Alexander Wan: What would you like to tell our readers?

Allan Gabor, Pfizer: Pfizer is a pharmaceutical company with strong global resources and capacities, and would like to build partnerships among the public, private, and patient health sectors to support health care reforms. We believe that emphasizing prevention, wellness, early diagnosis and early treatment can keep disease from many personal health care disasters. Pfizer China has provided philanthropic patient education on disease awareness on many disease categories, such as cardiovascular disease, mental disease, infectious diseases, men’s health, hepatitis B, and HIV/ AIDS even though we don’t have products right now for hepatitis B and HIV/AIDS in China. On average, there is savings of more than US$2 for every US$1 invested in early prevention programs.

Li Zhongyuan, China Health Care Group: The primary responsibility of the government should be to fix the basic healthcare coverage in China. Given the wealth differentiation, the healthcare industry should also encourage market-oriented premium health care services to the section of Chinese population who can afford them. The leading public hospitals should be permitted to engage in premium health care services in co-operation with credible offshore players in various forms. Public hospitals can only maintain their current positions as centres of excellence in various specialities by introducing contemporary health care ideas and practices and expertise by working with high-end patients systematically. The government should regulate public hospitals by encouraging and guiding them to do the right things and help them deal with the budgetary reality they face.

Anne Zhang, L’Oreal China: Settle on a practical hospital management policy as soon as possible:

1. Open up the hospital operation system as soon as possible: every hospital could have high charges for patients who want better and private service. The government could have a special price system for people who enjoy government medical insurance.

2. Decrease period of hospitalization and build a community medical service centre system for common diseases.

3. Cutting drug prices is not the right way to lower the whole package of medical fees.

4. The public bidding policy for drugs should not be controlled by government – it increases the corruption in government.

Vic Lazzaro, China Care Group: Require all public hospitals to provide emergency care. Such services should be paid for by the government on a fee-for-service basis in a pre-determined rate structure. All other services would be considered elective and would be paid for by the patient and his insurance policy where applicable. We should create a scale for determining the ability to pay based on income, assets or other methodology to determine who is medically indigent. It is the government’s responsibility to lead in this change process. However, the Chinese Hospital Association should be asked to create a committee of prominent hospital leaders to serve as a commission to assist the government.

David Jin, Philips Medical System: What I would like to say to the Chinese Government is to make it a top priority and significantly increase investment in the health care sector in order to build an effective health care system based on the contributions by both governmental and private sectors. I would like to see various stake-holders in the process jointly contribute to a sustainable growth model. Philips Medical Systems will definitely do its part by working together with various stake-holders towards the healthy development and long-term growth of China’s health care sector.

Dr Jonathan Seah, Parkway Group Healthcare:

As the largest private hospital group in Asia, we strongly believe that the development of private for-profit health services in any country should be closely co-ordinated with the public non- profit healthcare system. Properly executed, an effective private healthcare system can help reduce or maintain the total health care expenditure in a country.In Singapore, for example, where our company has the majority market share of private health care services, the total healthcare expenditure for the country is only around 3 per cent of GDP – and actual government expenditure constitutes only about a third of that (about 1 per cent of GDP). As a comparison, health care expenditure in the United States is around 12 per cent, in Canada about 9 per cent, in the United Kingdon and Japan about 7 per cent. This, however, can only happen when there is a good understanding of what the different roles of the public non- profit health care system and the private for-profit hospitals are. In Singapore, an important part of this strategy is limiting premium and elective services at public hospitals in order to reduce costs for the non-profit health care system, as well as to focus public resources on providing a good level of basic health care to a larger segment of the population. Patients who desire a premium level of care, or who seek elective services not considered “basic medical care” are cared for by the private for-profit healthcare system. Additionally, this system cannot evolve in a vacuum, but has to be developed along with other elements of the health care infrastructure.

Stanley Tam, MD, Harvard Medical School: What you are trying to do to reform the health care system is extremely critical to the health of the people and the eventual economic growth of China. The most efficient and effective plan is to involve both the public and private sectors, with clear guidelines and regulation governing the role of public institutions in the areas of public health and basic health care services, avoiding using public institutions in for- profit efforts. To improve the over all health care system, one must have clear metrics to measure any interventions, so that we could build on prior experiences. The private sector should be given freedom to operate under certain regulations so to benefit the entire health care system.

Alexander Wan: Can you share with us the roles your company would like to play in China’s health care reforms? Tell us your experience in other countries.

Allan Gabor, Pfizer: Pfizer is committed to supporting health care reforms in both urban and rural areas in China. Pfizer China has worked with the Ministry of Health to initiate an advanced hospital management training programme at Beijing University. The Advanced Hospital Management programme has exposed senior hospital management personnel nationwide to innovative management theories and practices to increase efficiency and effectiveness. Pfizer China has supported a pilot rural co-operative health care system in Yunnan programme to explore the best practices on health care reform in rural areas. In the United States, we launched A Healthy State health care management initiative in the state of Florida, called “Healthy Florida” to support health care reforms for ageing people.

Li Zhongyuan, China Health Care Group: We would like to nurture the creation of a rational and viable private health care service market in China by systematically introducing international expertise, capital and technology. The core component of such work is working with leading public hospitals and introducing advanced ideas and management in a commercially viable way. We have worked with partners in countries such as the United States, the United Kingdom and India.

Allan Choate, The Asia Foundation: With the support of the Pfizer Foundation, The Asia Foundation (TAF) has launched two pilot projects in China’s rural areas called “New Rural Cooperative Healthcare Scheme”, in collaboration with the Ministry of Health.

In the first place, the scheme – with a co-payment structure built in – is expected to fill an over-decade-long void of a health care safety net in China’s rural areas. Once the farmers participate in the scheme, they pay an annual fee of 10 yuan into a pool (matched by another 10 yuan subsidized by the provincial government and the central government respectively) and are entitled to get medical reimbursement. So, from the demand side (farmers) perspective, the new scheme is revolutionary in that it helps cover farmers’ medical cost in an unprecedented manner. Our programme has integrated the supply side reform (the reform of rural area hospitals, clinics, and other service output performers) so that both sides work well in parallel and contribute to the efficiency and sustainability of the new scheme.

Alexis Vannier: PSA Peugeot Citroen: Since last year, we have been deeply involved in road safety and education in China. We have already created five Road Safety Think Tanks in different major cities in China (Beijing, Chongqing, Wuhan, Guangzhou and Xi’an). Every two months or so, we invite a leading Chinese or international expert to give a lecture to these think tanks attended by the media as well as the authorities and medical officials.

Stanley Tam, MD, Harvard Medical School: I am currently the president and CEO of the new Huashan Pudong Hospital, the first Harvard Medical School-affiliated hospital. I have been a veteran in the Harvard medical community for many years. We intend to provide high-quality health care to patients in every economic and social class. We will provide valuable training and education.

Aug. 28–When Shari Daniels thought she was pregnant with her first child, she did what most women would: She visited the doctor. But he dismissed her queasy feeling after a urine test proved negative and suggested she see a psychologist because she was only “thinking yourself pregnant.”

“He talked to me like I was an idiot and gave me no credit for knowing my own body. There were no ultrasounds back then and pregnancy tests were extremely unreliable. I tested negative for all my three kids,” Daniel recalled.

That was 1971, in El Paso, Texas, and, after her experience with the doctor, Daniels searched for a midwife but couldn’t find one. She went to an obstetrician, who confirmed she was four months pregnant.

When it came time to deliver, the doctor left around 8 p.m. that day, because Daniels wasn’t dilating, and said to call if anything developed.

‘The first nurse on shift was nice but, around midnight, the ‘wicked witch of the west’ came in. She was somehow insulted that I wanted to have a drug-free birth and kept insisting that I take the epidural. She threatened, ‘You’ll be screaming for me to put you out of pain later,’ and actually locked my husband out of the room. I was all alone in there,” Daniels said.

A few minutes after the nurse left the room, Daniels began to push as she felt her daughter’s head emerging.

“I felt like I was sitting on a bowling ball at that point and they kept telling me to wait for the doctor,” she said. “I ended up delivering by myself. It was the most amazing feeling pulling my daughter’s shoulders out.”

The experience also left Daniels with a calling: to become a midwife, a profession she would practice first in Texas, then in other places, including overseas, and at a birthing center she opened in North Miami Beach, at 140 N.E. 119th St.

In the three decades since her first experience giving birth, Daniels, now in her 50s, has delivered 10,000 babies, by her count, and has trained perhaps 500 midwives from coast to coast.

“God chose this path for me,” she said. “My experience giving birth to my first daughter Trevin was very traumatic and I wanted young women to have the choices I didn’t have.”

Soon after her solo delivery, Daniels began offering free childbirth classes at her home and nearby churches and acting as a labor coach. Before she knew it, word had spread around her small Texan town and she began receiving unexpected visitors.

“One night I had a Mexican woman who was an illegal alien show up at my door in a taxi cab. She had labor pains and delivered right on my bed. I assisted her and made her child a U.S. citizen without charging her a dime,” she said.

Pregnant moms kept ringing her doorbell and soon Daniels was delivering twins for $25.

“My husband kept telling me, ‘Somebody’s gonna die one of these days and they’re gonna blame you. You gotta get more formal training,’ ” she said.

Daniels began studying with Raul Vilorio, a Cuban country doctor in Fabens, Texas, who gave her her first obstetrics book and taught her how to read a fetal scope. After further study, she felt ready to open her own maternity center.

“It was an old dilapidated building that I bought for $20,000,” she recalled. “I started working on it 21 hours a day, plastering, painting, doing some of the plumbing and carpeting. My dad was in construction, so he helped a lot. I bought the building in June and wanted to open by Aug. 15. Everyone thought I was crazy.”

But, sure enough, The Maternity Center Inc. opened on Aug. 15, 1976, the first midwife-run birth center in the United States, according to The History of Midwifery textbook. The nonprofit center was such a success Daniels opened three other centers within the next decade. Then came a tough year: 1986.

“I went through a very bad divorce, partly because I was so devoted to my job that I wasn’t home enough, and really considered quitting for a while. Also, one of the midwives I had trained had a maternal death and I was dragged into the lawsuit for answering her distress call and advising her to take the girl to the hospital,” Daniels said.

Her mind was made up: no more delivering babies. She handed over her maternity centers to members of her staff and decided to move to Israel, where she had close friends.

“I thought I was done but, sure enough, within three weeks of arriving in Israel, I had delivered a child,” she said.

To reconnect with her four children, especially her 12- and 15-year-old daughters, who were not happy with their new life in Israel, Daniels spent her savings traveling with them for 18 months.

“We visited Greece, Egypt, Vienna, Hungary, India, Hong Kong and Honolulu and spent some time in each place, before heading back to El Paso,” she said.

Daniels eventually settled in North Miami Beach, where she found “a nice Jewish community.” In 1995, she opened a birth center, along with the International School of Midwifery. This time around, she was able to balance her love life with the demands of her job and she remarried. Now, after 30 years as a midwife, she is learning a whole new trade: being a grandmother to daughter Joy’s newborn.

Although she still has a lot to learn from her mother, whose credentials read like the alphabet — Licensed Midwife, Certified Practicing Midwife, Master of Science in Education — Joy Luria decided to become a Licensed Midwife and join Daniels’ staff. Growing up in a birth center, peeking into delivery rooms in the midst of water breaking and baby’s first cries gave her some early training. Luria is also trained in Ayurveda, the ancient healing art of India, complementing her mother’s “Western medicine” with Eastern wisdom.

“After I got pregnant, I wanted to spend more time with my mom and, since she’s always working, the only way to do that was to work with her,” Luria said. “Maybe as a child or teenager I resented her not being home more. But now that I’m also a midwife and mother, I understand her better. She’s made up for a lot of that time away by baby-sitting my son Ashton. We’re even.”

Mothers are not the only ones who have taken notice of Daniels’ birth center. Discovery Health contracted with her and her staff to film 26 episodes of a new reality TV series called House of Babies.

Filmed at Miami Maternity, the show will air in January, with some preliminary episodes showing as early as October.

“I told the Discovery people, ‘I’m not putting makeup on, changing my uniform, repainting the place or doing things differently for you. I will keep on going to work every day to take care of mothers and babies, which is what I do best and not be distracted by your crew,’ ” she said.

Her no-nonsense attitude has served her well.

“There’s one thing I tell mothers when they walk through my door: I can’t make birth defects or complications go away but I can love you if you have to go through them, and take care of you and your baby like my life depends on it,” she said.

—–

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Copyright (c) 2005, The Miami Herald

Distributed by Knight Ridder/Tribune Business News.

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By Megan Rauscher

NEW YORK (Reuters Health) – Many labs in the US are using
outdated blood tests for genital herpes that often give
erroneous results, according to a new report.

“Genital herpes is the most prevalent sexually transmitted
disease in the United States affecting about a third of the
adult population,” Dr. Zane A. Brown commented to Reuters
Health.

The biggest concern with herpes is that it can be
transmitted to newborn infants with devastating results.
“Unfortunately, only 10 percent of adults infected with the
virus are aware of their infection and are therefore able to
spread the infection to sexual partners and newborns infants,”
Brown noted.

There are two types of herpes virus — HSV-1, which is
responsible for common ‘cold sores,’ and HSV-2, which causes
genital herpes.

As part of its test proficiency program, the College of
American Pathologists recently sent 172 participating
laboratories a sample of blood that was positive for HSV-1
antibodies and negative for HSV-2 antibodies.

While virtually all of the laboratories accurately detected
HSV-1 in the sample, more than half incorrectly reported that
the sample was positive for HSV-2 antibodies, Dr. Brown and Dr.
Rhoda Ashley Morrow report in the American Journal of
Obstetrics and Gynecology.

Currently, only tests based on a protein called
glycoprotein G have been proven effective in typing antibodies
to HSV, Morrow and Brown from the University of Washington
School of Medicine in Seattle note in their report.

Ninety-four of the laboratories reported the type of test
they used for HSV-2 antibody detection. All 44 sites that used
a glycoprotein G-based test accurately reported that the sample
did not contain HSV-2 antibodies. Labs that used
non-glycoprotein G-based assays, on the other hand,
“demonstrated high false-positive rates (14 percent to 88
percent) for HSV-2 antibodies.”

Brown said the inaccurate tests “will continue being
marketed until the companies voluntarily withdraw them from the
market. This places the burden on the health care provider
ordering the test to know which lab uses what test, which is
beyond the scope of training and capability of most health care
providers.”

If the spread of herpes is to be stopped, said the
researcher, “it is critical that laboratories use the approved,
accurate (type-specific) blood tests that have been readily
available in the U.S. since 1999.”

SOURCE: American Journal of Obstetrics and Gynecology,
August 2005.

Among several people in Norwood, what was going on behind the tinted glass doors at 504 Livingston St. was considered an open secret.

Tucked in a shopping center usually bustling with customers, the Jade Health Spa advertised itself as the “ultimate in beauty treatments and therapeutic massage” with “unparalleled personalized service.”

The spa was briefly closed after two of its female employees were arrested on prostitution charges in 2002. Soon after it reopened a few months later, the chatter began.

“There were a lot of rumors circulating about that place,” said Norwood Mayor Michael Kaplan.

Nearly two weeks ago, the spa was raided again, after undercover agents said they were solicited for sex. Three employees, including an alleged madam, were arrested on prostitution-related charges. The spa remains closed while a judge decides its fate.

The Norwood saga underscores the challenges that law enforcement and government officials face from massage parlors that serve as fronts for prostitution.

There is no state regulatory agency that oversees their operation. Business owners don’t have to obtain state permits to open a salon. Massage therapists don’t need licenses to rub down clients, nor are they required to undergo background checks.

Even legitimate spa workers have called for increased scrutiny, saying that the proliferation of illegal spas is tarnishing the image of their profession.

“Anyone can open up a place and put ‘Spa’ on the door,” said Joyce Fontaine, executive director of the luxury Fountain Spa in Ramsey, a proponent of regulation.

Municipalities across the state began taking matters into their own hands after a series of high-profile police raids a few years ago, including the closure of the infamous Ultima Spa in Lodi.

Among the patrons found at the Ultima Spa when it was raided in 2001 were 21 off-duty police officers. Luke Hoffman, a former FBI informant whose case opened a rift between Bergen County’s previous prosecutor and federal authorities, later admitted in court that patrons at his business could take women into private rooms for sex.

Bergenfield, Clifton, Fairview, Palisades Park and Wayne, among others, began toughening their ordinances, requiring background checks for anyone planning to open a spa or perform massages. They also began requiring workers to undergo strict health evaluations. And they laid out stringent sanitary regulations inside the spas. Some even specified the parts of the body that therapists could and could not touch.

Although the tightened rules certainly have given municipal governments more enforcement power, local officials admit they have done little to prevent illegal parlors from cropping up in their towns.

“I think it’s helpful to ensure that people performing massages have the proper credentials,” said Denville Mayor Gene Feyl, whose Morris County township adopted a massage parlor ordinance two years ago. “But whether it actually deters prostitution is another question.”

Norwood Police Chief Jeffrey Krapels said stronger massage parlor regulations likely would have allowed the borough to shut down the Jade Health Spa sooner. Norwood adopted a massage parlor ordinance two years ago, but the spa – which had already opened – was grandfathered in.

The ordinance “will probably prevent something like this from happening again, because it gives Norwood the teeth to close down illegal massage parlors,” Krapels said. “And we wouldn’t have to go through all these problems we had to go through with this particular one.”

The Jade Spa was allowed to reopen in 2002 after its owners said they were unaware that illegitimate activities were occurring there, Krapels said.

Last November, the state Legislature established a certification process for massage therapists – a policy that was years in the making. Developed by the New Jersey Board of Nursing, the rules were the state’s first attempt at regulating massage therapists.

So far, the state has certified 60 massage therapists, and there are 170 pending applications, said Jeff Lamm, a spokesman for the Division of Consumer Affairs.

But the new law requires certification only for those who want to represent themselves as “massage and body therapists” or “certified somatic therapists.” There are no criminal penalties. If a worker neglects to say he or she is a certified therapist, that person isn’t violating state law.

Assemblymen Peter Barnes and Patrick Diegnan, both D-Middlesex, and Assemblyman Gordon Johnson, D-Englewood, have proposed a bill that would go even further, requiring certification for anyone who performs a massage. The proposal has stalled in the Senate and Assembly because of concerns over its language.

Massage therapists say the bill, as it’s written, identifies all spas as “massage parlors” – a term many legitimate professionals consider derogatory.

Barnes, a retired police director, said that at the very least the proposal would present obstacles for spa owners who want to operate illegally. Johnson, a former Bergen County sheriff, agrees – though he acknowledges there are issues in the bill that need to be ironed out before it can move forward.

“It’s not going to eliminate prostitution,” Johnson said. “But it will create an obstacle that may prevent people from turning spas into brothels.”

Officials of the New Jersey chapter of the American Message Therapy Association said they are open to discussing their concerns over the bill’s language.

“We hope to work together with Barnes so he can accomplish what he wants and we can accomplish what we want,” said Susan Ring, a government relations specialist for the state AMTA.

The AMTA is also lobbying for the state to license massage, somatic and body-work therapists rather than simply issuing certificates.

New York, New Hampshire and Rhode Island license massage therapists, which some believe elevates the profession and weeds out some illegal practices.

“I’m surprised New Jersey doesn’t have it,” said Cheryl Chapman, president of the state AMTA. “It’s such a progressive state, but in this regard it’s so behind.”

***

E-mail: [email protected]

(SIDEBAR, page A01)

Rubdown rundown

A sampling of state regulatory requirements for massage therapy:

New York, license, 1,000 hours training.

Connecticut, license, 500 hours.

Florida, license, 500 hours.

New Jersey, certification, 500 hours.

New Mexico, license, 650 hours.

California, Illinois, Pennsylvania, no state regulation.

By Damian Wroclavsky

HAVANA (Reuters) – With his picture on rock band posters,
baseball caps and women’s lingerie, Marxist revolutionary Che
Guevara is firmly entrenched in the capitalist consumer society
that he died fighting to overturn.

The image of the Argentine-born guerrilla gazing sternly
into the distance, long-hair tucked into a beret with a single
star, has been an enduring 20th century pop icon.

The picture — taken by a Cuban photographer in 1960 and
printed on posters by an Italian publisher after Guevara’s
execution in Bolivia seven years later — fired the imagination
of rioting Parisian students in May 1968 and became a symbol of
idealistic revolt for a generation.

But as well as being one of the world’s most reproduced,
the image has become one of its most merchandised. And
Guevara’s family is launching an effort to stop it. They plan
to file lawsuits abroad against companies that they believe are
exploiting the image and say lawyers in a number of countries
have offered assistance.

“We have a plan to deal with the misuse,” Guevara’s Cuban
widow Aleida March said in an interview.

“We can’t attack everyone with lances like Don Quixote, but
we can try to maintain the ethics” of Guevara’s legacy, said
March, who will lead the effort from the Che Guevara Studies
Center which is opening in Havana later this year.

“The center intends to contain the uncontrolled use of
Che’s image. It will be costly and difficult because each
country has different laws, but a limit has to be drawn,” the
legendary guerrilla’s daughter, Aleida Guevara, told Reuters.

Swatch has used Guevara on a wristwatch. Advertising firms
have used his image to sell vodka. Supermodel Gisele Bundchen
even took to the runway in Brazilian underwear stamped with
Che’s face.

Guevara collectibles — from Zippo lighters to belt buckles
and key chains — can be bought online at thechestore.com.

But a successful copyright lawsuit against Smirnoff vodka
in Britain in 2000 set the precedent for legal action,
establishing ownership of the photographic image.

Lawyers say it will be an uphill struggle to deter
non-photographic use of such a widely reproduced image, other
than in countries like Italy where laws protect image rights.

KORDA VS SMIRNOFF

The famous picture was shot by Alberto Diaz, a fashion
photographer better known as Korda, at a funeral for victims of
the explosion of a French freighter transporting weapons to
Cuba one year after Fidel Castro’s revolution triumphed with
the help of Guevara.

Korda’s group photograph was not printed by his newspaper
the next day. Seven years later, when Italian publisher
Giangiacomo Feltrinelli showed up looking for a cover picture
for an edition of Che’s “Bolivian Diary,” Korda gave him two
prints for free.

Guevara was captured six months later in the Bolivian
jungle, where his bid to start an armed peasant revolution
ended in fiasco. On news on his death, Feltrinelli cropped the
photo and published large posters that quickly sold 1 million
copies.

The guerrilla fighter was transformed into martyr, pop
celebrity and radical chic poster boy.

Korda said he never received a penny from Feltrinelli.

But a year before his death in 2001, the photographer won a
lawsuit against London agency Lowe Lintas for unauthorized use
of the picture in a Smirnoff vodka advertising campaign. The
Smirnoff brand is now owned by Britain’s Diageo Plc .

Korda later donated the $70,000 award to children’s health
care in communist Cuba.

Razi Mireskandari, the London lawyer who filed the
copyright case, said Korda worried that the image of Che, who
did not drink, was being trivialized by its use in promoting a
alcoholic beverage that bore no relation to Cuba or his
political message.

“We felt there were so many people you could take action
against that we had to start somewhere,” Mireskandari said.
“The plan of action was to target one of these, which was
Smirnoff, and then, when we got the judgment, we were going to
go against everyone else,” he said in a telephone interview.

After the photographer’s death, his heirs never contacted
the lawyer for further action and are disputing among
themselves copyright ownership of the famous picture.

IMAGE PROTECTION

Korda’s daughter Diana Diaz has continued to fight
political misuse of the picture.

In 2003 she won a lawsuit against a Paris-based press
rights group for using the Che photograph in a poster campaign
aimed at dissuading French tourists from vacationing in Cuba
after the jailing of 29 dissident journalists.

Reporters Without Borders had superimposed Che’s face on a
picture of a baton-wielding riot policeman. The caption said:
“Welcome to Cuba, the world’s largest jail for journalists.”

Che fever was stoked last year by “The Motorcycle Diaries,”
a film about his eye-opening trip through poverty-stricken
countries of South America as a medical graduate.

Even Cuba sells Che’s image. Postcards and posters of
Guevara playing golf at the Country Club shortly after the
overthrow of dictator Fulgencio Batista in 1959 are popular
with tourists.

So are Cuban banknotes issued when Guevara was Central Bank
governor, simply signed “Che.”

GIVING clean needles to addicts is no way to solve the drug problems that plague our society. So the court decision last week to block such a program is OK with me. Needle programs only help drug addicts stay high.

The drug problem is more than rampant AIDS and hepatitis infections, which a clean needle program would fix.

While it is argued that they slow down the spread of HIV, clean- needle programs are inherently destructive. They address only one symptom, but give the illusion of solving the multi-pronged drug addiction problem.

The court’s ban is not absolute, however, and unfortunately needle-exchange programs are so pervasive that one is inevitable for cities in this state.

New Jersey’s Appellate Court ruled that the proposed needle- exchange program would violate state laws on drug paraphernalia. Only hospitals, clinics and health care professionals are legally permitted to have hypodermic needles.

Even though legislators could clear the way for New Jersey to adopt a limited needle-exchange policy, they should take the time to think this proposal through and reject what other NEP states have legitimized as an instant solution to drug problems

Clean needles are not a panacea.

Atlantic City and Camden were only looking for approval to try an experimental program, based on former Gov. Jim McGreevey’s declaration last year of a public health emergency. He said that adopting a program to legally put sterile needles in the hands of drug users was essential for controlling the spread of HIV.

Although clean-needle-exchange programs have been adopted by many cities, including New York City, it’s ultimately a bad idea. It addresses only HIV and hepatitis infections and does nothing about the other criminal, medical and social aspects of drug addiction.

For example:

* Giving out clean needles does not discourage drug dependence.

* Addicts still are prone to death, perhaps not from HIV, but from overdose, collapsed veins, poisoned dope, or the violence and criminality that go along with the illicit drug trade.

