cushing syndrome). Eighty percent of cases are in females and the majority in children. This apparent excess occurrence in women may be due to the fact that they appear nonfunctional in men and present only if there are features of malignancy. Estrogen-secreting tumors most frequently cause feminization in men between 20 and 50 years but are an occasional cause of precocious puberty in girls. A higher proportion is malignant, particularly in feminizing cases. The usual criteria must be applied to distinguish benign and malignant potential, but there are certain caveats. Tumor weights are extremely variable and even benign tumors may be very large. Also, compact cells are more common in androgen-secreting adenomas than in other subtypes.

ADRENAL CORTICAL TUMORS-GENERAL FEATURES

Adrenal Cortical Nodules

Adrenal cortical nodules are not uncommon at autopsy, with lesions reported in up to 54% of unselected cases.57 Larger lesions are usually defined as adenomas, but in many cases there are small, multiple, bilateral nodules.58 They are more common with increasing age and in those with hypertension or diabetes mellitus.58,59 The size ranges from microscopic to several centimeters. The cut surface is yellow with focal brown areas. They are usually circumscribed but not encapsulated. Most comprise ZF-like cells, although compact cells may predominate. Their pathogenesis is unclear, with some regarding them as compensatory hyperplasia following on local ischemia and atrophy,58 whereas others have presented evidence that at least the larger nodules are neoplastic. These nodules are now identified commonly in life, when the abdomen is scanned for other disease, forming the major proportion of so-called adrenal incidentalomas. 60 High-resolution computed tomography scans can detect lesions in approximately 4% of people.61 They are more common in older people with a prevalence of about 7% in people older than 70 years.62 Some have been shown to be associated with subclinical Cushing syndrome63 and these may be removed. There is still debate as to how to deal with the true nonfunctioning nodule64 and decisions on removal may be made on the basis of size or evidence of growth, because larger adrenal cortical tumors are more likely to be malignant.

Adrenal Cortical Adenomas

The true incidence of adrenal adenomas is unknown as, until recently, most were diagnosed in life only if associated with autonomous hormone secretion. However, an autopsy study has suggested an incidence of approximately 5%.65 Women are more frequently affected. The tumor is usually unilateral and solitary (Figure 2). However, bilateral adenomas have been reported.66 They are intraadrenal, often unencapsulated, but may show a true capsule or a pseudocapsule due to compression of the surrounding gland by the expansile pattern of growth. The cut surface is usually yellow with focal brown areas, possibly correlating to foci of compact cells. Some contain lipofuscin and/or neuromelanin. This is pronounced in the ”black adenoma” 67 but has no behavioral importance. Most comprise mainly lipid-laden ZF-like cells arranged in an alveolar pattern (Figure 3). However, compact cells often predominate in those associated with virilization. This may cause problems in the assessment of malignant potential, as discussed later.

Adrenal Cortical Carcinomas

Adrenal cortical carcinoma is a rare but highly aggressive tumor. It has an estimated prevalence of between 0.5 and 12 per million60,68-70 and accounts for 0.05% to 0.2% of all malignancies.71-73 The bulk of evidence suggests that women are more commonly affected. There is a bimodal age distribution, with a peak in early childhood and a second peak in the fifth to seventh decades. The prognosis is very poor, with 67% to 94% mortality. The median or mean survival from diagnosis lies between 4 and 30 months. Many are locally invasive and between 15% and 67% have metastasized at the time of first presentation. The most common sites of metastasis are liver, lung, retroperitoneum, and lymph nodes.

Functioning tumors comprise between 24% and 74% of cases. Cushing syndrome is most common, often accompanied by androgen excess (mixed Cushing syndrome). Virilization may occur alone; feminizing tumors are rare. Other symptoms include abdominal or loin pain, abdominal fullness, and fever. Most respond poorly to treatment. Complete surgical excision is the mainstay of cure but may not be possible. The tumor is extremely resistant to chemotherapy, which may be explained in part by the expression of P-glycoprotein74,75 and glutathione S-transferases, 76 which play roles in various types of drug resistance. Mitotane (o,p -dichlorodiphenyldichloroethane, a derivative of dichlorodiphenyltrichloroethane) has a nonspecific adrenolytic effect and may be of use in controlling the disease.

Most carcinomas weigh more than 100 g but small tumors have behaved in a malignant fashion. Grossly, they may appear encapsulated or may be obviously adherent to or infiltrating surrounding structures (Figure 4). Lobulation is common with fibrous tissue separating tumor nodules. The cut surface is fleshy, with variable coloration, ranging from pink-brown to yellow. Hemorrhage and necrosis are common and there may be cystic change. In occasional cases, there is gross evidence of vascular invasion.

The architecture is less ordered than in adenomas (Figure 5). Trabecular and diffuse patterns of growth are seen and alveolar arrangement is uncommon. Compact cells often predominate. Nuclear pleomorphism is common, sometimes with multinucleated giant cells. Mitotic activity is usually seen, often with atypical forms. Oncocytic variants have been described.77 Broad fibrous bands are present in many cases and confluent necrosis is common. Both sinusoids and veins may be invaded and capsular invasion can be seen. Both local invasion and distant metastasis define malignancy.

Diagnosis of Malignant Potential and Prognostic Markers

As indicated previously, the diagnosis of carcinoma is easy in many cases. However, the risk of malignant potential must be assessed in all adrenal cortical tumors, even intra-adrenal lesions. This is best done by an overview of clinical, biochemical, and histologic findings and multifactorial analysis. Features to be assessed have been identified by examining differences between tumors with known benign and malignant outcome. Virilizing, feminizing, or large nonfunctional tumors are more usually carcinoma. Malignant tumors are usually heavier, and extensive necrosis, broad fibrous bands, and capsular, venous, and sinusoidal invasion are all more common in carcinoma. The overall architecture is more usually trabecular or diffuse and the proportion of clear cells lower. Nuclear pleomorphism, high mitotic activity, and the presence of atypical mitoses are important. These latter features should be assessed in the areas showing most marked change. A number of protocols for diagnosis have been published. In some, there is a combination of clinical, biochemical, and morphologic features that have been given a numerical weighting.78,79 The sum of the scores in a specific case defines the tumor as adenoma, of uncertain malignant potential, or carcinoma.

However, the pathologist may not have all the appropriate information to apply these approaches and may be limited to a histologic assessment.Weiss80,81 assessed 9 features (Table) and the presence of any 3 of these indicated malignant potential. This system is widely used by pathologists. It was validated in a more recent study82 with a specificity of 96% and sensitivity of 100% and there was good correlation of the overall score (r = 0.94). However, there was poorer correlation on some of the individual features including nuclear pleomorphism and vascular invasion and the group proposed omitting these features and incorporating the others into a weighted numerical score. All of these systems have value, but they may not always give the same diagnosis in an individual case. In difficult cases all clinical and histologic information should be taken into account. In a few cases a diagnosis of indeterminate or borderline tumor may have to be made.

There are a few additional investigations emerging. The Ki-67 (MIB-1) index is higher in carcinomas with levels of more than 4% to 5% seen only in malignant lesions.83,84 A low Ki-67 index does not define behavior as many carcinomas have levels below this threshold. Adrenal carcinoma is associated with overexpression of IGF-2,85,86 which can be detected by immunohistochemistry. Abnormal expression of p53 protein and p53 mutations are present in most carcinomas and rarely in adenomas, so again immunopositivity is supportive of a malignant diagnosis.87-89

High proliferative activity is associated with more aggressive behavior, tumors with a mitotic rate greater than 20 per 50 high- power fields80 or a Ki-67 index of greater than 3%88 showing a shorter disease-free interval. However, there appears to be no correlation with overall survival.

Immunohistochemistry

Occasionally adrenal cortical carcinoma may have to be distinguished from hepatocellular carcinoma, renal cell carcinoma, or pheochromocytoma. Antibody D11 has been reported as useful in identifying adrenal cortical tumors, 90 as have immunoreactivity for inhibin alpha (Figure 6)91,92 and Melan-A clone A103.93 Immunopositivity for SF-1 and DAX-194,95 has been reported but is not yet widely used in diagnostic practice. Immunopositivity for cytokeratins is weak or absent and they are negative for epithelial membrane antigen. Renal cell carcinoma is usually positive for both cytokeratins and epithelial membrane antigen. Hepatocellular carcinoma may be positive for alpha-fetoprotein, alpha1- antitrypsin, and carcinoembryonic antigen. Adrenal cortical carcinoma can show positive staining for general neuroendocrine markers including synaptophysin, so chromogranin A is the only marker that will positively discriminate between adrenal cortical carcinoma and pheochromocytoma.96

Molecular Pathogenesis of Adrenal Cortical Tumors

Clonality studies based on X chromosome inactivation have demonstrated that carcinomas are monoclonal but that adenomas may be monoclonal or polyclonal.97,98 Comparative genomic hybridization, loss of heterozygosity, and interphase cytogenetics have been used to examine changes in individual chromosomes and some conflicting data have emerged. Chromosomal changes have been reported in between 28%99 and 51%100 of adenomas. There is evidence to suggest accumulation of changes in tumor progression.100,101 Losses have been found on chromosomes 1p, 17p, 22p, 22q, and 11q and gains on 5, 12, 19, and 4.100 Loss of heterozygosity or allelic imbalance have been demonstrated at 11q13 (>/=90%), 17p13 (&ge85%), and 2p16 (92%) in carcinomas.99,102 Changes in chromosomes 3, 9, and X may be early events.101

A number of oncogenes and tumor suppressor genes have been investigated. Adrenal cortical carcinoma is one of the tumors seen in Li-Fraumeni syndrome, associated with germline mutations in the p53 gene.103 The majority of sporadic adrenal cortical carcinomas also show abnormal p53 expression and/or p53 mutations, whereas few adenomas do.88,89,104 An unusual inherited mutation in the p53 gene is thought to account for the high numbers of childhood adrenal carcinomas in Brazil and is also found in a proportion of the adult cases.105 Conflicting data exist on the ras family of oncogenes. Although 2 studies have shown no involvement,89,106 others report 12.5% of tumors with mutations in N-ras but none in Ki-ras or Ha- ras107 and 46% of cases with mutations in Ki-ras, but none in Haras. 108 Expression of c-myc protein may vary with tumor type, but it does not seem to be involved in neoplastic transformation.109 Somatic mutation of the menin (MEN1) gene is rare in adrenal cortical tumors.110 Familial tumors also occur in Beckwith- Wiedemann syndrome, associated with dysregulation of a group of growth controlling genes on 11p15.5111 including paternal disomy of the IGF2 gene. Rearrangement at this locus and overexpression of IGF- 2 has been reported in the majority of sporadic cases.86,112 Other growth factor interactions that may be involved are transforming growth factor alpha and epidermal growth factor receptor, IGF-1, its binding proteins and receptors,86,113,114 and the activins and inhibins. 91,92,115 Mutations in the ACTH receptor are found in a subset of adrenal cortical tumors but are probably not of major importance in pathogenesis.116

Immortalization of cells by the action of the protein/ RNA telomerase complex, not normally expressed in differentiated cells, may also play a role in tumorigenesis Published data to date on expression in adrenal cortical tumors are equivocal.117,118 The role of apoptosis is unclear. 18,119

A microarray study using 10 000 genes120 has confirmed IGF2 as important in carcinoma and has identified new candidate genes including fibroblast growth factor receptor 1, osteopontin, and 11beta-hydroxylase (CYP11B1). A further investigation121 examined cancer-related genes and adrenal cortex-related genes, including steroidogenic enzymes, cyclic adenosine monophosphate (cAMP) signaling components, and the IGF2 system. On the basis of the analysis of a combination of 8 genes from the IGF2 cluster and 14 from the adrenal cluster, the predictive value for malignancy was similar to that of the Weiss histologic score. The adrenal cluster was more highly expressed in adenomas and the IGF2 cluster in carcinomas. In addition, using expression profiles of 14 genes, it was possible to separate recurring from nonrecurring tumors in a group of 13 carcinomas. Correlation of molecular markers with outcome suggest that loss of heterozygosity at 17p13 and 11p15 and overexpression of IGF2 are associated with shorter disease-free survival and 17p13 loss of heterozygosity is independently associated with recurrence.102 These data require validation.

Other Tumors

Adrenal oncocytomas resemble similar lesions at other sites and are characterized by large eosinophilic cells (Figure 7), due to mitochondrial accumulation.122,123 Although originally described as nonfunctioning and benign, hormone- secreting124,125 and malignant125 variants have been reported. Myelolipomas (Figure 8) comprise a mixture of mature adipose tissue and hemopoietic tissue. Their histogenesis has not been clear, but the recent demonstration of clonality in both elements suggests that they are neoplastic. 126 Focal myelolipomatous change may be seen in other adrenal cortical tumors and in cortical hyperplasia.

Histologic Features to Be Assessed to Determine Malignant Potential

Diffuse architecture

Clear cells =25% of total

Significant nuclear pleomorphism

Confluent necrosis

Mitotic count >/=6 per 50 high-power fields

Atypical mitoses

Capsular invasion

Sinusoidal invasion

Venous invasion

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87. Barzon L, Chilosi M, Fallo F, et al. Molecular analysis of CDKN1C and TP53 in sporadic adrenal tumors. Eur J Endocrinol. 2001;145:207-212.

88. McNicol AM, Nolan CE, Struthers AJ, Farquharson MA, Hermans J, Haak HR. Expression of p53 in adrenocortical tumours: clinicopathological correlations. J Pathol. 1997;181:146-152.

89. Ohgaki H, Kleihues P, Heitz PU. p53 mutations in sporadic adrenocortical tumors. Int J Cancer. 1993;54:408-410.

90. Komminoth P, Roth J, Schroder S, Saremaslani P, Heitz PU. Overlapping expression of immunohistochemical markers and synaptophysin mRNA in pheochromocytomas and adrenocortical carcinomas: implications for the differential diagnosis of adrenal gland tumors. Lab Invest. 1995;72:424-431.

91. Arola J, Liu J, Heikkila P, Voutilainen R, Kahri A. Expression of inhibin alpha in the human adrenal gland and adrenocortical tumors. Endocr Res. 1998; 24:865-867.

92. Munro LM, Kennedy A, McNicol AM. The expression of inhibin/ activin subunits in the human adrenal cortex and its tumours. J Endocrinol. 1999;161: 341-347.

93. Ghorab Z, Jorda M, Ganjei P, Nadji M, Melan A. (A103) is expressed in adrenocortical neoplasms but not in renal cell and hepatocellular carcinomas. Appl Immunohistochem Mol Morphol. 2003;11:330-333.

94. Shibata H, Ikeda Y, Mukai T, et al. Expression profiles of COUP-TF, DAX-1, and SF-1 in the human adrenal gland and adrenocortical tumors: possible implications in steroidogenesis. Mol Genet Metab. 2001;74:206-216.

95. Sasano H, Suzuki T, Moriya T. Recent advances in histopathology and immunohistochemistry of adrenocortical carcinoma. Endocr Pathol. 2006;17:345- 354.

96. Haak HR, Fleuren GJ. Neuroendocrine differentiation of adrenocortical tumors. Cancer. 1995;75:860-864.

97. Gicquel C, Leblond-Francillard M, Bertagna X, et al. Clonal analysis of human adrenocortical carcinomas and secreting adenomas. Clin Endocrinol (Oxf ). 1994;40:465-477.

98. Beuschlein F, Reincke M, Karl M, et al. Clonal composition of human adrenocortical neoplasms. Cancer Res. 1994;54:4927-4932.

99. Kjellman M, Kallioniemi OP, Karhu R, et al. Genetic aberrations in adrenocortical tumors detected using comparative genomic hybridization correlate with tumor size and malignancy. Cancer Res. 1996;56:4219-4223. 100. Sidhu S, Marsh DJ, Theodosopoulos G, et al. Comparative genomic hybridization analysis of adrenocortical tumors. J Clin Endocrinol Metab. 2002;87: 3467- 3474.

101. Russell AJ, Sibbald J, Haak H, Keith WN, McNicol AM. Increasing geArch Pathol Lab Med-Vol 132, August 2008 Lesions of the Adrenal Cortex-McNicol 1271 nome instability in adrenocortical carcinoma progression with involvement of chromosomes 3, 9 and X at the adenoma stage. Br J Cancer. 1999;81:684-689.

102. Gicquel C, Bertagna X, Gaston V, et al. Molecular markers and long-term recurrences in a large cohort of patients with sporadic adrenocortical tumors. Cancer Res. 2001;61:6762-6767.

103. Srivastava S, Zou Z, Pirollo K, Blattner W, Chang EH. Germline transmission of a mutated p53 gene in a cancer-prone family with Li-Fraumeni syndrome. Nature. 1990;348:747-749.

104. Reincke M, Karl M, Travis WH, et al. p53 mutations in human adrenocortical neoplasms: immunohistochemical and molecular studies. J Clin Endocrinol Metab. 1994;78:790-794.

105. Latronico AC, Pinto EM, Domenice S, et al. An inherited mutation outside the highly conserved DNA-binding domain of the p53 tumor suppressor protein in children and adults with sporadic adrenocortical tumors. J Clin Endocrinol Metab. 2001;86:4970-4973.

106. Moul JW, Bishoff JT, Theune SM, Chang EH. Absent ras gene mutations in human adrenal cortical neoplasms and pheochromocytomas. J Urol. 1993;149: 1389-1394.

107. Yashiro T, Hara H, Fulton NC, Obara T, Kaplan EL. Point mutations of ras genes in human adrenal cortical tumors: absence in adrenocortical hyperplasia. World J Surg. 1994;18:455-460; discussion 460-451.

108. Lin SR, Tsai JH, Yang YC, Lee SC. Mutations of K-ras oncogene in human adrenal tumours in Taiwan. Br J Cancer. 1998;77:1060-1065.

109. Liu J, Voutilainen R, Kahri AI, Heikkila P. Expression patterns of the cmyc gene in adrenocortical tumors and pheochromocytomas. J Endocrinol. 1997; 152:175-181.

110. Heppner C, Reincke M, Agarwal SK, et al. MEN1 gene analysis in sporadic adrenocortical neoplasms. J Clin Endocrinol Metab. 1999;84:216-219.

111. Li M, Squire JA, Weksberg R. Molecular genetics of Wiedemann- Beckwith syndrome. Am J Med Genet. 1998;79:253-259.

112. Gicquel C, Raffin-Sanson ML, Gaston V, et al. Structural and functional abnormalities at 11p15 are associated with the malignant phenotype in sporadic adrenocortical tumors: study on a series of 82 tumors. J Clin Endocrinol Metab. 1997;82:2559-2565.

113. Ilvesmaki V, Liu J, Heikkila P, Kahri AI, Voutilainen R. Expression of insulin- like growth factor binding protein 1-6 genes in adrenocortical tumors and pheochromocytomas. Horm Metab Res. 1998;30:619-623.

114. Weber MM, Auernhammer CJ, KiessW, Engelhardt D. Insulin- like growth factor receptors in normal and tumorous adult human adrenocortical glands. Eur J Endocrinol. 1997;136:296-303.

115. McCluggage WG, Burton J, Maxwell P, Sloan JM. Immunohistochemical staining of normal, hyperplastic, and neoplastic adrenal cortex with a monoclonal antibody against alpha inhibin. J Clin Pathol. 1998;51:114-116.

116. Latronico AC. Role of ACTH receptor in adrenocortical tumor formation. Braz J Med Biol Res. 2000;33:1249-1252.

117. Bamberger CM, Else T, Bamberger AM, et al. Telomerase activity in benign and malignant adrenal tumors. Exp Clin Endocrinol Diabetes. 1999;107: 272-275.

118. Mannelli M, Gelmini S, Arnaldi G, et al. Telomerase activity is signifi- cantly enhanced in malignant adrenocortical tumors in comparison to benign adrenocortical adenomas. J Clin Endocrinol Metab. 2000;85:468-470.

119. Bernini GP, Moretti A, Viacava P, et al. Apoptosis control and proliferation marker in human normal and neoplastic adrenocortical tissues. Br J Cancer. 2002; 86:1561-1565.

120. Giordano TJ, Thomas DG, Kuick R, et al. Distinct transcriptional profiles of adrenocortical tumors uncovered by DNA microarray analysis. Am J Pathol. 2003;162:521-531.

121. de Fraipont F, El Atifi M, Cherradi N, et al. Gene expression profiling of human adrenocortical tumors using complementary deoxyribonucleic acid microarrays identifies several candidate genes as markers of malignancy. J Clin Endocrinol Metab. 2005;90:1819-1829.

122. Sasano H, Suzuki T, Sano T, Kameya T, Sasano N, Nagura H. Adrenocortical oncocytoma: a true nonfunctioning adrenocortical tumor. Am J Surg Pathol. 1991;15:949-956.

123. Lin BT, Bonsib SM, Mierau GW, Weiss LM, Medeiros LJ. Oncocytic adrenocortical neoplasms: a report of seven cases and review of the literature. Am J Surg Pathol. 1998;22:603-614.

124. Xiao GQ, Pertsemlidis DS, Unger PD. Functioning adrenocortical oncocytoma: a case report and review of the literature. Ann Diagn Pathol. 2005;9: 295-297.

125. Golkowski F, Buziak-Bereza M, Huszno B, et al. The unique case of adrenocortical malignant and functioning oncocytic tumour. Exp Clin Endocrinol Diabetes. 2007;115:401-404.

126. Bishop E, Eble JN, Cheng L, et al. Adrenal myelolipomas show nonrandom X-chromosome inactivation in hematopoietic elements and fat: support for a clonal origin of myelolipomas. Am J Surg Pathol. 2006;30:838-843.

Anne Marie McNicol, BSc, MD, FRCPGlas, FRCPath

Accepted for publication February 28, 2008.

From the Pathology Department, University of Glasgow, Royal Infirmary, Glasgow, United Kingdom.

The author has no relevant financial interest in the products or companies described in this article.

Reprints: Anne Marie McNicol, BSc, MD, FRCPGlas, FRCPath, Pathology Department, University of Glasgow, Royal Infirmary, Castle Street, Glasgow, Lanarkshire G4 0SF, United Kingdom (e-mail: [email protected]).

Health

Nontuberculous Mycobacterial Infections

Written By: Sam Savage

Published Date: August 30, 2008 Last Edited: August 30, 2008

By Jarzembowski, Jason A Young, Michael B

* Context.-Nontuberculous mycobacteria include numerous acid- fast bacilli species, many of which have only recently been recognized as pathogenic. The diagnosis of mycobacterial disease is based on a combination of clinical features, microbiologic data, radiographic findings, and histopathologic studies. Objective.-To provide an overview of the clinical and pathologic aspects of nontuberculous mycobacteria infection, including diagnostic laboratory methods, classification, epidemiology, clinical presentation, and treatment.

Data Sources.-Review of the pertinent literature and published methodologies.

Conclusions.-Nontuberculous mycobacteria include numerous acid- fast bacilli species, many of which are potentially pathogenic, and are classified according to the Runyon system based on growth rates and pigment production. Their slow growth hinders cultures, which require special medium and prolonged incubation. Although such methods are still used, newer nucleic acid-based technologies (polymerase chain reaction and hybridization assays) can rapidly detect and speciate some mycobacteria-most notably, distinguishing Mycobacterium tuberculosis from other species. Infections caused by these organisms can present as a variety of clinical syndromes, not only in immunocompromised patients but also in immunocompetent hosts. Most common among these are chronic pulmonary infections, superficial lymphadenitis, soft tissue and osteoarticular infections, and disseminated disease. Treatment of nontuberculous mycobacterial infections is difficult, requiring extended courses of multidrug therapy with or without adjunctive surgical intervention. (Arch Pathol Lab Med. 2008;132:1333-1341)

Nontuberculous mycobacteria (NTM) comprise a variety of species and are responsible for a wide range of clinical syndromes. They encompass all mycobacterial species other than Mycobacterium tuberculosis complex (MTB) and Mycobacterium leprae. Nontuberculous mycobacteria have been known since the time of Robert Koch, but historically they have been overshadowed by tuberculosis and dismissed as contaminants. Their clinical significance has only been recently appreciated. With advances in molecular microbiology and knowledge of these organisms, NTM are now recognized as true pathogens and important causes of human infection.

MICROBIOLOGY

Classification

Nontuberculous mycobacteria generally are free-living organisms that are ubiquitous in the environment. Important reservoirs include water (including tap water), soil, animals, and dairy products; they can also be found as colonizers of medical equipment such as endoscopes and surgical solutions.1 Person-to-person spread has not been reported.1 More than 125 species of NTM have been identified, 2 approximately 60 of which are suspected or known to cause disease.1 Traditionally, NTM have been grouped into 4 broad categories according to the Runyon system (Table 1). In this classification, NTM are divided by growth rates and pigment production. Groups I to III are slow-growing NTM, and group IV are fast growers (ie, detectable in culture within 7 days). The slow-growing NTM are subdivided into group I photochromogens (pigment producers in the presence of light), group II scotochromogens (pigment producers in the absence of light), and group III nonchromogens. Although superseded by more modern genetic techniques, this classification system provides physicians with a clinically relevant, presumptive speciation. Clinically important species by group include Mycobacterium kansasii and M marinum (group I); Mycobacterium gordonae and M scrofulaceum (group II); Mycobacterium avium- intracellulare (MAI) and M ulcerans (group III); and Mycobacterium fortuitum, M chelonae, and M abscessus (group IV).

Laboratory Safety

Hospital-based laboratories performing a low volume of mycobacterial isolation, identification, and susceptibility testing are classified as ”low-risk” and must follow Biosafety Level 2 protocols.3 In addition to universal precautions, all specimen processing should be performed in a Class I or Class II biosafety cabinet, attempting to avoid aerosol formation during any liquid manipulations. Screening of laboratory personnel by (at least) annual purified protein derivative skin testing and appropriate postexposure clinical evaluation and testing are essential.3

Specimen Collection

As with all clinical specimens destined for microbiologic analysis, body fluids and tissue samples should be col lected in sterile, properly labeled containers and immediately transported to the laboratory.4,5 Specimens that cannot be sent within an hour or so should be refrigerated. 6,7 Although swabs have traditionally been considered unacceptable for mycobacterial work, several groups have reported adequate recovery of organisms from such samples. 8,9

Sputum is the preferred specimen for suspected pulmonary disease and is best obtained first thing in the early morning.2 Although the presence of MTB in any specimen is considered clinically significant, oral contamination from NTM is a possible source of false positivity with nonproductive efforts to induce sputum.10 For initial diagnostic purposes, specimen should be collected on 3 to 5 consecutive days; for evaluating therapeutic efficacy, specimens should be collected weekly starting 3 weeks after beginning treatment.4,11,12 Bronchoalveolar lavage fluid or bronchial washings may be submitted instead of sputum; these specimens should be collected directly into an aliquot of medium, such as Middlebrook broth.13 Gastric lavage fluid (swallowed sputum) is an acceptable surrogate for sputum in pediatric and neurologically compromised patients.14 The specimen is collected by aspiration through an orogastric or nasogastric tube and neutralized by immediately adding 100 mg sodium carbonate. False-negative results from gastric lavage specimens can occur when the stomach acid is not neutralized in a timely fashion causing degradation of mycobacteria.4 False-positive results may result from contamination by oral saprophytic mycobacterial species.10

Blood cultures can be performed using an automated system such as BACTEC (BD Diagnostic Systems, Sparks, Md) with specialized collection tubes designed to lyse cells, thereby releasing intracellular organisms. As with sputum, the first voided urine of the day gives the highest diagnostic yield. Midstream clean catch specimens should be collected in sterile containers. Stool cultures are useful for the identification of gastrointestinal disease in immunocompromised patients.15,16 Specimens should be aseptically collected and an aliquot sent to the laboratory. Fecal smears are rather insensitive (about 30%) and therefore should be cultured regardless of whether organisms are identified on the initial screen.17 Finally, tissue biopsies can be sent in parallel for histology and mycobacterial culture.

Specimen Processing

Aseptically collected specimens can be directly inoculated into appropriate medium, using a liquid sample or saline-based homogenate of sterile tissue.4,5 Potentially contaminated samples, on the other hand, pose a greater challenge. Because mycobacteria are slow growing and require extended incubation, contaminating organisms pose a greater problem than in routine bacteriology. Furthermore, mycobacteria may be lodged within viscous fluid or cellular debris, needing to be released prior to culture. Chemical and enzymatic treatment of the specimen can solve both these problems. Typically used reagents include sodium hydroxide, dithiothreitol, dilute sodium hypochlorite, and N-acetylcysteine, often used in combination; vortex mixing or physical disruption may also be useful.4,5,18 The optimal pretreatment regimen will depend on the specimen type, institutional experience, and laboratory workflow. Finally, to optimize culture sensitivity, concentration of the specimen (usually by centrifugation) prior to inoculation is recommended.19

Staining

Because culture of these relatively slow-growing organisms can take weeks, specimen smears can rapidly yield clinically relevant information. Properly performed smears are highly specific and relatively sensitive, around 50%.20,21 All mycobacteria are acid- fast bacilli, that is, they do not decolorize with acidified alcohol after staining with carbolfuchsin. This property is thought to exist due to the presence of mycolic acid in the lipid-rich bacterial cell wall. By the traditional Gram stain method, mycobacteria can occasionally stain positively (mimicking gram-variable organisms) or, more commonly, appear as unstained silhouettes against the background. As with any preparation, debris and other organisms may mimic the appearance of mycobacteria, requiring careful assessment of staining and morphologic features. At least 300 fields of a carbolfuchsin-stained smear should be thoroughly searched at high power ( x 1000) before declaring it to be negative.5,18 Fluorescently stained smears, using auraminerhodamine, highlight the organisms as orange-yellow rods against a black background and can be screened at lower magnification ( x 250) for correspondingly fewer fields (at least 30); these have become the preferred method of smear examination.2,4

Culture

Unfortunately, mycobacterial cultures are time-consuming and require specialized reagents. Lowenstein-Jensen media, an egg-based medium containing malachite green dye to inhibit growth of contaminating organisms, is the traditional solid media for culture of mycobacteria. The use of agar-based Middlebrook medium can facilitate ear ly detection of colony growth, but these plates are more expensive and outdate quickly.With either method, visible colony growth can take up to 6 weeks. With liquid media and modern culture systems (such as the BACTEC AFB or Mycobacteria Growth Indicator Tubes), growth can typically be seen in approximately 2 weeks. However, neither is 100% sensitive, and both should be used together.2,22 Although broth-based cultures are more sensitive and can yield quicker growth, solid-phase cultures allow assessment of colony morphology and longer-term storage. Although most mycobacteria grow optimally between 35 and 37[degrees]C in 5% to 10% CO2, a subset including M marinum, M ulcerans, M chelonae, and M haemophilum thrive better between 25 and 33[degrees]C. Identification and Speciation

As discussed previously, mycobacteria can be preliminarily and roughly classified by pigmentation and growth characteristics. Previously, further identification of mycobacterial species was a uniformly tedious process involving biochemical tests that could require weeks of subcultures. Most clinically important species can now be identified more rapidly via nucleic acid probes (eg, MAI and MTB) and by examining mycolic acid ester patterns via high- performance layer chromatography.23-28 The development of nonisotopically labeled DNA probes complementary to species- specific rRNA has allowed rapid identification of organisms using aliquots of broth culture or picked colonies.29-31 Many different polymerase chain reaction amplification-based assays, including the Mycobacterium Tuberculosis Direct Test (GenProbe, San Diego, Calif), the AMPLICOR MTC assay (Roche, Basel, Switzerland), and a plethora of ”homebrew” tests, have been created to detect M tuberculosis rapidly and directly from specimens.32-37 Depending on the particular assay, and specimen type and volume, reported sensitivities vary from 50% to 100% and specificity is usually greater than 95%. However, these molecular tests also detect nonviable organisms, precluding their use in proof of treatment. The polymerase chain reaction assays are best suited to rapid initial detection of infection, with the primary goal of identifying MTB to initiate prompt therapy (see reference 37 for a review of the various molecular techniques suitable for mycobacterial analysis).

Susceptibility

The antimicrobial susceptibility of MTB and rapidly growing NTM species (RGM) can be ascertained by traditional methods, such as broth dilution, Kirby-Bauer, or Etest,20,37-40 although broth-based methods are preferred.2 Unfortunately, there is little in the way of controlled trials correlating in vitro antibiotic susceptibility and clinical efficacy, with the exception of clarithromycin-based therapy for MAC and rifampin-based therapy for M kansasii.2With the exception of clarithromycin, in vitro susceptibility patterns of MAC correlate poorly with in vivo behavior; therefore, routine, broad antimicrobial susceptibility testing for MAC is not advised.38 Recommendations for initial antimicrobial susceptibility testing for other NTM species varies. Current recommendations for M kansasii and other slow-growing NTM species such as Mycobacterium malmoense, M xenopi, and M terrae complex include initial susceptibility testing to rifampin, and if rifampin resistant, testing of second-line agents such as amikacin, ciprofloxacin, clarithromycin, ethambutol, rifabutin, streptomycin, sulfonamides, and isoniazid should be done.2 For RGM (eg, M abscessus, M chelonae, M fortuitum, M smegmantis, M mucogenicum), broth microdilution antimicrobial susceptibility testing is recommended.2 There is no standard panel of antibiotic testing routinely recommended for these species. 2 However, agents that have been used to treat RGM infections have included amikacin, imipenem, cefoxitin, clarithromycin, ciprofloxacin, doxycycline, linezolid, sulfamethoxazole, and tobramycin. Additional testing for newer agents such as linezolid, moxifloxacin, and tigecycline can be considered, although there is little clinical experience with these agents. Of note, ciprofloxacin susceptibility testing, which correlates with susceptibilities to levofloxacin and ofloxacin, may not predict susceptibilities to the newer fluoroquinolone moxifloxacin.2 No initial antimicrobial susceptibility testing for M marinum is recommended.2

HISTOPATHOLOGY

Evidence of NTM infection may be seen in sampled lung, skin, bone marrow, lymph node, mediastinum, liver, or other sites (Figure, A through C). Many patients with disseminated NTM infection, especially in the immunocompromised population, lack granulomas or stainable organisms. Mycobacteria-laden histiocytes or macrophages may be seen in lieu of well-formed granulomas, especially on acid- fast stains such as Fite or Ziehl-Neelsen. For example, MAI infection of the small bowel may show organisms within macrophages distending the lamina propria, similar to Whipple disease (Figure, B).41,42 Therefore, although stains should be routinely performed when clinical suspicion for NTM is high, absence of histologic features does not rule out infection.

EPIDEMIOLOGY

The true prevalence of infection with NTM is unknown. Noncomprehensive, national survey data of mycobacterial isolates from the 1970s and 1980s estimate the rate of NTM infection at 1.8 cases per 100 000 in the United States.43,44 This number likely underestimates the current prevalence of NTM infection. More recent data have shown an increase in the number and distribution of mycobacterial infections. In contrast to the previously mentioned studies in which two thirds of mycobacterial isolates were MTB, a Centers for Disease Control and Prevention survey found that 74% of mycobacterial isolates in 1991 to 1992 were NTM despite an overall increase in the number of MTB isolates.45,46 This rise in NTM infections has been attributed to an increased recognition of NTM clinical syndromes and the emergence of the immunocompromised patient, particularly patients with human immunodeficiency virus/ acquired immunodeficiency syndrome (HIV/AIDS) but also those immunosuppressed for other reasons such as organ transplantation.47

Nontuberculous mycobacterium are more commonly isolated from young adults and elderly patients.45 It is thought that this reflects the predilection for disseminated and pulmonary NTM disease in these age groups, respectively. 47 Disseminated disease is most often seen in HIV/ AIDS, which predominantly afflicts a younger population, and chronic pulmonary NTM syndromes are more common among the elderly.

Mycobacterium avium-intracellulare is the most commonly encountered NTM in the United States. National surveys from the early 1980s found 61% of NTM isolates were MAI, 19% were M fortuitum complex, and 10% were M kansasii.43,44 From this same data, it was estimated that the prevalence of MAI infection was 1.1 cases per 100 000.43,44 As noted previously, these surveys were performed prior to the HIV/AIDS era and likely underestimate the prevalence of MAI infection. Reported rates of disseminated NTM infection in HIV/AIDS patients range from 5% to 40%,48-50 of which 96% were MAI.49

Nontuberculous mycobacteria infections vary geographically by species. For example, MAI is found worldwide but rarely causes disseminated infection in HIV/AIDS patients in Africa.47 Mycobacterium kansasii tends to be clustered in the central United States, and species rarely seen in the United States such as M xenopi and M malmoense are major pathogens in Canada/Britain and Scandinavia, respectively. 47

CLINICAL FEATURES

The spectrum of clinical infections caused by NTM varies widely and defies easy review. However, it can be divided into several broad categories: chronic pulmonary infections, superficial lymphadenitis, soft tissue and osteoarticular infections, disseminated disease, and iatrogenic infections.

