By John Dugan, The Marin Independent Journal, Novato, Calif.

Jun. 15–An 8-year-old girl was molested at the Barnes & Noble bookstore in Corte Madera on Saturday night, and police are seeking anyone who may have witnessed the assault.

The incident occurred between 7:30 and 7:40 p.m. in the store at the Town Center shopping mall. The girl was sitting in the children’s books section of the store when she was reportedly approached by a man who asked if her parents were nearby, Twin Cities police Detective Sean Kerr said.

The girl did not answer and tried to leave the area, but the man blocked her path. He then knelt and reached under the girl’s dress, Kerr said.

The girl found her mother nearby after the attack and described the incident. The mother quickly searched the store for the suspect, then alerted store security and called the police at about 8 p.m.

The girl described the man as Hispanic male, in his mid-20s to mid-30s. He was wearing a black T-shirt, black pants and black boots, with close-cropped dark brown hair. He was 5-foot-5 to 5-foot-10, and clean-shaven.

The man was holding a walkie-talkie or Nextel phone device, Kerr said. He was last seen leaving the front parking-lot entrance to Barnes & Noble.

“This is a very rare occurrence in Corte Madera,” Kerr said. “It’s a rather brazen attack on an 8-year-old girl in a bookstore, in public.”

The girl was taken to Children’s Hospital in Oakland, but was released with no injuries. Police are reviewing security camera tapes for any more information on the incident, Kerr

said.

Anyone who witnessed the event or saw a man matching the suspect’s description at the Town Center between 7:30 and 8 p.m. Saturday is asked to call Detective Mike Norton at 927-5175.

Contact John Dugan via e-mail at [email protected]

Read more Corte Madera stories at the IJ’s Larkspur, Corte Madera section.

—–

To see more of The Marin Independent Journal or to subscribe to the newspaper, go to http://www.marinij.com/.

Copyright (c) 2008, The Marin Independent Journal, Novato, Calif.

Distributed by McClatchy-Tribune Information Services.

For reprints, email [email protected], call 800-374-7985 or 847-635-6550, send a fax to 847-635-6968, or write to The Permissions Group Inc., 1247 Milwaukee Ave., Suite 303, Glenview, IL 60025, USA.

NYSE:BKS, NASDAQ-NMS:NIHD,

CHICAGO _ While secret shoppers are commonly used to improve customer service and quality in retail stores, restaurants and hotels, members of the American Medical Association don’t want them in doctors’ offices.

That was the prevailing opinion of doctors who testified before an AMA panel at Sunday’s annual meeting of the group’s policy-making House of Delegates in Chicago. Testimony before the panel is the first step in a process that could lead to becoming policy of the AMA, the nation’s largest doctor group, representing nearly 250,000 physicians.

The secret shopper concept is not being proposed to evaluate clinical skills but the way medical professionals manage relationships with patients, from the process of making appointments to such things as explanations of billing practices.

As health-care costs rise, health insurance companies, employers and consumers and others who pick up the tab for U.S. medical care are increasingly demanding quality information to ensure they are making informed choices about the kind of care and service they will receive at the doctor’s office. And as health plan deductibles become higher, patients are increasingly shopping around.

To accommodate such consumer demands, insurers and hospitals are increasingly becoming open to ratings and other information as a way to become more consumer-friendly. The use of secret shoppers, doctors say, is becoming part of the consumer health information wave with such data eventually fed back to those being rated or to third-parties who build their own databases for consumers.

But AMA members told the panel that they did not trust the secret shopper concept, saying such patients could get in the way of needed medical care for real patients. In addition, doctors say, information gathered could be used to cut payments to doctors or used by trial lawyers as a way to damage physicians in court.

“It is grossly unethical,” said Dr. Howard Chodash, an associate professor of gastroenterology at Southern Illinois University Medical School and an AMA delegate representing the Illinois State Medical Society.

Other doctors say they should be able to get enough feedback on how their practice is doing from their own patients.

“We should use real patients as sources of real information we need about quality of care,” said Dr. George Anstadt, an AMA delegate from Pittsford, N.Y., who is representing the American College of Occupational and Environmental Medicine. “This goes against the grain of the doctor-patient relationship.”

Chodash was among more than a dozen doctors who spoke before the panel, most voicing strong opposition to the use of secret shoppers. The issue is one of many the group will consider as part of its annual meeting held through Wednesday at the Hyatt Regency Chicago. The secret shopper concept could be endorsed, rejected or referred for more study when the 565-member House of Delegates votes on it later this week.

The AMA Council on Ethical and Judicial Affairs, which studied the issue and brought it before delegates this week, has asked the group to endorse such practices.

“It can highlight things that we are not aware of that can benefit our practices,” said Dr. Rex Greene, a member of the ethics panel who practices hematology-oncology in Lima, Ohio. “We would like certain parameters where ethically appropriate. This is a practice management tool.”

The idea of the secret shopper is to evaluate “most of the steps of the patient experience, from the ease of making an appointment over the phone, to the environment and flow of patients in the waiting room, to the encounter with the physician,” the ethics council wrote in a four-page report.

Greene said the idea is not to bring the secret shopper into the exam room to evaluate a doctor’s clinical skills. Rather, it should be used to find out, for example, whether the staff was professional, he said.

Greene said some doctors may not have a choice on whether they will one day be evaluated by secret shoppers, especially if they work for a large group practice. He said medical directors of group practices that employ physicians are conducting such evaluations already and the doctors in the practice have no choice but to go along with them.

“We are running a service business and we are not as focused on that as we should be,” Greene said in an interview.

___

(c) 2008, Chicago Tribune.

Visit the Chicago Tribune on the Internet at http://www.chicagotribune.com/

Distributed by McClatchy-Tribune Information Services.

For reprints, email [email protected], call 800-374-7985 or 847-635-6550, send a fax to 847-635-6968, or write to The Permissions Group Inc., 1247 Milwaukee Ave., Suite 303, Glenview, IL 60025, USA.

By Sim Bak Heng

JOHOR BARU: Two out of every three registered Chinese physicians (sinsehs) in the country are not qualified, and chances are they will diagnose ailments and prescribe medicines wrongly.

And the statistics are worrying for the Federation of Chinese Physicians and Medicine Dealers Association of Malaysia (FCPMDAM), considering there are over 7,000 registered Chinese physicians.

According to the federation, the huge number is the result of an abuse of the registration exercise for Chinese physicians as required by the Health Ministry since 1997.

To monitor the practice of Chinese physicians, the ministry had assigned three community-based associations to help in the registration of Chinese physicians so that they would get the annual practising certificates (APCs).

FCPMDAM chairman (Chinese Physician division) Tan Kee Huat said some associations took the opportunity to abuse the registration exercise by recruiting members indiscriminately, especially those who had no proper background in Chinese medicines.

He said the unqualified ones seeking the status of Chinese physicians would pay for membership as well as the APCs from those associations.

“This seems to be a win-win situation as the associations are able to enlarge their membership while, on the other hand, those unqualified ones are able to buy their membership and APCs which allow them to carry out their ‘profession’ legally.

“As a result, the number of Chinese physicians has risen from about 3,000 to over 7,000. Despite the meteoric rise in numbers, the numbers tell nothing, except that there are more unqualified Chinese physicians than before.”

It is learnt that some associations charge about RM600 for the registration fee of the annual practising certificate which normally cost RM100.

Tan said the presence of these unqualified Chinese physicians had greatly tarnished the image of the Chinese medicine fraternity.

He said a normal Chinese physician took five years to earn a degree, and another three years each for a Master’s and doctorate degree.

“Those unqualified ones who bought their APCs have no basic training in Chinese medicine. They might be just quack medicinemen, traditional healers or masseurs. If unsuspecting patients are to patronise their outlets, they might end up getting more sick and risk being cheated of their money.”

Tan, who is also the principal of the Johor Academy of Traditional Chinese Medicine, said the Health Ministry had agreed to continue using Chinese language in the teaching of Chinese medicine in local private colleges. He said Health Minister Datuk Liow Tiong Lai also assured them that the existing medium of instruction would remain.

(c) 2008 New Straits Times. Provided by ProQuest Information and Learning. All rights Reserved.

By Cleve Wiese, The News Virginian, Waynesboro, Va.

Jun. 15–Wards where Western State Hospital patients watched television and played board games 10 years ago now sit vacant each weekday as their occupants attend specialized, college-like classes geared toward recovery and release.

Other wards and buildings scattered over the sprawling, 300-acre campus, once filled with hundreds of long-term residents, have been emptied altogether, their windows boarded and their doors chained shut.

In 1977, when Director of Community Services John Beghtol came to work at the hospital — which treats mentally ill people from roughly half of Virginia’s total population — it housed 1,354 patients, many with little prospect of release. Patients spent their days mostly confined to wards, where social interaction was limited to a static group of fellow patients and staff members, Beghtol said.

“In the past, Western State was a warehouse,” Beghtol said. “There were wards filled with long-term patients who had been there over 30 years, some [had been there] 40 or 50 years … It was sad. People lost their whole lives here.”

Since the 1970s, a gradual shift, at the hospital and across the country, toward recovery-based programs and community-based outpatient services culminated in 1998, when a jolt of state funding enabled the hospital to shift to a “psycho-social rehabilitation” treatment model, moving the vast majority of its patient population off the wards and into classrooms.

Western State now houses no more than 260 patients at a time and operates perhaps the most comprehensive rehabilitation program of its kind, with more than 100 classes offered in five separate treatment “malls,” Beghtol said. On a typical day, 95 percent of patients attend classes. The average length of hospitalization is less than six weeks, he said.

Shifting from secure wards to often-unpredictable classrooms involved a degree of risk, Beghtol said, and many staff members were initially skeptical of the concept. But the results spoke for themselves: Within the first four years of the program, the restraint and seclusion rate fell by over 90 percent.

Western State’s most challenging patients — those with lowered cognitive ability and a history of violence — attend classes in the First Step treatment mall. Under the old system, many of them would be prime candidates for indefinite periods of hospitalization, Beghtol said.

On a recent weekday, the 26 First Step patients calmly moved from classroom to classroom between 20 minute sessions, sometimes gently guided by staff. Serious behavioral incidents are extremely rare, said Allen Layman, director of First Step. The release rate is remarkably high.

“We now have probably around 80 percent of these patients move on to community settings or back home,” Layman said. “But the biggest thing we’ve seen is the huge decrease in restraint and seclusion. We just don’t see it here much anymore because we try to provide other options to help patients manage their own frustration and anger.”

Most patients attend classes in the Stribling treatment mall, located in Western State’s recreation center — a function the facility still fulfills on afternoons and weekends. The Stribling mall has the feel of a casual college campus, with unlocked exterior doors and crowded hallways. The building houses four patient-staffed businesses — a restaurant, a greenhouse, an auto garage and a picture frame shop — designed to teach patients marketable “soft skills” key to finding jobs after their release.

Michael Poole, an occupational therapist in charge of the frame shop, said giving patients access to dangerous tools of the trade, such as circular saws, scalpels and oversized plates of glass, had yet to cause a serious problem.

“We go through our share of Band-Aids, but there have been no major incidents,” he said. “If you have high expectations, they’ll meet them.”

But the shift to a psycho-social rehabilitation model has not been without its difficulties, Beghtol said. The current Western State campus, built in the 1950s to house 1,800 patients, was never intended for a streamlined, therapy-based system. Not only have ill-suited ward spaces had to be converted into working classrooms, the risks of moving patients over long distances from residential areas to treatment malls each day have created security concerns and limited the degree to which some patients, particularly those transferred from jails and prisons, can interact with the larger hospital population.

The design of a new $110 million dollar hospital facility, slated for construction some time in the next couple of years, will specifically address those problems, Beghtol said. An architectural firm met with more than 100 hospital staff members in creating a preliminary plan for the building, which will probably be centered around a large courtyard with treatment malls toward the center and sleeping areas toward the periphery.

“The hospital itself will reflect the emphasis on rehabilitation and recovery,” Beghtol said.

—–

To see more of The News Virginian or to subscribe to the newspaper, go to http://www.newsvirginian.com.

Copyright (c) 2008, The News Virginian, Waynesboro, Va.

Distributed by McClatchy-Tribune Information Services.

For reprints, email [email protected], call 800-374-7985 or 847-635-6550, send a fax to 847-635-6968, or write to The Permissions Group Inc., 1247 Milwaukee Ave., Suite 303, Glenview, IL 60025, USA.

By Erin Wisdom, St. Joseph News-Press, Mo.

Jun. 15–An area nursing home has made improvements in order to continue receiving payment from the Centers for Medicare & Medicaid Services (CMS).

CMS announced in March that its agreement with Clinton Care and Rehab Center in Plattsburg, Mo., would be terminated June 3 due to the center failing to substantially comply with Medicare regulations. CMS removed this denial due to visits made to the facility on May 7 and June 2 that showed corrections had been made.

The main factor that kept the center from completing its corrections until right before the termination date was a requirement that it come up with an alternative power source to run its sprinkler system, said Shane McClain, assistant chief financial officer for Health Systems Inc., which manages Clinton Care and Rehab Center.

“A few years ago, we had to install a fire pump to run the sprinkler system, but it was determined that that was not a reliable power source,” he said. “Other than that, we had some nursing deficiencies that were never on the serious side.”

Documents provided by Paul Shumate, chief of the survey, certification and enforcement branch of CMS’ Kansas City regional office, detail the deficiencies the center showed between December 2007 and February 2008, as well as the center’s plans to correct them.

These included a failure to meet safety codes such as requirements to have smoke-barrier doors that fit properly and close completely, to show verification that all wallpaper is fire-resistant and to have battery-powered emergency lights on the building’s exterior.

Deficiencies were also listed in the care of some residents sampled and included a failure to follow physicians’ orders in applying splints or braces, to provide daily oral and incontinent care for every resident in need of them and to always follow the proper procedure for lifting and moving residents who aren’t fully mobile.

The center’s plan for correcting these and other deficiencies in nursing care included making sure all residents receive services in accordance with their individual plans of care and that all staff who work as nurse’s aides demonstrate competency through satisfactory participation in an approved training program.

Erin Wisdom can be reached

at [email protected].

—–

To see more of the St. Joseph News-Press or to subscribe to the newspaper, go to http://www.stjoenews-press.com/.

Copyright (c) 2008, St. Joseph News-Press, Mo.

Distributed by McClatchy-Tribune Information Services.

For reprints, email [email protected], call 800-374-7985 or 847-635-6550, send a fax to 847-635-6968, or write to The Permissions Group Inc., 1247 Milwaukee Ave., Suite 303, Glenview, IL 60025, USA.

By Mary Jo Balasco, The Herald, Rock Hill, S.C.

Jun. 15–Glencairn Garden’s 50th anniversary kick-off celebration will be from 3 to 5 p.m. June 22. The event, which will mark the beginning of a year-long celebration for Glencairn Garden, will feature a concert by the Blue Chip Band and a brief program reflecting the history and significance of the garden.

The concert will be on Crest Street in front of the Bigger House. Balloons and light refreshments will be available while supplies last. The event kicks off the “face lift” that the garden will undergo during the following months as construction begins on new phases of the garden’s master plan.

In case of inclement weather, call 329-5620 or visit www.rockhillrocks.com for event status. Crest Street will be blocked at Charlotte Avenue.

Parking will be available at Garden Sanctuary Church, with an entrance off Wilson Street. Other activities and special events will be held monthly in the garden through 2008 and again in 2009.

Richburg tractor show planned on Saturday

The Richburg tractor show will be from 9 a.m. to 2 p.m. Saturday at Lewisville High School, 3971 Lewisville High School Road, Richburg. Tractor owners are invited to bring their tractors and farm equipment to display.

Admission is free and there is no registration. Tom Weaver will demonstrate his binder and thrasher machines. Barbecue plates will be sold for $7.

The show is sponsored by the Richburg Masonic Lodge. Non-food vendors are welcome to participate, and tables are $20. For details, call Weaver at (803) 377-0502.

Lauren Pines area to host summer concert series

A free summer concert series, Music in the Pines, will be held in the Lauren Pines subdivision on S.C. 161, between S.C. 55 and U.S. 321 in York.

A preshow will be from 6:15 to 7 p.m. and a concert will be from 7 to 8:30 p.m. June 27, July 11 and 25 and Aug. 8 and 29. Bring blankets, chairs and picnic baskets. Food vendors will be available. For details, visit www.laurenpines.com.

Hudson family performing at Allison Creek event

The Hudson Family Band will perform at 7 p.m. Thursday at Allison Creek Bluegrass at Allison Creek Presbyterian Church, 5780 Allison Creek Road, York. Food is available at 6:30 p.m.

The band, consisting of the Hudson family — dad, mom, eight children and grandma — includes two five-piece bands. The event is free and open to the public.

Thursday’s show will conclude the spring series. The concerts will resume in August. For details, visit www.allisoncreekbluegrass.com.

City Hall gallery hosts Amanda Tucker’s work

The paintings of Lancaster artist Amanda Tucker are on display during June in the Rock Hill City Hall Rotunda Gallery, second floor, 155 Johnson St. Gallery hours are 9 a.m. to 5 p.m. Monday through Friday. For details, call the arts council at 328-2787, visit www.yorkcountyarts.org or e-mail [email protected].

Neighbor event planned in the Hagin/Fewell area

Taking the City Ministry will host a Bringing it to the Neighborhood event at the Hagin/Fewell Street substation at 4 p.m. June 28. The Outreach Ministry is in partnership with the Urban Rock Hill Weed and Seed program.

Activities will include live music, a youth praise dance, free food, words of encouragement and more. The event is free and open to the public.

PRT events include climbing, paddle trip

Rock Hill Parks, Recreation and Tourism will have the following trips:

— A parent and child climbing day trip to Pilot Mountain, N.C., Thursday. The group will depart at 8 a.m. from the Rock Hill City Hall parking lot, 155 Johnson St., and will return at 4:30 p.m. Transportation and equipment is provided. Participants should pack a lunch. Pre-registration is required. Cost is $40 per person.

— A paddle trip on the New River, June 28. The group will paddle a 10-mile stretch on the river through Ashe County, N.C., near North Wilkesboro. Participants can purchase a meal at Shatley Springs Inn Restaurant, which serves family-style home cooking. Previous paddling experience is recommended. Pre-registration is required. Cost is $65 per person or $50 for tagalongs with their own boat. Transportation is included in the cost.

To register or for details on either trip, call Tom Bell at 329-5632 or visit www.rockhillrocks.com.

Historical marker unveiling planned June 24 in Sharon

A new state historical marker will be unveiled at 5:30 p.m. June 24 at 4028 Woodlawn St., Sharon. Speaker will be Jerry West, historian and director of the Museum of Western York County.

West co-authored the text for the historical marker commemorative booklet with Culture and Heritage Museums historian Michael Scoggins. The marker will commemorate the First National Bank of Sharon, founded in 1909 and the oldest continuous operating bank in York County. First National Bank of Sharon was an independent national bank until it merged with First Citizens Bank in 1986. The event is free. For details, visit www.chmuseums.org.

Photo event, artist demos announced by arts council

The Arts Council of Rock Hill will have the following events:

— The fourth annual photography competition awards ceremony, opening reception and Art Crawl, 6 to 8 p.m. Thursday at the Center for the Arts, 121 E. Main St., Rock Hill. The event is free and open to the public.

— Earth Fare Supermarket store opening event with artist demonstrations and displays, live music and local entertainment, June 25 through 27 at the Earth Fare Store, 725 Cherry Road, Winthrop Commons, Rock Hill. Five percent of total store sales during the three-day event will be donated to the arts council. For details, call 327-2787 or visit www.earthfare.com.

Reading program planned at Hunter Street school

Hunter Street Elementary School in York will have a free summer reading program for its students. Students may check out library books and participate in fun literacy activities on these dates:

— Library hours, 9 a.m. to noon, activities 9:30 to 10:30 a.m., Monday.

— Library hours 3 to 6 p.m., activities 3:30 to 4:30 p.m., June 23.

— Library hours 9 a.m. to noon, activities 9:30 to 10:30 a.m., June 30.

— Library hours 3 to 6 p.m., activities 3:30 to 4:30 p.m., July 14.

— Library hours 9 a.m. to noon, activities 9:30 to 10:30 a.m., July 21.

— Library hours from 3 to 6 p.m., activities from 3:30 to 4:30 p.m. July 28.

— Library hours from 9 a.m. to noon, activities from 9:30 to 10:30 a.m. Aug. 4.

Vacation reading program includes special events

All York County libraries will offer a free vacation reading program for ages 3 to 12 through Aug. 1. For details, visit www.yclibrary.org or call 981-5888. Children can keep track of minutes read or being read to and will receive prizes when they meet goals.

A partial program schedule is:

— Dinosaur, 1, 2:30 and 4 p.m. Tuesday, Fort Mill Public Library; 1, 2:30 and 4 p.m. Wednesday, York County Library, Rock Hill; 10:30 a.m. Thursday, Clover Public Library; 2:30 and 4 p.m. Thursday, York County Library; and 10:30 a.m. Friday, Lake Wylie Public Library. Children are invited to help defeat T-Rex and help a lost dinosaur hatchling find its mother in a theater production by StageWorks Theatre.

— Insect-O-Mania, for ages 10 to 12, 11 a.m. June 23 and 3 p.m. July 29, York County Library, Rock Hill. Learn about the fascinating life of bees from a local beekeeper and make an earthworm hotel. To register, call 981-5888.

— Creepy, Crawly Critters, for ages 6 to 9, 3 p.m. June 24 and 11 a.m. July 22 at the York County Library. To register call 981-5888. Explore the lives of good and bad bugs with a special guest, The Orkin Lady, become a certified master bug hunter and make insect crafts.

— Teddy Time, 2:30 and 4 p.m. June 24 at the Fort Mill Public Library; 1, 2:30 and 4 p.m. June 25 at the York County Library; 10:30 a.m. June 26 at the Clover Public Library; 2:30 and 4 p.m. June 26 at the York Public Library; and 10:30 a.m. June 27 at the Lake Wylie Public Library.

The summer reading program for teens will be through Aug. 1 at all York County libraries, with programs, prizes and food for rising sixth through 12th graders. Some programs require advance registration. A sample of programs are listed below. For a complete schedule visit www.yclibrary.org or call 981-5830. Related events include:

— Teen Screen, 4 to 6 p.m. Thursday at the Clover Public Library and 2 to 4 p.m. June 30 at the York County Library. Teens can watch a movie; the title will be announced later.

— Teen Advisory Board, 5:30 to 7 p.m. June 24 at the York County Library. The teen advisory board selects materials for the young adult collection and plans events for teens.

— Anime Club, 6:30 to 8 p.m. June 23 at the York County Library. Join other fans to view and discuss anime and manga, hear guest speakers and share work.

— Green Teens: Make a jean purse, 4 to 6 p.m. June 26 at the Fort Mill Public Library. Call 547-4114 to register. Turn your jeans into a funky purse.

Library locations:

n The York County Library, 138 E. Black St., Rock Hill, 981-5858.

n The York Library, 21 E. Liberty St., York, 684-3751.

n The Clover Library, 107 Knox St., Clover, (803) 222-3474.

n The Fort Mill Library, 1818 Second Baxter Crossing, Fort Mill, 547-4114.

n The Lake Wylie Library, 185 Blucher Circle, Lake Wylie, (803) 831-7774.

Archaeology, planetarium events scheduled by CHM

The Culture and Heritage Museums will have the following events:

— Learn about archaeology finds at the future museum site. Brett Riggs and Stephen Davis will speak about Catawba archaeology, including their work, “Archaeology in the Old Catawba Nation,” from 6:30 to 7:30 p.m. Tuesday at the Fort Mill Public Library, 1818 Baxter Crossing. In 2007, work at the site revealed a large, compact circular town of rectangular, post-built houses. Excavations have yielded native pottery, animal bones, botanical remains, ammunition, glass beads and kaolin pipe fragments that point to the economic, political and military importance of the Catawba Nation to South Carolina. The event is free; reservations are required by Monday at 329-2121.

— Wonderful Wednesday series at 11 a.m. Wednesdays, through July 30 at the Museum of York County, 4621 Mount Gallant Road, Rock Hill. The series offers a different program each week. After the program, participants can explore the museum, take part in hands-on activities or bring a picnic. Cost is $7 adults, $6 seniors, $5 ages 4 to 17 and free for children ages 3 and younger and CHM members. Group rates are available. Groups of 15 or more must register by calling (803) 981-9182.

— Special planetarium show times are 11 a.m. and 2 p.m. Thursdays and Fridays; 11 a.m., 2 and 3 p.m. Saturdays and 2 and 3 p.m. Sundays through Aug. 3 at the Museum of York County’s Settlemyre Planetarium. For details, call 329-2121 or visit www.chmuseums.org. Special planetarium shows are available for groups of 30 or more with advance reservations by calling 981-9182.

Health lifestyles seminar offered for kids, youth

Learn about healthy lifestyles at the 4-H Food, Gardening and You seminar for youth sponsored by the Clemson Extension 4-H of York.

A seminar for ages 6 to 9 will last from 9 a.m. to noon Thursday and Friday at the York County Extension Office, 120 N. Congress St., York. A seminar for ages 7 to 10 will be from 10 a.m. to noon July 9 through 11 at the Rock Hill Learning Center, 825 Edgemont Ave. Registration fee is $15.

Participants will learn how to prepare and cook healthy foods and how vegetables grow and will see literature and videos about plants. For details, call Margie Sippel at 684-9919, Ext. 113, or e-mail her at [email protected].

Cattlemen, farm bureau offering scholarships

These scholarships are being offered:

— The South Carolina Cattlemen’s Association will award two $1,000 scholarships. One will go to a college student whose intent is to pursue a four-year degree in applied agricultural sciences. A second will be awarded to a college student who plans to pursue a four-year degree, with no restriction on the field. For more details or an application, visit www.sccattle.org or contact the SCCA office at (877) 859-9121. Entry deadline is July 1.

— The York County Farm Bureau is seeking applicants for its annual scholarship, awarded to a student pursing a higher education degree in agriculture or a related field, after completing a semester at a four-year school. The amount is $1,000 annually, to be awarded $500 each semester. The scholarship will be awarded to a York County resident based on character, demonstrated leadership abilities and dedication to agriculture or a related field. Applications are available at the York County Farm Bureau, 1735 Old York Road, York, and are due by June 30. For details, call Laverne Spoon, (803) 684-4235.