* Drug-addicted mothers will still deliver drug-addicted babies.

* Sterile needles don’t address the underlying problems addicts are avoiding.

* Sterile needles offer the path of least resistance rather than address underlying psychoses.

* Drugs destroy families when all the house money is paying for drugs, lawyers and treatment.

* It does nothing to stop drug gangs from killing one another.

Among the vocal opponents to the plan, state Sen. Ron Rice of Newark sees needles – clean or dirty – as another destructive element in the inner city communities that he represents. He’s one of the plaintiffs in a pending suit that challenges needle exchange.

Many of his constituents are not that ready to trust the motives of needle-exchange advocates. The distrust is deeply rooted in incidents like the Tuskegee experiment, which endangered the lives of residents infected with syphilis without their knowledge. And it’s not only the sting of past experience. More recently confirmed is decades of government-sanctioned testing of AIDS drugs on children in foster care.

Paterson Mayor Joey Torres had the good sense to keep his city from getting involved as a testing lab. He risks political opprobrium since his city has the third largest HIV rate in the state and a drug problem that The Record has recently chronicled.

Paterson was eligible to be one of nine demonstration cities for the needle exchange, but Torres declined to submit an application.

There are better ways of attacking the drug problem than legally sanctioning a clean-needle-giveaway – such as creating more opportunities for counseling, funding rehab clinics, and providing more health care coverage for uninsured drug users.

The clean-needle opponents should continue raising objections to this evil practice that makes it easier for drug addicts to stay drugged.

Needle-exchange programs have proven they can cut the death rate and the spread of HIV and hepatitis caused by sharing dirty syringes. But they don’t address the less tangible issues that lead people into drug dependence.

A needle exchange sanctions bad behavior. It suggests that if you’re persistent enough doing the wrong thing, you’ll be rewarded with official permission to keep doing it.

***

Record Columnist Lawrence Aaron can be contacted at [email protected]. Send comments about this column to [email protected].

Aug. 26–Stockton chiropractor Michael Hall Yates, 48, and three other chiropractors were arrested this week after an investigation by the California Department of Insurance and charged with multiple felony counts, including insurance fraud.

If convicted, each faces up to five years in prison and fines of up to $150,000, or double the amount of the fraud, whichever is greater, according to information from the state agency.

Bail was set at $50,000 each. The chiropractors have been released on bail. Yates is scheduled to return to work Wednesday.

Yates rents office space at 2308 N. California St. in Stockton, according to a receptionist in the building who works for another chiropractor not implicated in the case.

Yates uses the business name California Accident & Injury Centers. He also advertises a Lodi office at 1806 Kettleman Lane. The phone number advertised for that office is hooked up to a fax machine.

No one answered his Stockton office phone, and no message could be left.

Upon learning of a warrant for his arrest Tuesday, Yates turned himself in to authorities in Contra Costa County that night and was booked into jail in Martinez, officials said.

Department of Insurance investigators arrested three other chiropractors from out of the area Tuesday and booked them into the San Joaquin County Jail: Joseph R. Ambrose, 43, of El Dorado Hills; Richard Guadalupe Saucedo, 62, of Turlock; and Pedram Vaezi, 33, of Modesto.

Their arraignments are scheduled for today. Yates’ arraignment is scheduled for Sept. 23 in San Joaquin County.

The chiropractors are charged with filing false insurance claims and practicing medicine without certification. Yates and Ambrose also are charged with conspiracy to commit a crime, grand theft, workers’ compensation insurance fraud and unlawful rebates.

“We look to people in the medical profession to help us, not harm us,” California Insurance Commissioner John Garamendi said after the arrests. “But crimes such as those alleged in this case hurt us all by forcing insurance rates ever higher. We will prosecute these cases to the fullest extent possible to send a strong message that will help end these harmful scams.”

A source close to the investigation said Yates and Ambrose were two of six co-owners of the Sierra Hills Surgery & Medical Center, an outpatient surgery center on Folsom Boulevard in Sacramento that has been closed for several months.

They allegedly were directing and performing a surgical procedure known as manipulation under anesthesia, or MUA, but chiropractors — according to terms of their licensure — are prohibited from performing or even participating in medical-surgical procedures.

Hundreds of patients over the course of about 18 months underwent the procedure at Sierra Hills, according to the source. In medical circles, MUA is considered “very controversial,” and the insurance companies stopped paying Sierra Hills for performing it, the source said.

According to a Web site maintained by Trial Digest magazine, Yates is listed as an expert witness for chiropractic in civil litigation cases. He has standing as a qualified medical examiner, which could be in jeopardy if he’s convicted of a felony.

Insurance Department investigators learned of Yates while investigating the other three chiropractors as employees of Modesto-based Med-1 Medical Center. Med-1 is the focus of an ongoing joint investigation by the department and the San Joaquin County District Attorney’s Office.

—–

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

Copyright (c) 2005, The Record, Stockton, Calif.

Distributed by Knight Ridder/Tribune Business News.

For information on republishing this content, contact us at (800) 661-2511 (U.S.), (213) 237-4914 (worldwide), fax (213) 237-6515, or e-mail [email protected].

NEW YORK — After a stroke, some patients develop muscle spasm in their hand and wrist. A small study now indicates that the condition can be relieved with focused shock wave therapy, and the benefits may persist for at least 12 weeks after treatment.

Shock wave therapy is commonly used to break up kidney stones, and it has also proven useful in the treatment of various bone and tendon diseases, but there’s not much known about its use for abnormal muscle tension, or “hypertonia,” Italian researchers note.

Dr. P. Manganotti and Dr. E. Amelio, from the University of Verona assessed the outcomes of 20 patients with stroke-related hypertonia in the upper limbs who were first treated with sham stimulation and then, 1 week later, with shock wave therapy.

The treatment consisted of pressure pulses from a “lithotripter” device aimed at hypertonic muscles in the forearm and hand. Much lower energies were used than is customary for dealing with kidney stones, so the procedure was painless and patients didn’t need anesthesia.

Compared with placebo stimulation, shock wave treatment was associated with significantly greater improvements in muscle tone of the wrist and fingers, the researchers report in the American Heart Association’s journal Stroke.

After 4 weeks, shock wave therapy was tied to significant reductions in passive muscle tension in all the patients. At 12 weeks, half of the patients still showed a reduction in muscle tone.

None of the patients experienced any adverse effects from shock wave therapy, the report indicates.

The investigators say the results “could open new areas of research in the treatment of hypertonicity.”

SOURCE: Stroke, September 2005.

By Laura Myers

KEY WEST, Fla (Reuters) – Hundreds of millions of dollars
in silver bars, emeralds and gold chains have already been
recovered from the Spanish galleon Nuestra Senora de Atocha,
sunk during a Florida Keys hurricane in 1622.

But the mother lode of treasure discovered by Mel Fisher
two decades ago may not have finished yielding its fortunes,
his heirs believe, and there may be more to come.

“It’s still a trail of gold,” said Mel Fisher’s son Kim,
49, chief executive of Key West-based Mel Fisher’s Treasure,
the umbrella firm of the family’s 30 related companies.

The 110-foot (33.5-meter), 600-ton Atocha — one of a fleet
of ships laden with priceless gold, silver, emeralds and
Catholic artifacts — sank on September 5, 1622, near the
Marquesas Atoll, about 35 miles southwest of Key West, off the
southern tip of the Florida peninsula. On board, 260 passengers
died, while five survived by clinging to the mizzenmast.

Mel Fisher, known for saying “today’s the day,” and his
family searched for the Atocha treasure for 16 years,
weathering daunting debts and ridicule.

In a life-changing moment 20 years ago, they found treasure
from the Atocha worth an estimated $200 million to $400 million
at the time, and Kim Fisher believes loot worth a further $500
million still lies in the ocean.

HUNT HAUNTED BY TRAGEDY

In its long quest to find the Atocha, the family even
endured the tragic death of oldest son Dirk and his wife on
July 20, 1975, when the salvage boat Northwind capsized during
the night — 10 years to the day before the treasure hoard was
found. Dirk had located some of the Atocha’s 11-foot
(3.4-meter), 3,600-pound (1,633-kg) bronze cannons just days
before. Diver Rick Cage was also lost.

“It was devastating,” Kim told Reuters. “We almost threw in
the towel. We decided Dirk would want us to continue. I think
it actually made us try harder.”

On July 20, 1985, a magnetometer capable of tracking
cannons and cannon balls revealed a seabed target at a 55-foot
(16.8-meter) depth.

Divers Andy Matroci and a colleague discovered 1,041 silver
bars and hundreds of boxes, each with 3,000 coins. Other
treasure included 127,000 silver coins, 700 emeralds and likely
contraband consisting of 2,500 lighter stones, heavy gold
chains and jewelry, silver and crucifixes.

Ninety percent of the original mother lode has been
distributed to investors, crew and the Fisher family.

But Kim Fisher estimates there is another $500 million
worth of undiscovered treasure.

Among the suspected riches would be 300 silver bars
weighing 80 pounds (36 kg) each, 100,000 coins, eight to 10
bronze cannons and treasure from the stern castle, an area of
the ship where the riches of nobility, clergy and first-class
passengers were stored.

“There were 35 boxes that the Church had on board. They
always had good stuff,” Kim said.

SMUGGLING

Much of the treasure was contraband.

St. Augustine, Florida-based historian Eugene Lyon, who
researched the Atocha on a trip to Spain for Mel Fisher,
believes that most of the treasure’s emeralds, for example,
were smuggled.

“Smuggling was not just a cottage industry but a national
industry. Some of these Spanish wrecks were carrying way above
what they were supposed to be carrying,” added Jim Sinclair,
48, a St. Augustine, Florida-based marine archeologist who
worked as a Fisher treasure hunter during the mid-1980s.

Diver Matroci, 50, recently found a 9-inch, 22-carat gold
chain and more than 30 coins. “We’re finding treasure all the
time,” he said.

Matroci still captains a crew of five on the 100-foot
(30.5-meter) salvage vessel Magruder, working shifts of about
12 days, depending on the weather. They use sensors such as
magnetometers to scan the sea bed. Each find is tagged using
global positioning systems.

“Mel gave me a career I never knew existed and 25 years
later I’m still doing it,” said Matroci, who’s logged more than
21,000 hours underwater.

Mel Fisher, known to his crews as the optimistic “Uncle
Dad,” died of bladder cancer in 1998 at age 76.

He became a cult hero among salvagers when he won a U.S.
Supreme Court victory in 1982, three years before the actual
discovery, over ownership of the treasure if he found it. The
U.S. government had claimed that it was the owner of any
treasure because, under common law, it was the successor to the
prerogative rights of the monarch of England, but the court
ruled 5-4 that any treasure belonged to Mel Fisher.

These days, Spain often lays claim to any likely treasure
found from the wreck of one of its old sailing ships.

“With treasure finds now, the status is that it’s a lawsuit
from the time you find it,” said David Paul Horan, the attorney
who represented Fisher in his legal battles.

Key West last month celebrated the 20th anniversary of the
Atocha treasure find with a rowdy bikini contest. Middle-aged
men and women swilled rum and Coke and danced the hokey-pokey.

“It’s all part of my father’s legacy. If you have a dream,
go for it,” Kim said.

“My dad’s last words to me were, ‘Don’t let the small stuff
bother you.’ I still do the same things I always did. I never
used to worry about money. It really hasn’t made any
difference. It’s an incredible thrill to find gold and
emeralds. It’s too much fun to quit.”

Aug. 25–Area dermatologists are raising concerns about a prescription-strength skin cream that consumers have been able to purchase over the counter at least one West Palm Beach beauty supply store.

Fabulous Beauty Supply, in the plaza at the corner of Okeechobee Boulevard and Military Trail, has been selling a skin cream containing clobetasol propionate, a high-potency steroid that can thin and lighten the skin and cause health problems in children.

The store is selling two kinds of Lemonvate cream that contain 0.05 percent of the steroid. The creams’ packages indicate they are for skin diseases like psoriasis and eczema. But if used improperly, it can cause whitening of the skin, the growth of extra blood vessels and permanent thinning of the skin.

“That product should not be sold without a prescription,” U.S. Food and Drug Administration spokeswoman Laura Alvey said, adding that she had received no other media calls about the store or the steroid.

Dr. Jean Malecki, director of the county health department, said her agency had received a complaint about the creams and had passed it on to the FDA.

Local dermatologists say the steroid should not be used for more than a 2-3 weeks at a time, and always under the supervision of a doctor.

Dr. Kenneth Beer, a West Palm Beach dermatologist, said the steroid can cause children’s bodies to shut off hormone production, which can lead to immune suppression, stunted growth and infections. “From time to time what happens is a child… can get enough absorbed it can affect their hormones. It can make little kids really, really sick,” he said, adding that none of his patients have come in with the cream.

But Dr. Steven Rosenberg, a West Palm Beach dermatologist, learned last week that the steroid was being sold over the counter when one of his patients brought it into his office. She had used it on her face for about a year to treat acne.

Rosenberg said he thinks the cream actually made the woman’s acne worse, and it also left blotchy patches of discoloration on her skin. Rosenberg said she told him she bought the cream at Fabulous Beauty Supply.

The store’s owner, Nazar Osman, said Tuesday he had no idea the creams were prescription strength. He said the store has carried the creams since it opened three years ago, but he would not name the wholesaler he purchased the creams from.

“Wholesalers wouldn’t carry anything that would harm anybody. They only sell products that are FDA-approved. We deal with big people,” he said. Osman said he plans to stop selling the creams, which he said are not very popular.

On Monday, a Palm Beach Post reporter was able to buy two 30 milligram tubes of the cream at Fabulous Beauty Supply for $2.99 each. At Drugstore.com a 30 milligram tube of cream containing the steroid costs $15.53.

Fabulous Beauty Supply was selling two kinds of creams containing the steroid, one made in Milan, Italy, and the other made in the Grisons region of Switzerland. Both are labeled as Lemonvate Cream and both list clobetasol propionate as an ingredient on their packages.

Rosenberg said anyone using the cream without a prescription should talk to a dermatologist who might recommend they gradually wean off it.

Alvey said the FDA last had a problem with over-the-counter sales of clobetasol propionate in 1997, when a Madrid-based manufacturer was making sprays, shampoos and creams for dandruff, psoriasis and other skin disorders. It claimed that the active ingredient was zinc pyrithione, an over-the-counter treatment for some kinds of dandruff. But an FDA analysis found that the products, called Skin-Cap, actually contained clobetasol propionate.

“We had patients coming in saying, ‘I don’t need to see a dermatologist. I’m using this stuff because it’s natural and it helps me,’ ” Beer said. “They were doping it with very strong steroids.”

—–

To see more of The Palm Beach Post — including its homes, jobs, cars and other classified listings — or to subscribe to the newspaper, go to http://www.palmbeachpost.com.

Copyright (c) 2005, The Palm Beach Post, Fla.

Distributed by Knight Ridder/Tribune Business News.

For information on republishing this content, contact us at (800) 661-2511 (U.S.), (213) 237-4914 (worldwide), fax (213) 237-6515, or e-mail [email protected].

DSCM,

PAUL was my cousin but felt more like a brother. We were born six months apart and spent our early years living in the same tenement block. Then our families obtained council houses facing each other across a neat little street. For years, we spent every moment of our free time together. We fished, built dens, dammed streams and enjoyed an oldfashioned childhood exploring the beaches, woods and moorland around our home on the lower Clyde at Gourock. It never occurred to me that he couldn’t keep up, despite his yearround pallor and spindly limbs. We grew used to his regular spells in the old ear, nose and throat hospital, just as we stopped noticing the foul smelling sludge he was forced to consume before meals, to help him to gain nourishment from his food.

I was in London when he died, a few weeks short of his 23rd birthday.

I had completed a degree course and post-graduate studies. I was soon to be married, and looking forward to a career in journalism. But Paul had been unable to move on because of his illness. My grief was further blighted by guilt that I had left him behind in a race to embrace the exciting new adult world which was closed to him. Paul’s education had suffered through his long absences from school. He may well have had the same potential as his younger brother, who became a brilliant doctor of physics, but it was impossible for him to test his capabilities.

He bravely refused to give in, working when he could, keeping busy during the long periods when he was weak by building intricate models of the boats which obsessed us as children. During his last few months, he was sent to London for treatment, allowing us to spend some time together. He knew he was dying. On one occasion, we attended the motor show at Earls Court and I found him on a balcony, looking down over the vast exhibition space, visibly upset and overwhelmed. The huge scale of the place and the mass throng of humanity turned the individual into a tiny, insignificant speck. I imagine Paul felt like he was disappearing.

He was one of 7500 people in the UK suffering from cystic fibrosis, this country’s most common, inherited, life-threatening disease. Half are children, 70-per cent are aged under 20 and three of them die every week.

CF affects vital organs in the body, especially the lungs and digestive system, making it difficult to breathe and to break down food. Life expectancy is about 30 years, because the lungs are progressively destroyed through recurrent infections by a bacteria which causes no problem for healthy people.

But there is hope. After Paul died, scientists identified the CFTR gene, defects in which cause cystic fibrosis.

In 1992, they bred a mouse carrying a defective gene. As a result, we now know how the disease attacks the body and have developed new treatments. We know, for example, that CF mice can fight lung infections more effectively when given lipoxin, a substance related to aspirin and ibuprofen. We have discovered that increasing the amount of liquid in the airways helps prevent the mucus build-up which leaves patients needing intensive physiotherapy. The mice are key to developing gene therapies, and finding ways safely and effectively to deliver these into the lungs using viruses. Putting copies of the healthy gene on to common cold viruses has resulted in a 25-per cent improvement in lung function among the mice. Experiments on the animals have also helped researchers understand the damage to human digestion caused by CF – the reason my cousin was so thin. Only last year they found that the yellow pigment in turmeric can prevent gastrointestinal symptoms in the mice.

The challenge now is to replicate this success in people. Can anyone imagine a more noble use for the humble rodent? Mice have also played a key part in developing other life-saving treatments. These little mammals were used to develop insulin for diabetics; anti-coagulents, such as warfarin which prevents blood clots and heart attacks, antibiotics; vaccines to eradicate polio, whooping cough and Hib meningitis;

and chemotherapy treatments for leukaemia which mean that eight out of 10 children with the most common form of the disease now can expect long-term survival. Mice will also save lives in the future, not just in the privileged west, but right across the world. They are currently being used to develop an effective vaccine against malaria, which kills three million people a year, most of them children under five.

Guinea pigs may have a higher cuddliness quotient than mice, but as mammals they too have a vital role to play in the cause of medical research.

Studies using these rodents have helped to develop treatment for tuberculosis, diphtheria, kidney disease and asthma. They are particularly useful for research into the latter disease because their airways are sensitive to allergens. Without guinea pigs, children wouldn’t have inhalers.

None of this will make the slightest impression on the militant animal activists who this week forced a guinea pig breeder in Staffordshire to close because he supplied a laboratory. Like so many ideologues throughout history, they lack human empathy. Why would these people be moved by the story of my cousin’s short, painful life, burdened as it was by a cruel understanding of his own impending death? It was Robert Burns who defined the difference between mice and men with a poetic intelligence which is relevant today.

He pointed out that the field mouse, though its home was destroyed, was more fortunate than the ploughman because it could not anticipate the future. Only the present touches the dumb animal. The human being can guess and fear his future – like my cousin Paul in Earls Court, horribly aware of the fragility of his life.

The extremists’ exaggerated identification with animals masks emotional and psychological flaws.

How else can we explain their theft of the body of Gladys Hammond, the elderly lady whose son-in-law owned Darley Oaks farm? I’ve no doubt they argue that guinea pigs deserve more respect in life than human beings do in death. But their sinister campaign displays no more sensitivity to the living than it does to the dead. One farm worker had his name spelled out in gun cartridges on his lawn and was forced to quit his job when they threatened to kill his 71-year-old grandmother.

These are not isolated incidents, and they are terrifyingly effective. The Association of the British Pharmaceutical Industry reports that last year 113 firms supplying medical research establishments were forced to back out of the business because of harassment from extremists. This is not just an attack on science. It’s an attack on ordinary people whose lives could be saved by scientists.

By Rose Skelton

BISSAU (Reuters) – Exhaling a plume of marijuana smoke
while perched on the only chair in his shack, self-styled
“combat musician” Bob Tones looks an unlikely candidate for the
job of keeping Guinea-Bissau’s politicians in check.

“They have to know that we’re still here,” said Tones, who
was dressed in military-style fatigues, army boots and a red,
yellow and green “Rasta” woolen cap.

The singer is one of a group of artists who sing in defense
of democracy and justice in this tiny impoverished West African
country where simply finding electricity to power a guitar
amplifier is a challenge.

Tracing their ancestry back centuries to an oral tradition
that has long given singers an influential place in West
African society, the “combat musicians” now have a new battle.

After years of coups, counter-coups and civil war,
Guinea-Bissau held elections last month to establish a new era
of democratic rule and end years of instability that have
hobbled efforts to fight chronic poverty.

Former military ruler Joao Bernardo Vieira was proclaimed
the winner by electoral authorities but the results have been
rejected by the ruling PAIGC party and their candidate Malam
Bacai Sanha, raising fears of more unrest.

During the campaign, musicians were paid around $30 a day
— half the average monthly salary of a doctor — to accompany
candidates and hand out gifts like T-shirts or banknotes.

Tones backed Sanha but said he would have remained true to
his mission to keep politicians in check whatever the result.

“Even if my candidate was in power, I would continue with
my combat music, to let him know that we’re watching what he
does.”

“THE CHILDREN ARE CRYING”

Musicians have long played the role of watchdogs in West
African societies, where the strong oral tradition and low
literacy rates have put singers in a privileged position as
social and political commentators.

“Music really is the best way of communicating with the
people,” said Jacob, 22, an unemployed man. “Each politician
asks musicians to come and sing their praises.”

Tones, who lives in a compound surrounded by sugar cane in
the rundown capital Bissau, said musicians have more sway than
traditional leaders — a fact appreciated by politicians.

“If they asked the head of the village to talk to people,
no one would listen to him. Instead they asked the new
generation of musicians to go out and campaign for them, to
sing their praises, to mobilize the people,” said Tones.

This influence can be turned against those in power as
well, as Tones’s music shows.

“The children are crying because since yesterday they
haven’t eaten,” he sings in a song on his album “Alerta.”

“And why? Because the government didn’t pay their papa for
the work he did,” he sings, referring to civil servants’
chronic pay arrears in a country where more than one in five
children die before they reach five years of age.

Ancient heritage has given Guinea-Bissau’s modern musicians
a wide range of sounds — from electric guitars to traditional
percussion like the water drum, a gourd suspended in water that
produces a resonating “thud” when beaten with a closed fist.

Contemporary music has also been influenced by Cape Verdean
and Caribbean zouk with its easy-going, romantic rhythm often
known in Africa as “Zouk Love.”

“INTERVENTIONIST”

During Guinea-Bissau’s struggle against Portuguese
colonizers before independence in 1974, musicians accompanied
fighters to mobilize supporters.

The artists went on to criticize corruption among the ranks
of the first generation of rulers. Some were killed, others
disappeared and many blame the authorities.

Justino Delgado, Guinea-Bissau’s best-loved musician, wrote
a song in 1985 criticizing the government run by Vieira, who
took power in a 1980 coup and ruled until he was ousted in a
putsch in 1999 after a devastating civil war.

After writing his song, Delgado spent four months in jail
before being exiled to Portugal.

“A lot of things were not right in the government but
people were afraid to speak about it. I wrote the song to
reveal the reality as I saw it,” he said, his voice cracking
with emotion.

“I am more than an artist, I am an interventionist.”

During this year’s election campaign, Delgado was employed
as Sanha’s official singer, telling people to a rousing beat:
“Mothers, fathers: Malam Bacai has the solution for the
country, give him the key to the presidential palace.”

The words became the catchphrase of the campaign and were
sung or played wherever Sanha went.

Politicians are not the only ones to see the power of music
in Guinea-Bissau.

“If you are a businessman and want to be popular, you pay a
musician to sing nice things about you,” says Waldir Araujo, a
radio reporter.

LOS ANGELES – At 65, Frank White was in dire health. A four-pack- a-day cigarette habit for nearly 50 years, a bad diet and a heavy dependence on alcohol had left him with severe respiratory problems, high blood pressure and a leaky heart valve. He was also battling rheumatoid arthritis and was more than 50 pounds overweight. He was, he later admitted, “headed for the cemetery.”

But he changed his life: He joined Alcoholics Anonymous and gave up drinking, then smoking – and not long after that, he found himself in a yoga class. He would later say that “AA gave me my life … but yoga gave me a new life to live.”

Mr. White, who died of throat cancer on Aug. 13 at 85, became a committed yogi and an inspirational figure to many as a model of healthy, energetic living in one’s senior years. He was also a leading teacher of the discipline with a large, diverse and loyal following. He taught hundreds of students over a 17-year period.

His transformation was recorded as part of the 2003 documentary film “The Fire of Yoga,” narrated by Ali MacGraw. In the film, Mr. White – then 83 – talked candidly about his lost years and his awakening, and credited his yoga practice with helping him repair his relationships with his family.

Mr. White grew up in Chicago during the Depression. After serving in the Navy during World War II, he came to Los Angeles to study acting. He married Selma Browner in the late 1940s and eventually found work as a character actor in films and later television.

He and his wife socialized with Browner’s sister Juliet and her husband, artist Man Ray, who lived in Los Angeles during the 1940s.

As film and television careers go, Mr. White’s apparently was steady but not spectacular. His credits included “Rosemary’s Baby,””Hill Street Blues” and “St. Elsewhere.” When there was no acting work, he made his living in interior design and furniture sales.

By the time he was in his mid-40s, Mr. White said, his life was in a downward spiral. He started drinking and developed a serious problem over the next 20 years before he bottomed out, reached AA and quit.

He found yoga by accident. A gifted jazz and classical pianist as a young man, he went to Los Angeles City College for a guitar class and found it had been canceled. But there was a yoga class going on and he stopped in. He would later say he felt like he was finally home.