Pulmonary Infections

Chronic pulmonary infections are among the most common clinical manifestations of NTM disease. The NTM species most often associated with pulmonary disease in the United States is MAI followed by M kansasii.2 Less commonly reported organisms include M abscessus, M fortuitum, M szulgai, M simiae, M xenopi, M malmoense, M celatum, M asiaticum, and M shimoidei.2 As stated previously, the distribution of species causing disease varies geographically. For example, M xenopi, which is rarely found in the United States, is the second most commonly isolated organism in Canada and Europe.2

The clinical presentation with NTM-related pulmonary infection can be quite varied. Chronic cough is nearly universal, but fevers, malaise, weight loss, dyspnea, and hemoptysis are much more variable.2 Affected individuals typically are not severely immunocompromised. However, those with underlying lung pathology such as chronic obstructive pulmonary disease, bronchiectasis, prior MTB, cystic fibrosis, other pneumoconiosis, treatment with tumor necrosis factor inhibitors, or certain body habiti (eg, pectus excavatum or scoliosis, particularly in postmenopausal women) are at risk, although infection in individuals without risk factors is well reported.2

The clinical spectrum of pulmonary disease is quite variable as well. Both M xenopi and MAI have been reported to cause disease similar to MTB. Upper lobe involvement and cavitary lesions can be seen, particularly with M kansasii in which up to 90% of patients will have cavitary disease.46,47 Patients with this type of MTB- like lung involvement typically are middle-aged to elderly men with a history of smoking or underlying lung disease as noted previously.46,47 Pulmonary infiltrates without cavitation has also been reported. Affected individuals typically have bronchiectasis, such as can be seen in older individuals with a history of MTB or patients with cystic fibrosis. 2,46,51,52 A more unusual presentation of MAI is the socalled Lady Windemere syndrome.53 This syndrome is seen in elderly women without preexisting pulmonary conditions or a history of tobacco abuse. The typical clin ical scenario is of interstitial pulmonary infiltrates, often starting in dependent regions of the right middle lobe or lingula, with an absence of cavitation or hilar lymphadenopathy. 53 Mycobacterium avium-intracellulare has also been reported to cause solitary pulmonary nodules in the absence of other symptoms,46,52 and a newly described syndrome has been reported of hypersensitivity pneumonitis typically related to exposure to MAI in aerosolized household water, that is ”hot tub lung.” 54,55 Another hypersensitivity pneumonitis- like syndrome, presumably related to exposure to organic metal- working compounds, may also be seen.2 Isolated pulmonary disease has been the exception rather than the rule in HIV/AIDS. However, most reports of HIV-associated MAI disease are from an era prior to effective HIV therapy. With the development of highly active antiretroviral therapy and the ability to reconstitute CD4+ T-cell- based immune function, localized MAI disease in HIV/AIDS patients may become more frequent. The radiographic findings seen with NTM pulmonary infections are variable.2 Plain radiography can reveal cavitary lesions, frank parenchymal or interstitial infiltrates, bronchiectasis, volume loss, or solitary or multiple pulmonary nodules or be relatively unremarkable.46,56 Because of superior resolution, high-resolution computed tomography of the chest is now recommended if plain chest radiography does not reveal fibrocavitary disease.2 The pattern of lung lesions does not reliably distinguish between NTM species.

Nontuberculous mycobacteria pulmonary infection can be diagnosed via a combination of clinical, radiographic, bacteriologic, and histologic criteria as proposed by the American Thoracic Society and the Infectious Disease Society of America (Table 2).2 These guidelines apply to both HIV-positive and immunocompetent hosts. Briefly, the diagnosis of NTM lung disease requires appropriate symptomatology, radiographic evidence of pulmonary involvement (eg, infiltrates, nodules, or cavities on plain radiography or high- resolution computed tomography findings of multifocal bronchiectasis and/or small nodules), positive cultures or suggestive histologic findings, and exclusion of other diagnoses.2 Semiquantitative reporting of acid-fast bacilli smear positivity, which was part of the 1997 American Thoracic Society guidelines,46 is no longer recommended.

Treatment of NTM pulmonary infection can be difficult and involves prolonged courses of multiple antimycobacterial agents. The approach to treatment and the choice of medication varies according to the NTM species isolated. For MAI, current recommendations are for a minimum of 3 drugs. The backbone of any regimen should be a macrolide, either clarithromycin or azithromycin, which are the most effective agents for MAI, combined with a second or third agent to prevent the emergence of macrolide resistance.2 Monotherapy with clarithromycin or azithromycin has been shown to be clinically efficacious but should not be used as resistance and eventual treatment failure has been shown to develop when a macrolide is used alone.57,58 Treatment guidelines for MAI pulmonary disease vary with severity of disease.2 For initial therapy of nodular/bronchiectatic disease, the recommendations are clarithromycin 1000 mg 3 times a week or azithromycin 500 to 600 mg 3 times a week combined with ethambutol 25 mg/kg 3 times a week and rifampin 600 mg 3 times a week. For cavitary disease, clarithromycin 500 to 1000 mg per day or azithromycin 250 to 300 mg per day, ethambutol 15 mg/kg per day, rifampin 450 to 600 mg per day, with or without parenteral amikacin or streptomycin is recommended, whereas for severe or previously treated disease, the previous with parenteral aminoglycoside for the first 2 to 3 months is recommended. American Thoracic Society guidelines recommend obtaining sputum cultures monthly while on therapy. As a general rule, most patients treated with a macrolide- based regimen should improve within 3 to 6 months and convert their sputum to culture negative within 12 months.2 The role of surgical therapy is limited as MAI pulmonary disease tends to be a multifocal process but may be important for select individuals.2

Treatment of pulmonary disease resulting from M kansasii also involves a multidrug regimen, the backbone of which is rifampin. The current recommendation is a combination of isoniazid (300 mg per day), rifampin (600 mg per day), and ethambutol (15 mg/kg per day) until the sputum cultures remain negative for 12 months.2 Mycobacterium fortuitum is typically susceptible to fluoroquinolones, doxycycline, minocycline, sulfonamides, linezolid, and tigecycline, and 2-drug regimens until 12 months of negative sputum cultures are likely to be effective.2,46,59-61 Mycobacterium fortuitum typically tests sensitive to macrolides as well, although the recent discovery that this species carries the erythromycin methylase gene erm raises the possibility of inducible macrolide resistance.2 Pulmonary disease with M abscessus is more common than M fortuitum and much more difficult to treat. Antibiotic options are limited to clarithromycin and intravenous agents such as amikacin, cefoxitin, and possibly imipenem.2 The toxicity of these intravenous medications can be significant because of the prolonged length of therapy needed for probable cure. The newer fluoroquinolones, linezolid, and telithromycin do not have reliable activity against M abscessus but may be second-line options.2,59,61 Recent studies have found the novel glycylcycline tigecycline has excellent activity against the RGM, including M abscessus.60 Whether this will translate into clinical efficacy is unknown, but tigecycline is generally well tolerated and may provide another option for long- term therapy of M abscessus.

Lymphadenitis

Localized lymph node infection is the most common presentation of NTM disease in children.2 The most commonly affected lymph node chains are in the head and neck, particularly the anterior cervical chain but also the submandibular, submaxillary, and preauricular lymph nodes.1,2,46 Occasionally, mediastinal lymph nodes can be involved.1 The usual presentation is of painless swelling of one or more lymph nodes in a regional distribution without systemic symptoms.2 It is unilateral in 95% of cases and can result in chronic, draining fistulae to the skin.1,2,46

The peak incidence occurs in children ages 1 to 5 years.2 Lymphadenitis is uncommon in adults with the exception of HIV- infected patients in the post-highly active antiretroviral therapy era.62 Historically, NTM disease, overwhelmingly because of MAI, in HIV-infected individuals was almost uniformly a disseminated process. With the advent of effective antiretroviral therapy, lymphadenitis as part of the syndrome of immune reconstitution can be seen. Usually found in HIV-infected individuals with severe CD4+ lymphopenia and preexisting subclinical MAI infection, this syndrome presents as a constellation of fevers, leukocytosis, and lymphadenitis (cervical, thoracic, and/or abdominal) that can be seen with initiation of highly active antiretroviral therapy.62

The most common species found in lymphadenitis in children is MAI, which is found in approximately 80% of culture-positive cases.1,2,46 Mycobacterium scrofulaceum, the most common cause in the 1970s, is the second most commonly isolated species in the United States.1,2,46 Other species that have been reported to cause NTM lymphadenitis include the RGM, M malmoense, M kansasii,Mhaemophilum, M interjectum, M palustre, M tusciae, M heidelbergense, M elephantis, M lentiflavum, and M bohemicum.1 Approximately 10% of mycobacterial lymphadenitis in children is because of MTB. In contrast, more than 90% of cases in adults is because of MTB.2

Diagnosis of NTM lymphadenitis hinges on either positive culture for NTM or suggestive histopathology coupled with a negative evaluation of MTB. All persons should receive a purified protein derivative test to evaluate for MTB. Most individuals will have a mild ( 10 mm) reaction because of cross-reactivity between MTB and NTM proteins, but induration greater than 10 mm has been reported in nearly one third of children with NTM lymphadenitis.46 Lymph node tissue can be obtained either by fine-needle aspiration or excision of the involved lymph nodes.2 Classic histopathologic findings include caseating granulomata.2 Acid-fast bacilli may or may not be seen, and positive tissue cultures for NTM can be obtained in 50% to 80% of cases.2

Surgical removal without antimycobacterial therapy is the cornerstone of treatment of NTM lymphadenitis, in contrast to MTB- related lymphadenitis for which antibiotic therapy is paramount.2 This approach is curative in more than 90% of cases in children. It must be emphasized that complete excision of affected lymph nodes and not simple incision and drainage must be performed, because the latter approach frequently results in fistula formation and persistent disease. Antimycobacterial-based therapy should be reserved for those with recurrent disease or for whom surgical therapy is impractical, and the choice of antibiotics will depend on the NTM species isolated.2

Disseminated Disease

Disseminated NTM disease is most commonly found in patients with advanced HIV disease, particularly those with CD4+ cell counts less than 50 cells per L.2 More than 95% of disseminated NTM disease in HIV patients is because of MAI.2 Other NTM species reported to cause disseminated disease in HIV patients include M chelonae, M abscessus, M xenopi, M conspicuum, M gordonae, M kansasii, M genavense, M haemophilum, M fortuitum,Mmarinum, M simiae, M scrofulaceum, M celatum, M malmoense, M triplex, and M lentiflavum.1,46,47 The most common symptoms of disseminated NTM disease in HIV patients are fevers, night sweats, and weight loss.2 Diarrhea and abdominal pain are also frequently reported with MAI. Physical examination findings typically are nonspecific, although hepatosplenomegaly can be seen. Mycobacteria chelonae, M abscessus, and M haemophilum may present with diffuse subcutaneous nodules and abscesses, and disease withMkansasii is usually associated with pulmonary involvement.47 Laboratory findings are also nonspecific but may reveal severe anemia and an elevated alkaline phosphatase in MAI disease.2 Disseminated disease in non-HIV patients are usually found in those with severe immunosuppression from other conditions, such as organ transplantation, hematologic malignancies, and chronic steroid use.2,46,63,64 Nontuberculous mycobacteria infections have also been reported in individuals receiving therapy with tumor necrosis factor- alpha antagonists such as infliximab and etanercept.63,64 Reported NTM species from disseminated NTM disease in non-HIV patients include MAI, M kansasii, M chelonae, M abscessus, and M haemophilum.2 As a rule, MAI disease in immunocompromised, non-HIV patients also presents as fevers without localizing signs, whereas other NTM species will present with subcutaneous nodules or abscesses.2

Disseminated MAI can rarely present as single or multiple tuberculomas that mimic a neoplastic process. This syndrome of mycobacterial spindle cell pseudotumors is usually seen in patients with advanced AIDS, although it has also been reported in individuals immunocompromised for other reasons.65-71 As the name suggests, these lesions histologically are composed of expansile aggregates of proliferative spindle cells and epithelioid histiocytes that resemble a mesenchymal neoplasm.65-71 Mycobacterial spindle cell pseudotumors have been reported to involve lymph nodes, bone marrow, intestine, skin, lungs, retroperitoneum, and the brain, where they can resemble MTB tuberculomas or meningiomas.65-71

Diagnosis of disseminated NTM disease is made by positive culture from a normally sterile site such as blood or bone marrow. For those with cutaneous lesions, positive culture from skin biopsy in the appropriate clinical setting is also diagnostic. The sensitivity of blood culture in disseminated MAI disease in HIV patients is 90%.2

Treatment of disseminated NTM disease is based on multidrug therapy. Antimycobacterial regimens are similar to those recommended for NTM pulmonary disease.2 For MAI, macrolide-based therapy (clarithromycin or azithromycin) plus rifabutin and ethambutol is recommended. For those with severe symptoms, amikacin or streptomycin may be added for initial induction therapy. The use of rifabutin in HIV patients may be complicated by drug interactions with protease inhibitors and, to a lesser extent, efavirenz.72,73 Rifabutin enhances the metabolism of protease inhibitors, and protease inhibitors inhibit the metabolism of rifabutin.2,46,73 Pharmokinetic studies indicate that alternative dosing regimens of rifabutin, such as every other day administration, may allow patients to maintain therapeutic levels of protease inhibitors.46,72

Soft Tissue and Skeletal Infections

The spectrum of NTM-related soft tissue and skeletal infections (STSIs) is broad and ranges from chronically draining, localized abscesses or nodules to tenosynovitis to frank osteomyelitis. Soft tissue and skeletal infection usually arises as the result of direct inoculation such as penetrating trauma or soilage of open wounds and fractures. Infection can also be introduced iatrogenically, and NTM have been reported to cause infections following intravenous and peritoneal catheters, shunts, intramuscular injections, cosmetic surgery procedures, laser in situ keratomileusis procedures, and postsurgical wounds.1,2,46 The presentation of NTM STSI is typically indolent, and the clinical course variable. Minor cutaneous infections may resolve spontaneously during the course of 8 to 12 months.46 However, more serious disease, such as osteomyelitis, will likely progress over time.

The RGM species M abscessus, M fortuitum, and M chelonae are the most common species to cause STSI, although other species are associated with certain clinical syndromes. 2 Mycobacterium fortuitum has been noted to cause localized STSI is immunocompetent individuals, whereas patients with M chelonae and M haemophilum infection are typically immunosuppressed.1 Mycobacterium abscessus has been reported to cause localized STSI disease in both immunocompetent and immunocompromised persons.1 Mycobacterium marinum, MAI, M kansasii, and M terrae complex have been noted to cause chronic granulomatous infections of tendon sheaths, bursa, joints, and bone in addition to M abscessus, M fortuitum, and M chelonae.2 Mycobacterium marinum causes a peculiar clinical condition termed swimming pool granuloma or fish tank granuloma. This is typically seen in individuals who have had exposure to some type of marine environment (eg, fish, crustaceans, fish tanks) and presents as granulomatous lesions, usually on portions of the extremities prone to abrasions.1 The lesions usually begin as papules that then ulcerate and scar.1,46 Disease is often localized, but some patients can develop a nodular lymphangiitis similar to sporotrichosis. 1,46 Mycobacterium ulcerans causes a syndrome of chronic, necrotic skin lesions of the extremities called Buruli ulcer.2 This is usually seen in the tropics and Australia and starts as a pruritic nodule that eventually degenerates into a large, irregular, undermined ulcer.1,46,47

The diagnosis of NTM STSI can be made on the basis of histology and cultures. Treatment of NTM STSI often involves a combination of antibiotics and surgical excisions. As mentioned previously, minor cutaneous disease can often resolve without treatment. However, this can be a prolonged process, and surgical treatment likely can accelerate resolution of disease. For osteoarticular infections, surgical excision of infected tissue should be performed when feasible.2 When prosthetic material is involved, its removal should be considered mandatory as NTM infection in such a setting is unlikely to resolve with antibiotic therapy alone.46

For STSI caused by MAI, antimicrobial therapy should be a multidrug regimen with a macrolide base as recommended previously.46 The optimal length of therapy is unknown but likely can be shorter than for pulmonary or disseminated disease; current recommendations are for 6 to 12 months.46 Clarithromycin, rifampin, sulfas, and clofazimine have all been used to good effect, provided disease is not advanced.1 Drug therapy for RGM species is more problematic because of a lack of clinical trials and the toxicity of antibiotics known to be effective for RGM. Soft tissue and skeletal infection with M fortuitum and M chelonae should be treated for a minimum of 4 months.2 For bone infections, a minimum of 6 months is recommended. Expert opinion for M marinum recommends 2-agent therapy (a macrolide plus rifampin or ethambutol) for 1 to 2 months after symptoms resolve; surgical debridement may be indicated for deep structure infection.2 Catheter-related infections can be treated with a 6- to 12- week course of multiple antibiotics provided that the device is removed.1 The recommended length of therapy for slow-growing NTM species is 6 to 12 months.

CONCLUSION

Nontuberculous mycobacteria are a diverse group of mycobacterial species that cause a wide range of human disease. The spectrum of clinical infections caused by these organisms varies from minor, self-limited cutaneous disease to life-threatening widespread infection that may have no effective therapy. Historically thought to cause disease only in immunocompromised individuals, NTM are now recognized as major pathogens in immunocompetent individuals as well. Nontuberculous mycobacteria disease can be broadly grouped into pulmonary infections, lymphadenitis, disseminated disease, and STSI and typically present as indolent processes in both immunocompetent and immunocompromised patients. The most important pathogenic NTM species is MAI, which causes the bulk of pulmonary and disseminated disease in the United States and can rarely masquerade as a neoplastic process. The diagnosis of NTM disease is based on a combination of clinical features, microbiologic data, radiographic findings, and histopathologic studies. Treatment of NTM infection is difficult and requires long courses of multidrug therapy with or without adjunctive surgical intervention. For most NTM species, macrolide-based drug regimens are an effective option, although treatment failure and resistance may develop. RGM, especially M abscessus, pose a particular therapeutic challenge because of a lack of effective and well-tolerated antimycobacterial agents. However, the development of new antibiotics such as tigecycline with excellent activity against RGM may offer more successful and safe treatment options.

Table 2. American Thoracic Society/Infectious Disease Society of America Guidelines for Diagnostic Criteria for Pulmonary Infection With Nontuberculous Mycobacteria (NTM)*

Clinical

1. Pulmonary symptoms, nodular or cavitary opacities on chest radiograph, or a high-resolution computed tomography scan that shows multifocal bronchiectasis with multiple small nodules, AND

2. Appropriate exclusion of other diagnoses (eg, tuberculosis)

Microbiologic

1. Positive culture results from at least 2 separate expectorated sputum samples. If the results from (1) are nondiagnostic, consider repeat sputum AFB smears and cultures, OR

2. Positive culture result from at least 1 bronchial wash or lavage, OR

3. Transbronchial or other lung biopsy with mycobacterial histopathologic features (granulomatous inflammation or AFB) and positive culture for NTM or biopsy showing mycobacterial histopathologic features (granulomatous inflammation or AFB) and one or more sputum or bronchial washings that are culture positive for NTM. 4. Expert consultation should be obtained when NTM are recovered that are either infrequently encountered or that usually represent environmental contamination.

5. Patients who are suspected of having NTM lung disease but do not meet the diagnostic criteria should be followed until the diagnosis is firmly established or excluded.

6. Making the diagnosis of NTM lung disease does not, per se, necessitate the institution of therapy, which is a decision based on potential risks and benefits of therapy for individual patients.

* Reprinted from Griffith et al2 with permission from the American Thoracic Society. AFB indicates acid-fast bacilli.

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Jason A. Jarzembowski, MD, PhD; Michael B. Young, MD

Accepted for publication February 27, 2008.

From the Departments of Pathology, Medical College of Wisconsin and Children’s Hospital of Wisconsin, Milwaukee (Dr Jarzembowski); and Internal Medicine, Division of Infectious Diseases, University of Kentucky, Lexington (Dr Young).

The authors have no relevant financial interest in the products or companies described in this article.

Reprints: Jason A. Jarzembowski, MD, PhD, Department of Pathology, Children’s Hospital of Wisconsin, 9000 W Wisconsin Ave, Milwaukee, WI 53201 (e-mail: [email protected]).

Health

Polymeric Immunoglobulin Receptor-Negative Tumors Represent a More Aggressive Type of Adenocarcinomas of Distal Esophagus and Gastroesophageal Junction

Written By: Sam Savage

Published Date: August 30, 2008 Last Edited: August 30, 2008

By Gologan, Adrian Acquafondata, Marie; Dhir, Rajiv; Sepulveda, Antonia R

Context.-Polymeric immunoglobulin receptor (PIgR) expression has been found in gastric mucosa and gastric cancers, but it is not known whether PIgR expression is related to background intestinal metaplasia nor the patterns of PIgR expression in tumors arising in the distal esophagus and gastroesophageal (GE) junction. Objectives.- To identify clinicopathologic features of tumors associated with PIgR expression and to determine whether PIgR expression is associated with intestinal differentiation of tumors and intestinal metaplasia in background mucosa in 3 groups of upper gastrointestinal adenocarcinomas. These groups are (1) gastric adenocarcinomas, (2) adenocarcinomas of the distal esophagus and GE junction with background intestinal metaplasia, and (3) adenocarcinomas of the distal esophagus and GE junction without background intestinal metaplasia.

Design.-Expression of PIgR and CDX2 in nonneoplastic mucosa, intestinal metaplasia, and adenocarcinomas was examined by immunohistochemistry in 42 cases: 14 gastric and 28 from the distal esophagus and GE junction, including 13 with esophageal or GE junction intestinal metaplasia.

Results.-PIgR and CDX2 were expressed in all cases of intestinal metaplasia. PIgR expression was positive in 40% of group 3 versus 77% of group 2 and 71% of gastric adenocarcinomas (P = .06), and the expression of CDX2 was similar in all tumor groups (80%-83%). Metastaticpositive lymph nodes were more frequent in PIgR-negative tumors (94% vs 58%, P = .01).

Conclusions.-PIgR is uniformly expressed in intestinal metaplasia and in a subgroup of adenocarcinomas of the distal esophagus, GE junction, and stomach. Esophageal and GE junction adenocarcinomas that do not express PIgR show more frequent lymph node metastasis, suggesting that lack of expression of PIgR identifies a subgroup of more aggressive adenocarcinomas.

(Arch Pathol Lab Med. 2008;132:1295-1301)

Adenocarcinomas of the upper gastrointestinal (GI) tract are associated with several different underlying risk factors. Gastric carcinomas that develop in the setting of chronic Helicobacter pylori gastritis, showing extensive atrophy and intestinal metaplasia (IM) of gastric mucosa, and esophageal adenocarcinomas arising on a background of Barrett esophagus, which follows chronic gastroesophageal (GE) reflux, are two well-known pathways of cancer development.1,2 Tumors that involve the GE junction appear to include various types of neoplasms.3 Some cases are related to GE reflux, other cases may be associated with chronic H pylori carditis, and still other cases have unclear underlying mechanisms. The presence or absence of IM is a flag for cancer risk, and its presence or absence in background mucosa may be used to differentiate groups of tumors with potentially different underlying pathogenesis and molecular pathways of development and progression.

Several markers of intestinalization in the gastric and GE junction mucosa have been well characterized, such as the intestinal- type mucin MUC2,4-7 CDX2,8-14 CDX1,8,15 villin, 16-18 CD10,5,6,19 sucrase-isomaltase,17,20 human defensin, 21,22 and aminopeptidase.17 The CDX1 and CDX2 homeobox genes are expressed in the epithelia of the small and large intestines and have important roles in cell differentiation and proliferation.23 CDX2 expression has been reported in 85% to 94% of cases of gastric IM.8,10,11 CDX2 is also expressed in all cases of IM of Barrett esophagus, 12-14 representing a sensitive marker of intestinal differentiation.

The polymeric immunoglobulin receptor (PIgR) is a protein involved in the transport of immunoglobulin A (IgA) across mucosal membranes, from the basolateral aspect of epithelial cells to the luminal surface.24,25 PIgR is highly expressed in intestinal epithelial cells and is downregulated in adenocarcinomas of the colon.26 PIgR is not present in normal gastric mucosa. However, production of PIgR by gastric mucous cells is induced by H pylori infection. 27 Expression of PIgR also has been documented in IM of the gastric mucosa and stomach carcinomas, with progressive loss in advanced stages.28 The expression patterns of PIgR in adenocarcinomas of the GE junction and esophagus have not been reported. Because PIgR is associated with the intestinal epithelial cell defense functions, PIgR may be differentially expressed in upper GI tumors in a manner related to the intestinal phenotype and may correlate with the presence of IM in the background mucosa. Further, because IM has been linked to well-defined pathways of esophageal and gastric adenocarcinoma development, we hypothesized that markers of the intestinal lineage, CDX2 and PIgR, may segregate together during carcinogenesis into molecular subgroups related to a similar underlying pathogenesis.

The objectives of this study were to determine whether PIgR expression is associated with intestinal differentiation and to evaluate the clinicopathologic patterns of PIgR expression in 3 groups of upper GI adenocarcinomas, including gastric adenocarcinomas and tumors of the distal esophagus and GE junction, either associated with IM or without IM.

MATERIALS AND METHODS

Selection of Cases and Patient Demographics

A total of 42 cases of resected adenocarcinomas of the upper GI tract was selected from the files of the University of Pittsburgh Medical Center, and hematoxylin-eosin (H&E) stains, gross descriptions, and prior biopsy reports were reviewed. Based on the tumor location and presence or absence of background IM, after evaluation of the resection specimen and, when available, preceding biopsy results, the cases were separated into 3 groups that included (1) 14 primary gastric adenocarcinomas, (2) 13 adenocarcinomas of the distal esophagus and GE junction associated with background IM, and (3) 15 adenocarcinomas of the distal esophagus and GE junction not associated with background IM. The presence of IM was evaluated in the tubular esophagus, GE junction, and stomach in the resection specimens. The group of patients with gastric cancer included 3 African Americans, 1 Asian, and the remainder white, whereas all patients in groups 2 and 3 were white. There were 5, 1, and 2 women in groups 1, 2, and 3, respectively.

Histology and Immunohistochemistry

Sections of formalin-fixed, paraffin-embedded tissues were used for immunohistochemistry. Immunohistochemical staining was performed using anti-PIgR (1:4800; clone COMPO2, Lab Vision NeoMarkers, Fremont, Calif) and anti-CDX2 antibodies (1: 200; clone CDX2-88, BioGenex, San Ramon, Calif) using a standard biotin-avidin method, in a Dako Autostainer. Semiquantitative evaluation was performed as follows: 0, less than 10% positive cells; 1, 10% to 50% positive cells; and 2, more than 50% positive cells displaying cytoplasmic and membrane-associated immunoreactivity (PIgR) and nuclear staining (CDX2). Scores of 1 and 2 were interpreted as positive staining in the tumor tissues.

Statistical Analysis

Analyses were performed using Sigma Stat 3.0 (SPSS, Inc) software for Windows. Two-by-two contingency table analyses were performed using the 2-tailed Fisher exact test or chi-square, and the Student t test or Mann-Whitney rank sum test were used for noncategorical data. Survival analyses were performed with the log-rank test. Significant differences were considered for P

RESULTS

The group of cases studied included 14 primary gastric adenocarcinomas (group 1), 13 adenocarcinomas involving the distal esophagus and GE junction associated with IM (group 2), and 15 adenocarcinomas involving the distal esophagus and GE junction that were not associated with IM (group 3). The overall average age of patients in group 1, group 2, and group 3 was 69, 61, and 65 years, respectively. The gastric adenocarcinomas included 9 cases of antrum adenocarcinomas and 5 cases of gastric body adenocarcinomas. Two cases were of the diffuse type, and the others were of the intestinal type. The 2 diffuse-type adenocarcinomas in the gastric body were not associated with gastric IM and showed PIgR expression. Intestinal metaplasia in the background gastric mucosa was present in 78.6% (11/14) of cases of gastric adenocarcinomas. Helicobacter pylori organisms were not identified in any of the gastrectomy specimens. Immunohistochemical stains for PIgR in gastric, esophageal, and GE junction IM demonstrated cytoplasmic and membranous apical and lateral staining, whereas CDX2 was expressed in the nucleus (Figures 1 through 3). In adenocarcinomas, PIgR was expressed with a cytoplasmic and membranous apical and lateral pattern, with occasional accumulation within the lumen of the glands (Figures 1 through 3).

Figure 1 shows examples of esophageal IM and tumors arising on a background of IM in the distal esophagus and the GE junction. Figure 1, A (H&E), shows a representative case of esophageal IM; Figure 1, B, shows immunohistochemical staining for CDX2; and Figure 1, C, shows immunohistochemical staining for PIgR. CDX2 expression in tumors was detected in the nucleus (Figures 1 through 3). Figure 1, D (H&E), shows a representative case of poorly differentiated adenocarcinoma from the distal esophagus and GE junction; Figure 1, E, shows staining for CDX2; and Figure 1, F, shows staining for PIgR. Figure 1, G (H&E), shows a moderately differentiated adenocarcinoma from the distal esophagus and GE junction; Figure 1, H, shows staining for CDX2; and Figure 1, I, shows staining for PIgR. Figure 2 shows examples of tumors arising in the distal esophagus and GE junction without background IM. Figure 2, A (H&E), shows a representative moderately differentiated adenocarcinoma from the distal esophagus and GE junction; Figure 2, B, shows staining for CDX2; and Figure 2, C, shows staining for PIgR. Figure 2, D (H&E), shows a poorly differentiated adenocarcinoma from the distal esophagus and GE junction; Figure 2, E, shows staining for CDX2; and Figure 2, F, shows staining for PIgR.

Figure 3 shows a representative case of gastric IM and adenocarcinoma. Figure 3, A, shows gastric antral mucosa negative for IM and negative for PIgR by immunohistochemical staining. Gastric IM, positive for PIgR and CDX2, is shown in Figure 3, B and C, respectively. Figure 3, D (H&E), shows a poorly differentiated gastric adenocarcinoma; Figure 3, E, shows negative immunohistochemical staining for CDX2; and Figure 3, F and G, shows focal positive staining for PIgR. Lymph node metastases of this poorly differentiated carcinoma demonstrate negative CDX2 expression (Figure 3, H) and positive PIgR expression (Figure 3, I).

In the stomach, PIgR and CDX2 were extensively expressed in all cases of IM and only focally and weakly expressed in 42.9% and 25% of cases in nonneoplastic/ nonmetaplastic background glandular mucosa, respectively (P

PIgR and CDX2 expression in background nonneoplastic/ nonmetaplastic glandular mucosa of group 2 cases demonstrated focal positive staining for PIgR and CDX2 in 50% and in 22% of cases, respectively (Table 1), and the background nonneoplastic and nonmetaplastic glandular mucosa showed focal staining of foveolar epithelium for PIgR in 38.5% (5/13) of cases in group 3, whereas all these cases were negative for CDX2 (P

As shown in Table 1, the expression of CDX2 was similar among groups: group 1 (gastric adenocarcinomas), 83%; group 2, 80%; and group 3, 80%. PIgR expression was 77% in group 2 versus 40% in group 3 adenocarcinomas (P = .10) (Table 1). In addition, differential expression of PIgR versus CDX2 was seen in group 2 versus group 3 adenocarcinomas (P = .01, rank sum test).

There were 23 adenocarcinoma cases with IM in the background mucosa (including all group 2 and 78.6% of the gastric adenocarcinomas), whereas the remaining 19 of 42 cases studied did not have IM (these cases included group 3 and gastric adenocarcinomas without IM of the gastric mucosa). Overall, of the 23 cases with background IM, 17 expressed PIgR in the tumors, and of the 19 cases without IM, 9 expressed PIgR in the tumors (P = .10). There were 10 cases that did not have IM, and the tumor did not express PIgR; and there were 6 cases that had a PIgR-negative tumor with a positive background of IM. These data suggest that although there is overlap of PIgR expression in tumor tissue and the presence of an IM phenotype of the background mucosa, PIgR expression can be independent of the IM-carcinoma sequence.

All tumors were more frequent in men, reflecting the demographics associated with these neoplasms. There were no significant age differences between patients with tumors that expressed PIgR and those with tumors that did not (Table 2). There was no correlation of PIgR or CDX2 expression with tumor grade or tumor (T) stage (Table 3). Group 3 tumors showed lymph node metastasis at a higher rate than group 2 tumors, with lymph node metastases detected in 86.7% (13/15) and 53.9% (7/13) of cases, respectively, but the difference did not reach significance (P = .09).

Interestingly, of the 26 tumor cases positive for PIgR, including group 1 (gastric adenocarcinomas), group 2, and group 3 (Table 3), 15 (57.7%) had positive lymph nodes, whereas of the 16 cases negative for PIgR, 15 (93.7%) had positive lymph nodes, suggesting a better behavior of PIgR-positive adenocarcinomas (P = .01). This finding appears to be related to PIgR expression rather than grade or T stage of the tumors, because no statistically significant differences of grade and T stage were found in PIgRpositive versus PIgR-negative tumors (Table 3).

The pathologic stage among the 16 PIgR-negative tumors was T1 (1 case; 6%), T2 (6 cases; 37%), T3 (8 cases; 50%), and T4 (1 case; 6%). The PIgR-negative tumor with stage T1 did not have lymph node metastasis, whereas the remaining 15 cases were positive for lymph node metastatic tumor. The survival period for patients with PIgRnegative tumors in each T stage group was 25.1, 30.6, 34.4, and 24.5 months, respectively. These data suggest a high likelihood that PIgR-negative tumors with at least stage T2 will have positive lymph node metastasis. However, further studies with larger numbers of cases are warranted. The pathologic stage among the 26 PIgR- positive tumors was T1 (5 cases; 19%), T2 (5 cases; 19%), T3 (13 cases; 50%), and T4 (3 cases; 12%). The mean survival period for patients with PIgR-positive tumors in each T stage group was 45.2, 55.3, 32.2, and 23.7 months, respectively. Although the survival period for patients with PIgR-positive, stage T2 tumors was greater than that of patients with stage T4 tumors, the difference is not significant (P = .63).

Next we analyzed the data to determine whether the increased lymph node metastasis of PIgR-negative tumors was associated with a specific tumor group. This analysis was limited by the small number of cases in the subgroups. For gastric adenocarcinomas, there were 7 cases of positive lymph nodes of 10 PIgR-positive cases (70%) and 3 cases of positive lymph nodes of 4 PIgR-negative cases (75%). For group 2 tumors, there were 4 cases of positive lymph nodes of 10 PIgR-positive cases (40%) and 3 cases of positive lymph nodes of 3 PIgR-negative cases (100%). For group 3 tumors, there were 4 cases of positive lymph nodes of 6 PIgR-positive cases (67%) and 9 cases of positive lymph nodes of 9 PIgR-negative cases (100%). Combining group 2 and group 3 tumors, 50% of PIgR-positive cases had lymph node metastases, compared with 100% of PIgR-negative cases (P = .01). These data indicate that PIgR-negative tumors are most often lymph-node positive in tumors of the distal esophagus and GE junction, regardless of the presence or absence of background IM.

The overall survival rate of patients with tumors that expressed CDX2 versus tumors that did not and of patients with tumors that expressed PIgR versus tumors that did not was slightly higher, but the differences were not statistically significant (P = .43 and P = .19, respectively) (Figure 4, A and B).

COMMENT

Although the incidence of gastric cancer is decreasing, it remains the second leading cause of cancer-related deaths worldwide.29 Adenocarcinomas of the distal esophagus and GE junction have shown an increasing incidence in recent years, leading to increased interest in these tumors.30

PIgR expression has been studied in gastric cancers, but its expression in tumors of the distal esophagus and GE junction has not been reported. We studied 3 groups of upper GI adenocarcinomas: (1) gastric, (2) adenocarcinomas of the distal esophagus and GE junction with background IM, and (3) adenocarcinomas of the distal esophagus and GE junction without background IM. We found that PIgR expression was present in 71% of gastric adenocarcinomas and 77% of group 2 tumors, versus 40% of group 3 adenocarcinomas (P = .06), and the expression of CDX2 was similar in all tumor groups (80%-83%). Because we cannot exclude that some group 3 tumors developed on a background of short-segment Barrett esophagus in which the tumor overgrew the areas of IM, it is possible that some of the group 3 tumors fit into group 2 rather than group 3. Prospective studies are needed to clarify this point.

To examine the relationship between expression of PIgR in the background IM and expression in the tumor, we examined the expression of PIgR compared with that of CDX2, a well-known marker of intestinal differentiation, and found that both PIgR and CDX2 were extensively expressed in all cases of IM. However, among 19 cases without IM, 9 expressed PIgR in the tumors, and focal PIgR expression was detected in the nonmetaplastic and nonneoplastic background mucosa of some cases, suggesting that the expression of PIgR often parallels the intestinal phenotype but may develop independently. This notion is also supported by the finding that differential expression of PIgR versus expression of CDX2 was seen in group 2 versus group 3 adenocarcinomas (P = .01).

We noted a relatively high frequency of CDX2 expression in group 3 tumors, which could be explained by either intestinal differentiation of the tumor during cancer progression or by the presence of short-segment Barrett esophagus or IM at the GE junction, which was no longer detected in the specimen when the esophagectomy was performed. Both PIgR and CDX2 were expressed in the foci of IM in the esophagus and stomach, and the sensitivity of either of these markers to detect IM was 100%. Occasionally, focal PIgR and CDX2 expression was observed in gastric mucosa adjacent to areas of IM, in agreement with prior studies.12,13 It is postulated that such foci may represent epithelium in an earlier phase of intestinal phenotypic differentiation.

Importantly, of the tumor cases positive for PIgR among the 3 adenocarcinoma groups, 57.7% had lymph nodes positive for metastatic adenocarcinoma, whereas 93.7% of the cases negative for PIgR had positive lymph nodes, suggesting a more aggressive clinical behavior of PIgRnegative adenocarcinomas. This increased tendency for lymph node metastasis of PIgR-negative tumors appears to be related to PIgR and to be independent of tumor grade and stage, because PIgR expression was not associated with tumor grade or T stage in the tumors studied in our series. It is unclear from our study whether PIgR has a biologic role in tumor cells that affects tumor cell behavior or whether it is only a marker of better tumor behavior unrelated to the cellular functions of PIgR. It is tantalizing to speculate that PIgR may function to increase the local humoral immunity in the tumor and that, in cases with lower PIgR expression, changes in IgA-related immune response in the tumor environment may lead to increased metastatic potential of the tumor cells. In conclusion, expression of PIgR is focal or absent in the nonneoplastic mucosa but is uniformly expressed in IM of the stomach and esophagus. The data from our study suggest that a subgroup of the distal esophagus and GE junction adenocarcinomas that appear to develop in a mucosa without IM may express PIgR less commonly. Further prospective studies are needed to differentiate tumors that appear to arise from nonmetaplastic background from those that have overgrown foci of IM.