Entries sought for literary competitions

Entries for the Arts Council of York County’s 2008 literary competition are being accepted. Cash prizes will be awarded to winners in poetry and fiction.

Entry deadline is July 7. Winners will be announced by Aug. 1. For details and guidelines, visit www.yorkcountyarts.org, call the arts council at 328-2787 or e-mail [email protected].

Crescent Shrine Club is hosting steak night

The Crescent Shrine Club will have a steak night from 6 to 8 p.m. Thursday and every third Thursday of each month at the club, 2065 McConnells Highway, Rock Hill. Steak is $12 and hamburger steak is $9, and both plates include baked potato, tea or coffee, roll and salad bar. The event is open to the public.

Entertainers needed for Clover fall event

Entertainers are needed for the Clover Fall Festival on Sept. 20. Singers, dancers, groups or other performers interested should call Gina Bruce at Clover Parks and Recreation at (803) 322-9493. All acts are subject to approval and no one will be allowed to perform without registering. There is no cost to participate. Registration deadline is Aug. 30. The festival will raise money for underprivileged children.

Pet foster seminar offered in Lancaster

A free seminar on fostering pets will be from 9 a.m. to noon Saturday at the AFLAC store, 126 S. Main St., Lancaster. The Humane Society of Lancaster County will conduct the seminar, open to residents 21 or older. Space is limited. To register or for details, call (803) 285-1401 or (803) 289-9820 or e-mail [email protected].

Bethany honors heroes with its 2009 calendar

The 2009 calendar, “Bethany’s Heroes: The Men and Women of World War II and Korea,” is now being sold. The calendar features 87 veterans from the Bethany community, including more than 150 photos, first-hand stories and excerpts from the “Bethany Blab,” a school-sponsored newsletter during the 1940s that kept students and soldiers in touch during World War II.

Calendars are $15 and available at McGill’s Store, 12345 S.C. 55, Clover; Mac’s Store and Grill, 2403 S.C. 55, Clover; Medicap Pharmacy, 1120 Devinney Road, York, and Bethany Elementary School, 337 Maynard Grayson Road, Clover.

Proceeds benefit the Bethany Elementary School historical committee. Committee members plan to use funds to preserve and display artifacts given to the school’s historical museum.

The 2009 calendar was unveiled during a memorial service in May at the elementary school. For details, call Kathy McCarter, principal of Bethany Elementary School, (803) 222-4093.

Learn to line dance with Lancaster shaggers

Lancaster Shag Club line dancing lessons will begin at 7 p.m. every Thursday through the summer at the Lancaster Moose Lodge, 200 Moose Drive.

Each session will include a review of dances and instruction in new dances. Cost is $2 per person per lesson. For details, call club president Nita Brown at (803) 286-5694.

Master gardener classes will begin in August

Classes for the York County master gardener training program will last from 9 a.m. to noon Aug. 5 and continue through Oct. 28 at the Clemson Extension Office, 120 N. Congress St., York.

The program is open to all adults, regardless of gardening experience. Participants will learn about all aspects of gardening, such as soils, garden pests, beneficial insects, plant physiology, growing vegetables, fruits, trees, shrubs, flowers, lawns and more.

Class fee is $150, payable upon acceptance. The fee covers the cost of materials and literature. In addition to the fee, those successfully completing the program will be required to volunteer a minimum of 40 hours of community service, including answering gardening questions from consumers, community beautification projects or other gardening activities sponsored by the extension service.

For applications, call the York County Extension office at 684-9919, Ext. 114. Enrollment is limited and applications are due by July 2.

Local adult ed center offers computer training

Computer classes are offered at the Rock Hill Adult Education Center during July and August. Registration is from 8:15 a.m. to 4 p.m. Monday through Friday at the center, 1234 Flint St. Ext., Rock Hill. Cost is $75. For details, call (803) 981-1375. Classes offered are:

— Basic Introduction to Windows, 5:30 to 8:30 p.m. July 8, 10, 15 and 17.

— Microsoft Word level I, 5:30 to 8:30 p.m. July 22, 24, 29 and 31.

— Microsoft Word level II, 5:30 to 8:30 p.m. Aug. 5, 7, 12 and 14.

Lake Wylie fireworks needs local donations

The Lake Wylie community July 4 fireworks display fund is in need of donations. The display is funded solely through donations. Send donations to the Camp Thunderbird Fireworks Fund, 1 Thunderbird Lane, Lake Wylie, S.C. 29710.

Thrift store sale, golf tourney are among local fundraisers

The following will have fundraisers:

— Thrift Store Ministries of Western York County, 31 N. Congress St., York, will have a buy-one-get-one-free sale on all shoes and pocketbooks this week. The store needs donations of furniture, clothing, appliances and other items. Volunteers are needed. Store hours are 9 a.m. to 5 p.m. Monday, Tuesday, Thursday and Friday and 9 a.m. to noon Saturday; the store is closed Wednesday. Thrift Store Ministries serves needy families in the York school district. For details, call 628-0808.

— The 2008 Power of Mentoring golf tournament will be at 9 a.m. June 27 with a shotgun start at Waterford Golf Club, 1900 Clubhouse Drive, Rock Hill. A continental breakfast will be served at 8 a.m. Entry fee is $80 per person and $300 per four-person team. Fee includes range balls, green fee, GPS, online scoring cart, continental breakfast and lunch. Proceeds will benefit the Rock Hill schools mentoring program, which provides a support system to enhance the school experience. For details, call Zipporah Little at 981-1088 or e-mail her at [email protected].

— Faith Christian Ministries Men’s Ministry will have a fish fry beginning at 10:30 a.m. June 28 at 213 S. Anderson Road, Rock Hill. Fish sandwiches are $3.50 and fish plates are $6.50. Hot dogs and hamburgers will be sold. To pre-order or for delivery, call 328-2246.

American Legion, dancers announce gatherings

These groups announce meeting information:

— The Fort Mill American Legion Auxiliary will meet at 7 p.m. Thursday at the legion hall, 427 Banks St., Fort Mill. The installation of new officers will be held. This is the last meeting until Sept. 18, when a new itinerary and new committee positions will be offered. Members are reminded to drop off items for a bake sale for the legion’s Fourth of July stew by 11 a.m. July 4.

— The Ballroom Dance Club will have its fourth Friday dance from 8 to 10 p.m. June 27 at the Springs Recreation Complex, 971 Tom Hall St., Fort Mill. Disc Jockey will be Jim Wright. Dress is dressy casual and non-alcoholic beverages will be provided. Members are asked to bring snacks to share. Admission for first- and second-time visitors is $5 and other visitors are $10. Beginners and experienced dancers are welcome. For details, call Joyce at 366-9805 or visit www.theballroomdanceclub.com.

Local alumni groups announce reunion news

The following alumni are meeting:

— The Northwestern High School class of 1997 is organizing a planning meeting for its 12-year reunion. Anyone interested should contact Molly Myers at [email protected]. Alumni may send contact information to Myers’ e-mail address.

— The Fort Mill High School class of 1998 is seeking alumni contact information for its 10-year reunion. E-mail information to [email protected] or call 548-4801.

— The Finley High School class of 1966 will meet at 5 p.m. Saturday at Summit Food and Spirits Restaurant, 134 Main St., Chester. For details, call James Dunham at (704) 232-0793.

Clover preschool accepting registration

First United Methodist Church preschool, 124 Bethel St., Clover, is now enrolling 4-year-olds and children who will be age 3 before Sept. 1. Preschool hours are 8 a.m. to noon Monday through Thursday. For details, call Kathy Hall at (803) 222-3496, Ext. 13.

Red Cross drives planned around area

The American Red Cross is seeking blood donations. All blood or platelet donors who give through June 30 will be entered into a drawing for one of two $750 gas cards.

Donors must be 17 years or older, weigh at least 110 pounds, be in general good health and provide a valid form of ID. Donation takes about an hour. To schedule an appointment or for details, visit www.redcrossblood.org or call (800) 448-3543.

The York County chapter’s Bloodmobile schedule is:

— 2:30 to 7 p.m., Monday, Red Cross office, 200 Piedmont Blvd., Rock Hill.

— 3 to 7:30 p.m., Friday, Charlotte Knights Stadium, 2280 Deerfield Drive, Fort Mill.

— 2:30 to 7 p.m., June 24, downtown Ecumenical at First ARP Church, 201 E. White St., Rock Hill.

Family center has medical clinic

The Rock Hill Family Resource Center, 217 Orange St., will have a free medical clinic from 8:30 a.m. to 3:30 p.m. Friday for children through age 18 who do not have insurance or Medicaid. Other free pediatric clinics are located in Fort Mill, Clover and York. Services include immunizations, sick visits and physicals.

For appointments or directions, call (803) 322-6636. For details, call 980-2079. Parking is at the rear of the building and entrance is through the red door.

Fitness for seniors offered at Westminster

Westminster Towers of Rock Hill is beginning a new community fitness club for seniors hosted by Grace Lutheran Church. The club will meet from 9 to 10:30 a.m. beginning Monday at the church social hall, 426 Oakland Ave., Rock Hill.

Classes will meet on Mondays, Wednesdays and Fridays. The class is limited to 25 participants able to walk unassisted. The club will focus on improving the conditioning of active senior adults, ages 65 and older. Sessions will include light to moderate exercises that focus on cardiovascular conditioning, muscle strength, muscle flexibility, balance and agility.

Jonathan Kimball will conduct the program. Kimball is a certified strength and conditioning specialist with a master’s degree in fitness and wellness and is the wellness director at Westminster Towers Retirement Community. For details, call Kimball at 328-5211.

Health, wellness event is planned in Rock Hill

A health and wellness fair will be from 9 a.m. to noon June 21 at Foundation A.M.E. Zion Church, 1852 Neely Store Road, Rock Hill. Services include information and screening for blood pressure, heart disease, diabetes, cancer, stress management, osteoporosis, arthritis, respiratory and nutrition.

Health agencies will be on site, including the York County fire marshall, York County Teen Health Center, York County Sheriff’s Department, York County Council on Aging, American Red Cross, Safe Passage Sexual Resource Center, Keystone Substance Abuse Services, Rock Hill Rescue Squad and Catawba Mental Health. The event is free and open to the public. For details, call Diane Hicklin at 329-2762.

Senior expo planned in York

The 2008 Western York County Senior Expo will be from 9 a.m. to 1 p.m. June 24 at Filbert Presbyterian Church, 2066 Filbert Highway, York. The expo invites seniors, caregivers and health professionals to view products, benefits and services for the elderly in York County.

Free health services, screenings and information will be provided. Admission, food and beverages are free. There will be entertainment and door prizes. The Greater York Chamber of Commerce with the Greater Clover Chamber of Commerce and Individuals Caring for the Elderly are sponsoring the event.

Movement, music are topics of program

A program about the benefits of movement and music, Move to the Music, will be at 6 p.m. Thursday at Sterling House of Rock Hill, 1920 Ebenezer Road.

Guest speaker will be Stephanie Campbell of Total Care Home Health. Admission is free and there will be door prizes and refreshments. For reservations or details, call Geri Tucker at 366-1189.

Volunteer training offered by Hospice

Volunteer training for Hospice and Community Care will be from 9 a.m. to 4 p.m. Saturday at the campus, 2275 India Hook Road, Rock Hill. Positions include knitting prayer shawls for patients, helping during community events, clerical work, assisting with children’s programs, patient companionship and more. For details, call the volunteer department at 329-1500.

Free HIV testing offered in York

Free HIV testing will be from 11 a.m. to 3 p.m. June 27 at Galilee Baptist Church, 15 Galilean Road, York. June 27 is National HIV Testing Day, a national mobilization effort to encourage people to get tested. Refreshments and prizes will be available.

Catawba Care Coalition is sponsoring the event. The coalition provides free walk-in HIV testing from 9 a.m. to 4 p.m. Monday through Thursday at 1151 Camden Ave., Rock Hill.

[email protected]

Deadline for Tuesday and Thursday columns is 5 p.m. two business days before publication. Deadline for Sunday is 5 p.m. Wednesday.

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To see more of The Herald, or to subscribe to the newspaper, go to http://www.heraldonline.com.

Copyright (c) 2008, The Herald, Rock Hill, S.C.

Distributed by McClatchy-Tribune Information Services.

For reprints, email [email protected], call 800-374-7985 or 847-635-6550, send a fax to 847-635-6968, or write to The Permissions Group Inc., 1247 Milwaukee Ave., Suite 303, Glenview, IL 60025, USA.

NASDAQ-OTCBB:FCIS, NYSE:AFL,

By Winston Townsend, The Miami Herald

Jun. 15–It’s 5 a.m. When the phone rings at that hour, it’s never good.

This time, it’s as bad as it gets.

Daddy, George is dead!

My daughter, Stephanie, mother of three small girls and pregnant with a fourth, has just found her husband lifeless in their bed in Ashburn, Va. He was 41, born the year before my wife, Robin, and I were married. He died of sleep apnea.

Daddy, I need you here now!

Over the next seven hours, I get a flight, pack fast and land at Dulles International Airport. Somehow, I feel as if I’m on the outside looking at an event that just must not be real.

But it is.

On the plane, I take some time to work out a game plan. When we arrive, I understand my role: Try, somehow, to make this family whole again.

This is the kind of work fathers do. They repair what’s broken. They make safe homes for children in an unpredictable, dangerous world. These responsibilities are now mine, again, at 62, 20 years after Stephanie left home.

I remember my mama once telling me that God never hands you more than you can handle. I hope she was right.

On that morning, Feb. 17, 2006, six lives were about to change in ways none of us could have imagined. Courtney, 7, Ryley, 3, and Sydney, 1, would grow up without the daddy they loved. Oakley would never even know him.

Stephanie is now a 40-year-old widow. Robin and I, empty nesters for two decades — with all the flexibility and tranquility that implies — are about to roll back the calendar to a time of bedtime stories, PTA meetings and endless laundry.

MOVING FORWARD

The memorial service goes well, if those things ever go well. There’s a large portrait of George wearing a hockey jersey — he coached a youth-league team — and a montage of family pictures that a neighbor assembled.

After the service, everyone returns to the house to share food and memories. In a quiet moment, I see Ryley looking at the pictures of her daddy, kneeling and putting her hand on his chest in the big picture.

That’s when I finally lose it.

But we quickly start planning for our new lives: Robin retires from her job performing mammogram examinations at Homestead Hospital. She’ll help Stephanie and the girls move to our five-acre grove in the Redland when school ends. Our avocados, mangoes, lychees and limes are soon going to have little girls enjoying them.

I begin remodeling our house.

My plan is to carve out some temporary storage, to handle the influx until we can build an addition. I’m creating closets wherever there’s space. I’m building backyard playground equipment — things I never thought would be in our yard.

But then, I didn’t imagine child car seats in my pickup either, or that I’d be helping to settle my young son-in-law’s estate.

Moving day in mid-July: Who knew that they make moving vans that huge? The driver says it’s the biggest load ever in his truck, and that monster is 53 feet long.

We somehow manage to stow everything and start the process of meshing as a family. I’m now not only a proud granddaddy, but the father figure to these beautiful children — not to mention homework tutor and driver (to school, field trips, class parties, soccer, church).

At times I’m convinced that my life will never again be made up of complete sentences.

Overprotective? I worry about the girls’ safety to a point that Robin and Stephanie think I’m nuts. I have to learn that life will hand them some scrapes and bruises and they will recover.

They’ve already survived the greatest hurt of all.

A TRANSFORMATION

The girls have changed me in ways I didn’t anticipate. I grew up attending church but somehow got away from it. They attend school at Saint John’s Episcopal in Homestead, which has drawn me closer to the church. That, in turn, has brought me comfort, and helped me move forward. (Ryley, the observant one, says I look like a bald monk when I put on an alb and help at the altar during Sunday services.)

School nights: I come home to hugs. They call me Papa or Papa Poo or, if they’ve had a Spanish lesson that day, Papi. They can call me whatever they want; my heart melts when they wrap their arms around me.

Bath time: Things can go from calm to hurricane vortex and back again in two minutes. Try explaining to three soaked and shrieking little girls that the palmetto bug really won’t hurt you.

Spring break: Disney World. Where else? Mouse ears in quadruplicate, please.

Oct. 24, 2006: The most emotional day for me — for the whole family — since George died. Stephanie is in labor. I’m downtown when the word comes, and I need to pick up Courtney from school and get to Baptist Hospital ASAP.

Oakley enters the world about the same time Courtney and I enter the room. For a moment, I think I’m going to faint, but I don’t tell anybody. I can’t cry — tough men don’t do that, right? Later, I step away for a few minutes alone, and let it go.

It’s a cocktail of tears: happy tears because I’m living this beautiful event; sad that the person who created this baby isn’t here to share in the joy of her arrival.

It’s easy to tell that these four girls are sisters.

Courtney is very much the big sister. I see her as the troop leader.

Ryley is a charmer. The other day, I was getting after her for doing something she shouldn’t have and she interrupted, saying, “Papa . . . I need a hug.” The scolding stopped right there.

Sydney is the girly girl, the one who just has to wear heels when they play dress-up.

And Oakley is flowering before our eyes. Every day is a new surprise for me watching her grow.

Each day brings a new adventure, and I have to work hard at keeping things in perspective — remembering that children don’t deal from the same playbook we do. Robin and Stephanie are pros at the perspective thing; I’m working on it.

Maybe it’s a guy thing. I have always been able to fix most problems — not always to everyone’s satisfaction, but I try. When Stephanie has a tough day, she says she wants her life back. Those days, it’s rough being a daddy. I can’t fix that.

SEEKING A BALANCE

Each day, I pray for the wisdom to strike the right balance of love, hope, faith, fun and discipline for these girls. Some days, the mountain seems too high to climb, but somehow we get to the top. Then we head for the next one.

In between, there are valleys where my girls bloom and grow.

The other day, Courtney, Ryley and Sydney, wearing sun hats and toting water bottles in their wagon, headed toward the grove where the lychees are ripening and the little avocados hang, bright and green.

Courtney called it a field trip on “their” property to see how many different fruits they could identify.

“Their” property. They feel ownership and a sense of belonging. I smile.

You don’t try to do right by your kids because there’s a big payoff somewhere down the line. But just in case fate decides I’m entitled to one, this is what I’d ask: Let me stick around long enough to see these little girls grow to adulthood. Let me walk each of them down the aisle.

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To see more of The Miami Herald or to subscribe to the newspaper, go to http://www.herald.com.

Copyright (c) 2008, The Miami Herald

Distributed by McClatchy-Tribune Information Services.

For reprints, email [email protected], call 800-374-7985 or 847-635-6550, send a fax to 847-635-6968, or write to The Permissions Group Inc., 1247 Milwaukee Ave., Suite 303, Glenview, IL 60025, USA.

By Louise Continelli, The Buffalo News, N.Y.

Jun. 15–Today on Father’s Day Jennifer Case of Buffalo feels especially fortunate she has her dad.

How great is a father’s love? Robert Case gave his daughter his own kidney.

“He gave me life twice,” Jennifer said.

Today also is the Walk this Father’s Day in Kidney Walk 2008 event, taking place at Dunn Tire Park beginning at 10 a. m.

Both Cases are doing so well, they also participated in the Mother’s Day Elephant Run in Delaware Park to benefit the Marcena Lozano Memorial Scholarship Fund, helping young people who have had a second chance at life obtain an education to secure their future.

This morning’s walkers include former Buffalo Sabre Ric Seiling, whose 15-year-old son Jeremy was diagnosed at age 12 with IgA nephropathy, an autoimmune disease that can lead to kidney failure.

A shockingly high number of Western New Yorkers — 170,000 — experience chronic kidney disease, according to the the National Kidney Foundation of Western New York.

Jennifer, a nursing student who has benefited from the Marcena scholarship, was once on the other side of that medical clipboard, having been diagnosed with end-stage renal disease.

At first she thought she just had the flu.

But it was “a long bout,” she said, recalling a “bloody nose, hiccups, swollen ankles and hands, shortness of breath.”

“I couldn’t lie down; I couldn’t breathe because of all the fluid in my chest. I couldn’t walk more than 10 feet without stopping. I had all the classic symptoms of renal failure.”

She was told she would need a kidney transplant. And finding the donor was assured.

“She’s my daughter,” Bob Case said. “I had no second thoughts.”

On Oct. 16, 2001, she received her new kidney — after six months of dialysis to get healthy enough for the operation.

“My father and I went through many tests and exams to make sure we were both healthy enough to go through the transplant process. My dad was in the hospital for 1z 2/3 1/2 y 1/3 and I was in for 10. I’m doing great and so is my father,” Jennifer said.

The surgery was a life-altering event in other ways.

“I decided to become a nurse because of all the caring and compassionate nurses I have come in contact with during my illness at ECMC,” said Jennifer, who graduates from Trocaire College next year. “I hope to be able to affect one person, the way they have, and continue to affect me. My goal is to be a dialysis nurse.”

And she will be able to do that with the help of Lori and Kevin Lozano, who chose her as one of the Marcena Lozano Scholarship recipients. The scholarship is named after their late daughter Marcena, who won three gold medals in swimming at the U. S. Transplant Games at the University of Utah, and underwent two heart transplants.

Have an idea about a local person whose life would make a good profile or a neighborhood issue worth exploring? Write to: Louise Continelli, Sunday Profile, The Buffalo News, P. O. Box 100, Buffalo, NY 14240

Or e-mail [email protected]

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To see more of The Buffalo News, N.Y., or to subscribe to the newspaper, go to http://www.buffalonews.com.

Copyright (c) 2008, The Buffalo News, N.Y.

Distributed by McClatchy-Tribune Information Services.

For reprints, email [email protected], call 800-374-7985 or 847-635-6550, send a fax to 847-635-6968, or write to The Permissions Group Inc., 1247 Milwaukee Ave., Suite 303, Glenview, IL 60025, USA.

By Madison Park, The Baltimore Sun

Jun. 15–Will was the model student, lacrosse captain, student president at school. The Harford Technical High School whiz landed a four-year scholarship to the Johns Hopkins University. Everyone who knew William Garrett said the intelligent, affable teenager would one day be the president.

Soon after arriving at college, he started hearing voices. Will accused his father of poisoning their dog. His grades in college began to falter. And he began seeing things, said his younger sister, Nicole Kanyuch.

Nicole, 14, told the story of her older brother, who was diagnosed with schizophrenia last year, to a room full of police officers.

“The voices insult and aggravate him,” she said. “He worked long and hard to lead a successful life, and it was destroyed in six months.”

She spoke at the end of a four-day training session during which 35 police officers from five agencies policing Harford County learned about responding to situations involving people with mental health illnesses.

The purpose of the crisis-intervention training is to better understand mental illnesses and people with the conditions, said Sharon Lipford, executive director for the Office of Mental Health.

“Officers are learning skills to deescalate and stabilize the situation,” she said.

Many people with mental illnesses end up in hospital emergency rooms or at the county’s detention center, officials said.

“The Detention Center has turned into an infirmary and a homeless shelter,” said Sheriff L. Jesse Bane. “If we could remove those people from the Detention Center, we wouldn’t have to build another jail. At times, the number of who’s in there that shouldn’t be there is as high as 70 to 75 percent. When we look at that and do nothing about it, it’s shame on us.”

The Sheriff’s Office, the Maryland State Police and police officers from Harford’s three municipal departments teamed up with staff members from the county’s Office of Mental Health and Upper Chesapeake Health to create a crisis intervention team for transferring people with mental illness from police custody to mental health systems.

Officers learned about personality disorders, schizophrenia and dementia, and how to recognize them. In one lesson, they wore headphones and were assigned to perform everyday tasks while they listened to voices.

The officers are part of the crisis team and will respond to mental illness-related calls. At the end of their training Thursday, Nicole reminded them of why they were there.

“The real truth why you should care about the mentally ill is that they’re all people,” she said. “The homeless, the sick, they’re people, too. The mentally ill are people who stood before us — neighbors, friends, sisters, brothers and parents.”

[email protected]

—–

To see more of The Baltimore Sun, or to subscribe to the newspaper, go to http://www.baltimoresun.com.

Copyright (c) 2008, The Baltimore Sun

Distributed by McClatchy-Tribune Information Services.

For reprints, email [email protected], call 800-374-7985 or 847-635-6550, send a fax to 847-635-6968, or write to The Permissions Group Inc., 1247 Milwaukee Ave., Suite 303, Glenview, IL 60025, USA.

By PATRICIA WEST-BARKER

Growers: Demand for young plants soars

The sound of marimbas floated through the air as early morning shoppers greeted friends, sipped coffee and browsed through mounds of fresh greens, radishes, spring onions, garlic, blood-red cherries and crisp green peas of all varieties. The Santa Fe Farmers Market was in full swing in the PERA parking lot on Paseo de Peralta on Saturday morning.

Despite almost a month of bulletins from the U.S. Food and Drug Administration about the suspected link between certain types of raw tomatoes and the salmonella outbreak that has sickened hundreds of Americans, none of the four vendors who sell only tomatoes lacked for customers.

Most were not aware that Saturday New Mexico was officially added to the FDA list of areas not associated with the outbreak.

But things had not looked so rosy for at least one vendor Friday morning. Consumer confusion and the potential loss of some commercial accounts had put a hold on their orders until the FDA officially cleared New Mexico-grown tomatoes. That motivated Kim and Steve Martin of Alcalde-based Growing Opportunities to get in touch with a number of state and federal agencies handling the salmonella investigation.

The staff of U.S. Sen. Jeff Bingaman was helpful in getting New Mexico-grown tomatoes onto the list, Kim Martin said, as was the traceback team at the FDA’s Washington, D.C., office, and the New Mexico

secretary of agriculture. Once the FDA was assured, in writing, by state authorities that no New Mexico-grown tomatoes were ever shipped out of the state, Kim Martin said, the federal agency moved quickly to declare the local produce safe and include it in a Web site update Saturday.

Even the loss of a large delivery or two could have impacted their business by thousands of dollars, Kim Martin said, and threatened their livelihood.

“Our state government was so responsive and understanding of our concerns once they knew (the warnings were having) an effect on local growers,” Kim Martin said. “We applaud them,” she added, smiling as she weighed a bag of her hydroponically grown tomatoes for the next customer.

Other vendors were less affected by the crisis.

Ross Bird, who owns Ross’ Tomatoes in Estancia, has been selling his hothouse-grown, pesticide-free beefsteak tomatoes at market for several months. He hasn’t noticed any change in his sales, he said, since the New Mexico Department of Health and the FDA began issuing salmonella warnings associated with large, red, raw, round and Roma tomatoes in late May. “I’ve been selling out since spring,” Bird said, noting he still had no tomatoes left at the end of the day.