He embraced the discipline and its spiritual, mental and physical aspects with the fervor of the converted. After two years of study, as a practitioner and as a budding instructor, Mr. White was on his way to fitness and looked a decade younger. He was able to stop taking much of the medication he had been using to treat his maladies. And he became a vegetarian.

After earning his teaching certification, he took his practice to the downtown Los Angeles Athletic Club and, at the age of 68, started teaching classes. He is credited with developing the program there, and the club’s yoga studio was named in his honor.

His mantra to his followers was basically that if he could do it at his age, they could at least give it a try.

“Life is soft and supple,” he said in an L.A. Athletic Club publication. “Death is hard and brittle. So choose one.”

Over the years, Mr. White believed he was able to reverse the aging process and control many of his health issues through yoga and holistic medicine, but he still had to contend with chronic obstructive pulmonary disease. His health declined further with cancer over the last six months but, his friends say, he was optimistic that there might be a reversal so he could get back to yoga.

His wife died in 1975. He is survived by two sons, Kevin and Rick; a grandson, Austin, and a brother, Jerry.

By Patrick Lannin

STOCKHOLM (Reuters) – “It’s easier with a Latvian,”
promises the recruitment agency’s Web site. To drive the point
home, it adds that staff from the Baltic state will cut a
Swedish employer’s wage costs by 50 percent.

The offer from a Latvian firm is the latest challenge to
Sweden’s decades-old system of setting wages through
sector-wide deals with employers in a country where 85 percent
of workers belong to a trade union.

The arrival of cheaper workers from new European Union
members has inflamed the debate, with trade unions describing
the practice of hiring low-cost migrants as modern slavery.

It’s a delicate issue in a country where unemployment
stands at a relatively high 7.1 percent.

The trade unions’ concerns are echoed across Europe, which
embraced 10 new members from mainly eastern European countries
last year. Some “old” European Union countries worry that the
bloc’s expansion will see locals replaced by migrant workers.

Maris Sergeyenko, who runs the Swedish arm of Latvian
recruitment firm Eiropas Eksperti through the www.hyrlett.nu
Web site, disputed the “slavery” label and said business was
good.

“Earlier we had 30 to 40 people in Sweden. Now it is around
100 and it could be around 400 to 500 by the end of the year if
all goes as it is going now,” the 24-year-old Latvian said.

The appeal for Latvians is clear. “Europe’s money will
become yours,” proclaims Eiropas Eksperti’s Latvian Web site.

Sergeyenko said the salaries offered by his company were
below those Swedes would earn but were still higher than those
offered in Latvia. Average salaries in Sweden are almost 10
times higher than in Latvia.

“They are lower, but it’s not slave labor like the unions
say,” he said, adding that his company also provided
accommodation for the workers.

“APARTHEID LABOR”

Sweden’s trade unions say the use of low-cost workers
threatens the “Swedish model” of fair labor. The dispute has
soured relations between the two countries.

“We don’t accept any apartheid labor market in Sweden where
you have one wage for Swedes and one for others,” said Erland
Olauson, senior official at powerful trade union federation

LO.

Last year, Latvian building firm Laval had to stop work on
a school in Vaxholm near Stockholm after unions refused to work
with Latvians who were not paid under a Swedish collective
deal.

Another Latvian builder, Bygg-Lett, has also faced strikes
while carmaker Volvo had to negotiate with unions and raise
salaries for Slovaks employed by a supplier.

Under EU rules citizens are free to settle and work
anywhere in the bloc but the ex-communist newcomers were forced
to accept restrictions on free labor movement for up to seven
years in most states. Sweden was among the few that opened its
markets.

A recent report from a civil rights watchdog, the European
Citizen Action Service, found the EU’s expansion had not
unleashed floods of cheap labor. Official data showed migration
west at well below 1 percent of the workforce.

EU IMPLICATIONS

Olauson said foreign firms were welcome in Sweden, as long
as they abided by rules on collective deals that provide a
floor for salaries in a country with no legal minimum wage.

The collective wage deal system began in 1938 and is viewed
as having fostered harmonious industrial relations.

With the welfare state, funded by the world’s highest tax
take, it is part of the “Swedish model” of economic management
which has made the country one of the richest in the world.

Olauson said strikes were an effective tool against firms
believed to be bending the rules, although it was difficult to
target firms operating through the Internet.

Christer Walivaara, international secretary at builders’
union Bygnadd, said some employers also said foreigners were
self employed, meaning collective deals did not apply.

The issue could be complicated further by EU legislation.
After the Vaxholm conflict, Sweden’s labor court asked for a
ruling from the European Court of Justice.

It wanted to know whether Sweden’s system was in line with
EU rules on the free movement of labor and whether industrial
action could be taken against a foreign company, even if it had
a collective wage deal in its land of origin.

“If EU law would make it impossible to take industrial
action in the way we normally do then this would be a big
problem,” Olausen said.

A judgment is likely to take between one and two years.

An added worry for unions comes from Sweden’s main
employers’ group. It wants change in collective wage deals and
is covering the Latvian firm’s costs for the EU court case.

Sergeyenko said his agency did not want to undercut Swedes,
but help reduce gaps in wealth on either side of the Baltic
Sea.

Building union official Walivaara said pressures for change
were mounting. “It is a critical time right now. We believe
this a good system, it’s what made Sweden so strong when it
comes to workers instead of having constant conflict,” he said.

Q. I want to lose weight, keep it off and have more energy. What diet do you recommend?

A. I am asked this question often.

I have even been asked specifically what I eat so a person could follow my precise eating habits.

What I have learned in 25 years of helping people reach their health and fitness goals is that you must discern what is best for you.

I can help you by giving you some guidelines, but you must be willing to take that information and think, plan, experiment, fail and succeed.

This is the best way for you to create your diet. And by following it, you will lose weight, keep it off and have tons of energy.

Julies Golden Guidelines

for Your Diet

1. Tell your physician. You are embarking on a healthful eating plan to lose weight, so obtain his OK. If there are any special circumstances, please consult with a registered dietician to help you create your diet.

2. Eat a variety of foods. If I lined up 50 people, the thinnest ones would be those who eat the greatest variety of foods.

3. Moderate calories. I have found that most people can lose weight on a plan of 1,500 to 1,800 calories a day.

Give this a try for two weeks. If you lose about one to two pounds a week, great.

If you dont lose any weight, back off to 1,400 calories a day.

Continue to adjust calories until you are consistently losing one to two pounds a week.

4. Keep fat intake to 30 percent. An easy method to figure this is to stick with the rule that any meal or snack should have one gram of fat to every 100 calories.

5. Think balance. Some carbohydrate, some protein, some fat.

6. Eat fiber. Fiber is the single best nutritional habit you can add to your life.

It helps you feel full, keeps food moving through your system, requires your body to work at digestion and is found only in healthful, nutritious foods.

Women need 20 grams a day, men 25.

7. Limit processed foods. Try not to eat them more than eight times a month.

8. Limit alcohol and sweets. Dont consume more than 500 calories a week.

You need the majority of your calories to come from high-energy, high-value foods.

9. Eat more often. Six small meals a day keep you thinking clearly so you will not be inclined to make poor choices.

10. Study nutrition. Look at food labels, watch healthful cooking shows on TV, take a few cooking classes, and read food magazines.

11. Write it down. Get a grip on what you are really eating by keeping a meal diary. Add up portions, calories, fiber, protein, fat and sugar.

This will aid you in two ways. First, you will become a savvy eater. You will know exactly what is in the foods you eat and how much is too much or just right.

Second, you will be acutely aware of what works.

12. Just say no. Discipline builds character and a lovely, energized body.

Julie Luther is a certified fitness trainer and the president of PurEnergy Health & Wellness Services. Write to Getting Fit, c/o Life Department, News & Record, P.O. Box 20848, Greensboro, NC 27420.

By Svetlana Kovalyova

SEBORGA, Italy (Reuters) – Tourists ran after Giorgio
Carbone as he crossed a square in the village of Seborga in
northern Italy. They all wanted pictures of the nondescript man
with the graying beard, tired-looking eyes and simple suit.

That’s because Carbone is, in fact, Prince Giorgio I of
Seborga, a former flower seller dedicated to promoting this
medieval village’s claim of independence.

At first sight, Seborga is a typical picture postcard
village on the Italian Riviera with minute squares and narrow
streets meandering beneath an imposing bell tower.

But a sign proclaiming “Welcome to the Principality of
Seborga” and blue-and-white striped flags fluttering from its
buildings set it apart from the other villages dotting the
coastline between Genoa and the French border.

“We are the oldest principality in the world,” said
Carbone, who peppers his speech with swear words, making
tourists blush and earning him the nickname “Sua Tremendita” or
“Your Tremendousness” among the villagers.

Seborgans believe their independent history dates back to
954 when the counts of nearby Ventimiglia gave the land to
Benedictine monks who established a sovereign Cistercian state.

When the monks sold Seborga to the King of Savoy and
Sardinia in 1729 the deal was not registered, local historians
say. Since then, Seborga has been missing from historical
records, including the acts of the unification of Italy in 1861
and the formation of the Italian Republic in 1946.

Carbone’s years of research into Seborga’s past finally
convinced the villagers to elect a prince in 1963. Despite his
lack of royal blood and gruff ways, Carbone’s dedication to the
cause made him a natural choice.

NO REVOLUTION

Seborga’s go-it-alone aspirations find an echo in a string
of tiny principalities across Europe. Just along the coast from
the Italian village is the city-state of Monaco, ruled by the
Grimaldi dynasty for more than seven centuries.

There is also Andorra, tucked away on the border between
France and Spain, and the Alpine state of Liechtenstein.

Carbone believes his village is as independent as flashier,
more famous Monaco.

“We have always been independent. We don’t need to be
recognized by any other state. They have to be recognized by
Seborga,” he said, sipping local wine at a bar.

The 69-year-old said Italy had never spoken out against
Seborga’s claim of independence. He also believes the Vatican
tacitly supports the village despite an official silence.

“We want to run our own home. We don’t want to be part of
European political or monetary union. We want to be a happy
quiet island in Europe, which is engulfed in globalization that
can only trigger revolutions,” he roared in his hoarse voice.

Giorgio I himself is planning no revolution.

His mission is to create a state free of crime, corruption
and other vices, not to stop Seborga’s 300 inhabitants from
paying Italian taxes or voting for the national parliament.

Nonetheless, Seborga now has its own constitution,
government, parliament and court.

It mints own coin — a Luigino, which is fixed at $6.00 and
which circulates within the principality alongside the euro.
Seborga issues passports and car number plates, also valid only
within its limits.

“BORN LIKE A GAME”

Mayor Franco Fogliarini said the influx of curious visitors
to Seborga had increased over the last 10 years as news of its
independence claim spread.

“The whole story was born like a game,” said Fogliarini,
recalling that as a boy he and his friends used to dress up in
medieval costumes, set up a roadblock on the way to the village
and issue special passes for tourists.

Now the mayor hopes that Seborga’s story of independence
will attract tourists, boost its budget and create jobs.

Fogliarini also toyed with the idea of fiscal autonomy, but
the prospect of full independence did not inspire him.

“Who would manage it? And how? It’s a difficult and
impractical thing,” he said.

International law experts say Seborga’s claim to be an
independent state is not valid because it does not exercise
state authority on its territory in the region of Liguria.

Local historian Marco Cassini doubted that Seborgans wanted
true independence anyway.

“Like people from all small towns in Liguria, Seborgans
have a strong local pride and an independent spirit,” Cassini
said. “They have a unique history and they have just been smart
enough to take advantage of it and attract tourists.”

Dear Dr. Gott: My wife, 42, had a seizure in 1994 that her doctor attributed to alcohol withdrawal. She was placed on Dilantin, and the Department of Motor Vehicles revoked her driver’s license. She continues to test “sub-therapeutic” and the DMV will not return her license until her doctor says it’s OK for her to drive. She’s had no more seizures and is alcohol-free. She doesn’t want to remain on medication for the rest of her life. What’s the alternative?

Dear Reader: Sudden cessation of heavy drinking can cause seizures; this is the reason that alcohol is considered addictive. The body becomes dependent on it. When the alcoholic stops drinking without medical supervision (and prescription drugs to assist detoxification), seizures can result.

At that point, the doctor placed her on anticonvulsant medication. Subsequent blood tests have shown a suboptimal level of Dilantin in her system, but she has been seizure-free.

Therefore, I conclude that she did, indeed, experience a single convulsive episode, probably related to alcohol. If she doesn’t drink, she won’t have any more seizures.

This is where the picture becomes less clear. Most doctors would have stopped the medication after a few months, obtained a brainwave test (to check for epilepsy, an inherited seizure disorder) and monitored your wife’s health. If she remained seizure-free for a year, the majority of motor vehicle departments would reissue her license provided that she remained abstinent and the doctor confirmed that she was no longer a threat on the road.

I’m confused as to why she is still on medication. I do not understand why, while taking therapy, her Dilantin blood levels were not taken more seriously. It would be customary to increase the dose of the drug until a therapeutic level was obtained. The doctor can’t have it both ways; either he would discontinue treatment or make sure that she receives an appropriate amount. If she doesn’t need the Dilantin, she shouldn’t have to take it for the rest of her life.

In my view, she has two choices:

1. Return to the physician for clarification of the issues I raised and a letter to the state authorities allowing them to re- license her.

2. Seek a consultation with a neurologist — or, if her treating doctor is such a specialist, a second neurologist. The new doctor should be able to sort things out and get your wife’s license back.

To give you related information, I am sending you a copy of my Health Report “Epilepsy: The Falling Sickness.” Other readers who would like a copy should send a long, self-addressed, stamped envelope and $2 to Newsletter, P.O. Box 167, Wickliffe, OH 44092. Be sure to mention the title.

Write Dr. Gott c/o United Media, 200 Madison Ave. 4th floor, New York, NY 10016

CHEMICALS in hair dye could raise the risk of dementia, research suggests.

A study of millions of death records has revealed that certain jobs increase the chances of developing brain diseases such as Alzheimer’s and Parkinson’s.

And it appears hairdressers face a higher than normal risk of suffering early- onset dementia, Alzheimer’s disease and motor neurone disease.

The researchers say the findings may be explained by hairdressers’ daily exposure to powerful chemicals in dyes and other products in salons.

Such chemicals have previously been known to trigger allergies, skin problems, headaches and coughing.

Other studies have suggested they might be linked to cancer with rates of bladder tumours in women who dye their hair twice that of those who keep their natural colour. It is thought chemicals may build up in the bladder and so damage cells.

One Swedish study found that women who use hair dye for 20 years could be doubling their risk of developing arthritis.

Another report suggested the dye could cause birth defects in unborn children when absorbed through a pregnant mother’s scalp and into her bloodstream.

The latest research, by the National Institute for Occupational Safety and Health in Ohio, was based on more than 2.6million American death certificates issued between 1992 and 1998.

Overall, 4 per cent of deaths were found to have been caused by degenerative brain diseases.

The study, published in the American Journal of Industrial Medicine, found there were some distinctive patterns linked to jobs.

Hairdressers were found to have a higher risk of early-onset dementia, Alzheimer’s and motor neurone disease, but not Parkinson’s.

Their risk was between 23 and 38 per cent higher than the general population.

Farmers and welders, who are also exposed to powerful chemicals- were found to have a higher risk of all four brain conditions.

Members of the teaching, clergy and banking professions were all more likely than normal to develop conditions such as Alzheimer’s and Parkinson’s.

Dentists and the clergy were particularly likely to get earlyonset dementia and vets faced a higher than normal risk of getting motor neurone disease.

The researchers suggested that may be because those in more ‘ professional jobs’ had healthier lives and ate better diets.

As a result, this may mean they avoided dying early from heart disease and so succumbed to brain conditions in later life. The researchers called for more studies to confirm their findings, acknowledging that at best their study could show only general patterns.

Ray Seymour, general secretary of the National Hairdressers’ Federation, said he had never heard of a link between hair dyes and dementia. ‘Looking at the different occupations, it is hard to see any common chemicals in the workplace that would link hairdressers, welders, teachers and members of the clergy,’ he added.

‘It is such a wide diverse group that you would need to try to identify which factors were relevant and if lifestyle played a part.

It may be down to something totally unrelated to their job.’

[email protected]

Summary

This article examines spirometry as a method of detecting lung disease, particularly chronic obstructive pulmonary disease (COPD). Methods of producing an accurate assessment and identifying acceptable traces are outlined, and contraindications are discussed.

Author

Rachel Booker is COPD module leader and head of student support, the National Respiratory Training Centre, Warwick. Email: [email protected]

Keywords

COPD, Lung disorders, Respiratory system and disorders

These keywords are based on the subject headings from the British Nursing Index. This article has been subject to double-blind review. For related articles and author guidelines visit our online archive at www.nursing-standard.co.uk and search using the keywords.

RESPIRATORY DISEASE is a major cause of morbidity and mortality in the UK. More people die from respiratory disease than coronary heart disease or cancer, and respiratory illness is the most common reason for emergency hospital admission. Almost a third of the population will visit their GP with a respiratory condition at least once a year (British Thoracic Society (BTS) 2000). Objective diagnosis, monitoring and appropriate management of respiratory disease require measurement of lung function. The latest asthma guideline (BTS and Scottish Intercollegiate Guidelines Network (SIGN) 2003) highlights the need for objective diagnosis and recommends spirometry to assist with this.

The first national guideline on the management of chronic obstructive pulmonary disease (COPD) (BTS 1997) recommended spirometry for the early and accurate diagnosis of COPD. The recent COPD management guideline from the National Institute for Health and Clinical Excellence (NICE) (National Collaborating Centre for Chronic Conditions (NCCCC) 2004) supports the use of spirometry for diagnosis and monitoring of COPD, and recommends that spirometry be widely available in all healthcare settings. There has been an increase in spirometry use and nurses are more frequently performing the procedure and interpreting results.

Definition

A spirometer is a piece of equipment that an individual blows into through a mouthpiece. It is used to measure lung volume and the rate at which air can be exhaled during forced exhalation.

There are a variety of spirometers available. The simplest, volumetric spirometers, measure volume directly. Types of volumetric spirometers include:

* Water-sealed spirometers.

* Rolling-seal spirometers.

* Wedge bellow spirometers.

Volumetric spirometers tend to be large. A wedge bellow spirometer, for example, is the size of a large microwave and water- sealed and rolling-seal spirometers are even larger.

Volumetric spirometers are most commonly used in secondary care settings in outpatient clinics and pulmonary function laboratories where they do not need to be moved around. They cost between 1,500 and 3,000, although may cost more. Other spirometers use a variety of technologies to sense airflow and electronically calculate volume from flow. They are smaller and generally more suitable for use by health professionals in primary care and community settings. These include:

* Pneumotachographs.

* Anemometers.

* Turbine spirometers.

* Ultrasound spirometers.

They range from ‘desktop’ models, which are about the size of a laptop computer, to small hand-held devices. These spirometers range in price from 300-500 for a basic hand-held spirometer to 1,000- 1,500 for a desktop spirometer. Compared with volumetric spirometry, the performance is the same as long as the equipment is used appropriately. The main difference is that the technique is less easy to assess with some electronic flow measuring devices.

Measurement

A spirometer measures accessible lung volume vital capacity. ‘Accessible’ refers to the fact that spirometers can only measure the air that is exhaled and inhaled. There is always some air remaining in the lungs at the end of the exhalation that cannot be measured with a spirometer. This is known as the residual volume. The residual volume plus the vital capacity make up the total lung capacity. Accessible lung volume is measured in two ways:

* Relaxed vital capacity (RVC). A relaxed exhalation from maximal inhalation to maximal exhalation.

* Forced vital capacity (FVC). A forced exhalation from maximal inhalation to maximal exhalation using maximum effort.

The volume of air exhaled in the first second of forced exhalation is also measured:

* Forced expired volume in one second (FEV^sub 1^).

These lung volumes are expressed as both absolute volumes, in litres, and as a percentage of the predicted reference value for someone of that age, gender, height and ethnic group. Normative values for the UK population are available (Quanjer et al 1993, NCCCC 2004).

The FEV^sub 1^ is also expressed as a percentage of FVC or RVC (if this is greater):

* FEV^sub 1^% or FEV^sub 1^/FVC, FEV^sub 1^/RVC.

FEV^sub 1^% is the marker of airflow obstruction. Values of less than 70 per cent are diagnostic of obstructive airways disease. Abnormal spirometry, however, cannot confirm a diagnosis. Spirometry must only be interpreted in the light of a good history and other diagnostic tests.

RVC, FVC, FEV^sub 1^ and FEV^sub 1^ % are the most important parameters of lung function. Most electronic spirometers will also produce an array of other measurements, most of which are not essential for simple spirometry.

BOX 1

Calculation of forced expired volume in one second as a percentage of forced or relaxed vital capacity (FEV^sub 1^%)

Spirometry results can be presented graphically in two ways:

* A volume/time graph of volume exhaled in litres (vertical axis) against the time taken in seconds to exhale completely (horizontal axis).

* A flow/volume graph of flow rate in litres per second (vertical axis) against volume in litres (horizontal axis).

Disease and spirometry measurement

In patients with normal lung function:

* The FVC should be the same or slightly greater than RVC.

* The FVC should be greater than 80% of the predicted value for an individual of that age, gender, height and ethnic group.

* The FEV^sub 1^ should be greater than 80% of the predicted value for an individual of that age, gender, height and ethnic group.

* The FEV^sub 1^% (that is, the FEV^sub 1^ expressed as a percentage of the FVC or RVC if that is greater) should be between 75 and 85% to be within normal range.

* The FEV^sub 1^ % is a different measurement from the FEV^sub 1^ as a percentage of the predicted FEV^sub 1^.

Obstructive lung diseases, such as asthma and COPD, obstruct airflow and will reduce the volume of air exhaled in one second (FEV^sub 1^), so that it is less than 80% of the predicted value, and reduce FEV^sub 1^ %. An FEV^sub 1^ % that is less than 70% is diagnostic of airflow obstruction.

FVC and FEV^sub 1^ will be less than 80% of the predicted value where lung volumes are restricted, for example, in pulmonary fibrotic diseases such as fibrosing alveolitis, or musculoskeletal disease such as kyphoscoliosis. However, these disorders do not obstruct airflow and FEV^sub 1^ % is unaffected. In restrictive disorders, FEV^sub 1^ % is more than 75 % and is of ten greater than 8 5 %.

In severe airflow obstruction, dynamic airway collapse during forced exhalation traps air in the lungs and reduces FVC causing restriction and obstruction. In such cases, RVC will be significantly higher than FVC and will more accurately reflect vital capacity than FVC . Calculation of FEV^sub 1^ as a percentage of RVC (Box 1 ) may reveal a reduced FEV^sub 1^ % indicative of airflow obstruction that may otherwise be missed.

Table 1 summarises the parameters of lung function affected in various respiratory diseases. The effects of obstructive, severe obstructive and restrictive diseases on volume/time and flow/volume traces are shown in Figures 1 and 2.

Peak expiratory flow

Peak expiratory flow (PEF) is defined as: ‘the maximum flow achieved during an expiration delivered with maximal force starting from maximal lung inflation’ (American Thoracic Society 1995).

Measurement of PEF is easy. PEF meters cost less than 10, are portable and available on prescription. This makes them suitable for patients to use and keep at home, and they are useful for detection and ongoing monitoring of variable airflow obstruction: the hallmark of asthma. PEF is of limited use in other respiratory conditions.

PEF measures flow rate in the first tenth of a second of a forced exhalation. PEF measures flow rate and FEV, is a measure of volume. They are not interchangeable and PEF cannot be predicted from FEV1 or vice versa. Reference predicted PEF values are less robust than spirometric values. PEF is insufficiently sensitive to detect early airflow obstruction in COPD and can seriously underestimate the degree of airflow obstruction in more severe COPD. Therefore, spirometry is more suitable for assisting in the diagnosis of COPD (NCCCC 2004). A further limitation of PEF is that, unlike spirometry, it does not measure lung volumes and cannot be used to detect restrictive lung diseases, such as pulmonary fibrosis.

TABLE 1

Effect of respiratory disease on spirometry

FIGURE 1

Abnormal volume/time traces

Criteria for optimal spirometry

The BTS and the Association for Respiratory Technology and Physiology (ARTP) (BTS and ARTP 1994) suggest four optimal criteria for a spirometer (Box 2).

Most mid-price range and desktop el\ectronic spirometers fit the above criteria. Hand-held spirometers are relatively cheap, but may not have a visual display. Unless they are linked to a computer, it is not possible to verify adequacy of the technique and hard copies of results may not be produced. Charts of reference values may have to be used to manually calculate and interpret the results, creating the potential for error.

Some electronic spirometers have additional mechanisms for checking the adequacy of the patient’s technique. They will detect errors, such as a slow start to the forced blow, early stoppage, hesitation, and poor effort. An additional feature of some electronic spirometers is the ability to interface with the patient’s computerised medical record. This allows easy storage and retrieval of results, or emailing of results for quality-control purposes (Box 3).

Performance and interpretation

Spirometry, like PEF, is a relatively easy measurement, but it does require effort and cooperation from the patient. It is also essential that the health professional taking the measurements is trained in the technique and is able to recognise technically acceptable results and correct technique errors. It is also vital that whoever interprets the results is trained and competent. Poorly performed and interpreted spirometry is likely to lead to misdiagnosis or missed diagnosis (Woolhouse and O’Hickey 1999). The NICE COPD guideline recommends that quality-control mechanisms are set up to support primary care spirometry services (NCCCC 2004). In accordance with their Code of Professional Conduct (NMC 2004), nurses responsible for recording or interpreting spirometry must ensure they are appropriately trained.

BOX 2

Four optimal criteria for a spirometer

FIGURE 2

Abnormal flow/volume traces

Contraindications

There are no absolute contraindications to spirometry but common sense should be exercised. Where there are any grounds for concern, assessment at a lung function laboratory may be advisable.