The finding that PIgR-negative adenocarcinomas of the distal esophagus and GE junction are associated with reduced survival and increased lymph node metastasis suggests that this subgroup of patients might benefit from different treatment approaches, such as specific adjuvant therapy. Future studies are required to address these hypotheses.

References

1. Gologan A, Graham DY, Sepulveda AR. Molecular markers in Helicobacter pylori-associated gastric carcinogenesis. Clin Lab Med. 2005;25:197-222.

2. Spechler SJ. The natural history of dysplasia and cancer in esophagitis and Barrett esophagus. J Clin Gastroenterol. 2003;36:S2- S5; discussion S26-S28.

3. Ectors N, Driessen A, De Hertog G, et al. Is adenocarcinoma of the esoph agogastric junction or cardia different from Barrett adenocarcinoma? Arch Pathol Lab Med. 2005;129:183-185.

4. Chaves P, Cruz C, Dias Pereira A, et al. Gastric and intestinal differentiation in Barrett’s metaplasia and associated adenocarcinoma. Dis Esophagus. 2005;18: 383-387.

5. Niwa T, Ikehara Y, Nakanishi H, et al. Mixed gastric- and intestinal-type metaplasia is formed by cells with dual intestinal and gastric differentiation. J Histochem Cytochem. 2005;53:75-85.

6. Ikeda Y, Nishikura K, Watanabe H, et al. Histopathological differences in the development of small intestinal metaplasia between antrum and body of stomach. Pathol Res Pract. 2005;201:487- 496.

7. Steininger H, Pfofe DA, Muller H, et al. Expression of CDX2 and MUC2 in Barrett’s mucosa. Pathol Res Pract. 2005;201:573-577.

8. Almeida R, Silva E, Santos-Silva F, et al. Expression of intestine-specific transcription factors, CDX1 and CDX2, in intestinal metaplasia and gastric carcinomas. J Pathol. 2003;199:36- 40.

9. Moons LM, Bax DA, Kuipers EJ, et al. The homeodomain protein CDX2 is an early marker of Barrett’s oesophagus. J Clin Pathol. 2004;57:1063-1068.

10. Bai YQ, Yamamoto H, Akiyama Y, et al. Ectopic expression of homeodomain protein CDX2 in intestinal metaplasia and carcinomas of the stomach. Cancer Lett. 2002;176:47-55.

11. Seno H, Oshima M, Taniguchi MA, et al. CDX2 expression in the stomach with intestinal metaplasia and intestinal-type cancer: prognostic implications. Int J Oncol. 2002;21:769-774.

12. Phillips RW, Frierson HF Jr, Moskaluk CA. Cdx2 as a marker of epithelial intestinal differentiation in the esophagus. Am J Surg Pathol. 2003;27:1442-1447.

13. Groisman GM, Amar M, Meir A. Expression of the intestinal marker Cdx2 in the columnar-lined esophagus with and without intestinal (Barrett’s) metaplasia. Mod Pathol. 2004;17:1282-1288.

14. Eda A, Osawa H, Satoh K, et al. Aberrant expression of CDX2 in Barrett’s epithelium and inflammatory esophageal mucosa. J Gastroenterol. 2003;38:14-22.

15. Silberg DG, Furth EE, Taylor JK, et al. CDX1 protein expression in normal, metaplastic, and neoplastic human alimentary tract epithelium. Gastroenterology. 1997;113:478-486.

16. Regalado SP, Nambu Y, Iannettoni MD, et al. Abundant expression of the intestinal protein villin in Barrett’s metaplasia and esophageal adenocarcinomas. Mol Carcinog. 1998;22:182-189.

17. Osborn M, Mazzoleni G, Santini D, et al. Villin, intestinal brush border hydrolases and keratin polypeptides in intestinal metaplasia and gastric cancer: an immunohistologic study emphasizing the different degrees of intestinal and gastric differentiation in signet ring cell carcinomas. Virchows Arch A Pathol Anat Histopathol. 1988;413:303-312.

18. MacLennan AJ, Orringer MB, Beer DG. Identification of intestinal-type Barrett’s metaplasia by using the intestine- specific protein villin and esophageal brush cytology. Mol Carcinog. 1999;24:137-143.

19. Sarbia M, Donner A, Franke C, et al. Distinction between intestinal metaplasia in the cardia and in Barrett’s esophagus: the role of histology and immunohistochemistry. Hum Pathol. 2004;35:371- 376.

20. Wu GD, Beer DG, Moore JH, et al. Sucrase-isomaltase gene expression in Barrett’s esophagus and adenocarcinoma. Gastroenterology. 1993;105:837-844.

21. Shen B, Porter EM, Reynoso E, et al. Human defensin 5 expression in intestinal metaplasia of the upper gastrointestinal tract. J Clin Pathol. 2005;58: 687-694.

22. Inada K, Tanaka H, Nakanishi H, et al. Identification of Paneth cells in pyloric glands associated with gastric and intestinal mixed-type intestinal metaplasia of the human stomach. Virchows Arch. 2001;439:14-20.

23. Silberg DG, Swain GP, Suh ER, et al. Cdx1 and cdx2 expression during intestinal development. Gastroenterology. 2000;119:961-971.

24. Brandtzaeg P. Molecular and cellular aspects of the secretory immunoglobulin system. APMIS. 1995;103:1-19.

25. Brown WR, Isobe Y, Nakane PK. Studies on translocation of immunoglobulins across intestinal epithelium, II: immunoelectron- microscopic localization of immunoglobulins and secretory component in human intestinal mucosa. Gastroenterology. 1976;71:985-995.

26. Traicoff JL, De Marchis L, Ginsburg BL, et al. Characterization of the human polymeric immunoglobulin receptor (PIGR) 3’UTR and differential expression of PIGR mRNA during colon tumorigenesis. J Biomed Sci. 2003;10:792-804.

27. Kaneko T, Ota H, Hayama M, et al. Helicobacter pylori infection produces expression of a secretory component in gastric mucous cells. Virchows Arch. 2000;437:514-520.

28. Takemura K, Hirokawa K, Esaki Y, et al. Distribution of immunoglobulins and secretory component in gastric cancer of the aged. Cancer. 1990;66:2168-2173.

29. Kelley J, Duggan J. Gastric cancer epidemiology and risk factors. J Clin Epidemiol. 2003:1-9.

30. Blot WJ, Devesa SS, Kneller RW, et al. Rising incidence of adenocarcinoma of the esophagus and gastric cardia. JAMA. 1991;265:1287-1289.

Adrian Gologan, MD; Marie Acquafondata, BS; Rajiv Dhir, MD, PhD; Antonia R. Sepulveda, MD, PhD

Accepted for publication January 14, 2008.

From the Department of Pathology, McGill University, Sir Mortimer B. Davis-Jewish General Hospital, Montreal, Quebec (Dr Gologan); and the Department of Pathology, University of Pittsburgh, Pittsburgh, Pa (Ms Acquafondata and Drs Dhir and Sepulveda).

The authors have no relevant financial interest in the products or companies described in this article.

Reprints: Antonia R. Sepulveda, MD, PhD, Department of Pathology and Laboratory Medicine, Hospital of the University of Pennsylvania, 3400 Spruce St-Founders Six, Philadelphia, PA 19104 (e-mail: [email protected]).

Health

New $4 Million Helipad Tops Off AAMC Expansion

Written By: Sam Savage

Published Date: August 29, 2008 Last Edited: August 29, 2008

By EARL KELLY Staff Writer

A gentle breeze blew across Anne Arundel Medical Center’s new helipad yesterday, a $4 million rooftop landing area that will be linked by elevator directly to the hospital’s emergency room.

The pad will go into service in December, hospital officials said.

AAMC’s current helipad is about a quarter of a mile away from the hospital, on the far side of Jennifer Road.

“We have to call an ambulance (that’s on contract with the hospital), get a crew, go pick up the patient, and come back,” said nurse Lillian Banchero, director of patient access.

Until last year, the helipad was located closer to the hospital, but still required patients to be exposed to the elements when being transferred. That landing area was closed when a new garage was built next to the hospital.

Ms. Banchero said designated medical staff will begin training in November, learning how to work with helicopters in the new facility.

From the rooftop pad, it is possible to see the Chesapeake Bay, the tops of the Bay Bridge’s towers and the State House. The landing area is surrounded by lightning rods, and has a metal safety net around the edges to catch anyone who steps off the ledge.

The steel landing area will measure 60 feet by 55 feet, and will accommodate one large helicopter at a time, hospital personnel said.

“The helipad is sized to handle a Black Hawk helicopter,” said medical center Senior Vice President Carolyn W. Core, who oversees strategic planning. “In 9/11, they grounded all the private helicopters, and the only people who could transport patients were the military.”

For comparison purposes, a military Black Hawk weighs about 17,000 pounds, or roughly four times as much as a Maryland State Police medevac helicopter.

The helipad itself was installed during the first three weeks of June.

Safety has been a big part of the design, Ms. Core said, and the new landing area has systems for de-icing the surface, catching any fuel spills and suppressing fires.

Anne Arundel Medical Center averages about 15 takeoffs and landings a month, Ms. Core said, with many flights involving transferring patients from AAMC to specialized hospitals.

Patients who might be transported include a premature infant who needs specialized care, or a trauma victim who couldn’t be flown directly to a shock trauma center, perhaps because of bad weather.

Most of the inter-hospital flights are flown by medevac companies such as MedStar, a non-profit corporation that operates medical transportation systems.

Ms. Core said there is no plan to make AAMC a shock trauma center.

“Running a shock trauma operation is so different from running a (typical) hospital,” she said, noting the large and costly staff that trauma centers must have around the clock.

Next door to the hospital, a crew is preparing the groundwork for a new eight-story wing that will include 50 patient rooms, plus eight additional operating rooms.

Besides housing the 50 new beds, the 300,000-square-foot, $240 million addition will have two floors, or about 30 beds, in reserve capacity, said hospital spokesman Justin Paquette. These rooms can be added if the state certifies there is a need. Also, three more floors can be built atop the new structure, if they are ever needed.

“This will allow us to keep the options open as the hospital grows,” Mr. Paquette said.

Across Medical Parkway from the main building, work continues on a new seven-story, 240,000 square-foot ambulatory services pavilion, which will include doctors’ offices, classrooms and a 400-seat auditorium.

The new facility is being built next to the Sajak Pavilion and will include a 950-space parking garage, and will be linked to the hospital by a pedestrian bridge crossing the parkway.

The bridge will be lifted into place by crane on the weekend of Oct. 25, Ms. Core said. The complete $424 million AAMC campus expansion will be finished in 2010 will nearly double the size of the current hospital.

The added space is needed, hospital officials said, because of the aging population and the influx of new households as a result of Base Realignment and Closure, or BRAC. {Corrections:} {Status:}

Health

Indiana Tobacco Prevention and Cessation Awards Grant to Clarian Tobacco Control Center

Written By: Sam Savage

Published Date: August 29, 2008 Last Edited: August 29, 2008

INDIANAPOLIS, Aug. 29 /PRNewswire/ — Indiana Tobacco Prevention and Cessation (ITPC) recently awarded Clarian Tobacco Control Center (CTCC), a part of the Clarian Health network, a grant to implement new tobacco cessation guidelines, set by the U.S. Public Health Service (PHS), throughout its statewide network.

The grant follows the release of the PHS 2008 Clinical Practice Guideline Update: Treating Tobacco Use and Dependence. The Guideline aims to provide clinicians and health care systems a more consistent and effective approach when treating patients who smoke. According to PHS, “many clinicians lack knowledge about how to identify smokers quickly and easily, which treatments are effective, how such treatments can be delivered, and the relative effectiveness of different treatments.”

“Indiana data show that even brief interventions by our doctors, dentists, nurses and assistants can increase the number of Hoosiers who try to quit,” Karla Sneegas, executive director for ITPC, said. “These new guidelines provide a ‘blueprint’ for clinicians and health care systems, describing how smokers can access effective treatments, how clinicians can provide such treatments quickly and effectively, and how health care systems can support both smokers and clinicians in smoking cessation efforts. We’re pleased to award a grant to Clarian Health to begin implementing these practices.”

The Guideline has been approved nationally by more than 55 major organizations, public health and medical officials, and former U.S. Surgeon General, C. Everett Koop.

“Tobacco dependency should be treated as a chronic disease,” Judy Monroe, M.D., State Health Commissioner, said. “Nicotine addiction often requires repeated intervention and multiple attempts to quit, which is why support from health care providers is essential.”

According to a press release issued by the Indiana State Health Department advocating the new treatment Guideline:

Indiana ranks sixth among all states for adult smoking, with more than 1 million smokers estimated statewide. Sneegas strongly believes that Hoosiers want to quit smoking. Increased calls to the free Indiana Tobacco Quitline (1-800-QUIT-NOW) have increased in the past year; however, patients need support. Sneegas says health care providers are perfectly positioned to reach additional Hoosiers who want to quit smoking and provide them the necessary tools in order to be successful.

“Identifying smokers and providing them with brief advice and help with quitting in clinical practice are both very effective and cost effective,” Deborah Hudson, program manager, CTCC, states. “Tobacco cessation is among the top three highest priority and cost-effective preventive services. As a healthcare professional, I found this to be true very early in my practice as a respiratory therapist. While we are asking about smoking status, national benchmarks show there is much room for improvement in delivering cessation assistance. The Community Intervention Trial for Smoking Cessation (COMMIT) showed that 75 percent of people were being asked about use, 49 percent advised to quit, and only 25 percent being offered assistance, like medications. When more than 60 percent of our smokers want to quit, we as health professionals need to be providing the means to assist them. It has become clear over the last decade that providing smoking cessation counseling may be similar to that of annual colon cancer screening, annual flu vaccinations, mammograms and cholesterol screening. This is why the Clarian Tobacco Control Center has launched an effort to assist healthcare providers in integrating evidence-based components that will allow them to provide brief cessation intervention.”

CTCC will use the ITPC grant to ensure that Hoosier patients that smoke are treated for their disease, alongside any additional health issues. Dr. Monroe and Sneegas hope that other health care providers will also employ the Guideline in their facilities. To request a Health Care Provider Tobacco Cessation Kit, contact ITPC at (317) 234-1787 or [email protected] . For more information about CTCC, visit http://www.clarian.org/ctcc . Visit http://www.surgeongeneral.gov/tobacco to learn more about the new Guideline.

Indiana Tobacco Prevention and Cessation

CONTACT: Stefanie Walker, of Borshoff for Indiana Tobacco Prevention andCessation, +1-317-631-6400, [email protected]

Web site: http://www.clarian.org/ctcchttp://www.surgeongeneral.gov/tobacco

Health

TomTec Introduces 2D CPA a Vendor Independent Solution for Strain and Time to Peak Velocity Analysis Based on Speckle Tracking

Written By: Sam Savage

Published Date: August 29, 2008 Last Edited: August 29, 2008

TomTec launches its 2D Cardiac Performance Analysis package as part of TomTec’s CardioArena(TM) multimodality imaging solution at the European Society of Cardiology congress 2008 in Munich.

2D Cardiac Performance Analysis(C) allows a cardiologist to study the behaviour of the heart muscle quickly and easily. Quantitative assessment of displacement, velocity and strain in individual muscle segments is available. This helps in diagnosing pathologies like hypertrophic cardiomyopathy or also dyssynchronous ventricles that might have to be treated by cardiac resynchronisation therapy.

2D Cardiac Performance Analysis(C) is a speckle tracking based analysis tool which can analyze 2D data from various ultrasound machines. The user can work with different ultrasound systems in his network and is not limited to specific vendors.

“2D Cardiac Performance Analysis runs within TomTec’s CardioArena(TM) environment which provides connectivity to multivendor Echo labs. This solution is user oriented and fulfills the demands of cardiologists towards a simplified workflow!” said Frank Schlau, TomTec’s Chief Marketing Officer.

About TomTec:

TomTec Imaging Systems GmbH, with headquarter located in Munich Germany holds an inventive leadership position in the field of diagnostic medical imaging applications and Cardio PACS solutions. The company maintains close working relationships with many leading universities and device manufacturers around the world. TomTec’s product portfolio encompasses a wide range of 2D and 3D/4D technologies for visualization, analysis, reporting and archiving of multimodality imaging data. TomTec solutions are applicable in the fields of Adult- and Pediatric Cardiology as well as Obstetrics, Gynaecology, Radiology, and Vascular Imaging.

Visit TomTec’s web site at www.tomtec.de

Health

Centene Names President and CEO of Indiana Subsidiary

Written By: Sam Savage

Published Date: August 29, 2008 Last Edited: August 29, 2008

US-based Centene, a multi-line healthcare enterprise, has appointed Patrick Rooney as president and CEO of the company’s Indiana subsidiary, Managed Health Services.

Mr Rooney is based in Managed Health Services’s corporate office in Indianapolis and reports to Christopher Bowers, senior vice president of health plan business unit.

Mr Rooney has more than 14 years of experience in the healthcare financial industry. Most recently, he was vice president of health plan finance for Centene, in which he provided leadership for the centralized finance and accounting departments. Previously, Mr Rooney held financial positions with Mercy Health Plans and Group Health Plans in St Louis.

Mark Eggert, Centene’s executive vice president of health plan business unit, said: “Mr Rooney brings a wealth of healthcare experience and company insight to Managed Health Services. As a seasoned executive in finance and management, he will help support and execute the health plan’s vision of providing better health outcomes to its members at lower costs to the state.”

Entertainment

Sweet’s Ballroom Swings into New Entertainment Era in Oakland

Written By: Sam Savage

Published Date: August 29, 2008 Last Edited: August 29, 2008

By Angela Woodall

Walking into Historic Sweet’s Ballroom — all crimson and gold and grand — evokes the vision of couples whirling across the dance floor and an exuberant time when diversion was easy to find on a warm summer night in Oakland.

Who knows how many romances were sparked at the art deco dance palace. Young men in suits and their corsage-wearing sweethearts jitterbugged, Lindy-hopped, jived, waltzed and otherwise moved their bodies across the floor worn smooth and pale from the generations of Oaklanders — including, local legend has it, a young Ron Dellums.

All the big band greats swung through Oakland. But dancing made the Uptown District, turning it into a locale for night life. Then it went dark, as though someone pulled a black veil over the area that stretches from the Frank Ogawa Plaza to where Broadway melds with Telegraph Avenue and a little past West Grand Avenue.

But on some nights, the vision of a revival of the area is vivid, and the air pulses with energy generated by the constellation of venues large and small that have sprung up in what is becoming an entertainment district: The Uptown, Flora, Franklin Square Wine Bar, the Stork Club, Cafe Van Kleef, the Paramount and Fox theaters, Geoffrey’s Inner Circle and Historic Sweet’s Ballroom.

Whether the effort succeeds depends on people’s willingness to have a good time.

Oaklanders should be able to rise to the occasion.

In the district’s heyday, the willingness to slap down a dollar for a few hours of diversion kept Sweet’s and a dozen other dance floors such as the Ali Baba, Rose Room, Melody Lane and Danceland busy for decades.

As for the generation that came before, then-Oakland Mayor Frank Mott furiously denounced the inventor of the “turkey trot” dance, whom the mayor said should be hamstrung.

“All our troubles over dances are due to these fancy dances. They ought to be all abolished,” the mayor fumed at an Aug. 1, 1913, City Council meeting.

But Oaklanders were determined to dance. Sweet’s stepped in to teach them.

The founder, William Sweet, quit his job as an agriculture professor to open the dance school at 480 20th St. in the 1920s with his brother Eugene.

The ballroom moved several times, and the brothers simultaneously operated the Ali Baba ballroom at 111 Grand Ave., which was demolished in 1981. And all that is left today of an early 14th Street ballroom location is a dusty AAMCO parking lot.

One by one, the ballrooms and dance halls started disappearing after 1965, including the Savoy, where lonely men paid “taxi dance” girls a dime a dance. By 1971, not long before the 387 12th St. hall closed, three dances for a dollar was the bargain rate.

Historic Sweet’s Ballroom, now wedged between Sears and H. Johns Gentleman’s Clothing shop at Broadway and 19th Street, is the only one of the Sweet’s ballroom locations that still exists.

The ballroom building at 1933 Broadway was empty from 1980 to 1998, when an Episcopalian priest, Matthew Fox, borrowed $50,000 on his house to save the building from being torn down to make way for a high-rise BART office building. Fox also is president of Friends of Creation Spirituality. He sold Sweet’s in 2002 to Uptown Broadway Partners, which leased the ballroom back for 35 years. Nearly three years ago, Steve Snider, 39, and Andrew Jones, 23, of Oakland Box Theater fame, stepped in to run things.

They tore out the mangy carpeting, painted over the blue paint and started booking special events — everything from Ethiopian New Year’s Eve celebrations to Mexican “bandas” to ecstatic dance and private parties.

Now they are revving up to turn Sweet’s into something like the House of Blues in Chicago or San Francisco’s Fillmore.

Live music and dancing, Jones said, is something Oakland has missed for a long time.

While the Fox and Paramount are sit-down, cabaret-style venues, patrons at Sweet’s can “have a drink, mingle and get their groove on,” instead of being stuck in their seats, said Jones, an Oakland native.

Snider, who is from Chapel Hill, N.C., said he pictures an entertainment district like that in New Orleans, where shows are happening every night of the week.

That scenario might be easier if the city would change the street- cleaning schedule in what they want to be the entertainment district to a time other than midnight to 3 a.m. — prime entertainment time. Slapping revelers with $48 tickets might not be good for business.

Can someone look into this?

Even so, the trade-off would be a rockin’ night of dancing and music that, Jones said, brings people from all walks of life together and makes them feel good.

That’s all for now, ladies and gentlemen. But if you have a cool shindig, e-mail me at [email protected] or visit the Night Owl blog www.ibabuzz.com/nightowl for more events and oddities.

Originally published by Angela Woodall, Oakland Tribune.

Health

Super Gym Planned in Pleasanton

Written By: Sam Savage

Published Date: August 29, 2008 Last Edited: August 29, 2008

By George Avalos

PLEASANTON — People in and around Hacienda Business Park will have a chance to get more fit, now that 24 Hour Fitness has struck a deal to occupy a former newspaper building here.

A super sport club, the second-highest level operation offered by 24 Hour Fitness, is expected to be the type of outlet planned for the building, located at 4770 Willow Road in Pleasanton.

City officials embraced the advent of the new fitness center.

“It’s really exciting,” said Pamela Ott, Pleasanton’s economic development director. “It’s a great opportunity for our residents and employees who might use 24 Hour Fitness. There are a lot of amenities that go with that kind of operation.”

The fitness company was tight-lipped about the timing for the new center and the details of the lease agreement.

“A new club is coming and it will be at that location,” said Joe Streng, a spokesman for 24 Hour Fitness.

24 Hour Fitness leased the entire 56,000-square-foot building. The deal was arranged through Colliers International brokers Gabe Arechaederra and Brian Lagomarsino. The city’s planning commission has approved the project.

“This is going to be huge for the city of Pleasanton,” Arechaederra said. “This will be the high end for the 24 Hour Fitness product type.”

Potentially, that could include a basketball court, cardio equipment, circuit training, free weights, group cycling, group exercise, a small juice bar, kids’ club, pool, sauna, spa, steam room, and whirlpool, according to the 24 Hour Fitness online site.

The two-story building contained the operations of the Tri- Valley Herald newspaper for about two decades, including a newspaper printing plant, offices, and a warehouse.

“It’s an unusual building,” Arechaederra said. “We had three different users who were trying to lease the building.”

The building also has a new owner, according to Arechaederra. For a number of years, Hawaii-based Kaonoulu Ranch owned the property, located near the corner of Owens Drive.

Recently, a local property investor and developer, Robison Family Trust, bought the building. The purchase price was roughly $25 million, market observers estimated.

“It’s nice to know that this building will be reinvented and have a new life,” Ott said.

George Avalos covers jobs, economic development, commercial real estate, finance and oil companies. Reach him at 925-977-8477 or [email protected]

Originally published by George Avalos, staff writer.

Health

MCG Layoffs a Potential Side Effect

Written By: Sam Savage

Published Date: August 29, 2008 Last Edited: August 29, 2008

By Tom Corwin

Cuts in Medicaid payments could trigger layoffs at Medical College of Georgia Hospital and Clinics as the state tries to fill a budget hole.

The board of the Georgia Department of Community Health meets today, and the Medicaid budget is on the agenda.

Gov. Sonny Perdue has asked state agencies to prepare plans for cuts of 6 percent, 8 percent and 10 percent to meet a budget shortfall of at least $1.6 billion and perhaps as much as $2.2 billion, said Don Snell, the CEO of MCG Health Inc., which runs the school’s health system.

Officials of MCG Health had hoped Medicaid would look at cutting back on benefits, but now it might be a 5 percent payment cut to providers. For MCG Health, that would mean nearly $14 million less in payments and supplemental payments, Chief Financial Officer Dennis Roemer said.

And that would mean fewer personnel, Mr. Snell said.

“If we have to reduce those kinds of dollars, it’s going to be pretty draconian,” he said. “It would be a large personnel reduction. I would try to keep it away from direct patient care areas, because if they affect the payment rates, we would still see the patients.”

The obvious targets would be in administration and support services, Mr. Snell said.

The health system and the school are hoping to avoid a reduction in the direct appropriation to the health system that would result in a cut in support for the school’s residency training programs. At 6 percent, that would be $2.1 million. MCG President Daniel W. Rahn said that would be on top of a 6 percent cut of about $9.5 million and would actually be a bigger hit for MCG than others in the University System of Georgia are experiencing.

“The assumption of an additional $2 million reduction at a minimum would be extremely problematic on the campus side,” Dr. Rahn said.

The school and health system had been at odds over funding for residency training earlier this year. The two sides compromised, with the Board of Regents kicking in an additional $2 million to help settle the matter. Having gone through that process, and with the School of Medicine expanding to a branch campus in Athens and satellite campuses in Savannah and Albany, Mr. Snell said he hopes the regents will forgo that part of the cut.

“With the state’s priority of training more physicians and a priority on the medical education initiative, that there ought to be a cut, it doesn’t make sense,” he said.

Reach Tom Corwin at (706) 823-3213 or [email protected].

Originally published by Tom Corwin Staff Writer.

Education

Theoretical Soundness, Proven Effectiveness, and Implementation Fidelity of the HOSTS Language Arts Program Among Children Identified As At-Risk in Urban Elementary Schools

Written By: Sam Savage

Published Date: August 29, 2008 Last Edited: August 29, 2008

By Senesac, Barbara V Burns, Matthew K

In order to fully evaluate the quality of evidence for any educational innovation, research is needed regarding consistency with theory, demonstrated effectiveness, and consistent implementation. The Help One Student to Succeed (HOSTS) Language Arts program was specifically mentioned in the No Child Left Behind act as a program that incorporates community involvement to improve student reading skills. However, few published studies exist with which the quality of evidence could be evaluated. The current study examined existing research regarding theoretic soundness and demonstrated effectiveness, and conducted a study to examine the large-scale fidelity of implementation. Participants consisted of 51 elementary schools in urban areas, and 1,354 students. Results suggested that a high level of fidelity was obtained significantly more frequently than could be expected, and students in HOSTS programs that were implemented in a consistent manner achieved better reading outcomes. Potential implications for practice are included. The No Child Left Behind Act (NCLB) mandated research- based educational practices in American schools. As a result, there seems to be an increased interest in highquality research driving practical educational decision making (Berends & Caret, 2002; Eisenhart & Towne, 2003; Slavin, 2002). However, Berends and Caret (2002) claimed that informed educational policy debates require data from surveys or assessments from a representative sample of schools. Thus, it could be argued that both randomized or quasi-experimental and applied studies are needed to fully examine the utility of an educational program.

Ellis (2001) reviews research on several educational innovations and provides amodel with which research can be used to evaluate an innovation. Educational programs, according to Ellis, should be supported by research on three levels. Level I research is basic research, which leads to a sound theoretical base, or examines the consistency of an innovation with a given theory. Level II research is conducted in applied settings and examines the efficacy of the educational program in improving the education of children. Randomized controlled research could occur in either Le vel I or II, with controlled settings such as a laboratory being appropriate for Level I and applied settings such as schools being Level II. Level II research is also consistent with the NCLB call for data from quasi-experimental studies. Finally, Level III research examines the effectiveness of the innovation after wide-scale implementation. Innovations implemented on a large scale, but that lacked a sound theoretical base and/or researched effectiveness, could be considered an educational fad (Ellis, 2001).

In addition to mandated evidence-based practices NCLB (2001) advocated structured programs or learning systems that incorporate parent and community involvement to assist students in improving their reading skills and overall school performance. Singled out as a model of such a program is the Help One Student to Succeed (HOSTS) Language Arts Program; the only program specifically cited in the NCLB Conference Report (2001). The HOSTS Language Arts Program is a structured technology-based learning system designed to supplement the school’s literacy curriculum and is delivered by community volunteer tutor/mentors. With the NCLB requirement of making average yearly progress on state standards, some failing schools are implementingthe HOSTS Language Arts Program for supplemental educational services provided for under Title I funding.

Given that the HOSTS Language Arts Program is being used to as a supplemental service and is mentioned in the NCLB report (2001), it seems necessary to examine the evidence-base for this program. The purpose of the current article is to describe the research from Levels I and II (Ellis, 2001) for HOSTS Language Arts Program and to discuss a study which examined data from a state-wide implementation of the HOSTS program. The specific research questions that guided the study asked 1) Can the HOSTS program be implemented on a large- scale with fidelity, and 2) What effect did fidelity of implementation have on student reading outcomes?

HOSTS Language Arts

As the name of this program suggests, Helping One Student to Succeed (HOSTS) Language Arts Program is a one-on-one intervention for students at risk of reading failure. The basic premise of this program is that struggling readers can improve their reading skills when instruction is tailored to their individual needs and with tutoring by a caring mentor (HOSTS Corporation, 2000; Blunt & Gordon, 1998). Developed in Vancouver, Washington in 1971, this forprofit tutoring/mentoring program targets primarily K-8 students who need assistance in reading, vocabulary, writing, thinking and study skills. In addition, the program focuses on such affective goals as improving behavior, attitudes and self-esteem. Individual computer-based assessments are conducted with students experiencing reading difficulties in order to identify their reading needs. Based on this information and available instructional resources, personalized interventions are computer-generated for each student and are incorporated into daily and weekly lesson plans implemented by trained volunteer tutor.

Lesson plans are implemented by having the HOSTS teacher/ coordinator prepare a personalized weekly folder for each student that includes daily lesson plans along with the activities, strategies, books and other necessary materials that the tutor is to use with the student. The student receives 30 minutes of one-on-one instruction in a learning center setting Monday through Thursday and may have a different tutor each day. The tutor/mentors are recruited from the community and may include college students, office workers, salespersons, firefighters, police officers, ministers, engineers, administrators, military personnel, retirees, homemakers, parents, grandparents and others (Blunt & Gordon, 1998; Cardenas & Chahin, 1999). The HOSTS teacher/coordinator trains the volunteer tutors and is present during tutoring session to monitor the instruction, providing assistance and feedback to the tutors.

Level I: The Research Base

The HOSTS Language Arts Program is a diagnostic, prescriptive and continuous progress model derived primarily from behaviorist theories of learning. Basic to the HOSTS Language Arts Program are mastery learning (Bloom, 1968) and direct instruction (Rosenshine, 1979, 1986; Rosenshine & Stevens, 1984). Both of these approaches are essentially behaviorist in orientation because they focus on objective and observable outcomes, and emphasize events in the individual environmental events such as reinforcement, frequent assessments, rapid feedback, and incentives (DeGrandpre & Buskist, 2000).

Bloom (1968,1987) described mastery learning as task-oriented with content and skills broken down into sequenced units for study, formative quizzes, feedback, and corrective procedures until the student can pass the test at an acceptable level of mastery (80%100%). Recognizing individual differences, the assumption is that nearly all students can reach mastery if provided quality instruction and adequate time. Rosenshine (1979, 1986) describes direct instruction as a teacher directed, skills-oriented approach involving clear goals, sequenced and structured tasks and materials, sufficient time for instruction, high student engagement, monitoring of student progress, immediate feedback, and an atmosphere of warmth and cooperation. Fundamental to both mastery learning and direct instruction is the philosophy that there is a core of fundamental knowledge and skills to be mastered. Some are prerequisites for more complex skills and others are important each in its own right.

Reductionism is the key to the systematic approach of HOSTS Language Arts Program as literacy is broken down into a taxonomy of skills and subskills (HOSTS, 2000). In accordance with the essential components of reading instruction identified by National Reading Panel (2000), each student’s personalized reading prescription addresses phonemic awareness, phonics, fluency, vocabulary, and comprehension. Each 30minute tutoring session includes activities in reading and discussing a piece of literature, vocabulary, writing, and skills development (HOSTS, 2000). Although the amount of time engaged in learning has been found to correlate with the amount and degree learned (Brophy, 1988), tutoring has the potential to maximize the time on task when focusing on one student’s needs and directing the student’s attention and efforts by demonstration, guidance and feedback.

While the HOSTS Language Arts Program has clearly a behaviorist theoretical basis, it also draws on elements of social interactional theories of learning and development. Vygotsky’s (1978) theory suggests that by interacting with more knowledgeable and responsive people who provide supportive assistance, students are able to perform tasks at a higher level than they could do independently. Within this zone of proximal development, the student learns how to perform tasks with guidance and feedback until able to internalize the process and function autonomously. HOSTS uses a continuous student assessment model with the intent that each lesson be designed for the student’s zone of proximal development. The role of the tutor is to provide scaffolding guidance and feedback on an as- needed basis until the student reaches mastery of the skill. Tutors are trained in scaffolding techniques such as breaking the task down into smaller steps, prompts, hints, modeling, and encouraging the student to verbalize thinking involved in the task (HOSTS, 1999). As part of this process, another goal of HOSTS is to increase the student’s self concept related to learning or self-efficacy and, as a result, motivation to master reading skills. Social cognitive learning theory (Bandura, 1977, 1986; Schunk, 1989) suggests that students who believe they are capable of doing well on an academic task are motivated to attempt similar tasks thus leading to higher achievement in that particular domain. While providing,scaffolding and feedback to support the student in mastery of the task, the HOSTS tutor also gives encouragement conveying the belief that the student can achieve the goal. In then-training, tutors learn a variety of supportive statements and body language to show their confidence in the student’s ability and to encourage the student to persist (HOSTS, 1999). Level II: Efficacy in Applied Settings

In order to adequately evaluate an educational innovation, research in applied settings is needed to examine the efficacy in improving educational outcomes for children (Ellis, 2001). Although numerous evaluations have examined effectiveness of HOSTS on reading achievement for at-risk populations, independent research is in its infancy.

Studies conducted by HOSTS and school districts in which HOSTS was implemented consistently found significant gains in student reading skills. Amultistate study compared normal curve equivalents (NCE) gains for first, second and third graders who participated in HOSTS to schoolwide and statewide gains. Results suggested gains that exceeded schoolwide and statewide gains by 15 points for first- grade, and 25 points for second and third graders (HOSTS, 1994). Single school district evaluations also reported substantial gains in the reading achievement of at-risk students receiving HOSTS tutoring (Gallegos, 1995; HOSTS, 1994,1998). Moreover, a study of six exemplary HOSTS sites found that most students in the HOSTS program achieved grade level reading proficiency in one year and those who did not reached grade level within the second year of participation (Cardenas & Chahin, 1999).

Although the number of independent evaluations of HOSTS effectiveness in an applied setting is comparably fewer than the number of those conducted by HOSTS or HOSTS schools, results also suggest positive outcomes (Bryant.Edwards.&LeFlies, 1995; Wilbur, 1995). The largest of these studies examined data for over 6,600 students at 136 schools in Delaware, Michigan and Texas. Resulted suggested average reading gains of 2.0 grade levels for students in grades 2 through 4 as measured by pre- and post-test scores on an informal reading inventory (Holden, Simmons, & Holden, 1998).

Only one study found in the literature examined HOSTS effectiveness with an experimental and control group design. Burns, Senesac, and Symington (2004) compared gains on standardized measures of reading, using a 5-month test-retest interval, between 129 students who participated in the HOSTS program to a control group of 127 students who were identified as at-risk for reading failure, but did not participate in HOSTS. Analyses of covariance suggested that reading growth experienced by the experimental group significantly exceeded that of the control group on measures of reading fluency, reading comprehension, initial sound fluency, and overall reading skills (Bums et al.,2004). Therefore, although more research is needed including field-based randomized controlled trials, data support the effectiveness of the HOSTS program in improving reading skills of children identified with reading difficulties.

Level III

Research at Level III examines the effectiveness of an innovation after wide-scale implementation (Ellis, 2001). As stated above, the purpose of this paper is to examine existing research for Levels I and II, and to collect data with which Level III could be examined as well. The two research questions addressed were can the HOSTS program be implemented on a large-scale with fidelity, and what effect does fidelity of implementation have on student reading outcomes? These questions were examined by collecting reading data from 51 elementary schools, in 10 school districts in Michigan that began the HOSTS program during the 2001-2002 school year. Each school was classified into two groups according to the HOSTS Success Indicators (HSI) score, which is a measure of implementation fidelity, and reading gain scores were compared. The two groups were High Implementation and Average to Low implementation.