Robert Ensor, who had a printout of the FDA salmonella warning posted in a corner of his booth, concurred with Bird. He thought the number of hydroponically grown Taos tomatoes he was selling was about the same as it had been before the outbreak. “It’s consistent,” Ensor said. “But people do want to be reassured.”

Paul Cross, the farmer/owner of Charybda Farms in Arroyo Hondo, sells 12 kinds of large, round, red dirt-grown organic tomatoes he started in a greenhouse Jan. 29. He also sells tomato plants through Santa Fe Greenhouses, Wild Oats, Whole Foods, La Montanita and Vitamin Cottage.

Unlike Bird and Ensor, Cross had noticed a drop in sales of his fresh tomatoes in the past few weeks — “people are scared,” he said — but he’s also seen an increased demand for his tomato plants, perhaps the result of home gardeners deciding the only tomatoes they could trust were those they’d grown themselves.

Charlene Cerny of Santa Fe purchased a yellow pear tomato plant because she likes that particular variety, she said, not because she was worried about salmonella. But when asked if she felt safer buying locally grown tomatoes at the farmers market, she looked surprised. She hadn’t realized the rich red orbs surrounding her were on the FDA’s list of approved tomato purchases, she said. “I didn’t get that message,” she said. “I thought that ‘locally grown’ meant grown in the backyard.”

Contact New Mexican food editor Patricia West-Barker at 986-3085 or [email protected].

(c) 2008 The Santa Fe New Mexican. Provided by ProQuest Information and Learning. All rights Reserved.

By SANDRA J PENNECKE

By Sandra J. Pennecke

Correspondent

Each time life has thrown Margaret Morton a curveball, she’s caught it and turned it into an opportunity to help others.

Morton, 79, was recently awarded the William G. Ashman Lifetime Achievement Award for 20 years of service with the Retired and Senior Volunteer Program .

She received the honor recently during the Senior Services of Southeastern Virginia’s 33rd annual luncheon .

A 1947 graduate of Maury High School, Morton is vice president of Grief and Loss, formerly Widowed Persons Service, a support group for those who have lost spouses .

The group, with about 35 members, meets weekly at First Baptist Church of Norfolk, 312 Kempsville Road , and at Virginia Beach Christian Church to hear speakers, enjoy potluck dinners, play cards, take outings and work through their grief.

Morton’s late husband, Gordon , who was the first chapter president for AARP Chapter 4212 , recommended her for the position in 1988.

“They needed someone to fill the president of the widowed person group, and he said I could do it,” she said, explaining that she and Gordon were both widowed from their first spouses. She married Gordon in 1986.

Her experience with losing a spouse enabled her to help others. When Gordon, known as Mr. AARP, died six years ago, Morton found herself leaning on the same group she ran.

“I did what I tell people to do,” Morton said. “Widowhood is something you can’t imagine what to experience until you experience it.”

The group focuses on getting widows and widowers of all ages back on their feet to continue living. “We want to make sure they are able to take care of themselves,” she said.

The mother of two and grandmother of three also serves on the auxiliary board at Lake Taylor Transitional Care Hospital, the same place she sought help following knee replacement surgeries and a back injury.

She is a health representative with AARP Chapter 4212 and, as a breast cancer survivor, also volunteers with Reach to Recovery , sharing her experience with recently diagnosed breast cancer patients.

For the past 18 years, Morton has worked two days a week as a bookkeeper and teaches Sunday school at Community United Methodist Church in Virginia Beach. She also serves on Stephen Ministries, a one-on-one ministry to help people experiencing tough times sort out their options.

“Margaret is an exceptional volunteer,” said Bob Jarrell , RSVP coordinator. “She’s served on boards, councils, committees and special projects.

“People like the Mortons get down and get their hands dirty to help the people who really need the help. They want to make a difference and she truly does.”

Said Morton: “I hope I can do this until the day I die.”

Sandra J. Pennecke, [email protected]

going?

What Grief and Loss, a support group for those who have lost spouses, is open to all ages

Virginia Beach 1 to 2:30 p.m. Thursdays at Virginia Beach Christian Church, 2225 Rose Hall Drive. Call 481-3494.

Norfolk 7 to 8:30 p.m. Tuesdays at First Baptist Church of Norfolk, 312 Kempsville Road. Call 461-3226.

going?

What Grief and Loss, a support group for those who have lost spouses, is open to all ages

Virginia Beach 1 to 2:30 p.m. Thursdays at Virginia Beach Christian Church, 2225 Rose Hall Drive. Call 481-3494.

Norfolk 7 to 8:30 p.m. Tuesdays at First Baptist Church Norfolk, 312 Kempsville Road. Call 461-3226.

Originally published by BY SANDRA J. PENNECKE.

(c) 2008 Virginian – Pilot. Provided by ProQuest Information and Learning. All rights Reserved.

By Pamela Hale-Burns

Described as a man who inspired change, Dr. Matthew Owen Locks was proud to see the possible presidential nomination of an African- American or of a woman.

But he wouldn’t get to witness it. The 89-year-old died of heart failure only hours before the Democratic nomination was apparently sewn up by Sen. Barack Obama on June 3.

“We were watching the results on the television in his hospital room,” said his daughter, Wendy Locks.

Born and raised in New York City, he received his bachelor’s degree from Cornell University in 1940 and went on to graduate at the top of his class from Cornell University Medical College in 1943.

After his residency, he began a private medical practice in internal medicine in Westport, Conn.

In 1959 he gave up his private practice and moved his family to California to pursue a specialty in pulmonary medicine at the the Long Beach Veteran’s Administration Medical Center.

“He had a very lucrative practice, but he cared about helping people,” his daughter said. “For him it was more important to help people than to make money. He always worked in public institutions after moving here.”

As a clinician, professor and administrator, Locks contributed significantly to the pulmonary medicine field.

Throughout his 65-year career, he held many positions at several medical institutions in Southern California. He also published articles on pulmonary disease and consulted for many institutions.

In 1985 he won the Renteln Award, California’s highest honor for contributions to tuberculosis control.

“I thought he was a wonderful man,” said Dr. Helene Calvet, city health officer at Long Beach Health and Human Services who worked with Locks at the TB clinic. “Even until his last days, he had a hunger for learning things.”

Even after retiring as the medical director of Rancho Los Amigos Medical Center in 1988 at the age of 70, Locks remained active in his field.

“He was still working as a licensed physician and consultant when he passed away,” Wendy said. “He had a fascination for science and caring for human beings.”

He served as an expert reviewer and consultant for the Medical Board of California, as an expert witness for plaintiffs in medical malpractice cases, and as a clinician on mobile units for the homeless TB screening in Los Angeles County.

“When I had difficult cases, I would collect those cases and call him, and he would come in and look at chest X-rays and discuss what to do,” Calvet said.

Locks also served as treasurer of the Long Beach Area Chapter of League of Women Voters for seven years.

“He encouraged women to get education and have a career,” said daughter Nancy Locks. “He treated women with respect.”

Not only did he respect women, Locks taught his children to love and respect all mankind.

“From our childhood we learned to love all cultures and to love people,” Wendy said.

“I learned to treat people justly and to never judge people by their religion or their skin color,” Nancy said. “He taught us basic humanity and how to treat people on the basis of what kind of people they were. I think that was really important.”

When he wasn’t caring for people, Morty, as he was affectionately known, loved music and doing crossword puzzles.

“I’ll miss his company,” Nancy said. “We did crossword puzzles every Sunday and I will miss his companionship.”

Lock and his high school sweetheart, Florence, loved music and the theater. “He and my mother loved going to the theater and the Long Beach Symphony,” Wendy said.

His wife of 64 years died in 2006.

With his many contributions to medicine, Locks’ colleagues are hoping plans will be approved to name the Long Beach Health and Human Services Tuberculosis Clinic after him.

“He was not only a wonderful doctor and a wonderful person, he was a wonderful citizen,” Calvet said. “He always wanted to give back to the community.”

According to his family, Locks, at 89, was attending the Osher Lifelong Learning Center at CSULB, where he was taking digital photography, Photoshop and Shakespeare classes.

He missed his last two classes due to his illness.

“He was completely sharp up until the end,” Calvet said. “He never mentally slowed down.”

He also is survived by another daughter, Amy, his brother, Richard, and seven grandchildren.

The family asks that donations be made to CTCA Scholarship Fund, indicating the Matthew Locks Memorial Scholarship, to the California TB Controllers Association, to Friends of the Long Beach Public Library Memorial Books or to the Osher Lifelong Learning Center at CSULB.

[email protected], 562-499-1476

(c) 2008 Press-Telegram Long Beach, CA.. Provided by ProQuest Information and Learning. All rights Reserved.

REDLANDS – Summer Day Camp at the Boys & Girls Club of Redlands begins June 23 and ends Aug. 8, running from 7 a.m. to 6 p.m.

Each week will have a different theme, with Outer Space Week planned for the last week of June.

Activities at the camp will include water olympics, container gardening, arts and crafts and trips to regional parks.

Costs include a one-time $12 annual Boys & Girls Club membership fee, as well as $55 a week for travel, materials, breakfast, lunch and an afternoon snack.

Summer Day Camp is intended for children ages 6 to 12, and is limited to the first 50 who sign up.

Signups are at the Hansberger Clubhouse, 1251 Clay St., Redlands.

Information: 798-4599.

(c) 2008 Redlands Daily Facts. Provided by ProQuest Information and Learning. All rights Reserved.

ALLENTOWN, Pa. _ The quest to root out genetic diseases such as cystic fibrosis or sickle cell anemia got a powerful tool a decade ago with the development of an embryo-screening technology.

Today, in a temperature-controlled lab tucked in a nondescript building in Salisbury Township, Pa., reproductive endocrinologist Bruce Rose also uses the emerging technology in a more controversial way: To help couples choose the sex of their babies.

The practice _ condemned in some religious and medical circles mostly because it involves discarding unwanted embryos _ was non-existent a decade ago, but is now offered in nearly half of the nation’s fertility clinics.

“We have the capability, we know it’s effective and we think it’s a choice patients should be allowed to make,” said Rose, who performs three to five gender-selection procedures a year from his practice, Infertility Solutions.

The technique _ Pre-Implantation Genetic Diagnosis _ is banned in many European countries for sex selection. However, no regulations or laws about how it should be used exist in the United States.

But Rose, who also uses the technology to screen for genetic diseases, said the procedure fulfills a centuries-old quest to choose the sex of a baby _ though he said the procedure is too costly, complex and invasive to spark any kind of widespread demand.

Critics worry that using the technology to choose gender is a first step toward designer babies, a move that could tempt couples to one day ask doctors to probe embryos to control traits like eye color or sexual orientation.

“Gender is not a disease and not something clinics should be testing for,” said Art Caplan, executive director of the Center for Bioethics at the University of Pennsylvania. “It’s not the way medicine should be going. It’s really the first step towards designing babies.”

For area clinics offering PGD for gender selection _ in Salisbury, Bucks County and Reading _ family balance is the primary motivator for clients.

“This is not a situation in which any one is saying that boys or girls are better than one another,” said Rose, who began using PGD for sex selection in 2004. “It’s for family balancing. They have a couple of boys and just want to see what life would be like with a girl baby. Those who go through this do this totally out of love _ not for low-end reasons.”

According to a 2006 study by Johns Hopkins Genetics and Public Policy Center, 42 percent of the country’s 415 fertility clinics surveyed offered clients the service of choosing the gender of their baby, though guidelines for the procedures vary widely from clinic to clinic.

For example, the Reproductive Science Institute, which has offices in Bucks County and Reading, advertises PGD on its Web site, but states that it will administer PGD for gender selection only if a woman is between 18 and 39, married and has at least one other child.

Though some local fertility doctors advertise the procedure on their Web sites, few area doctors will openly discuss it. Little information exists on exactly where and how often the procedure is performed for sex selection.

The Johns Hopkins survey, which kept clinics’ location and names confidential, found that many doctors grappled with ethical challenges and refused to use the high-tech procedure to meddle with fate.

“Couples for millenniums have attempted to control the sex of future children; there are all kinds of folk tales on how to do it. Well, here is a way for it to be done scientifically,” said Susanna Baruch, the director of reproductive genetics at Johns Hopkins and lead author of the study, which does not take a position on the issue. “Science has permitted it, but who is responsible for setting limits if limits are appropriate? Are the doctors responsible or are the patients?”

Baruch said most hospitals refuse to allow PGD for gender selection, a position that is reflected locally. Lehigh Valley Hospital reserves PGD for medically justifiable cases only. St. Luke’s Hospital doesn’t offer the procedure. Sacred Heart Hospital, a Catholic-run institution, refuses to screen embryos outside the body for any reason.

Yet Caplan, the bioethicist, agrees some gray areas exist when it comes to high-tech tinkering. Using the procedure to choose gender for family-balancing reasons “is arguable,” he said.

“I think there may be a family with four boys who wants a girl; that argument has a little bit of clout if they want a different child-bearing experience,” he said. “It makes a little sense.”

Denise Cummins, a labor and delivery nurse from Sacramento, Calif., said it’s difficult to explain the emotional pull that led her to make a choice that most people question.

But the mother of five boys wanted a girl, and she learned about the embryo-screening technique to stack the odds in her favor. She poured more than $11,000 into the first procedure, which identified the gender of a fertilized egg before it was implanted in her womb. It didn’t result in a pregnancy the first time. But after her second try a year later, which cost another $12,000, she got her girl.

“It was a desire that was in my heart and I couldn’t explain why it was there or why it wouldn’t go away,” Cummins said. “I wanted a daughter, and I wanted a guarantee of gender and that seemed like the only way to do it.”

Rose said he uses two procedures to help couples choose one sex over the other _ MicroSort, a sperm-sorting method that’s done before conception and doesn’t necessarily create excess embryos. Then there is PGD, the more controversial and more accurate procedure that involves creating embryos, fertilizing them through in-vitro fertilization _ removing a cell from the embryo and testing it for male or female chromosomes. Embryos of the desired sex are then transferred to the womb. Embryos of the undesired sex are frozen, donated or discarded _ a decision left up to the patient to decide, Rose said.

The Rev. John Hilferty, chairman of Sacred Heart Hospital’s ethics committee, said the destruction of embryos is the moral equivalent of abortion. The procedure, he wrote in a prepared statement, “violates the fundamental moral teachings of the Catholic Church” since it involves “choosing embryonic human beings with normal or desirable genetic characteristics to continue living and then destroying those embryonic human beings with unwanted characteristics.”

Rose said the fate of the embryo should be left up to the patient.

“Once an embryo is created, it is up to the person they belong to _ the source of the cell that made up that embryo _ to decide what they think is best for that embryo,” Rose said.

Not many people get to that point, though. Less than 5 percent of patients undergoing in-vitro fertilization opt for PGD to choose the gender of their baby, he said. Once the procedure is explained, the complexities and risks dissuade most people from attempting it, Rose said.

“If you could select the sex of a baby, for example, by just eating celery for two weeks, people would do gender selection,” said Rose, adding that insurance doesn’t typically cover the procedure. “But the whole process of going through it and getting involved in this part of life is not something most people want to do.”

However, he believes it’s important that patients are informed and allowed to make their own choices.

“If people have the ability to pay for the technology and think it will enrich their lives by having another child of a different sex, I think it’s a good thing,” he said. “We make choices all the time that are much more expensive and much more frivolous.”

Jolene Sedano believes in gender selection, but even as a mother who worked to sway the gender of her third child, there were boundaries that she wouldn’t cross.

The 31-year-old remembers the day she was told by doctors her third baby would be a boy, news that left her in tears _ since she had two boys and desperately wanted a girl.

“That’s when we thought about going high-tech,” she said.

But PGD, she said, wasn’t an option since it required discarding or donating embryos.

“Being a Catholic, I couldn’t do that. It’s discarding of life and it’s against my faith,” Sedano said. “I looked into sperm sorting, but at the end of the day, we thought it was too much of playing God.”

Instead, Sedano purchased a book, “Choose the Sex of Your Baby” that introduced her to a gender-swaying method _ dubbed the Shettles technique _ one she believes helped her produce a girl. The Shettles’ theory suggests that _ since male sperm swim faster, but die faster than female sperm _ couples should have sex three days before ovulation to conceive a girl. Though she opted against PGD, she understands the emotional experience that drives people to more invasive options.

“There are too many people out there like me who feel bad about their feelings to want a girl or a boy,” Sedano said. “It’s a desire, not disappointment that drives this. There is nothing wrong with boys, but you want the chance to raise both.”

Wendy Schillings, a reproductive endocrinologist at Lehigh Valley Hospital, said she is approached weekly by patients who want to know what they can do to have a boy or a girl. Most of them aren’t seriously seeking gender selection, she said, but they have a preference. Some, however, want to know how technology can help.

“Once I tell them what’s involved, they back away on their own,” Schillings said.

David Adamson, president of the American Society for Reproductive Medicine, said the group recommends against sex selection for nonmedical reasons, though the decision to offer the service is ultimately in the hands of doctors and clinics. Overall, doctors are not the ones pushing it, he said.

“The reason it’s occurring is because patients are demanding it,” said Adamson, adding that the practice, at this time, is not widespread enough for consequences to skew the population. “It’s driven by people’s desires. There have and will be some people who for whatever reason prefer to have one gender over the other.”

New York fertility specialist Norbert Gleicher was one of the first doctors in the nation to offer the procedure for gender selection. Gleicher, chairman of the Center for Human Reproduction in Manhattan, said he wrote the ASRM a letter in 2001, asking the group to take a position on gender selection procedures. In a 2001 statement, the society’s ethics committee discouraged PGD for non-medical reasons, but found that sperm-sorting _ the form of gender selection that doesn’t require the discarding of embryos _ is acceptable for family balancing.

“Up to that point, no one in the profession offered any form of gender selection,” said Gleicher, who added that it was almost taboo for doctors to talk about. “There were doctors up and down Park Avenue offering sperm-sorting, but nothing was proven to work and it wasn’t taken seriously. Now, we have a technology that’s really accurate.”

Though the ASRM ruled that sperm sorting was ethically acceptable, but PGD, was not, Gleicher said he felt it was his obligation to give patients a choice in the type of technology used.

“A decade ago, if I was approached about gender selection, I simply said, `we don’t do that,'” he said. “Once it was declared ethically appropriate, I have the obligation to offer it in the best and most responsible way. If there is a superior method of doing something, we have an obligation of telling patients and making it available to them.”

Annette Lee, of Abington Reproductive Medicine in Montgomery County, however, refuses to do PGD for gender selection. She said her clinic performs PGD to screen for gender-linked diseases but refers patients who want the procedure strictly for gender-selection to other area clinics.

“It’s more of an ethical dilemma for myself,” she said. “A lot of us went into this field to help people create babies. In this case, it seems like you’re knowingly creating embryos that have no chance. It goes against what we set out to do.”

Lee also said PGD offers little guarantee of success _ since there is no way of knowing how many embryos of the desired sex can be produced. She said it can be a long, drawn-out procedure that doesn’t result in pregnancy.

“There’s a 50 percent chance that a couple may spend $15,000 and end up with nothing,” said Lee, adding that older women face greater odds.

Cummins experienced that disappointment first hand _ when her first shot at PGD didn’t work.

“It was emotionally devastating to go through all that, know you have two female embryos and not get pregnant,” she said. “I never thought it wouldn’t work because I’m fertile. But it’s not a guarantee.”

On her second try, Cummins merged two gender-selection technologies, investing in MicroSort the sperm-sorting method and PGD. In April 2004, her baby girl Leigha was born.

“I did what I felt I needed to do,” said Cummins, who works as a labor and delivery nurse. “I’m thrilled with my boys and adore them. That wasn’t the issue. Something in my heart yearned for a girl, that relationship between mother and daughter. There was a drive in my heart led me down this path. I don’t have one regret.”

___

(c) 2008, The Morning Call (Allentown, Pa.)

Visit The Morning Call at http://www.mcall.com/

Distributed by McClatchy-Tribune Information Services.

For reprints, email [email protected], call 800-374-7985 or 847-635-6550, send a fax to 847-635-6968, or write to The Permissions Group Inc., 1247 Milwaukee Ave., Suite 303, Glenview, IL 60025, USA.

Homeopathy student Jacqui Schwartz will be providing advice about natural health solutions at Boots The Chemist at Exe Bridges, Exeter, next Thursday as part of Homeopathy Awareness Week.

Ms Schwartz will explain how homeopathy can help with everyday health issues between 2pm and 5pm.

The aim of the awareness week is to introduce and help people understand how homeopathic remedies work to help tackle problems by triggering the body’s system of healing. Homeopathy particularly helps people with allergies and is popular with many high profile people and celebrities including Prince Charles.

Natural healthcare specialist Nelsons has launched a new website with information and a free health guide available from www.healingthroughhomeopathy.com.

(c) 2008 Express & Echo (Exeter UK). Provided by ProQuest Information and Learning. All rights Reserved.

MINNEAPOLIS, Minn. _ Far from home, Lonni Mooreland has been cuddling her 9-month-old daughter a little more. Smelling her baby’s hair. Feeling, deep in the pit of her stomach, how fleeting that baby scent might be.

On Friday, Lonni and Jay Mooreland learned that researchers had judged their daughter healthy enough to undergo an experimental treatment that could save her from an excruciating disease or kill her.

The Folsom, Calif., family has been in Minneapolis for two weeks, preparing for daughter Sarah to become the third child in the world to get a bone marrow transplant that might cure a rare disease called epidermolysis bullosa.

Their doctor was blunt. The transplant itself can be lethal somewhere between 8 percent and 20 percent of the time.

“It is very scary,” Lonni Mooreland said. “You weigh that vs. a lifetime of pain, to die in her teens or early 20s from skin cancer or something else.”

Epidermolysis bullosa, or EB, is the latest in a string of once incurable diseases that could be yielding ground to the stem cells contained in bone marrow, umbilical cord blood or elsewhere in the body.

Bone marrow transplants, once primarily used in cancer treatment, have cured sickle cell anemia and other genetic disorders.

Stem cells from marrow and cord blood are being used or considered for a wide range of inborn errors, when the complex mechanics that maintain the human body miss a step, with shattering consequences.

In the recessive dystrophic form of EB that Sarah Mooreland has, what’s missing is the ability to produce collagen type VII. That’s a protein that helps form the little anchors that attach the upper layer of skin to the one beneath it.

Without those anchors between epidermis and dermis, the skin simply rubs away. At the slightest friction, skin sloughs off the body. Internally, linings of the mouth, stomach and intestines can blister and erode.

“This is one of the worst diseases I’ve ever seen,” said Dr. John Wagner, head of clinical research at the University of Minnesota’s stem cell institute. “It’s painful. It’s scar-forming. If you would see pictures of 17- and 18-year-olds, you would be horrified.”

There are kinder versions, but Sarah Mooreland’s form of EB turns the body into a mass of painful wounds. Children must be wrapped and bandaged, but still they blister. Toes and fingers fuse together. The scarring skin contracts around joints. Digestion is so badly disabled that a teenager can weigh 50 pounds.

If they outlast malnutrition and infection, people with this variant of EB die in their teens or 20s of skin cancer triggered by the constant cellular breakdown and repair.

At the University of Minnesota, a research review committee agreed the disease is so virulent it merits a dangerous counterattack even in a little girl whose kidneys already are impaired.

The committee met Thursday to wrestle with whether Sarah Mooreland is healthy enough to undergo a transplant. Her own bone marrow will have to be killed with chemotherapy before she can get new marrow from her brother, a well-matched donor. But kidney problems unrelated to her EB have left her with roughly half of normal kidney function, potentially making the chemo risker.

Wagner and the Moorelands got the answer Friday. Go ahead.

Sarah Mooreland will get a bone marrow transplant with a twist.

Bone marrow can be filtered to optimize the types of stem cells needed to treat certain diseases. Based on work his colleagues did in mice, Wagner believes the standard filtration would not work, because it would screen out whatever seems to help the body make collagen VII. So, he is doing very little treatment on the bone marrow before transferring it.

Wagner is cryptic about the details because he wants his work to be peer reviewed and published, and scholarly journals frown on having data discussed first in a newspaper.

“This is not the way we normally do things,” said Wagner. “I typically communicate to the medical community first, then the families hear about it.”

Nothing about the evolution of this treatment was typical.

Wagner is known for his work in cord blood transplants. He is noted or notorious for helping parents of children with genetic diseases give birth to a child that could be a donor for its sibling.

“He’s very solid. He’s not a person who does the wrong things,” said Dr. Rainer Storb, who heads the transplantation biology program at the Fred Hutchinson Cancer Research Center in Seattle. At the same time, though, “John Wagner especially likes publicity. It’s just his style,” Storb said.

Four years ago, when Wagner was giving a talk in New York City, a mother of two sons with EB asked him to try a cord blood transplant.

He said no, not without doing animal research to see if that could even work.

Wagner had plenty of leukemia research funds, but nothing for EB. So the mother, Theresa Liao, went out and raised about $40,000. Wagner found a little more. His colleagues tested different approaches on mice that have a form of EB, and they were able to cure three of them.

Partly because of Liao’s fundraising, and partly because of the closeness of parents whose children have EB, Wagner said, there has been publicity all along the way.

“We’re all watching with great interest and anxiety and enthusiasm,” said Lynn Anderson, a Bay Area woman who lost two children to EB and co-founded the EB Medical Research Foundation. “I can’t say how much I am hoping it will work.”

Her foundation has helped fund researchers at Stanford University who are working on genetically altered skin as a potential treatment. They are still awaiting FDA approval to try that gene therapy for people 18 and older. The Stanford researchers won’t start out on children, and they won’t venture an opinion about Wagner’s work, because they haven’t seen his data or peer-reviewed results.

“This isn’t a competition,” Wagner said.

Ultimately, doctors will opt for whatever is safest and works best. No one knows yet what that will be.

After the success in just a few mice, Wagner did the first bone marrow transplant for EB last fall in Theresa Liao’s son Nate. An older son, Jake, got the second transplant two weeks ago, once it was clear that Nate was producing collagen VII although not as much as a healthy person would.

So far Jake, who didn’t have as closely matched a donor, isn’t doing as well as his brother something that made Lonni Mooreland’s heart sink when she heard it earlier this week.