Forced expiration using maximum effort raises intra cranial, intrathoracic and intraabdominal pressure. Therefore, consider deferring spirometry for about six weeks in patients who have had recent eye, chest or abdominal surgery, or who have recently had a myocardial infarction or cerebrovascular accident (BTS and ARTP 1994).

Spirometry can produce bronchospasm, particularly in patients with chest infections and bronchial hyperreactivity. Spirometry readings will progressively worsen with each effort and further attempts should be abandoned. Spirometry should be performed when the patient is clinically stable and free of infection whenever possible.

Cross-infection and risk minimisation

Contamination of spirometry equipment and the potential for cross- infection need to be considered. Although there is no study or case report that has demonstrated that spirometry poses a significant risk to patients, common sense and good hygienic practices should be used.

Ultrasonic and anemometer spirometers use disposable single- patient-use mouthpieces that prevent cross-infection. The use of one- way mouthpieces with other spirometers can prevent accidental inhalation through the spirometer, and are a minimum requirement to reduce infection risk.

If inhalations are required, a bacterial and viral filter will be needed. Patients suspected of having active chest infection, particularly tuberculosis, should not be tested. If spirometry is clinically necessary, patients with chest infection should be tested at the end of the day with equipment that can be disinfected after use. Patients who are immunocompromised should be tested at the beginning of the day on newly disinfected equipment.

BOX 3

Essential features of a spirometer

Flow sensors, such as pneumotachographs and turbines need to be cleaned and disinfected according to manufacturers’ instructions. Flow sensors cannot be autoclaved and the use of inappropriate sterilising fluids can damage or destroy them. Disinfection of volumetric spirometers is difficult and costly. Therefore, it is essential that the correct mouthpieces are used and care is taken to protect patients from cross-infection.

Spirometer calibration

Calibration of all spirometers should be regularly checked and a log kept of this procedure. Electronic spirometers should be checked before each session using a calibration syringe. Although current flow sensors are often robust and reliable, it is necessary to check that the equipment is recording accurately.

Technically acceptable and meaningful results

RVC should be recorded as a baseline measurement. It is important to ensure that the patient has taken a maximal inhalation. The mouthpiece is positioned so that the tongue and teeth do not occlude it and the lips are sealed around it to prevent air leaks. A nose clip is used to prevent air leakage down the nose.

The patient needs to exhale steadily, in a relaxed manner until he or she is unable to exhale any further. This should be repeated at least twice, or until the two best readings vary by less than 5% and 100ml.

A minimum of three forced exhalations needs to be recorded so that the best two readings of FEV^sub 1^ and FVC vary by less than 5% and 100ml. If necessary, eight exhalations can be undertaken to achieve this level of reproducibility. Vigorous verbal encouragement to exhale continuously with force will help ensure maximum effort to FVC.

FIGURE 3

Acceptable volume/time and flow/volume traces

The acceptability of the forced exhalations needs to be checked by looking at graphic traces of volume/time and flow/volume. Traces should be smooth and free of irregularity. The volume/time trace should curve smoothly upwards to a plateau and the flow/volume trace should rise almost vertically to a peak and should merge smoothly with the horizontal axis. Inadequate blows must be rejected. Spirometry cannot be interpreted unless acceptability and reproducibility criteria are met. Technically acceptable traces showing normal lung function are shown in Figure 3.

Conclusion

Spirometry was, until recently, only available routinely in secondary care settings. The publication of disease management guidelines (BTS 1997, BTS and SIGN 2003, NCCCC 2004) has prompted increased spirometry use in primary care (Halpin and Rudolph 2002). The new General Medical Services Contract (Department of Health 2003), which financially rewards general practices for diagnosing and monitoring COPD with spirometry, has prompted the widespread use of spirometers in general practice.

There are concerns about the quality of spirometry practice in primary care and the ability of some primary healthcare professionals to interpret results ( Woolhouse and O’Hickey 1999). However, with appropriate training, continued practice and good quality control, respiratory patients in all healthcare settings can have lung function objectively assessed and be diagnosed and treated appropriately (Schermer et a/2003)

Booker R (2005) Best practice in the use of spirometry. Nursing Standard. 19, 48, 49-54. Date of acceptance: March 18 2005.

References

American Thoracic Society (1995) Standardization of spirometry, 1994 update. American Journal of Respiratory and Critical Care Medicine. 152, 3, 1107-1136.

British Thoracic Society and the Association for Respiratory Technology and Physiology (1994) Guidelines for the measurement of respiratory function. Respiratory Medicine. 88, 3,165-194.

British Thoracic Society (1997) BTS guidelines for the management of chronic obstructive pulmonary disease. Thorax. 52 (Suppl 5), S1- S28.

British Thoracic Society (2000) The Burden of Lung Disease. BTS, London.

British Thoracic Society and Scottish Intercollegiate Guidelines Network (2003) British guideline on the management of asthma. Thorax. 58 (Suppl 1)1 il-94.

Department of Health (2003) Investing in General Practice: The New Genera/ Medical Services Contract www.dh.gov.uk/assetRoot/04/07/ 19/67/04 071967.pdf (Last accessed: July 29 2005.)

Halpin DMG, Rudolph M on behalf of the BTS COPD Consortium (2002) Implementing the BTS COPD Guidelines: how far have we come? European Respiratory Journal. 20 (Suppl 38), 1637

National Collaborating Centre for Chronic Conditions (2004) Chronic obstructive pulmonary disease. National clinical guideline on management of chronic obstructive pulmonary disease in adults in primary and secondary care. Thorax. 59 (Suppl 1), 1-232.

Nursing and Midwifery Council (2004) The NMC Code of Professional Conduct: Standards for Conduct, Performance and Ethics. NMC, London.

Quanjer PH, Tammeling GJ, Cotes JE, Pedersen OF, Peslin R, Yernault JC (1993) Lung volumes and forced ventilatory flows. Report Working Party Standardization of Lung Function Tests, European Community for Steel and Coal. Official Statement of the European Respiratory Society. European Respiratory Journal Supplement 16, 5- 40.

Scheriner T, Eaton T, Pauwels R, van Weel C (2003) Spirometry in primary care: is it good enough to face demands like World COPD Day? European Respiratory Journal. 22, 5, 725-727.

Woolhouse I, O’Hickey SP (1999) Accuracy of spirometry measured in general practice compared to a hospital pulmonary function laboratory. European Respiratory Journal. 14 (Suppl 30), 273s.

RESOURCES

Short course in basic spirometry and interpretation is available from The National Respiratory Training Centre: www.nrtc.org.uk

Certification of competence in spirometry and its interpretation is available from The Association for Respiratory Technology and Physiology: www.artp.org.uk

British Thoracic Society chronic obstructive pulmonary disease consortium publications: www.brit-thoracic.org.uk/iqs/copd- publications-library.html

Copyright RCN Publishing Company Ltd. Aug 10-Aug 16, 2005

This was a prospective study performed in a Department of Veterans Affairs Medical Center. The aim of this study was to use endoscopic and histological examinations to determine the potential diagnostic origins of chronic gastrointestinal symptoms among patients who were part of the deployment of troops to the Persian Gulf after August 1990. Twenty-four (8%) male patients (mean age, 42 years) of 308 patients in the Persian Gulf War Registry agreed to undergo endoscopic examination of chronic symptoms, including heartburn (29%), dyspepsia (33%), dysphagia (8%), diarrhea (63%), Hemoccultpositive stool (21%), and rectal bleeding (17%). There were 17 upper endoscopies, 18 colonoscopies, and 4 flexible sigmoidoscopies performed, all with biopsies. Five (33%) of 15 patients had positive serological findings for Helicobacter pylori. With upper endoscopy, major findings included esophagitis (12%), Schatzki’s ring (12%), hiatal hernia (47%), antral erythema (59%), and duodenal erythema (29%). With lower endoscopy, major findings included ileitis (5%), lymphoid hyperplasia (9%), polyps (27%), diverticulosis (23%), and hemorrhoids (23%). Major histopathological findings included microscopic esophagitis (24%), gastritis with H. pylori (35%), gastritis without H. pylori (18%), Crohn’s disease (5%), tubular adenoma (5%), hyperplastic polyps (18%), and melanosis coli (5%). Most patients with chronic heartburn or dyspepsia have evidence of esophagitis or H. pylori. Individuals with these chronic symptoms should undergo evaluation.

Introduction

In August 1990, the United States began deployment of 697,000 troops to the Persian Gulf region.1 Of these troops, 77,000 individuals were being compensated by the U.S. government for chronic symptoms and another 23,000 individuals were awaiting a decision on compensation for their chronic symptoms in 1998.2

Prevalence data for chronic symptoms obtained from registries developed after the Persian Gulf War have yielded variable results. In the original registry developed by the Department of Veterans Affairs (VA), 48,251 individuals were included and diarrhea was reported by 5% of these individuals.1 In a more recent registry developed by the Department of VA, 9,002 individuals were included and diarrhea was reported by 14% of these individuals.1 The Department of Defense has had a separate evaluation program; of 27,747 individuals registered in this program, diarrhea was reported by 27%.1

Epidemiological studies of troops from the United States have also been performed. In surveys of National Guard units from Pennsylvania and another state, the prevalence of chronic symptoms in four units deployed to the Persian Gulf was examined and compared with that in four units that were not deployed to the Persian Gulf War.3 The size of the units deployed to the Persian Gulf War ranged from 119 to 470 individuals. The prevalence of diarrhea among these individuals ranged from 10 to 27%, and the prevalence of gastrointestinal gas and pain ranged from 18 to 38%. By comparison, the size of the units not deployed to the Persian Gulf ranged from 364 to 1,397 individuals. The prevalence of diarrhea among nondeployed troops ranged from 2 to 3%, and the prevalence of gastrointestinal gas and pain ranged from 10 to 14%.

An epidemiological study of a single National Guard unit has also been reported from Boston, Massachusetts.4 This study included 57 individuals who had served in the Persian Gulf War and 44 individuals who had not been deployed. The current presence of abdominal pain was reported by 70% of the deployed troops compared with 9% of the control group. The current presence of loose bowel movements was reported by 74% of deployed individuals compared with 18% of control subjects. The current presence of excessive gas was reported by 74% of deployed individuals compared with 23% of control subjects. Current nausea or emesis was reported by 23% of deployed individuals compared with 2% of control subjects. Current heartburn was reported by 33% of deployed individuals compared with 7% of control subjects.

Chronic gastrointestinal symptoms have also been reported by other Persian Gulf War coalition troops. There was deployment of 53,462 British troops. In a medical assessment program, 1,000 patients were initially examined, of whom 21.8% received a diagnosis of vomiting, diarrhea, or stomach problems.5 In a postal survey, flatulence or burping was reported by 34.1% of individuals deployed to the Persian Gulf region, whereas these symptoms were reported by 16.4% of individuals who had been deployed in Bosnia.6,7 Among Danish Persian Gulf War veterans, the prevalence of gastrointestinal symptoms was 9.1% compared with 1.7% among age-, gender-, and professionmatched control subjects.8 Questionnaire data8 suggested that patients with chronic symptoms might have suffered an environmental exposure (burning of waste or manure, contact with insecticide, or tooth brushing with, bathing in, or drinking of contaminated water).

Despite multiple epidemiological studies documenting the presence of chronic gastrointestinal symptoms, there is a dearth of information concerning the reasons why patients present with chronic gastrointestinal symptoms. The aim of this study was to use endoscopic and histological examinations to determine the potential diagnostic origins of chronic gastrointestinal symptoms among patients who were part of the deployment to the Persian Gulf. This prospective study included evaluation of laboratory results, endoscopic findings, and histopathological examination of biopsies obtained from veterans who were referred to the gastroenterology clinic because of chronic gastrointestinal symptoms that developed during and after service in the Persian Gulf War.

Methods

Permission for human studies was granted by the Human Studies Subcommittee at the Louis A. Johnson VA Medical Center in Clarksburg, West Virginia, on September 25, 1997. At the Louis A. Johnson VA Medical Center, there is a formal Persian Gulf War Registry that includes 308 patients and is made up of individuals who have been seen for evaluation of chronic symptoms for potential compensation by the U.S. government. This was a prospective study performed in a Department of VA Medical Center with patients who were included in the Persian Gulf War Registry and who were referred to the gastroenterology clinic for further evaluation of chronic gastrointestinal symptoms that developed during or after the Persian Gulf War.

In this study, dyspepsia was defined as episodic upper abdominal pain or discomfort.9 Heartburn was defined as pyrosis or regurgitation into the chest, or both.10 Chronic diarrhea was defined as a >3-week difficulty with an increase in the patient’s stool frequency or a change in fluid consistency.11

Twenty-four male patients (8%) agreed to undergo endoscopic examination for further evaluation of chronic gastrointestinal symptoms (Table I). Their age range was 26 to 62 years, with a mean of 42 years. The upper intestinal symptoms for which patients were referred to the gastroenterology clinic included chronic heartburn (29%), chronic dyspepsia (33%), chronic nausea (4%), hematemesis (4%), and dysphagia (8%). The lower intestinal symptoms for which patients were referred to the gastroenterology clinic included chronic diarrhea (63%), rectal bleeding (17%), Hemoccult-positive stool (21%), and fecal incontinence (4%).

Laboratory testing was offered to all patients to examine infectious or endocrine origins for chronic diarrhea or dyspepsia. All patient histories, physical examinations, and endoscopic procedures were performed by one of us (T.R.K.). Endoscopy was then performed with a video-endoscopy system. Seventeen patients underwent esophagogastroduodenoscopy, with three or four routine biopsies being obtained from the distal duodenum, the gastric antrum and body, and the distal esophagus. Eighteen patients underwent colonoscopy, with three or four routine biopsies being obtained from the ileum, ascending colon, descending colon, and rectum. Four patients underwent flexible sigmoidoscopy, with three or four routine biopsies being obtained from the sigmoid colon and rectum. These biopsies were incubated overnight in Formalin, embedded, sectioned, and stained with the hematoxylin and eosin method. All biopsies were then sent to the Armed Forced Institute of Pathology in Washington, DC, and reviewed by one of us (T.S.E.).

TABLE I

REFERRAL SYMPTOMS FOR PATIENTS WITH GULF WAR EXPOSURE

At the time of evaluation and at the time of endoscopy, no patient was being treated with a hydrogen/potassium-ATPase inhibitor. Of these 24 patients, 9 patients were being treated with a nonsteroidal anti-inflammatory drug (ibuprofen, 7; indomethacin, 1; aspirin, 1). Of the 24 patients, 8 patients were being treated with a histamine-2 receptor antagonist (ranitidine, 3; cimetidine, 4; famotidine, 1). Four patients were simultaneously receiving a nonsteroidal anti-inflammatory drug and a histamine-2 receptor antagonist.

Results

Laboratory Evaluations

The majority of the patients in this study completed laboratory evaluations to examine potential endocrine and infectious causes of diarrhea and dyspepsia (Table II). These studies included normal serum creatinine, glucose, and potassium levels for all patients. Thyroid-stimulating hormone and ser\um albumin levels were normal for all 23 patients examined, and serum calcium levels were normal for all 19 patients examined. Erythrocyte sedimentation rates were normal for all 17 patients tested. Fifteen patients underwent Helicobacter pylon serological testing and five (33%) had significant elevations of their antibody titers. All patients had normal white blood cell counts, hemoglobin levels, platelet counts, and mean corpuscular volumes, and there was no evidence of eosinophilia. Leishmaniasis serology was obtained for 16 patients, and all tests were negative. Lactose tolerance tests were performed for 12 patients, and 1 patient had evidence of lactose intolerance. A normal lactose tolerance test was defined by a peak glucose level that was >30 mg/dL over baseline, 20 minutes after a 50-g oral dose of lactose. Stool ova and parasite examinations were negative for eight patients. Stool cultures yielded only normal fecal flora for six patients and, in eight stool examinations for fecal leukocytes, only one patient had a few neutrophils identified.

Upper Endoscopic Findings

Seventeen patients underwent esophagogastroduodenoscopy (Table III). Among these patients, two patients had evidence of esophagitis (12%) and two patients had a Schatzki’s ring (12%). Eight patients had a hiatal hernia (47%) and one patient had a gastric polyp (6%). Ten patients were noted to have antral erythema (59%) and one patient had a gastric ulcer (6%). Five patients had duodenal erythema (29%) and one patient had a duodenal ulcer (6%).

Lower Endoscopic Findings

Eighteen patients underwent colonoscopy with routine intubation of the terminal ileum and four patients underwent flexible sigmoidoscopy (Table III). Ileltis consistent with Crohn’s disease of the terminal ileum was identified in one patient (5%). Two patients had lymphoid hyperplasia (9%). Six patients had colonic polyps (27%), five patients had diverticulosis (23%), and five patients had hemorrhoids (23%).

TABLE II

LABORATORY EVALUATIONS FOR PATIENTS WITH GULF WAR EXPOSURE

TABLE III

ENDOSCOPIC FINDINGS FOR PATIENTS WITH GULF WAR EXPOSURE

TABLE IV

HISTOLOGICAL FINDINGS FOR PATIENTS WITH GULF WAR EXPOSURE

Histological Findings

Among the histological findings (Table IV) from examination of biopsies obtained at upper endoscopy, four patients had microscopic esophagitis (24%) and six patients had gastritis associated with H. pylon (35%). Three patients had gastritis without evidence of H. pylori (18%).

During examination of biopsies obtained at lower endoscopy (Table IV), one patient had evidence of Crohn’s disease of the ileum (5%). One patient had a tubular adenoma (5%) and four patients had hyperplastic polyps (18%). Melanosis coli was identified in one patient (5%).

Among the nine patients receiving a nonsteroidal anti- inflammatory drug, seven patients underwent upper endoscopy and six patients underwent lower endoscopy. Among the seven patients who underwent upper endoscopy, gastric biopsies were normal for four individuals, with one case interpreted as gastritis with H. pylori and two cases interpreted as gastritis without H. pylori Among the six patients who underwent lower endoscopy, colon and rectal biopsies were normal for four individuals, with one patient with hyperplastic polyps and one patient with melanosis coli.

Discussion

We are unaware of any complete reports describing medical diagnoses among patients with chronic gastrointestinal symptoms after Persian Gulf War exposure. The U.S. Senate Committee on Veteran’s Affairs, in their summary report stated that these veterans are suffering from unexplained illnesses.1 The concern that initiated the present study was that such a position suggests that Persian Gulf War veterans do not have identifiable gastrointestinal disorders and evaluation of patient symptoms would therefore be unrewarding.

The patients in the present study did not fulfill the diagnostic criteria for irritable bowel syndrome, as defined by either the Rome I criteria12 or the Manning criteria, requiring ≥3 symptoms. 13 We propose that the results of the present study support the evaluation of patients with symptoms after Persian Gulf War exposure. Evaluation of patients with upper intestinal symptoms would more likely be diagnostically useful, compared with evaluation of patients with chronic diarrhea alone. Because of the size of the present study, it would be difficult to extrapolate its results to all individuals with chronic gastrointestinal symptoms who served in the Persian Gulf War region. In addition, the patients in the present study live in a rural environment and might be exposed to other environmental agents.

Among patients with upper intestinal symptoms, the majority of patients were found to have evidence either of gastroesophageal reflux disease (as manifested by endoscopic esophagitis, Schatzki’s ring, or microscopic esophagitis) or of antral gastritis, related either to H. pylori infection or to the use of nonsteroidal anti- inflammatory drugs in two patients. In addition, two patients had gastroduodenal ulcer disease. Our finding of gastroesophageal reflux disease would be consistent with a previous study that reported pulmonary and laryngeal complications among Persian Gulf War veterans.14 Because the patients in the present study had not received treatment with proton pump inhibitors, the potential benefit of treatment with high-dose therapy for ≥3 months is presently unknown.

The presence of antral gastritis was likely related to H. pylori infection for six patients and to the use of nonsteroidal antiinflammatory drugs for two patients. Presently, it is unclear but possible that eradication of H. pylon infection among patients with nonulcer dyspepsia may lead to long-term symptomatic relief.1516 It is unclear but possible that discontinuation of nonsteroidal anti-inflammatory drugs or conversion to cyclooxygenase- 2 inhibitory agents for patients with nonulcer dyspepsia may lead to long-term symptomatic relief. Because this prospective study was not designed as a treatment trial, there were no results obtained to examine these possible therapeutic alternatives.

The origin and mechanisms for the development of chronic diarrhea among these patients remain major questions. This study examined the mucosal responses of patients after Persian Gulf War exposure with endoscopic and histopathological examinations. We are unaware of complete colonic motility studies or colonie perfusion studies of patients with chronic diarrhea after Persian Gulf War exposure.

The identification of chronic symptoms among individuals after their presence at a common location suggests exposure to a yet unidentified environmental agent. There has been an extensive focus on the possibility that chronic symptoms among these patients might have resulted from exposures suffered by these individuals during their service in the Persian Gulf.17 Self-reported exposures included antidote given for potential exposure to chemical warfare agents (pyridostigmine), solvents or petrochemicals, smoke or combustion products, infectious diseases (including leishmaniasis), psychological stress, lead from fuels, pesticides, radiation (spent uranium used in shells), physical trauma, and possible chemical warfare agents.17

Of these potential exposures, there has been extensive evaluation of the potential for exposure to contamination during and after the demolition of a chemical depot in Khamisiyah, Iraq, on March 10, 1991.18 This chemical depot contained sarin and cyclosarin. Based on a meteorological model, it was predicted that a plume or cloud created by demolition could have led to the exposure of 98,910 troops. Among the problems with this model, troop locations during the Persian Gulf War remain uncertain. Among the patients in the present study, few were certain of their locations during the time period of interest. Of interest, individuals who did know their locations during the conflict often came to their gastroenterology clinic visits carrying still photographs of the purported explosion and in one instance carrying a videotape of the purported demolition. Because other sites were destroyed during the Persian Gulf War, it is possible that the development of chronic symptoms among 100,000 U.S. troops could be related to an additional but as yet unidentified exposure.

In toxicology studies, exposure to individual agents does not seem sufficient to explain the symptoms described by Persian Gulf War veterans. There have been preliminary data from an animal model that show that individual exposures are minimally toxic.19 However, with administration of two agents in combinations that included pyridostigmine bromide, permethrin, and JV.lV-diethyl-m-toluamide (insect repellent), there was enhanced neurotoxicity.19

We suggest that additional work should be encouraged to develop potential markers that could be used to screen patients with Persian Gulf War exposure and chronic diarrhea. These potential markers could include mediators of immunity or cytokines, tissue antioxidants, neurotransmitters and their receptors, or products of apoptosis. Without the availability of a marker, it will remain difficult for physicians to screen and evaluate patients with chronic diarrhea.

Acknowledgments

Published Persian Gulf War documents were obtained from the offices of the United States Senate. We thank Colonel John Graham. British Liaison Officer (Gulf Health), for his helpful discussions in the preparation of this work.

References

1. Committee on Veterans’ Affairs, United States Senate: Report of the Special Investigation Unit on Gulf War Illnesses. S. PRT 105- 39, Part I. Washington, DC, U.S. Government Printing Office, 1998.

2. Committee on Veterans’ Affairs, United States Senate: Report of the Special Investigation Unit on Gulf War Illnesses. S. PRT 105- 39, Part II. Washington. DC, U.S. Government Printing Office, 1998.

3. Kizer \KW, Joseph S, Moll M, et al: Unexplained illness among Persian Gulf War veterans in an Air National Guard unit: preliminary report: August 1990-March 1995. MMWR 1995; 44: 443-7.

4. Sostek MB, Jackson S, Linevsky JK, et al: High prevalence of chronic gastrointestinal symptoms in a National Guard Unit of Persian Gulf veterans. Am J Gastroenterol 1996; 91: 2494-7.

5. Coker WJ, Bhatt BM, Blatchley NF, et al: Clinical findings for the first 1000 Gulf War veterans in the Ministry of Defence’s medical assessment programme. Br Med J 1999:318:290-4.

6. Unwin C, Blatchley N, Coker W, et al: Health of UK servicemen who served in Persian Gulf War. Lancet 1999; 353: 169-78.

7. Coker WJ: A review of Gulf War illness. J R Navy Med Serv 1996; 82: 141-6.

8. Ishoy T, Suadicani P, Guldager B, et al: Risk factors for gastrointestinal symptoms. Dan Med Bull 1999; 46: 420-3.

9. Fisher RS. Parkman HP: Management of nonulcer dyspepsia. N Engl J Med 1998; 339: 1376-81.

10. DeVault KR, Castell DO: Updated guidelines for the diagnosis and treatment of gastroesophageal reflux disease. Am J Gastroenterol 1999; 94: 1434-42.

11. Ammon HV, Koch TR: Diarrhea and constipation. In: Bockus Gastroenterology, Ed 5, pp 87-112. Edited by Haubrich WS, Schaffner F, Berk JE. Philadelphia. PA, WB Saunders, 1995.

12. American Gastroenterological Association: American Gastroenterological Association medical position statement: irritable bowel syndrome. Gastroenterology 1997; 112:2118-9.

13. Camilleri M, Prather CM: The irritable bowel syndrome: mechanisms and a practical approach to management. Ann Intern Med 1992; 116: 1001-8.

14. Das AK, Davanzo LD. Poiani GJ, et al: Variable extrathoracic airflow obstruction and chronic laryngotracheitis in Gulf War veterans. Chest 1999; 115: 97-101.

15. Slum AL, Talley NJ, O’Morain C, et al: Lack of effect of treating Helicobacter pylori infection inpatients with nonulcer dyspepsia. N Engl J Med 1998; 339: 1875-81.

16. McColl K, Murray L, El-Omar E, et al: Symptomatic benefit from eradicating Helicobacter pylori infection in patients with nonulcer dyspepsia. N Engl J Med 1998; 339: 1869-74.