Participants

The HSI scores for a majority of the 51 schools (n = 32,62.7%) fell within the High Implementation range, with only 19 schools (36.3%) being rated within the Low to Average Implementation category. Atotal of 1,354 students participated in the HOSTS program within these 51 schools, with 897 in the High Implementation group and 467 in the Low to Average Implementation group.

As shown in Table 1 ,the two groups were generally equal for all variables. AfricanAmerican students were overrepresented in both groups as compared to national norms, but prevalence rates were consistent with previous research among mostly urban and at-risk populations. Both groups had a high representation of students eligible for the federal free and reduced lunch program equaling 80.0% of the High Implementation group and 70.5% of the Average to Low group. However, only 2% and 3.6% of the students respectively were eligible for special education services.

Variables

Gains in reading skills served as the dependent variable for the study. In September and May of the 2001-2002 school year each student in the study was administered the Basic Reading Inventory (8th ed.; BRI; Johns, 2001) to assess reading levels. The BRI is an individually administered reading assessment tool used to estimate a child’s instructional reading level (IRL) that results in grade level scores (e.g., 2.0, 2.5, etc.). Like most assessments developed from an informal reading inventory paradigm, the BRI involves orally reading passages written at various grade levels and answering comprehension questions. IRL scores for September were subtracted from the May score to create a reading change score that served as the dependent variable.

The HSI score served as the primary independent variable for the study. Each school completes an HSI form in the spring with the assistance of a consultant from HOSTS. The HSI is a scale consisting of six components with three to five items in each. Components consisted of Diagnostic Assessment,Individualized/ PrescriptiveStrategies, Mentoring, Communication, Administralive Support, and Program Impact. Each item within the components was rated on a four-point scale labeled as superior, strong, developing, and incomplete. Although those labels seem subjective, each is linked to objective data. For example, the first item for Diagnostic Assessment addresses how many of the students were administered the BRI with at least 90% within the first 2 weeks being superior, at least 80% within the first month being strong, fewer than 75% within the first year was developing, and less than 50% was incomplete. Acoefficient alpha was computed to estimate reliability of the scale. The resulting coefficient of .76 suggested adequate reliability for research purposes.

After completing the scale, the score is summed and divided by total possible points and multiplied by 1OO to obtain a percentage. An HSI score of 90% is considered high implementation (HOSTS, 2003). As stated earlier, 32 schools met or exceeded 90% and were classified as High Implementation. An additional 15 schools scored between 80% and 89%, and four schools were rated between 70% and 79%. Therefore, to better assure a comparable number of schools within groups, all schools that scored less than 90% were grouped together as one group called Average to Low Implementation.

In addition to BRI and HSI scores, the number of student absences and mentoring sessions for the year were collected and recorded. Themeannumberof student absences were 10.65 (SD = 9.72) for the High Implementation group and 11.12 (SD = 10.20) for the Average to Low group with the difference between the two groups not being significant t = (1429) .83, p = .41. Students in the High Implementation group averaged 59.43 (SD= 31.77) mentoring sessions during the school year, as compared to 44.76 (SD = 27.29) in the Average to Low group. Therefore, the average number of mentoring sessions was significantly greater f (1465) = 8.43 ,p

Procedure

The HOSTS Corporation was contacted to generate a list of elementary schools that implemented the HOSTS program during the 2001-2002 school year. Next, the principals of those buildings were contacted to recruit participation and get HOSTS scores. Finally, the schools sent September BRI data in October and May BRI data in June. The data received in June also included number of student absences, number of mentoring sessions, and demographic data. Schools were provided a report that detailed data analyses for their particular HOSTS program in exchange for participating in the study.

The first research question examined how frequently high implementation ratings occurred by conducting a chi squared analysis with the number of schools rated between 90% and 100%, between 80% and 89%, and less than 80%. The second question asked if level of implementation fidelity wouldaffect reading gains and was examined by conducting an analysis of covariance (ANCOVA) between reading gains scores of schools in the High and Average to Low Implementation groups. The number of sessions was used as the covariate because there was a significant difference in mean frequency of sessions between groups. All analyses required an alpha level of less than .01 to establish significance. Table 1

Demographic Data for Students in Two Implementation Groups

Results

The first research question asked if the HOSTS program can be implemented with fidelity. Almost two-thirds (n = 32) of the schools had ratings that exceeded 90% and were considered a High Implementation group. The remaining schools were considered Average to Low implementation, with 15 of the schools receiving an HSI score between 80% and 89%, and four between 70% and 79%. A chi squared analysis revealed significant results X^sup 2^ (2) = 23.41, p

The second research question asked if level of implementation fidelity would affect reading gains. As shown in Table 2, students in the High Implementation group outperformed their peers in the Average to Low group using the number of mentoring sessions for each student as the covariate. The difference between groups was also examined by computing Cohen’s (1988) d, which equaled .29 and suggested a small to perhaps moderate effect.

Discussion

A review of research suggested that the HOSTS tutoring program was developed from sound theory and data exist to support its effectiveness. However, consistency of implementation is also needed to assure success when using an educational innovation (Ellis, 2001). The current study suggested that a high level of implementation occurred on a large scale. Moreover, given that these schools were within the first year of implementation and were still frequently rated highly in implementation fidelity, it would seem that consistency in implementation would be somewhat easily obtained perhaps due to HOSTS’ structured and frequentlymonitored model.

The literature is replete with evidence that one-on-one tutoring can be a powerful intervention in accelerating the literacy development of struggling readers (Cohen, Kulik, & Kulik, 1982; Elbaum, Vaughn, Hughes & Moody, 2000; Wasik, 1998; Wasik & Slavin, 1993, Shanahan, 1998; Morrow & Woo, 2001). However, implementation fidelity must also be considered when evaluating effectiveness data (Elbaum et al., 2000), especially given that previous research suggested that some tutoring programs were implemented in a manner that was inconsistent with expectations (Roe & Vukelich, 2003). The current study found that children participating in programs rated to be implemented with high fidelity demonstrated larger gains than students in schools with moderate or low implementation. This finding supports the importance of implementation fidelity and suggests confidence in data supporting the effectiveness of the HOSTS tutoring program as intervention for struggling readers . However, the small effect size suggested that both groups experienced gains in reading scores. The effect size may have been larger if comparison groups were high, moderate, and low implementation instead of high and low to moderate implementation, but this was not possible given the infrequency of a low implementation rating.

Table 2

Mean Gain Scores and ANCOVA Results Two Implementation Groups

The Peer Assisted Learning Strategy (PALS; Fuchs, Fuchs, Mathes, Simmons, 1997) is an often referenced tutoring model that relies on peers to deliver classwide tutoring for children experiencing academic difficulties. PALS, like HOSTS, is often implemented with high fidelity (Mathes, Torgesen, & Allor, 2002; Mathes, Howard, Alien, & Fuchs, 1998) and presents a cost effectiveoption for tutoring students. Research on PALS as an intervention for Iow achieving readers in elementary grades found effect sizes similar in magnitude to the .29 standard deviation units found in the current study (.33, Fuchs, Fuchs, Mathews, & Martinez, 2002; median of .23, Fuchs et al., 1997; median of .42 Mathes et al., 1998). It should be noted that the Moreover, the current effect size is also consistent with previous research using adult tutors with children experiencing reading difficulties (median of .27Allor & McCathren, 2004; median of .44, Baker, Gersten & Keating, 2000).

Although data in the current study suggest some implications for practice, limitations of the data need to be considered. First, the data were obtained from the BRI, which is an informal reading inventory with unknown psychometric properties (Bums, 2003). It can probably be assumed that data from the BRI were sufficiently reliable for research purposes (Burns, 2003), but that would be an assumption without empirical support. secondly, data were collected by the teachers who implemented the program, which suggests the potential for bias. Finally, these data were from one school year and do not address the program’s sustainability.

NCLB requires schools deemed in need of improvement to use 20% of their Title I funds for tutoring. However, the potential costs to provide expert teacher tutoring for students to achieve grade level standards is staggering.far exceeding available funds (Allington,2004). HOSTS may provide a more cost effective option in that trained volunteers provide the one-on-one structured tutoring under the supervision of a trained teacher. Moreover, given that high levels of implementation appear somewhat easily obtained and level of implementation affected results, the likelihood of implementing a successful program could be high.

References

Allington, R. L. (2004). Setting the record straight. Educational Leadership, 61,22-25.

Allor, J. & McCathren, R. (2004). The efficacy of an early literacy tutoring program implemented by college students. Learning Disabilities Research & Practice, 19,116-129.

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Correspondence concerning this article should be addressed to Barbara V. Senesac at [email protected]

Education

Opinions of Prospective Social Studies Teachers on the Use of Information Technologies in Teaching Geographical Subjects

Written By: Sam Savage

Published Date: August 29, 2008 Last Edited: August 29, 2008

By Akengin, Hamza

Use of information technologies in the field of geography, one of the important disciplines that comprise the social studies course, contributes to rendering abstract phenomena and concepts concrete in terms of primary education students, thereby increases their interest in social studies. In this context, the basic purpose of this study is to evaluate the use of information technologies in teaching geographical subjects within the scope of the social studies course. The semi-structured interview technique from among the qualitative research approaches was used, and additionally a content analysis was conducted in the study. The data were collected through interviews with 20 prospective teachers, who studied at the Social Studies Teaching Program in the 2006-2007 academic year, on voluntary basis. Numerical analysis and descriptive analysis techniques were used in the analysis of the research data. According to the results obtained, prospective teachers were acquainted with the computers, the Internet and projectors the most from among the information technologies, and think that these technologies were utilized at schools and teacher training programs. Furthermore, the prospective teachers, who consider that biggest reason for inadequate use of the information technologies is the lack of sufficient equipment, regard these technologies as important particularly in terms of visuality and they recommend that the existing equipment be increased and the courses intended for information technologies be intensified. Since its existence, mankind has perpetually produced and distributed information and used this information for its own needs. All methods such as carrier pigeons, the Morse code and smoke used for distribution of information in the past are the examples of information technologies. Today, these have been replaced by such devices as computers, satellite antennas, pagers, and mobile phones. The most basic difference between old and new technology is the speed in the distribution of information. The high speed that the new technologies provide increased the amount of information. All these changes have been achieved as aresult of the growth in microelectronic technologies, and electronic devices replaced the mechanical ones in accessing and using information (Makitya and Hind, 1992; Karahan, 2001).

With this change, the world gradually transforms into a digital form. This transformation also affects the education system as well as all other systems, and this situation becomes a must. Use of information technologies particularly in education has resulted in re-questioning and redefinition of the educational objectives, methods, and techniques, as well as of the equipment used. Computers that are primarily used in administrative services at schools have gone beyond their limits and strongly secure their place among other educational materials and equipment in classrooms (Lankshear, Snyder, 2000). Until recently, the understanding of educational technology brought to mind the equipment such as radios, televisions, filmstrips, overhead projectors, cassette players and video players. However, the conception of educational technology has changed rapidly in the last 10-20 years and begun to be used to mean technologies based largely on computers,e.g.CD-ROMs,Interactive audio, interactive video discs, local area networks, hypermedia and telecommunication (Ozturk and Inan, 1998).

Information technology can be defined as creating, collecting, accumulating, processing, retrieving, distributing, preserving information, and the means assisting them (Karahan, 2001). The information technologies are called the “teaching technologies” in education. The widespread use of information technology has caused the societies to transform into “information society” today. New technologies have affected both the economic structure and social and educational structure, and therefore societies are forced to follow technological advancements (Akkoyunlu, 1998). In our century, when time has become the most important factor, individuals should not be late to keep abreast of the age and technology. Rapid and easy completion of this adaptation process is only possible through education the individuals are to receive. And, this could be achieved through making best use of the opportunities provided by the educational technology and effective utilization of new technologies in education (Karalar & Sari, 2007). In this context, computers, databases, the Internet and numerous new hardware and software provide students with considerable facilities and time savings by allowing them to enjoy a variety of experiences in accessing information and in integrating, analyzing and evaluating this information, and to create new information through obtaining detailed information about the past. Therefore, citizenship education challenging the 21st century has to prepare students for being capable of using such means in the problem-solving and decisionmaking processes (Fontana, 1996).

Particularly in the school programs, social studies are the primary course responsible for citizenship education. One of the primary questions that the social studies programs seek an answer is how individuals (citizens) can keep abreast of the rapid change of technology (Turner, 1996). The United States National Council of Social Studies (NCSS) supports integration of technology into social studies classrooms to change the teaching methods for the contents of the social studies course and relevant skills (Doolittle & Hicks, 2003). According to Mason et al (2000), in social studies teaching, the technology provides unforeseeable facilities in teaching the contents of the social studies when compared with the traditional classrooms. Accordingly, the principles of the social studies course such as meaningfulness, integrativity, value- basedness.challengeability, and effective learning, which are essential for the course to bring up effective citizens, would make more sense when supported with technology. According to Rose and Fernlund (1997), the information technologies make meaningful, integrate and activate the learning-teaching process in achieving the principles for a powerful social studies learning. On the other hand, Braun and Risinger (1999) indicate that many social studies educators assist students to explore their own worlds critically using the information technologies in order to develop civic responsibilities.

The Turkish Ministry of National Education has progressively implemented a new Social Studies Curriculum in line with the developments in the world as from the 2005-2006 school year. It was stated that the approach taken as basis in the curriculum was constructivism. While the use of technology was underdeveloped in theory in the traditional approach,constructivist approach constitutes one of the theoretical bases that surround the integration of technology into social studies teaching (Doolittle and Hicks, 2003). Because, as the learner’s constructing the knowledge is the basis in constructivist learning environments (Tezci and Gurol, 2001), learning environments are so organized that individuals interact with their environment more and enjoy richer learning experiences. Therefore, it is important for teachers to support the data and basic sources with skillful and interactive materials (Demirel, 2001). At this point, use of technology in constructivist learning environments is both significant and necessary in order to create interactive learning environments.

According to Mason et al. (2000), another basis for the requirement for the technology to be an integral part of social studies classrooms is that technology could be learned within context in a better way. In other words, students must use technology as a tool not only in computer courses but in all courses as well. Because this use is driven by a specific purpose, effective learning can be achieved. The situation has more critical significance for social studies course. Particularly in the twenty- first century, when concepts such as e-government, e-citizenship are used predominantly, this course that is responsible for effective citizenship education must be integrated with utilization of technology.

People and history, cultures, social structures and beliefs of those people are studied to a large extent at social studies courses in primary education.Additionally climate,flora and similar natural facts are also dealt with (Akengin, 2007). Most of these subjects are abstract. Use of information technologies enables students to participate in the learning process more actively and prepares the environment for concretizing the subjects (Sunal and Haas, 2002).

Abstract social sciences disciplines such as Anthropology, Economics, Geography, History, Political Science, Psychology and Sociology play an important and necessary role in social studies course in primary education (Turner, 1994). Use of information technologies particularly in the field of geography, which is one of the major disciplines of the social studies course, makes abstract phenomena and concepts concrete in terms of the primary education students, and consequently increases their interest in this course. In this context, the primary objective of this study is to evaluate the state of use of information technologies in teaching geographical subjects within the scope of social studies course based on the opinions of prospective social studies teachers. It is expected that the findings of the study will provide considerable contributions to implementors. The primary objective of this study is to evaluate the state of use of information technologies in teaching geographical subjects within the scope of social studies course based on the opinions of prospective social studies teachers.

Method

This section covers the model of the study, the participants, and the collection, analysis and interpretation of the data collected.

Model of the Study

Because it was intended in this study to obtain the opinions of prospective social studies teachers regarding the state of use of information technologies in teaching the geographical subjects within the scope of the social studies course, the semi-structured interview technique from among qualitative research approaches was used. The reason why this technique was used is that an interview process intended for exploring the experiences of the researchers interviewed was aimed in line with the purpose of the study.

Participants

Criterion-sampling method from among purposeful sampling methods was used in this study. Purposeful sampling involves studying information-rich cases in depth and detail (Patton, 1997). On the other hand, the primary understanding in criterion-sampling method is to study all the cases that meet a number of previously determined criteria.The aforementioned criterion or criteria can be created by the researcher or a list of criteria prepared beforehand can be used (Yildirim and Simsek, 2005). Accordingly, the criteria list was created taking into consideration the qualifications of the prospective social studies teachers.

The primary criterion in selection of the prospective teachers to participate in the study was that they should be senior students at the Social Studies Teaching Program, who completed all the theoretical and practical courses that provide them with the foundation to become social studies teachers. In accordance with this primary criterion, interviews were conducted with 20 prospective teachers meeting the criteria listed on the criteria list from among 110 senior students studying at the Social Studies Teaching Program in the 2006-2007 academic year.

Data Collection Process

Semi-structured interview technique was used as data collection method. In this context, a semi-structured interview form was prepared to collect data in accordance with the problem of the study. Acomprehensive literature review was taken as basis in preparation of the form. Main questions were determined after obtaining the opinions of 3 specialists from the Department of Educational Sciences and 2 specialists from the Social Studies Teaching program at the Ataturk Faculty of Education at Marmara University. These questions are as follows:

1. What do the information technologies mean to you and what do they cover?

2. What information technologies could be utilized in teaching geographical subjects in the context of social studies course?

3. What information technologies are currently utilized in teaching geographical subjects in the social studies course?

4. Which of the following information technologies can you use effectively within this scope?

a. Power-point

b. Interactive CDs

c. The Internet

d. Google earth

e. Flash

f. Other

5. What kind of contributions and disadvantages would these information technologies offer with respect to teaching geographical subject in the social studies course?

6. What can be done for more effective use of the information technologies?

a. At teacher training programs

b. At schools

c. Other

A sound recording device was used to collect the data precisely. Permission was obtained from each participant with respect to the use of the sound recording device.

Analysis and Interpretation of the Data

Content analysis was conducted using numerical analysis, and descriptive analysis techniques were used to analyze the data collected. Sound recordings recorded during interviews with each prospective teacher were first transcribed into written texts.Then, similar expressions relating to the use of information technologies were determined and transferred to tables for use as numerical data. While the frequencies were specified in the quantitative analysis, direct quotations were provided in descriptive analysis in order to reflect the opinions of the interviewees with their own perspectives. Thereby, the reliability of the study was attempted to be achieved. False names were not used instead of the real names of the prospective teachers, whose opinions are included in the text of this study.

Findings and Interpretations

20 prospective teachers were interviewed face to face. The findings obtained from the answers the prospective teachers gave during the interviews were given through direct quotations and line numbers under themes and sub-themes. In direct quotations, the answers with higher frequencies are provided.

Opinions of the Prospective Teachers about What the Information Technologies Mean and What They Cover

Table 1

The Answers the Prospective Teachers Gave to the Question “What Do Information Technologies Mean to You and What Do They Cover?”

Prospective teachers were asked, “What do the information technologies mean to you and what do they cover?” as the first question. While four prospective teachers could not express any opinions about what they meant, all of the prospective teachers expressed their opinions about what they cover. The opinions of the prospective teachers concerning the answer to this question and their frequency distributions are given in Table 1.

As it can be seen in Table 1, the most common opinion about what computer technologies meant was the expression of 7 prospective teachers: “Tools that enable and facilitate accessing information.” This expression is followed by the opinions of 4 prospective teachers ‘Tools that facilitate and increase learning and perception”; “auxiliary factors utilized for and facilitating the presentation of information”; “Use of technological equipment in lessons”; and “They facilitate learning” respectively. While Zeynep, one of he prospective teachers who expressed their opinions about what the information technologies mean, said, “Information technologies (…) could be the technological things that we use to spread information, or to transmit information to others, or to spread that information, or that facilitates others to understand the information., Remzi said, “The information technology (…) means the auxiliary factors used to transfer the acquisitions obtained from a specific unit to students. We can say that these are the most important aids of teachers to convey the subjects to the students in a better way. Furthermore, it also assists the children to understand better and to equip the children with relevant necessary skills”.

Table 2

The Answers the Prospective Teachers Give About “Which Information Technologies Could be Used in the Instruction of the Geographical Issues within the Context of Social Studies?”

When the opinions regarding what information technologies cover in the Table 1 are examined, it is seen that the prospective teachers mentioned the computers (13), overhead projectors (11) and the Internet (9) the most. While Faruk, who stated that the computers and the Internet from among information technologies were significant, said, “(…) these are what we generally use fromamong the information technologies.But today computers and the Internet are popular”, Hakan said, “I mostly use computers from among the information technologies. In addition to this, I use the Internet along with the computer. The Internet is an incredible bookcase, a library for me (…).

Opinions of the Prospective Teachers about What Information Technologies could be Utilized in Teaching the Geographical Subjects in the Context of Social Studies Course

The question “What information Technologies could be used in teaching the geographical subjects in the context of social studies course?” was asked to the prospective teachers as the second question. Apart from one prospective teacher, all of them stated their opinions. The opinions of the prospective teachers concerning the answer to this question and their frequency distributions are given in Table 2.

As it can be seen in Table 2, with respect to what information technologies could be used in teaching geographical subjects, prospective teachers stated that mostly projectors (14), overhead projectors (12), computers (9), power-point presentations (6) and the Internet (5) could be used in teaching the geographical subjects respectively.

Murat, one of the prospective teachers who expressed their opinion on this matter, said with respect to the use of projectors, computers, overhead projectors and the Internet in teaching the geographical subjects:

Table 3

The Answers of the Prospective Teachers “Which Information Technologies Could be Benefited in the Instruction of the Geographical Issues at the moment?”

“Geography describes, well, the distribution of the world, the people, animals, other living creatures, their mutual interaction, mountains, stones, in other words the natural environment. Natural environment must be shown to the students visually. From this point of view, it would be very useful to use projectors, etc. in the geography course. For example, we did not see such visual aids at high school. Therefore, I know that visuality is an important thing in education.” ,

while Remzi said, “(…) especially landforms can be shown to the students through computers, projectors or overhead projectors. It would be good for presentation of the subjects visually for the students ” Faruk also said:

“In terms of geography, we can utilize information technologies to prepare teaching materials. In addition to that, we can make use of the technologies in conducting researches (…), preparing maps, or preparing images (….). It could be the most beneficial in conducting researches. This is generally based on computers and the Internet. As far as I can think, computer technology could contribute to researches”. Opinions of the Prospective Teachers about the Information Technologies Currently Utilized in Teaching Geographical Subjects in the Social Studies Course

As the third question, the prospective students were asked, “What information technologies are currently used in teaching geographical subjects in the social studies?”

Except for three teachers, all other teachers expressed their opinions on this matter. The opinions of the teachers are given in two basic groups as current situation of use at schools and at the teacher training program and under main themes that present the opinions all together. The opinions of the prospective teachers concerning the answer to this question and their frequency distributions are given in Table 3.

As it can be seen in Table 3, the prospective teachers expressed their opinions about the information technologies utilized in teaching geographical subjects at schools under three main themes. Accordingly, according to the prospective teachers, who expressed their opinions about what information technologies are used at schools, projectors and overhead projectors (6) are used the most at schools. As for me teacher training programs, the information technologies used the most are projectors (7), overhead projectors (6) and computers (6).

Seven of the prospective teachers, who stated that the information technologies were not utilized at schools, expressed the reason as “They exist at schools, but they are not used by teachers”, and 5 of them said, “There is no adequate equipment at schools”. The prospective teacher Elif, who expressed this kind of opinion, said the situation arose from the lack of necessary equipment by saying:

“At the schools where I went for practical training, there were no computers, overhead projectors in every classroom (…) Always, I mean, the same classical method of teaching ;teacher uses a piece of chalk and draws on the board. They are used at the university, but they do not exist at primary education schools where we go for practical training. I asked the teachers why they do not use anything, why they do not use visual equipment, for the education requires it. They said such equipment did not exist at school and that there was a queue for use. Even if they exist, there is only one, I think therefore they are not used, because there is no adequate equipment.

The prospective teacher Soner stated that teachers did not use the existing resources by saying, “(…) at the primary education schools, there are monitors installed on the tables of teachers, computer monitors, and there are also keyboards. Teachers can use them upon their will, but they are packaged, they have not been opened at all, the buttons are untouched, their packages are intact. (…)”.

Five of the prospective teachers, who thought that the level of use of information technologies was inadequate, stated that the utilization was inadequate due to “inadequacy of necessary equipment” in terms of schools. 4 prospective teachers stated that they find the utilization inadequate due to the fact that “it is limited to the individual efforts of academics” and 3 others due to “utilization of limited equipment as much as possible”. Faruk, one of the prospective teachers who expressed this kind of opinion, said, “(…) we experience the same thing at our university. We couldnotfind a projector to give a lecture. We struggled with that for two weeks. Actually lam not so unfamiliar with the situation, because, set aside the primary education schools, we study at university (….), we do not use and we cannot utilize information technologies”.

Opinions of Prospective Teachers about which Information Technologies They can Use Effectively

The question “Which information technologies can you use effectively within this scope?” was asked to the prospective teachers as the fourth question in the study. All the teachers expressed their opinions. The opinions of the prospective teachers concerning the answer to this question and their frequency distributions are given in Table 4.

As it can be seen in Table 4, prospective teachers expressed their opinions under three categories as “I know and I can use effectively,””I know but I cannot use effectively,” and “I do not know.” Accordingly, the information technologies the prospective teachers can use most effectively are the Power Point presentations (17). This is followed by the Internet (15) and interactive CD’s (14). The least known information technology is Flashes. 10 prospective teachers stated that they had no idea about flashes. This is followed by Google Earth, which 6 of the students said they did not have any information about.

Table 4

The Answers Prospective Teachers Gave to the Question: “Which Information Technologies can you Use Effectively within this Scope?”

With respect to how to utilize the Internet in geography course, the prospective teacher Zeynep said:

“For example, I can find the map of a place where I have no knowledge about from the Internet. In geographical terms, I can learn about a country where I have never been or known before easily. You can learn about their clothing, geographical forms, how they live, their languages, religions and everything”, on the other hand Gulcin said about the use of Power Point, “Yes, I think I can use the Power Point very effectively in teaching”.

Opinions of Prospective Teachers about what kind of Contributions would the Information Technologies Provide With Respect to Teaching Geographical Subjects in the Social Studies Course

As the fifth question in the study, prospective teachers were asked the question “What kind of contributions and disadvantages would these information technologies offer with respect to teaching geographical subject in the social studies course?” All teachers expressed their opinions. The opinions of the teachers have been given in two basic groups. The opinions of the prospective teachers concerning the answer to this question and their frequency distributions are provided in Table 5.

As it can be seen in Table 5, prospective teachers expressed their opinions respectively as, “It provides visuality” (12), “It provides permanent learning” (7), “It makes the information concrete” (4), and “It increases students’ interest”. Accordingly, prospective teachers think that the most important contribution of information technologies is visuality.

Songul, one of the prospective teachers who expressed their opinion on this subject, said: “(…) it is the most important contribution for it increases visuality. It is easy to have students involvedin the lesson. (…) The knowledge becomes permanent, because sound and vision are harmonious. It also creates distinction and arouses interest”. Uygar said, “Perhaps it provides permanence in learning. Because it is said that you learn more if you see it. Also it makes information concrete (…), for example parallels and meridians are abstract things, but if you study them visually, thisfacilitates learning (…)”. Hakki said, “It helps us to learn more productively. Because whenyou see it, knowledge becomes permanent when we get it. Because, I think visual learning is more permanent. Eda said, “(…) in geographical subjects, for example, we say stalactite, stalagmite, we say meander; because geographical subjects are concrete, visuality is a must. Therefore, if there is no visuality, it is not possible to educate students. If students learn geography without visual aids, they may forget the knowledge in a short while later. (…) It is definitely for sure that visuality is a must for geography”.

Table 5

The Answers of the Prospective Teachers concerning the Question “What kind of Contributions and Disadvantages in the Instruction of Geographical Subjects within Social Studies Course do Information Technologies Provide?”

As it can be seen in Table 5, prospective teachers expressed their opinions concerning the disadvantages of the information technologies with respect to teaching the geographical subjects in the social studies course respectively as “It may result in research laziness” (5). Sevket, one of the prospective teachers who expressed their opinions concerning the matter, said, “It may have a disadvantage (…). Plus, it has another aspect, researching from the Internet or somewhere else is not something like reading a book. Perhaps at the same time it may lead students to laziness. For example, they would never go to library, and may not think what library means (…). Zeynep said, “It may have a disadvantage. It may be laziness for example. In the past, students would use encyclopedias, and other books, but now there is the Internet, you can copy and paste the information from there, and the homework is done! Perhaps it may lead to laziness to some extent”.

Opinions of Prospective Teachers about What can be Done for More Effective use of Information Technologies

Prospective teachers were asked, “What can be done for more effective use of the information technologies in your opinion?” as the sixth question. All teachers expressed their opinions. The opinions of the prospective teachers were given in two basic groups as at teacher training programs and at schools. The opinions of the prospective teachers concerning the answer to the question and their frequency distributions are given in Table 6.

Table 6

The Answers of the Prospective Teachers to the Question, “What could be done to Use Information Technologies more Effectively?”

As it can be seen in Table 6, prospective teachers made suggestions as to what could be done in teacher training programs for more effective use of information technologies as “Reinforcing the relevant lessons at school” (6), “Reinforcing the relevant equipment” (5) and “The education can be provided by specialists in relevant fields” (4) respectively. Oguzhan, one of the prospective teachers who expressed their opinion concerning the matter, said, “If these are supposed to be very significant for us in the training we receive (…), they must be given in more details by more experienced academics and I do not believe it is done so”. Sedasaid,”Inmy opinion, the equipment we use is very limited. (…) That is, it does not work, there is only a few, the number of equipment must be increased, and they must be kept somewhere we can have easy access when we need them. It would be better if our classrooms were equipped in that way (…)”, and Selim said, “I think it could be prepared better. For example, some academics come and lecture without using them, if only they used visual equipment such as computers, they must not be limited to only social studies course, it must be spread across all our courses (…).

As it can be seen in Table 6, prospective teachers made suggestions as to what could be done at schools for more effective use of information technologies as “Reinforcing the relevant equipment” (11) and “Training the teachers” (4) respectively. Murat, one of the prospective teachers who expressed their opinion concerning the matter, said:

“Well, there should be an overhead projector or a projector, or something to show the students at each school, in each classroom. There was only one or two at schools we went for practical training. Even we could not find aprojector at this school (University). I means, I cannot imagine the situation of other schools. (…). First of all, schools should be supported financially and every classroom must be provided with a projector (…) and teachers lacking relevant skills should be trained accordingly. Training should be given to both teachers and students, but primarily to teachers. Every classroom in every school should be equipped in this way. Every classroom should have its own equipment”.

Discussion

Rapid development of information and technology in the field of education, rapid change of social structure and needs clear the ground for the change and development of the teaching programs as well (Acun, 2006). The field knowledge of the teachers, who implement the changing curriculums at classrooms, and their command of the information technologies, as well as the learning-teaching process should be supported with necessary equipment (Yasar and Gultekin, 2006). As Sevket expressed, because particularly the geographical subjects include abstract concepts (such as meridians and parallels), supporting the subjects with visual materials using information technologies facilitates learning.

It is very important to improve the competency of teachers with respect to utilization of information technologies in accordance with the developments in the curricula. It is known that particularly the prospective teachers’ utilization of information technologies relating to the field in which they receive training, and relating the information technologies with subjects would not only enable the education to attain its goals, but also increase the permanence of knowledge. Among the objectives of the geographical subjects in the social studies program is to develop the critical thinking. Sharma and Elbow (2000) point out that use of information technologies develops critical thinking skills in geographical subjects. Taking into consideration the fact that it is necessary to know about the subject for critical thinking, as Zeynep stated,use of the Internet resources enables students “in geographical terms, to learn about a country where they have never been or known before easily, with its people, clothing, geographical forms, how they live, religion and everything.”

Cooler, Kautzer and Knuth (2000) assert that the technological competence of teachers must include technical skills and the educational use of these skills. It is seen by the expression of Songul that some of the prospective teachers forming the experimental group for this study and the teachers serving at schools, where prospective teachers go for practical training, are adequate in terms of the use of technology and educational applications.

Emphasis is put on the fact that increasing the number of equipment at schools, training the teachers (Table 6), providing visual aids and thus increasing permanency of knowledge, using the information and communication technologies in teacher training would assist in societies to be equipped with the necessary human characteristics in the information age. Accordingly, it is an important result that the prospective teachers, who provided this study with the necessary data, express that they would be able to use some of the information technologies effectively (Table 4).

According to Diem (1999), the main challenge for social studies teachers is “to learn how to develop the skills to use the technology, new equipment and techniques effectively to increase understanding of the content”. Furthermore, emphasis is also put on the fact that the information increases rapidly in today’s societies owing to the innovations achieved in the field of information technologies, that access to information has become easier owing to the information technologies, and that there are certain standards aimed at use of computers as one of the information access tools effectively particularly in the field of education. It is pointed out that the most important standard is competency (Kahraman, Kose and Kara, 2005). The fact that the prospective teachers find themselves incompetent (Table 4) with respect to the use of Google Earth and flash programs, as well as of the easy-to-use equipment such as overhead projectors (Doganay, 2002), which can particularly be effectively used in teaching the geographical subjects, indicate that there are problems in terms of the competency of some of the prospective teachers forming the research group, in terms of use of the information technologies.

Even though there are many studies indicating that the information technologies support teaching activities in all areas of education, and increase the permanence of knowledge (Acun, [2006], Yasar and Gultekin [2006], Sharma and Elbow [200O]), it was also emphasized by the prospective teachers that, in addition to the contributions made by the information technologies to geographical subjects in social studies course, they may also lead to disadvantages such as research laziness in students, unfavorable results if not prepared and used effectively, and decrease in the efficiency of students (Table 5). Furthermore, it was also expressed that easy access to information in the Internet environment, instead of researching encyclopedias and books, may lead students to do their home works using the cut and past technique (Zeynep).

It is known that information technologies assist children in researching, organizing and arranging the geographical information in very different ways (OFSTED; 2004). The fact that the prospective teachers, such as Murat and Faruk, have approaches that support OFSTED with respect to teaching geographical subjects draws attention. However, it can also be concluded from the interviews that lessons continue to be conducted through ordinary methods at schools with inadequate technological equipment.

References

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Akengin, H. (2007). Egitim Programlannda Cografyanin Yeri Nedir? Cografya Nasil Ogrctilmelidir? (What is the Locus of Geography in the Curriculum? How must be Geography Taught?), Ilkogretimde Alan Ogretimi [Ed.: Ayla Oktay, Ozgol Polat Unutkan]. Istanbul: Morpa pp. 143-158

Akkoyunlu, B. (1998). “Egitimde Teknolojik Gelijmeler”. Cagdaj Egitimde Yeni Teknolojiler. (“Technological Developments in Education.” New Technologies in Contemporary Education. [Ed.: Bekir Ozer]. Eskisehir: Anadolu Universitesi Acikogretim Fakultesi Yaymlan pp. 1-12

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Diem, R. (1999 September / October). Editor’s notes. Social Studies and Young Learner, 2 (1), 2.

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Dolittle, P. & Hicks, D. (2003). Costructivizm as a theoretical foundation for the use of technology in Social Studies. Theory and Research in Social EDucation, 37(1), 72-104

Fontana, A. L. (1996). “Online Learning Communities Implications for the Social Studies.” Interactive Technologies and Social Studies. [Ed.: Peter Martorella]. Albany: State University of New York Press.

Cooler, D., Kautzer, K. & Knuth R. (2000). Teacher Competencies in Using Technologies: The Next Big Question. PERL Briefing Paper. ERIC document.

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Karahan, M. (2001). Egitimde Bilgi Teknolojileri (Ders Notu) (Information Technologies [Lecture Notes]). Malatya. URL: webdnonu.edu. tr/~mkarahan/calismahaim/egtbilgitek.pdf.Retrieved at 21st May, 2007 Karalar, H. & San, Y. (2007). Bilgi Teknolojileri E|itiminde BDO Yazihmi Kullanma ve Uygulama Calijmalanna Yonelik Bir Cabsma. A Study Directed for the Use of Computer-Assistant Learning and its Implications. Akademik Bilijim 2007. Dumlupmar University, Kutahya 31st January-2nd February, 2007. URL: http://ab.org.tr/ab07/ bildiri/l .pdf Retrieved at 21st May, 2007

Lankshear, C, Snyder, 1. (2000) Teachers and Techno-Literacy : Managing Literacy technology and Learning in Schools. Sydney, NSW, AUS: Alien & Unwin

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School : case Studies for the Teachers. Florence, KY, USA: Routledge.

Mason C., Bergson M., Diem, R., Hick, D., Lee, J., & Dralle, T. (2000). Guidelines for using technology to prepare social studies teachers. Contemporary Issues in Technology and Teacher Education. 1 (1), 107-116.URL: http://www/citejoumal.org/voll 1/issl/ currentissues/socialstudies/article1.htm Retrieved at 21stay, 2007.

NCSS (1992). “A Vision of Powerful Teaching and Learning in the Social Studies: Building Social Understanding and Civic Efficacy,” available at /http://www.socialstudies.org/positions/powerful/>, retrieved at 21″ February, 2005

OFSTED(2004).ICTinSchool:TheImpactofGovernment Initiatives: Five Years On. http://www.ofsted. gov.uk/publications/ index.cfm?fuseaction=pubs. displayfile&i d=3652&type=pdf

Oturk, C. & Inan. N.U. (1998). “Ilkogrctim Sosy al Bilgiler Dersinde Kullanilabilecek Ban Bilgisayar Yazilimlanmn Degerlendirilmesi” (“Consideration of some Computer Software that could be Used in Social Studies Course”), IV. Ulusal Simf Ogretmenligi Sempozyumtt, Pamukkale University Education Faculty, 15th 16th October 1998, Denizli: Pamuakkle Universitesi Egitim Fakultesi, Ozel Sayi.