Still, she and her husband are ready for Sarah to get transplant No.3.

The Moorelands have been living since early June in a two-bedroom hotel suite a crunch for a family with a 5-year-old, a 3-year-old, and a baby who needs regular bandage changes and has to be fed through a tube because she cannot swallow.

When the medical tests let up a little this past week, the Moorelands took their kids to the children’s museum, and put them on rides at the Mall of America’s amusement park.

The zoo is next on their list, along with one essential thing before Sarah’s treatment starts this week.

The Moorelands have only one family portrait of all five of them, a shot taken soon after Sarah was born that doesn’t really capture her personality, her mother said.

Lonni Mooreland wants to make sure they take one more.

___

(c) 2008, The Sacramento Bee (Sacramento, Calif.).

Visit The Sacramento Bee online at http://www.sacbee.com/

Distributed by McClatchy-Tribune Information Services. For reprints, email [email protected], call 800-374-7985 or 847-635-6550, send a fax to 847-635-6968, or write to The Permissions Group Inc., 1247 Milwaukee Ave., Suite 303, Glenview, IL 60025, USA.

GULFPORT, Miss. _ A federal magistrate has denied bond again for a doctor and pharmacist whose support group is so strong that friends had offered to mortgage their homes to raise bail money.

And in the doctor’s case, a half-dozen people were willing to take her place in jail pending trial Aug. 18.

“I’ve never seen anything like it,” said Michael W. Crosby, a Gulfport, Miss., attorney representing Dr. Victoria Van.

Van and pharmacist Nick Tran were allowed re-consideration of bond Friday. They’re accused of conspiring to dispense controlled substances outside the scope of professional practice.

Or as a DEA agent has testified, they’re accused of providing prescriptions to drug-seekers without proper examination, leading to an influx of narcotics on the street and contributing to at least nine deaths by drug overdose.

U.S. Magistrate Judge John M. Roper heard new information Friday from attorneys hired after the defendants’ arrests May 21. Roper decided he still considers them flight risks for reasons including the possibility of hidden assets, especially for Van and her husband, and Tran’s questionable transfers of money.

“I remain of the opinion that there is no condition of release that will ensure their future appearance,” Roper said.

Also charged in the 22-count indictment are Van’s husband, Dr. Thomas Trieu, and Richard Trieu, their office manager at the now-closed Family Medical Center in Biloxi, Miss.

Crosby and Tran’s attorney, Albert Fong of Houston, presented testimonials describing Van’s and Tran’s character and efforts to help others. Both were educated in America after they fled Vietnam with their families in 1975 during the fall of Saigon to communism.

Van’s father, pastor of a California church, was among about 50 people who showed up Friday for moral support. Van has done mission work and devoted her life to helping the impoverished, including survivors of Hurricane Katrina, her attorney said.

She and her husband have two toddlers.

Tran wept openly as a neighbor and golf buddy testified he would house him and drive him to work at a $12-an-hour job as a hotel clerk if given bond. Tran claimed $1.9 million in gross receipts on his 2006 income taxes. He’s not trying to hide money, his attorney said.

Tran is accused of filling 18 questionable prescriptions and Van is accused of writing two questionable prescriptions. Van’s attorney said the prescriptions were for a patient of her husband who had run out of refills and needed a cough syrup. Van was the clinic’s pediatrician, said Crosby, and primarily treated children and women.

DEA Agent Terry Davis said he was suspicious of $38,000 Tran paid a company whose primary business appears to be wiring money. Tran also wrote checks totaling $85,000 to two casinos, raising concerns of a gambling problem, Davis said.

Crosby accused the DEA of unfairly targeting the defendants. In questioning, Davis confirmed no medical experts had been called in to review records or allegations before the arrests were made.

Assistant U.S. Attorney John Meynardie said a medical expert has been hired, but records from the clinic are being scanned and have not yet been reviewed.

“I’m astounded,” said Crosby, “that they could let a DEA agent decide what’s a proper medical exam without allowing a licensed medical doctor to review it. They just threw them all in jail. If the DEA had concerns about the clinic, believed people were taking advantage of them or that lives were at stake, then why didn’t they go to the doctors and discuss it with them?”

The drugs in question are hydrocodone (Lortab), alprazalom (Xanax) and the cough syrup promethazine with codeine (Phenergan with codeine).

The clinic didn’t prescribe stronger, more commonly abused drugs such as Oxycontin or methadone, according to Van’s written testimony. The indictment doesn’t accuse her of prescriptions involved in the alleged deaths.

___

(c) 2008, The Sun Herald (Biloxi, Miss.).

Visit The Sun Herald Online at http://www.sunherald.com/

Distributed by McClatchy-Tribune Information Services. For reprints, email [email protected], call 800-374-7985 or 847-635-6550, send a fax to 847-635-6968, or write to The Permissions Group Inc., 1247 Milwaukee Ave., Suite 303, Glenview, IL 60025, USA.

By Kandace McCoy, Mt. Vernon Register-News, Ill.

Jun. 14–MT. VERNON — Co-workers of a local woman are banding together for a benefit in her name as she battles a rapidly progressive cancer.

Gretchen Lampke, 33, formerly of Scheller and currently living in Mt. Vernon, was first diagnosed with mesothelioma last month. According to friend Tonya Isett, doctors now are not quite sure what type of cancer is progressing rapidly throughout Lampke’s body. But Isett and her co-workers are rallying behind their friend to help offset medical and transportation costs.

According to Lampke’s fiance, Sean Tolley, she was originally diagnosed with mesothelioma following a biopsy of a tumor in her abdomen. However, three weeks ago, Lampke had to undergo emergency surgery at Barnes-Jewish Hospital in St. Louis due to the tumor increasing pressure on her bowels. During the course of that surgery, doctors performed another biopsy on the tumor and studied its basic composition. Tolley said it was at that time it was discovered the cancer had become “rapidly aggressive” in a manner that mesothelioma does not.

“While [the cancer] appears to have some of the properties of mesothelioma, the doctors said it’s more like a more common cancer like ovarian — but it’s not ovarian cancer. They explained the composition of the cancer is along the same lines as if a woman had ovarian cancer,” said Tolley.

Due to the aggressive growth of the tumor, Tolley continued, doctors began chemotherapy treatment for Lampke last Friday. “That went pretty well. The doctors said there’s no way to tell if she’s responding positive, but based on the latest X-rays, it seems like the cancer has stopped.”

Lampke’s parents, Karen and Jim Lampke, have been staying with her at Barnes-Jewish Hospital day and night, while Tolley, who is a teacher at Mt. Vernon Township High School, travels back and forth to the hospital, dividing his time at Lampke’s side and back here to be with their 16-month-old son, James.

According to the National Cancer Institute, mesothelioma is a rare form of cancer in which malignant cells are found in the mesothelium, a protective sac that covers most of the body’s internal organs. Most people who develop mesothelioma have worked on jobs where they inhaled asbestos particles. However, the disease has been reported in some individuals without any known exposure to asbestos.

About 2,000 new cases of mesothelioma are diagnosed in the United States each year, the NCI reports, with the disease occurring more often in men than in women.

“She’s pretty weak and is in and out of consciousness because of pain killers and anti-nausea medication,” Tolley reported. “Her family helps out with James, and so has Barb Hamilton,” he said of a close friend and co-worker. He added that if not for Isett, Hamilton and others, the benefit would not be possible. “[They’re very] proactive. They’ve really just come together and put out 100 percent to help with bills and gas … It’s taken me by surprise how generous and kind people have been.”

“[The cancer was] spreading fast. She’s very weak and not able to talk on the phone,” Isett said. “She’s walked many miles for us, and we want to do the same for her. They say she gets better some days, and some days are bad. But she’s not well enough to accept company to see her,” Isett said.

And while Lampke’s family and Tolley stay close to her bedside, their vigil is a positive one. “I’m trying to remain as positive as I can because I’m no use to Gretchen if I drag down through the whole thing. I’ll be as useful as I can and help her when I can,” said Tolley.

Lampke is also the niece of Donna Vancil.

A trust fund has been set up in Lampke’s name, and those wishing to make donations may send them to Peoples National Bank, c/o Mark Kabat, 4413 S. 34th St., Mt. Vernon, IL 62864.

The benefit for Lampke will be held June 21 from 6 to 9:30 p.m. at the Rolland Lewis Building with entertainment from the Gospel Crusaders. A white elephant exchange and silent auction will also be held. Items on the menu include a spaghetti dinner, salad, breadsticks, dessert and drink.

Tickets can be purchased in advance or at the door and are $7.50 for adults and $3.50 for children.

Another benefit is being planned for July 26 at the Waltonville VFW, Tolley noted.

For ticket information, to make a donation or further information, contact Isett at 316-3274 or Lana Glasco at 697-0389.

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To see more of Mt. Vernon Register-News or to subscribe to the newspaper, go to http://www.register-news.com/.

Copyright (c) 2008, Mt. Vernon Register-News, Ill.

Distributed by McClatchy-Tribune Information Services.

For reprints, email [email protected], call 800-374-7985 or 847-635-6550, send a fax to 847-635-6968, or write to The Permissions Group Inc., 1247 Milwaukee Ave., Suite 303, Glenview, IL 60025, USA.

By Alexis Garrobo, The Beaufort Gazette, S.C.

Jun. 14–Sweat drips from workers’ bodies and brows even as the sun sets behind the 12-foot chain-link, barbed wire fence that surrounds a Lands End migrant camp.

Workers retreat from tomato fields to about 10 migrant camps attached to various farms — Sanders Farm, Six L’s Dempsey Farms and Capers Island Farm.

About 1,000 workers travel from Florida, Mexico, Honduras or Guatemala following the tomato season into Beaufort County. And as they arrive, volunteers largely organized through The Franciscan Center on St. Helena Island pack boxes of beans, rice, cookies and other food and flock to the migrant camps to provide during a period when many do not have food.

Food waits until the first paycheck arrives.

But the local social services, such as The Franciscan Center and the migrant health clinic, are grappling with the effects that recent illegal immigration legislation and negative perceptions toward Hispanics have had on the financial support the organizations receive.

Foreign migrant workers are required to have temporary or permanent government permission to work, according to state and federal laws. But there is no way to pin down whether all migrant workers are legal.

According to the National Center for Farmworker Health, a recent study shows 52 percent of farm workers are not citizens or legal residents, but another report maintains that the majority of them are legal. People who provide services to migrant workers tend to err on the legal side.

Despite the fact that migrants and illegal immigrants are not the same, local residents working with two migrant community outreach programs claim the policies aimed at cracking down on illegal immigration are having perceivable impacts on what they do.

Despite the fact that the migrant population’s economic impact on the state ranks in the billions of dollars, according to the S.C. Chamber of Commerce Web site, two recent policies are mirroring the growing attention that illegal immigration is getting.

Gov. Mark Sanford signed into law June 4 the South Carolina Illegal Immigration Reform Act, which aggressively tries to curb illegal immigration by requiring employers to verify employees through a federal work authorization program, bans them from college scholarships and allows workers fired and replaced by an illegal immigrant to sue the employer.

In Beaufort County, Sheriff P.J. Tanner announced Monday that four local deputies will begin enforcing federal immigration laws after they receive training from Immigration and Customs Enforcement officials.

Perception is half the battle

Although many of the social services, such as the migrant health care clinic, provide service regardless of legal status, the perceptions and policies targeting illegal immigrants also mean some migrants who might not fully understand the system and new measures are more hesitant to seek out services fearing legal consequences.

Roland Gardner, Beaufort-Jasper-Hampton Comprehensive Health Services executive director, said he’s noticed a decrease in patients seeking treatment coincided with anti-illegal immigration legislation.

Patients seeking OB-GYN services, which is one of the major services provided to migrant workers, have decreased both at the clinic and at Beaufort-Jasper-Hampton Comprehensive Health Services, said LaFrance Ferguson, the primary clinic physician. But center director Carolyn Davis said she could not determine if the decrease could be attributed to illegal immigration policies because the clinic does not inquire about the patients’ legal status.

“Our focus is health care and public health,” Davis said. “The migrant population can be hesitant to access service anyway because they aren’t familiar with the system or area.”

Without the community support, on which these social services rely heavily, services to the migrant community would be reduced.

Seasonal food outreach program feels a strain

The food donations given to migrant camps costs about $12,000, and the majority of that comes from community donations, said Sister Shelia Byrne, who helps organize the Franciscans’ drive. She said without that money, and also annual box donations from Georgia-Pacific, the Franciscan Center would not be able to do what it does, and many workers would go hungry.

Sister Shelia said they were concerned people wouldn’t be as supportive of the outreach effort because of all the negativity toward illegal immigration.

“(But we found) not everybody out there lumps Hispanics together; (that) was the best year as far as input,” Sister Shelia said. She said workers in the local farms should not be considered illegal, but she did mention that in the past, some migrants left their jobs to stay in Beaufort in violation of their work permits.

“That won’t happen now. It’s too risky,” she said.

A hand in the health care field

Spanish and English mingle in the waiting room at the evening migrant clinic at the Leroy E. Brown Medical Center as nurses figure out who needs to be treated.

Gardner said the federal and statewide policies on illegal immigration have affected the center financially. Beaufort-Jasper-Hampton Comprehensive Health has operated the clinic since 1970, and most recently has gotten its funding through a $458,000 federal grant for providing health care to migrant workers through the National Association of Community Health Centers. Gardner said the amount has remained constant for the past five or six years while health care costs continue to rise.

The center opens after the workday Monday through Thursdays at 7 p.m.to treat migrant workers who would not otherwise be able to go to a health care center. The center remain open until everyone is treated, often as late as midnight or 1 a.m. The center offers dental, pre-natal, general practice, acute care, and X-ray services, Davis said. Half of the patients seen in the dental clinic have never been to a dentist before.

“These people are the poorest of the poor. We provide care for them even though on their hierarchy of needs food on the table comes before their health,” she said. Davis said many of the patients they see wait until they come to Beaufort before receiving any type of health care.

Returning the favor

In the migrant camp, personal touches are visible from screen doorways: a curtain here or a quilt there. Water spurts into the grass from a washing machine that sits outside on the concrete slab. There are community bathrooms and kitchens, but no air conditioning. Young men sit on overturned plastic buckets outside the doors. They joke with friends or relax from the day. Music thumps out of one of the windows. A few kids scurry around the camp.

“My family started here,” said Marlin Arana, a recent Beaufort High School graduate who said she plans to attend the University of South Carolina Beaufort to study education in the fall.

This year will be the fourth thatshe and her family have helped deliver boxes for the Franciscan Center.

Several of the volunteers were once migrants who have made better lives for themselves in Beaufort. Arana said the center was instrumental in her family settling in Beaufort, particularly Sister Shelia and Sister Stella Breen.

Arana said while her family and many others in the community help the migrant community, it is an unknown world to a large part of the local community, particularly her peers.

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To see more of The Beaufort Gazette or to subscribe to the newspaper, go to http://www.beaufortgazette.com.

Copyright (c) 2008, The Beaufort Gazette, S.C.

Distributed by McClatchy-Tribune Information Services.

For reprints, email [email protected], call 800-374-7985 or 847-635-6550, send a fax to 847-635-6968, or write to The Permissions Group Inc., 1247 Milwaukee Ave., Suite 303, Glenview, IL 60025, USA.

By Theresa Churchill, Herald & Review, Decatur, Ill.

Jun. 14–DECATUR — Alex Wall said he wouldn’t have known how to swaddle his daughter after her birth nine years ago if he hadn’t watched nurses doing it in the hospital.

“Boys are socialized differently than girls,” he said. “They don’t play with dolls or see themselves as parents in the future; they play with sticks and swords and see themselves as race car drivers and firefighters.”

That’s one reason dads often fail to be full partners in parenting after their children are born.

“Then we moms fuss at them like they can’t possibly do it right, so they withdraw,” said Pam Burkhart, project coordinator for Macon County Safe from the Start.

To change that, Wall and Burkhart, co-teachers of a six-session Nurturing Fathers series co-sponsored by Safe from the Start and New Life Pregnancy Center, are now trained to teach a new parenting class aimed at new fathers but open to anyone interested in learning how to care for an infant.

Called Real Dads Rock, the free class is being provided in Decatur through February 2009 under a $50,000 grant awarded to the Macon County Health Department by Circle of Parents, a Chicago-based national network of statewide nonprofit organizations and parent leaders dedicated to preventing child abuse and strengthening families.

It uses the Conscious Fathering curriculum developed by Parent Trust for Washington Children, which covers how to handle, feed, burp, change and clean a baby and respond to his or her needs.

“We’ll focus on tips for calming babies when they cry and helping babies and parents sleep better,” Burkhart said. “We won’t say this to participants, but it’s child abuse prevention 101.”

Not all new parents know, for example, that infants often signal they’re getting hungry by licking their lips, sticking out their tongue and/or turning their heads to the side.

Burkhart said participants will also be encouraged to write down when baby eats to get a better sense of when the child is going to want to eat again. Wall said breastfeeding is the only aspect of parenting that dads can’t do but that involvement by the father is a leading indicator for successful breastfeeding.

Judy Gibbs, maternal child health special projects coordinator at the health department, said the hope is to set up a regular schedule for the class and to incorporate it into existing programs.

This includes childbirth preparation classes at Decatur Memorial and St. Mary’s hospitals, Phoenix II for expectant and new parents at Central Christian Church and the Nurturing Fathers series.

A related support group that will meet twice a month will also be set up.

Gibbs said the agency checkup requirement of the grant is causing the health department to look at ways of making all its services friendlier to fathers.

“This is such a fantastic program,” she said. “Our goal is raise money to send more people for training and go on after the grant period is up.”

Theresa Churchill can be reached at [email protected] or 421-7978.

If you go

WHAT: Real Dads Rock, a free 2 1/2 -hour class on infant care

WHEN: First classes are 9:30 a.m. Saturday, June 21, Macon County Health Department, 1221 E. Condit St.; also 5:30 p.m. Monday, June 23, and 9:30 a.m. Tuesday, July 1, New Life Pregnancy Center, 1698 E. Pershing Road.

TO REGISTER: E-mail [email protected] or call 422-6294.

—–

To see more of Herald & Review, or to subscribe to the newspaper, go to http://www.herald-review.com

Copyright (c) 2008, Herald & Review, Decatur, Ill.

Distributed by McClatchy-Tribune Information Services.

For reprints, email [email protected], call 800-374-7985 or 847-635-6550, send a fax to 847-635-6968, or write to The Permissions Group Inc., 1247 Milwaukee Ave., Suite 303, Glenview, IL 60025, USA.

Celgene International Sarl (Nasdaq:CELG) announced that data presented today at the 13th Congress of the European Hematology Association (EHA) in Copenhagen, Denmark found that patients previously treated for multiple myeloma receiving REVLIMID (lenalidomide) in combination with dexamethasone experienced a significant survival gain regardless of the number of prior therapies they had received.

The results showed that not only was the use of REVLIMID and dexamethasone associated with a substantial improvement in survival, but also was cost-effective with the incremental cost-effectiveness threshold range from GBP 20,000 to GBP 30,000 per quality adjusted life year (QALY). This is widely considered to be an acceptable value for an additional QALY, compared to patients receiving dexamethasone alone.

The results from the analysis presented at EHA were obtained from the assessment of pooled data from several clinical trials, including two large, multi-center, international phase III randomized clinical trials (MM-009/010) evaluating REVLIMID in patients who had previously been treated for multiple myeloma and were applied to the management costs reflective of NHS Wales.

Patients treated with REVLIMID and dexamethasone had an increase in side effects as compared to patients treated with dexamethasone plus placebo. Grade 3/4 toxicities included neutropenia, thrombocytopenia and anemia. Deep vein thrombosis and pulmonary embolism occurred in 9.0 percent of patients treated with lenalidomide plus dexamethasone, compared to 6.0 percent of patients treated with dexamethasone plus placebo in MM-010, and deep vein thrombosis and pulmonary embolism occurred in 14.1 percent of patients treated with lenalidomide plus dexamethasone, compared to 3.4 percent of patients treated with dexamethasone plus placebo in MM-009.

Multiple myeloma is the second most commonly diagnosed blood cancer. There are approximately 80,000 people with the disease in Europe at any given time and according to the International Myeloma Foundation, there are an estimated 750,000 people with multiple myeloma worldwide.

About REVLIMID(R)

REVLIMID is an IMiDs(R) compound, a member of a proprietary group of novel immunomodulatory agents. REVLIMID and other IMiDs compounds continue to be evaluated in over 100 clinical trials in a broad range of oncological conditions, both in blood cancers and solid tumors. The IMiDs pipeline is covered by a comprehensive intellectual property estate of U.S. and foreign issued and pending patent applications including composition-of- matter and use patents.

About Multiple Myeloma

Multiple myeloma (also known as myeloma or plasma cell myeloma) is a cancer of the blood in which malignant plasma cells are overproduced in the bone marrow. Plasma cells are white blood cells that help produce antibodies called immunoglobulins that fight infection and disease. However, most patients with multiple myeloma have cells that produce a form of immunoglobulin called paraprotein (or M protein) that does not benefit the body. In addition, the malignant plasma cells replace normal plasma cells and other white blood cells important to the immune system. Multiple myeloma cells can also attach to other tissues of the body, such as bone, and produce tumors. The cause of the disease remains unknown.

About Celgene International Sarl

Celgene International Sarl, located in Boudry, Switzerland, is a wholly owned subsidiary and international headquarters of Celgene Corporation. Celgene Corporation, headquartered in Summit, New Jersey, is an integrated global pharmaceutical company engaged primarily in the discovery, development and commercialization of innovative therapies for the treatment of cancer and inflammatory diseases through gene and protein regulation. For more information, please visit the Company’s website at www.celgene.com.

This release contains certain forward-looking statements which involve known and unknown risks, delays, uncertainties and other factors not under the Company’s control, which may cause actual results, performance or achievements of the Company to be materially different from the results, performance or other expectations implied by these forward-looking statements. These factors include results of current or pending research and development activities, actions by the FDA and other regulatory authorities, and those factors detailed in the Company’s filings with the Securities and Exchange Commission such as Form 10-K, 10-Q and 8-K reports.

Abstract # 0804

By Janice Gaston, Winston-Salem Journal, N.C.

Jun. 14–Two years ago, Karen Steers, 43, celebrated what she thought would be her last Mother’s Day with her five children — her 18-month-old daughter, her 8-year-old triplets and her 16-year-old son.

Three days before the holiday, doctors had told her that the lump in her side was a tumor caused by stage-four colon cancer, as bad as it could get.

Yesterday, Steers, now in remission, celebrated life with about 300 other cancer survivors, caregivers, advocates and health-care professionals from all over the state at the N.C. Comprehensive Cancer Program Survivorship Summit. The free, daylong gathering at the Marriott in the Twin City Quarter included seminars and informal sessions that covered the physical and emotional aspects of cancer.

Steers, who lives in Holly Springs, is one of more than 300,000 cancer survivors in North Carolina. Walter Shepherd, the Comprehensive Cancer Program’s executive director, delivered some sobering statistics in the opening session. Each day, 119 people in North Carolina are told, “You have cancer.” And each day, 46 people with cancer die.

But the emphasis in yesterday’s program was on living, sparked by the keynote speaker’s speech on hope and healing. Wendy Schlessel Harpham, a doctor from Dallas, Texas, has undergone repeated treatments for recurrences of non-Hodgkins lymphoma since 1990. She is the author of several books on life after cancer.

Participants also had a chance to send a message to legislators about the need for better health care for cancer patients by signing the Fight Back Express, a charter bus sponsored by the American Cancer Society. Thousands of people around the country have signed the bus in honor or in memory of loved ones who have battled cancer.

Steers and her family turned to hope and faith in May 2006 after doctors told her that the tumor on her liver was cancerous and then found that the primary site of her cancer was in her colon. They removed her gall bladder and portions of her colon and liver. The initial diagnosis was jolting, she said, but then she told herself, “I’m going to be OK.”

She and her family were in the process of moving from Maryland to North Carolina when Steers started chemotherapy, and her insurance company required that she receive all her treatments in Maryland. While trying to settle into a new house, get her children adjusted to a new town and new schools, she flew to Maryland every two weeks and spent three days in treatment.

Steers tried to keep up with her children’s activities as much as she could and to help her husband with their Internet business. She stayed so busy that she didn’t have time to worry and get depressed, she said.

She finished her treatments in December of 2006. Since then, tests run every three months have shown no recurrences.

“It’s an amazing miracle,” she said.

Now, she speaks out about people being allowed to receive medical treatment wherever they need to, not where insurance companies tell them to.

Marie Miranda of Raleigh, 38, is living her own miracle. She will soon become the mother of an adopted child. Miranda was 28, single and living in her native Puerto Rico when she underwent a complete hysterectomy for cervical cancer.

“Being told, at 28, that I was not going to be able to have babies — I was heartbroken,” she said. Because her cancer was caught at an early stage, she did not have to undergo chemotherapy or radiation.

“I was blessed,” she said.

But cancer has taken a toll on her family. An aunt died of non-Hodgkin’s lymphoma. Her grandfather died of intestinal cancer at 51. A cousin died of breast and bladder cancer at 32. Her mother has just celebrated five years of survival after a bout with breast cancer.

Miranda is the public-health consultant and training coordinator for the N.C. Department of Health and Human Services’ Office of Minority Health and Health Disparities. She is also an avid volunteer with the American Cancer Society.

At yesterday’s conference, she led a session on working with diverse cultural and ethnic groups, during which she talked about her pride in being a cancer survivor.

“Survival is the first step,” she said.

“Living is what matters.”

Janice Gaston can be reached at 727-7364 or at [email protected].

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To see more of the Winston-Salem Journal, or to subscribe to the newspaper, go to http://www.journalnow.com/.

Copyright (c) 2008, Winston-Salem Journal, N.C.

Distributed by McClatchy-Tribune Information Services.

For reprints, email [email protected], call 800-374-7985 or 847-635-6550, send a fax to 847-635-6968, or write to The Permissions Group Inc., 1247 Milwaukee Ave., Suite 303, Glenview, IL 60025, USA.

NYSE:MAR,

By Karin Shaw Anderson, The Dallas Morning News

Jun. 14–Reina Iglesias knows the clinic staff well.

The 36-year-old mother of four says someone in her family falls ill about once a month.

Friday it was 4-year-old Josue Iglesias, who woke up with a fever and an ear infection.

For Ms. Iglesias, a trip to the doctor could nip about $50 from her paycheck for co-payments and prescriptions.