17. Iowa Persian Gulf Study Group: Self-reported illness and health status among Gulf War veterans: a population-based study. JAMA 1997; 277: 238-45.

18. Gray GC. Smith TC, Knoke JD, et al: The postwar hospitalization experience of Gulf War veterans possibly exposed to chemical munitions destruction at Khamishiyah, Iraq. Am J Epidemiol 1999; 150: 532-40.

19. Abou-Donia MB, Wilmarth KR, Jensen KF, et al: Neurotoxicity resulting from coexposure to pyridostigmine bromide, DEET, and permethrin: implications of Gulf War chemical exposures. J Toxicol Environ Health 1996; 48: 35-56.

Guarantor: Timothy R. Koch, MD

Contributors: Timothy R. Koch, MD*[dagger]; Theresa S. Emory, MD[double dagger]

* Lewis A. Johnson Veterans Affairs Medical Center, West Virginia University, Morgantown, WV.

[dagger] Current address: Section of Gastroenterology, Washington Hospital Center, Washington, DC 20010.

[double dagger] Division of Gastrointestinal Pathology, Department of Hepatic and Gastrointestinal Pathology, Armed Forces Institute of Pathology, Washington, DC 20306-6000.

This manuscript was received for review in January 2003 and was accepted for publication in March 2003,

Reprint & Copyright @ by Association of Military Surgeons of U.S., 2005.

Copyright Association of Military Surgeons of the United States Aug 2005

Summary

Cardiovascular diseases exert a huge burden on individuals and society, with coronary heart disease (CHD) the single most common cause of death in the United Kingdom and other developed countries (British Heart Foundation 2004). Improved clinical care has been responsible for around two fifths of the decline in mortality from CHD in England and Wales over the past decade (Unal et al 2004). This article describes how developments in cardiac care, most of which have closely engaged nurses, have contributed to improvements in care for patients with acute myocardial infarction and other acute coronary syndromes.

Keywords

Cardiovascular system and disorders; Nurse-led services

These keywords are based on the subject headings from the British Nursing Index. This article has been subject to double-blind review. For related articles and author guidelines visit our online archive at www.nursing-standard.co.uk and search using the keywords.

THE BRITISH Heart Foundation (BHF) (2004) statistics database sets out in stark detail the burden of cardiovascular diseases in the UK:

* Diseases of the heart and circulatory system are the main causes of death in the UK, responsible for 238,000 deaths, or one in three of all deaths in 2002.

* Half of all deaths from cardiovascular disease are from coronary heart disease (CHD), the single most common cause of death in the UK. CHD is also the commonest cause of premature death (before the age of 75 years), causing more than 40,000 such deaths each year.

* There are an estimated 268,000 episodes of acute myocardial infarction (AMI) in the UK each year, 92,000 occurring in men and women under 65 years of age.

Death rates from CHD have been falling over recent decades, mostly because of reductions m important risk factors, especially smoking. About two fifths of the reduction in deaths resulted from improvements in medical care. In the case of AMI, emergency treatment, particularly early defibrillation, prompt administration of aspirin, and to a lesser extent hospital-based thrombolytic treatment, have made important contributions to improved outcomes (Unal et al 2004).

Goodacre et al (2005) reported that 6 per cent (700,000) of adult accident and emergency (A&E) department attendances in England and Wales annually are due to chest pain and related complaints. While only a minority of patients had electrocardiogram (ECG) changes suggestive of acute coronary syndromes (ACS) at presentation, two thirds were admitted to hospital. The burden of chest pain on health services, whether or not associated with an ACS diagnosis, is therefore substantial.

The coronary care unit

Coronary care units (CCUs) were developed in the 1960s to reduce deaths following AMI. They provided a specialised hospital facility staffed and equipped to monitor patients with suspected AMI and facilitate rapid defibrillation of patients in cardiac arrest (Julian 1987). Nurses trained in resuscitation were crucial in providing 24-hour expertise in rhythm recognition and early defibrillation to patients at the bedside. Despite some early controversy about the effectiveness of coronary care in reducing mortality when compared to home care (Rawles and Kenmure 1980), most acute hospitals maintain a CCU.

The success of the CCU concept was, and remains, highly reliant on the expertise of nurses working in close collaboration with medical colleagues. From the early days of the CCU, there has been recognition of the value of nurses developing specialist knowledge and skill in, for example, ECG interpretation, the understanding of treatment of AMI complications and expertise in cardiopulmonary resuscitation (Meltzer 1964). The formative years of the CCU arguably provide the earliest examples of nurses taking on ‘advanced’ roles, usually the preserve of physicians (Killip and Kimball 1967).

The tradition of developing a highly skilled, expert cadre of CCU nurses to respond immediately in the event of serious complications to benefit vulnerable patients has continued to develop (Quinn 1995, Simoons et al 1997), accompanied by further devolution of such skills to the A&E department and ambulance service (Quinn et al 2002, Quinn and Morse 2003).

Thrombolytic treatment

The advent of thrombolytic therapy – intravenous (IV) medication used to break down or ‘lyse’ blood clots occluding coronary arteries which lead to AMI – brought new opportunities for CCU nurses to develop and use their expertise in patient assessment and ECG interpretation to benefit patients by expediting treatment.

The introduction of IV thrombolytic treatment into routine clinical practice following a series of large trials in the mid- 1980s ensured a renaissance for the CCU following the controversies described above. The trials provided strong evidence that the sooner patients with AMI were treated with a thrombolytic agent, the better their chances of survival (Fibrinolytic Therapy Trialists’ Collaborative Group 1994). A meta-analysis of hospital and pre- hospital thrombolysis trials reinforced the time-dependent nature of this treatment (Boersma etal!996). Most benefit, in terms of lives saved by thrombolysis, is seen in patients treated within the first hour following symptom onset – the concept of a ‘golden hour’ for thrombolysis has been proposed (Boersma et al 1996).

The importance of very early treatment to open occluded coronary arteries in the context of AMI has been reinforced by more recent studies comparing thrombolytic treatment with primary percutaneous coronary intervention (PPCI), which will be discussed later in this article.

The importance of saving time to reduce deaths from AMI has resulted in the development of standards of care from professional societies and governments in many countries. In England, the National Service framework (NSF) for Coronary Heart Disease (Department of Health (DH) 2000) sets national standards for improved prevention and treatment. For patients with AMI who present with ST-segment elevation or new left bundle branch block on 12- lead ECG, these standards relate to reducing delays to thrombolysis so that patients begin treatment within 60 minutes of the call for professional help, in line with guidelines published by the European Society of Cardiology and European Resuscitation Council (1998). Although in the first few years of implementing the NSF there was a focus on optimising hospital systems so that patients started thrombolysis within 20-30 minutes of arriving at hospital, the national standard for England is now focused on starting treatment within 60 minutes of the patient calling for professional help (DH 2003). Other UK countries have set similar standards for cardiac care (National Assembly for Wales 2001, Scottish Executive Health Department 2002).

The National Audit of Myocardial Infarction Project (MINAP) for England and Wales developed to help improve the quality of acute cardiac care in line with the NSF standards, has recently reported more than three quarters of eligible AMI patients starting thrombolysis within 30 minutes of hospital arrival (Birkhead etal 2004). A major factor in reducing delays has been the shift from CCU to A&E as the main place where thrombolysis is given, since this is where the majority of AMI patients present. Before publication of the NSF, approximately one third of A&E departments were routinely providing this treatment (Hood et al 1998 ). Administering thrombolytic therapy in A&E is feasible and safe, and adverse incidents including cardiac arrest during transfer to CCU are rare (Edhouse et al 1999). Direct admission to CCU, although popular and effective in a minority of hospitals, has largely been superseded by such developments.

The focus has recently shifted to ensuring improvements in care across the whole patient pathway, including pre-hospital care provided by ambulance services, but where primary care and NHS Direct staff also play important roles.

Nurse-led and nurse-initiated thrombolysis

Nurse-led thrombolysis describes a situation where a nurse assesses a patient with suspected AMI for eligibility to receive thrombolysis but the treatment decisions are made by medical staff.

Nurse-initiated thrombolysis refers to a situation where a nurse assesses a patient with suspected AMI for eligibility to receive thrombolysis and administers the treatment under a Patient Group Direction (PGD).

Most of the reports on the safety and efficacy of nurse-led and nurse-initiated thrombolysis have been small-scale observational studies, or associated with clinical audit. Only one randomised trial has been reported, demonstrating a trend towards improved care in a South Australian hospital (Kucia et al 2001).

One small pilot study conducted in York compared CCU nurses’ decision-making regarding patients’ eligibility for thrombolysis with that of junior doctors and found no difference (Quinn 1995). In Scarborough, this was taken a step further in practice by Gaunt (1996) who described the positive impact of empowering suitably competent nurses to administer thrombolytic treatment before the patient was assessed by a hospital doctor. There have been several reports since these early observations of nurses initiating thrombolysis safely and effectively under PGDs or equivalent arrangements.

Recent examples include the empowerment of CCU nurses to initiate thrombolysis following direct admission to CCU (Wilmsh\urst et a/ 2000, Qasimei al 2002). However, the increasing use of A&E departments as the appropriate setting for thrombolytic treatment has resulted in several successful A&E-based schemes. For example, Heath etal (2003) demonstrated the superiority of A&E-based nurse- initiated thrombolysis over the largely redundant ‘fast-track’ processes of transferring patients from A&E to CCU for thrombolysis. In all reported studies thrombolytic treatment was given faster if initiated by nurses under PGD, or similar arrangements, than if patients waited for assessment by a physician. There does not appear to be an increased rate of inappropriate treatment with nurse- initiated thrombolysis compared with medical decision-making. Nurse- initiated thrombolysis accounted for 8.5 percent of hospital thrombolysis in 2003; most decisions to administer thrombolysis are made by emergency department medical staff (Birkhead et al 2004).

Another strategy to reduce delays is for nurses to assess patients presenting with symptoms suggestive of ACS rapidly, record an ECG and, if there are clear ECG changes indicating AMI and the patient does not have obvious contraindications, to ask for urgent medical assessment. In such cases it is medical staff who prescribe the treatment. Several reports of nurse-led thrombolysis have demonstrated the safety and efficacy of this approach (Somauroo et al 1999, Lloyd et al 2000).

It is generally accepted that it is not the job title or profession of the individual initiating thrombolytic treatment that is the key consideration. It is the competence of that individual to safely undertake the intervention. Generic competencies for the assessment and treatment of patients with suspected ACS have therefore been proposed (Box 1 ) (Quinn etal 2002, Skills for Health 2004). An influential report from the British Cardiac Society and Royal College of Physicians (2002) recommends that: ‘All patients with an indication for thrombolysis, and where there is no contraindication, should receive this treatment from the first available qualified person able to provide coronary care, whether this is a primary care physician, paramedic or hospital based clinician.’

On this basis, regulatory changes have been enacted in England (Box 2) and other parts of the UK to facilitate earlier treatment.

BOX 1

Key areas for proposed generic competencies for administration of thrombolysis in acute myocardial infarction

Pre-hospital care

The dramatic reductions in ‘door-to-needle’ times for patients with ST-elevation MI (STEMI) have had a positive influence on patient outcome, given the evidence that the benefits of thrombolysis are time dependent. Around half of all patients eligible to receive immediate thrombolytic treatment do so within 60 minutes of calling for help ( Birkhead et al 2004). This situation has improved markedly since 1995 when just 10 per cent of patients were treated within this time (Quinn et al 2003).

There is growing consensus that further reductions in delay will only be achieved through the widespread introduction of pre- hospital thrombolysis, delivered mostly by paramedics (Boyle 2004). Pre-hospital thrombolysis has been the subject of a meta-analysis which demonstrated a 17 per cent reduction in all-cause mortality (Morrison et al 2000). More recent UK studies have added to the supporting evidence base: Keeling etal (2003) assessed the feasibility of paramedic thrombolysis and concluded that autonomous paramedic pre-hospital thrombolysis seemed feasible and safe and was associated with improved call-to-needle times. Pedley et al (2003) reported that the likelihood of a patient starting treatment within 60 minutes of calling for help was markedly improved when pre- hospital thrombolysis was available, applying this argument to both rural and urban settings. To date more than 2,000 patients in England with AMI have received thrombolysis from a paramedic (Ambulance Service Association 2005). The balance between the risk and benefit of providing pre-hospital thrombolysis in an urban setting with presumed short transport times is, however, subject to debate (Stephenson et al 2002) and the precise model adopted will depend on local circumstances.

BOX 2

Regulatory changes in England

Acquisition and, if possible, transmission of a 12-lead ECG from an ambulance to the receiving hospital, have been shown in several studies to reduce treatment delays and improve care for patients with AMI (Ioannidis et al 2001). The availability of 12-lead ECG machines as part of advanced life support facilities is recommended by international guidelines on emergency cardiac care (Antman et al 2004). In England, provision of this equipment on emergency ambulances has been made possible by investment from the New Opportunities Fund (part of the National Lottery).

Clinical governance issues arise from the transmission of 12- lead ECGs, and it is important that clear arrangements are in place to maintain patient safety by, for example, recording advice given by hospital staff and actions taken by paramedics when such technology is used. Recent data from Australia suggest that ECG transmission and pre-alerting hospitals that an AMI patient is en route are worthwhile and help to reduce delay (Goodacre et al 2004a), particularly in less urban settings. These findings confirm to some extent those of a recent UK report by Gamon et al (2004).

Pharmacological or mechanical treatment of myocardial infarction

Thrombolytic therapy has several limitations. Occluded coronary arteries associated with AMI are fully reopened in only a minority of patients given streptokinase, and although this is not such a concern with newer agents such as reteplase and tenecteplase, mechanical treatment with primary coronary intervention (angioplasty and stenting) or PPCI is reported to produce better results. A meta- analysis of trials comparing PPCI versus hospital thrombolysis suggested significantly lower death rates in the PPCI-treated patients. Patients treated with PPCI also had less adverse events including haemorrhagic stroke and the need for repeat angiography than those who had received thrombolysis (Keeley et al 2003).

There are concerns, however, that this analysis may not reflect modern UK practice where thrombolysis is given promptly. For example, in MINAP 60 per cent of patients were treated within three hours of symptom onset (Birkhead etal 2004). Moreover, PPCI has not been proven superior to very early thrombolysis. A Cochrane Review of the evidence concluded (Cucherat etal2003): ‘Angioplasty provides a short-term clinical advantage over thrombolysis which may not be sustained. Primary angioplasty, when available promptly at experienced centres, may be considered the preferred strategy for myocardial reperfusion. In most situations, however, optimal thrombolytic therapy should still be regarded as an excellent reperfusion strategy.’

A PPCI approach may reduce overall costs compared to thrombolysis in patients who are within one hour travel time from a hospital able to provide this intervention (Machecourt et al 2005). This is a rapidly developing field of research and clinical practice. The secretary of State for Health (DH 2004b) has established a project led jointly by the National Director for Heart Disease and the British Cardiac Society, evaluating whether provision of a PPCI service is feasible in England.

Patients with atypical presentations

While the focus of national and international guidelines has generally been on expediting care for patients who meet standard eligibility criteria for thrombolysis based on clinical and ECG evidence, it is important to recognise the higher morbidity and mortality observed in patients with ACS who present without chest pain, but whose main symptom is syncope, nausea and vomiting, or dyspnoea. These patients, often older and/or with diabetes, are frequently misdiagnosed and undertreated (Brieger et al 2004). There is also evidence that patients from certain minority ethnic groups are more likely to present with non-classic features (Barakat et al 2003). Nurses and others (for example, paramedics) involved in early assessment and triage processes should have a low threshold of suspicion for recording a 12-lead ECG in these circumstances.

Patient help-seeking behaviour

The NSF (DH 2000) and related standards for ‘call-to-needle time’ measure the time from a patient with AMI calling for professional help to the time that thrombolytic treatment, where indicated, is administered. While this part of the patient pathway has improved over recent years, patients are taking longer to call for help following symptom onset. The complex reasons for this phenomenon are outside the scope of this article. A recent systematic review concluded that there was little evidence that media or public education interventions reduced delay, and there is some evidence that they may result in an increase in emergency switchboard calls and A&E department visits (Kainth et al 2004).

The changing role of coronary care units

Most thrombolysis is now given outside the CCU environment, representing a major and effective change in practice since publication of the NSF (DH 2000). While many CCU nurses have been fully engaged in supporting A&E departments in safely delivering, assessing and treating ACS patients, thrombolytic treatment is increasingly the preserve of emergency staff and will devolve to paramedics, ensuring further benefits for patients.

The role of CCU nurses, which has continued to evolve since the advent of the CCU more than 40 years ago, is changing and requires further evaluation to define the modern scope of practice and the competencies required. So-called ‘thrombolysis nurses’, while effective in reducing door-to-needle time, are unlikely to be a cost- effective use of valuable resources if they focus solely on assessing and treating patients with MI (DH 2003). Their role is arguablyakin to that of the resuscitation training officer, establishing systems and processes, including training of relevant staff, to ensure that patients receive optimal care irrespective of who is on duty. The key challenge facing CCU nurses in the future is how best to care for patients with other manifestations of ACS.

In routine clinical practice, nurses and their paramedic colleagues will assess and record a 12-lead ECG on patients with chest pain and related symptoms who are not eligible for thrombolysis, many of whom will have an ACS diagnosis ultimately excluded. A recent Scottish study reported that rates of AMI admissions were declining while ‘chest pain’ was increasingly the discharge diagnosis (Murphy et al 2004) and the total number of A&E department attendances in England and Wales with chest pain is estimated at 700,000 per annum – a minority of these patients having sustained AMI (Goodacre et al 2005). Patients with a final diagnosis of ACS who present with ST-depression on admission have been shown to have worse outcomes than those with ST-segment elevation (Savonitto etal 1999) and it is possible that this group of patients will form the main population admitted to CCU in future years, for intensive management with powerful medications including antiplatelet and antithrombotic therapies.

Whether all patients with suspected ACS should be admitted directly to a hospital with interventional cardiology facilities is a matter of debate (Van de Werf et al 2005). Management of this group of patients in the UK differs from that observed in other countries: while more UK patients with AMI receive reperfusion than elsewhere, and statin use is higher, patients outside the UK are more likely to receive revascularisation (bypass surgery or angioplasty ) for other manifestations of ACS, and more likely to receive glycoprotein Ilb/IIIa inhibitors (Carruthers et al 2005). Hospital mortality rates do not, however, differ between the UK and elsewhere, although worse outcomes are observed for UK patients at six-month follow up. Significant delays in transferring patients to an interventional centre following admission to a hospital without such facilities have been reported (Miller ei al 2003).

It is possible that other functions of the CCU, including the ongoing assessment of patients with acute chest pain, will at least in part be devolved to specialist ‘chest pain observation units’ within A&E departments (Goodacre et al 2004b). All such changes are occurring as worldwide debate continues about what clinical and pathological characteristics now constitute an AMI and the implications for patients (Fox et al 2004).

Conclusion

This article has provided an overview of recent developments in the care of patients with AMI and other manifestations of ACS. It has not, however, been possible to address pathophysiology or pharmacology in depth. Nor have the wider aspects of cardiac care such as management of arrhythmias, shock or heart failure, or the management of patients successfully resuscitated from cardiac arrest, been addressed. Cardiac care continues to evolve rapidly, as it has done since the advent of the CCU more than 40 years ago. The next few years are likely to see further developments including:

* More (probably most) reperfusion in ambulances or cardiac catheter laboratories.

* More patients bypassing general hospitals for specialised centres following assessment by paramedics.

* Most patients with chest pain being assessed in A&E departments.

* More use of online 12-lead ECGs and telemedicine.

* More online decision support facilitating outof-hospitalcare.

* Point of care testing, for example, cardiac markers and other risk assessment, in ambulances.

* Further refinement of the definition of AMI.

* Improved access to timely angiography and intervention where required.

These developments should result in further reductions in treatment delays and help to save lives following an acute event. The further development of nurses and other health professionals, including paramedics, in terms of assessment skills, prescribing and decisionmaking will be essential to collaborate with other members of the healthcare team in achieving better care for patients

Quinn T (2005) The role of nurses in improving emergency cardiac care. Nursing Standard. 19, 48, 41-48. Date of acceptance: April 29 2005.

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Author

Tom Quinn is professor of cardiac nursing, Coventry University, Coventry, and consultant cardiac nurse. Email: [email protected]

Copyright RCN Publishing Company Ltd. Aug 10-Aug 16, 2005

Aug. 19–Normal canine activities like sniffing behind a bush in the mountains or playing in the desert can leave dogs vulnerable to a rattlesnake bite, but a new vaccine may be able to ease their pain.

After a two years on the market in California, the vaccine was released in New Mexico earlier this summer.

The vaccine is targeted at the western diamondback and the prairie rattler, both prevalent in southern New Mexico, but may offer protection against other breeds as well, said Hilary Ward, administrative manager at Red Rock Biologicals, the company that developed and marketed the vaccine.

The only breed of rattlesnake that the vaccine does not seem to cover is the Mojave rattler, she added.

Tina Parks, who lives with four dogs in Las Palomas south of Truth of Consequences, has experience with snake bites, so she had her pets vaccinated as soon as the drug was available.

“Two of my dogs were bitten last year. One was bitten twice,” Parks said.

“It’s very painful to the dogs — extremely painful.” The symptoms of snake bites can be severe and are distinct from any other bites or wounds a dog can incur, said Mikala Hale, who works at the Animal Hospital of Las Cruces.

Dogs may have swelling and extensive tissue damage around the site of the bite, including discoloration and hemorrhaging, and the dog may go into shock.

But the severity depends on the size of the dog and the amount of venom injected, and not all cases are so extreme.

The standard treatment for rattlesnake bites is a round of anti-venom shots that cost several hundred dollars and can have harmful side-effects.

The vaccine costs about $30 per shot, and two doses are needed for the first vaccination. Though this is more expensive than most vaccines, price is not a factor for some pet owners.

“They’re my babies, I don’t care how much it costs. If it had been $1,000 I would have taken them in,” Parks said.

But Jody Kincaid, a holistic veterinarian in Anthony, does not put as much value on vaccines as traditionally trained doctors do, and cautioned pet owners against using the vaccine.

“The vaccines are far more dangerous than the snake bites,” he said, because they are foreign to the dog’s body and must be very strong to combat rattlesnake venom.

“Vaccines that are as potent as something like that cause severely destructive effects,” he said.

Ward said tests had shown no severe side effects.

“We’ve had a few adverse reactions, but they’re all really very mild and the rate is low,” Ward said, adding that they effects included diarrhea and vomiting but only occurred in .03 percent of dogs.

Some pet owners have reservations about the vaccines.

“It’s not something I would say yes or no to right now, but I would consider it,” said dog owner Susanne Richter, who lives off Roadrunner Parkway in Las Cruces Richter said she had concerns about the side effects of the drug and did not necessarily think it was needed for her dog, Freckles, as she rarely sees rattlesnakes in her area.

The vaccine has currently been licensed for a one-year conditional period, and Ward was confident it would be approved after a few more tests.

Even with the vaccination, Ward said dogs should be taken to the clinic immediately if they are bitten by a rattler.

SNAKE BITE VACCINE

–Vaccine: protects dogs from the effects of rattlesnake bites

–Cost: $30, price at individual veterinary clinics may vary

–Dosage: 2 shots spaced four weeks apart for first treatment; once yearly after that

–Availability: vaccine is available at Las Cruces veterinarians and must be administered by a professional

HOW TO KEEP YOUR PET SAFE FROM A SNAKE BITE:

–keep dogs on a leash when they are in the desert, mountains or other snake territory

–avoid areas with thick brush, stacked rocks or clustered roots

–clear away wood piles and other clutter where snakes may hide

–seal all open areas leading into your home

IF YOUR PET IS BITTEN BY A SNAKE:

–take pet to a local veterinary clinic where antidote can be administered

–do not use home remedies of any type

—–

To see more of the Las Cruces Sun-News, or to subscribe to the newspaper, go to http://www.lcsun-news.com.

Copyright (c) 2005, Las Cruces Sun-News, N.M.

Distributed by Knight Ridder/Tribune Business News.

For information on republishing this content, contact us at (800) 661-2511 (U.S.), (213) 237-4914 (worldwide), fax (213) 237-6515, or e-mail [email protected].

DOWNERS GROVE, Ill., Aug. 18 /U.S. Newswire/ — Advocate Good Samaritan Hospital, located at 3815 Highland Avenue, is sponsoring the following health events for August and September. All events are free, unless otherwise announced. To register for events, or for more information, please contact the Health Advisor at 1-800-3- ADVOCATE or visit http://www.advocatehealth.com. Tambien tenemos represetantes que habian espanol. (TDD 630.990.4700)

Location Codes:

G- Advocate Good Samaritan Hospital

W- Good Samaritan Health and Wellness Center

N- Naperville Professional Building

L- Good Samaritan Professional Building

PW- Downers Grove Public Works Building

O-Other

— Part 1 of 2

Advocate Good Samaritan Hospital Festival 2005: Masqurade Ball-O

Join Co-Chairs Vickie Hankes and Krista Miller along with the Festival 2005 Benefit Committee as they announce the 2005 Good Samaritan of the Year, John Anderson! Proceeds from Festival 2005 will benefit Cancer Care Programs and Cardiovascular Disease Diagnostics and Treatment. For more information please call 630.275.6518, or to register online, visit us at: http:// www.advocatehealth.org/foundation, and type in the key word masquerade.

Thank You To Our Sponsors:

Silver Level Benefactor ($25,000 donation)

— Radiologists of DuPage

Partner Level Benefactors ($5,000 donation)

— Cliff and Bette Carney

— Dan Krause Construction Services

— Mary Lou Shearhod

Crystal Level Benefactor ($2,500 donation)

— Annette Goetz

—

When: Saturday, October 29, 2005

Reception: 6 p.m.; Dinner: 7:30 p.m.