Rose, S.A. & Phyllis M. F. (1997). Using Technology for Powerful Social Studies Learning. Social Educational (3), 60-66.

Sharma, M. B & Elbow, G. S. (2000). Using Internet Primary Sources to Teach Critical Thinking Skills in Geography. London: Greenwood Press.

Sunal, C.S. & Haas, M:E. (2002)., Social Studies for the Elementary and Middle Grades. A Constructivist Approach, Boston: A Person Education Company.

Tezci, E. & Gurol, A. “Olusmrmaci Egitim Tasanmmda Teknolojinin Rolu” (“The Role of Technology in Constructivist Educational Design”), Sakarya Universitesi Egitim Fakultesi Dergisi, 3: 151- 156, 2001.

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Yasar, S. & Gultekin, M. (2006). Sosyal Bilgiler Oretiminde Arac Gerec Kullamnu (Use of material and Equipment in Social Studies Instruction) Hayat Bilgisive Sosyal Bilgiler Ogretimi. [Ed.:Cemi; Ozturk]. Ankara: PegemA Yayincihk pp. 287-311

Yazilmu Kullanma ve Uygulama Sonuclanna Yonelik Bir Cahsma (A Study Intended for the Use of Software and Implication Results). Akademik Bilisim 2007. Dumlupinar University, Kutahya 31st January- 2nd February 2007.URL:http://ab.org.tr/ab07/bildiri/1.pdf Retreieved at 21st May, 2007.

Hamza Akengin, Maratnara University, Ataturk Faculty of Education, Department of Primary Education.

Correspondence concerning this article should be addressed to Hamza Akengin at [email protected]

Education

Favoritism in the Classroom: A Study on Turkish Schools

Written By: Sam Savage

Published Date: August 29, 2008 Last Edited: August 29, 2008

By Aydogan, Ismail

Favoritism is among the most popular topics in educational institutions. Teachers are said to favor certain students over others at school and especially in their classes. Despite this popularity, there are very few studies on this topic. In Turkey, discussion of the topic does not go beyond newspaper articles. This study was therefore undertaken to establish the perceptions of Turkish high school students as to whether their teachers were engaged in favoritism. A total of 896 high school students were contacted for their opinions. Data was collected through questionnaires and analyzed with respect to students’ gender, economic status and academic success. The students were found to believe that those whose parents were friends or relatives with the teacher, occupied powerful positions or were economically privileged, and those who held similar political views to the teacher or were physically attractive were favored by the teachers. The ethical principles of the teaching profession include professionalism, responsible service, fairness, equality, loyalty, maintaining a healthy and safe environment, honesty and integrity, trust, objectivity, professional loyalty and continuous development, respect, effective use of resources, respect for human freedom, and compassion (Aydm, 2003; Keith-Spiegel,Witting, Perkins, Balogh & Whitley, 1993) .Additionally, by signing the United Nations Convention against Discrimination in Education, many countries, including Turkey, have adopted the principle of non-discrimination in education for all citizens regardless of race, color, gender, language, religion, political or other affiliations, national or ethnic background, economic power or birth rights. Despite these ethical principles and the existence of the Convention, allegations of discrimination or favoritism sometimes surface in education (Milliyet, 7 October 2006).

Favoritism is the inclination to favor some person or group not for their abilities but for some irrelevant factor such as a characteristictheypossess.or their personal contacts.or merely out of personal preferences (Employee Favoritism, 2006). It destroys equality as it brings certain advantages to people who did not earn them and it also hurts others’ good intentions (Nadler and Schulman,2006).One of the most basic themes in ethics is fairness, stated this way by Aristotle: “Equals should be treated equally and unequals unequally.” Favoritism interferes with fairness because it gives undue advantage to someone who does not necessarily merit this treatment. Comparing the effort distribution of the “normal” pupils with the one of the “special” pupils leads to an observation which might be counterintuitive from the perspective of folk-psychology: Regardless of the question whether ornot they are highly talented in reality and no matter with what kind of teacher they are matched, “special” pupils never become top achievers in a situation where they are potential favorites (Mechtenberg, 2006). I strongly believe that the biggest dilemma presented by favoritism is that few people see it as a problem.

Favoritism in the classroom is one of the most important reasons affecting instruction and thus student success. Factors leading to favoritism among teachers may be listed as follows (Brophy, 1983;Clifton,Perry,Parsonson andHryniuk, 1986; Delamont 1983;Ritts, Patterson and Tubbs, 1992; Dembo, 1994; Bilton, Bonnett, Jones, Stanworth, Sheard, Webster, 1993; Feldman and Saletsky, 1990; Braun, 1976; Kenealy, Frude, Shaw, 1988; Mortimore, Sammons, Stoll, Lewis, Ecob, 1994): student success, student’s social or economic status,gender,physical appearance, familiarity between student and teacher or student’s family and teacher (blood relations or friendship), and Parallelism between the ideology (political or religious) of students or their family and the teacher.

Student Success

Building a positive relationship between the teacher and students helps students become more successful and have more motivation (Al- Houli, 1999;Bhushan, 1985). A teacher’s relationships with students both within and outside the classroom affect their attitudes towards and motivation for that class (McGarity & Butts, 1984). However, teachers are sometimes affected by student success or failure. More precisely, teachers may criticize less successful students more harshly and have less contact with them, thus breaking their motivation to learn. On the other hand, they may perceive certain other students as more successful and thus develop a more positive attitude towards them, which ultimately supports them in gaining more success (Jussim, Smith, Madon & Palumbo, 1998).

Social and Economic Status

Another influential factor in teacher favoritism is the social class to which students belong. Students from a middle class background are observed to be better favored than those from a lower class background (Jussim et.al., 1998). In studies conducted on primary school teachers, it was found that whenever teachers were knowledgeable about students’ socio-economic background, they were also behaving in favor of those from higher social classes (Ozturk, Sahin and Koc, 2002). Sprinthall and Sprinthal (1990) state that in cases where students belong to a lower social class than the teacher, the end result may be teacher favoritism for students that come from a similar background to themselves.

Gender

Gender is an inborn and easily understandable characteristic. Sometimes teachers may be influenced by the gender of a student. Female teachers may have a tendency to favor male students, and male teachers may favor female students. The opposite, that is favoring the students of the same gender, is also a common tendency. Various psychological or social reasons may underlie such teacher behavior. Unconsciously or not, we cannot deny the fact that teachers usually tend to give special attention to boys. What is worse, boys somehow seem too notice that and start to assume a controlling attitude, interrupting girls and demanding more from teachers (Vicente, 1999).

Physical Appearance

Starting from pre-school, teachers have been observed to evaluate student talent relying solely on their physical features. At the very least, they build their first impression on students’ physical appearance and favor those who are better-looking (Jussim et.al., 1998;DusekandJoseph,1983).Acorrelation has been reported in the literature between the perceived attractiveness of a student by the teacher and perceived academic intelligence (Tauber, 1997). Investigating with 17 teachers and 400 middle school students whether physical attractiveness-based teacher expectations are reflected in student grades, Felson (1980) found that physically attractive students were thought to be more talented and thus assigned higher grades, and further, he concluded that physically unattractive students were openly discriminated against (Tauber, 1997). Similarly, in a different study conducted on female primary school, high school and college students, physically attractive students were found to get better grades (Ritts et.al., 1992).

Familiarity between Student and Teacher or Student’s Family and Teacher (Blood Relations or Friendship)

Teachers may sometimes be the guardian, relative, or a family friend of the student. Favoritism is highly probable in such cases. In her paper, Mechtenberg (2006), states ” I consider a one shot cheap talk game with two different type of senders (biased teachers and fair teachers), two types of receivers (“normal” and “special pupils”) and uncertainty about the sender type on the side of the receiver. I demonstrate that the group of pupils who, in expectation, get either too much or too little encouragement will have less top achievers and a lower average achievement than the group of pupils who get a more accurate feedback message, even if the prior talent distribution is the same for both groups of pupils”. I assume that the discriminatory behavior has its roots in the preferences of those who exhibit this behavior. I personally think that “special pupils” are either favorites or victimsofdiscrimination.Theirtalents may blur with being teacher’s favorite.

Parallelism between the Ideology (Political or Religious) of Students or Their Family and the Teacher

Teachers may favor certain students with whom they share a certain political view, religion or sect. In such circumstances, they may give better grades to those who share their view or they may give worse grades to those who support another view or belong to a different religion or sect. It is believed that in the middle eastern countries favoritism and nepotism are regarded as part of everyday life. According to a survey done by the Coalition for Accountability and Integrity (AMAN) ’32 % of those surveyed indicated that they were asked to intervene, or one of their family members or their friends was asked to intervene, so that somebody can acquire a job (The Coalition for Accountability and Integrity, 2004).

Problem

Favoritism has been a rather popular research topic recently. An examination of the literature shows that most studies focus on the home, i.e. favoritism among children and interpersonal relationships. These studies were based on teacher and guardian opinions (Haris and Howard, 1983; Bank, 1987; McHaIe, Sloan & Simeonsson, 1986). At the same time, studies on practical classes at schools also exist (Roy and Roy, 2004). The study is different from the other studies in many ways. It examines the topic from a practical viewpoint. This study aims to clarify the concept of favoritism in classrooms by determining whether a) student success, b) gender c) parents occupying powerful positions, d) good economic status, e) physical appearance, f) holding similar ideologies to the teacher, and g) familiarity or blood relations between parents and teachers make a difference in teacher behaviors.

The aim of the study is to reveal whether students attending public high schools believe that teacher favoritism results from student characteristics. In other words, it aims to show whether student gender, success and economic status leads to a difference in the perception of teachers’ instruction, communication, discipline and evaluation behaviors.

Method

While most educational research can be classified as quantitative or qualitative, there are some additional types that they do not align well with either of these two classifications. These can be called analytical studies. Analytical research is a mode of inquiry in which events; ideas, concepts, or artifacts are investigating by analyzing documents, records, recordings, and other media. Like qualitative studies (some researchers classify analytical studies, as described here, as qualitative), contextual information is very important to accurate interpretation of the data (McMillan, 2004). In this study analytical method was used. This study takes as its population students attending public high schools affiliated to the National Education Directorate in Melikgazi, Kaysen. There are 12 public high schools in the town and, at the time of the study, 12,648 students were attending these schools. Due to the large size of the population,only those students attending 11th grade (senior students) were chosen for the study. As the number of these students was still high at 4,200, random sampling of students from 6 of the high schools was undertaken. A scale was employed to collect data which was sent to the randomly selected schools and administered by 20 students enrolled in the non-thesis MA program of Erciyes University Institute of Social Sciences. The respondents had one week to complete the scale. Students who had classes during this week and thus were attending school were invited to volunteer to complete the scale. A total of 896 students agreed to complete the questionnaire. The scale response rate was 99%.

Data Collection

The scale mentioned above was used to collect data. In developing this tool, the researcher first reviewed the literature on ethics in education and favoritism. Later, the researcher obtained the opinions about favoritism of twenty 11th grade students at a school which he visited for a conference. As a result of the literature review, a draft scale with 47 items was prepared. Following this, three lecturers specializing in Measurement and Evaluation and four specializing in Educational Management and Inspection at Erciyes University, Faculty of Education, Department of Educational Sciences were asked about the reliability, intelligibility and representativeness of the items on the scale in order to turn them into statements about teacher behaviors involving favoritism. The statements in the scale were scored as a 5-item Likert scale in the following way ” 1 =disagree totally” and “5=agree totally”.

Table 1

Post-Varimax Factor Loads and Reliability Analyses of Scale of Teachers’ Favoritism Behaviors in the Classroom

In order to test the structural validity of the scale, the data set was first given a factor analysis. The analysis started with 47 items and the initial results of the factor analysis showed that the factor loadings of 15 items were below .35. These items were consequently removed from the scale, and the remaining 32 items were given another factor analysis. As a result of principal components and Varimax rotation procedure, four factors were found on the scale with an (eigenvalue) of 1.00 or higher. The variance percentages accounted for by the factors were 43.46, 6.53,4.35 and 3.72 respectively. At the same time, in the preliminary validity studies of the scale, the congruity of the data obtained from the piloting of the tool with the sample was found to be 0.937 with KMO and 5106.056 with the Barlett Test at the level 0.000. Table 1 presents the items distributed to factors and factor loadings according to analysis and rotation results.

Composed of eight items and accounting for 43.46% of total variance, Factor I is called instruction. This factor includes situations where teachers engage in favoritism based on gender, success, parents occupying powerful positions, high economic status, physical attractiveness, familiarity with parents, and similar ideologies.

Accounting for 6.53% of the total variance and consisting of eight items, Factor [Eth] is named discipline. This factor includes situations where teachers engage in favoritism based on gender, success, parents occupying powerful positions, high economic status, physical attractiveness, familiarity with parents, and similar ideologies in overlooking violation of classroom rules.

Composed of eight items and accounting for4.35%of total variance.Factor III is called assessment. This factor includes situations where teachers engage in favoritism based on gender, success, parents occupying powerful positions, high economic status, physical attractiveness, familiarity with parents, and similar ideologies in assessing students.

Composed of eight items and accounting for 3.72% of total variance, Factor IV is called communication. This factor includes situations where teachers engage in favoritism based on gender, success, parents occupying powerful positions, high economic status, physical attractiveness, familiarity with parents, and similar ideologies in establishing communication with students.

Findings

A total of 896 students, 46% (n=416) females and 54% (n=480) males ,participated in the research. Concerning family earnings, 34% (n=307) had families with a monthly income of 500-1000 US Dollars or less, 43% (n=386) had families with a monthly income between 1000- 1500 Dollars, and the remaining 23% (n=204) had families with a monthly income of 1500 Dollars or more. The cumulative grade of 23% (n=210) of the participating students was between 3.00 and 4.00, that of 46% (n=408) was between 2.00-2.99 and that of the remaining 31% (n=278) was between 1.00 and 1.99.

Table 2 shows the students’ mean scores on the factors of instruction, discipline, communication and assessment, standard deviations and t-test values according to gender.

It was found that girls and boys did not differ statistically meaningfully in their perceptions of teacher behaviors with respect to instruction (t=-1.90, p> .05) and assessment (t=.47, p> .05); but that they differed meaningfully in theirperceptions of teachers’ discipline (t=-4.84, p

Table 2

Factor analysis according to gender

The analysis based on students’ cumulative grade point average (CGPA) revealed that in the factors instruction (F=9.6, p .05) and communication (F=I .7, p> .05). According to this, moderately successful students (CGPA 2.00-2.99) believed that teachers treated students differently based on their gender, and that they favored successful students, those with powerful parents, those who are well- off, those who are physically attractive, those whose parents are familiar and those who hold similar ideologies. On the other hand, successful students (CGPA 3.00-4.00) believed that teachers assessed their students differently based on their gender, and that they favored successful students, those with powerful parents, those who are well-off, those who are physically attractive, those whose parents are familiar and those who hold similar ideologies (Table 3).

Table 3

Factor Analysis According to Student Success

Table 4

Factor Analysis According to Students’ Economic Status

Student income is parallel to family income. The analysis that took into consideration family economic status showed that studentperceptions about teacher behaviors in the factors discipline (F=8.19, p

The strongest relationship was found between the factors discipline and assessment (r=.18; p

Discussion and Conclusion

This study aims to determine whether student success, gender, parents occupying powerful positions, good economic status, physical appearance, holding similar ideologies to the teacher, and familiarity or blood relations between parents and teachers make a difference in teacher behaviors. Teacher behaviors were treated in the dimensions of allowing students to speak out and practice in the classroom (instruction), violation of classroom rules and displaying undisciplined behaviors (discipline), establishing communication (communication), and assessing exams and classroom activities (assessment). Student perceptions pertaining to these dimensions were analyzed with respect to gender, economic status and student success.

No difference was found between the opinions of girls and boys about the factors instruction and assessment. In other words, both agreed with the characteristics about teacher behaviors during instruction and assessment. A difference was observed between the opinions of girls and boys in the discipline factor. Accordingly, girls agreed more than boys that stdent characteristics were influential in teacher behaviors when rules were violated or when there were discipline problems. In the communication factor, boys agreed more with the belief that student characteristics affected teacher behavior with respect to communication (Table 2).

Table 5

Correlations between factors

When student perceptions about the effects of student characteristics on teacher behavior were analyzed with respect to student success, those whose CGPA was between 2.00-2.99 were observed to agree more with the instruction factor; and those whose CGPA was between 3.00-4.00 agreed more with the assessment factor, as shown by the Turkey test.

With respect to the economic status of families, difference between the four factors was observed only in the discipline and assessment factors. Students whose families earned more than 1500 Dollars agreed less than others with the discipline factor; whereas those whose families earned between 500-1000 Dollars agreed more than other with the assessment factor, as shown by the Turkey test.

The only relationship which was not statistically meaningful appeared between the communication and assessment factors, according to correlation analysis (r=.04; p>.01). This is a noteworthy result. It implies that even though teachers may consider student characteristics when establishing communication in the classroom, this does not seem to be effective in the assessment of students.

Student characteristics and success affect teacher expectations. To illustrate, Jussim et.al. (1998) state that teachers usually give successful students more opportunities to speak out and learn. Roy and Roy (2004) emphasize that teacher favoritism does not happen willfully but through spontaneous positive feedback. In our study too, the students have said that students’ success was partially effective in teacher behaviors (during class time or practice). This may mean that students think successful students are teachers’ favorites. Thus, teachers need to make an effort towards egalitarianism during class time or practice time. Additionally, teachers may be treating students differently depending on their expectations from them. Oztiirk, Koc and Sahin (2003) have found that almost all teachers in their study (%93) treated high and low- expectation students differently.

Tauber (1997) states that teachers develop different expectations from and reactions towards the two genders. In addition to this, teacher attitudes and behaviors have also been shown to vary according to the physical attractiveness of students by Ritts et.al. (1992), therefore implying that physically attractive students get better grades on tests. In the current study, both girls and boys seemed to think that students’ gender is partially effective in teacher behaviors.

Ozturk et.al. (2002) attract our attention to the fact that when teachers know about students’ socio-economic background, they develop different expectations in favor of children coming from higher socio-economic levels.

Student perceptions with respect to sex, student success and economic situation show that favoritism doesexist in teacher behaviors, albeit only partially. Agreement from the perspective of all variables is on a moderate level, which should not be underestimated. Even though student characteristics may only partially affect teacher behaviors, this shows that it is of utmost importance to set classroom rules. As stated by Roy and Roy (2004), the prevention of favoritism in the classroom can be achieved through setting rules. If teachers follow these class rules rigorously, students will be less likely to think they favor certain students. Ojeca and Fernandez-Dols (2001) write that rules are very important in group relations and favoritism. Doyle (1986) views class rules as an important element of classroom management, thus emphasizing the significance of a well-managed class in efficient instruction. Therefore teachers need to establish a system of rules (discipline) before the semester starts (Aydm, 2006). As rules are there for everyone, they ensure the elimination of bias and allow the teacher to say no to individual requests. At the same time, they make the use of authority easier (Karip, 2002), which stops students from forming beliefs that the teacher engages in favoritism.

As a developing country and an EU candidate, Turkey is undertaking many educational reforms. A major reform has been promotion of ethical behavior among teachers. This study implicated that teachers working at general high schools do engage in favoritism. Although it is good that this does not happen to a great extent, this still shows a need for measures against favoritism. In order to overcome such behavior, the acquisition of ethical behavior must be emphasized in in-service teacher education programs. It is also important that teachers attach importance to the formation of rules in their classes. Forming them in a participatory manner with the students will make the rules more feasible.

References

Al-Houli, AE., (1999) .Teachers’ perceptions of parental involvement in elementary schools in the state of Kuwait. Dissertation Abstracts International, 60(05), 1509A

Aydm, B.(2006). Ogretmenlerin kendi simf discipline sistemlerini olujturmasi (creation of teacher’ own classroom discipline system). Sosyal Bilimler Ara$tirmalan Dergisi (Journal of Research in Science Social). 2,19-32.

Aydm, 1. (2003). Egitim ve ogretimde etik. (Ethics in education and instruction). Ankara: PegemA.

Bank, S (1987) Favoritism, Journal of Children in Contemporary Society, 19(374), 77-89.

Bhushan, V. (1985). Relationship of teacher attitude to the environment in his/her class. (Abstract), ERIC Reproduction No. ED260118.

Bilton, T., Bonnett, K., Jones, P., Stanworth, M.,Sheard,K.&Webster,A.(1993).Introductory sociology (2nd Ed). London: Macmillan.

Braun,C.(1976).Teacherexpectation: sociopsychological dynamics. Review of Educational Research, 46(2), 185-213.

Brophy,J.E.(1983).Researchon the self-fulfilling prophecy and teacher expectations. Journal of Educational Psychology,,75 (5), 631- 661.

Bu okulda aynmcilik var. (This school practises discrimination).(2006,Ekim/October7).Milliyet Gazetesi (Milliyet Daily Newspaper), p.6.

Clifton, R. A., Perry, R. P., Parsonson, K. & Hryniuk, S. (1986). Effects of ethnicity and sex on teachers’ expectations of junior high school students. Sociology of Education, 59,58-67.

Delamont, S.(1983). Interaction in the classroom: contemporary sociology of the school (2nd Ed).London:Routledge.

Dembo, M. H. (1994). Applying educational psychology (5th. Ed). New York: Longman.

Doyle, W. (1986). Handbook of research on teaching. In Merlin C. Wittrock (Ed.), Classroom organisationandmanagementJ(\iana: Muncie, Kenealy, P., Frude, N. & Shaw, W. (1988), Influence of children’s physical attractiveness on teacher expectation. The Journal of Social Psychology, (128$), 373-383

Mc Garity, J.R., & Butts, O.P., (1984). The relationship among teacher classroom management behavior, student engagement, and student achievement of middle and high school science students of varying aptitude. Journal of Research in Science Teaching, (21,1) 55- 61.

McHaIe, S., Sloan, J., & Simeonsson, R.(1986). Sibling relationship of children with autistic, mentally retarded, and non- handicacapped brothers and sisters, Journal of Autism and Developmental Disorders, 16,399-413.

McMillan, James H. (2004). Educational research : fundamentals for the consumer. Boston : Pearson/AandB,

Mechtenberg, L.(2006). Cheap talk in the classroom. http:// sfb649.wiwi.hu-berlin.de/papers/pdf/SFB649DP2006-019.pdf

Mortimore,P.,Sammons,P.,Stoll,L.,Lewis, D. & Ecob, R. (1994). Teacher expectation. In A. Pollard and J. Bourne (Eds.). Teaching and learning in the primary school. (99-113) London: Routledge.

Nadler, J. & Schulman M.(June 2006). Favoritism, cronyism, and nepotism. Retreived May 12, 2007, from http://www.scu.edu/ethics/ practicing/focusareas/government_ethics/introduction/cronyism, hrml.

Oceja.L.V. & Femandez-Dols, JM. (2001). Perverse effects of unfulfilled norms:a look at the roots of favoritism, Social Justice Research, 14(3),289-300.

Ozturk, B., Sahin, F. T., and Koc, G. (2002). Ukogretim okullarmda ogretmen beklentilerini etkileyen ogrenci davranijlan (Student behaviors that affect teacher expectations in primary schools). Kuram ve Uygulamada Egitim Yonetimi (Educational Management in Theory and Practice), 8(31), 390-413.

Oztrk.B; Koc.G. veSahin,F.T. (2003). Sinif ogretmenlerinin ogrenci leri arasinda ay inm y apma durumu ve bu ayinmin bazi de|is,kenler acisindan incelenmesi (situation of teachers’discrimination behavior between their sudents and examination of this discrimination in point of some variables) Turk E&itim Bilimleri Dergisi (Turkish Education Sciences Journal). 1,109- 120,

Ritts, V., Patterson, M. L. & Tubbs, M. E. (1992). Expectations, impressions and judgments of physically attractive students: a review. Review of Educational Research, 62(4), 413-426.

Roy, M. H & Roy F. C. (2004). An empirical analysis of favoritism during business training. Industrial and Commercial Training, 36(6), 238-242

Sprinthall, NA; Sprinthall, R.C.(1990).Educational psychology. New York: McGraw-Hill.

Tauber, R.T. (1997).Self-fulfilling prophecy: a practical guide to its use in education. London: Preager.

The Coalition for Accountability and Integrity (30 and 31 December 2004).Opinion poll on corruption in the Palestinian society WASTA(FavoritismandNepotism),Retreived22 december, 2007, from http:/ /www.transparency. org/content/download/1587/8162/file/palestine_ poll.pdf

Vicente, H.D.(1999). Gender relations in the classroom. New Routes in ELT, 16-17,

AsistProf.lsmail Aydogan, Assistant Professor, Education Faculty, Erciyes University, Kayseri-Turkey.

Correspondence concerning this article should be addressed to Professor Aydogan at aydogani @ erciyes .edu .tr

Health

Severe Anoxic Brain Injury From Blunt Chest Trauma: A Case Study Involving Commotio Cordis As an Etiology of Systemic Anoxia

Written By: Sam Savage

Published Date: August 29, 2008 Last Edited: August 29, 2008

By Lue, Aurora Bapineedu, Kuchipudi; Sori, Alan J; Fares, Louis II

To the Editor: I am writing about a case which involved a 14- yearold boy who was brought to our Trauma Center via ambulance unresponsive and intubated after he collapsed during a baseball game after being struck in the chest. He was the pitcher at the game and received a hard line drive to the chest. After a few seconds he collapsed and was assessed by a dentist in attendance as being cyanotic and pulseless. CPR was promptly initiated. An automated external defibrillator was reported to be on site but never implemented during the confusion. On arrival of the paramedics, the child was assessed and noted to have vomitus within the oropharynx, a lack of spontaneous breathing, and no pulse. He was subsequently intubated without any use of sedatives or paralytics. The electrocardiograph on the portable defibrillator revealed ventricular fibrillation. He then received an electric shock of 200 Joules and another 100 Joules for pulseless ventricular tachycardia that finally converted his arrhythmia to normal sinus. During the process he received both epinephrine and lidocaine intravenously. By this time, approximately 6 to 8 minutes had elapsed since he first collapsed.

In the trauma room, the child was connected to a ventilator and was found to be unresponsive but hemodynamically stable. Physical examination disclosed reactive pupils consistent with anisocoria with the left pupil (4 mm) being slightly larger than the right (3 mm), and a large erythematous discoloration was evident on his chest. The area of injury over the precordial area measured approximately 5 x 5 inches and was located to the left of his sternum (1 inch) and medial to his left nipple (1 inch). Cardiovascular rubs and murmurs were absent while pulmonary rales were detected. The Babinski reflex was also absent and upon insertion of a nasogastric tube no gag reflex was elicited. The child did not open his eyes and portrayed decorticate movements in response to pain. Apart from this, no other physical abnormalities were discovered. All initial laboratory tests, except the EKG recording of right bundle branch block in leads I, III, Vl and V2, were within normal limits. A FAST (Focused Assessment with Sonography for Trauma) exam confirmed the absence of a pericardial effusion and a preliminary echocardiogram lacked any structural abnormalities in either of the ventricles, chordae tendinae, or valves, only mild dyskinesia. CT scans were consistent with systemic anoxia and pulmonary aspiration. There was diffuse cerebral edema with small ventricles, massive pulmonary infiltrates and edema bilaterally, and ischemic viscera causing shock bowel and shock liver. An arterial blood gas confirmed metabolic acidosis.

The patient was admitted to the pediatric intensive care unit with a diagnosis of severe anoxic brain injury secondary to commotio cordis and a course of mannitol and fosphenytoin was initiated. On the second day of admission, the right bundle branch block resolved and T wave inversions developed in leads V3-V5. His cardiac enzymes increased dramatically from a TnI of 1.7 to 44.7, a creatinine kinase (CK) of 231 to 922 and a creatinine kinase MB (CKMB) of 13.5 to 75.7 and 6 days later normalized to 0.1, 598, and 1.1 respectively. A formal echocardiogram was performed and verified the absence of any mechanical or structural abnormalities. The patient’s neurological status improved slightly and he was placed on midazolam for increased agitation. A repeat CT scan on the third day of admission showed a decrease in cerebral swelling and more prominent sulci. Neurological assessment exhibited flexion and eye opening in response to pain and a positive gag reflex. In contrast, an MRA performed on the sixth day of admission was conclusive for hypoxia and ischemia with loss of the gray and white matter differentiation. Unfortunately the patient did not fully recover and the decision for a tracheostomy, feeding tube, and rehabilitation was facilitated. Eight months after the incident, his motor and verbal skills have improved although he is still unable to fully express himself and experiences spastic muscle movements.

The exact pathophysiology of commotio cordis is unknown. Link et al.1 proposed a vascular model in 1998 and hypothesized that the transient nature of abnormalities such as cardiac enzymes, ST elevation, complete heart block, and left bundle branch block, was possibly secondary to coronary artery vasospasm. However, in 1999, they furthered their investigation and demonstrated that the underlying cause of the cardiac disturbance was instead due to the activation of cardiac ATP-dependent K+ channels.2 These channels are normally inactive and inhibited by ATP but become active in cases of hypoxia such as myocardial ischemia due to the reduction in the ATP/ ADP ratio. The study demonstrated a dramatic reduction in ventricular fibrillation secondary to commotio cordis when the channels were chemically blocked. Nevertheless the experiments were conducted using juvenile swines which raised questions regarding the differences in physiology and anatomy.

Analysis of the 128 cases reported in the United States Commotio Cordis Registry in 2001 revealed a broad spectrum of ages ranging from 3 months to 45 years.3 Although emphasis has been made on Little Leagues, these concerns are not unfounded with 44 per cent of cases being 12 years or younger versus 22 per cent who were 18 years or older.3 Investigation into the possibility of protective gear for those high-risk individuals such as athletes exposed to projectile objects (including physical contact) has lead to much resistance. Athletes cite the cumbersome and impractical nature of heavy pads and strict dress codes preventing them from using any unauthorized equipment. Although rare, occurrence of commotio cordis remains the second leading cause of death in young athletes (95% male),3 justifying a concerted effort to better protect athletes from preventable cardiopulmonary arrest. Survival rates drop significantly from 25 per cent to 3 per cent when CPR and defibrillation are delayed for over 3 minutes.4

In conclusion the minimum recommendation should be the presence of an automated external defibrillator at every sporting event with at least one ACLS/BCLS certified supervisor in attendance. Incidents involving commotio cordis often draw much attention and concern as children are the victims. This in turn has lead to an increase in public awareness about the dangers of commotio cordis. As of July 7, 2007, as a direct result of this case, within the state of New Jersey the use of all types of metal bats have been banned from baseball and softball games for children under the age of 18.5 Investigations showed that balls struck using aluminum bats had a much greater velocity when compared to wooden bats6 making it difficult for children who have slower reaction times, to avoid impact. However, though this restriction may have some positive results, it is too early at this time to be sure.

REFERENCES

1. Link MS, Ginsburg SH, Wang PJ, et al. Cardiovascular manifestations of a rare survivor. Chest 1998;114:326-8.

2. Link MS, Wang PJ, VanderBrink BA, et al. Selective activation of the K+ATP channel as a mechanism by which sudden death is produced by low energy chest-wall impact (commotion cordis). Circulation 1999;100:413-8.

3. Maron BJ, Gohman TE, Kyle SB. Clinical profile and spectrum of commotio cordis. JAMA 2002;287:1142-6.

4. Salib EA, Cyran SE, Ciley RE, et al. Efficacy of bystander cardiopulmonary resuscitation and out-of-hosptial automated external defibrillation as life-saving therapy in commotion cordis. Journal of Pediatrics. 2005;147:863-6.

5. Assembly No. 3388. State of New Jersey, 212th Legislature. Introduced June 26, 2006. Available at: http://www.njleg.state .nj.us/2006/Bills/A3500/3388_R3.PDF.

6. Greenwald RM, Penna LH, Crisco JJ. Differences in batted ball speed with wood and aluminum baseball bats: A batting cage study. Journal of Applied Biomechanics 2001;17:241-52.

Address correspondence and reprint requests to Aurora Lue, M.D., 361A South Huntington Avenue Unit 1, Jamaica Plain, MA 02130. E- mail: [email protected].

Aurora Lue, M.D.

Kuchipudi Bapineedu, M.D.

Alan J. Sori, M.D.

Louis Fares II, M.D.

Seton Hall University School of Graduate Medical Education

St. Joseph’s Regional Medical Center

Level Il Trauma Center, Paterson NJ

St. Francis Medical Center, Trenton NJ

Health

Does Cholecystectomy Prior to the Diagnosis of Pancreatic Cancer Affect Outcome?/DISCUSSION

Written By: Sam Savage

Published Date: August 29, 2008 Last Edited: August 29, 2008

By Gray, Stephen H Hawn, Mary T; Kilgore, Meredith L; Yun, Huifeng; Christein, John D

Early diagnosis and curative resection are significant predictors of survival in patients with pancreatic cancer. We hypothesize that cholecystectomy within 12 months of pancreatic cancer affects 1- year survival. The Surveillance Epidemiology and End Result (SEER) database linked to Medicare data was used to identify patients diagnosed with pancreatic cancer who underwent cholecystectomy 1 to 12 months prior to cancer diagnosis. The SEER database identified 32,569 patients from 1995 to 2002; 415 (1.3%) underwent cholecystectomy prior to cancer diagnosis. Patients who underwent cholecystectomy had a higher proportion of diabetes (40.2% vs 20.5%; P

Cholecystectomy is recommended for those who experience biliary colic, acute cholecystitis, cholangitis, or gallstone pancreatitis.8 The introduction of laparoscopic cholecystectomy has led to increased cholecystectomy rates and a decreased threshold for surgical intervention.9-13 Biliary-type symptoms have shown improvement after cholecystectomy, although the definition of these symptoms has varied and are often vague.14, 15 Unfortunately, actual symptoms caused by gallstones are incompletely understood, making it difficult to define symptoms that will be cured by cholecystectomy.16 As a result of the lack of specificity of pancreatic cancer symptoms while still at an early stage of disease, patients are often treated for more common disorders such as gallstones prior to more extensive evaluation.

Furthermore, prior studies have demonstrated that early stage at diagnosis and curative resection are the key factors determining outcome in patients with pancreatic cancer.6, 17 We hypothesize that cholecystectomy within 12 months prior to the diagnosis of pancreatic cancer affects outcomes. The aim of this study is to describe a cohort who underwent cholecystectomy within 12 months prior to the diagnosis of pancreatic cancer and its effect on survival.

Methods

The Surveillance, Epidemiology and End Results (SEER)-Medicare Database, a linkage of the SEER Program of the National Cancer Institute and the Medicare claims data for covered health services for individuals from the point of eligibility to death, was used to obtain the patient population for this study.18 The SEER allows epidemiologic surveillance of population-based tumor registries tracking cancer incidence and survival. Data collected include demographics (age, sex, and ethnicity), cancer specifics (date of diagnosis, type of cancer), follow-up vital status, and cause of death. The Medicare database includes claims data and International Classification of Diseases, 9th Revision, Healthcare Common Procedure Coding System, or Diagnostic-Related Group codes to identify diagnoses and procedures.

The SEER data cover a service area that includes approximately 14 per cent of the U.S. population, represented by Connecticut, Hawaii, Iowa, and New Mexico and the metropolitan areas of Detroit, San Francisco-Oakland, Atlanta, Seattle-Puget Sound, Los Angeles County, and San Jose-Monterey. The SEER data are highly valid, and the program’s standard for completeness is 98 per cent.18 Medicare provides health insurance for approximately 96 per cent of the population aged 65 and older. Only persons covered by traditional Medicare Parts A and B and not enrolled in managed care are included in this analysis. The SEER-Medicare population is similar to the entire U.S. population aged 65 and older in terms of age and sex distribution but is less likely to be white (79.8% vs 86.7%), impoverished (9.5% vs 12.8%), or to experience cancer mortality (1,039 per 100,000 persons aged 65 and older vs 1,128) and more likely to be living in an urban area (86.9% vs 73.0%) and participating in a health maintenance organization (approximately 26.0% vs 17.0%).

Medicare data were used to identify patients who underwent a cholecystectomy within 12 months prior to the diagnosis of pancreatic cancer. Patient comorbid conditions and demographics were obtained from 12 months prior to diagnosis of pancreatic cancer or at the time of cholecystectomy.

This research received approval from the University of Alabama at Birmingham Institutional Review Board.

Analysis

Statistical analyses were performed using Stata v9.0 (StataCorp., LP, College Station, TX). Comorbidities specifically related to pancreatitis or pancreatic cancer were identified using International Classification of Diseases, 9th Revision diagnosis codes (Table 1). Descriptive statistics were calculated and chi^sup 2^ tests were used to test the significance of differences between patients with cancer undergoing a previous cholecystectomy with those who did not. Multivariable logistic regressions were used to identify significant predictors of receiving a prediagnosis cholecystectomy more than 1 month but within 12 months of the cancer diagnosis and to test the significance of any association between prediagnosis cholecystectomy and 1-year survival.

Results

Of the 32,569 patients available for analysis, 54.0 per cent were men and median age was 74.4 years old. Overall, there was documentation of cholecystectomy in 415 (1.3%) patients within the 12 months prior to diagnosis of pancreatic cancer. There were significant differences in patient comorbidities among patients who underwent cholecystectomy. There was a higher proportion of diabetes, obesity, jaundice, presence of gallstones, weight loss, abdominal pain, steatorrhea, and cholecystitis among patients who underwent a cholecystectomy prior to the diagnosis of pancreatic cancer (Table 2).