But the school custodian doesn’t fret over the cost of frequent doctor visits. Josue’s appointment was free, and the prescription antibiotic cost her only a few dollars at the Mesquite Employee Health Center.

“It’s been very convenient for me,” Ms. Iglesias said through a translator.

Lanny Frasier, the Mesquite school district’s assistant superintendent for personnel services, says the 16-month-old employee clinic — which the school district shares with the city — has been a good deal for everyone. School officials anticipate seeing about $1 million a year in savings for health benefit offerings.

“We think it’s one of the best things we’ve done,” Mr. Frasier said.

As health-care costs rise, running in-house health clinics appears to be penciling out for cities and school districts.

Several school districts in the Rio Grande Valley have opened similar clinics to trim the cost of employee health claims. The Pharr-San Juan-Alamo school district has averaged more than $300,000 a year in savings since it opened its health clinic three years ago. The city of Garland opened its own health clinic in 2003 with an average annual savings of about $500,000. Now Frisco school officials are exploring the idea.

Savings first appear when staff members and their families choose to visit an employee clinic — where the city or school district’s costs are fixed — instead of their regular physician’s office, where billing rates are typically higher.

Mr. Frasier said there are also long-term savings that can’t be quantified.

The employee doesn’t pay a deductible or co-payment to visit a district-operated clinic, so employees are more likely to go to the doctor sooner.

“They’ve been able to catch some major things early and get them on treatment,” he said. “Those kinds of savings will be on the back end somewhere.”

For years, it seemed only large corporations could afford to operate employee health clinics.

“It has not been our experience that we’ve seen these in groups of less than 5,000 employees before,” said Ted Troy, the Frisco school district’s insurance consultant. “But now we’re seeing them down to 2,500 employees, and it begins to be something that we ought to consider.”

Now, larger corporations are finding new ways to bring down health-care costs.

Two years ago, Plano-based retailer JC Penney Co. struggled with high medical claims and low enrollment in its health care plan. But the company has since seen a cost savings through a so-called Personal Nurse Program, where teams of nurses work to improve the health of JC Penney’s sickest employees. That 16 percent of the workforce was driving 85 percent of the costs, according an April 9 presentation before the Dallas and Fort Worth health care business leaders.

Clinics are popping up in downtown office buildings as a way for tenants to cut health-care costs for employees. A clinic at the bottom floor of the Irving office building at 222 W. Las Colinas Blvd. serves tenants’ employees and their dependents with convenient medical care and disease prevention services with less wait time than a traditional setting.

The format also has been expanded to the general public, as retailers such as Wal-Mart and CVS have invested millions to open nurse practitioner clinics inside stores.

However, groups such as the American Medical Association and the American Academy of Family Practitioners argue that the clinics fragment the health care system and may offer lower quality health care.

Frisco school officials said they wanted to hear from area doctors before making a decision on the proposed employee health clinic.

The financial risk for the district is minimal, Mr. Troy told several Frisco school board members at an employee benefits committee meeting last month.

“You can always shut the thing down if it doesn’t work, and you can always expand it if it does,” he said.

Jane Brown, a branch library manager in Mesquite, sees the shared city and school district clinic as a job perk.

Her primary care doctor is at Presbyterian Hospital of Dallas, so she popped into the employee clinic Friday for a quick blood test.

“If I just have the sniffles or something and don’t want to make the trip to my doctor in Dallas, this is in the city and close,” Ms. Brown said. “With the price of gas, I don’t want to drive too far.”

Staff writer Jason Roberson contributed to this report.

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To see more of The Dallas Morning News, or to subscribe to the newspaper, go to http://www.dallasnews.com.

Copyright (c) 2008, The Dallas Morning News

Distributed by McClatchy-Tribune Information Services.

For reprints, email [email protected], call 800-374-7985 or 847-635-6550, send a fax to 847-635-6968, or write to The Permissions Group Inc., 1247 Milwaukee Ave., Suite 303, Glenview, IL 60025, USA.

NYSE:JCP, NYSE:WMT,

By Allison M. Heinrichs, The Pittsburgh Tribune-Review

Jun. 14–When Dr. Don L. Fisher graduated from medical school in 1943, the world was experiencing an explosion in medical advances brought by World War II. Blood transfusions were refined, penicillin was saving lives and the tetanus shot was going mainstream.

On Friday, the cardiologist took one of medicine’s latest inventions — a surgical robot — for a test drive.

“I can think of so many uses for this,” said Fisher, 89, after he used his fingertips to command the robot to precisely maneuver tiny surgical instruments. “For minimally invasive surgery, there are great advantages. With no massive tissue recovery, you could send patients home in a day.”

Allegheny General Hospital held an open house to show off its $1.5 million da Vinci Surgical Robot. For the past two months, surgeons at the North Side hospital have been using it to treat prostate cancer and gynecological conditions for which incisions would only be about a centimeter. They’re considering it for cardiac surgery.

West Penn Hospital in Bloomfield, UPMC Shadyside, the Veterans Affairs Hospital in Oakland and about 700 hospitals nationwide also have the robotic system, said Craig Nicholson, clinical sales representative for Intuitive Surgical in Sunnyvale, Calif., which markets the da Vinci. The company named the device after Renaissance artist Leonardo da Vinci because he is credited by some with creating the first robot.

UPMC has used it since 2004 for cardiac, gynecological, prostate, plastic, gastric bypass and gastroesophageal reflux disease surgeries.

“They’re certainly growing in popularity and there have been a lot of patient benefits documented in the medical literature,” said Sally Garneski, spokeswoman for the American College of Surgeons.

The robot is about the size of a large man hunched over a surgical table. Four arms hover over the patient like a giant spider, each ending in an interchangeable surgical tool, such as miniature forceps or scissors.

Several feet away, the surgeon sits at a console with a screen projecting a three-dimensional image of the surgical site. The surgeon’s index finger and thumb rest in small velcro loops. By pinching and twisting his fingers, the surgeon controls where and how the robot moves its arms. Foot pedals control magnification.

“The first time I sat down at the console, I came home to my wife and said, ‘This is the next phase in surgery,’ ” said Dr. Eugene Scioscia, chairman of obstetrics and gynecology at Allegheny General. “In a few years, residents are going to say to me, ‘Dr. Scioscia, how did you operate without this?’ “

Scioscia said the robot eliminates tremors from a surgeon’s hand, which could be disastrous if a vital organ or cancerous tumor were nicked. It also reduces fatigue because the surgeon doesn’t have to hold his arms up and steady for the long time required in many operations, he said.

Eight surgeons in the West Penn Allegheny Health System use the robot.

Dr. Priya Jagga, an obstetrics and gynecology resident at Allegheny General, tried out the robot yesterday.

“It is less complex than I expected,” she said. “You still need to be skilled in your procedures, but it gives you so much more precision.”

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To see more of The Pittsburgh Tribune-Review or to subscribe to the newspaper, go to http://www.pittsburghlive.com/x/pittsburghtrib/.

Copyright (c) 2008, The Pittsburgh Tribune-Review

Distributed by McClatchy-Tribune Information Services.

For reprints, email [email protected], call 800-374-7985 or 847-635-6550, send a fax to 847-635-6968, or write to The Permissions Group Inc., 1247 Milwaukee Ave., Suite 303, Glenview, IL 60025, USA.

NASDAQ-NMS:ISRG, NYSE:AYE,

By Mary Beth Breckenridge, The Akron Beacon Journal, Ohio

Jun. 14–Lucky Janice Lindstrom.

For several years the Hudson resident bought five tickets every year for Keep Akron Beautiful’s Dreamscape raffle. This year, she cut back to one, but it was the right one. Lindstrom’s name was pulled June 5 as the winner of a $10,000 landscape makeover.

Lindstrom wins a front- or backyard makeover designed by James Arch of Vizmeg Landscape Inc. Donor companies will work together to install the new landscape in a blitz the first week of August.

The raffle netted $25,165 for Keep Akron Beautiful’s Flowerscape program, which plants and maintains 40 public gardens annually.

First runner-up was Mary Collins of Akron, who won a master landscape plan by Francis Weng of Garden Designs. Second runners-up Karen and Bob Capron of Akron won $200 worth of blown-in mulch from TerraScape Ltd., and third runner-up Nancy Heslop of Akron won $150 worth of tree maintenance or stump grinding by Walent Tree Service.

Jon Weingart of Akron won a $100 gift certificate to Canton Road Garden Center, and Walter Keith of Akron won $100 worth of gardening supplies from Graf Growers. Hanging baskets were awarded to the top ticket sellers, Don Mittiga of Keep Akron Beautiful’s board of directors and Eric Jones of the KAB beautification board.

These vendor partners also pledged goods or services to Dreamscape 2008: Dayton Nurseries Inc., KB Compost Services, Henry Bierce Co., Copley Tool Rental, Donzell’s Flower and Garden Center, Hoffman’s Garden Center, Suncrest Gardens, Paul’s Greenhouse, Akron Brick and Block, Belgard Sales, W.L. Beck Printing-Design, Cascade Lighting, Gates Landscape Co., Green Ideas Landscape Management, Hawkins Electric, Hitchcock Fleming & Associates, Naragon Irrigation, Pam’s Perennial Plant Farm, R.B. Stout Inc., R.G. Thomas Landscape & Design Inc., Star Printing Co. Inc., Wilson Plumbing & Heating Inc. and YES Press.

Stan Hywet symposium

Stan Hywet Hall & Gardens is planning its first symposium Oct. 17 and 18 to explore historical, architectural and preservation issues.

On Display: Historic Homes and Great Estates will explore the cultural, architectural and social history of America’s Industrial Revolution and Gilded Age, as well as efforts to preserve this history for future generations. It’s intended for both scholarly and general audiences.

Keynote speaker will be Jerry L. Rogers, retired associate director of cultural resources for the National Park Service and retired keeper of the National Register of Historic Places.

The symposium represents a collaboration by Stan Hywet, the University of Akron and Kent State University.

Cost is $145 if the registration form is postmarked no later than Sept. 16 and $175 for registrations postmarked later. Registration must be received by Oct. 10.

Information is at http://www.stanhywet.org, or contact Mark J. Heppner at 330-315-3227 or [email protected].

Events, programs

–Avon Heritage Duct Tape Festival, 11 a.m. to 11 p.m. today and 11 a.m. to 5 p.m. Sunday, Veterans’ Memorial Park, 38975 Detroit Road, Avon. Duct tape sculptures, crafts, fashions and games with a pirate theme, as well as traditional festival attractions. Parade starts 10 a.m. today. Information: 866-818-1116 or http://www.AvonDuctTape-Festival.com.

–Open house, 9 a.m. to 2 p.m. today, Garden of Roses of Legend and Romance, Ohio Agricultural Research and Development Center, 1680 Madison Ave., Wooster Township. Garden features some 500 types of heirloom roses. Event includes tours led by rose experts, pruning demonstration at noon, walks through a new labyrinth and sale of rose plants propagated from those in the garden. Free. Information: 330-263-3612.

–Green With Envy garden tour, 10 a.m. to 4 p.m. today, starting at Angel Falls Coffee Co., 792 W. Market St., Akron. Self-guided tour of eight city gardens, sponsored by the West Hill Neighborhood Organization. Tickets $12. Handicap accessibility is limited. Proceeds support the organization’s community-involvement and neighborhood-advocacy efforts. Information: 330-867-0370.

–Historic Home and Garden Tour, 11 a.m. ro 4 p.m. today, starting at Fellowship Hall, 3909 Broadview Road, Richfield. Three homes open for tours, along with Richfield Historical Society and several businesses. $12. Information: 330-659-6819.

–Father’s Day Picnic Pots, 1-3 p.m. Sunday, Hershey Children’s Garden, Cleveland Botanical Garden, 11030 East Blvd. During this drop-in program, children can make a botanical holder for Dad’s barbecue utensils. Free with admission: $7.50; children ages 3 to 12, $3; members and younger children, free. Information: 216-721-1600 or http://www.cbgarden.org.

–Rose show, 1-4 p.m. Sunday, Parmatown Mall, 7899 W. Ridgewood Drive, Parma. Presented by the Western Reserve Rose Society.

–Aquatic Plants, 6 p.m. Monday, Hoffman’s Garden Center, 1021 E. Caston Road, Green. Learn about the varieties available and their benefits, care, dividing and repotting. Free, but reservations required. Registration: 330-896-9811 or 800-870-4479. Information: http://www.hoffmansgardencenter.com.

–Men’s Garden Club of Akron meeting, Monday evening, Goodyear Heights Metro Park Memorial Pavilion, 2077 Newton St., Akron. Strawberry festival and potluck dinner. Grill available starting 5:30 p.m.; dinner starts at 6:30. Bring a salad or vegetable dish to share, table service and meat to grill. Information: 330-825-5315, 330-673-3553 or http://www.acorn.net/mgcakron.

–Warm Up Akron meetings, 3:30 and 6:30 p.m. Tuesday, Mogadore branch, Akron-Summit County Public Library, 144 S. Cleveland Ave. Members knit and crochet rectangles that are used to make afghans for needy people in the Akron area, and they’ll teach others the skills. Information: 330-699-3252 or http://www.geocities.com/warmupakron.

–North Canton Clutter Club meeting, 7-8:30 p.m. Thursday, North Canton Public Library, 185 N. Main St. Club provides participants with organizing ideas. Free. Information: 330-309-5280 or http://www.realsolutionsforliving.com/clutterclub.html.

–Home & Garden Tour, 10 a.m. to 5 p.m. Thursday through next Saturday, Hudson. Self-guided tour of homes and gardens, presented by the Hudson Garden Club. Tickets: $15 in advance at the Learned Owl Book Shop, 204 N. Main St., or Acme, 116 W. Streetsboro Road, both in Hudson, or $20 on tour days at the ticket booth on the Village Green or at the Garden Shop (after noon) in the Hudson Middle School, 77 N. Oviatt St. Proceeds fund tree planting in Hudson, scholarships, grants and community gardening projects. Information: http://www.hudsongardenclub.org.

–Floor sample sale, 5-8 p.m. Friday and 9 a.m. to 4 p.m. next Saturday, Ohio Design Centre, 23533 Mercantile Road, Beachwood (off Chagrin Boulevard, west of Interstate 271). Seven showrooms, normally open only to decorators and their clients, will sell floor samples to the public at discounted prices. All items are sold as is, and all sales are final. No admission charge. Information: 216-831-1245 or http://www.ohiodesigncentre.com.

–Ohio Lavender Festival, Friday through June 22, DayBreak Lavender Farm, 2129 Frost Road, Streetsboro. Presentations, demonstrations, workshops, Johnny Appleseed re-enactor and more. Hours: 9 a.m. to 6 p.m. Friday and next Saturday, 10 a.m. to 6 p.m. June 22. $7; families (two parents plus up to four children younger than 13), $20; three-day pass, $20. Free parking and shuttle service at the old Wal-Mart, 9440 State Route 14. Information: http://www.ohiolavenderfestival.com or 330-626-3235.

–Pond Construction With Bog Filtration, 9:15 a.m. next Saturday, Hoffman’s Garden Center, 1021 E. Caston Road, Green. Free, but reservations are required. Registration: 330-896-9811 or 800-870-4479. Information: http://www.hoffmansgardencenter.com.

–Sustainable Gardening, 11 a.m. next Saturday, Donzell’s Flower & Garden Center, 937 E. Waterloo Road, Akron. Learn about working with nature to build healthy soil and grow healthy plants. Topics will include organic products and composting methods. Free, but reservations are requested. Registration: 330-724-0550, Ext. 110.

–The Basics of Woodland Ownership, 9 a.m. to 3 p.m. June 24, Plum Creek Park North, 2390 Plum Creek Parkway, Brunswick Hills Township. $35 (includes lunch and handouts). Paid registration due Wednesday. Class size is limited. Registration: 614-688-3421 or [email protected]. Information: http://woodlandstewards.osu.edu or 330-725-4911.

–Zensai: The Horticulture of Japan, through June 29, Cleveland Botanical Garden, 11030 East Blvd. Show includes programs, exhibits of art and photographs, tours of the Japanese Garden and displays of ikebana flower arranging and bonsai, the art of miniaturizing plants. Hours: 10 a.m. to 5 p.m. Mondays-Saturdays (open till 9 p.m. Wednesdays), noon to 5 p.m. Sundays. Admission: $7.50; children ages 3-12, $3; members and younger children, free. Information: 216-721-1600 or http://www.cbgarden.org.

–Great Garden Adventure, through Oct. 31, Stan Hywet Hall & Gardens, 714 N. Portage Path, Akron. Imagination Stations throughout the grounds help visitors reconnect with nature and learn about natural phenomena. Displays of flower sculptures made by “junkyard artist” P.R. Miller and whimsical bugs and butterflies made by area students. Hours: 10 a.m. to 6 p.m. Tuesdays-Sundays. Closed Mondays except Labor Day. Various admission options are available, with adult prices ranging from $8-$25. More information: 330-836-5533 or http://www.stanhywet.org. Mail notices of classes, programs and events two weeks in advance to: Home and Garden News, Features Department, Akron Beacon Journal, P.O. Box 640, Akron OH 44309-0640. Please include your name and telephone number. All events must be open to the public.

Mary Beth Breckenridge can be reached at 330-996-3756 or [email protected].

—–

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Copyright (c) 2008, The Akron Beacon Journal, Ohio

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NYSE:WMT,

By Ricketts, Reva Tamboli, Pheroze; Czerniak, Bogdan; Guo, Charles C

* Tumor-to-tumor metastasis is a rare phenomenon. Renal cell carcinoma is the most common recipient of tumor-totumor metastasis in malignant tumors. However, renal angiomyolipoma has not been reported to be a recipient. Here we report 2 cases of tumor-to- tumor metastasis to renal angiomyolipoma. In one case, the donor tumor originated from neuroendocrine carcinoma of the pancreas, and in the other case the donor tumor was from adenocarcinoma of the lung. The donor tumors showed morphologic features that did not easily fit into renal angiomyolipoma, and they also demonstrated patterns of immunoreactivity consistent with the primary tumors rather than with renal angiomyolipoma. To our knowledge, these are the first reported cases of tumor-to-tumor metastasis to renal angiomyolipoma. An awareness of this phenomenon is important to avoid an incorrect diagnosis when encountering unusual morphologic features in renal angiomyolipoma. (Arch Pathol Lab Med. 2008;132:1016-1020)

Tumor-to-tumor metastasis is a rare phenomenon. Fewer than 100 cases have been reported since it was first documented by Berent in 1902.1 The most common donors of tumor-to-tumor metastasis are carcinomas of the lung, followed by carcinomas of the breast, gastrointestinal tract, prostate, and thyroid.2 Although meningioma appears to be the most common recipient of tumor-to-tumor metastasis in benign tumors, renal cell carcinoma is the most common recipient of metastasis in malignant tumors. 3,4 Although also arising in the kidney, renal angiomyolipoma is a benign mesenchymal tumor that demonstrates distinct biologic and clinical characteristics when compared with renal cell carcinoma. Here we report 2 cases of tumor- to-tumor metastasis to angiomyolipoma of the kidney.

REPORT OF CASES

Case 1

A 53-year-old man with a history of neuroendocrine carcinoma of the pancreas presented with an enlarging left renal mass. ee years previously, this patient developed a 6.3-cm tumor in the pancreas and multiple masses in the liver. Fine-needle aspiration biopsy of the liver masses revealed a low-grade neuroendocrine carcinoma, consistent with a metastasis from the pancreas primary. During the evaluation for neuroendocrine carcinoma of the pancreas, a 2.5-cm exophytic tumor was also identified at the upper pole of the left kidney. The patient subsequently received multiple rounds of chemotherapy for the metastatic neuroendocrine carcinoma, and his condition improved. The renal tumor remained unchanged in follow-up imaging studies until 2 1/2 years later, when the tumor increased to a size of 3.5 cm. On computed tomography (CT), no adipose tissue was identified in this renal mass. Therefore, this tumor was thought most likely to be a renal cell carcinoma. Additional radiographic studies showed that the tumors in the pancreas and liver did not progress. The patient elected to undergo a partial nephrectomy.

Case 2

A 75-year-old man developed a dry cough accompanied with shortness of breath a year prior to presentation. At that time the patient was suspected of having pneumonia and had been treated with multiple antibiotics. Unfortunately, his cough did not improve. A CT scan of the abdomen demonstrated a 4.5-cm mass in the superior pole of the right kidney. His bone scan revealed multiple focal areas of increased activity in the thoracic spine, ribs, and right iliac crest, suspicious for metastatic disease. He underwent a CT-guided renal biopsy.

PATHOLOGIC FINDINGS

The partial nephrectomy specimen in case 1 measured 6.0 x 3.5 x 3.0 cm. Sectioning revealed a gray-white circumscribed mass measuring 3.5 x 2.6 x 2.1 cm. This exophytic tumor pushed against but did not penetrate the renal capsule. The cut surface was firm and granular without hemorrhage or necrosis. Microscopically, the tumor was composed largely of smooth muscle cells and thickwalled blood vessels with scant adipose tissue (Figure 1, A). The smooth muscle cells were intimately associated with the outer layers of the muscular walls of blood vessels. Intracytoplasmic vacuoles were also present in some smooth muscle cells. These features are consistent with angiomyolipoma of the kidney. However, within the angiomyolipoma, there were small foci of atypical cells arranged in trabecular, insular, or acinar patterns (Figure 1, B). These cells exhibited amphophilic cytoplasm and uniform nuclei with granular chromatin and inconspicuous nucleoli, which were suggestive of neuroendocrine cells. The atypical cells were not identified in the nonneoplastic renal parenchyma. Immunohistochemical studies were performed. The majority of the tumor showed positive signals for HMB- 45 and negative signals for cytokeratin, consistent with an angiomyolipoma. However, those small foci of neuroendocrine-like cells were diffusely positive for pancytokeratin (Figure 1, C), MOC- 31, synaptophysin (Figure 1, D), and CD56; focally positive for chromogranin and AE1/AE3; and negative for HMB-45. Therefore, these foci of atypical cells represented metastatic neuroendocrine carcinoma from the pancreas. After this partial nephrectomy, the patient’s previous fine-needle aspiration of liver masses was reviewed and demonstrated atypical cells with similar neuroendocrine features (Figure 1, E), and these atypical cells were positive for cytokeratin and synaptophysin (Figure 1, F), consistent with metastatic neuroendocrine carcinoma from the pancreas.

The renal biopsy specimen in case 2 consisted of multiple fragments of soft tan-pink tissue (0.5 x 0.1 x 0.1 cm in aggregate). Microscopically, the tumor was mostly composed of spindle cells, thick-walled blood vessels, and adipose tissue, admixed in a haphazard fashion, consistent with an angiomyolipoma (Figure 2, A). In addition, there are atypical nested epithelioid cells with enlarged hyperchromatic nuclei (Figure 2, B). On immunostains, the majority of the tumor was positive for smooth muscle actin and HMB-45 and negative for cytokeratin, consistent with renal angiomyolipoma. In contrast, those small foci of atypical cells showed strong positive signals for pancytokeratin and cytokeratin 7 (Figure 2, C), and negative signals for smooth muscle actin and HMB-45. In addition, these atypical cells were also positive for thyroid transcription factor 1 (Figure 2, D) and surfactant, supporting a metastasis of lung primary. Subsequently, a CT scan of the chest was performed and demonstrated a 3.5 x 2.1- cm nodular area with consolidation in the left upper lung. This lung mass was biopsied by fine-needle aspiration and cytology examination revealed malignant cells with enlarged round nuclei and prominent nucleoli (Figure 2, E). These malignant cells were positive for thyroid transcription factor 1 (Figure 2, F), consistent with adenocarcinoma of the lung.

COMMENT

Angiomyolipoma is a benign mesenchymal tumor composed of various combinations of adipose tissue, smooth muscle cells, and characteristic thick-walled blood vessels. 5 Angiomyolipomas occur most often in the kidney, but they have also been found in the liver, ovary, fallopian tube, spermatic cord, palate, and colon. Renal angiomyolipomas, such as the previous 2 cases, are usually asymptomatic and discovered by radiographic screening techniques. The demonstration of adipose tissue in a renal mass on radiographic images excludes renal cell carcinoma and is indicative of angiomyolipoma. However, in rare cases of angiomyolipoma, the tumor may be composed mostly of smooth muscle cells and thick-walled blood vessels, with minimal adipose tissue. In such cases, angiomyolipoma is often confused with renal cell carcinoma on radiographic imaging, thus leading to unnecessary surgical excision.6

The presence of predominant epithelioid cells in angiomyolipoma has led to the recognition of epithelioid angiomyolipoma, a malignant tumor with the capacity to be locally aggressive and metastasize.7 Epithelioid angiomyolipoma is usually composed of round to polygonal cells with abundant acidophilic cytoplasm in sheets. The tumor cells have enlarged vesicular nuclei with prominent nucleoli, resembling ganglion cells. Epithelioid angiomyolipoma has a pattern of immunoreactivity similar to that of the usual angiomyolipoma: positive staining for melanoma markers (HMB-45, Melan-A, and tyrosinase) and smooth muscle markers (smooth muscle actin and musclespecific actin). Epithelioid angiomyolipoma usually lacks immunoreactivity for cytokeratins. In the 2 cases we present, the atypical cells show diffuse and strong positive reactivity for cytokeratins (pancytokeratin, MOC-31, AE1/ AE3, and cytokeratin 7) and negative reactivity for smooth muscle actin and HMB-45. These immunoreactive patterns are more compatible with metastatic carcinoma rather than epithelioid angiomyolipoma.

Another possibility to consider in the case of unusual morphology in angiomyolipoma is a collision tumor. A collision tumor results when 2 morphologically distinct tumors develop in the same location. This phenomenon has been documented in the kidney. In a study of 36 cases of concurrent angiomyolipoma and malignant renal tumors, Jimenez et al8 found that clear cell renal cell carcinoma was the most common malignancy, accounting for approximately two thirds of the tumors. In most clinical settings, angiomyolipoma was an incidental finding. In the 2 cases we describe, the specimens were thoroughly examined, and no renal cell carcinoma is present. In addition, immunohistochemical studies demonstrate patterns of immunoreactivity that are consistent with the patients’ known primary tumors: the tumor in case 1 shows reactivity for neuroendocrine markers (synaptophysin, chromogranin, and CD56), consistent with neuroendocrine carcinoma of the pancreas; the tumor in case 2 shows positive reactivity for cytokeratin 7, thyroid transcription factor 1, and surfactant, consistent with adenocarcinoma of the lung. At the advanced stage, malignant tumors may metastasize to the kidney. In a study of 11 328 autopsies of cancer patients, Bracken et al9 found that 7.2% of the patients had metastases from the primary tumors to the kidney. Virtually any carcinoma can metastasize to the kidney. However, the most common primary tumors to metastasize to the kidney were tumors of the lung, breast, and skin (melanoma). Up to 28% of renal cell carcinomas metastasized to the opposite kidney. Generally, metastatic tumors were multiple, bilateral, less than 3 cm, and presented throughout in the renal parenchyma. When a renal tumor presents with unusual morphologic features as a primary lesion, the possibility of metastasis should always be considered.