Black tie attire

Please respond by October 17, 2005

Entertainment by Gentlemen of Leisure

Where: Oak Brook Hills Resort

3500 Midwest Road, Oak Brook, Illinois

Cost: $250.00 per person

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Sponsored By The Auxiliary Of Good Samaritan Hospital:

Mayflower Tour: Charleston and Savannah-O

7-day Air Tour of Charleston and Savannah, featuring Jekyll Island, departing May 6. Your tour includes: round trip airfare from Chicago, round trip airport transfers, Travelers Protection Plan, a fully escorted experience and $35 in future travel credits. For more information, please contact Mayflower Tours at 630.435.8525 or 1.800.728.0724.

Code: No code

When: Please call to register.

Cost: Per person rate: $1,834

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Ohhh! MY ACHING FEET -L

Presented by: Kumar Raigaga, D.P.M., Podiatrist, Metro Foot & Ankle Center

Join Dr. Kumar for an open discussion on the following:

— Common foot and ankle pain and complaints

— Sports injuries of the foot and ankle

— Shoegear and exercises

— Diabetic education and foot care

— Importance of visiting a Podiatrist or a foot & ankle specialist if you have problems

Code: 4G46

When: Monday, October 3, 7 to 8:30 p.m

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HOW WILL MEDICARE REFORM AFFECT YOU-W

Cathy Gleason will present information on changes which will affect your Medicare benefits, including proposed prescription drug benefits.

IF YOU RECEIVED INFORMATION FROM MEDICARE IN THE MAIL REGARDING THESE CHANGES, PLEASE BRING THIS TO THE LECTURE.

Code: —

When: Wednesday, October 12, 1 to 3 p.m.

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COUMADIN AND YOU….TAKING COUMADIN WISELY-G

Presented by: Jordan Weinstein, M.D., Interventional and Clinical Cardiologist

Midwest Heart Specialists, Good Samaritan Hospital

If you or a loved one is on Coumadin, come hear Dr. Weinstein review what every patient needs to know about this blood-thinner. Be sure to bring your questions!

Code: 4C30

When: Thursday, October 13, 7 to 8:30 p.m

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FIRE PREVENTION AND FIRST AID FOR OLDER ADULTS-W

Join Marsha Geisler, Downers Grove Fire Department as she discusses prevention for fire safety and demonstrates basic home first aide. A MOCK EMERGENCY CALL BY THE FIRE DEPARTMENT WILL ALSO BE INCLUDED IN THE DEMONSTRATION.

Code: —

When: Friday, October 14, 9 to 11 a.m. and Wednesday, October 19, 1 to 3 p.m.

—

Breast Health for Women-W

Join Breast Health Specialist Mary Jo Osowski, RN, to learn how to perform a breast self-exam (BSE) in a safe and supportive environment. Discover what to do when changes are discovered. Includes a free shower card, discussion of normal breast anatomy, and information about non-cancerous conditions.

Code: 4C48

When: Tuesday, October 18, 5:30 to 6:30 pm.

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Sponsored By The Auxiliary Of Good Samaritan Hospital: Books Are Fun Book Sale-G

A great opportunity to purchase books, gift items, games and toys.

Code: No code

When: Wednesday, October 19, Thursday, October 20 and Friday, October 21

8 a.m. to 3 p.m.

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Couples Massage -W

Join Licensed and Certified Massage Therapists Sue Gibson and Christine Jiskra to learn simple techniques to give and receive nurturing, intentional touch with your partner. Techniques based on Swedish massage. Wear loose-fitting, comfortable clothing so that you may actively participate.

Code: 4N87

When: Friday, October 21, 7 to 9 p.m.

Cost: $30.00-Wellness Center Member Couples

$60.00-Non-member Couples

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Fitness and Wellness Day -W

Experience the benefits of exercise. Bring your workout clothes, take a tour, use the equipment on the fitness floor and in the free weight area, jog on the track, shoot baskets, swim in the pools, relax in the whirlpool, and participate in scheduled classes.

Code: No code

When: Friday, October 21, 5 a.m. to 10 p.m.

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Alternative Therapy to Manage Menopause -W

Dr. Xiaoping Xu, a specialist in internal medicine and medical acupuncture, introduces therapies including acupuncture, mind/body medicine, Yoga, and other alternatives to manage common issues associated with menopause, including insomnia, mood swings, hot flashes, reduced mental clarity, and heavy menstrual periods.

Code: 4W18

When: Monday October 24, 6 to 7 p.m.

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Incontinence and Pelvic Pain Therapies -W

Licensed Physical Therapists Mona Barkauskas and Sarah Oldham partner with physical therapy assistant Marianne Conone to review exercises and non-surgical, physical therapy treatment options for these common women’s health issues.

Code: 4W17

When: Wednesday, October 26, 6 to 7 p.m.

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HORMONE REPLACEMENT: FACT AND FICTION-G

Presented by: Allyn Schaub, M.D., Obstetrician/Gynecologist, West Suburban Obstetrics Gynecology, Ltd., Good Samaritan Hospital

Dr. Allyn Schaub will discuss the recent information surrounding hormone use in relation to breast cancer risk, osteoporosis risk, colon cancer risk and heart disease.

Code: 4W08

When: Wednesday, October 19, 7 to 8:30 p.m.

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Fall Into Health Family Wellness Fair-L

Meet and Greet: Lemont Medical (Internal Medicine)

M & M Orthopaedics, Ltd.

Midwest Digestive Disease Specialists

Midwest Heart Specialists

Allison E. Murchison, M.D. (Ophthalmology)

Faith Myers, D.O., Pediatric Wellness Center

Oak Brook Allergists

Good Samaritan Physical Therapy

Free health information for parents and kids

Free health screenings and lectures

Special visit by paramedics

Enjoy fun and games

Refreshments and drawings

Tour our The Lemont Walk In Care Facility and

Our New Imaging Center (includes CT Scan, General X-Rays and Digital Mammography)

“MEET OUR VERY OWN SPIDERMAN tm”

7 days a week (no appointment necessary) and Our New Imaging Center (includes CT Scan, General X-Rays and Digital Mammography) For more information, please call: 630-243-7100.

Code: 4N86

When: Saturday, October 22, 8 a.m. to 12 p.m.

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Hospice Volunteer Training-W

Training prepares volunteers with skills necessary to accompany the terminally ill and their families with openness and compassion. Concepts on spiritual care, communication, grief, death and dying and bereavement will be discussed. Please contact Loni Weidemann at 630.963.6800 for more information.

Code: No Code

When: Friday, October 21, 7 to 10 p.m.

Saturday, October 22, 10 a.m. to 7 p.m.

Sunday, October 23, 10 a.m. to 6 p.m.

Cost: $15.00

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INCONTINENCE AND PELVIC PAIN THERAPIES W

Willaim H. Kobak, M.D., Denise Elser, M.D., Urogynecologists, Illinois Urogynecology, Margaret Roberts, MD, Ph.D, Physiatrist, Illinois Urogynecology, LTD, and Licensed Physical Therapists Mona Barkaukas and Sarah Oldham along with Marianne Conone, Physical Therapy Assistant

Join us to learn about innovative surgical techniques which can be done under local anesthetic in the outpatient setting and bladder Botox for pelvic pain. Also, join our physical therapists to review exercises, bio-feedback and non-surgical and physical therapy treatment options for these common women’s health issues.

Code: —

When: Wednesday, October 26, 6:30 to 9 p.m.

—

6th Anniversary Free Workout Week -W

You are invited to live well and feel great during our 6th Anniversary Fitness and Wellness Week! Bring your workout clothes, take a free tour, use the equipment on the fitness floor and in the free weight area, jog on the track, shoot baskets, swim in the pools and participate in group exercise classes. Participate in free lectures and mind/body demonstrations. Health screenings for blood pressure, body composition, and body mass index available. For schedules, go to the Wellness Center web site, www.advocatehealth.com/goodsam, Fitness and Wellness link. Photo identification required; must 18 years and older.

Code: —

When: Monday through Friday, October 31 to November 4, 5 a.m. to 10 p.m.

—

Advocate Good Samaritan Hospital Festival 2005: Masqurade Ball-O

Join Co-Chairs Vickie Hankes and Krista Miller along with the Festival 2005 Benefit Committee as they announce the 2005 Good Samaritan of the Year, John Anderson! Proceeds from Festival 2005 will benefit Cancer Care Programs and Cardiovascular Disease Diagnostics and Treatment. For more information please call 630.275.6518, or to register online, visit us at: http:// www.advocatehealth.org/foundation, and type in the key word masquerade.

Thank You To Our Sponsors:

Silver Level Benefactor ($25,000 donation)

— Radiologists of DuPage

Partner Level Benefactors ($5,000 donation)

— Cliff and Bette Carney

— Dan Krause Construction Services

— Mary Lou Shearhod

Crystal Level Benefactor ($2,500 donation)

— Annette Goetz

When: Saturday, October 29, 2005

Reception: 6 p.m.; Dinner: 7:30 p.m.

Black tie attire

Please respond by October 17, 2005

Entertainment by Gentlemen of Leisure

Where: Oak Brook Hills Resort

3500 Midwest Road, Oak Brook, Illinois

Cost: $250.00 per person

(More/more)

http://www.usnewswire.com

By Karla Gale

NEW YORK (Reuters Health) – Genetically engineered tissue dressings derived from fetal skin cells have been used successfully to treat second- and third-degree burns without scarring in pediatric patients, researchers in Switzerland report.

The use of fetal tissue in wound repair could avoid difficulties of tissue engineering, such as immune rejection, small growth capacity and incompatibility, Dr. Lee Ann Laurent-Applegate and colleagues note in their report, published online August 18 by The Lancet.

“The main advantage was that we could avoid a (skin graft) procedure in all cases,” study co-author Dr. Patrick Hohlfeld told Reuters Health.

The research team, based at University Hospital of Lausanne, obtained a 4-cm skin donation from a 14-week aborted male fetus. Cells were expanded in culture and used to seed collagen sheets, and then grown for two more days before the sheets were applied to the burn wounds.

The fetal cells were used to treat eight children considered to be candidates for traditional skin grafting, approximately 10 days after their injury. As the cells biodegraded, they were replaced every three to four days.

“These cells stimulate spontaneous healing of the wound through secretion of multiple growth factors,” Hohlfeld said. The average time to healing was 15.3 days after the first cell application.

The cosmetic and functional results “were excellent in all eight children,” who had little degradation of the new skin with no retraction or breakdown of the healed surfaces, the research team reports. The one patient who had dark skin had recovery of skin pigmentation.

The researchers estimate that the one fetal skin donation could yield “several million” skin constructs. “We only need one very small biopsy once, giving us the potential to treat thousands of people,” Hohlfeld pointed out. He considers it possible to obtain effective skin cells from miscarriages of second trimester fetuses.

And although fetal skin cells have not yet been used to treat adults, he expects that similar tissue dressing constructs will be successful in treating other types of wounds, such as bedsores and venous leg ulcers.

SOURCE: The Lancet, August 18, 2005.

SHIGATSE, China — It’s evening in Shigatse and the lights are coming on.

In the Chinese district of the Tibetan mountain town, strings of twinkling lights flicker around rows of shopfronts where women perch waiting for customers and men stumble out from backroom corridors.

“There are a lot of prostitutes here. They’re all from the countryside. Maybe they don’t have parents to look after them or anything else to do,” says Jirga, an 18-year-old vendor.

Hundreds of miles away in a nunnery in Tibet’s capital, Lhasa, a group of young Buddhist nuns sit stitching yards of maroon cloth into the robes that are the iconic uniform of the clergy.

“The life here is very good. If I wasn’t doing this, I’d probably be a farmer,” said nun Ani La, 30, speaking over the din of a thunderstorm that rolled in from the mountains.

The Lhasa nuns and the prostitutes of Shigatse may have little in common on the surface, but both are part of the same demographic group — young, rural, Tibetan women — and analysts say their ranks are growing.

As development draws herders and farmers to towns in search of wage labor, Tibet’s women find themselves with few choices and little know-how for getting by in a market economy.

“Often where there is a concentration of nuns there is concentration of sex workers. The same forces are drawing young women away from villages,” said Charlene Makely, a Tibet specialist at Reed College in the U.S. state of Oregon.

FEW OPTIONS

Jirga, the vendor, shakes her head when asked how much schooling she has had. The answer is none. Her parents run a small stall selling jewelry and trinkets and she was raised to do the same.

At the Lhasa nunnery, more than 100 nuns live within the quiet yellow courtyard filled with potted plants and the sounds of chanted prayers, an oasis from the jumble of narrow streets of the city’s old quarter.

Of the eight children in Ani La’s family, three are nuns and two are monks. The others work on the family farm and one is a driver.

“This nunnery is popular because it’s in the city, but the ones in the countryside are pretty popular now too,” she said.

The nuns say their numbers have grown by a third in the past decade and would be higher if it weren’t for government restrictions, imposed as part of a series of controls to keep nuns, who along with monks have a history of political activism, in check.

China imposed communist rule in Tibet in 1950 and has faced periodic unrest since. Tibet’s spiritual leader, the Dalai Lama, led a failed uprising in 1959 that led to his exile. Trouble flared throughout the late 1980s, too.

Most famous among Tibet’s activist women were the “singing nuns,” imprisoned for speaking out against Chinese rule and who became renowned after secretly recording songs in prison. The tapes were smuggled out and circulated underground.

The last of the singing nuns was released in 2004.

But in Tibet, where rural incomes are well under $1 a day, some young women don’t make it as far as the nunnery in their efforts to find security.

Their flight from village poverty ends in the sex trade.

“Men can go outside and look for work but for women it’s not that easy. They can’t do that,” said 19-year-old Da Wa Qu Zong, who lives with relatives in Lhasa, looking after their son.

“PROSPERITY OF THE FEW”

Many grow up in remote villages or in nomad families, herding yak and doing farmwork as Tibet’s cities and towns experience a boom fueled by massive central government investment — a boom critics say benefits more skilled Han Chinese migrants at the expense of Tibetans.

“Tibetans are not only poorer, their extremely low level of education makes their chances of getting a steady and lucrative job in the cities as good as nonexistent,” the Tibet Information Network said in a report documenting the rise in prostitution.

“In Tibet, prostitution is not just a symptom of poverty, but is triggered also by the growing prosperity of the few,” the report said.

It’s also a problem officials are loath to recognize, let alone begin to address.

“There is no prostitution here,” said Bian Ba Ci Ren, an official in Shigatse. The government compound where he addresses reporters is just blocks from the city’s red-light district.

HIV/AIDS cases are below 100 in the region, according to World Health Organization figures. But views such as Bian Ba Ci Ren’s have raised concerns the disease could spread, especially as the number of sex workers increases.

The official’s pronouncement will also come as news to the young women in the shopfronts of Shigatse’s euphemistically named “beauty parlors.”

“I’m used to it by now,” says one woman from the countryside when asked about what she thinks of her city vocation.

She returns to watching the street, where groups of men stumble drunkenly from shop to shop, leering at the women in the doorways.

Sure, everyone is busy. But some folks have crazier schedules than others. Doctors on call, maybe. Police working a big case. A caterer during the holidays.

And news people.

Butch Hughes, general manager of The Commercial Appeal, and WREG- TV Channel 3 weathermen Jim Jaggers, Todd Demers and Austen Onek know a thing or two about a busy lifestyle.

But they also know more than they want to about extra pounds, and they’re taking the Healthy Memphis Challenge along with the other participants you’ve been reading about for the past few months.

Like our other challengers, each of our celebrities started their quest for fitness in April. Now it’s time for you to get to know them.

Our general manager

Butch Hughes weighed 210 pounds and stood 6-foot-3 when he played football in high school. The weight crept on over the years, and on Dec. 4, 2003, he got a jolt.

“That was a bellwether day for me,” he said. “I got on the scales and I weighed more than 320 pounds.”

Sound impossible for more than 100 pounds to sneak up? Think of it this way: It was less than four pounds a year.

A third of a pound a month.

He went on the Atkins diet and when he moved to Memphis from Knoxville last August, he’d lost 55 pounds.

But there’s good food in Memphis, and Hughes, the married father of one, was eating out frequently.

“I think I went through every barbecue place in Memphis,” he said.

“I gained 25 pounds of the 55 I lost after just eight months in Memphis.”

He recently joined the Weight Watchers group that meets on Thursdays at The Commercial Appeal.

He knows that exercise is a key element in successful weight loss and he’s trying to carve out time despite the long days he puts in at the office. Already busy as general manager, he assumed additional duties when the newspaper’s former president and publisher John Wilcox left last month.

Hughes plays golf when he can and he walks at the track at Evangelical Christian School near his Cordova home. Even though he knows the gym is good for him and regular exercise is his primary fitness goal right now, he’s not convinced that a treadmill or an elliptical machine is going to hold his interest.

“The gym to me is boring,” Hughes, 49, said. “My personality is such that I want to be out and doing something. I’ve got to see that I’m going from Point A to Point B.”

The weather team

Talk about really crazy schedules. Demers is out of bed at 2:30 a.m. to get to the Channel 3 studio by 3:30. Jaggers starts his day at 4 a.m. Onek works 30 of his 40 hours on Saturday and Sunday – and when bad weather comes our way, these guys can be in the studio for hours on end. But they’re doing their best to squeeze in fitness.

Jaggers, 49, is working out twice weekly with a personal trainer at the Fogelman Downtown YMCA, but he’s got a schedule he’s sticking to on his own, too.

He’s up so early because he does radio broadcasts in the morning, but he carves out time in those early hours for exercise. Around 4:30 a.m., after he’s prepared for the first live broadcast at 5 a.m., he exercises at home, maybe some crunches, leg lifts – whatever he feels like doing. After the broadcast, he manages a two- mile bike ride around his Bartlett neighborhood before the later broadcast.

Like all the weather guys, he’s cutting back on what he eats but isn’t following a formal plan. The biggest change in his diet is that he usually eats fruit and yogurt for lunch and has consequently dramatically increased his fruit intake. Otherwise, he’s just watching portion size.

He’s not weighing, but he’s gone down a notch in his belt.

“I’m not as concerned with the weight loss as in what I see on camera or in photos,” said Jaggers, who is married and has two young children at home and two grown and gone.

Although he’s done some sort of exercise for years, really committing to a serious fitness routine was tough at first.

“But I started thinking that it’s the Healthy Memphis program, it’s my station’s program, and I want to support them so I’ll do it,” he said. “Then it became a routine.”

Like Jaggers, Demers, 43, isn’t weighing – and it’s deliberate.

“My goal has been to not really look at the scale, because that just hasn’t worked for me for the past 10 or 15 years,” he said.

He’s the father of five and three of them are at home – and under the age of 7. Since his day is well under way before they’re even out of bed, spending time with them before he has to tuck in early at night is important.

So he tries to get to the Y twice a week before he goes home for the day. He does 20 minutes of weight training, 20 minutes on cardio equipment and swims laps for 20 minutes.

And he’s got a great trick for making the time pass quickly on the treadmill: He takes the crossword puzzle from The Commercial Appeal with him and completes it.

In his head.

“It makes it a little more challenging if you don’t use a pen,” he said. “I love it.”

While Demers, who lives in Bartlett, admits he still relies on fast food for some of his meals, he selects grilled chicken or even grilled fish, and he’s said goodbye for now to fries.

Onek, 37, is a single parent to his 7-year-old son.

“I think the stress might’ve helped contribute to my weight gain over the past few years,” he said.

Not that he’s complaining; he’s just stating what single moms already know. Juggling parenting, career and housework can be exhausting.

But knowing that someone is depending on you can be inspiring, too.

“The one thing that got me motivated is that I’ve got to lose weight for health reasons,” he said. “I’ve got to be here for my son.”

He tries to get to the East Memphis YMCA, which is close to his home, to swim laps for about an hour once or twice a week.

He walks around his neighborhood, parks his car so he’ll have to walk farther, takes the stairs and makes his housework routine more energetic to help burn calories.

“I’ve never been a couch potato,” he said. “It’s just that with my schedule and parenting being what it is, my approach is you get it when you can.”

So far, he’s dropped 27 pounds on his scales at home, but says they’re iffy, “subject to the earth’s magnetic forces or something.”

He’s cooking healthier meals, cutting back portions, and sticking with diet drinks instead of sugary sodas – but not entirely.

“I will not drink a diet root beer,” he said. “I’m a root beer connoisseur. Can’t do it.”

Healthy Memphis is a joint effort by The Commercial Appeal, WREG- TV Channel 3 and the Healthy Memphis Common Table aimed at encouraging and helping Memphians to become more fit and healthy. To find out more about Healthy Memphis, go to commercialappeal.com and click on the Healthy Memphis link under Lifestyle. You can access information about getting fit and and eating better, participate in our Healthy Memphis blog and link to our partner sites.

– Jennifer Biggs: 529-5223

By Helen Nyambura

MOROGORO, Tanzania (Reuters) – When Monica Mathe married
her South African husband, she also married his ideals,
embracing the beliefs of an exiled member of the anti-apartheid
African National Congress.

Elias Mathe fled white rule in his homeland in the 1970s
and underwent military training in Tanzania, where he met and
married his wife.

“I was a freedom fighter and got all the rights accorded to
one,” said Mathe, who works as a nurse in a hospital on the
outskirts of the central Tanzanian town of Morogoro.

“I got free education paid for by the ANC on this very
campus,” she said as she carefully wrapped steel surgical
instruments in green hospital linen.

When apartheid began to crumble in the mid-1990s, Mathe’s
husband went home. He never came back and never sent for her.

Mathe is one of scores of Tanzanian women who married
exiled ANC fighters and who now, more than a decade after the
end of apartheid, feel cheated and forgotten either by the men
they married or the movement that came to dominate their lives.

Tanzania, one of the so-called Frontline States which
hastened the end of white rule by pressing for sanctions and
assisting the exiled ANC, trained more ANC fighters than any
other African state during the 27 years that anti-apartheid
icon Nelson Mandela was imprisoned.

The ANC set up camps in central Tanzania and many men took
Tanzanian wives. The women worked for free in the ANC camps and
were promised wages once the fighters secured majority rule.

They were told they would be embraced into the wider ANC
family and live better lives as citizens of South Africa.

ABANDONED

When the apartheid system finally fell apart in the
mid-1990s, many ANC men living in “Frontline States” like
Tanzania, Zambia, Zimbabwe and Mozambique headed home. Some
took their families but others left alone, promising to return.

In many cases, the men re-married when they got home and
made no provisions for the “exile families,” a senior ANC
official in Johannesburg told Reuters.

The ANC has no public position on the problem, but
officials say privately that every conflict leaves deep wounds,
citing the families left behind in Tanzania as well as the many
ANC members who disappeared during the years of apartheid.

The tales of those left behind in Tanzania differ in the
detail, but the sense of betrayal is the same.

Anna Bhutto carefully stores away the only thing that links
her to her father — a photo of him in an officer’s uniform.

He left to study in Zimbabwe when Bhutto was 4 and she has
not seen him since.

“This guy has betrayed us, he has denied his children. He
knows he left children behind but … he does not care.”

Monica Mabuya’s South African husband died in Tanzania,
leaving her with four children. She still lives near the farm
where they once reared pigs to feed ANC fighters living at the
nearby Solomon Mahlangu ANC camp.

The camp is now a university campus and still goes by the
name of Mahlangu, a 23-year-old hanged for murder by the
apartheid government during student unrest in the late 1970s.

When Mabuya’s husband died, the ANC took her and her
children into the Mahlungu camp and took care of them.

But when fighters began to return home, she and her family
were left behind with other widows.

“They gave me a card to say that I am ANC. They knew I
helped the ANC,” she said. “When leaving, they should have left
me the pig project to support my children.”

The ANC widows of Morogoro say a representative of the
South African Embassy visited them once and took down their
names but there has been no contact since.

Richard Ndlovu’s South African father died when he was a
teen-ager but he still speaks the Zulu his father taught him.

He lives near Bhutto in a mud-brick house with his disabled
mother, sister and wife. They scrape by on his wages from
casual labor and the money his sister makes selling charcoal.

Ndlovu, 30, is happy to stay in Tanzania but he would like
some help from his father’s homeland.

“The solution is not going to live in South Africa. Life
can be anywhere if you have a way to live,” Ndlovu said in
Zulu.

“All we ask you (the South African government) is to help
us. We are tired.”

Aug. 17–Dr. J. David Thompson, former director of orthopedic surgery at Cardinal Glennon Children’s Hospital, has sued the hospital and St. Louis University, claiming his complaints about hospital conditions and patient care led to the loss of his job last year.

The suit, filed Friday in St. Louis Circuit Court, alleges that the hospital’s orthopedic clinics were overwhelmed by the volume of patients, creating safety problems and leading to shortcuts in care. Medical residents occasionally performed surgery without a supervising physician present during crucial moments, the suit said, a violation of state regulation and the code of the Accreditation Council for Graduate Medical Education.

The suit does not reference specific incidents of inadequate supervision. In a phone interview Tuesday, Thompson declined to give any details about the “ghost” surgeries, but said, “There is no allegation that can’t be proven.”

Neither St. Louis University, which employed Thompson as an associate professor, nor the hospital would comment on the lawsuit. Bob Davidson, a hospital spokesman, said the university and hospital comply with all federal regulations for supervision of residents.

The hospital is “committed to providing compassionate and clinically excellent care for children,” President Doug Ries said in a statement.

SLU medical school hired Thompson, 51, in June 2000 to fill the orthopedic slot at Cardinal Glennon. He worked under an annual contract that was allowed to expire June 30, 2004.

Medical school faculty make up the majority of the physician staff at the Catholic nonprofit hospital, which is part of SSM Health Care-St. Louis.

The suit alleges Thompson was terminated in violation of a state law that encourages employees to report problems affecting patient safety in hospitals. The suit seeks $775,000 in actual economic damages and an unspecified amount in compensatory and punitive damages for harming Thompson’s career and causing emotional distress.

The suit alleges administrators at SLU and Cardinal Glennon ignored Thompson’s repeated complaints about unsafe staffing levels, inadequate security, unclean conditions and a lack of equipment.