Patients who underwent cholecystectomy had a lower proportion of distant stage (Stage IV) disease at the time of diagnosis (40.2% vs 45.6%; P = 0.05). However, patients who underwent cholecystectomy prior to diagnosis had similar 1-year survival (25.0% vs 27.6%; P = nonsignificant) in univariate analysis.

Logistic regression analysis of patient factors associated with cholecystectomy prior to the diagnosis of pancreatic cancer found a significant association in patients who presented with cholelithiasis, jaundice, weight loss, cholecystitis, abdominal pain, steatorrhea, and distant stage disease (Table 3). Models were adjusted for age at diagnosis, sex, marital status, race, and patient comorbidities. Regression analysis of 1-year survival demonstrates the occurrence of a previous cholecystectomy is associated with a significantly decreased likelihood of survival (Table 4). Models were adjusted for age at diagnosis, sex, marital status, race, and patient comorbidities.

TABLE 1. International Classification of Disease, 9th Revision (ICD-9) Codes Used to Identify Comorbidities

TABLE 2. Patient Comorbidities Identified at Time of Cholecystectomy or 12 Months Before Cancer Diagnosis

TABLE 3. Regression Model for Cholecystectomy Defined as Greater Than 1 Month and No More Than 12 Months Before Pancreatic Cancer Diagnosis

Discussion

Our study found that cholecystectomy prior to the diagnosis of pancreatic cancer is associated with decreased 1-year survival. Of the cohort analyzed, 1.3 per cent underwent cholecystectomy within the 12 months prior to the diagnosis of pancreatic cancer. The occurrence of cholecystectomy was significantly associated with cholelithiasis, jaundice, weight loss, cholecystitis, abdominal pain, and steatorrhea prior to the diagnosis of cancer.

Over 70 per cent of the patients who underwent cholecystectomy had cholelithiasis; however, a significant proportion of patients was jaundiced and had experienced weight loss at the time of cholecystectomy. These symptoms attributed to gallstones are not specific to biliary pathology, and the presence of cholelithiasis does not confirm a biliary source. Our regression models demonstrate a greater than threefold increase in the rate of cholecystectomy among patients with pancreatic cancer with jaundice or steatorrhea. Jaundice, weight loss, and steatorrhea are commonly associated with malignancy and, in this age group, should prompt a workup to exclude malignancy. TABLE 4. Regression Model for 1-Year Survival After a Diagnosis of Pancreatic Cancer

A previously published study demonstrated that 9 per cent of patients with pancreatic cancer had undergone cholecystectomy within 2 years before the diagnosis of pancreatic cancer. Additionally, prior cholecystectomy was associated with a decreased rate of curative resection.19 Pancreatectomy is underused for early-stage pancreatic cancer; 38.2 per cent of patients without identifiable contraindication failed to undergo surgery.20 We hypothesize that the symptoms leading to cholecystectomy were likely the result of pancreatic cancer in the setting of incidental cholelithiasis. Factors most associated with survival are stage of disease at presentation and the margin of resection at operation.6, 17, 21 Both stage and resection margin are adversely affected by delay in diagnosis.

The threshold for cholecystectomy has decreased since the introduction of laparoscopic cholecystectomy.9-13 The diagnosis of malignant disease, including colon and pancreatic cancer, is often missed at the time of laparoscopic cholecystectomy.1, 22, 23 The lack of tactile sensation, limited visualization of the lesser sac, and patient body habitus can make the diagnosis of malignancy during laparoscopy difficult. This emphasizes the necessity of recognizing symptoms suspicious for pancreatic cancer prior to cholecystectomy, including weight loss, jaundice, and steatorrhea. Although benign biliary pathology is much more frequent than pancreatic cancer, these warning signs warrant more extensive evaluation.

The primary limitation of this study is that it uses retrospective analysis of observational data. Additionally, the limitations of the data set do not allow complete analysis of all patient variables of interest. However, our data do illustrate the need for increased screening and diagnostic workup prior to cholecystectomy with the potential for earlier diagnosis and cure for a subset of patients with pancreatic cancer. A prospectively collected observational study of patients undergoing cholecystectomy may help to define which patients would benefit from increased diagnostic workup prior to cholecystectomy.

Early diagnosis allowing the potential for curative resection is currently the most significant predictor of survival in patients with pancreatic cancer. Our regression model demonstrates a significant association between the occurrence of a cholecystectomy prior to pancreatic cancer diagnosis and decreased odds of survival at 1 year. The occurrence of a cholecystectomy is likely a marker of attributing vague biliary symptoms and incidental cholelithiasis to benign biliary pathology. Unfortunately, cholecystectomy leads to a delay in the diagnosis of pancreatic cancer and may allow for disease progression. For patients older than 65 years of age, further evaluation prior to cholecystectomy may be necessary to exclude pancreatic cancer, especially in patients with weight loss, jaundice, and steatorrhea.

REFERENCES

1. Greenlee RT, Murray T, Bolden S, Wingo PA. Cancer statistics, 2000. CA Cancer J Clin 2000;50:7-33.

2. American Cancer Society. Pancreatic adenocarcinoma. In: American Cancer Society Facts and Figures 2007. Atlanta, GA: American Cancer Society, 2007.

3. Cameron JL, Riall TS, Coleman J, Belcher KA. One thousand consecutive pancreaticoduodenectomies. Ann Surg 2006; 244:10-5.

4. Millikan KW, Deziel DJ, Silverstein JC, et al. Prognostic factors associated with resectable adenocarcinoma of the head of the pancreas. Am Surg 1999;65:618-23.

5. Richter A, Niedergethmann M, Sturm JW, et al. Long-term results of partial pancreaticoduodenectomy for ductal adenocarcinoma of the pancreatic head: 25-year experience. World J Surg 2003;27:324- 9.

6. Wagner M, Redaelli C, Lietz M, et al. Curative resection is the single most important factor determining outcome in patients with pancreatic adenocarcinoma. Br J Surg 2004;91:586-94.

7. Kleeff J, Michalski C, Friess H, Buchler MW. Pancreatic cancer: From bench to 5-year survival. Pancreas 2006;33:111-8.

8. Johnston DE, Kaplan MM. Pathogenesis and treatment of gallstones. N Engl J Med 1993;328:412-21.

9. Steiner CA, Bass EB, Talamini MA, et al. Surgical rates and operative mortality for open and laparoscopic cholecystectomy in Maryland. N Engl J Med 1994;330:403-8.

10. Escarce JJ, Chen W, Schwartz JS. Falling cholecystectomy thresholds since the introduction of laparoscopic cholecystectomy. JAMA 1995;273:1581-5.

11. Shea JA, Berlin JA, Bachwich DR, et al. Indications for and outcomes of cholecystectomy: A comparison of the pre and post- laparoscopic eras. Ann Surg 1998;227:343-50.

12. Legorreta AP, Silber JH, Costantino GN, et al. Increased cholecystectomy rate after the introduction of laparoscopic cholecystectomy. JAMA 1993;270:1429-32.

13. Aslar AK, Ertan T, Oguz H, et al. Impact of laparoscopy on frequency of surgery for treatment of gallstones. Surg Laparosc Endosc Percutan Tech 2003;13:315-7.

14. Berger MY, Olde Hartman TC, Bohnen AM. Abdominal symptoms: Do they disappear after cholecystectomy? Surg Endosc 2003;17:1723-8.

15. Jorgensen T. Abdominal symptoms and gallstone disease: An epidemiological investigation. Hepatology 1989;9:856-60.

16. Berger MY, Olde Hartman TC, van der Velden JJ, Bohnen AM. Is biliary pain exclusively related to gallbladder stones? A controlled prospective study. Br J Gen Pract 2004;54:574-9.

17. Sohn TA, Yeo CJ, Cameron JL, et al. Resected adenocarcinoma of the pancreas-616 patients: Results, outcomes, and prognostic indicators. J Gastrointest Surg 2000;4:567-79.

18. Warren JL, Klabunde CN, Schrag D, et al. Overview of the SEER- Medicare data: Content, research applications, and generalizability to the United States elderly population. Med Care 2002;40(Suppl):IV- 3-18.

19. Ghadimi BM, Horstmann O, Jacobsen K, et al. Delay of diagnosis in pancreatic cancer due to suspected symptomatic cholelithiasis. Scand J Gastroenterol 2002;37:1437-9.

20. Bilimoria KY, Bentrem DJ, Ko CY, et al. National failure to operate on early stage pancreatic cancer. Ann Surg 2007;246: 173- 80.

21. Ferrone CR, Brennan MF, Gonen M, et al. Pancreatic adenocarcinoma: The actual 5-year survivors. J Gastrointest Surg 2008;12:701-6.

22. Sharp EJ, Springall RG, Theodorou NA. Delayed diagnosis of malignant tumours missed at laparoscopic cholecystectomy. Br J Surg 1994;81:1650.

23. Malouf AJ, Murray AW, MacGregor AB. Major intraabdominal pathology missed at laparoscopic cholecystectomy. Br J Surg 2000;87:1434-5.

STEPHEN H. GRAY, M.D., M.S.P.H.,* MARY T. HAWN, M.D., M.P.H.,* MEREDITH L. KILGORE, Ph.D.,[dagger] HUIFENG YUN, M.S.,[dagger] JOHN D. CHRISTEIN, M.D.*

From the * Department of Surgery and the [dagger] School of Public Health, University of Alabama at Birmingham, Birmingham, Alabama

Presented at the Annual Scientific Meeting and Postgraduate Course Program, Southeastern Surgical Congress, Birmingham, AL, February 9-12, 2008.

Address correspondence and reprint requests to John D. Christein, M.D., University of Alabama, 1530 3rd Avenue South, KB 417, Birmingham, AL 35294. E-mail: [email protected].

DISCUSSION

DIMITRIOS STEFANIDIS, M.D. (Charlotte, TN; Opening Discussion): Pancreatic cancer is the fourth leading cause of cancer-associated mortality in the United States with a dismal 5-year survival rate. Stage for stage, pancreatic cancer is associated with the lowest survival rate of any cancer site. Advanced stage at presentation is the result of the lack of early specific symptoms. The aggressive nature of such cancers and the limited effectiveness of adjuvant treatments are thought to be the main reasons for the poor outcomes. Thus, the imperative clearly exists to determine modifiable risk factors to develop methods to detect pancreatic cancer at earlier stages in the general population and to identify individuals at high risk who would benefit from more intensive screening. Such risk factors have been found to include cigarette smoking, family history of pancreatic cancer, diabetes mellitus, and even history of cholelithiasis and cholecystectomy.

The authors of this article identified patients with pancreatic cancer who had undergone cholecystectomy the year before their cancer diagnosis by reviewing the SEER database and linking to Medicare data. They conclude that recent cholecystectomy is associated with decreased 1-year survival among patients with pancreatic cancer and recommend that patients older than 65 years of age are worked up for pancreatic cancer before cholecystectomy, especially if they are jaundiced.

How do the authors explain their findings that patients who had undergone prior cholecystectomy had a lower proportion of Stage IV disease at diagnosis but also a lower 1-year survival rate? Do these statements not contradict each other?

In your discussion, I did not see an explanation as to why cholecystectomy leads to worse pancreatic cancer outcomes. What is your hypothesis? What makes cholecystectomy harmful? If it is delay in diagnosis, as you imply, then why did those patients have a lower incidence of Stage IV disease at presentation? Could it be related to the higher incidence of comorbid conditions that you demonstrated for the cholecystectomy group? Does postsurgical immunosuppression play a role?

Some authors have suggested that cholelithiasis and the need for cholecystectomy are a consequence of the presence of pancreatic cancer rather than representing true risk factors for its development. Could this also be true for your findings as well? Finally, based on your study, how do you recommend we change our practice when we see an elderly patient who is a candidate for cholecystectomy?

STEPHEN H. GRAY, M.D. (Birmingham, AL; Closing Discussion): Based on our study, we would suggest that these patients who present with atypical benign pathology should have further workup before their cholecystectomy to exclude the cholecystectomy being performed for incidental cholelithiasis. These symptoms are actually symptoms of pancreatic disease that are being misinterpreted.

Regarding the lower proportion of Stage IV disease, if these patients at the time of the cholecystectomy had postperitoneal spread, this would be seen at that time of cholecystectomy. A decreased 1-year survival rate is likely the result of a delay in their diagnosis. These were patients who may have progressed from having a resectable disease when they initially presented for the cholecystectomy to unresectable disease at the time the pancreatic cancer is actually diagnosed.

MURRAY F. BRENNAN (New York, NY): Cholecystectomy does not affect the outcome of pancreatic cancer. Cholecystectomy is associated with it as you so nicely said. I think it is what is called the “black swan syndrome.” We look for information that supports our biases, when we should be looking for information that proves our biases wrong. One way you might have done that was to take the survival from the date of cholecystectomy.

WILLIAM C. WOOD, M.D. (Atlanta, GA): I fear that this is the tip of the iceberg. If we look carefully at a variety of operations that are done before another operation, we will find that these are cases in which we are missing something. I think specifically of a series of chondrosarcomas of the pelvis I resected. Over 50 per cent of them had a lumbar laminectomy in the preceding 12 months because their symptoms were assumed to be the more common disease herniated disk than the more rare. This is an alert to all of us.

STEPHEN H. GRAY, M.D. (Birmingham, AL; Closing Discussion): This points out the difference between association and causation and demonstrates that it may be impossible to tell the difference between a patient with symptoms of pancreatic cancer and gallbladder disease. Imaging studies may not show evidence of pancreatic cancer. If those patients do not get well after cholecystectomy and remain symptomatic, a red flag should go up, and you should evaluate those patients promptly for the possibility of other pathology.

KENNETH LIPSHY, M.D. (Hampton, VA): A retrospective review from our institution 10 years ago studied patients before and after the laparoscopic era. We assessed patients who were subsequently admitted within a 2- to 6-month time period after cholecystectomy to determine if there was an association of potentially missed lesions resulting from our rapid intervention in the laparoscopic cholecystectomy era versus the prior era when we tended to do a few more studies before an open operation. Often there appeared to be a rush to proceed with laparoscopic cholecystectomy, and occasionally another lesion was missed.

KAUSHIK MUKHERJEE, M.D. (Nashville, TN): Any thought of doing a preoperative endoscopic retrograde cholangiopancreatography, particularly in patients who were jaundiced?

STEPHEN H. GRAY, M.D. (Birmingham, AL; Closing Discussion): Our study was a retrospective study of the SEER database. An interesting question would be to prospectively collect this data so we could ascertain which patients undergoing cholecystectomy would benefit from an increased diagnostic workup.

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Isolated Lymphoplasmacytic Sclerosing Pancreatitis Involving the Pancreatic Tail

Written By: Sam Savage

Published Date: August 29, 2008 Last Edited: August 29, 2008

By Kim, Tad Grobmyer, Stephen R; Dixon, Lisa R; Hochwald, Steven N

We present an interesting case of a 62-year-old woman with a 3- month history of vague, left-sided abdominal pain. CT imaging revealed a hypodense lesion in the tail of the pancreas. The patient had no history of pancreatitis or autoimmune diseases. Laboratory testing revealed a normal CA19-9 (33 U/mL) and an elevated IgG4 (133 mg/dL). Due to concerns of pancreatic malignancy, she underwent operation. We found a dense, inflammatory mass in the tail of the pancreas, which was removed via an open distal pancreatectomy with splenectomy. Histologic analysis revealed a pancreas with sclerotic ducts and surrounding lymphoplasmacytic inflammation most consistent with lymphoplasmacytic sclerosing pancreatitis (LPSP). LPSP, also termed autoimmune pancreatitis, is a benign disease of the pancreas, which can mimic pancreatic adenocarcinoma. It is the most common benign finding diagnosed on pathology after pancreatic resection for presumed malignancy. LPSP most commonly involves the head and, more uncommonly, the tail of the pancreas. It can be successfully treated with steroids obviating the need for resection. IgG4 levels may assist in recognition of this disease. As our experience with utilization of IgG4 testing and knowledge of the systemic nature of LPSP increase, patients with this disease may be spared unnecessary resection. LYMPHOPLASMACYTIC SCLEROSING pancreatitis (LPSP), also referred to as autoimmune pancreatitis, is a unique form of pancreatitis characterized by irregular narrowing of the main pancreatic duct, enlargement of the pancreas, lymphoplasmacytic inflammation, and responsiveness to steroid therapy.1 LPSP presents most commonly with obstructive jaundice and can clinically mimic pancreatic adenocarcinoma or cholangiocarcinoma.2, 3 It has previously been shown that approximately 2.5 per cent of pancreaticoduodenectomies performed for presumed malignancy were in fact cases of LPSP.4 Most cases are diagnosed after resection and subsequent pathologic examination due to the difficulty in distinguishing LPSP from pancreatic or biliary adenocarcinoma.

Several different sets of criteria exist for the diagnosis of LPSP.5 Commonly cited criteria include: 1) imaging to demonstrate narrowing of the main pancreatic duct, 2) elevated IgG4 levels or autoantibodies, 3) histopathology revealing lymphoplasmacytic infiltration and fibrosis, and 4) response to steroids.6, 7 Although imaging is important, it is by itself not sufficiently sensitive enough to preoperatively diagnose LPSP and distinguish this from malignancy. Demonstration of serum IgG4 elevations can help confirm the diagnosis and possibly help avoid unnecessary surgery.8, 9

We recently reported a retrospective analysis of seven consecutive patients with LPSP compared with 23 patients with pancreatic malignancy. Six of the seven LPSP patients presented with obstructive jaundice, and five of the seven LPSP patients were found to have a discrete pancreatic mass on imaging-all but one of which were in the head of the pancreas. We found that the median IgG4 levels were significantly higher in patients with LPSP compared with those with carcinoma and that, interestingly, these levels in our Western population were not elevated to the extent seen in Japan.10

Thus, consistent with other published reports, our experience has shown us that pancreatic lesions in LPSP most commonly occur in the head of the pancreas, and these patients can present identically to pancreatic adenocarcinoma or cholangiocarcinoma.11, 12 Also, we found that serum IgG4 determination may help us avoid unnecessary operation in patients who may respond to steroid treatment. However, the typical imaging features of the narrowing of the pancreatic duct and/or diffuse pancreatic enlargement are not present in all cases of LPSP. There are also atypical imaging criteria, as described by Chari et al.,11 and these include pancreatitis, focal pancreatic mass, focal pancreatic duct stricture, pancreatic atrophy, and pancreatic calcification. In concordance with this, we present an unusual case of a patient with LPSP who presented with a pancreatic tail mass.

Case

Clinical Information

A 62-year-old type II diabetic female presented with a 3-month history of intermittent, vague, left-sided abdominal pain. She had no symptoms of jaundice, weight loss, or anorexia. She reported no past history of pancreatitis or autoimmune conditions. Past medical history consisted of diabetes, hypertension, and gastroesophageal reflux disease. Physical examination was unremarkable overall with a soft, nontender abdomen and no palpable lymphadenopamy. An extensive work-up was initiated, including a computed tomography (CT) scan of the abdomen and pelvis, which revealed a hypodense mass in the tail of the pancreas most consistent with pancreatic adenocarcinoma. She was consented for and underwent an open distal pancreatectomy and splenectomy.

Radiological Findings

Contrasted CT scan of the abdomen revealed a 3.3 cm x 2.4 cm hypodense mass in the tail of the pancreas with minimal enhancement on the delayed phase and no arterial enhancement. There was no evidence of calcification within the pancreas. The intra and extrahepatic bile ducts and pancreatic duct were not dilated. There was no evidence of local invasion or metastatic disease. The findings were most consistent with adenocarcinoma of the tail of the pancreas (Fig. 1).

Laboratory Findings

The serum IgG4 level was 133 mg/dL, above the upper threshold of normal (range 6-89 mg/dL). Her serum cancer antigen (CA) 19-9 level was normal (33 mg/dL).

Intraoperative Details

We initially performed an exploratory laparoscopy, and there was no evidence of liver metastases or peritoneal disease. We proceeded with an open exploration and identified a hard, gritty mass in the tail of the pancreas. The pancreas proximal to this mass was soft and normal in appearance. Our differential diagnosis at this point was malignancy versus focal pancreatitis. We proceeded with a distal pancreatectomy and splenectomy.

FIG. 1. CT scan demonstrating hypodense mass in the tail of the pancreas (arrow).

Macroscopic Findings

Grossly, there was a firm, well circumscribed nodule measuring 1.4 cm x 2.2 cm x 2.9 cm in the tail of the pancreas with no evidence of invasion into surrounding tissue. The remaining pancreas was finely lobulated and appeared normal.

Microscopic Findings

Histologically, this lesion showed dense fibrosis surrounding pancreatic ductal structures and a predominantly plasmacytic inflammatory infiltrate. Venulitis and reactive ductal changes were present, and the surrounding uninvolved parenchyma was atrophic. Areas of necrosis with surrounding inflammation were noted. Immunohistochemical (CD20 and CD3) and in situ hybridization studies were performed, confirming that this was not a lymphoproliferative process. The final diagnosis was autoimmune pancreatitis or LPSP (Fig. 2).

Postoperative Course and Follow-Up

The patient’s postoperative course was unremarkable and on 2- week follow-up, she reported feeling well without anymore episodes of abdominal pain. She has not developed any other autoimmune diseases in the following 10 months.

Discussion

Lymphoplasmacytic sclerosing pancreatitis is a rare condition that can affect patients of a wide age range, from 14 to 70 years, with most patients being older than 50 years.11 Based on several large series, there seems to be a 2:1 to 4:1 predominance in men.2, 3, 11-13 The clinical presentation is variable, but most commonly includes obstructive jaundice, weight loss, and abdominal pain.11 Radiographic findings are also variable with some patients demonstrating diffuse enlargement of the pancreas, but with other patients demonstrating a focal mass.14, 15

FIG. 2. Histopathologic findings in LPSP: a) Periductal infiltrates composed of lymphocytes and plasma cells; b) Plasma cells and Russell bodies (arrowheads [black right triangle]); and c) Intense lymphoplasmacytic infiltrate surrounding a smaller duct.

Various sets of criteria have been created to improve our diagnosis of this rare condition, and each has its strengths and weaknesses. By the Japan Pancreas Society criteria (Table 1), our patient did not meet the requirements to diagnose LPSP, whereas by the HISORt criteria (Table 2), which accounts for atypical imaging features (i.e., discrete pancreatic lesion), our patient did meet criteria to diagnose LPSP.

When LPSP does present with a discrete pancreatic lesion, it is most commonly in the head of the pancreas.16, 17 In fact, approximately 80 per cent of LPSP involves the head.3, 14 There are series in the literature reporting incidences of LPSP involving the pancreatic tail anywhere from 0 to 22 per cent and only two previous case reports of LPSP presenting with tail masses (Table 3).3, 12, 13, 17-20 Plaza et al.21 reported a case of a patient presenting with left flank pain and thickening of the pancreatic tail found on MRI; the radiographic differential included chronic pancreatitis and pancreatic adenocarcinoma. She underwent distal pancreatectomy and was found to have LPSP on histopathologic examination. Taniguchi et al.22 reported a case of LPSP in a patient who was referred with a 3 cm hypoechoic lesion in the tail of the pancreas. CT imaging demonstrated swelling of the pancreatic tail, with greater enhancement on the delayed phase-a feature uncharacteristic of pancreatic cancer. The patient was treated with and responded well to steroids, avoiding surgery. Serum IgG4 levels can help differentiate LPSP from pancreatic cancer. In 2001, Hamano et al.8 published their seminal findings describing patients with autoimmune pancreatitis who had significantly higher levels of serum IgG4 than patients with pancreatic cancer. The authors reported accuracy, sensitivity, and specificity of 97 per cent, 95 per cent, and 97 per cent, respectively, in using IgG4 levels to diagnose LPSP. The Western experience includes a Mayo Clinic study by Ghazale et al.23 of 45 patients with LPSP, which reported sensitivity, specificity, and positive predictive values of 53 per cent, 99 per cent, and 75 per cent for IgG4 of >280 mg/dL in diagnosing LPSP.

TABLE 1. Diagnostic Criteria of LPSP 2006 by the Japan Pancreas Society

TABLE 2. HISORt Diagnostic Criteria for LPSP

TABLE 3. Reports Describing Location of Pancreatic Involvement with LPSP

We have reported a series of seven cases of LPSP demonstrating IgG4 elevation above 100 mg/dL compared with controls with median IgG4 levels of 24 to 28 mg/dL; however five of these cases had levels below the technical upper limit of normal.10 Interestingly, Deheragoda et al.24 reported a series of 11 patients, six of whom did not demonstrate elevated serum IgG4. Subsequent immunostaining of pancreatic and extrapancreatic tissue showed increased numbers of IgG4-positive plasma cells (>10/high power field) in five of those six patients without serum IgG4 elevation. The diagnostic yield was improved from less than 20 per cent to 73 per cent. Based on the above data, it seems that in LPSP, median IgG4 levels in the United States are elevated but to a smaller extent compared with levels seen in Japan. This would suggest the need for either decreasing the upper limit threshold for serum IgG4, or performing more accurate differentiation of total IgG levels with the subfractions including IgGl, IgG2, IgG3, and IgG4. After biopsy or surgical resection has been performed, adding IgG4 immunostaining to our diagnostic armamentarium may be of assistance.

In conclusion, our one case demonstrates the difficulty of differentiating LPSP from pancreatic cancer, due to both similar clinical presentation and radiographic appearance. Although LPSP most commonly presents with obstructive jaundice and pancreatic head involvement, a discrete, isolated mass in the tail of the pancreas is also possible. Serum IgG4 may be a useful adjunct to increase the accuracy of diagnosing LPSP. Novel strategies are needed to assist in the preoperative diagnosis of LPSP to help reduce otherwise unnecessary operations in this benign condition.

REFERENCES

1. Finkelberg DL, Sahani D, Deshpande V, Brugge WR. Autoimmune pancreatitis. N Engl J Med 2006;355:2670-6.

2. Kawa S, Hamano H. Clinical features of autoimmune pancreatitis. J Gastroenterol 2007;42:9-14.

3. Weber SM, Cubukcu-Dimopulo O, Palesty JA, et al. Lymphoplasmacytic sclerosing pancreatitis: Inflammatory mimic of pancreatic carcinoma. J Gastrointest Surg 2003;7:129-39.

4. Hardacre JM, Iacobuzio-Donahue CA, Sohn TA, et al. Results of pancreatidoduodenectomy for lymphoplasmacytic sclerosing pancreatitis. Ann Surg 2003;237:853-9.

5. Kim M, Kwon S. Diagnostic criteria for autoimmune chronic pancreatitis. J Gastroenterol 2007;42:42-9.

6. Members of the Criteria Committee for Autoimmune Pancreatitis of the Japan Pancreas Society. Diagnostic criteria for autoimmune pancreatitis by the Japan Pancreas Society. J Jpn Pancreas Soc 2002;17:585-87.

7. Kim KP, Kim MH, Kim JC, et al. Diagnostic criteria for autoimmune chronic pancreatitis revisited. World J Gastroenterol 2006;12:2487-96.

8. Hamano H, Kawa S, Horiuchi A, et al. High serum IgG4 concentrations in patients with sclerosing pancreatitis. N Engl J M 2001;344:732-8.

9. Hughes DB, Grobmyer SR, Brennan MF. Preventing pancreaticoduodenectomy for lymphoplasmacytic sclerosing pancreatitis: Cost effectiveness of IgG4. Pancreas 2004;29:167.

10. Hochwald SN, Hemming AW, Draganov P, et al. Elevation of serum IgG4 in Western patients with autoimmune sclerosing pancreatocholangitis: A word of caution. Ann Surg Oncol.

11. Chari ST, Smyrk TC, Levy MJ, et al. Diagnosis of autoimmune pancreatitis: The Mayo Clinic experience. Clin Gastroenterol Hepatol 2006;4:1010-6.

12. Zamboni G, Luttges J, Capelli P, et al. Histopathological features of diagnostic and clinical relevance in autoimmune pancreatitis: A study on 53 resected specimens and 9 biopsy specimens. Virchows Arch 2004;445:552-63.

13. Hirano K, Komatsu Y, Yamamoto N, et al. Pancreatic mass lesions associated with raised concentration of IgG4. Am J Gastroenterol 2004;99:2038-40).

14. Kloppel G, Luttges J, Sipos B, et al. Autoimmune pancreatitis: Pathological findings. JOP. 2005; 6(Suppl):97-101.

15. Sahani DV, Kalva SP, Farrell J, et al. Autoimmune pancreatitis: Imaging features. Radiology 2004;233:345-52.

16. Toomey DP, Swan N, Torreggiani W, Conlon KC. Autoimmune pancreatitis: Medical and surgical management. JOP. 2007;8:335-43.

17. Farrell JJ, Garber J, Sahani D, Brugge WR. EUS findings in patients with autoimmune pancreatitis. Gastrointest Endose 2004; 60:927-36.

18. Nakazawa T, Ohara H, Sano H, et al. Difficulty in diagnosing autoimmune pancreatitis by imaging findings. Gastrointest Endose 2007;65:99-108.

19. Wakabayashi T, Kawaura Y, Satomura Y, et al. Clinical and imaging features of autoimmune pancreatitis with focal pancreatic swelling or mass formation: Comparison with so-called tumorforming pancreatitis and pancreatic carcinoma. Am J Gastro 2003; 98:2679- 87.

20. Kobayashi G, Fujita N, Noda Y, et al. Lymphoplasmacytic sclerosing pancreatitis forming a localized mass: A variant form of autoimmune pancreatitis. J Gastroenterol 2007;42:650-6.

21. Plaza JA, Colonna J, Vitellas KM, Frankel WL. Lymphoplasmacytic sclerosing pancreatitis. Ann Diagn Pathol 2005 ;9: 298-301.

22. Taniguchi T, Seko S, Azuma K, et al. Autoimmune pancreatitis detected as a mass in the tail of the pancreas. J Gastroenterol Hepatol 2000; 15:461-4.

23. Ghazale A, Chari ST, Smyrk TC, et al. Value of serum IgG4 in the diagnosis of autoimmune pancreatitis and in distinguishing it from pancreatic cancer. Am J Gastroenterol 2007;102:1-8.

24. Deheragoda MG, Church NI, Rodriguez-Justo M, et al. The use of immunoglobulin G4 immunostaining in diagnosing pancreatic and extrapancreatic involvement in autoimmune pancreatitis. Clin Gastroenterol Hepatol 2007;5:1229-34.

TAD KIM, M.D.,* STEPHEN R. GROBMYER, M.D.,* LISA R. DIXON, M.D.,[dagger] STEVEN N. HOCHWALD, M.D.*

From the * Division of Surgical Oncology and the [dagger] Department of Pathology, Immunology and Laboratory Medicine, University of Florida College of Medicine, Gainesville, Florida

Presented at the Annual Scientific Meeting and Postgraduate Course Program, Southeastern Surgical Congress, Birmingham, AL, February 9-12, 2008.

Address correspondence and reprint requests to Steven N. Hochwald, M.D., Division of Surgical Oncology, University of Florida College of Medicine, 1600 SW Archer Road, P.O. Box 100286, Gainesville, FL 32610. E-mail: steven.hochwald@ surgery.ufl.edu.

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Duodenal Derotation As an Effective Treatment of Superior Mesenteric Artery Syndrome: A Thirty-Three Year Experience

Written By: Sam Savage

Published Date: August 29, 2008 Last Edited: August 29, 2008

By Ha, Chi D Alvear, Domingo T; Leber, David C

We evaluated the use of duodenal derotation as a surgical option for superior mesenteric artery syndrome (SMAS) in two groups of young patients. Sixteen patients with SMAS diagnosed by barium upper gastrointestinal series (UGI) from 1974 to 2001, and six patients diagnosed by computerized tomography with three-dimensional reconstructions (3D CT) from 2001 to 2007 were referred to our surgical service, 19 of whom underwent duodenal derotation as the primary surgical treatment after a failed trial of conservative treatment. The main measured outcomes were the resolution of typical symptoms of SMAS and the development of long-term surgical complications. Of the first 16 patients, three (19%) responded to nasojejunal feedings. Of 13 patients undergoing derotation, only one (7.7%) failed derotation and required a gastrojejunostomy bypass, whereas 12 (92%) became asymptomatic after the derotation procedure. After a mean follow-up of 5.13 years (range 0.1-15), two patients (15%) presented with small bowel obstructions and were treated with a simple lysis of the adhesion. All six patients from 2001 to 2007 responded well to surgical derotation. Overall, duodenal derotations successfully relieved symptoms in 18 out of 19 (95%) patients with SMAS, with two (11%) major long-term surgical complications. No volvulus was observed in our patients at the mean follow-up of 4.37 years. SUPERIOR MESENTERIC ARTERY syndrome (SMAS) was first fully described by Rokitansky in 1861.1 Based on the autopsies on a group of young asthenic females with postprandial abdominal discomfort and intermittent emesis of copious amounts of bilious fluid, Rokitansky attributed the cause of the symptoms to the compression of the duodenum between the aorta and the superior mesenteric artery (SMA).1 The study stimulated a small series of case reports until 1927 when Wilkie published the largest case series of 75 patients diagnosed witii SMAS based on clinical presentations and barium upper gastrointestinal series (UGI).2 However, from 1927 to the 1960s, many authors showed skepticism about this disease entity because there was no clearly defined diagnostic standard. The interest in the disease was resurrected when hypotonic duodenography and angiography allowed the measurements of the aortomesenteric angle and distance in the 1960s.3 Since the 1980s, SMAS has been widely accepted as a true disease entity due to the capability of computerized tomography to measure the aortomesenteric angle and distance with ease; and witii computerized tomography with three- dimensional reconstructions (3D CT), the duodenal compression could be evaluated in reference to the surrounding organs (Fig. IA-C).4

The prevalence of the disease is generally unknown. Some authors report a prevalence of 0.13-0.3 per cent based on barium UGI,5, 6 and an incidence of 0.5 per cent in patients with surgery for scoliosis or spinal cord injury.7, 8 These studies however have always been criticized for the lack of clear diagnostic criteria. Most authors would agree that approximately twothirds of the patients are female,2 75 per cent within the age range of 10 to 39 years,9 and up to 80 per cent with an asthenic body habitus.10

The symptomatology of this disease has been well characterized, especially by Wilkie.2 Patients usually experience epigastric fullness and nausea shortly after food ingestion, then epigastric pain approximately 30 minutes after meals. Emesis is uncommon, and when present, is bilious and episodic. The symptoms can be severe enough to lead to early satiety, food-fear, and weight loss, which consequently enhance the anatomic compression due to the reduction in the fat pad at the mesenteric root. Most patients find some relief with postural (Goldthwaite) manipulations after meals by assuming a recumbent, left or right lateral decubitus, and/or knee- to-chest positions. The patients usually describe a period of intense flatulence 30 minutes after assuming the positions, followed by the relief of the symptoms.

FIG. 1. 3D CT of a patient with SMAS. The stomach and proximal duodenum are severely distended on the coronal view (A). The third portion of the duodenum (arrows) is compressed at the aortomesenteric angle on cross-sectional (B) and sagittal (C) views. The aortomesenteric angle and distance are approximately 16[degrees] and 6 mm, respectively, in this case.

The classic treatment option for SMAS has been duodenojejunostomy, first proposed by Bloodgood in 1907,11 and first performed by Stavely in 1908,12 which has up to a 90 per cent success rate in terms of symptomatic relief in patients undergoing the procedure.13 The most important advantage of this approach is the ease of performing the procedure. As a general intraoperative finding, the duodenum is redundant, dilated, and allows an easy anastomosis with a segment of the jejunum. However, major disadvantages of this approach are the possibilities of bleeding, leakage, and stricture of the anastomotic site. There is also the creation of a nonphysiologic bilious circulation loop, the significance of which is unknown.

We have advocated an anastomosis-free procedure that preserves the intact flow of the existing intestinal tract.14 This involves the derotation of the intestinal tract in such a way that the duodenum is on the right of the aortomesenteric angle (AMA) and the colon is on the left. The end result is the third portion of the duodenum being rotated out of the AMA. This article summarizes our experience with this technique since 1974.

Methods

The data was collected in two separate periods to make two distinct study groups. In the first period from 1974 to 2001, the patients’ records were reviewed retrospectively, and the information on gender, age, symptoms, treatment, and response to treatment was collected. The diagnosis in this period was based on clinical presentations and UGI. In the second period from 2001 to 2007, patients were diagnosed by clinical presentations and 3D CT, and were evaluated prospectively as a cohort. The data on gender, body mass index, symptoms, signs, other studies before 3D CT, length of hospital stay, days required to be asymptomatic, and long-term follow-up were collected.

Before consideration for SMAS, all patients had at least a 6- week history of persistent postprandial abdominal discomfort, nausea, with or without emesis, and weight loss. During this period, other common causes were usually ruled out by the referring physicians with complete radiologic, endoscopic, and psychologic evaluations, most of which were nondiagnostic. If other common causes were not found, workup for SMAS was initiated. For our patients within the first period from 1974 to 2001, a confirmation study with a UGI showed all of the following features: dilated first and second duodenal portions, an abrupt vertical compression of the third duodenal portion, antiperistaltic flows (“to-and-fro” peristalsis) proximal to the vertical obstruction, and a delay of transit into the jejunum of at least 4 hours. Since 2001, when 64- slice 3D CT became readily available in our service area, the confirmation study was switched from UGI to 3D CT. An aortomesenteric distance of 8 mm and an aortomesenteric angle of 20[degrees] were used as the critical measurements for our study. These were obtained using a maximum intensity projection protocol on the three-dimensional reconstructions (Fig. 1C).4

Upon diagnosis of SMAS, all patients underwent at least 6 weeks of conservative treatment. Older children, who could follow instructions, were directed to have multiple small frequent meals (6- 8 meals/day), in addition to a peristalsis-stimulating agent such as metoclopramide. All were given instructions on postural (Goldthwaite) treatment consisting of the following: assuming a recumbent position, raising the pelvis, kneeling, and lowering the shoulders to allow the flatulence to pass. Nasojejunal feeding tubes were offered to these patients, but they were generally refused. In younger children, who had difficulty following instructions or those with a severe malnutritional status, a nasojejunal feeding was initiated for at least 6 weeks.