Tumor-to-tumor metastasis is a rare phenomenon. Although any tumor may be a potential recipient of metastasis, renal cell carcinoma is by far the most common recipient among malignant tumors. Two factors may contribute to the preferential homing of metastatic cancer to renal cell carcinoma: one is the rich vascularization of renal cell carcinomas, which renders them more accessible to metastatic tumor cells in the circulating blood, and the other is the high lipid and glycogen content in renal cell carcinoma, which may provide a nutrient-rich microenvironment for metastatic tumor cells. Because angiomyolipomas are also characterized by rich vascularization and abundant lipid content, they too may be suitable hosts for metastases. However, most renal angiomyolipomas are identified by CT scan and are usually not resected. The extreme rarity of tumor metastasis to angiomyolipoma is probably because renal angiomyolipoma is underestimated in surgical series, accounting for less than 1% of all tumors surgically removed from the kidney.

In summary, we present 2 cases of tumor-to-tumor metastasis to angiomyolipoma of the kidney. To the best of our knowledge, this is the first report of tumor-to-tumor metastasis into renal angiomyolipoma. Although tumorto- tumor metastasis is extremely rare, an awareness of this phenomenon is important to avoid an incorrect diagnosis when encountering a tumor with a strikingly dimorphic appearance.

References

1. Berent W. Seltene metastsenbildung. Zentralbl Allg Pathol. 1902;13:406.

2. Ro JY, Sahin AA, Ayala AG, et al. Lung carcinoma with metastasis to testicular seminoma. Cancer. 1990;66:347-353.

3. Honma K, Hara K, Sawai T. Tumour-to-tumour metastasis: a report of two unusual autopsy cases. Virchows Arch A Pathol Anat Histopathol. 1989;416:153- 157.

4. Sella A, Ro JY. Renal cell cancer: best recipient of tumor-to- tumor metastasis. Urology. 1987;30:35-38.

5. L’Hostis H, Deminiere C, Ferriere JM, et al. Renal angiomyolipoma: a clinicopathologic, immunohistochemical, and follow- up study of 46 cases. Am J Surg Pathol. 1999;23:1011-1020.

6. Hafron J, Fogarty JD, Hoenig DM, et al. Imaging characteristics of minimal fat renal angiomyolipoma with histologic correlations. Urology. 2005;66:1155- 1159.

7. Eble JN, Amin MB, Young RH. Epithelioid angiomyolipoma of the kidney: a report of five cases with a prominent and diagnostically confusing epithelioid smooth muscle component. Am J Surg Pathol. 1997;21:1123-1130.

8. Jimenez RE, Eble JN, Reuter VE, et al. Concurrent angiomyolipoma and renal cell neoplasia: a study of 36 cases. Mod Pathol. 2001;14:157-163.

9. Bracken RB, Chica G, Johnson DE, et al. Secondary renal neoplasms: an autopsy study. South Med J. 1979;72:806-807.

Reva Ricketts, DO; Pheroze Tamboli, MD; Bogdan Czerniak, MD, PhD; Charles C. Guo, MD

Accepted for publication December 17, 2007.

From the Department of Pathology, University of Texas M. D. Anderson Cancer Center, Houston.

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

Reprints: Charles C. Guo, MD, Department of Pathology, University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd, Unit 085, Houston, TX 77030 (e-mail: [email protected]).

Copyright College of American Pathologists Jun 2008

(c) 2008 Archives of Pathology & Laboratory Medicine. Provided by ProQuest Information and Learning. All rights Reserved.

By Lisa Adams

BRITAIN’S toughest life coach, Steve Miller,may hate fat people, but his brutally direct new book, Get Off Your Arse And Lose Weight, is flying off the shelves.

“Fat people need to get off their blubbery backsides,” said Steve, 39.

“People say obesity is a complex issue. It’s not. It’s straightforward. I’m not a bully, I just tell it like it is.

“Stop shovelling food in, get tough and make yourself shape up through the power of your mind. I’ve never found a fat person who is happy with themselves.”

Steve, who is 5ft 7in, knows exactly what it feels like to pile on the pounds. He felt miserable after his weight ballooned to 14st 10lb because of a couch potato lifestyle and a love of fattening takeaways.

But he dropped down to 11st 2lb thanks to healthy eating, getting active and most important of all, steely self-discipline.

“I looked like a real weeble wobble,” said Steve. “I looked in the mirror and thought I looked pretty ugly. My stomach stood out so much I looked like a question mark.

“When a man’s belly is so big you can’t see your willy, you get a bit worried.

“I had become so greedy. There was no excuse. I stuffed my face with food and drank bottles of wine. My stomach just got bigger. I can’t put it down to any genetic thing. I was just completely lazy.

“That was the last thing I wanted to happen.

I got really tough on myself. I told myself to stop acting like a silly little victim.

“The only way I lost the weight was to come up with a plan of action which worked. At the heart of it was giving myself a real kick up the backside. I look and feel sexier now.

You can too.”

So here, if you’re brave enough, are Steve’s top 10 no-nonsense tips to getting the body you really want.

1 Stop making excuses for being fat The world of therapy is poison because it’s making excuses for people.

It’s showing too much empathy with people for being fat. There are a minority of people who have very deep psychological problems or a genetic reason for being fat, but 90 per cent of people are fat because they are lazy.

Take responsibility for being fat and do something about it, not tomorrow, today.

2 Burn your diet book and ban all diet clubs Diets are a complete waste of time. They’re arip-off. People get so wrapped up on all these diets, but what’s really lacking is agood kick up the arse and a healthy, balanced diet.

Instead you need to eat more fruit and vegetables. Weight loss goodies to stock up on include eggs, bananas, broccoli, couscous, lean chicken, cottage cheese, lean steak, salmon, skimmed milk, whole grain pasta and tomatoes.

You must eat regular meals, breakfast, lunch and dinner.

Satisfy cravings with healthy alternatives to high-fat, high- sugar processed snacks like carrot sticks, fruit and nuts.

3 Clean out your cupboards Remove the troublemakers – crisps, chocolate, biscuits and ready meals.

Take them to the bin and literally smash them into it. Beware of the other baddies, that includes chips, full-fat cheese, fizzy drinks, ice cream, pastries, butter, onion bhajis, pizza, sausage rolls and beef burgers.

Take time to explain to your kids why empty calories in food like this end up becoming a chain that drags you down.

Grill, don’t fry food. Forget about the two for one offers on processed food in supermarkets. Isn’t it nice of the supermarkets to help clog up your arteries with fatty foods?

4 Booze bust Alcohol is as calorific as liquid cream cakes and too much makes men fart more, snore and suffer penile dysfunction. Women who drink too much look cheap and may as well have a For Sale sign on their back.

Make sure you don’t drink every day. Have dry nights for four out of seven. Instead drink water to keep your body hydrated and help it burn calories. Drink a pint of water before eating and you’ll eat less.

5 Get your arse off that sofa Say to yourself, “hey you big fat lump, get off the sofa and do something”.

Exercise doesn’t mean feeling the burn or doing high impact exercises that can damage your joints.

Try power walking in the park for an hour aday. It’s the best form of exercise you can do. Don’t kid yourself that you don’t have time. There is always time, no matter how busy you are. Make it a priority.

It makes you healthier and will, in all probability, extend your life. You will be around longer for your partner, children, friends and family. That has to be the greatest incentive there is to get moving.

Take the stairs rather than the lift. Get off the bus a stop or two early and walk the rest of the way home.

6 Hate fat people Feel disgusted by fat people around you. Make a conscious effort to observe fat people. Notice how they often eat more than others. Don’t be sympathetic about it.

If their seemingly never-ending hunger is not related to a medical condition, they should stop feeding their fat.

It’s okay to be fat, but remember, it’s the slim and healthy people who pay for your treatment when your health fails. Why should we pay for your lack of self-control?

Instead set realistic goals for your own weight loss and, for a good incentive, put a picture of your ideal body shape in your kitchen and look at it when you feel lacking in willpower. Picture yourself as you really want to be.

7 Take it away for good Rip up all your takeaway menus.

That junk food should be delivered straight into the bin.

Every time you’re tempted to buy a takeaway, put the money you would have spent in a tin.

Pretty soon you will be able to buy some fab new clothes – in a smaller size. Walk tall past the takeaways. Imagine the server’s dirty fingernails, see the fatties in the queue. Start to associate the over-used cooking smell with the smell of vomit andyou will break the habit.

8 Leave food on your plate You will soon enjoy the feeling of achievement this gives you. Choose smaller plates. Forget about eating everything because there are people starving in the world. You eating everything isn’t going to help feed them. If you’reworried about poverty, donate to a charity.

9 Slow down Eat slowly and be proud to admit it when you are full. Chewing your food slowly is a natural way to eat less because your stomach will get around to telling your brain it’s full more quickly.

Compare this to when you are wolfing down packets of biscuits or a takeaway. You want more and don’t feel your hunger is satisfied. Then suddenly after you’ve gorged yourself, you feel stuffed and hate yourself for eating so much.

Clean your teeth after each meal. This gives a signal to your brain that you’ve eaten enough by cleaning your taste buds.

10 Forget comfort eating If you are an emotional eater it’s time to get agrip. If your problems are the result of a bereavement, divorce or depression, then visit your GP for support.

If you’re simply moping about not getting that job you applied for, then get over it.

One of the physical causes of emotional eating is an increased level of cortisol, the stress hormone which can create cravings for food.

It may also be caused by childhood conditioning. Parents often provide children with sweets to make up for difficult experiences.

Some of us grow up associating these foods with feeling better when faced with stress. Recognise this behaviour and then let go of it. Learn to let go of stress through relaxation and exercise instead.

Get off your Arse and Lose Weight by Steve Miller costs pounds 7.99 and is published by Headline.

‘Get off the bus a stop or two early and walk the rest of the way’

(c) 2008 Daily Record; Glasgow (UK). Provided by ProQuest Information and Learning. All rights Reserved.

By diSibio, Guy French, Samuel W

* Context.-Many studies have addressed metastatic patterns seen among various cancers. No recent studies, however, provide quantitative analyses of such patterns arising from a broad range of cancers based primarily on postmortem tissue analyses. Objective.- To provide a quantitative description of metastatic patterns among different primary cancers based on data obtained from a large, focused autopsy study.

Design.-Review of data from 3827 autopsies, performed between 1914 and 1943 on patients from 5 affiliated medical centers, comprising 41 different primary cancers and 30 different metastatic sites.

Results.-Testicular cancers were most likely to metastasize (5.8 metastases per primary cancer), whereas duodenal cancers were least likely to do so (0.6 metastases per primary cancer). Preferred metastatic sites varied among the primary cancers analyzed. Overall, regional lymph nodes were the most common metastatic target (20.6% of total), whereas testes were the least common (0.1% of total).

Conclusions.-Not surprisingly, different primary cancers tended to metastasize, with differing frequencies, to different sites. These varying metastatic patterns might be helpful in deducing the origins of cancers whose primary sites are unclear at presentation.

(Arch Pathol Lab Med. 2008;132:931-939)

Malignant neoplasms are, by definition, those that metastasize. By involving anatomic structures distant from the primary site and potentially disrupting their function, tumor metastases add to disease morbidity and mortality; hence, metastases from a known primary cancer will have dramatic effects on disease staging, prognosis, and treatment.1 Additionally, cancers that present initially as metastases distant from their sites of origin (or cancer from unknown primary site) often require extensive investigation to determine their primary source to optimize treatment. In either scenario, whether cancer is tracked prospectively (from a known primary) or retrospectively (from an unknown primary), detailed observational templates that highlight expected metastatic patterns would be of great clinical benefit in both diagnosis and treatment.

By facilitating thorough postmortem examination of all tissues within the body, large-scale autopsy studies offer a powerful approach toward developing such templates. Perhaps owing to the general decline in hospital-based autopsies,2-4 however, few such general studies are available in the current literature. Most contemporary autopsy studies focus on one specific type of primary cancer or site of metastasis but fail to address the broad spectrum of metastatic behaviors likely to be encountered in a clinical setting.5,6 Other studies that do address this broad spectrum do not use postmortem tissue analysis as a primary source.7 Indeed, we have found only one other autopsy study, published in 1950, that is of sufficient scope to address this broad spectrum.8 Although data from more recent studies using such sophisticated technologies as whole- body magnetic resonance imaging,9 positron emission tomography,10 and computed tomography11 have unquestionably contributed to the current understanding of metastatic disease, actual postmortem histologic analysis arguably remains the gold standard in the study of many disease processes,12-14 including cancer metastasis. In the present study, we were fortunate to have access to a large archival collection of carefully documented postmortem histologic data on primary malignancies and metastatic sites.

MATERIALS AND METHODS

Archival data were examined from 4012 autopsies that included examination of all organ systems, performed on 2108 male and 1904 female patients between 1914 and 1943 at Harvard (Boston, Mass), Huntington (Huntington, Mass), Palmer (Palmer, Mass), Pondville (Walpole, Mass), and Westfield (Westfield, Mass) medical centers. None of these patients received chemotherapy or radiation treatment. Each autopsy fell into 1 of 46 different primary neoplasm categories (cases involving leukemia, endothelioma, lymphoma, and neuroblastoma were not included). The number of male versus female cases for each primary malignancy was not recorded; therefore, relative proportions of primary malignancies and metastases were calculated among all patients (male and female). Metastatic lesions generated by all neoplasms were quantified among 32 different anatomic sites, with the number of metastases generated from all primary neoplasms at a given site noted. The total number of metastases was 10 062. All primary neoplasms and metastases were analyzed by gross examination and on histologic sections. After review of these original data, 2 primary neoplasm categories were excluded from the final analysis because of ambiguity in the record. Three other primary neoplasm categories (mediastinum, lymph node, and brain) were also excluded because of insufficient numbers of events. Our final data set includes 3827 autopsies (41 primary neoplasms) and 9484 metastases (30 metastatic sites).

RESULTS

Figure 1 shows the distribution of the 3827 autopsies by primary malignancy (y-axis) and metastatic site (x-axis), each listed in alphabetic order. Listed in blue are individual numbers of each primary neoplasm. As shown by the blue bars in Figure 2, the most common primary cancers were, in descending order, rectum (11.4%), breast (11.3%), cervix (10.9%), stomach (9.1%), and prostate (5%). Also shown in Figure 1 is the distribution of the 9484 metastases generated by the 3827 primary neoplasms among 30 different anatomic sites (numbers in green). The total contribution from each primary malignancy to all metastatic sites is listed in red numbers. The red bars in Figure 2 illustrate the relative proportion of metastases that each primary malignancy contributed to the final metastatic pool. Comparing corresponding red and blue bars indicates that some primary malignancies, including breast, lung, kidney, and testes, generated a disproportionate number of metastases, relative to their representation within the total pool of primary cancers (see also Figure 4, A).

Metastasis to each site, in decreasing frequency, is shown in Figure 3. Consistent with their putative function as primary mechanical barriers against many metastatic cancers,15 local and regional lymph nodes were the most frequent metastatic targets (20.5% and 12.9%, respectively). Liver, lung, and bone were the next most common metastatic targets, with 11.1%, 10.7%, and 6.5%, respectively, of all primary malignancies targeting these sites of high vascular flow. Indeed, most of the different primary neoplasms listed in Figure 1 metastasized, at varying frequencies, to these common sites. Conversely, the 5 least common metastatic sites are shown in order of decreasing frequency in Figure 3: stomach (0.6% of metastases), vagina (0.3% of metastases), prostate (0.3% of metastases), skeletal muscle (0.2% if metastases), and testes (0.1% of metastases).

The tendency for certain cancers to metastasize more readily than others is illustrated in Figure 4, A, which shows the average number of metastases per primary neoplasm. For each type of malignancy, values were derived by dividing the total number of metastases (Figure 1, numbers in red) by the total number of primary neoplasms (Figure 1, numbers in blue). Figure 4, B, depicts the distribution of the metastases among all 30 metastatic sites by the 10 malignancies that generated the highest average number of metastases per primary neoplasm (testes, breast, adrenal, skin, lung, retroperitoneum, ovary, kidney, eye, and pancreas). Breast cancer (in yellow) contributed the greatest proportion of metastases to the broadest range of sites.

Figure 5 depicts the frequencies at which all primary malignancies were distributed among the 5 most and least common metastatic sites (see also Figure 3). As previously noted, most primary malignancies metastasized to varying degrees among regional lymph nodes (38 primaries of 41 analyzed). Of these primary malignancies, cervical cancer was the most common and appendix was the least common, seen in 11.9% and 0.1%, respectively, of all metastases to regional lymph nodes. Conversely, the least common metastatic site, testes, was targeted by only 9 primary malignancies. Of these testicular metastases, those from prostate were found most commonly (33% of metastases), and unknown primaries were found least commonly (8.3% of metastases).

COMMENT

Findings from this study provide a comprehensive overview of metastatic behaviors as seen among both common and uncommon cancers during the 29-year period in which they were collected. As actual postmortem tissue analyses from the largest cohort of autopsies reported to date in the medical literature, these findings provide a sensitive, quantitative baseline of metastatic patterns seen among the analyzed malignancies. Figures 1 through 5 illustrate the utility of such a baseline, whether following potential metastases from a known primary malignancy or predicting the origin of an unknown primary malignancy by its metastatic behavior. For a given neoplasm, Figures 1 and 2 show its representation and relative propensity to metastasize, and Figure 4, A, shows its absolute propensity to metastasize. For a given metastatic site, Figure 3 shows the frequency at which that site was targeted, whereas Figure 4, B, shows the representation of each of the 10 most highly metastasizing primary malignancies at that site. Finally, Figure 5 highlights the representation of all primary malignancies among the most and least common metastatic targets. Our hope is that such an integrated picture will not only contribute to the general knowledge base of cancer behavior but also facilitate the development of testable hypotheses that drive more targeted studies on these clinical phenomena and their underlying mechanisms. A comparison between the findings of this study and those reported in the 2006 National Center for Health Statistics report reveals marked decreases in deaths attributed to some cancers. Stomach cancer, which represented 9.1% of our cases, currently accounts for only 2% of cancer deaths. Another striking example is cervical cancer, which represented 10.9% of cases in the current study but now accounts for only 1.4% of female cancer deaths in the United States.16 Beckman et al17 document the historic decrease in the incidence of cervical cancer in the United States, from 30 per million in 1930 to 10 per million in 1980; this decrease has been attributed to widespread early screening and treatment procedures that were not available in the past. Other examples of medical advances that have changed the proportion of deaths attributed to primary malignancies, including several found in the current study, may be found. By this reasoning, our cohort of patients who died between 64 and 93 years ago represents essentially untreated human subjects. Compared with more contemporary cohorts, it is therefore more likely that the primary malignancies analyzed in our study have been allowed to run their full pathologic course. Modern chemotherapy and radiation treatment might predictably alter metastatic patterns and reduce metastasis as a whole. Specific examples are discussed in the following discussion.

Breast Cancer

Breast cancer accounted for 11.3% of all primary neoplasms, making it the second most common malignancy in this study. Breast cancer is currently the fifth most common cause of cancer death worldwide (502 000 deaths per year), after lung (1.3 million deaths per year), stomach (1 million deaths per year), liver (662 000 deaths per year), and colon (655 000 deaths per year) (http:// www.who. int/mediacentre/factsheets/fs297/en/index.html [February 2006]). The robustness with which breast cancer metastasized in the current study is striking: It both represented a high proportion (11.3%) of all primary malignancies (Figure 2) and generated a large number of metastases (5.2 per primary malignancy; Figure 4, A). As a result, breast cancer contributed 23.6% of all metastases (Figure 2), the highest number among all analyzed malignancies. This tendency toward widespread metastasis is consistent with the continuing difficulties in treating primary breast cancer18,19 and for the frequent identification of breast primaries among cancers that present initially as metastases from an unknown primary site.20,21

Breast cancer was nonselective in its metastatic targets (Figure 4, B, yellow bars) and in general contributed the largest proportion of metastases among most different sites, with lymph nodes and lung constituting the most frequent sites (Figure 6). The breast was itself a rare metastatic target in this data set, receiving only 0.7% of all metastases (Figures 1 and 3). Yet 87.1% of all metastases to breast were classified as having originating from the breast itself in the archival data set (Figure 4, B). This finding is of interest in light of the current difficulties in resolving whether breast lesions more likely represent metastases from contralateral primaries22 or second (ipsilateral) primary malignancies.23,24 In retrospect, it therefore appears likely that the former assumption was made at the time that these data were collected and should be evaluated cautiously.

Prostate Cancer

Low-grade prostate cancer is typically an indolent disease that is monitored primarily by serial prostate-specific antigen measurements alone, with interventions dictated largely by abnormal rises in this marker, a practice that may be more beneficial in the patients’ quality of life.25,26 However, metastasis to regional lymph nodes in up to 10.7% of patients without abnormal prostate- specific antigen elevations indicates a need for close clinical monitoring in addition to prostate-specific antigen screening.27 Frequently cited metastatic targets for prostate cancer, including bone,9,28,29 lung,29 and liver,30 often present with clinical manifestations. The 5 most common metastatic targets for prostate cancer in the current study included regional lymph nodes (26.2%), bone (19.7%), distant lymph nodes (18.4%), lung (12.8%), and liver (7.8%) (Figure 7). Contemporary studies of prostate cancer continue to demonstrate a high degree of metastasis to these sites.31

Interestingly, prostate cancers represented a significant proportion (36%) of metastases to the testes (Figure 5), an otherwise unusual metastatic target that harbored only 0.1% of all metastatic lesions in the current study (Figure 3). Contemporary studies also document testes as an important site of subclinical prostatic metastases,32 albeit one whose significance in disease staging remains controversial. 33 Our results emphasize the importance ofmonitoring testicular metastases in a patient with known prostate cancer; moreover, metastases to this site by an unknown primary malignancy may eventually prove relatively specific for prostate cancer. This latter hypothesis will require further investigation.

Testicular Cancer

Testicular tumors were rare in this study (0.7% of all primary neoplasms; Figure 2). The 2006 National Center for Health Statistics reported similar rates with an overall incidence of only 1% of all male cancers.16 Yet testicular cancer remains not only the most common tumor in males between the ages of 15 and 35 years but also the most treatable one, with recently reported survival rates with prompt diagnosis and treatment as high as 90%.34 Therefore, as testicular cancer frequently presents among young males with cancer from unknown primary site, a thorough documentation of the metastatic behavior of this malignancy that enables prompt diagnosis would be of tremendous value. Once treatment has been initiated, such documentation might also facilitate monitoring of disease progression.

As shown in Figure 2 (compare corresponding blue and red bars), testicular primaries generate a disproportionate number of metastases. Figure 4, A, indicates that each primary malignancy generated an average of 5.8 metastases, the most for any primary malignancy. However, because of the low frequency of this primary malignancy in our study (Figure 2), testicular malignancies generated only 1.5% of all metastases. These metastases were broadly distributed, ranging from 0.9% of pleural to 12.5% of skeletal muscle metastases (Figure 4, B). Figure 8 further quanti- fies the metastatic behavior of testicular tumors. The most common metastatic sites are distant lymph nodes (14.4%), liver (13%), lung (12.3%), kidney (7.5%), and bone (5.5%). The latter site is notable, in that it represents a rare target for germ cell metastasis for testicular malignancies treated by current protocols. As a result, treatable metastases to bone are occasionally missed in the contemporary setting because of low clinical suspicion.35

Of note, Figure 5 shows that testicular cancers metastasized to unusual sites. For example, the prostate gland, a target for only 0.3% of all metastases (Figure 3), nonetheless received a single metastasis. Similarly, although only 0.2% of all metastases were found in skeletal muscle (Figure 3), 2 testicular metastases, or 12.5% of the total, were found there (Figure 5). Given the low absolute number of primary testicular malignancies identified in the current analysis, our findings suggest 2 important clinical implications that might benefit from further, more targeted studies. First, metastasis of an unknown primary to an unusual site (eg, stomach, prostate, skeletal muscle) in a male patient between the ages of 15 and 35 years might raise suspicion for a testicular origin. Second, these uncommon sites might be of value in monitoring relapse among treated patients with known testicular cancers.

CONCLUSION

The present study was based on an unusually rich set of autopsy data, comprising a large number of patients and a broad array of cancer types and metastases. Furthermore, as a uniquely broad study of actual postmortem tissues on patients who died before the advent of contemporary therapies, the findings of this study likely represent a close approximation for the progression of untreated malignancies in humans. Attesting to the unique value of these data, to our knowledge there are no studies analogous to the current one in either breadth or scale in the current literature. Given the current trend toward fewer hospital autopsies,2,3,36 it is difficult to envision future studies on postmortem tissue of this scale. Fortunately, several interesting implications emerge from the current study that, in conjunction with more contemporary, targeted studies, may prove a useful baseline in patient management. Moreover, it is our hope that this baseline will facilitate further studies to clarify the clinical and molecular behaviors of specific malignancies cited in this study, particularly those that occurred with less frequency.

We thank Harvey Goldman, MD, from the New England Deaconess Hospital for permission to reproduce these data.We thank Carol Newton, MD, PhD, from the Biomathematics Department at the UC Los Angeles/Geffen School of Medicine for helpful discussions regarding data interpretation and presentation.

References

1. Govindan R. The Washington Manual of Oncology. Philadelphia, Pa: Lippincott Williams & Wilkins; 2002.

2. Peacock SJ, Machin D, Duboulay CE, Kirkham N. The autopsy: a useful tool or an old relic? J Pathol. 1988;156:9-14. 3. Roberts WC. The autopsy: its decline and a suggestion for its revival. N Engl J Med. 1978;299:332-338.