Thompson said in the suit that he sent a memo to Ries on May 6, 2002, complaining about a new policy charging doctors for parking. Thompson told Ries in response to an “ongoing lack of support,” he intended to admit some future patients to nearby St. Louis University Hospital. That institution is not licensed for pediatric patients.

According to the suit, Ries advised Thompson that his malpractice coverage through Cardinal Glennon would be void for non-approved admissions to other hospitals.

Thompson’s suit said that in the fall of 2002, he alerted Dr. Max Burgdorf, director of Glennon Care Pediatrics Associates, to problems at hospitals connected with Glennon Care for Kids. That program puts Cardinal Glennon physicians in emergency rooms in Missouri and Illinois. In turn, those hospitals refer patients to Cardinal Glennon.

Thompson alleges orthopedists on emergency room call at unidentified hospitals served by Glennon Care refused emergency and follow-up care to children covered by Medicaid. Instead, they illegally referred them to Glennon, a practice known as dumping, the suit said.

Thompson declined Tuesday to identify the hospitals he accused of the practice.

He said he told Burgdorf in a follow-up memo that children turned away by emergency room doctors had suffered “negative medical consequences.” He declined to elaborate Tuesday.

According to the suit, Thompson began to personally screen all requests to transfer orthopedic patients from other emergency rooms. He said he refused admission when Cardinal Glennon had inadequate staffing, over-tired staff or insufficient operating room time to care for patients. On Feb. 27, 2003, Thompson declined to accept two transfer patients, a decision that angered Ries, the suit said.

On April 2, 2003, Thompson learned he was being replaced as director of pediatric orthopedic surgery because he “couldn’t get along with the administration at Cardinal Glennon Children’s Hospital.” The suit maintains he was told by a medical school administrator that he could continue to work at the hospital at his current pay rate.

On May 29, 2003, the suit said, he was told the medical school would not renew his contract after June 2004 and that his pay would be reduced in the interim.

In his final medical school performance review, Thompson was informed his patient care was “very good” but his administrative performance was unsatisfactory. The review advised Thompson that his primary goal for the year should be to find another job, the suit said.

—–

To see more of the St. Louis Post-Dispatch, or to subscribe to the newspaper, go to http://www.stltoday.com.

Copyright (c) 2005, St. Louis Post-Dispatch

Distributed by Knight Ridder/Tribune Business News.

For information on republishing this content, contact us at (800) 661-2511 (U.S.), (213) 237-4914 (worldwide), fax (213) 237-6515, or e-mail [email protected].

Aug. 12–Oklahoma City’s newest niche medical center is the $20 million McBride Clinic Orthopedic Hospital at 9600 Broadway Extension.

It is scheduled to open Aug. 29, with a ribbon-cutting ceremony and reception Sept. 12.

The 100,000-square-foot hospital will have six operating rooms, 40 acute-care beds and 40 rehabilitation beds.

McBride Clinic needed to open a specialty hospital to accommodate an increasing demand for orthopedic services, officials said Thursday.

The staff includes 15 orthopedic surgeons, five arthritis specialists, sports medicine specialists and a foot doctor.

The hospital is on 15 acres at Broadway Extension and Britton Road.

“This new hospital exemplifies the very core values that the McBride Clinic was founded upon back in 1919,” said Troy Hensarling, hospital chief executive officer. “We want to do everything we can to hold true to the vision that Dr. McBride had when he started this practice.”

“We wanted to care for patients without the distractions of the needs in a general hospital,” said Dr. Tom Howard, president of McBride Clinic.

Howard, an orthopedic surgeon, said McBride Clinic’s patient load at the affiliated Bone and Joint Hospital had become so overloaded that a niche hospital specializing in orthopedic services was needed.

“McBride Clinic has been continuously growing and expanding services since it was founded in 1919,” Howard said.

McBride Clinic and the 77-bed Bone and Joint Hospital will remain open.

Medical practitioners at the new northside orthopedic hospital will perform total joint replacements of the knee, hip and shoulder, along with a full range of spinal procedures and surgeries.

It also will have an emergency room devoted primarily to orthopedic-related injuries.

The hospital is at the northeast corner of Broadway Extension and Britton Road, just north of the Surgery Center of Oklahoma and One Benham Place. Access will be available from the Broadway Extension service road and Oklahoma Avenue.

McBride Clinic staffers also will continue to treat patients at clinics in Edmond and Norman and at the McBride Clinic Occupational Health Center, 4901 W Reno in Oklahoma City.

—–

To see more of The Daily Oklahoman, or to subscribe to the newspaper, go to http://www.newsok.com.

Copyright (c) 2005, The Daily Oklahoman

Distributed by Knight Ridder/Tribune Business News.

For information on republishing this content, contact us at (800) 661-2511 (U.S.), (213) 237-4914 (worldwide), fax (213) 237-6515, or e-mail [email protected].

They were the babies who were not expected to survive. With no suitable drugs available for those born with HIV in the late 1980s, around 50 per cent were dead by the time they were 10. Today, however, many children born with HIV are now approaching adolescence and some are even parents. Their prognosis changed dramatically following the introduction, in 1997, of triple-drug therapy ” a combination of three medications that work together to fight the virus (but which won’t to kill it). Death rates consequently dropped five-fold.

‘Children diagnosed with HIV who are started on these medicines do extremely well,’ says Professor Di Gibb, a paediatrician and epidemiologist who works at Great Ormond Street, and is working on research into children with HIV at the Medical Research Council Clinical Trials Unit.

There are currently over 1,250 children known to be infected with HIV in the UK, and around 90 per cent contracted the virus through their mothers. Sixty to 70 per cent of the children recently diagnosed in this country were born and infected abroad, largely in African countries, compared to 20 per cent of those first diagnosed in the early 1990s.

While the prognosis for HIV-infected children has improved, they do, however, face complications, such as the as-yet-unknown consequences of long-term use of their medicines. ‘It is a little early to be able to forecast how long these children are going to live for,’ says Gibb. ‘It will be into adult life for most, but I don’t want to underestimate the difficulties for these children in terms of living with a chronic illness.’ n

The names of the case studies have been changed. For information and support, contact Children with Aids Charity, tel: 020 7247 9115 or visit www.cwac.org

Tanya Fletcher

19, lives in London and is a student

It’s likely that I was born with HIV. My parents and I don’t speak, so we never got to the point of them telling me how I got it. I don’t know whether they’re infected. My mother lives in South Africa, and my father is here.

I found out that I had it when I was about 13. It was my dad who told me and I don’t think he’s ever got his head around me having it. I felt numb when he told me. I didn’t want to take the medication because if you’re going to die you’re going to die. I rebelled, I was suicidal, and I didn’t want to be at home, so I was put in care. From the age of 14 to 18 I was either in a children’s home or being looked after by foster parents.

Now, I lead a pretty normal life, doing everything a 19-year-old would want to do. Some of my friends know, and I’ve never had a bad reaction from anyone I’ve told. I’ve only had one sexual partner and he was one of the first people I told. I don’t want to have children. I know there’s a chance of my child having HIV and I don’t think I could cope with that.

I know if I continue to take the medication and keep healthy, my HIV status is likely to take a very long time to develop into Aids. I’m happy with who I am now, and you can’t be miserable. You have to stop questioning yourself because you only live once. I could have 40, 50, or 60 years. I’m not angry: if I didn’t have HIV I could have been one of those teenage mums with four children, and that would be awful.

Matthew Callaghan

22, lives alone in London and works part-time in a shop

My mum was infected through a blood transfusion following a miscarriage. I was born in England after my parents moved here from Zimbabwe. They separated and I grew up with my mum. She died of Aids when I was five, which is when I was told by a social worker that I had HIV. I didn’t know what it was and replied, ‘Can I go and play football now?’ It didn’t matter to me as I’d just lost my mum.

My brother was fours years older than me, and he and I were allowed to stay in our house because they saw us as a special case. For the first year we had five different foster carers. Social services didn’t think I was going to live very long. My brother died of Aids when I was 13 and my father died when I was 20, but I don’t know what from. You just carry on with life.

When I was in secondary school I realised what HIV was. I didn’t tell anyone because of the stigma, although the close friends I’ve got now know. I feel as if I live two different lives with the friends who know and those who don’t. I try not to let it affect my life: you name it, I do it ” clubbing, raving…

One of the hardest things is relationships, and I didn’t have sex until I was 18. I always wear a condom, but I don’t tell everyone who is just a one-night-stand that I’m infected. I tell them if they’re long-term relationships. I’ve got an 18-month-old son, but recently broke up with his mother after four years. The baby wasn’t planned ” there were times when we were careless about using a condom, but neither she nor the child is infected. It’s great to be a father, as it’s motivated me to do more in life. I want to travel and become a designer.

I’m not worried about developing Aids as I know I could go outside and get hit by a bus. I have sat and cried and thought, why me? But now I don’t worry. If you get depressed it will mess your head up.

Jordan King

15, he lives in London with his father, who is unemployed

I got HIV from my mum, who became infected through a blood transfusion following a car crash in Kenya. She died of Aids when I was seven. I was upset for a long time. They immediately gave me some tests and then my dad told me that I was infected too. I didn’t think anything of it.

I found out what it meant when I was about 11. I told a girl and she told her brother, and then he told everyone else. Someone said to me that I could die of it. I then decided to do whatever I wanted, not what people wanted me to do.

I’ve been excluded from school for the past two years, but I was only bad in a cheeky way. Some kids have asked me if I’ve got HIV, but I’ve always said no. If anyone found out, I might try to hurt them. I started taking medication at seven, but I’ve been off it for 18 months as the hospital said I could. I want to go into the Army, but my dad says I can’t because of HIV. [The Army does not accept applicants who admit to having the virus.] If I can’t do anything that I want to do then I will just have to do something illegal.

I don’t worry about getting Aids, but I do worry that the children I’ll have will be infected. I’m excited at the thought of having children, but I would never tell a girl I had HIV unless I was going to stay with her for the rest of my life, because girls have got big mouths. I always use a condom as I don’t want to give anyone HIV ” it’s like giving someone cancer.

I feel angry that I’ve got it and it makes me want to go out to do bad stuff, like robbing or fighting people. People are just walking around the street all happy and they don’t know what’s really going on. I think they’re too happy. I don’t care for them because I know they don’t care for people with HIV. If they did, then there would be no stigma. I feel like the odd one out, and if I didn’t have it, things would be different. I worry that I might die sooner than everyone else and I worry about what people would say if I just died out of the blue.

The high rate of co-occurrence of substance use disorders and other psychiatric disorders is well established. The population of people with co-occurring disorders is heterogeneous, and the prevalence of comorbidity differs by diagnostic group. One of the overarching issues in the area of comorbidity is the nature of the connection between psychiatric disorders and substance use disorders. The rapid development of technical advances in the neurosciences has led to a better understanding of the molecular biology, neurotransmitter systems, and neural circuitry involved in mental illness and substance use disorders. The authors discuss the neurobiological interface between substance use disorders and other psychiatric disorders with an emphasis on emerging data concerning four psychiatric disorders that commonly co-occur with substance use disorders: depression/ mood disorders, posttraumatic stress disorder, attention deficit hyperactivity disorder, and schizophrenia. Better understanding of the connection between substance use disorders and psychiatric disorders could have a profound effect on prevention and treatment.

(Am J Psychiatry 2005; 162:1483-1493)

The high rate of co-occurrence of substance use disorders and other psychiatric disorders is well established (1, 2). The implications of comorbidity are far-reaching and raise important questions that are unlikely to have simple answers. One of the overarching issues is the question of why substance use and other mental disorders so often co-occur. Are there genetic mediators and/ or neurobiological connections between these disorders that drive the comorbidity? Do different psychiatric disorders have differing relationships with various substances of abuse? Better understanding of the connection between substance use disorder and mental illness could have a profound effect on both prevention and treatment.

In this article, we focus on four psychiatric disorders- depression/mood disorders, posttraumatic stress disorder (PTSD), attention deficit hyperactivity disorder (ADHD), and schizophrenia- because research concerning the neurobiological and mechanistic connections between these disorders and substance use disorders is particularly active. With the rapid development of technical advances in the neurosciences, the amount of information concerning the molecular biology, neurotransmitter systems, and neural circuitry involved in mental illness and substance use disorders has increased dramatically. In this article, we conceptualize chronic distress as a central construct underlying the association of each of these four psychiatric disorders with substance use disorders and examine emerging neurobiological findings within this framework.

Prevalence: Epidemiological and Clinical Perspectives

Epidemiological surveys in the 1990s emphasized the prevalence of comorbid psychiatric and substance use disorders in community samples of adults (1, 3, 4). In the Epidemiologic Catchment Area study (3), an estimated 45% of individuals with alcohol use disorders and 72% of individuals with drug use disorders had at least one co-occurring psychiatric disorder. In the National Comorbidity Study (1), approximately 78% of alcohol-dependent men and 86% of alcohol-dependent women met the criteria for a lifetime diagnosis of another psychiatric disorder, including drug dependence. The risk relationship appears to be reciprocal, with psychiatric disorder predicting increased risk of later substance use and vice versa. A study involving a subset of National Comorbidity Study subjects found that active psychiatric disorders predicted an increased risk for the first onset of daily smoking and progression to nicotine dependence (5). Comorbidity is greater in individuals who are dependent on illicit drugs, compared to alcohol- dependent individuals, and individuals with multiple dependencies experience the highest rates of psychiatric comorbidity (6). Because acute intoxication and withdrawal from drugs of abuse can mimic symptoms of psychiatric disorders, the overlap of symptoms can be problematic in making an accurate diagnosis of a psychiatric disorder in an individual with a substance use disorder. This difficulty may account for some of the high Comorbidity rates reported in epidemiological studies, which are not generally designed to tease apart substance-related and independent psychiatric symptoms. Despite this caveat, even conservative estimates suggest a high rate of comorbidity between psychiatric disorders and substance use disorders.

Etiological Relationships: Theoretical Perspective

Although convincing data support a strong association between a variety of psychiatric disorders and substance use disorders, the nature of the relationship is complex and may vary depending on the disorder in question and substance that is used. Several theories have been proposed to explain the high co-occurrence. Certain psychiatric disorders may be risk factors for development of substance use disorders or may modify the course of substance use disorders. One of the more overarching theories of addiction is that drugs and their specific psychotropic effects are used to cope with emotional distress (7). Psychiatric disorders have been conceptualized as chronic distress states associated with neurobiological alterations in brain stress circuits (8-10). On the other hand, chronic drug use is associated with neuroadaptations in brain reward pathways that produce secondary psychiatric symptoms during acute and protracted withdrawal states (10). With increasing severity of addiction, neuroadaptations in stress and reward circuits occur, and these changes may underlie the increasing emotional distress often associated with substance use disorders (11, 12).

A growing body of evidence from basic science and translational studies implicates common neurobiological pathways and abnormalities involved in addiction and a number of psychiatric disorders. Within a neurobiological framework, at least two hypotheses can be postulated to explain comorbidity: 1) addiction and other psychiatric disorders are different symptomatic expressions of similar preexisting neurobiological abnormalities, and 2) repeated drug administration, through neuroadaptation, leads to biological changes that have common elements with the abnormalities mediating certain psychiatric disorders (13).

One of the bridging constructs between psychiatric and substance use disorders is the role of stress in the development and relapse of substance use disorders and other psychiatric disorders. Figure 1 provides a heuristic model of the relationship between chronic distress states, substance use disorders, and psychiatric comorbidity. Although the model conceptualizes chronic distress as the bridging construct, various genetic and environmental vulnerability factors contribute to the development of the distress states, as noted in Figure 1. Additional research on these factors will contribute to a more specific understanding of the mechanisms underlying the associations between psychiatric and substance use disorders.

Corticotropin-releasing factor (CRF), one of the key hormones involved in the stress response, has been implicated in the pathophysiology of anxiety, affective, and addictive disorders (8, 14). Preclinical evidence suggests that CRF and noradrenergic pathways are involved in stress-induced reinstatement of drug- seeking behavior in drug-dependent laboratory animals (15). Stress stimuli that activate CRF circuits are also known to potentiate mesolimbic dopaminergic reward pathways in laboratory animals (16). Similarly, human laboratory studies have shown that emotional stress and negative affect states increase drug craving in drug-dependent individuals (17, 18). Evidence of an association between severity of depressive symptoms in patients with major depression and the subjective reinforcing effect of an acute dose of dextroamphetamine (19) suggests dysregulation of reward systems with increasing levels of distress in major depression. In animal models, early life stress and chronic stress result in long-term changes in stress responses (20). Such changes can alter the sensitivity of the dopamine system to stress and can increase susceptibility to self-administration of substances of abuse (16, 21, 22).

Corticolimbic dopamine and noradrenergic pathways modulate prefrontal cortical function under conditions of increasing cognitive or emotional demand, including persistent distress states, tasks involving high levels of cognitive challenge, and working memory tasks (23, 24). Glutamatergic and γ-aminobutyric acid (GABA)-ergic pathways are also important in modulating prefrontal cortical function (25).

It is important to note that different substances of abuse have widely varying effects on neurobiological systems. Cocaine and amphetamines have a stimulating effect on catecholaminergic systems. Opioid analgesic drugs act through a complex system of opioid receptors, and nicotine acts through specific nicotinic receptors distributed throughout the central and peripheral nervous systems. GABA-ergic and glutamatergic systems are particularly important in acute intoxication and withdrawal from alcoholand benzodiazepines. Clearly, the effects of acute intoxication and withdrawal differ for each of these drugs, and the effect on psychiatric disorders also differs by drug. It is interesting to note, however, that there appear to be common neurobiological pathways operating across substances of abuse. Dopamine activity in the nucleus accumbens has been implicated in the mechanism of reinforcement for almost all drugs of abuse (26). Furthermore, drugs of abuse activate the CRF/ hypothalamic-pituitary-adrenal (HPA) axis during use/abuse, and alterations in the CRF/HPA and noradrenergic systems during acute withdrawal/abstinence are also well documented (11, 12, 26). Some animal models of reinstatement (i.e., stress-induced reinstatement, cue-induced reinstatement) operate across substances of abuse, also arguing for some common mechanisms.

In the following sections, we review emerging data that shed light on the neurobiological connections between various substance use disorders and the four psychiatric disorders considered here (depression/mood disorders, PTSD, ADHD, and schizophrenia). Figure 2 summarizes the neurobiological evidence cited in the following sections and identifies the overlapping neurotransmitter systems and associated brain regions.

FIGURE 1. Schematic Model of Chronic Distress and Perpetuation of Psychiatric Symptoms and Drug Use in Individuals With Comorbid Disorders(a)

Depression and Substance Use Disorders

Epidemiological studies reported rates of comorbidity of major depression with nicotine, alcohol, and illicit drug abuse ranging from 32% to 54% (1, 27, 28). Individuals with major depression are more likely to develop substance use disorders, and individuals with substance use disorders are at greater risk for the development of major depression, compared to the general population (27-29). Clinical similarities exist between major depression and substance use disorders. Depressive symptoms are commonly reported during acute and chronic withdrawal from drugs of abuse. Irritability, sleep difficulties, anxiety, and trouble with attention/ concentration are associated with both protracted withdrawal states and major depression.

Neurobiological similarities between major depression and substance use disorders likely contribute to both symptom overlap and high rates of comorbidity (13). Substantial data indicate that extrahypothalamic CRF and HPA axis abnormalities (8) and alterations in catecholamine, serotonin, GABA, and glutamate systems are associated with major depression (30, 31). Neuroadaptations associated with chronic drug abuse are associated with alterations in these neurotransmitter systems, especially during acute withdrawal states (13). CRF/HPA response during acute drug withdrawal has a positive association with withdrawal-related distress and with depressive symptoms (32, 33). In addition, a growing amount of evidence indicates that the neurobiological alterations associated with acute withdrawal last for varying time periods and contribute to drug craving and relapse in substance use disorders (12). In a recent study (34), individuals with substance use disorders, both with and without depressive symptoms, were found to have significantly lower ACTH and cortisol response to CRF stimulation, compared to healthy subjects. These findings are consistent with studies of abstinent smokers, alcoholic subjects, and subjects with polysubstance dependence in which a blunted cortisol response to standard psychological stressors was demonstrated (12). Blunted cortisol and prolactin responses to d- fenfluramine challenge in abstinent heroin-dependent individuals with and without depression have also been reported (35). Blunted peripheral stress hormone responses may be a marker for increased HPA axis activity (36, 37).

FIGURE 2. Central Systems/Pathways Involved in the Comorbidity of Psychiatric and Substance Use Disorders

Evidence of altered neuroendocrine response to stress challenges in substance use disorders is consistent with clinical observations that individuals with substance use disorder have difficulty managing stressful situations and emotional distress states and often relapse in the face of stressful situations (12, 38). In laboratory studies, stress and negative affect states increase drug craving and emotional distress in abstinent substance-dependent individuals (17, 39-41). These changes are accompanied by physiological arousal (18), and this finding suggests that drug- craving states that are marked by increased levels of anxiety and distress are accompanied by biological stress responses. Increased distress-related drug craving is associated with vulnerability to continued drug use and relapse (12, 42), and this association suggests a mechanistic connection between depressive symptoms and substance use disorders.

In other studies, specific associations between monoamine oxidase (MAO) activity in smoking and major depression have been examined. MAO (with A and B subtypes), an enzyme involved in oxidizing serotonin, norepinephrine, and dopamine in the brain, has long been associated with negative mood and depression. For example, MAO inhibitors are known to have antidepressant properties. It is interesting to note that smokers show reduced MAO-A and MAO-B levels in the brain, compared to non-smokers and former smokers (43, 44). These findings provide some support for the notion that smoking may have antidepressant effects through inhibition of MAO-A and MAO-B activity and suggest a pharmacological explanation for the high rates of smoking reported among individuals with major depression.

Recent findings from neuroimaging studies implicate similar alterations in frontal-limbic brain circuitry in substance use disorders and major depression. Reduced frontal metabolism and hypoactivity of the anterior cingulate have been reported in individuals with substance use disorders (45, 46). Significant reduction in dopamine D^sub 2^ receptors, particularly in frontal- striatal regions, has been noted in cocaine- and alcohol-dependent individuals, compared to healthy subjects (45). Reduced frontal- limbic metabolism has also been found in subjects with major depression, relative to healthy subjects (47). Such findings are consistent with postmortem studies showing reduced cell density and gray matter volume in individuals with a diagnosis of major depression (48). Furthermore, amygdala hyperactivity and anterior cingulate hypoactivity are associated with major depression (47), and studies of individuals with substance use disorders indicate activation in the amygdala associated with cue-induced drug craving (49, 50). Under conditions of distress, cocaine-dependent subjects exhibited decreased activity in frontal regions such as the medial prefrontal cortex and the anterior cingulate, similar to that seen with negative mood in subjects with major depression (51, 52). Similarly, a recent study (53) reported lower levels of glucose metabolism in the anterior cingulate and insula, but higher levels in the orbitofrontal region, amygdala, middle and posterior cingulate, and ventral striatum in methamphetamine abusers with severe mood and anxiety symptoms, compared to healthy subjects.

In conclusion, neuroendocrine and neuroimaging studies indicate dysregulation in frontal-limbic systems associated with stress and reward pathways in both major depression and substance use disorders. This common dysregulation is likely to contribute to the high rate of comorbidity of these illnesses. Evidence concerning negative affect and stress-related drug seeking/craving provides additional insight into emotional distress states and drug use in drug-experienced individuals. A better understanding of these connections will contribute to the development of new treatments for major depression, substance use disorders, and the comorbidity of these disorders.

PTSD and Substance Use Disorders

The high prevalence of the comorbidity of substance use disorders and PTSD has been reported in a number of studies. Initial reports focused on veterans with PTSD, of whom 64%-84% met the criteria for a lifetime alcohol use disorder and 40%-44% met the criteria for a lifetime drug use disorder, including nicotine dependence (54, 55). In civilian populations with PTSD, estimates of the lifetime prevalence of substance use disorders range from 22% to 43% (56, 57), far higher than the estimates for substance use disorders in the general population.

As in other comorbidities, PTSD and substance use disorders have a number of connecting pathways. Substance intoxication may heighten the likelihood of exposure to trauma, hence the likelihood of developing PTSD. Furthermore, chronic substance use and withdrawal may increase anxiety/arousal states, making it more likely that individuals with substance use disorders will develop PTSD after trauma exposure. On the other hand, PTSD could increase the risk of developing a substance use disorder, because individuals may abuse substances in an attempt to relieve symptoms of PTSD. Substance use could also exacerbate symptoms and/or prolong the course of PTSD by preventing habituation to traumatic memories. These pathways are not mutually exclusive, and new evidence is emerging concerning the neurobiological underpinnings of potential causal pathways. In one recent study (58), individuals who had experienced any trauma and developed PTSD had an increased risk for the development of drug dependence, particularly nicotine dependence, but not alcohol dependence. This finding suggests specificity between substance of abuse and psychopathology.

The HPA axis, extrahypothalamic CRF, and the noradrenergic system are all intimately involved in the stress response, PTSD, and the pathophysiology of substance use disorders. Evidence is accumulating to support a role for CRF in mediating the effects of stress in increasing self-administration of drugs. Studies inrats have also demonstrated that withdrawal from chronic cocaine (59) or alcohol administration (60) in rats is associated with increases in CRF in the hypothalamus, amygdala, and basal forebrain. Elevated CSF CRF has been found in humans during alcohol withdrawal (61). Two studies examining CSF concentrations of CRF have demonstrated higher levels in individuals with PTSD, compared to healthy subjects (62, 63). This finding is of particular interest because elevated brain CRF levels, especially in the amygdala, potentiate fear-related behavioral responses (64). As such, elevated levels of CRF may mediate both the symptoms of hyperarousal and the increased risk for substance use disorders in PTSD. Increased CRF may enhance the reinforcing properties of some drugs, worsen the severity of withdrawal symptoms, and exacerbate symptoms of PTSD.