Before a derotation procedure, intraoperative confirmation was obtained by examination of the duodenum to ensure that the diameters of the first and second portions were at least 50 per cent larger than that of the fourth portion and the proximal jejunum, and that an abrupt compression of the third portion within the aortomesenteric angle was appreciated. We also evaluated the duodenum for its usual location to rule out malrotation. We believe these intraoperative findings are highly specific for SMAS.

All of our laparotomies for SMAS were performed through a transverse right upper quadrant incision. We first incised the retroperitoneal reflection within the right gutter and mobilized the right colon and terminal ileum as well as their mesenteries from the retroperitoneal attachment (Fig. 2A-B). The goal was to expose the third part of the duodenum as well as to shift the right colon weight completely to the left side of the aortomesenteric angle. We always performed an incidental inversion appendectomy. At this point, the inferior aspect of the third part of the duodenum was usually well identified, usually being dilated and compressed by the aortomesenteric angle. We continued to free up the inferior aspect of the third part from the retroperitoneal attachment, from right to left and toward the ligament of Treitz (Fig. 2C). This ligament was then ligated from the superior duodenal fossa to straighten out the duodenojejunal junction (Fig. 2D). To completely rotate the distal third part and fourth part downward and toward the right, away from the aortomesenteric angle, we sometimes had to sacrifice some small blood vessels between the duodenum and the tail of the pancreas (Fig. 2E). Care was taken not to injure the inferior mesenteric vein. To avoid the future risk of volvulus as well as to bring the center of gravity of the colon close to the aortomesenteric angle, the cecum was sutured into the splenic flexure, and the anterior free tenia of the ascending colon and that of the transverse colon were sutured together. The end result of our derotation procedure was a configuration similar to that seen in a congenital intestinal malrotation after the Ladd’s procedure with the entire duodenum to the right of the aortomesenteric angle and the entire colon to the left (Fig. 2F). If the derotation was successful, the duodenal distention immediately resolved with the passage of gas and liquid distally. This was an excellent predictor for the resolution of the symptoms after the surgery. We did not have adequate data on the operating time for the first group of patients; however, the average operating time for the latter six patients was 120 minutes (range: 90-150). Postoperatively, patients were discharged when they tolerated a regular diet, and they were followed weekly until asymptomatic, then every year until 21 years of age or lost to follow-up. Results

Over a 27 year period from 1974 to 2001, 15 patients (M:F = 1:3; mean age = 11.8) were diagnosed with SMAS based on clinical presentations and UGI (Table 1). A 6-month-old female who suffered intermittent postprandial bilious emeses since birth and failure to thrive was diagnosed initially with a duodenal atresia by UGI. However, on exploration the patient had the typical intraoperative findings of SMAS and responded to derotation. Of 16 patients diagnosed within this period, three (19%) responded to 4 to 6 weeks of nasojejunal feeding, one with typical cast syndrome and another with SMAS due to the compression from retroperitoneal lymphoma. Of 13 patients who underwent derotation, only one (7.7%) failed the derotation and required a gastrojejunostomy 6 weeks later, which resulted in resolution of the symptoms. Although the reason for the failure of this derotation procedure was unknown, it was likely due to the difficulty in separating the third portion of the duodenum from the body and tail of the pancreas without causing too much disruption in the blood supply to the distal duodenum. This probably resulted in an incomplete derotation. All other patients in this group became asymptomatic and began to gain weight approximately 2 weeks postoperatively. Two small bowel obstructions due to adhesions occurred in this group, one of who was the patient with the failed derotation. Both patients were treated with simple lysis of adhesions.

FIG. 2. Duodenal derotation procedure.

A cohort of six patients diagnosed by 3D CT was followed by our practice (Table 2). Most were female teenagers (M:F = 1:5) with the mean age of 15 years (range: 12-18), mean body mass index of 18 (range: 16-20), and mean duration of symptoms before the diagnosis of SMAS of 18 months (range 2-60). They all had multiple diagnostic studies before being referred. Interestingly, a 17-year-old female was diagnosed with biliary dyskinesia and underwent a laparoscopic cholecystectomy without relief of symptoms. On 3D CT, their aortomesenteric angles and distance averaged 18.2[degrees] (range: 16-20) and 4.8 mm (range: 2-8), respectively. All six failed conservative treatment consisting of small frequent meals, metoclopramide, and postural modifications for 4 to 6 weeks, and required an average of 5 days of hospital stay (range: 3-12) after the derotation. All six then became asymptomatic after an average of 14 days (range: 7-29) postoperatively. Other than one patient who developed mild gastroesophageal reflux symptoms after the surgery, no major surgical complications have been encountered at the mean follow-up of 4.37 years in this group.

TABLE 1. Characteristics of Patients with SMAS Diagnosed by UGl (1974-2001)

Overall, of 19 patients [M:F = 5:14; mean age: 14 years (range: 0.5-18)] undergoing derotation for SMAS, 18 (95%) became asymptomatic, with two (11%) long-term adhesive complications and no recurrence. We have observed no volvulus in either group thus far.

Discussion

Late in the fifth week of gestation, the midgut grows faster than the embryonic abdominal cavity and herniates through the umbilical cord. The superior mesenteric artery is the blood supply to the herniated bowel and the yolk sac. The herniated bowel rotates around the superior mesenteric artery axis 90 degrees counterclockwise so mat the future duodenum is to the right of the superior mesenteric artery and the colon to the left. During the tenth week, the proximal small bowel returns to the abdominal cavity, followed by the colon. During this retraction, the intestine rotates an additional 180 degrees counterclockwise so that the third part of the duodenum is posterior to the SMA and the transverse colon anterior. The duodenojejunal junction is tethered to the right crus of the diaphragm by the ligament of Treitz, a band of smooth muscle and fibrous tissue. As a result, the duodenal third portion is tightly secured between the angle formed by the aorta and the SMA, the aortomesenteric angle.

The cause of SMAS is likely multifactorial and includes both congenital and physiological components. We theorize that there are two major factors that contribute to the pathophysiology of SMAS. The first factor is a short ligament of Treitz, which, we assume, is a congenital factor. This can cause problems in one of two ways: 1) drawing the third portion of the duodenum upward toward the narrow part of the AMA, or 2) creating an acute bending angle of the small bowel right at the duodenojejunal junction. 15 The second factor is an increase in angular torque on the third portion of the duodenum. This factor can be eimer congenital or acquired. If we treat the small bowel and colon, as well as their associated mesenteries, as pendulums suspended by the SMA branches to the point where the SMA diverges from the aorta, then the angular torques exerted by the weights of the small bowel and colon on the third part of the duodenum are directly proportionate to length of the pendulums (the lengths of the SMA branches), me weights of me pendulums (me weights of the small bowel and colon as well as their associated mesenteries), and me sine values of the angles formed by the aorta and the SMA branches (essentially AMA) (Fig. 3). The smaller the angles, the larger are their sine values.

TABLE 2. Characteristics of the Patients with SMAS Confirmed by Computerized Tomography Arteriogram (2001-2007)

Based on the concept of angular torque, we can divide the causes of the SMAS into three different groups with a high aortomesenteric angular torque on the third portion of the duodenum. The first group has a large pendulum length, in other words, an elongated mesentery with the bowel contents sagging into the pelvic cavity. Wilkie refers to this group as having visceroptosis which can be either congenital or acquired.2 For instance, SMAS caused by acquired visceroptosis has been well described in patients undergoing protocolectomy with ileal J-pouch anastomosis.16 In the second group, an increased mass of the pendulum due to the large weights of the mesentery and the bowel contents secondary to factors such as tumors can theoretically augment the angular torque on the duodenum. To our knowledge however, SMAS simply due to mesentery or bowel tumors has not been reported in the literature. Most patients with SMAS belong to the third group with a severely acute AMA. This angle is supported by the mesenteric root fat pad. The reduction in this fat pad in patients with rapid weight loss due to eating disorders17 or gastric bypass18 can result in a reduction in the AMA, and as a sequela, SMAS. The well-known Cast Syndrome in spinal surgeries is SMAS caused by the reduction in the AMA associated with manipulations of the vertebral column.7, 8 Aortic aneurysm can also reduce the AMA. 19 Other potential causes of a reduced AMA due to an extrinsic compression are mesenteric lymphadenopathy secondary to an infection or metastasis, and primary pancreatic, stomach, or colon malignancy. In the pediatric population, especially teenagers, SMAS is due to a rapid growth in height without an equivalent growth in weight. This may result in an elongated mesentery (the pendulum length) as well as the loss of mesenteric root fat pad (the pendulum angle). This may explain why most of our patients are teenagers experiencing growth spurts. Needless to say, SMAS likely develops as a combination of multiple congenital and physiological factors. The congenital predisposition has been supported by the findings of SMAS in a family cluster20 and in identical twins.21

FIG. 3. Pendulum concept of SMAS.

It is important to emphasize that SMAS is a compression phenomenon on the duodenum by the AMA, and not an ischemic phenomenon due to compression of the SMA by the duodenum. However, when the compressed duodenum becomes too severely dilated, it may exert compression on the SMA. This explains the occasional epigastric vascular bruits in some of our patients. Also, the compression on the duodenum in a true SMAS is often intermittent and incomplete. The patients are usually asymptomatic between the episodic attacks, and even during the attacks, gastric and duodenal contents can still slowly pass through the AMA. In such cases, we may appreciate a highpitched epigastric bowel sound on exam. We advocate the use of the terms primary and secondary SMAS where primary SMAS is defined as one without an associated disease process and secondary SMAS is associated with a clearly defined disease process. Pathophysiologically, patients with primary SMAS must have both attributing factors as already discussed: a short ligament of Treitz and an increased aortomesenteric angular torque which is not due to an organic disease such as tumor or retroperitoneal lymphadenopathy. Clinically speaking, these patients must have a typical presentation of SMAS and must undergo complete pre and intraoperative evaluations to rule out other organic causes of the symptoms. Most patients with primary SMAS turn out to be pediatric patients at their growth spurts or adult patients with a rapid weight loss. These are perfect candidates for a duodenal derotation procedure. On the other hand, if an SMAS can be attributed to any other organic disease, it should be considered as secondary SMAS. The treatment is then to provide aggressive nutritional support and to correct the underlying disease if possible. Two patients in our series are considered to have secondary SMAS: one with Body Cast Syndrome after a motor vehicle accident, and one with retroperitoneal lymphoma. Both responded well to nutritional support alone. Other examples of secondary SMAS are those with retroperitoneal tuberculosis, retroperitoneal sarcoma, or pancreatic tumor. If nutritional support fails to resolve the symptoms in these patients, a duodenojejunostomy procedure should be considered. A duodenal derotation can be technically challenged.

Traditionally, SMAS is a diagnosis of exclusion because me symptoms of SMAS can imitate many other common diseases such as gallbladder disease, peptic ulcer disease, irritable bowel syndrome, or gastroperesis.10 Therefore, most patients experience the symptoms of postprandial fullness, abdominal discomfort, and nausea for many months before SMAS becomes a part of the differential diagnosis. Up until the 1980s, UGI was the confirmatory test of choice for the syndrome. Many authors argue for strict UGI criteria which must show all of these five elements: 1) A dilatation of the 1st and 2nd parts of the duodenum, 2) An abrupt vertical or oblique compression of the 3rd portion, 3) Antiperistaltic flow of the contrast proximal to the compression, 4) Delay of transit of the contrast into the jejunum of at least 4 to 6 hours, and 5) A relief of the compression and symptoms in a knee-to-chest or left lateral decubitus position.10, 22 Even with this strict criteria, UGI does not seem to be sensitive enough for SMAS because the symptoms are often intermittent and are experienced in unpredictable ways. UGI is generally only appropriate during an active attack. To overcome this problem, some authors propose a concept of hypotonic duodenography where an antiperistaltic agent is used to slow down the evacuation of the duodenum to induce the symptoms during a UGI study.3, 23 This improves the sensitivity of the UGI study; however, it is nonphysiologic and may not reflect a true SMAS.4 Since the 1960s, angiographies have helped in delineating AMA, and in conjunction with UGI, measuring aortomesenteric distance (the distance between the aorta and the SMA where it passes over the third portion of the duodenum). The normal angle is estimated to be 25 to 60[degrees], with 7 to 22[degrees] to be considered as abnormal. The normal distance is estimated to be 10 to 28 mm, with 2 to 8 mm to be considered as abnormal.3, 23, 24 The major limitation of angiography is mat the angle and distance are usually derived from only one (usually lateral) view and may not represent the real angle and distance. The 3D CT solves this problem. A multiplanar reformatted reconstruction can be rotated using a maximum intensity projection protocol to find the largest values of the AMA and distance where the duodenum passes over.4 Moreover, the dilated duodenum can be evaluated in reference to the surrounding anatomic structures especially the aorta and the SMA.4 The ranges of normal and abnormal AMA and distance are comparable to those found on angiography; however, the aortomesenteric distance seems to be superior to the AMA in diagnosing SMAS.25 In fact, a cut-off value of 8 mm has up to 100 per cent sensitivity and specificity in predicting SMAS.26 In addition to the cut-off value of 8 mm, we also look for the signs of obstruction such as distended stomach, dilated proximal duodenum, abrupt compression of duodenum at the AMA, and minimal passage of contrast distal to the obstruction. As already mentioned, these signs may not always be present due to the intermittent nature of the disease, and a repeat study may be needed. They are, however, found in all of our six patients with 3D CT.

If exposure to iatrogenic radiation from 3D CT is a concern, especially in younger patients, abdominal ultrasonography with color Doppler or endoscopic ultrasonography can provide diagnostic information equivalent to mat of 3D CT.27, 28 However, these studies are operator-dependent and not readily available in most community hospitals.

In regard to treatment, our principal belief is that a true primary SMAS is transient. In other words, certain physiological or psychological issues aggravate the aortomesenteric angular torque on the duodenum in most patients with certain congenital predispositions to SMAS. We argue that these issues are either temporary or correctable. This concept is most applicable in teenagers, the most common presenting group, at their growth spurts. In fact, if these patients wait long enough until their weight growth catches up with the height growth, the mesenteric fat pad would increase, and the symptoms would spontaneously resolve. Therefore, the treatment of choice for all patients with SMAS is nutritional support, aiming at increasing the mesenteric fat pad, which in turn increases the AMA. Reportedly, this treatment has been up to 100 per cent successful in orthopedic patients with spinal surgeries.29, 30 In patients who can comply with a conservative regimen, small, frequent meals together with postprandial postural modifications such as side-lying or chest-to-knee and the use of properistaltic agents such as metoclopramide are recommended.9, 10 These postural modifications hypothetically increase the AMA. Younger children or critically ill patients may not be able to tolerate this regimen well. In such cases, a postobstruction or jejunal tube feeding and/or total parenteral nutrition may be indicated. These regimens must be instituted for at least 4 to 6 weeks before any consideration of a surgical approach.

Only three of our 22 patients (14%) responded to conservative treatment. These are critically ill, hospitalized patients with the nasojejunal feeding tubes sutured in their nose for several weeks. The rate of compliance with conservative treatments in our pediatric patients is low. These patients, in general, are highly functional at home and in school apart from intermittent severe postprandial symptoms. Active younger patients, who have difficulty following instructions, also have difficulty maintaining a nasojejunal tube in place for several weeks. Multiple reinsertions of the tube would result in an erratic feeding schedule. On the other hand, most of our patients are teenagers at growth spurts, who have no fear of surgery. Some actually are cheerleaders. Asking these patients to have a nasojejunal tube for several weeks is impossible. All of our patients and their parents generally agree to a several-week trial of multiple daily meals with high protein supplements, and most request a surgical treatment eventually.

Traditionally, the treatment for SMAS is duodenojejunostomy, which bypasses the obstructed third part of the duodenum. The best result is associated witii preoperative radiographic findings of a severe duodenal stasis.13 Laparoscopic cases have been reported.31 We believe that this approach is most appropriate for secondary SMAS with unbeatable underlying causes such as pancreatic cancer, mesenteric lymphadenopathy due to lymphoma and tuberculosis, and abdominal aortic aneurysm.

Other alternative surgical approaches have been reported in the literature. A gastrojejunostomy is recommended if both the stomach and the duodenum are severely dilated, or when the duodenum is ulcerated rendering a duodenojejunostomy unsafe.2, 32 Additionally, a reanastomosis of the duodenum anterior to the SMA has also been described.33

We have been promoting duodenal derotation as the primary surgical treatment for SMAS since 1974.14 The technique preserves the primary flow of the intestinal tract without an anastomosis. We believe this is most appropriate in primary SMAS, especially in pediatric patients. The procedure was pioneered by Strong34 in 1958 when he stressed the significance of the mechanical obstruction on the duodenum caused by a tight attachment of the third duodenal portion into an acute AMA. The same concept was actually touched upon by Wilkie2 30 years earlier. The attachment is maintained by the ligament of Treitz as well as by the adhesion of the duodenum to the retroperitoneal space and to the pancreas. The treatment, therefore, simply focuses on the release of this attachment by ligating the ligament of Treitz and liberating the third and fourth parts of the duodenum from the distal pancreas and from the retroperitoneum. Consequently, the distal duodenum becomes an intraperitoneal rather than a retroperitoneal organ. More importantly, this results in a rotation of the third and fourth portion as well as the mesentery downward and to the right of, and away from, the AMA. This rotation is in the direction opposite to that of the embryonic midgut rotation, hence, the term derotation. The procedure is simple and effective enough to have been performed laparoscopically in four patients, three of whom became asymptomatic.35 We follow this concept and technique with one modification: to also mobilize the colon to the left of the AMA. There are two major advantages of this modification. First, mobilizing the right colon and the mesentery off the right gutter would facilitate the access to the inferior aspect of the third duodenal portion, which in turn, facilitates the derotation process. Second, by fixation of the ascending colon to the transverse colon along the anterior free tenia starting with attaching the cecum to the splenic flexure and suturing toward the hepatic flexure, we theoretically reduce the pendulum length, which subsequently reduces the angular torque caused by the weight of the colon on the duodenum if an incomplete or unsuccessful derotation is to occur. The fixation also prevents the potential risk of a volvulus of the free segment of the colon. Despite the fact that it has never been done, we believe that this procedure is laparoscopically feasible.

There were only two long-term surgical complications observed in our study. One patient experienced mild symptoms of heart burn which were temporary and successfully treated with a proton pump inhibitor. Two patients with small bowel obstructions were found to have intra-abdominal adhesions which were successfully lysed. Although being a theoretical risk, no volvulus complication has been observed to date.

The major limitation of our study is the data on long-term follow- up. We attempt to correct this problem by monitoring the new cohort of patients diagnosed by 3D CT as long as we can. However, as with any observational study in the pediatric population, it is extremely difficult to obtain long-term data. Our surgical practice routinely follows our patients up to 21 years of age. However, most will be lost in followup due to family relocation, departure for college, marriage, and transfer of care to general surgeons.

Conclusion

With the availability of 3D CT as the new gold standard for the diagnosis of SMAS, we expect a more general acceptance of this disease entity. It is therefore important to distinguish between the primary and secondary conditions because the treatment options may vary depending on that distinction. In our opinion, SMAS in elderly patients should be considered as a sign rather than a disease, and an extensive workup should be undertaken to find the underlying cause. All patients with SMAS should have a trial of at least 4 to 6 weeks of conservative treatment with optimal nutritional support. A derotation procedure should be offered as an option for the patients with primary SMAS, especially the pediatric patients in whom the disease is mostly temporary. If the derotation fails to resolve the symptoms, a duodenojejunostomy or gastrojejunostomy is always possible at a later time.

REFERENCES

1. Rokitansky C. Lehrbuch der pathologischen Anatomie, 3rd Ed, Vol 3. Vienna: BraumuUer, 1861, ? 187.

2. Wilkie DP. Chronic duodenal ileus. Am J Med Sci 1927; 173:643- 9.

3. Lukes PJ, Rolny P, Nilson AE, et al. Diagnostic value of hypotonic duodenography in superior mesenteric artery syndrome. Acta Chir Scand 1978;144:39-43.

4. Konen E, Amitai M, Apter S, et al. CT angiography of superior mesenteric artery syndrome. AJR Am J Roentgenol 1998; 171:1279-81.

5. Ylinen P, Kinnunen J, Hockerstedt K. Superior mesenteric artery syndrome. J Clin Gastroenterol 1989;11:386-91.

6. Rosa-Jimenez F, Rodriguez Gonzalez FJ, Puente Gutierrez JJ, et al. Duodenal compression caused by superior mesenteric artery: Study of 10 patients. Rev Esp Enferm Dig 2003;95: 4804-59.

7. Altiok H, Lubicky JP, DeWald CJ, Herman JE. The superior mesenteric artery syndrome in patients with spinal deformity. Spine 2005;30:2164-70.

8. Gore RM, Mintzer RA, Calenoff L. Gastrointestinal complications of spinal cord injury. Spine 1981;6:538-44.

9. Geer D. Superior mesenteric artery syndrome. Mil Med 1990;155:321-3.

10. Barnes J, Lee M. Superior mesenteric artery syndrome in an intravenous drug abuser after rapid weight loss. South Med J 1996; 89:331-4.

11. Bloodgood JC. Acute dilatation of the stomach: Gastromesenteric ileus. Ann Surg 1907;46:736.

12. Stavely AL. Acute and chronic gastromesenteric ileus with a cure in a chronic case by duodenojejunostomy. Bull Johns Hopkins Hosp 1908;19:252.

13. Fromm S, Cash J. Superior mesenteric artery syndrome: An approach to the diagnosis and management of upper gastrointestinal obstruction of unclear etiology. S D J Med 1990;43:5-10.

14. Marchant E, Alvear D. True clinical entity of vascular compression of the duodenum in adolescence. Surgery, Gynecology & Obstr 1989;168:381-6.

15. Akin J, Skandalakis J, Gray S. The anatomic basis of vascular compression of the duodenum. Surg Cli of N Amer 1974; 54:1361-70.

16. Goes RN, Coy CS, Amarai CA, et al. Superior mesenteric artery syndrome as a complication of ileal pouch-anal anastomosis. Report of a case. Dis Colon Rectum 1995;38:543-4.

17. Adson DE, Mitchell JE, Trenkner SW. The superior mesenteric artery syndrome and acute gastric dilatation in eating disorders: A report of two cases and a review of the literature. Int J Eat Disord 1997;21:103-14.

18. Goitein D, Gagne DJ, Papasavas PK, et al. Superior mesenteric artery syndrome after laparoscopic roux-en-Y gastric bypass for morbid obesity. Obes Surg 2004;14:1008-11.

19. Kim HR, Park MW, Lee SS, et al. Superior mesenteric artery syndrome due to an aortic aneurysm in a renal transplant recipient. J Korean Med Sci 2002;17:552-4.

20. Ortiz C, Cleveland RH, Blickman JG, et al. Familial superior mesenteric artery syndrome. Pediatr Radiol 1990;20:588-9.

21. Iwaoka Y, Yamada M, Takehira Y, et al. Superior mesenteric artery syndrome in identical twin brothers. Intern Med 2001; 40:713- 5.

22. Hines JR, Gore RM, Ballantyne GH. Superior mesenteric artery syndrome. Diagnostic criteria and therapeutic approaches. Am J Surg 1984;148:630-2.

23. Gustafson T, Sjolund K, Berg NO. Intestinal circulation in coeliac disease: An angiographic study. Scand J Gastroenterol 1982;17:881-5.

24. Mansberger AR Jr, Hearn JB, Byers RM, et al. Vascular compression of the duodenum. Emphasis on accurate diagnosis. Am J Surg 1968;115:89-96.

25. Hearn JB. Duodenal ileus with special reference to superior mesenteric artery compression. Radiology 1966;86:305-10.

26. Unal B, Aktas A, Kemal G, et al. Superior mesenteric artery syndrome: CT and ultrasonography findings. Diagn Interv Radiol 2005;11:90-5.

27. Neri S, Signorelli SS, Mondati E, et al. Ultrasound imaging in diagnosis of superior mesenteric artery syndrome. J Intern Med 2005;257:346-51.

28. Lippl F, Hannig C, Weiss W, et al. Superior mesenteric artery syndrome: Diagnosis and treatment from the gastroenterologist’s view. J Gastroenterol 2002;37:640-3.

29. Munns SW, Morrissy RT, Golladay ES, McKenzie CN. Hyperalimentation for superior mesenteric artery (cast) syndrome following correction of spinal deformity. J Bone Joint Surg Am 1984;66:1175-7.

30. Hutchinson DT, Bassett CS. Superior mesenteric artery syndrome in pediatric orthopedic patients. Clin Orthop 1990;250: 250- 7.

31. Nana AM, Closset J, Muls V, et al. Wilkie’s syndrome. Surg Endose 2003;17:659.

32. Tatar G, Coskun T, Simsek H. Superior mesenteric artery syndrome. A case report. Turk J Pediatr 1996;38:367-70.

33. Christie PM, Schroeder D, Hill GL. Persisting superior mesenteric artery syndrome following ileo-anal J pouch construction. Br J Surg 1988;75:1036.

34. Strong EK. Mechanics of arteriomesenteric duodenal obstruction and direct surgical attack upon etiology. Ann Surg 1958; 148:725-30.

35. Massoud WZ. Laparoscopic management of superior mesenteric artery syndrome. Int Surg 1995;80:322-7.

CHI D. HA, M.D., DOMINGO T. ALVEAR, M.D., F.A.C.S., DAVID C. LEBER, M.D., F.A.C.S.

From the Departments of Surgery, Pinnacle Health Hospitals, 201 S. Front Street, BMAB-9, Harrisburg, Pennsylvania

Presented at the Annual Scientific Meeting and Postgraduate Course Program, Southeastern Surgical Congress, Birmingham, AL, February 9-12, 2008.

Address correspondence and reprint requests to Chi D. Ha, M.D., Department of Surgery, Pinnacle Health Hospitals, 201 South Front Street, BMAB-9, Harrisburg, PA 17104. E-mail: ha_md@ surgeonsknot.com.

Health

Osteonecrosis of the Femoral Head Following an Electrical Injury to the Leg

Written By: Sam Savage

Published Date: August 29, 2008 Last Edited: August 29, 2008

By Vanderstraeten, L Binns, M

We report a case of osteonecrosis of the femoral head in a young man who is a carrier of the prothrombin gene mutation. We suggest that an electrical injury to his lower limb may have triggered intravascular thrombosis as a result of this mutation with subsequent osteonecrosis of the femoral head. No case of osteonecrosis of the femoral head secondary to a distant electrical injury has previously been reported. Abnormalities of coagulation may be associated with osteonecrosis of the femoral head.1,2 We present a patient who was a carrier of the prothrombin gene mutation who developed osteonecrosis after being electrocuted.

Case report

A 36-year-old Caucasian man was working on a wet building site when his right lower leg and foot made contact with an exposed (live) 500 V electrical cable through his wet footwear. He sustained an electrocution with muscular contractions for approximately 30 seconds, but was subsequently able to pull himself away from the cable, thereby breaking the circuit. He did not seek medical advice.

Approximately 18 months later he presented with increasing pain in the right groin. He denied any trauma to the right hip. He drinks a moderate amount of alcohol and has never taken steroids.

Examination revealed shortening of the right leg of 2 cm. The range of movement in the right hip was restricted and painful. A fullblood count, including mean corpuscular volume, erythrocyte sedimentation rate, C-reactive protein, liver function tests fbilirubin, alanine transaminase), bone profile (calcium, phosphate, alkaline phosphatase] lipid profile (cholesterol, triglycerides) and coagulation screen (prothrombin time, partial thromboplastin time and fibrinogen) were all within normal limits.

Radiographs of the hip showed advanced degenerative changes of the hip joint with collapse of the femoral head. A provisional diagnosis of osteonecrosis of the femoral head was made (Fig. 1).

A further detailed medical history focusing on drugs and diseases associated with osteonecrosis of the femoral head was negative. A haematological evaluation was carried out aimed at identifying any of the hypercoagulable disorders that have most recently become implicated with osteonecrosis of the femoral head.5 Tests for protein C and S deficiency, Factor V Leiden, activated protein C resistance, antithrombin III deficiency, hyperhomocysteinaemia, anticardiolipin antibodies (IgG and IgM), lupus anticoagulant, lipoprotein (a), tissue plasminogen activator antigen levels, plasminogen activator inhibitor-1 antigen levels and plasminogen activator inhibitor activity were all found to be within their normal ranges. However, he tested positive (heterozygous) for the presence of the prothrombin gene mutation.

He underwent total hip replacement (THR) and the femoral head was submitted for histological examination, which showed features consistent with avascular necrosis (Fig. 2).6,7

More than five years after the injury the patient’s THR was functioning well and the opposite hip remained clinically and radiologically normal.

Discussion

Non-traumatic osteonecrosis of the femoral head is quite common; between 15 000 and 20 000 new cases are diagnosed annually in the United States, and this contributes to approximately 10% of the indications for primary THR. Young adults between 20 and 45 years of age are most frequently affected, and the condition is bilateral in approximately 50% of patients at presentation.5

Fig. 1

Anteroposterior radiograph of the patient at presentation.

Fig. 2

Unstained sections of the femoral head, showing fibrocartilage on the articular surface with areas of granulation tissue replacing bone marrow. Sclerotic bone with foci of new bone formation were seen.

Despite the fact that electrical injuries are comtriort, and that there is a wealth of information in relation to electrical soft- tissue injuries, there is a paucity of literature describing the bony changes. This may reflect the fact that electrical currents of low, commercially-available voltages are rarely the cause of bone pathology. The consequences of electrical injuries to bone may present immediately or after a delay of months to years; in addition, the bony injuries may exist near the entry point, or at a point distant from it.

Most reports to date relate to high-voltage injuries (i.e. currents over 1000 V).8-11 These currents take a direct path between entry and exit point. Blood vessels and nerves are severely damaged as are muscle and skin damage, resulting in amputation in over 50% of cases.8-11 The radiological features of the skeleton following this type of injury are varied, bur in most cases are non-specific and can be interpreted only with knowledge of the injury (e.g. osteonecrosis, osteoporosis, growth disturbances). Only osteoschisis (longitudinal diaphyseal zigzag fractures) and ‘bone pearls’ are thought to be pathognomonic.12,13

Low-voltage currents (

Govoni et al18 described a 52-year-old woman who received a 220 V electrical shock to the right hand, and who was subsequently shown to have osteonecrosis of the ipsilateral humeral head. The author questioned whether, despite a negative history of previous shoulder complaints, the electrical injury had not just merely drawn attention to a pre-existing osteonecrosis of the humeral head.

The paucity of reports and studies linking electrical injuries to osteonecrosis suggests that not only anatomical factors determine the outcome of this type of injury. A concept unifying traumatic and non-traumatic osteonecrosis has recently been proposed. Osteonecrosis appears to be the final common pathway of ischaemia; more specifically in the case of non-traumatic osteonecrosis, poorly- regulated coagulation, either genetic or acquired in origin, is activated by a variety of diseases or events resulting in thrombosis and ischaemia.19 The scientific literature has recently identified an increasing number of hereditary and acquired coagulation abnormalities with thrombotic potential. These studies increasingly demonstrate an association between the thrombophilia (an increased likelihood of blood clotting) or hypofibrinolysis (a reduced ability to lyse clots) and osteonccrosis of the femoral head.20-28

The prothrombin gene mutation (G20210A) that affected our patient was first described by Poort29,30 and colleagues in 1996. They noted that 18% of patients with venous thrombosis and approximately 1% of a comparable group of healthy volunteers had a G to A mutation at nucleotide position 20210 of the prothrombin gene. This mutation increases prothrombin levels; heterozygous carriers were found to have approximately 30% higher prothrombin levels, and presumably this is the mechanism through which it exerts its effect.29,30 The prevalence of this mutation among healthy individuals varies from 0.7% to 4% among Caucasians; it is rare among Africans and Asians.29,30 Although well recognised as a hypercoagulable syndrome, the prothrombin gene was only recently demonstrated to be a risk factor for osteonecrosis of the femoral head in adults by Bjorkman et al.1 Zalavras et al2 also found a considerably higher incidence of this mutation in patients with osteonecrosis compared with controls, but attributed the lack of statistical significance to the insufficient power of their study. To our knowledge, the prevalence of osteonecrosis of the femoral head among carriers of the prothrombin gene mutation is unknown.

The risk factor for venous thrombosis for carriers of this mutation is relatively low, and most carriers will not experience a thrombotic event by the age of 50 years.31,32 More significantly this mutation requires an additional environmental event for the clinical expression of its thrombotic potential. Surgery, trauma, pregnancy and oral contraceptives are among the most commonly recognised ‘triggers’.31,32

Most coagulation defects have a fairly high prevalence in the general population, and it is, therefore, unlikely that the presence of one or several of these defects alone is sufficient to trigger thrombosis and subsequent osteonecrosis. It is currently thought that, through these coagulation defects, a predisposition exists in most patients with osteonecrosis which could be acquired (e.g. antiphospholipid antibodies) or genetic in nature (e.g. the prothrombin mutation). These subclinical coagulation defects could result in clinical dis ease when challenged by environmental factors, the so-called ‘second hit’ (e.g. trauma, alcoholism, steroids).19 Indeed, a recent study demonstrated that over 80% of patients with non-traumatic osteonecrosis of the femoral head had at least one coagulation abnormality detected on screening.33 The author did not find any significant difference in the prevalence of these coagulation abnormalities among the major causative groups recognised so far (steroids, alcohol, trauma, mixed).33 This suggests that osteonecrosis will occur with a given frequency in the presence of a thrombotic coagulation abnormality once a second hit is present, regardless of the latter’s nature. With this in mind, we believe that a low-voltage current could qualify as such a second hit, and selectively and indirectly damage the blood supply to the femoral head. It is probably self-evident that this essentially vascular process would express itself most obviously in an area where the microcirculation is most vulnerable, such as in the femoral head. There is a strong causative link between alcohol consumption and osteonecrosis of the femoral head. Although self- declared levels alcohol use in a labourer may be somewhat suspicious, there was no clinical or biochemical evidence of chronic heavy alcohol use in this patient. Despite the emergence of newer, albeit not yet fully-established, techniques for screening and monitoring alcohol use/ abuse,34 testing with mean corpuscular volume and alanine transaminase remains in widespread use because of their favourable test characteristics. Chronic alcohol abuse (defined as a consumption of more than 60 g per day over a period of two weeks) would cause the mean corpuscular volume to be elevated for several months, despite the individual ceasing drinking. Elevated alanine transaminase levels are a non-specific indicator of liver disease. When otherwise healthy people drink large amounts of alcohol, alanine transaminase levels in the blood increase.34 Both mean corpuscular volume and alanine transaminase results were within normal limits in our patient. ‘Excessive’ alcohol intake remains difficult to define, particularly in relation to osteonecrosis. One prospective study suggested that a weekly intake of more than 400 g of alcohol (approximately 60 g per day) would increase the relative risk of osteonecrosis tenfold.35 This level of exposure to alcohol in our patient was firmly refuted by his normal biomarkers and he was not ‘at risk’ in relation to his alcohol use.

The clinical fact that this commonly bilateral disease remains unilateral in this patient after more than five years suggests that a unilateral second hit occurred. If a systemic condition is to affect both hips, it will usually become apparent in the second hip within two years of diagnosis in the first.34 Bradway and Morrey36 studied a group of 15 patients who had undergone unilateral THR for non-traumatic ischaemic necrosis of the femoral head triggered by alcohol abuse, steroid use or idiopathic factors. The contralateral ‘silent’ hip was asymptomatic and radiologically normal at the time of entry into the study, and was at no time subjected to invasive investigations or prophylactic treatment. The authors observed that all the hips studied progressed rapidly to collapse within five and a half years, with over three-quarters collapsing within three years.36

The time delay of 18 months between the electrical injury and the clinical presentation of osteonecrosis is in keeping with our suggested association: when there is a known and isolated predisposing event, the condition may be identified as early as three months and as late as five years following that event.37

We believe a relatively low-voltage electrical current was the cause of the osteonecrosis in our patient. Our patient was genetically primed for osteonecrosis by a prothrombotic coagulation abnormality which under normal conditions would probably have remained without effect during his lifetime. However, the low- voltage current probably sufficed to cause enough local damage to overwhelm the abnormal clotting cascade, resulting in ischaemia and osteonecrosis. Whether this electrical current damaged the arterial or venous vasculature remains conjectural.

No benefits In any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article.

References

1. Bjorkman A, Svensson PJ, Hillarp A. Factor V Leiden and the prothrambin gene mutation: risk factors for osteonecrosis of the femoral head in adults. Clin Orthop 2004;425:168-72

2. Zalavras CG, Vartholomatas G, Dokou E, Malizos KN. Genetic background of osteonecrosis: associated with thrombophilic mutations? Clin Orthop 2004;422:251-5.