4. Chariot P,Witt K, Pautot V, et al. Declining autopsy rate in a French hospital: physician’s attitudes to the autopsy and use of autopsy material in research publications. Arch Pathol Lab Med. 2000;124:739-745.

5. Schon CA, Gorg C, Ramaswamy A, Barth PJ. Splenic metastases in a large unselected autopsy series. Pathol Res Pract. 2006;202:351- 356.

6. Butany J, Leong SW, Carmichael K, Komeda M. A 30-year analysis of cardiac neoplasms at autopsy. Can J Cardiol. 2005;21:675-680.

7. Hess KR, Varadhachary GR, Taylor SH, et al. Metastatic patterns in adenocarcinoma. Cancer. 2006;106:1624-1633.

8. Abrams HL, Spiro R, Goldstein N. Metastases in carcinoma. Cancer. 1950; 3:74-85.

9. Venkitaraman R, Sohaib SA, Barbachano Y, et al. Detection of occult spinal cord compression with magnetic resonance imaging of the spine. Clin Oncol (R Coll Radiol). 2007;19:528-531.

10. Lee ST, Berlangieri SU, Poon AM, et al. Prevalence of occult metastatic disease in patients undergoing F-FDG PET for primary diagnosis or staging of lung carcinoma and solitary pulmonary nodules. Intern Med J. 2007;37:753-759.

11. Lee WS, Yun SH, Chun HK, Lee WY, Yun H. Clinical usefulness of chest radiography in detection of pulmonary metastases after curative resection for colorectal cancer. World J Surg. 2007;31:1502- 1506.

12. Aalten CM, Samson MM, Jansen PA. Diagnostic errors; the need to have autopsies. Neth J Med. 2006;64:186-190.

13. Hofmeister CC, Marinier DE, Czerlanis C, Stiff PJ. Clinical utility of autopsy after hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2007;13:26-30.

14. Sharma BR, Gupta M, Harish D, Singh VP. Missed diagnoses in trauma patients vis-a-vis significance of autopsy. Injury. 2005;36:976-983.

15. Nagata H, Arai T, Soejima Y, Suzuki H, Ishii H, Hibi T. Limited capability of regional lymph nodes to eradicate metastatic cancer cells. Cancer Res. 2004; 64:8239-8248.

16. Jemal A, Siegel R, Ward E, et al. Cancer statistics, 2006. CA Cancer J Clin. 2006;56:106-130.

17. Beckman CRB, Ling FW, Herbert WNP, Laube DW, Smith RP, Barzansky BM. Obstetrics and Gynecology. Baltimore, Md: Lippincott, Williams & Wilkins; 1998:822.

18. Bloom HJ, Richardson WW, Harries EJ. Natural history of untreated breast cancer (1805-1933): comparison of untreated and treated cases according to histological grade of malignancy. Br Med J. 1962;2:213-221.

19. Bailar JC III, Gornik HL. Cancer undefeated. N Engl J Med. 1997;336: 1569-1574.

20. Richardson RG, Parker RG. Metastases from undetected primary cancers. Clinical experience at a radiation oncology center. West J Med. 1975;123:337- 339.

21. Lenzi R, Hess KR, Abbruzzese MC, Raber MN, Ordonez NG, Abbruzzese JL. Poorly differentiated carcinoma and poorly differentiated adenocarcinoma of unknown origin: favorable subsets of patients with unknown-primary carcinoma? J Clin Oncol. 1997;15:2056-2066.

22. Broet P, de la Rochefordiere A, Scholl SM, et al. Contralateral breast cancer: metastasis or second primary cancer? [in French]. Bull Cancer. 1996;83:870- 876.

23. Wedam SB, Swain SM. Contralateral breast cancer: where does it all begin? J Clin Oncol. 2005;23:4585-4587.

24. Harvey EB, Brinton LA. Second cancer following cancer of the breast in Connecticut, 1935-82. Natl Cancer Inst Monogr. 1985;68:99- 112.

25. Brenner H, Arndt V. Long-term survival rates of patients with prostate cancer in the prostate-specific antigen screening era: population-based estimates for the year 2000 by period analysis. J Clin Oncol. 2005;23:441-447.

26. Katz G, Rodriguez R. Changes in continence and health- related quality of life after curative treatment and watchful waiting of prostate cancer. Urology. 2007;69:1157-1160.

27. Weckermann D, Wawroschek F, Harzmann R. Is there a need for pelvic lymph node dissection in low risk prostate cancer patients prior to definitive local therapy? Eur Urol. 2005;47:45-50, discussion 50-41.

28. Ye L, Kynaston HG, Jiang WG. Bone metastasis in prostate cancer: molecular and cellular mechanisms [review]. Int J Mol Med. 2007;20:103-111.

29. Maeda T, Tateishi U, Komiyama M, et al. Distant metastasis of prostate cancer: early detection of recurrent tumor with dual-phase carbon-11 choline positron emission tomography/computed tomography in two cases. Jpn J Clin Oncol. 2006;36:598-601.

30. Attila T, Datta MW, Sudakoff G, Abu-Hajir M, Massey BT. Intrahepatic portal hypertension secondary to metastatic carcinoma of the prostate. WMJ. 2007;106:34-36.

31. Arai Y, Kanamaru H, Yoshimura K, Okubo K, Kamoto T, Yoshida O. Incidence of lymph node metastasis and its impact on long-term prognosis in clinically localized prostate cancer. Int J Urol. 1998;5:459-465.

32. Escoffery CT, Shirley SE. Testicular metastases from carcinoma of the prostate. West Indian Med J. 1999;48:235-237.

33. Kirkali Z, Reid R, Deane RF, Kyle KF. Silent testicular metastasis from carcinoma of the prostate. Br J Urol. 1990;66:205- 207.

34. Bosl GJ, Motzer RJ. Testicular germ-cell cancer. N Engl J Med. 1997;337: 242-253.

35. Benedetti G, Rastelli F, Fedele M, Castellucci P, Damiani S, Crino L. Presentation of nonseminomatous germ cell tumor of the testis with symptomatic solitary bone metastasis: a case report with review of the literature. Tumori. 2006; 92:433-436.

36. Loughrey MB, McCluggage WG, Toner PG. The declining autopsy rate and clinicians’ attitudes. Ulster Med J. 2000;69:83-89.

Guy diSibio, MD, PhD; Samuel W. French, MD

Accepted for publication December 14, 2007.

From the Department of Pathology, Harbor-UCLA Medical Center, Torrance, Calif.

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

Presented as a poster at the annual meeting of the United States and Canadian Academy of Pathology, San Diego, Calif, March 26, 2007.

Reprints: Guy diSibio, MD, PhD, Department of Pathology, Harbor- UCLA Medical Center, 1000 W Carson St, Torrance, CA 90509 (e-mail: [email protected]).

Copyright College of American Pathologists Jun 2008

(c) 2008 Archives of Pathology & Laboratory Medicine. Provided by ProQuest Information and Learning. All rights Reserved.

By Hicks, David G Kulkarni, Swati

* Context.-Overexpression of human epidermal growth factor receptor 2 (HER2) is an adverse prognostic parameter for patients with breast cancer. Patients with HER2- positive tumors are, however, likely to gain significant benefit from targeted therapy with trastuzumab. Four largescale trials have assessed the efficacy and safety of adjuvant trastuzumab. In all 4 trials, disease-free survival and overall survival were significantly improved with adjuvant trastuzumab (36%-52% and 33%-41%, respectively), and improvements were observed in all patient subgroups. Objective.-To describe, in detail, the clinical benefits of using trastuzumab in the adjuvant setting, and to emphasize the importance this places on the pathologist to correctly identify all patients with HER2- positive tumors with a high degree of accuracy.

Data Sources.-Published literature on both HER2 testing and the adjuvant use of trastuzumab.

Conclusions.-Immunohistochemistry and/or fluorescence in situ hybridization are routinely used to determine HER2 status. Maintaining quality assurance throughout a standardized testing process is essential to achieve accurate and reproducible assay results. Adherence to the new American Society of Clinical Oncology/ College of American Pathologists HER2 testing guidelines will help to ensure correct identification of all patients who may benefit from adjuvant trastuzumab and has significant implications for patient outcomes.

(Arch Pathol Lab Med. 2008;132:1008-1015)

Success in the clinical setting has led to trastuzumab (Herceptin; Genentech, Inc, South San Francisco, Calif) becoming an important part of the adjuvant treatment algorithm for patients with human epidermal growth factor receptor 2 (HER2)-positive disease.1 Given the significant clinical benefits available to patients with HER2-positive breast cancer, it is of paramount importance to accurately identify all patients eligible for this therapy. Input from pathologists early in the treatment decision process is therefore vital to determine tumor HER2 status. Here we provide an overview of trastuzumab clinical data in the adjuvant setting and discuss the issues that pathologists may face when identifying patients who may benefit from this therapy.

Breast cancer is the most common form of cancer in women, and nearly half a million new cases are expected to be diagnosed every year in the United States and Europe alone.2 Although in recent years there has been a downward trend in the incidence of breast cancer, it will still account for 25% to 30% of new cancer cases and mu16% of cancer-related deaths in women.2,3 Of these patients, 25% to 30% will have HER2 gene amplification or protein overexpression.4 This has an important bearing on disease course and prognosis, as HER2-positive breast cancer is aggressive and associated with poor clinical outcomes.4-7 Although normal levels of HER2 are important for physiologic cellular function, overexpression of HER2 promotes receptor activation, increased signaling, and excessive cellular division.8 HER2-positive tumor cells therefore have increased proliferation and survival characteristics that typically result in aggressive tumors.4,9-12 As adverse pathologic prognostic factors (higher grade, larger size, lymph node involvement, increased proliferative index) are also associated with HER2 status, this further emphasizes HER2 status as a key molecular marker, which drives both the biology of the tumor as well as the clinical course for the disease.

TRASTUZUMAB

Trastuzumab is an anti-HER2 monoclonal antibody that has been used for the treatment of HER2-positive breast cancer in 420 000 patients worldwide during the last decade (Genentech, data on file). Although the mechanisms of action for trastuzumab are not yet fully defined, key mechanisms include effects on both the extracellular and intracellular domains of the HER2 receptor. Action via the extracellular domain results in antibody-dependent cellmediated cytotoxicity and constant HER2-receptor inhibition. Subsequent actions via the intracellular domain lead to downstream signal transduction inhibition, cellcycle arrest, reduction in angiogenesis, and inhibition of extracellular domain cleavage resulting in HER2-positive cell stasis and death.13-23

Trastuzumab has an antiproliferative effect, and patients with tumors that overexpress the HER2 protein, most commonly resulting from amplification of the HER2 gene, gain the most clinical benefit from this treatment.24-27 Trastuzumab is indicated for use with paclitaxel as firstline treatment or as monotherapy for patients with metastatic breast cancer who have previously received chemotherapy. 28

More recently, 4 large trials have assessed the benefits of adjuvant trastuzumab either in combination with or following chemotherapy for early-stage breast cancer. Results obtained from the 2 randomized, controlled clinical trials in the United States have led to the US Food and Drug Administration (FDA) approving trastuzumab for use in the adjuvant setting. Trastuzumab can now be included as part of a treatment regimen containing doxorubicin, cyclophosphamide, and paclitaxel for patients with HER2- positive, node-positive breast cancer in the United States.28

ADJUVANT TRASTUZUMAB

Trial Design

Four large-scale trials have assessed the efficacy and safety of trastuzumab use in the adjuvant setting. These are the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-31 trial (US; N = 2043); the North Central Cancer Treatment Group (NCCTG) N9831 trial (US; N = 1633); the Herceptin Adjuvant (HERA) trial (non-US; N = 5102); and the Breast Cancer International Research Group (BCIRG) 006 trial (worldwide; N = 3222).

The primary endpoint was disease-free survival (DFS) in all of these multicenter, randomized trials. The adjuvant trial designs are summarized in Figure 1. In general, patients with node-positive and HER2-positive breast cancer were enrolled. Definitions of HER2 positivity are discussed in a later section.

The NSABP B-31 trial compared the outcomes of anthracycline- cyclophosphamide (AC; doxorubicin and cyclophosphamide) with or without trastuzumab.29 Patients were randomized to 1 of 2 arms. Arm 1 received doxorubicin (60 mg/m^sup 2^) and cyclophosphamide (600 mg/ m^sup 2^) for four 3-week cycles, followed by paclitaxel (175 mg/ m^sup 2^) for four 3-week cycles. Arm 2 received the same chemotherapy regimen plus concomitant trastuzumab, administered as a loading dose (4 mg/kg) with the first dose of paclitaxel, then as weekly doses of 2 mg/kg for 51 weeks.

In the NCCTG N9831 trial, patients were randomized among 3 arms.29 Arm A received AC therapy (as in NSABP B-31 arm 1) followed by 12 weekly doses of paclitaxel (80 mg/m^sup 2^). Arm B received the same chemotherapy regimen as arm A, followed by a course of post- pac litaxel trastuzumab therapy. Trastuzumab was given as a loading dose (4 mg/kg) followed by weekly doses of 2 mg/kg for 51 weeks. Arm C received the same chemotherapy regimen as arm A with the addition of concomitant trastuzumab (dosed as described for arm A).29

In the NSABP B-31 and NCCTG N9831 trials, the control arms (arms 1 and A, respectively) and treatment arms 2 and C, respectively, are identical; therefore, the FDA approved a joint analysis of the comparable arms.29

In the HERA study, patients who had previously received a predefined neoadjuvant or adjuvant chemotherapy regimen (for a minimum of 4 cycles or 4 months) with or without radiation therapy were randomized to 1 of 3 arms.30 Arm A received no trastuzumab (observation only control arm). Treatment arms B and C received a loading dose of trastuzumab (8 mg/kg) followed by 6 mg/kg in 3-week cycles for 1 year (arm B) or 2 years (arm C).30,31

In the BCIRG 006 study, patients were randomized among 3 treatment arms.32 As with the NSABP B-31 and NCCTG N9831 trials, the BCIRG 006 study design was based on four 3-week cycles of AC therapy, followed by four 3-week cycles of taxane therapy. Doxorubicin (60 mg/m^sup 2^) was used in combination with cyclophosphamide (600 mg/m^sup 2^), and docetaxel (100 mg/m^sup 2^) replaced paclitaxel in the taxane phase of chemotherapy for arm A and arm B. After completion of docetaxel therapy, arm B also received weekly trastuzumab for up to 1 year (2 mg/kg). Arm C assessed a nonanthracycline chemotherapy combination, as anthracyclines have been associated with an increased risk of cardiac dysfunction in patients receiving concurrent trastuzumab.26,33,34 Arm C was based on the synergy among the 3 agents and efficacy in treating metastatic disease9 and comprised six 3-week cycles of docetaxel (T) (75 mg/m^sup 2^) and carboplatin (C) (AUC6) with a weekly standard dose of trastuzumab (H) during chemotherapy (2 mg/kg), switching to 3-week cycles for 1 year of follow-up. This arm is referred to as the TCH arm.

Efficacy Data

In all 4 adjuvant trials, DFS was significantly higher in the trastuzumab-containing arms compared with control/ observation arms (Figure 2). In the updated joint analysis of NSABP B-31 and NCCTG N9831 (median follow-up of 2.9 years), the addition of trastuzumab to adjuvant chemotherapy significantly improved DFS by 52% compared with chemotherapy alone (hazard ratio [HR] = 0.48; 95% confidence interval [CI], 0.41-0.57; P < .001).35 This improvement in DFS is consistent with an earlier interim analysis (52% HR = 0.48; P < .001).29 In a 2-year follow-up of the HERA trial, DFS was significantly improved by 36% (P < .001) with trastuzumab versus observation only.31 In the BCIRG 006 trial, addition of trastuzumab to adjuvant chemotherapy reduced the risk of recurrence by 33% (P < .001) and 39% (P < .001) for nonanthracycline- and anthracycline- containing adjuvant chemotherapy, respectively.32 Differences in the trastuzumab- containing arms were not statistically signifi- cant.

In subset analysis, improvements in DFS were observed in all groups assessed. DFS was similar for patients with hormone receptor- positive or -negative tumors, in all patient age groups ranging from younger than 40 years to older than 60 years, regardless of tumor size.29,32,36

Overall survival (OS) was measured as a secondary endpoint in these trials. In the NSABP B-31 and NCCTG N9831 trials, OS was significantly increased by 35% at 4 years (P < .001; HR = 0.65; 95% CI, 0.51-0.84).35 Patients enrolled in the HERA (34%; P = .01) trial also achieved significant OS benefit in the trastuzumab-containing arms.31 In the BCIRG 006 trial, improvement in OS was 41% (P < .001) in the anthracycline-containing arm and 34% (P = .02) in the nonanthracycline arm.32

Additional data are also available for the smaller FinHer (Finland Herceptin) trial. A total of 232 patients with HER2- positive early breast cancer were randomized to receive either docetaxel or vinorelbine with or without a short course (9 weeks) of trastuzumab therapy followed by combination chemotherapy.37 Relapse- free survival was significantly higher (58% improvement) in those patients receiving trastuzumab at 3 years (89% vs 78%; HR = 0.42; P = .01). Although these data are interesting, this trial has limitations. The number of patients enrolled was small, the responses were inconsistent (indicated by the confidence interval range), and the follow-up time was short.

The results from the large adjuvant trials demonstrated that trastuzumab significantly improves DFS and OS compared with adjuvant chemotherapy alone in patients with HER2-positive early breast cancer. The National Comprehensive Cancer Network guidelines currently recommend adding 1 year of trastuzumab to standard adjuvant chemotherapy for HER2-positive breast cancer.1

CARDIAC SAFETY

Overall, there was little imbalance in adverse events among all treatment arms. Trastuzumab was generally well tolerated in all 4 trials, and no unexpected adverse events were reported.29,31,32,38

In the 4 large trastuzumab adjuvant trials, the difference in cumulative incidence of congestive heart failure or death due to cardiac causes was less than the Independent Data Monitoring Committee safety cutoff of 4%. This was assessed in patients receiving trastuzumab-containing treatment compared with non- trastuzumab-containing treatment, indicating acceptable cardiac safety.31,36,39,40 The incidence of congestive heart failure was higher in tras tuzumab-treated patients, but this was generally responsive to standard medical treatment.29,31,32,38 Direct comparisons between trials are difficult due to differences in analysis time points, eligibility criteria, and definition of cardiac events. However, the difference in cumulative incidence of congestive heart failure is typically 1.5% to 2.7% (trastuzumab vs nontrastuzumab arms).31,32,35,40 Potential risk factors for cardiac events have been identified and include age (>/=50 years), the need for hypertension medication, and pretrastuzumab left ventricular ejection fraction levels of 50% to 54%.33,38,41 Furthermore, an NCCTG N9831 substudy of cardiac biomarkers indicated that brain natriuretic peptide and troponin I may be promising as predictors of cardiac toxicity.42

IDENTIFYING PATIENTS ELIGIBLE FOR ADJUVANT TRASTUZUMAB THERAPY

Although each trial had specific eligibility criteria (node status, tumor size, hormone receptor status, prior therapy), all patients must have had confirmed HER2-positive breast cancer. HER2 status was assessed by immunohistochemistry (IHC) and/or fluorescence in situ hybridization (FISH). Each assay is discussed in detail below. A score of IHC 3+ (more than moderate staining in >> 10% of tumor cells) and a FISH HER2/centromere of chromosome 17 (CEP17) ratio greater than 2.0 were considered positive for trial entry. The criteria used to define HER2 status have recently been reevaluated and incorporated into updated testing guidelines and are discussed below.43 With the increasing utilization of needle core biopsies for the primary diagnosis of breast cancer, it has become common practice to perform HER2 testing on these samples. While there is an advantage to having information on the HER2 status at this earlier time in terms of treatment planning, it remains debatable whether doing predictive marker testing on needle biopsies is clearly preferable to testing the excision specimen.

An Immunologic Approach to HER2 Testing

The research assay developed for patient enrollment into the early trastuzumab clinical trials served as the developmental prototype for 2 FDA-approved commercially available HER2 IHC-based assays, the HercepTest assay (Dako North America, Inc, Carpinteria, Calif) and the Ventana PATHWAY assay (Ventana Medical Systems, Tucson, Ariz). In order to semiquantitively assess HER2 expression, a 4-point scale was developed to record both the pattern and intensity of the staining reaction. Staining is recorded as negative (0 and 1+), equivocal for HER2 overexpression (2+), or strongly positive (3+). Only the degree and completeness of membrane staining are regarded as significant in the evaluation of a HER2 IHC assay. An IHC 3+ score was required for entry into the adjuvant clinical trials. This was defined as 10% of tumor cells showing a thick, complete membrane pattern of staining, based on previously established guidelines. The new American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guidelines have updated the IHC definitions. An IHC result of 3+ is defined as uniform complete cell membrane staining in greater than 30% of invasive cancer cells. A score of IHC 2+ most typically demonstrates a nonuniform or weak intensity membrane staining in greater than or equal to 10% of cells or more rarely, intense membrane staining of less than 30% of cells.43

Although some tumors are readily defined as HER2 positive by demonstrating a diffuse and intense staining reaction, a score of IHC 2+ should be considered an equivocal result. These tumors typically have poor correlation with HER2 gene status, and this result should be considered as inconclusive. Tumors with a HER2 IHC 2+ score should be reflex tested for HER2 gene amplification using FISH, as recommended in the updated guidelines.43

Detecting HER2 Gene Amplification by FISH Analysis

In contrast to quantifying the amount of HER2 protein, FISH analysis is designed to assess HER2 gene copy number and detect gene amplification using fluorescence microscopy. The HER2 gene is located on chromosome 17. Interpretation of FISH assays depends on scoring the exact number of HER2 hybridization signals per tumor cell nucleus using a fluorescent-labeled nucleic acid probe specific for the HER2 gene. In the FDA-approved PathVysion assay (Vysis Inc, Downers Grove, Ill), the ratio of the average number of copies of HER2 to the average number of copies of CEP17 helps to distinguish true gene ampli- fication (HER2/CEP17 >> 2) from pseudo- amplification due to multiple copies of chromosome 17 (polysomy; HER2/CEP17 ratio of <2). The INFORM HER2 assay has a different approach and uses the absolute level of HER2 gene signal. This approach could be considered a nuclear criterion of gene amplification (average number of HER2 gene signals per tumor cell nucleus) as opposed to the chromosomal criterion for gene amplification (HER2/ CEP17 ratio) utilized by the PathVysion assay. Both FISHbased assays use defined cutoffs to identify gene ampli- fication. For entry into the adjuvant trials, FISH positivity was defined as a HER2/CEP17 ratio greater than or equal to 2.

Current guidelines now define HER2-positive tumors by FISH as having an average HER2 gene copy number of more than 6 gene copies per nucleus or as a HER2/ CEP17 ratio of more than 2.2.43 The equivocal range for FISH assays is defined as HER2/CEP17 ratio of 1.8 to 2.2 or an average gene copy number between 4.0 and 6.0.

Approximately 3% of tumors will have a HER2/CEP17 ratio very close to the previous 2.0 boundary.43 Although a FISH ratio of 1.8 to 2.2 has now defined a new subgroup, the clinical significance for the HER2 status for tumors in this range remains unclear. The potential benefit from HER2-directed therapy for patients with tumors that fall within this borderline (equivocal) category has not yet been fully evaluated and requires further study.43 Treatment of these women depends on the overall clinical picture and can be facilitated by a discussion between the pathologist and oncologist.

The incidence of polysomy for chromosome 17 is an additional consideration when performing FISH assays. As this is not fully defined in terms of HER2 status and response to trastuzumab, the updated ASCO/CAP guidelines do not address this issue.43,44

ADDRESSING HER2 TESTING ISSUES: APPLYING GUIDELINES TO CLINICAL PRACTICE

Early analysis of the adjuvant trials with trastuzumab highlighted the importance of accurate HER2 testing. Preliminary data from patients enrolled in adjuvant trastuzumab trials revealed poor concordance between local and central laboratory assessments of HER2 status.45,46 To ensure the enrollment of patients with the highest probability of benefiting from trastuzumab, eligibility criteria for these trials were subsequently modified to require central laboratory confirmation of HER2 status. The potential reasons for this discordance and the importance of accurate HER2 testing are discussed below. Central Versus Local Testing

One of the aims of the NSABP B-31 trial was to assess concordance between local and central laboratories.45 Initially, a local HercepTest IHC 3+ score or gene amplifi- cation by FISH allowed participation in the trial. Central review of the first enrolled patients (n = 104) demonstrated that 79% (82/104) of tumors were IHC 3+ by HercepTest with 21% being discordant. A total of 79% (82/104) of tumors were FISH positive by PathVysion assay, with a 21% discordance rate.45

Importantly, there was less discrepancy identified between HER2 tests when a high-volume laboratory (mean tumors assessed per month, >>100) performed the assay, compared with laboratories with lower throughput. In response to this finding, the eligibility criteria for the NSABP B-31 trial were amended to include only those patients whose tumors were IHC 3+ according to an NSABP-approved reference laboratory or tumors demonstrating gene amplification by FISH from any laboratory. The rate of IHC discordance (via central review) subsequently reduced to ~3% (n = 240). A similar analysis has reported comparable findings for the NCCTG N9831 trial (n = 119) with a discordance rate of 26% (local vs central testing).46 In an additional study comparing local and central laboratory testing, there was a marked difference in rates of false-positive results (local vs central IHC, 14%; local IHC vs central FISH, 16%) and false-negative results (local vs central IHC, 18%; local IHC vs central FISH, 23%).47 The question arises as to why these differences occur. Two key factors are likely to be of prime importance: the standardization of testing protocols and differences in test interpretation based on individual pathologist experience.48

Persons and colleagues49 recently reported results from HER2- related FISH surveys. Interlaboratory reproducibility of HER2 analysis was high for tumors with no ampli- fication or high amplification of the HER2 gene. But, as with IHC analysis, the challenge of assessing tumors with low-level or equivocal/ borderline amplification was highlighted as problematic. Testing with FISH found 92% concordance between local and central laboratories versus 77.5% with local versus central IHC. Fluorescence in situ hybridization analysis may therefore be more accurate when central laboratory testing is unavailable.50

Discordance Between Methodologies

Immunohistochemistry 3+ staining and gene amplifi- cation by FISH can both be used to identify those patients who are most likely to benefit from trastuzumab therapy. In theory, IHC and FISH assays should give complementary results with the advantages of each providing additional supportive interpretative data. This is especially important for those patients with equivocal test results.