3. Jones JP. Risk factors potentially activating intravascular coagulation and causing nontraumatic osteonecrosis. In: Osteonecrosis: etiology, diagnosis and treatment. American Academy of Orthopaedic Surgeons, 2001:89-96.

4. Etienne G, Mont MA, Ragland PS. The diagnosis and treatment of nontraumatic osteonecrosis of the femoral head. Instr Course Lect 2004;53:67-85.

5. Steinberg M. Osteonecrosis: etiology, pathophysiology and treatment. In: Orthopaedic knowledge update 2: hip and knee reconstruction. AAOS, 2000:127-36.

6. Bauer TW, Stulberg TN. The histology of osteonecrosis and its distinction from histological artefacts. In: Schoutens A. Ariel J, Gardeniers JWM, Hughes SPF, eds. Bone circulation and vascularisation in normal and pathological conditions. New York: Plenum Press, 1993:282-92.

7. Sugano N, Kubo T, Takaoka K, et al. Diagnostic criteria for non-traumatic osteonecrosis of the femoral head a multicentre study. J Bone Joint Surg [Br] 1999;81-B:590-5.

8. Barber J. Delayed bone and joint changes following electrical injury. Radiology 1971;99:49-54.

9. Leibovici D, Shemer J, Shapira SC. Electrical injuries: current concepts. Injury 1995;26-623-7.

10. Brinn LB, Moseley JE. Bone changes following electrical injury: case report and review of the literature. Am J Roentgenol Radium Ther Nucl Med 1966;97:682-6.

11. Wang X, Lu CS. Wang NZ, et al. High tension electrical burns of upper arms treated by segmental excision of necrosed humerus: an introduction of a new surgical method. Burns Incl Therm Inj 1984;10:271-81.

12. Kolar J. Locomotor consequences of electrical and radiation injuries, burns and freezings. Bailliers Clin Rheumatol 1989;3:99- 110.

13. Resnick D, Niwajama G. Diagnosis of bone and joint disorders. WB Saunders 1988;3018-23

14. Nichter LS, Bryant CA, Kenney JG, et al. Injuries due to commercial electrical current. J Burn Care Rehabil 1984;5:124-37.

15. Williams DB, Karl RC. Intestinal injury associated with low- voltage electrocution. J Trauma 1981;21:246-50.

16. Howe WW Jr, Lacey T, Schwartz RP. A study of the gross anatomy of the arteries supplying the proximal portion of the femur and the acetabulum, J Bone Joint Surg [Am] 1950;32-A:856-66.

17. Wheeless CR, Lins RE, Knelson MH, Urbaniak JR. Digital subtraction angiography in patients with osteonecrosis of the femoral head. In: Urbaniak JR, Jones JP, eds. Osteonecrosis: etiology, diagnosis and treatment. AAOS, 1997:241-5.

18. Govoni M, Orzincolo C, Bigoni M, et al. Humeral head osteonecrosis caused by electrical injury a case report. J Emerg Med 1993;11:17-21.

19. Aaron RK, Ciombor DMcK. Coagulopathies and osteonecrosis. Cur Opinion Orthop 2001;12378-83.

20. Jones JP Jr. Concepts of etiology and early pattiogenesis of osteonecrosis. Instr Course Lect 1994;43:499-512.

21. Jones LC, Mont MA, Le TB, et al. Procoagulants and osteanecrosis. J Rheumatol 2003;30783-91.

22. Glueck CJ, Freiberg RA, Fontaine RN, Tracy T, Wang P. Hypofibrinolysis, thrombophilia, osteonecrosis. Clin Orthop 2001;386:19-33.

23. Korompilias AV, Ortel TL, Gilkeson GS, et al. Hypercoagulability and osteonecrosis. In: Urbaniak JR, Jones JP, eds. Osteonecrosis: etiology, diagnosis, and treatment AAOS, 1997:111-16.

24. Tektonidou MG, Amoutsopoulos HM. Immunologic factors in the pathogenesis of osteonecrosis. Orthop Clin North Am 2004;35:259-63.

25. Glueck CJ, Freiberg R, Gruppo R, et al. Thrombophilia and hypofibrinolysis: reversible pathogenetic etiologies of osteonecrosis. In: Osteonecrosis: etiology, diagnosis, and treatment. AAOS, 1997:105-10.

26. Glueck CJ, Fontaine RN, Gruppo R, et al. The plasminogen activator inhibitor-1 gene, hypofibrinoiysis. and osteonecrosis. Clin Orthop 1999;366:133-46.

27. Lieberman JR, Berry DJ, Mont MA, et al. Osteonecrosis of the hip: management in the 21st century. J Bone Joint Surg [Am] 2002;84- A:834-53.

28. Jones LC, Hungerford DS. Osteonecrosis: etiology, diagnosis and treatment. Curr Opin Rheumatol 2004;16:443-9.

29. Federman DG, Kirsner RS. An update on hypercoagulable disorders. Arch Intern Med 2001;161:1051-6.

30. Crowther MA, Kelton JG. Congenital thrombophilic states associated with venous thrombosis a qualitative overview and proposed classification system. Ann Intern Med 2003;21:128-34.

31. De Stefano V, Rossi E, Paciaroni K, et al. Different circumstances of the first venous thromboembolism among younger or older heterozygous carriers of the G20210A polymorphism in the prothrombin gene. Haematologica 2003;88:61-6.

32. Tirado I, Mateo J, Soria JM, et al. Contribution of prothrombin 20210A allele and factor V Leiden mutation to thrombosis risk in thrombophilic families with other hemostatic deficiencies. Haematologica 2001;86:1200-8. 33. Korompilias AV, Ortel TL, Urbaniak JR. Coagulation abnormalities in patients with hip osteonecrosis. Orthop Clin North Am 2004;35:265-71.

34. Peterson K. Biomarkers for alcohol use and abuse. Alcohol Research and Health 2004/2005:28:30-7

35. Matsuo K, Hironata T, Sugioka Y, Ikeda M. Fukuda A. Influence of alcohol intake, cigarette smoking and occupational status on idiopathic osteonecrosis of the femoral head. Clin Orthop 1988;234:115-23.

36. Bradway JK, Morrey BF. The natural history of the silent hip in bilateral atraumatic osteonecrosis. J Arthroplasty 1993;8:383-7.

37. Steinberg M, et al. Avascular necrosis of the femoral head. In: The hip and its disorders. Philadelphia: WB Saunders 1991:623- 42.

L. Vanderstraeten,

M. Binns

From Pontefract

General Infirmary,

Pontefract, England

* L. Vanderstrseten, FRCS,

Associate Specialist in

Orthopaedics and Trauma

* M. Binns, FRCS, Consultant

Orthopaedic Surgeon

Pontefrsct General Infirmary,

Mid Yorkshire Hospitals NHS

Trust, Friarwood Lane,

Pontefract WF8 1PL, UK.

Correspondence should be sent to Mr L. Vanderstraeten; e-mail: louis.vanderstraeten@midyorks. nhs.uk

doi : 10.1302/0301-620X.90B8. 19971 $2.00

J Bone Joint Surg [Br] 2008;9D-B:1101-4.

Received 17 July 2007; Accepted after revision 14 April 2008

Health

Bumblebees Defy Odds With Swimming and Flight

Written By: Sam Savage

Published Date: August 29, 2008 Last Edited: August 29, 2008

The little pool in my backyard is busier than the Atlanta airport. In the late afternoon, bumblebee bombers are landing and taking off four and five at a time. Their landings are not quite touch and go. They seem to be tanking up. They rest on the water just long enough for a drink.

They are showing remarkable traits, and raising more questions than they answer.

It is urban legend that bumblebees cannot fly – a legend disproved by the obvious evidence. Nevertheless, it is true that bumblebees do not have the characteristics we normally connect to aerodynamic flight.

They seem large for their wings – somewhat like a small stone with cobwebs. They are not sleek, but covered with hairs and dragging pollen buckets on their legs. They do not seem very hydrodynamic either. Their fat little bodies look as if they should immediately sink when touching the water.

A close look reveals they are relying on surface tension to rest lightly on the water surface, denting it, but not breaking through the outer layers of water molecules enough to sink.

Upon takeoff, they seem to fly up nearly vertically, with no taxiing and no smooth, flat climb.

They can fly faster than a person can run. Recently, scientists have begun to understand more about bumblebee flight.

Bumblebee wings (two pair, lightly attached in sets on each side) are rather rigid on the leading edge, but with very flexible surfaces and trailing edges. In this, they are rather like costumer wings for kindergarten butterflies – a stick or wire with cloth attached.

Bumblebees rely on their wings for lift and propulsion, unlike modern fixed-wing aircraft. The motion of the wings is rather subtle: out, twist and return. The result is to generate vortexes in the air in a way that provides lift, thrust and directional control.

Some scientists have studied this motion by attaching small slivers of mirror to bumblebees and tracking their motion with laser light.

Military scientists are interested in this peculiar style of flight, because small insect-size robotic fliers have military uses for observation.

Bumblebee landings on water raise some questions I need to answer with further study. Do bumblebees drink from ponds and streams regularly? Is this just a dry weather and drought phenomenon?

Would bumblebees normally get enough moisture from the flowers whose nectar they harvest? Are the flowers too dry to provide enough moisture?

How curious it is that in a bumblebee hive, all the bees except the queen die off in the winter. In the spring, the queen lays eggs and begins a new hive.

Virginia’s science Standards of Learning encourage students to apply scientific concepts, skills, and processes to everyday experiences (Goal 4) and to develop scientific dispositions and habits of mind including curiosity. The study of animal behavior and habitat begins in first grade (1.7) and continues in 2.7, 3.4, and higher grades.

On the Web

Bumblebee facts: www.bumblebee.org/

Plight of the Bumblebee:

http://science.the-environmentalist.org/2007/10/plight-of-bumble- bee.html

Bumblebees around the house: http://hgic.clemson.edu/factsheets/ hgic2500.htm

Bumblebee flight research: www.physorg.com/news89459870.html

Walter R.T. Witschey is professor of anthropology and science education at Longwood University.

ILLUSTRATION: PHOTO

MEMO: SCI-KIDS

Originally published by WITSCHEY; SPECIAL CORRESPONDENT.

Health

Monkey Trials and Gorilla Sermons: Evolution and Christianity From Darwin to Intelligent Design

Written By: Sam Savage

Published Date: August 29, 2008 Last Edited: August 29, 2008

By Day, Matthew

doi: 10.1017/S0009640708000863 Monkey Trials and Gorilla Sermons: Evolution and Christianity from Darwin to Intelligent Design. By Peter Bowler. New Histories of Science, Technology, and Medicine. Cambridge, Mass.: Harvard University Press, 2007. x + 258 pp. $24.95 cloth. Rummaging around for a title to his now-classic study of the religious movements that rocked central and western New York state during the first half of the nineteenth century, Whitney Cross decided that he could do no better than to lean on Charles Grandison Finney. These territories represented a burned-over district, he concluded, a land exhausted by decades of religious fervor and creativity.

Almost a century and a half has passed since the publication of Origin of Species, and in many ways the historiography of religious responses to Darwin’s “dangerous idea” represents another kind of bumed-over district. The tales of how Christian communities have assimilated, resisted, or ignored Darwinian evolution have been told so often and by so many different parties that one might be excused for doubting that there is much left to say about the matter. Because of this, I don’t believe it is a criticism of Peter Bowler’s latest book to observe that while it occasionally gestures toward new terrain-such as the counter-cultural ties that bind Scientific Creationism and Immanuel Velikovsky’s work on the veracity of ancient myths (205-208)-it never quite breaks new ground. Nevertheless, because Bowler knows the features of this landscape so well, Monkey Trials and Gorilla Sermons is a notable achievement.

The book’s structure is admirably clear and efficient. Chapter 1 (“The Myths of History”) offers a survey of the key historical developments with an eye toward undermining the passe notion that religion and science are ineluctably at war. Chapter 2 (“Setting the Scene”) explores the intellectual trends that prepared the way for Darwin’s theoretical innovations, including very useful discussions of Robert Chambers, Jean-Baptiste Lamarck, and William Paley. Chapter 3 (“Darwin and His Bulldog”) examines the structure of Darwin’s evolutionary gambit, the philosophical ambitions of the firstgeneration “Darwinians,” and the liberal Protestant willingness to see divine purpose in evolutionary progress. Chapter 4 (“The Eclipse of Darwinism”) analyzes the apparent collapse of Darwinian selection theory during the early days of the “genetical” revolution and the liberal Christian embrace of nonmaterialist models of evolution. Chapter 5 (“Modern Debates”) argues that appreciating the historical complexity of the engagement between Christianity and evolutionary theory necessarily undermines the rhetorical simplicity of both hard-line Darwinians who belittle religious people and unrepentant creationists who ridicule scientists.

As one might gather from this brief outline, Monkey Trials and Gorilla Sermons does not set out to radically re-imagine the historical contours of the continuing struggle over evolution. Yet, because it assembles the crucial figures and events in an easily accessible and wonderfully economical package, the book is exceptionally well-crafted for its intended general authence. Indeed, reading Bowler’s book is a bit like watching a major league baseball player take batting practice. Even when routine, it is satisfying to watch a professional make something difficult look easy.

Matthew Day

Florida State University

Health

Intra-Abdominal Sepsis Following Pancreatic Resection: Incidence, Risk Factors, Diagnosis, Microbiology, Management, and Outcome/ DISCUSSION

Written By: Sam Savage

Published Date: August 29, 2008 Last Edited: August 29, 2008

By Behrman, Stephen W Zarzaur, Ben L

Intra-abdominal sepsis (IAS) following pancreatectomy is associated with the need for therapeutic intervention and may result in mortality. We retrospectively reviewed patients developing IAS following elective pancreatectomy. Risk factors for the development of sepsis were assessed. The microbiology of these infections was ascertained. The number and type of therapeutic interventions required and infectious-related mortality were recorded. One hundred ninety-six patients had a pancreatectomy performed, 32 (16.3%) of who developed IAS. Infected abdominal collections were diagnosed and therapeutically managed at a mean of 11.8 days after the index procedure (range, 4-33). Eleven of 32 (34%) of these infections were diagnosed on or before postoperative day 6, 10 of who had Whipple procedures. Statistically significant risk factors included an overt pancreatic fistula (18.8% vs 5.5%) and a soft pancreatic remnant (74.2% vs 42.3%), but not the lack of intra-abdominal drainage, an antecedent immunocompromised state, postoperative hemorrhage, or the preoperative placement of a biliary stent. Fifty-five per cent had polymicrobial infections and 26 per cent of isolates were resistant organisms. Nineteen per cent and 48 per cent of patients had an isolate positive for fungus and a Gram-positive organism, respectively. Fortyseven therapeutic interventions were used, including 10 reoperations. Length of stay was significantly prolonged in those with IAS (28.5 vs 15.2 days) and mortality was higher (15.6% vs 1.8%). We conclude: 1) septic morbidity after pancreatectomy is associated with a soft pancreatic remnant and an overt pancreatic fistula and in this series resulted in a prolonged length of stay and a significant increase in procedure-related mortality; 2) infected fluid collections may occur very early in the postoperative period before frank abscess formation, and an early threshold for diagnostic imaging and/or therapeutic intervention should be entertained in those with clinical deterioration; and 3) these infections are often polymicrobial and frequently include resistant and nonenteric organisms. MORBIDITY FOLLOWING PANCREATIC resection remains common and has been reported in up to 50 per cent of patients in recent series.1-4 Pancreatic and biliary fistulae as well as delayed gastric emptying are most prevalent and have been the focus of study in the majority of the literature.1, 5-10 While these complications increase hospital length of stay, they rarely require further diagnostic and/or invasive therapeutic procedures and mortality is exceptional. Intraabdominal sepsis occurs less frequently but remains important.1-8, 11 In contrast to other morbidity following pancreatectomy, abscess and/or other infected abdominai fluid collections are most often associated with the need for nonoperative and operative intervention, a prolonged hospital length of stay, and an increase in mortality. The pathogenesis and microbiology associated with these infections has received relatively little attention. Furthermore, management and outcome that impact so significantly on this patient population, most of who have carcinoma, have been poorly described. We reviewed our experience with intra-abdominal sepsis following pancreatic resection with a focus on the diagnosis, bacteriology, and management of this problematic and sometimes catastrophic complication in hopes of improving future patient outcome and survival.

Methods

The records of patients developing intra-abdominal sepsis following elective pancreatic resection at the University of Tennessee, Memphis, affiliated hospitals from 1997 to 2007 were retrospectively reviewed. Data examined included disease process and type of resection. Risk factors for the development of intraabdominal abscess or intra-abdominal sepsis (IAS), including preoperative biliary stenting, a pre-existing immunocompromised state (other than carcinoma), the presence or absence of intraperitoneal drainage, the need for blood transfusion, the development of a pancreatic fistula, postoperative hemorrhage, and the consistency of the remnant pancreas, were examined. An immunocompromised state included diabetes, steroid use, and a history of neoadjuvant therapy. Blood transfusions were recorded within the first 24 hours of surgery. A pancreatic fistula was defined according to the International Study Group of Pancreatic Fistula consensus.12 The time from operation until the clinical development of intra-abdominal sepsis was noted. We specifically focused on the offending microbiologic pathogens recovered during treatment and note was made of resistant organisms or unexpected flora if present. The type (operative vs nonoperative) and number of invasive procedures used in an attempt to eradicate the septic focus were evaluated critically. The impact of postoperative IAS is on hospital length of stay and procedure-related mortality was assessed.

For the purposes of this study, IAS was categorized as follows. An intra-abdominal abscess was defined as a discrete, rim-enhancing fluid collection with or without the presence of gas occurring on or after postoperative day 7. An infected fluid collection was considered as ill-defined, localized, or diffuse, nonrimenhancing fluid noted on or before postoperative day 6. Peritonitis was defined as diffuse abdominal tenderness with rebound on physical examination within the clinical context of sepsis. Patients with a frank pancreaticoenteric anastomotic breakdown (Grade C fistula defined by the International Study Group of Pancreatic Fistula) were included as a result of the ensuing sepsis that developed.

All patients received routine prophylactic perioperative antibiotics for 24 to 48 hours at the time of the index procedure. In addition, during the last 3 years, we have maintained rigid glucose control (80 to 120 mg/dL) in the operating room with hourly blood glucose monitoring. Such levels are maintained in the postoperative period with the use of an insulin drip in the intensive care unit if necessary.

Comparisons between groups were made using Student’s t test for continuous variables and chi^sup 2^ analysis for discrete variables. Significance was assessed at the 95m percentile. Univariate and multivariate logistic regression analysis was used to determine the relationship between potential risk factors and the development of IAS following elective pancreatic resection. Potential risk factors were first assessed with univariate logistic regression. Risk factors with a P

Results

One hundred ninety-six patients underwent pancreatic resection during the 10-year time period with 32 patients (16.3%) developing postoperative IAS (Table 1). Of those with infections, 24 had Whipple procedures with seven and one having distal and total pancreatectomy, respectively. Twenty-four of 32 patients (75%) developing postoperative sepsis had operations performed for carcinoma or premalignant conditions, and this was not different from those avoiding infectious sequelae. The mean age of those with postoperative abdominal infection was 58.3 years and was not different from those without sepsis. Those developing infectious complications had a female predominance in contrast to those without postoperative sepsis; however, this difference was not significant.

Risk factors for the development of postoperative IAS were analyzed by univariate analysis (Table 2). Postoperative infection was not associated with age, operating time, the need for blood transfusion, preoperative biliary stenting, the presence or absence of abdominal drainage, perioperative hemorrhage, the type of procedure performed (distal vs proximal resection), or a preoperative immunocompromised state. In addition, there was no decrease in the incidence of postpancreatectomy sepsis with the institution of rigid glucose control (Fig. 1). In contrast, a pancreatic fistula and a soft pancreatic remnant were predictive of future infectious complications. Pancreatic duct stenting, fibrin glue application to the pancreaticoenteric anastomosis, and the perioperative use of octreotide did not prevent the development of postoperative sepsis. Only the development of a pancreatic fistula following elective pancreatic resection was associated with IAS on multivariate analysis.

TABLE 1. Patient Demographics

TABLE 2. Risk Factors for the Development of Intra-abdominal Sepsis

FIG. 1. Number of pancreatic resections and intra-abdominal sepsis per year.

Intra-abdominal infections were diagnosed at a mean of 11.8 days following the index procedure. Clinical and laboratory findings at the time of diagnosis of IAS are presented in Table 3. Notably, peritonitis and abdominal pain were uncommon. In contrast, more subtle findings such as oliguria, mental status changes, and an increase in the percentage of bands on differential analysis of the white blood cell count were not unusual. Eleven of 32 (34%) patients developing infectious sequelae were diagnosed on or before postoperative day 6 before the development of a frank abscess. This included three patients with a Class C pancreatic fistula. Ten of these 11 with infected fluid collections had Whipple procedures. Six of the 11 patients (55%) developing early infection ultimately required open surgical drainage to eradicate the septic focus versus four of 21 (19%) developing infection (abscess) on or after postoperative day 7. TABLE 3. Clinical Assessment and Laboratory Analysis Prompting Intervention

Fifty-eight pathogens were recovered on culture from these 32 patients (Table 4). Twenty-eight (48%) of these isolates were Gram- positive organisms. Eleven of 58 pathogens (19%) were fungi. Fifteen isolates (26%) comprised resistant organisms, including methicillin- resistant Staphylococcus aureus, vancomycin-resistant Enterococcus faecalis, and extendedspectrum beta-lactamase-producing Gram- negative bacteria. Fifty-four per cent of patients with IAS had polymicrobial infections. Four of 32 patients developing postoperative infections had placement of a preoperative biliary stent. There was no correlation between stent placement and the development of nonenteric or resistant organisms on final culture.

Forty-seven therapeutic interventions were used in an attempt to eradicate the septic focus on this study population (Table 5). Procedures used included percutaneous drainage of infected collections (26 of 32 [81%]) and open surgical drainage (10 of 32 [31%]). Up-front surgical drainage was used in six patients. Four of these six had Whipple procedures and required repeat laparotomy for severe sepsis before postoperative day 6 (including two with Class C fistulas). Two patients having up-front surgery developed subphrenic abscesses following distal pancreatectomy that were not amendable to percutaneous drainage. Twenty-one of 32 patients had one procedure alone, but 11 patients (34%) required multiple procedures. Four of 11 patients requiring multiple therapeutic interventions had open surgical drainage following failed percutaneous drainage. These four patients all had infected fluid collections diagnosed on or before postoperative day 6, including one with a Class C fistula. In total, only four of 26 patients (15%) developing IAS following pancreatic resection failed initial percutaneous, non-operative drainage. Six patients avoiding reoperation required more than one percutaneous drain placement for definitive eradication of sepsis.

TABLE 4. Microbiology of Intra-abdominal Sepsis (n = 32)

TABLE 5. Therapeutic Interventions (n = 47)

Length of stay was significantly prolonged in those who developed IAS versus those who did not (28.5 vs 15.2 days; P

Discussion

Mortality following pancreatic resection has diminished significantly in the past decade, especially when performed in high- volume centers with multispecialty expertise.13-15 In contrast, morbidity following pancreatectomy remains substantial ranging from approximately 30 per cent to 60 per cent in recent series with the vast majority involving an intra-abdominal process. The surgical literature has primarily focused on the incidence, management, and sequelae of pancreatic anastomotic complications as well as delayed gastric emptying. 9, 10, 16 While important in terms of a prolongation in length of stay and a delay in recovery, in the absence of a Class B or C pancreatic fistula, which are uncommon, these complications infrequently require invasive therapeutic intervention or result in mortality.12 Intra-abdominal sepsis following pancreatic resection has received relatively little attention. While less common than other complications, postoperative septic fluid collections or frank abscess formation mandate therapeutic drainage either by the percutaneous route or, not infrequently, repeat laparotomy.1, 4, 5, 11, 16 In addition, the development of IAS increases the cost associated with pancreatic resection, delays recovery, and has a distinct associated mortality rate, especially if reoperation is required in an attempt to eliminate the septic focus.1, 5, 16

The incidence of IAS ranges from 5 per cent to 16 percent inclusive of this study.1, 2, 5, 6, 11, 16, 17 Unfortunately, this rate of infection has not changed significantly in the last two decades despite a myriad of refinements and technical adjuncts involved in pancreatic resection and reconstruction. While a Class C pancreatic fistula remains uncommon, it is almost universally associated with sepsis that requires aggressive nonoperative and operative management.12, 18 In this scenario, sepsis results not so much from leakage of pancreatic juice, but from leakage of enteric contents within the peritoneal cavity. Three of 32 patients in this series developed a Class C fistula as defined by the International Study Group of Pancreatic Fistula classification scheme. All occurred after reconstruction to a soft gland. These patients became septic very early in their postoperative course (before day 6) and all required reoperation (including one after failed percutaneous drainage) for definitive control of their infection. Aggressive intervention failed to prevent one death in this group.

The use of preoperative biliary stenting and the lack of peritoneal drainage following pancreatectomy have been associated with infectious morbidity in some but not all studies and their relationship to septic morbidity remains controversial.2, 19-21 In this study, LAS was not associated with either the preoperative placement of a bile duct stent or the lack of peritoneal drainage. Other risk factors, including intraoperative blood loss, the need for perioperative blood transfusion, and a preoperative immunocompromised state, were not associated with IAS in this study. Only a soft pancreatic remnant and the development of a postoperative pancreatic fistula were significantly associated with the development of IAS by univariate analysis and just the development of a fistula by multivariate analysis. This finding is in common with most, but not all, studies in the literature.1-3, 5, 6, 10, 11, 16, 22

Measures potentially protective of the pancreatic anastomosis such as stenting, fibrin glue application, and the perioperative use of octreotide had no impact on the prevention of septic complications. Despite mese latter results, we continue to use these adjuncts to pancreatic reconstruction in those with a soft pancreatic remnant. Finally, data from the general and cardiac literature suggest that rigid glucose control in the perioperative period reduces infectious morbidity and indeed, this has become a quality initiative monitored by the Center for Medicare and Medicaid Services.23, 24 Despite the implementation of a rigid protocol for normalization of glucose in the perioperative period in the last 3 years, we did not appreciate any decrease in the incidence of IAS in this study. It may be that a 5 per cent to 15 per cent risk of postoperative IAS is inevitable following pancreatectomy with reconstruction to, or closure of, a soft gland. We feel further study might better focus on the early diagnosis of intra-abdominal infections, the recognition of commonly encountered pathogens, and the application of aggressive therapeutic intervention.

The diagnosis of IAS can usually be suspected based on clinical criteria, including fever and tachycardia. Abdominal tenderness and/ or peritonitis may or may not be present, especially if sepsis occurs early in the postoperative period. In addition, more subtle clues such as mental status changes and evidence of renal failure were noted in older patient populations in our review. When suspected, a manual differential has been particularly helpful demonstrating a shift to immature forms even in the face of a normal or depressed white blood cell count. We have been impressed with the rapidity with which these infections develop in the postoperative period. One-third of our patients developed infected fluid collections documented by percutaneous aspiration or reoperation on or before postoperative day 6. The development of an early infected fluid collection following pancreatic resection prior to frank abscess formation (7 to 10 days) has been suggested by others.11, 22 Our three Class C pancreatic fistulas occurred in this group suggesting that when these fistulas occur, they do so early in the postoperative period. Ten of 11 infected fluid collections developing early occurred following reconstruction to a soft gland and in all but one case following a Whipple procedure. Thus, early sepsis, especially following pancreaticoduodenectomy and reconstruction to a soft pancreas, should mandate immediate diagnostic imaging. Our review of patient records for mis study was noteworthy for the frequency with which early sepsis following pancreatic resection was mistakenly attributed to other etiologies such as atelectasis, pneumonia, line sepsis, and urinary tract infection by the treating surgeon as a result of the absence of abdominal physical findings. Our data suggest that if sepsis occurs early in the postoperative period, it is imperative mat an intra- abdominal source should be excluded with early CT scan. In patients with postresection sepsis, we recommend that any free fluid noted on CT be treated with at least percutaneous drainage.

To our knowledge, no prior study has specifically addressed the pathogens associated witii abdominal infections developing after elective pancreatic resection. In contrast to enteric pathogens that might be anticipated in these infections, over one-half of isolates obtained from our 32 patients included either a Gram-positive or fungal organism with no correlation noted between early and late infections or the preoperative placement of a biliary stent. Furthermore, the early presence of resistant organisms was not uncommon. The flora encountered in this study are more common in those developing tertiary peritonitis following laparotomy for secondary peritonitis.25, 26 All of our patients received prophylactic perioperative antibiotics alone, suggesting mat there was little selection pressure for these tertiary padiogens. One- fourth of isolates from patients with postoperative sepsis were resistant organisms and one-half had polymicrobial infections. Importantly, of the five deaths in those with IAS, three patients had fungal pathogens and one had methicillin-resistant S. aureus. We believe mat confirmation of these results from other centers performing pancreatic resection is clearly necessary. However, in the absence of further data and although it is difficult to speculate that earlier treatment would positively impact on outcome, we recommend the institution of broad-spectrum antibacterial coverage, including empiric antifungal therapy and treatment directed at methicillin-resistant S. aureus in those witii postpancreatectomy sepsis until final cultures are obtained. Not unexpectedly, all patients in this series developing postoperative IAS required therapeutic intervention. Although the vast majority of abscesses/fluid collections were amendable to percutaneous drainage, approximately one-tiiird of these infections ultimately required repeat laparotomy and open drainage as has been reported by other centers.1, 11, 16 Six of seven patients avoiding reoperation required more than one drain placement in common with results reported by Sohn et al.11 This was most often necessary as a result of noncontiguous fluid collections. We are aggressive in monitoring clinical improvement after drain placement as well as performing early follow-up CT scans to identify those that might require more than one percutaneous intervention. Four of 32 patients (12.5%) failed initial percutaneous drainage, greater than the 0.5 per cent reported by Sohn. This may simply reflect the smaller number of patients in this study. Open drainage was uniformly required in the three patients with Class C pancreatic fistulas, one after failed percutaneous drainage. Seven of 10 patients requiring reoperation had a pancreaticoduodenectomy as their index procedure, five of whom had reconstruction to a soft gland.

As might be anticipated, length of stay was prolonged in those developing IAS following pancreatic resection and in this study was nearly double that of those who did not have an infectious complication. This prolongation in hospitalization was not different than that previously reported in a series of patients requiring postoperative radiologic intervention for a variety of complications, including IAS following the Whipple procedure.11 More disturbing was a significant increase in procedure-related mortality in those with infectious complications. Our death rate related to infectious morbidity following pancreatic resection was slightly higher than that reported elsewhere.11, 16

The need for therapeutic intervention, the exaggerated length of stay, and the increase in mortality following the development of IAS after pancreatectomy emphasizes the need for early recognition and aggressive treatment of these infections. Based on our data and that of others, one must anticipate infectious complications, especially if a soft pancreas is managed or if a clinically relevant pancreatic fistula develops following surgical excision. Septic morbidity may develop very early in the postoperative period with subtle clinical and laboratory signs before the time period typical of abscess formation. We recommend the institution of early diagnostic imaging in those with clinical deterioration in the early perioperative period. Urgent operative and nonoperative intervention to drain intra-abdominal fluid collections should be used even if there is not a suggestion of frank abscess formation. Our review of the microbiology of these infections suggests a significant per cent is associated with nonenteric and resistant organisms. Early diagnosis, broad initial antimicrobial coverage, and prompt intervention to eradicate septic foci will hopefully ameliorate the morbidity and mortality associated with intra-abdominal infections after pancreatic resection.

REFERENCES

1. Yeo CJ, Cameron JL, Sohn TA, et al. Six hundred fifty consecutive pancreaticoduodenectomies in the 1990’s. Ann Surg 1997;226:248-57.

2. Conlon KC, Labow D, Leung D, et al. Prospective randomized clinical trial of the value of intraperitoneal drainage after pancreatic resection. Ann Surg 2001;234:419-29.

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STEPHEN W. BEHRMAN, M.D., BEN L. ZARZAUR, M.D., M.P.H.

From the Department of Surgery, University of Tennessee, Memphis, Tennessee.

Presented at the Annual Scientific Meeting and Postgraduate Course Program, Southeastern Surgical Congress, Birmingham, AL, February 9-12, 2008.

Supported in part by the Herb Kosten endowment for pancreatic cancer research and care at the University of Tennessee, Memphis.

Address correspondence and reprint requests to Stephen W. Behrman, M.D., F.A.C.S., Associate Professor of Surgery, University of Tennessee, Memphis, Department of Surgery, 910 Madison Avenue, Suite 208, Memphis, TN 38163. E-mail: sbehrman@ utmem.edu.

DISCUSSION

JOHN R. GALLOWAY, M.D. (Atlanta, GA; Opening Discussion): This single institution review of 196 elective pancreatectomies for both benign and malignant diseases focused on the postoperative intra- abdominal sepsis that occurred in 16 per cent. Soft pancreas is identified as a major risk factor for postoperative leak and postoperative infection. Fever, tachycardia, altered mental status, oliguria, and hemodynamic changes are signs of developing intraabdominal sepsis. The authors appropriately advocate early CT imaging to effectively diagnose and treat infected fluid collections and abscesses. Based on their analysis, the bacterial flora obtained from such collection, the early institution of broadspectrum antimicrobial antibiotics against methicillinresistant S. aureus, Gram-negative rods, and antifungal agents are recommended. This is certainly in keeping with the sepsis protocol guidelines put forth by the Society of Critical Care Medicine. The authors accurately note the valuable role of CT drainage using multiple drains, if necessary, and the early follow-up CT scan to document efficacy. In those patients who cannot be safely drained or fail drainage, they advocate the expeditious role of surgical intervention.

Despite this aggressive program of management, postpancreatectomy intra-abdominal sepsis remains a terrible, devastating problem for the patient. Length of stay in the successfully treated patients is more than doubled, and mortality increases from 2 per cent to 16 per cent. Short of never cutting into the soft pancreas, are there any other ways to prevent this complication?

The authors state their own data does not support the use of intraoperative drainage, stenting of the pancreaticojejunostomy, fibrin glue application, or the use of perioperative octreotide. Nevertheless, in their discussion, when confronted with a soft pancreas, they do indeed use these techniques. Do these measures aid in preventing sepsis in a soft gland? How do you handle the cut edge of the pancreas in your patient with distal pancreatectomy?

STEPHEN W. BEHRMAN, M.D. (Memphis, TN; Closing Discussion): Other series, as well as our own results, suggest with a soft pancreas, a 10 per cent to 15 per cent leak rate will occur. My approach is to do everything in a soft gland: fibrin glue, octreotide, omentum, and so on.

I will typically invaginate those anastomoses. With a cut edge, I will individually ligate the duct of Wirsung and then place vertical mattress sutures across the cut edge. In addition, I will place fibrin glue and omentum over it.

JOSE J. DIAZ, JR., M.D. (Nashville, TN): Have you looked at any intraoperative differences during those cases that did and did not develop an intra-abdominal infection (that is, periods of hypotension, length of operation, perioperative antibiotic, timing, redosing during the procedure, and so on)?

STEPHEN W. BEHRMAN, M.D. (Memphis, TN; Closing Discussion): In the uni- and multivariate analyses, we did not find any difference. We have not been able to get our rate of sepsis below the 10 per cent to 15 per cent level.

TAD KIM, M.D. (Gainesville, FL): Do abscesses occur despite having intraperitoneal drains placed intraoperatively?

STEPHEN W. BEHRMAN, M.D. (Memphis, TN; Closing Discussion): I stopped draining pancreatic resections approximately 3 to 4 years ago. One of the things I wanted to look at was whether that made an impact on whether or not these patients developed sepsis. In our analysis, it had no impact on the development of this complication after pancreatectomy.

ROBERT MAXWELL, M.D. (Chattanooga, TN): I would like to get your thoughts on the soft gland and ligating or stapling the gland off.

STEPHEN W. BEHRMAN, M.D. (Memphis, TN; Closing Discussion): That has been reported in the surgical literature; the pancreatic fistula rate is higher when stapled versus hand-sewn.

GARY C. VITALE, M.D. (Louisville, KY): I think if you can convert these to a fistula, you are less likely to have sepsis that leads to death. Does it not make sense even though placing drains may promote fistulization and you end up with a higher fistula rate, that it might lead to less sepsis collections that need to be reoperated early? Could you comment about those in whom you did place drains and whether there was a little higher fistula rate but lower sepsis and collection rate?

STEPHEN W. BEHRMAN, MD. (Memphis, TN; Closing Discussion): I noted in the abstract that the sepsis postoperative sepsis rate was higher in mose who did not have intraperitoneal drains placed. I was very disturbed by that. For the subsequent follow up, I then placed drains in the 16 patients who I added to this series. The data showed there was no difference whether or not they had placement of intraperitoneal drains. My preference is to still not drain these patients because the drains are not effective in evacuating these fluid collections.

DAVID FELICIANO, M.D. (Atlanta, GA): Would it not be safer to put a JP drain in? I may be naive because I do not do pancreatic resections everyday, but although there is a fixed leak rate, I am not convinced that everyone has a high rate of abscesses.

STEPHEN W. BEHRMAN, M.D. (Memphis, TN; Closing Discussion): I have tried all sorts of drainage, and I have still not found one that works. I still place drains occasionally, but I am not sure if the intraperitoneal drain is the panacea to preventing this underlying complication. In all of our patients, the fistula probably occurred before postoperative day 6. We are really aggressive in investigating these patients early, so perhaps we are detecting collections earlier than we had in the past. These are not frank abscesses, but appear to be ascites or postoperative fluid that can accumulate after any operation. Because of the clinical condition of the patient, we are very aggressive with early percutaneous drainage.