In practice, however, discordant results (IHC 3+/FISH negative or IHC <3+/FISH positive) between the 2 methodologies have been reported. Discussion is ongoing as to whether this is due to real biologic differences in protein (HER2 receptor) versus gene expression or an artifact of the assay methodology. A number of plausible explanations have been put forth in the literature to try to explain the reported discrepancies encountered between HER2 IHC and FISH. For example, variation in HER2 testing could occur due to adverse effects of variable fixation.51,52 This would tend to have a more detrimental effect on IHC assays given the stability of DNA versus HER2 protein. The potential role of polysomy for chromosome 1753-56 and its effect on HER2 gene expression remains to be fully defined and is a likely explanation for some cases of discrepancy between FISH and IHC. Finally, the inherent subjectivity and reproducibility of IHC scoring criteria, 51,57,58 along with differences in sensitivity and specificity between antibodies used for IHC assays,7,51,59 have been put forth as another explanation for some cases of discordant results.

Despite the lack of concordance that can be encountered between the 2 methodologies, when properly performed and interpreted, patients with tumors characterized as either IHC 3+ (independent of FISH status) or FISH positive (independent of IHC status) had comparable times to progression and overall survival with a trastuzumab-containing therapy.

Of interest is the fact that despite the underlying biology, concordance rates similar to those seen in frozen tumors have not been reported when using IHC for HER2 evaluation in formalin-fixed tissue samples. Good correlation has been reported for HER2 protein/ gene results in formalin-fixed, paraffin-embedded tumor samples by many investigators. Others, however, have reported significant discordant results between FISH and IHC and have questioned the accuracy of IHC HER2 testing in formalin- fixed tissues.7,60-66 The FDA approval for both the IHC and FISH assay methodologies requires that all tissues should be fixed in 10% neutral buffered formalin. Non-formalin-based fixatives or alternative fixation methodologies for breast specimens are discouraged as performance data are limited and extrapolation from formalin- fixed data can be unreliable.43 Current guidelines suggest that tissue fixation should occur as soon after acquisition as possible and that fixation for 6 to 48 hours is optimal. Furthermore, tissue should be transported from the operating room to the pathology department within 30 minutes and an immediate gross examination should be performed to facilitate rapid fixation of the tissue sample. How do these findings and subsequent recommendations impact on pathology laboratory practice? To identify all patients who may benefit from trastuzumab, rigorous quality control together with standardization of reagents, assay performance, and test interpretation are needed to improve agreement between HER2 IHC and FISH results in the clinic.

Adherence to strict laboratory quality control, improvements in tissue fixation and embedding procedures, standardization of IHC methodologies, and the use of automated image analysis to remove some of the subjective nature of assay interpretation may all increase the accuracy of IHC testing for HER2 status.60,67 Computerized automated cellular imaging systems are now commercially available and can improve the precision and reliability of analysis. The high degree of correlation between IHC analysis using automated cellular imaging systems and results obtained using FISH highlights that mistakes in manual IHC interpretation may contribute to discordant results.68 These findings underline the need for standard ization of all aspects of the HER2 testing process from tissue acquisition to accurate assay interpretation and reporting.

The Future of HER2 Testing: Toward Greater Accuracy

In addition to the need to reappraise the HER2 algorithm and assay result definitions, issues surrounding test variation and accuracy were a key driver for the development of the recent ASCO/ CAP task force guidelines. It is important that all pathology laboratories establish a high degree of quality assurance by maintaining high concordance rates (>/=95%) between the 2 assay methodologies and offer only fully validated IHC and FISH tests for clinical decision making. Assay validation must include using comparable and established fixation and tissue handling protocols (in at least 25-100 tumors), demonstrating a high degree of concordance against a previously validated assay methodology. Laboratories must also routinely record a standardized set of reporting elements (methods, dates, controls, etc) for both test methodologies. Pathologists will also undergo ongoing assessments to ensure correct and accurate interpretation of assays. Furthermore, from 2007 onward, external assessment of HER2 testing accuracy in CAP-accredited laboratories will demand performance above 90% (via proficiency testing). Standard laboratory inspection will assess all aspects of the HER2 testing protocol from tissue handling through test validation to assay interpretation as a part of laboratory accreditation.

A key conclusion of the ASCO/CAP expert consensus panel was that the 2 methodologies for assessing HER2 status are both acceptable for identifying patients who are likely candidates for response to trastuzumab therapy. The important point is that the tests must be properly performed and interpreted to identify the eligible patients. Both methodologies have performance and interpretive challenges, and they should be viewed as complementary rather than one versus the other.

FUTURE DIRECTIONS

Early preliminary data from the NSABP B-31 trial suggest that benefit from adjuvant trastuzumab may not be confined to those patients with HER2-positive tumors (IHC 3+ and FISH positive [HER2/ CEP17 ratio >> 2.2]) using our current definitions for HER2 status.69 In this analysis, as expected, those patients with HER2- positive tumors gained benefit from trastuzumab. In addition, there was a limited subset of patients who had tumors that were FISH negative and graded less than IHC 3+ who also achieved significant benefit (P = .03) from adjuvant trastuzumab. Identifying potential differences will help explain why these patients responded to trastuzumab despite testing negative for HER2. These data suggest that the criteria pathologists use to identify HER2- positive tumors may need to be reevaluated and/or modified in the adjuvant setting, but clearly more research is needed. These data are intriguing but preliminary, and caution should be exercised in interpreting the results until further data on more patients can be analyzed.

Current HER2 testing algorithms may need to be modified to account for low-level amplification and other genotypic abnormalities that can be seen in some tumors. Kaufman and colleagues70 demonstrated that tumors with increased chromosome 17 polysomy (low-level amplification; see below), but conventionally defined as HER2 negative for amplification by the HER2/CEP17 ratio, may responded favorably to trastuzumab-based therapy. These data raise the possibility that the HER2/CEP17 ratio may not be the best way to evaluate the HER2 status in all cases and that the absolute HER2 gene copy number (whether increased through amplification or polysomy) may be the more important determinant for trastuzumab response for some patients. Together, these studies suggest the intriguing possibility that even when a patient has a FISH-negative tumor (and

SUMMARY

The significant gains in DFS and OS from adjuvant trastuzumab have been demonstrated in 4 large trials. It is vital that all patients eligible for treatment are accurately identified. Pathologists play a central role in this process.

Immunohistochemistry and FISH are both valid methodologies for assessing HER2 status. Studies showing a lack of concordance between HER2 testing results from different laboratories emphasize the need for standardization in methodology and rigorous quality control. The ASCO/CAP guidelines provide useful recommendations for optimizing HER2 testing, and strict adherence to these guidelines, combined with new testing technologies, should ensure improved accuracy and reproducibility of HER2 testing and ultimately lead to improvements in patient outcomes.

Support for third-party writing assistance for this article was provided by Genentech, Inc.

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David G. Hicks, MD; Swati Kulkarni, MD

Accepted for publication January 8, 2008.

From the Department of Pathology and Laboratory Medicine, University of Rochester, Rochester, NY (Dr Hicks); and Department of Surgical Oncology, Roswell Park Cancer Institute, Buffalo, NY (Dr Kulkarni).

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

Reprints: David G. Hicks, MD, Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, 601 Elmwood Ave, Box 626, Rochester, NY 14642 (e-mail: David=Hicks@urmc. rochester.edu).

Copyright College of American Pathologists Jun 2008

(c) 2008 Archives of Pathology & Laboratory Medicine. Provided by ProQuest Information and Learning. All rights Reserved.

By Jeremy Wise, The Enterprise Ledger, Ala.

Jun. 14–As the summer heats up, the activities follow suit at the Enterprise YMCA.

With the increase in temperatures, much of the action occurs in the pool said Richard Pipkin, YMCA director.

Water aerobics, taught monthly, are one activity in demand.

Swimming lessons are given for all ages, including an adult class, which will have a session from June 23-26 and June 30 — July 3. The classes last from 6 to 6:45 p.m.

There is even something for the very young as children from 6 months to 36 months can participate in Water Babies.

The classes occur in two age groups July 7-11. Babies from 6 to 18 months swim from 5:15 p.m. to 6 p.m., while children ages 19 months to 36 months swim from 6 p.m. to 6:45 p.m.

The fitness center is also busy during the summer as cycling classes, aerobics and weightlifting are available. A personal trainer, Sally Brodeur, is also available, Pipkin said.

Tennis lessons are also given at the YMCA monthly, while some opt for “Early Bird” basketball.

Players meet at the YMCA at 6 a.m. Tuesdays, Thursdays and Fridays to play hoops until 7 a.m.

Taekwondo lessons are also given.

Pipkin added registration for the YMCA’s fall soccer league will occur soon.

Of course, the main activities at the YMCA in the summer are the summer camps.

Pipkin said about 300 children from ages 2 1-2 to 12 are participating in the summer camps from 7 a.m. to 6 p.m.

Campers are involved in a vast array of activities including fitness training, swimming, arts and crafts, playing sports and games and watching movies.

Pipkin also said Christian values are taught in summer camps.

Pipkin added nursery care is available at YMCA.

“I want to thank the community for volunteering and their support financially to help us overcome the tornado,” the director said.

For more information on activities available at the YMCA, call 347-4513 or 347-0214.

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To see more of The Enterprise Ledger or to subscribe to the newspaper, go to http://www.eprisenow.com/.

Copyright (c) 2008, The Enterprise Ledger, Ala.

Distributed by McClatchy-Tribune Information Services.

For reprints, email [email protected], call 800-374-7985 or 847-635-6550, send a fax to 847-635-6968, or write to The Permissions Group Inc., 1247 Milwaukee Ave., Suite 303, Glenview, IL 60025, USA.

By David Pittman, Amarillo Globe-News, Texas

Jun. 12–A day of job shadowing last year at Pampa Regional Medical Center changed Ashley Murray’s life.

The girl, now about to start her junior year at Groom High School, witnessed her first delivery of a baby last summer while at the hospital for a summer camp aimed at sparking teen interest in health care careers.

Since then, Murray has volunteered in labor and delivery at the Pampa hospital.

“I saw a delivery at the camp last summer, and it made me look at the career more,” Murray said of the Panhandle Area Health Education Center’s MASH camp.

Since 2005, Panhandle AHEC has hosted the four-day camp that offers a glance at a range of health careers.

The center targets young people, particularly from rural areas, to steer them toward careers in the health industry.

“For us to get them hooked, we have to start early,” Program Coordinator Jennie Russell said.

The center also makes presentations to area schoolchildren and connects rural health providers with potential future employees.

If students enter a medical field, they can help ease a growing shortage of health care workers.

Center Director Tommy Sweat said almost every rural hospital is hiring for positions across the board from physicians to nurses’ aides to X-ray techs.

Federal grants fund Panhandle AHEC through the Texas Tech University Marie Hall Institute of Rural and Community Health. Tech subcontracts out with West Texas A&M University College of Nursing and Health Sciences to run Panhandle AHEC.

“We try to give people education and connect people because one of the missions of AHEC is to make people healthier through education,” Sweat said.

Campers who come from Amarillo and surrounding communities such as Memphis, Cal Farley’s Boys Ranch, Dalhart and Happy pay $55 for the camp.

Seven campers attended this year’s advanced camp. Twenty-seven just completed a basic camp.

The students visited the Texas Tech School of Pharmacy, job shadowed at Pampa Regional Medical Center, studied athletic training with WT athletic staff, trained on simulation mannequins at the WT school of nursing and participated in other health-related activities.

Twenty-eight students who graduated from high school in 2006 or 2007 have either attended a Panhandle AHEC summer camp or job shadowing experience, Sweat said.

As of last summer, 15 were pursuing a medical career, including nursing, pre-medicine and pre-pharmacy.

This is the second summer Gwen McGaugh has attended a Panhandle AHEC camp.

McGaugh, a rising senior at River Road High School, is considering becoming an emergency room doctor, pediatric surgeon or veterinarian.

“I found out this is what I want to do,” McGaugh said.

—–

To see more of the Amarillo Globe-News, or to subscribe to the newspaper, go to http://www.amarillonet.com.

Copyright (c) 2008, Amarillo Globe-News, Texas

Distributed by McClatchy-Tribune Information Services.

For reprints, email [email protected], call 800-374-7985 or 847-635-6550, send a fax to 847-635-6968, or write to The Permissions Group Inc., 1247 Milwaukee Ave., Suite 303, Glenview, IL 60025, USA.

PARIS, June 13 /PRNewswire/ — Patients who suffer the chronic and debilitating effects of rheumatoid arthritis (RA) — despite treatment with current therapies — achieved significant improvements in signs and symptoms when treated with Roche’s ACTEMRA(R) (tocilizumab) alone or in combination with methotrexate compared with methotrexate alone, according to two international Phase III studies presented by researchers at the European Congress of Rheumatology (ECR) held by the European League Against Rheumatism (EULAR) in Paris.

Data from two new Phase III studies — RADIATE and AMBITION trials — will be highlighted as oral presentations at the congress, along with 21 additional abstracts involving ACTEMRA, a novel interleukin-6 (IL-6) receptor inhibitor being studied for the treatment of moderate to severe RA. Importantly, findings from the RADIATE study were also published online this week in the Annals of the Rheumatic Diseases.

In the RADIATE study, which evaluated difficult-to-treat patients who failed to respond to prior anti-TNF therapies, 50 percent of ACTEMRA-treated patients achieved a 20 percent (ACR20(1)) reduction in signs and symptoms. The AMBITION study showed that significantly more patients receiving ACTEMRA achieved a 20 percent improvement in their signs and symptoms [ACR20: 70%]. No previous biologic therapy has demonstrated statistically significant superiority compared to methotrexate in this important clinical parameter at week 24. In addition, nearly one-third of all ACTEMRA patients from both studies reached disease remission (as defined by DAS28

“We are very encouraged by the results of the AMBITION study that shows for the first time that treatment with a single biologic agent is superior to methotrexate at six months of therapy,” said Graeme Jones, M.D., lead investigator of the AMBITION trial and Associate Professor at the University of Tasmania in Hobart, Australia. “Overall, these compelling results further establish the efficacy and safety of ACTEMRA in treating the chronic signs and symptoms of RA that dramatically affect the lives of patients.”

About AMBITION Study

The main AMBITION (Actemra versus Methotrexate double-Blind Investigative Trial In mONotherapy) study, a two-arm, randomized, double-blind, placebo-controlled study, was designed to evaluate the non-inferiority and subsequent superiority of ACTEMRA monotherapy in patients with RA compared with methotrexate alone at 24 weeks. Patients who had not received methotrexate for at least six months beforehand were randomized to receive either ACTEMRA (8 mg/kg) intravenously every four weeks plus placebo capsules weekly or placebo infusions every four weeks plus methotrexate weekly. The study evaluated 673 patients from 252 trial sites in 18 countries, including the United States.

In the AMBITION study, 70 percent, 44 percent and 28 percent of patients in the ACTEMRA (8 mg/kg) arm achieved ACR20, ACR50 and ACR70 compared, respectively, with 53 percent, 34 percent and 15 percent, respectively, of patients treated with methotrexate alone. Disease remission (DAS28

ACTEMRA was generally well tolerated; the most common adverse reactions reported more frequently in the ACTEMRA arm of the AMBITION trial were upper respiratory tract infections, headache and nasopharyngitis.

About RADIATE Study

The RADIATE (RheumAtoiD ArthritIs Study in Anti-TNF FailurEs) trial, a three-arm, randomized, double-blind, placebo-controlled study, was designed to evaluate the safety and efficacy of ACTEMRA plus methotrexate compared with placebo plus methotrexate in patients who failed to adequately respond to anti-TNF medications alone. Between 12-18 percent of the study population experienced three or more prior anti-TNF failures. Patients were randomized to receive either ACTEMRA intravenously (4 mg/kg or 8 mg/kg) plus methotrexate every four weeks or placebo infusions plus methotrexate weekly for 24 weeks. The study included 499 patients from 128 trial sites in 13 countries, including the United States.

In the study, 50 percent, 29 percent and 12 percent of RA patients treated with ACTEMRA (8 mg/kg) plus methotrexate achieved ACR20, ACR50 and ACR70, respectively, compared with 10 percent, 4 percent and 1 percent, respectively, of patients treated with placebo infusions plus methotrexate weekly.

Treatment with ACTEMRA and methotrexate showed significant clinical benefits even in the subgroup analysis of difficult-to-treat patients who received up to three anti-TNFs therapies that failed. Furthermore, disease remission (DAS28

The most common adverse reactions reported more frequently in the ACTEMRA arms of the RADIATE trial were nausea, headache, nasopharyngitis, diarrhea, and upper respiratory tract infections.

“These study results are very promising for RA patients who need a variety of treatment options, particularly when they have failed to achieve adequate pain and symptom relief with anti-TNF therapies,” said Professor Paul Emery, lead study investigator of the RADIATE trial and Professor of Rheumatology, University of Leeds in the United Kingdom.

In both studies, patients treated with ACTEMRA alone or with methotrexate achieved greater improvements in quality-of-life measures, including fatigue, pain, and physical and mental functions, compared with methotrexate. Levels of C-reactive protein (CRP), a marker of inflammation and hemoglobin levels, showed significant and rapid improvement as early as two weeks in ACTEMRA (8 mg/kg) patients in the AMBITION trial, compared with patients treated with methotrexate alone.

“We are extremely pleased with these results which help us work toward establishing ACTEMRA as a new first-line biologic treatment, which blocks a different inflammatory target than current therapies. We are encouraged that we will soon be able to offer this new treatment option and meaningful benefit to those who need it the most — the RA patients,” said Lars Birgerson, M.D., Ph.D., Vice President, Global Head Medical Affairs, Roche.

About ACTEMRA (tocilizumab)

ACTEMRA is the first humanized interleukin-6 (IL-6) receptor-inhibiting monoclonal antibody. Studies suggest that reducing the activity of IL-6, one of several key cytokines involved in the inflammatory process, may reduce inflammation of the joints and relieve certain systemic effects of RA. The extensive clinical development program conducted by Roche includes five clinical studies and has enrolled more than 4,000 patients in 41 countries, including the United States. Five Phase III studies are completed and have reported meeting their primary endpoints. The LITHE trial evaluating ACTEMRA in RA is an ongoing two-year study and is expected to report complete data evaluating the effects of ACTEMRA on the inhibition of structural joint damage in 2009. ACTEMRA is awaiting approval in the United States and Europe.

ACTEMRA is part of a co-development agreement with Chugai, a Japanese company. In June 2005, ACTEMRA was launched by Chugai in Japan as a therapy for Castleman’s disease; in April 2008, additional indications for rheumatoid arthritis, juvenile idiopathic arthritis and systemic-onset juvenile idiopathic arthritis were also approved in Japan.

The serious adverse events reported in ACTEMRA clinical trials were serious infections and hypersensitivity reactions including anaphylaxis. The most common adverse events reported in clinical studies were upper respiratory tract infection, nasopharyngitis, headache and hypertension. Increases in liver function tests (ALT and AST) were seen in some patients; these increases were generally mild and reversible, with no hepatic injuries or any observed impact on liver function.

About IL-6

IL-6 is a common protein found in all joints in the body and is a natural substance that can raise inflammation. Everyone has IL-6 in their body, but people with RA may have too much. If approved, ACTEMRA will be the first and only medication to specifically target IL-6 in patients with RA.

About Rheumatoid Arthritis

Rheumatoid arthritis is a progressive, systemic autoimmune disease characterized by inflammation of the membrane lining in the joints. This inflammation causes a loss of joint shape and function, resulting in pain, stiffness and swelling, ultimately leading to irreversible joint destruction and disability. Characteristics of RA include redness, swelling, pain and movement limitation around joints of the hands, feet, elbows, knees and neck that leads to loss of function. In addition, the systemic symptoms of RA include fatigue, decreased hemoglobin, osteoporosis and may contribute to shortening life expectancy by affecting major organ systems. After 10 years, less than 50 percent of patients can continue to work or function normally on a daily basis. RA affects more than 21 million people worldwide with approximately 1.3 million adults affected in the United States.

About Roche

Hoffmann-La Roche Inc. (Roche), based in Nutley, N.J., is the U.S. pharmaceuticals headquarters of the Roche Group, one of the world’s leading research-oriented healthcare groups with core businesses in pharmaceuticals and diagnostics. For more than 100 years in the U.S., Roche has been committed to developing innovative products and services that address prevention, diagnosis and treatment of diseases, thus enhancing people’s health and quality of life. An employer of choice, in 2007 Roche was named Top Company of the Year by Med Ad News, one of the Top 20 Employers (Science) and ranked the No. 1 Company to Sell For (Selling Power). In previous years, Roche has been named as a Top Company for Older Workers (AARP) and one of the Best Companies to Work For in America (Fortune). For additional information about the U.S. pharmaceuticals business, visit our website: http://www.rocheusa.com/. Product and treatment information for U.S. healthcare professionals is available at http://www.rocheexchange.com/.

   All trademarks used or mentioned in this release are protected by law.     (1) ACR20, ACR50, ACR70 represent the percentage of reduction (20%, 50%,       70%) in certain RA symptoms and measures the number of tender and       swollen joints, pain, patient's and physician's global assessments and       certain laboratory markers.    (2) The Disease Activity Score (DAS)28 is a combined index that measures       disease activity in patients with RA. It combines information from 28       tender and swollen joints (range0-28), erythrocyte sedimentation rate,       and a general health assessment on a visual analog scale. The level of       disease activity is interpreted as low (DAS28 less than or equal to       3.2), moderate (3.25.1). DAS28
 Roche 
 CONTACT:  Ginny Valenze of Roche, Office, +1-973-562-2783, or Cell,+1-973-943-9219, [email protected] 
 Web site:  http://www.rocheusa.com/http://www.rocheexchange.com/

DENVER, June 12 /PRNewswire/ — Cancer Clinics of Excellence (CCE), the nation’s only practice-owned and physician driven network of community oncologists has announced its management slate and Board of Directors. Effective immediately, J. Ike Nicoll is President/COO of CCE. Most recently, he was the interim President of CCE. In addition, Linda Bosserman, MD, Wilshire Oncology Medical Group was named Chief Medical Officer. Dr. Bosserman had previously served as CCE’s Chief Quality Officer.

(Logo: http://www.newscom.com/cgi-bin/prnh/20080612/AQTH094LOGO)

“Ike brings management breadth to CCE with his expertise in a wide variety of healthcare issues including administrative and claims management, drug discovery/FDA approval, clinical trials, supply chain management, payer/provider operations, provider contracting and revenue cycle management,” stated CCE Chairman, Arthur “Chip” Staddon, MD. “Dr. Bosserman is a nationally renowned expert in the field of quality management, outcomes measurement and electronic medical record implementation. With Ike and Dr. Bosserman leading CCE in our business and clinical objectives, CCE is well placed to lead the most needed initiatives to improve oncology care in the United States,” added Dr. Staddon.

The CCE Board of Directors is comprised of Arthur Staddon, MD, Pennsylvania Oncology; Frederick Schnell, MD, Central Georgia Cancer Care, Shahab Dadjou, CEO, Redwood Regional Medical Group; Paul Julian, EVP and Group President, McKesson Corporation and Patrick Blake, President, McKesson Specialty Care Solutions.

“The structure and breadth of the CCE Board of Directors represents the strength of our national network and the support of our strategic partner the McKesson Corporation,” stated Arthur “Chip” Staddon, MD. “CCE provides our membership with a robust set of tools and resources, including our proprietary Evidence Based Treatment Protocols, to enhance our clinical efficiency and effectiveness.”

These announcements were made at CCE’s First Annual Membership meeting in New Orleans, LA. Over 100 clinicians attended the meeting which was created to fulfill the needs of both the clinicians and practice administrators. Clinical presentations by Frank Giles, MD, UT San Antonio; Funmi Olopade, MD, University of Chicago; Michael Fisch, MD, MD Anderson; Barbara Murphy, MD, Vanderbilt Ingram; Alan Sandler, MD, Vanderbilt Ingram; Ezekiel Emanuel, MD, National Institutes of Health; Bert O’Neil, MD, University of North Carolina; and Robert Vescio, MD, Cedars Sinai were complemented by practice management sessions on Malpractice Management, Compliance Pitfalls for Ancillary Services, New Revenue Generation and Integrating Orals into Your Practice.

About Cancer Clinics of Excellence

Cancer Clinics of Excellence is the only practice owned and physician driven network that empowers oncologists to deliver proven, evidence-based treatment in community settings while ensuring the performance of their practices. For more information, visit us at http://www.cce.us.com/.

Photo: http://www.newscom.com/cgi-bin/prnh/20080612/AQTH094LOGOAP Archive: http://photoarchive.ap.org/PRN Photo Desk, [email protected]

Cancer Clinics of Excellence

CONTACT: Kate Dobson, Vice President Education and Communication ofCancer Clinics of Excellence, +1-415-259-6622, [email protected]

Web site: http://www.cce.us.com/

A Levittown, N.Y., woman has been discharged from the hospital after being infested with bird mites from a nest in her bathroom vent.

Nina Bradica, 47, was taken in a hazardous materials suit last week to Nassau University Medical Center. The mites, a common parasite on wild birds, were treated with a simple topical cream where they had infested Bradica’s pelvic and chest regions. But she was placed in quarantine for 48 hours as a precautionary measure until doctors determined she was not contagious, Newsday reported Wednesday.

Eventually it was determined the mites do not pose a serious threat beyond irritating skin and are not likely to spread from Bradica’s rented Saddle Lane home. She has not returned to the house since being discharged from the hospital.

TriMix Laboratories has presented new research data which showed that among men who previously failed to achieve erections on Viagra, Levitra and Cialis type tablets, 40% achieved an erection sufficient for penetration during sexual intercourse after given a single dose of a novel treatment called TriMix gel.

The research involved 42 men diagnosed with erectile dysfunction and various other conditions such as high blood pressure, high cholesterol, diabetes and removal of the prostate. The average age was 55. All trial participants had previously failed on Viagra, Levitra or Cialis type tablets.

Test results were documented using various methodologies such as penile buckling pressures, RigiScans and Erection Hardness Scores (EHS). All test participants experienced some degree of tumescence or increased blood flow and 17 of the patients or 40%, experienced erections sufficient for penetration during sexual intercourse.

TriMix gel does not require refrigeration and does not use a needle. It allows the patient to carry the medicine on his person at room temperature. More importantly, an erectile dysfunction (ED) patient would not have to use a needle to self inject before sexual intercourse.