Evidence implicating abnormalities in noradrenergic systems has been found for both PTSD and substance use disorders. Individuals with PTSD have elevated urinary excretion of both norepinephrine and epinephrine and elevated plasma levels of norepinephrine (65). Markers of noradrenergic activity are increased in both alcohol and opioid withdrawal (66-68). Brain CRF and noradrenergic systems modulate each other in a number of ways. Stress increases CRF in the locus ceruleus (69), and intraventricular administration of CRF increases norepinephrine turnover in the hypothalamus, hippocampus, and prefrontal cortex (70). In the amygdala, norepinephrine stimulates the release of CRF (71). Koob and colleagues (72, 73) hypothesized that interactions between CRF and the noradrenergic systems can function as a “feed-forward” system, with progressive augmentation of the stress response with repeated stress exposure. Specifically, substance use or withdrawal or other stress may stimulate CRF release in the locus ceruleus, leading to the release of norepinephrine in the cortex, which would, in turn, stimulate the release of CRF in the hypothalamus and amygdala. This interaction could help to explain the attempt to self-medicate PTSD symptoms with substances of abuse, the worsening of PTSD symptoms during substance withdrawal, and the increase in vulnerability to the development of PTSD in traumatized individuals with substance use disorders.

Neuroimaging studies have shed light on the connection between PTSD, other anxiety disorders, and substance use disorders. Amygdala activation occurs during symptom provocation in PTSD, panic disorder, and social phobia (74). As mentioned earlier, increased amygdalar blood flow is also seen in cocaine-dependent individuals presented with cocaine-related cues (50, 75).

ADHD Spectrum and Substance Use Disorders

Substantial evidence suggests that ADHD, conduct disorder, and oppositional defiant disorder co-occur at high rates among children and adolescents. This group of disorders, conceptualized as externalizing disorders, is associated with shared genetic and environmental risk factors (76-78). Externalizing disorders are commonly comorbid with substance use disorders in adolescents, with prevalence estimates ranging from 30%-50% (79). Adolescents with comorbid substance use disorder and ADHD, conduct disorder, and/or oppositional defiant disorder have an earlier age at onset and a more severe course of substance use disorder (80-82). Research has identified genetic, neurobiological, and psychosocial risk factors that contribute to the core pathophysiology in the development of comorbid ADHD and substance use disorders.

Externalizing disorders are characterized by behavioral disinhibition and personality traits such as aggression, high levels of impulsivity, and poor self-control (77, 78, 83). Substantial evidence suggests that externalizing disorders are associated with problems in higher-order “executive” (frontal) cognitive function. In fact, ADHD has often been characterized as a disorder of frontal and prefrontal cortex dysfunction (23, 71). Children with ADHD, conduct disorder, oppositional defiant disorder, and early-onset substance use disorder showed poor performance on neuropsychological tests of abilities involving the prefrontal cortex, including planning, attention, cognitive flexibility, working memory, self- monitoring, and behavioral and motor control (71).

In a large twin study that examined P3 amplitude-a robust electrophysiological marker with a strong genetic basis-lower P3 amplitude was associated with presence of ADHD, conduct disorder, oppositional defiant disorder, and substance use disorder in adolescent boys (78). Lower P3 amplitude at age 17 years predicted development of substance use disorder at age 20 years. Although genetic factors contribute to the development of comorbid ADHD, conduct disorder, and oppositional defiant disorder, a single shared environmental factor, identified as parent-child conflict (i.e., negative social interactions between parents and children), accounts for an even larger proportion of the variance (84). Negative parent- child interactions, high levels of negative affect, and emotional distress are also known to increase the risk of substance use disorder in adolescents (85). These data suggest that coping with high levels of family conflict may play an important role in the development of both ADHD and substance use disorders.

Preclinical research has demonstrated that dopamine and norepinephrine modulate prefrontal cortical function (23, 86) and that stress impairs prefrontal cortical function (86, 87). Evidence from brain imaging studies indicates that the prefrontal cortex and anterior cingulate cortex play important roles in cognitive conflict monitoring (88, 89) and self-regulation processing (90, 91). Difficulties in response inhibition and self-regulation are core symptoms of externalizing disorders (78, 83). Compared to healthy subjects, boys with comorbid ADHD, conduct disorder, and oppositional defiant disorder show greater behavioral aggression, heart rate reactivity, and higher levels of anger in a laboratory- induced provocation paradigm (92). Furthermore, in boys with externalizing symptoms, lower cortisol levels and the personality traits of low levels of self-control and harm avoidance are associated with the development of substance use disorders (93, 94). Thus, consistent with preclinical evidence indicating that stress impairs prefrontal cortical function, human studies suggest that individuals with ADHD and early-onset substance use disorders have poor stress-related coping and poor self-regulation.

The prefrontal cortex and anterior cingulate cortex are also important in regulating behavior related to future rewards. Primate studies have shown that the prefrontal cortex and anterior cingulate cortex are involved in assessing reward expectancy (95) and motor responses based on future reward (96). These data are consistent with the critical role of the prefrontal cortex in drug self- administration and in the reinforcement and reinstatement of drug use (97, 98). Children with ADHD and conduct disorder show disinhibited physiological and behavioral responses during reward- related cognitive tasks (99, 100). These findings are consistent with decreased prefrontal cortical and striatal activity and increased activity in posterior and sensory cortices in ADHD (101, 102) that is normalized by chronic methylphenidate treatment (103). Preliminary findings indicated that decreasing catecholamine input to the prefrontal cortex by means of α^sub 2^-adrenergic agonists such as guanfacine, which inhibit norepinephrine centrally, enhances prefrontal cortical function and decreases ADHD symptoms (104). It is interesting to note that other α^sub 2^- adrenergic agonists, such as clonidine and lofexidine, attenuate stress-induced reinstatement of drug-seeking behavior in laboratory models (105, 106). To the extent that stress and reward dysfunction contribute to prefrontal cortical deficits in ADHD and substance use disorders, α^sub 2^-adrenergic agonists may be beneficial in addressing this comorbidity.

Schizophrenia and Substance Use Disorders

Recent studies have demonstrated that up to 50% of individuals with schizophrenia have either alcohol or illicit drug dependence and more than 70% are nicotine dependent (2, 107, 108). In addition to having the expected adverse medical consequences, substance use in schizophrenic patients is associated with poor social function, symptom exacerbation, frequent hospitalization, medication noncompliance, and poor treatment response (109, 110). Schizophrenia and substance use are connected by multiple potential links, including genetic vulnerability, medication side effects, negative symptoms, and psychosocial factors. Self-medication has been commonly invoked to explain the high comorbidity. Specifically, self- medication of negative symptoms, such as social withdrawal and apathy, and drug use in the attempt to decrease discomfort from the side effects of typical antipsychotic medications have been suggested as explanations for the high prevalence of substance use disorders in individuals with schizophrenia. Although these factors may play some role, advances in neurobiology suggest that the neuropathology of schizophrenia affects the neural circuitry mediating drug reward, leading to an increased vulnerability to addiction. Specifically, Chambers and colleagues (111) hypothesized that abnormalities in hippocampal-cortical function in schizophrenia impair the inhibitory hippocampal projections to the nucleus accumbens, resulting in reduced inhibitory control over dopamine- mediated functional hyperresponsivity to dopamine release. In this model, dysregulated neural integration of dopamine and glutamate in the nucleus accumbens resulting from frontal and hippocampal dysfunction could lead, in subjects without prior drug exposure, to neural and motivational changes similar to those in long-term substance use. \Thus, the predilection of schizophrenic patients to substance use disorders may be a primary disease symptom.

Recent studies focused on the neurobiological interface between schizophrenia substance use disorders support this hypothesis. In one study (112), magnetic resonance images in groups of subjects with schizophrenia, schizophrenia plus alcohol dependence, and alcohol dependence only were compared with those from a matched control group. Gray matter deficits were found in all three patient groups, but were greatest in the group with comorbidity. The most prominent deficits were in the prefrontal and anterior superior temporal regions, indicating that comorbidity compounded the prominent prefrontal cortical deficits that are present independently in schizophrenia and alcohol dependence. Lifetime alcohol consumption in subjects with comorbidity was approximately five times less than that in the alcohol-dependent subjects, yet the subjects with comorbidity exhibited the full detrimental effects of alcohol, which suggests an interactive effect.

One area of particular interest is nicotine dependence and schizophrenia. It has been estimated that 70%-90% of individuals with chronic schizophrenia are nicotine dependent (113). Nicotine interacts with many of the same central pathways involved in schizophrenia, including the dopaminergic and glutamatergic pathways in the mesolimbic areas. Several abnormalities associated with schizophrenia are improved with nicotine administration, including deficits in the inhibitory gating of the P-50 evoked response to repeated auditory stimuli (114) and deficits in smooth pursuit eye movement dysfunction (115). George and colleagues (116) found deficits in visuospatial working memory in schizophrenic and nonschizophrenic individuals with nicotine dependence. With increasing periods of abstinence, the nonschizophrenic smokers had improvements in visuospatial working memory, whereas the schizophrenic smokers experienced further impairment in visuospatial working memory. The authors postulated that the high rates of cigarette smoking in schizophrenic patients may be related to the effects of smoking in alleviating some of the cognitive dysfunction associated with the presumed hypofunctionality of cortical dopamine systems in schizophrenia. In a recent study of more than 14,000 adolescents followed over a 4-16-year period, adolescents who smoked more than 10 cigarettes/ day at the initial evaluation were significantly more likely to be hospitalized for schizophrenia during the follow-up period (117). These findings suggest that smoking might constitute self-medication of premorbid symptoms, might reflect an intrinsic, disease-related disorder of nicotinic transmission, or might play a causative role in the development of schizophrenia through chronic activation of mesolimbic dopaminergic neurotransmission in vulnerable individuals. The development of novel approaches based on nicotinic receptor mechanisms may have implications for both prevention and treatment of schizophrenia.

Data from small, largely uncontrolled studies suggest that treatment with clozapine and other atypical antipsychotics may be associated with decreases in substance abuse in schizophrenic patients. Although the data are limited, this favorable response to atypical agents is consistent with the theory that dysfunction of the brain reward system leads to an increased vulnerability to addictions in schizophrenia (118). Typical antipsychotic agents are potent antagonists of D^sub 2^ receptors. Although this blockade may initially decrease the reinforcing properties of some substances of abuse, with chronic use there may be enhancement of the substances’ reinforcing properties. Studies in rodents demonstrated that chronic treatment with haloperidol increased the reinforcing properties of cocaine, presumably through up-regulation of the postsynaptic dopamine receptor secondary to chronic blockade (119). In contrast, atypical agents, such as clozapine, have varied actions on a number of neurotransmitter systems and are much weaker D^sub 2^ antagonists. It is possible that these agents have a normalizing effect on the signal detection capabilities of the mesocorticolimbic reward circuitry, and this action may explain the association with decreased substance use.

Conclusions

Although the nature of the relationship between psychiatric disorders and substance use disorders is complex and multifaceted, there are likely to be unifying constructs. Neuroadaptations in brain stress and reward pathways associated with chronic stress may predispose or unmask a vulnerability to psychiatric disorders, substance use disorders, or both. Dysfunction in the prefrontal cortex and frontal cortex associated with deficits in self- monitoring and behavioral control are evident in ADHD, other externalizing disorders, and substance use disorders. Emerging evidence suggests that abnormalities of glutamatergic function in schizophrenia and other psychiatric disorders may mediate vulnerability to the development of substance use disorders.

Although the focus of this article has been on neurobiological connections between psychiatric and substance use disorders, it is important to note that these connections constitute just one facet of a complex issue. Further exploration of overlapping neural circuitry and mechanistic relationships will be essential in guiding treatment and prevention efforts. However, improvement in our understanding of co-occurring disorders will be useful only if there is a treatment system in place to implement these findings. Clearly, change at public policy levels will be necessary to maximize the benefits derived from the findings of neurobiological explorations in order to improve the lives of individuals with comorbidity.

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Kathleen T. Brady, M.D., Ph.D.

Rajita Sinha, Ph.D.

Received Oct. 8, 2004; revision received Jan. 12, 2005; accepted Jan. 27, 2005. From the Clinical Neuroscience Division, Institute of Psychiatry and Behavioral Sciences, Medical University of South Carolina; and Connecticut Mental Health Center, Yale University School of Medicine, New Haven, Conn. Address correspondence and reprint requests to Dr. Brady, Clinical Neuroscience Division, Institute of Psychiatry and Behavioral Sciences, Medical University of South Carolina, 69 President St., Charleston, SC 29425; [email protected] (e-mail).

Supported by grant 1 P50 AR-049551 from the National Institute of Arthritis and Musculoskeletal and Skin Diseases, grants 5 M01 RR- 01070-26 and M01 RR-00125 from the National Center for Research Resources, and grants K24 DA-00435-04, 1 P50 DA-016556, and K02-DA- 017232 from the National Institute on Drug Abuse.

Copyright American Psychiatric Association Aug 2005

By Louise Egan

FRAY BENTOS, Uruguay (Reuters) – The cows grazing
peacefully in the pastures of Fray Bentos don’t know how lucky
they are.

Their ancestors were herded into the Uruguayan town’s meat
packing plant by the hundreds to be slaughtered, chopped,
pulverized and packed into cans only to reappear as corned beef
on a dinner plate in London.

Those days are long gone and all that’s left of the giant
factory, maker of the world-famous Fray Bentos meat pies, is
some crumbling old buildings with peeling paint and broken
windows.

The cows may be happy but the people in the unassuming town
of 22,000 people northwest of Montevideo miss those days when
their company town was abuzz with activity.

The beef plant closed in 1979 after 117 years in operation
but at its peak 4,000 workers from 60 countries kept it
humming, their children gorged on beef daily and the British
owners held glitzy garden parties.

To relive that heady past when Fray Bentos fed the Allies
in World War Two and was dubbed “one of the largest kitchens of
the free world” some local history buffs have created what they
call the museum of the industrial revolution.

“It’s like a fairy tale for our children,” said Olma
Villalba, whose grandmother was head housekeeper at the
so-called casa grande, the British bosses’ mansion.

“This place is the lifeblood of the town. Everything still
revolves around the old meatpacking plant,” she said of the
now-decrepit “Anglo” neighborhood that once encompassed the
state-of-the-art factory, a port, worker housing and a school.

Tourists have been able to tour the cobwebbed grounds since
1990 and in March 2005 the museum itself opened its doors.

THE COW’S ‘MOO’

A two-headed calf in a jar, dated 1938, is one of the first
displays to greet visitors to the museum.

Another cheerful exhibit shows the production chain from
cow to OXO beef extract with colorful arrows depicting how even
hooves, tendons and thyroid glands were transformed into some
commercial product.

“What is the only part of the cow that wasn’t used?” the
interactive panel asks, urging the visitor to push a button to
hear the answer: a cow’s moo.

Fertilizer was made from animal blood, bonemeal and the
contents of their stomachs in the site that is now the museum,
tour guide Diana Cerrilla explains.

But tourists who signed the guest book don’t seem daunted
by the sordid details.

“This museum makes me hungry. The first thing I’m going to
do when I get home is get a corned beef sandwich,” says one
typical entry signed “U.S.”

Fray Bentos became synonymous with comfort food for
millions of Europeans who were raised on the tinned meats
during times of war and instability. Britain’s Prince Charles
fondly reminisced on the Fray Bentos cuisine of his childhood
in a visit to Uruguay years ago.

The plant exported 16 million tins of corned beef in 1943
and during the war slaughtered some 12,000 animals a day,
including pig, rabbit, chicken and turkey.

Everything from frozen sides of beef to steak and vegetable
pie with puff pastry was shipped from Fray Bentos to the
world’s pantries. And not only foreigners squeal in delight at
the kitschy labels for some 200 subproducts showcased here.

Villalba licks her lips recalling how her parents brought
home loads of beef from the company store. “As you can imagine,
we all have high cholesterol now,” she laughs.

The factory was built in 1863 by a German chemist who
patented beef extract and in 1924 came under British ownership
and was called “Anglo del Uruguay.”

The Fray Bentos brand name is now owned by Campbell Soup
Co. and the products made elsewhere.

The museum’s name is inspired by the original steam engine
that powered the plant and transformed Fray Bentos as it
transformed Britain in the industrial revolution. The rusty
turbines sit intact in a dank room full of pigeon droppings.

After the world wars, Uruguay could not keep up with the
technological changes overtaking Europe and the plant began to
lose money. The owners sold it in 1970 to the Uruguayan state
which shut it down a few years later, spelling the demise of
Fray Bentos.

“We built this museum using our hearts, our creativity and
recycling materials out of deep respect for our parents, our
grand parents and our great grandparents who labored here,”
said museum director Rene Boretto.

Key words: Antiepileptic drugs * Carbamazepine * Epilepsy * Erectile dysfunction * Oxcarbazepine

ABSTRACT

Oxcarbazepine is an antiepileptic drug (AED) indicated for use as monotherapy and add-on therapy in adults and children 4 years of age and older. Despite being structurally related to carbamazepine, oxcarbazepine differs substantially in its pharmacokinetic and safety profile; oxcarbazepine has a much lower risk of pharmacokinetic drug-drug interactions than carbamazepine. Carbamazepine has also been shown to induce the hepatic synthesis of sex hormone-binding globulin, thus reducing free serum testosterone levels and possibly causing erectile dysfunction (ED) in some men; these effects have not been observed with oxcarbazepine. This paper provides a discussion of recent clinical experience with men who presented in private clinical practice with complaints of ED while being treated with carbamazepine for seizure disorders. The four illustrative case studies presented in this report suggest that switching AED treatment from carbamazepine to oxcarbazepine in men with epilepsy can reduce the ED side effects observed with carbamazepine.

Introduction

Carbamazepine is a commonly used antiepileptic drug (AED) that is associated with a wide range of adverse reactions, including central nervous system dysfunction; gastrointestinal, hepatic, and endocrine disturbances; and teratogenic effects1. In addition, carbamazepine can increase plasma levels of sex hormone-binding globulin (SHBG), consequently decreasing the unbound biologically active form of testosterone, which leads to sexual dysfunction in some men2,3. In particular, complaints of erectile dysfunction (ED), hypoactive sexual desire disorder, inhibited orgasm, and premature ejaculation have been reported in men taking carbamazepine4-5.

Oxcarbazepine, a more recently developed AED, is indicated for use in the United States as monotherapy or adjunctive therapy in adult and pediatric patients ≥ 4 years old with partial seizures with or without secondary generalization. Oxcarbazepine is a structural variant of carbamazepine, although results from preclinical and clinical studies have demonstrated some distinct differences between the two drugs. In particular, oxcarbazepine is associated with fewer side effects and appears to be better tolerated than carbamazepine6’7. Oxcarbazepine does not increase the risk of sexual side effects; despite observed hormonal changes at high doses in one study, SHBG levels were increased but testosterone activity was unaffected8.

The lack of sexual side effects associated with oxcarbazepine suggests that the ED in men who are taking carbamazepine will improve once they are switched to oxcarbazepine. In fact, normalized endocrine effects, namely restoration of normal SHBG plasma levels, were observed after carbamazepine was replaced with oxcarbazepine9. The following case presentations illustrate the effect of this hormonal normalization after a switch in anticonvulsant regimen; the erectile function in four men who experienced ED while being treated with carbamazepine improved after being switched to oxcarbazepine (see Table 1 for a summary of the most relevant data from these cases). These men were all seen in a neurology epilepsy practice at the University Hospital and were selected for inclusion in this report based on information they volunteered without direct questioning by the physician during follow-up visits. We originally identified these patients in an informal case review, from among those who visited the clinic over the previous two months.

Case 1

This 221-pound, 48-year-old married man (TM; here and later, these are not real patient initials] is a maintenance worker at a large northeastern university. TM has a history since childhood of simple and complex partial seizures progressing to generalized seizures; the etiology of his epilepsy is postnatal meningitis leading to cortical vein thrombosis. Magnetic resonance imaging (MRI) indicated encephalomacia in the right temporal lobe, and a computed tomography scan showed abnormalities in the right frontotemporal-parietal region. An electroencephalogram obtained in 1986 indicated bilateral abnormalities.

The patient’s AED treatment history included primidone, phenobarbital, phenytoin, and carbamazepine; however, the refractory nature of his seizure disorder prompted physicians to perform a right temporal lobectomy. There were no postsurgical complications, and adequate seizure control was achieved with carbamazepine 2200mg/ day monotherapy. However, TM complained of ED and decreased libido during the course of his AED therapy that was most severe with phenytoin and improved only somewhat after he was switched to carbamazepine. Conditions such as vascular disease or major depressive disorder (MDD) were ruled out as the cause of his ED. Nevertheless, TM tolerated the sexual side effect of carbamazepine because his seizures were well controlled by the medication.

Table 1. Summary of data from case studies

TM began to experience intolerable visual side effects (blurring and diplopia) on carbamazepine and was switched to monotherapy with oxcarbazepine dosed initially at 3000mg/day and tapered to 2700mg/ day. His seizures remained well controlled, and the visual abnormalities resolved within a few days after the initiation of oxcarbazepine. Moreover, at the next follow-up visit, TM volunteered that he was experiencing a substantially increased libido and improved erections that enabled satisfactory sexual intercourse. Clinical laboratory analyses conducted after the switch to oxcarbazepine indicated no abnormalities in liver function test results, serum sodium levels, or plasma lipid profile. His most recent serum testosterone level was 306ng/dL (10.6nmol/L), normal range 241-827ng/dL (8.4-28.7nmol/L), and steady-state concentration of oxcarbazepine monohydroxy derivative (MHD) was 34g/mL. TM remains seizure free on oxcarbazepine monotherapy and is satisfied with his sexual function. The treatment plan is to further taper the oxcarbazepine dose to 2400mg/day.

Case 2

This 224-pound, 51-year-old man (SF) works for a pharmaceutical company and has been married for 14 years. He has hypertension that is being controlled with antihypertensive polytherapy. He began experiencing seizures in 2001, most probably secondary to a mild stroke, although an MRI revealed no abnormalities. SF experienced normal erectile function while receiving only antihypertensive therapy, but complained of ED with normal libido upon coadministration of carbamazepine. SF accepted this adverse effect because his seizures were well controlled and, when offered sildenafil as a treatment for his ED, he refused. However, SF subsequently requested the carbamazepine be discontinued because it interfered with his concentration at work.

One year ago, SF was switched to oxcarbazepine 1500-1800 mg/day. The change significantly improved his erectile function but caused dizziness, nausea, and hyponatremia (serum sodium 125mEq/L [125mmol/ L], which improved with fluid restriction to 131mEq/L [131 mmol/ L]); all adverse effects resolved after 3 months of oxcarbazepine treatment. His most recent serum testosterone level was 421 ng/ dL (14.6nmol/L), normal range 241-827ng/dL (8.4-28.7nmol/L), and his MHD concentration was 36g/mL. He remains seizure free with normal erectile function on oxcarbazepine monotherapy.

Case 3

This 225-pound, 50-year-old married man (JD) who works for a delivery service began to experience seizures in 1997, most often simple partial with occasional generalized involvement. His MRI was normal, and his two most recent electroencephalograms revealed normal findings. He had sleep apnea and elevated serum lipids (low- density lipoprotein cholesterol and triglycerides), although his blood pressure was normal. He was also diagnosed with MDD, which was treated unsuccessfully with fluoxetine, escitalopram, and sertraline; he is currently maintained on extended-release venlafaxine 112.5mg/day. While JD’s seizures were controlled on carbamazepine, he experienced ED with normal libido for which he was prescribed 1OO mg sildenafil. After being switched to oxcarbazepine dosed initially at 2400 mg/day and tapered to 1800 mg/day, he experienced improvement in erectile function; his sildenafil dose was reduced to 50 mg and then ultimately discontinued. His most recent testosterone level was 328ng/dL (11.4nmol/L), normal range 241-827ng/dL (8.4-28.7nmol/L), and his MHD concentration was 29g/ mL. His seizures are currently well controlled on oxcarbazepine 1800 mg/day.

Case 4

This 191-pound, divorced, 60-year-old man (BV) works occasionally as a laborer, loading and unloading trucks. He has had partial complex seizures since childhood that were not completely controlled by AED therapy, and he underwent a left temporal lobectomy in 1985. BV has hypertension that is currently managed with ramipril and MDD currently managed with paroxetine SOmg/day.

Postsurgically, BVs seizures were controlled with carbamazepine 1800mg/day, but he experienced ED that was managed with sildenafil 50mg/day. He was switched to oxcarbazepine 2400mg/day 1 year ago, and his ED improved significantly within 3 months. For the past 9 months, he has not required the sildenafil to achieve erections satisfacto\ry enough to engage in sexual intercourse. His most recent MHD concentration was 37g/mL; a testosterone level was not obtained. BVs seizures are currently well controlled on oxcarbazepine 1800mg/day.

Discussion

Because sexual function is an important aspect of the male identity10, ED can significantly affect a man’s quality of life and perception of self. Sexual dysfunction, including ED, occurs in nearly two thirds of people with epilepsy and is attributed to changes in sex hormone levels due to the disease or treatment with AEDs11. In particular, iatrogenic sexual dysfunction in men resulting from carbamazepine has been well documented4’5. As shown in the four cases of men with epilepsy presented in this report, switching from carbamazepine to oxcarbazepine may have significantly improved erectile function in carbamazepine-induced ED.

Carbamazepine has been shown to significantly increase plasma levels of SHBG and consequently decrease free testosterone in men. Brunei et al. measured SHBG levels and free testosterone index in 51 men with epilepsy12. Their results showed that patients receiving carbamazepine monotherapy had higher concentrations of SHBG and lower levels of free testosterone than control subjects; AEDs such as carbamazepine may induce the hepatic synthesis of SHBG, leading to reduced serum testosterone levels. Rtty et al. reported similar results in 22 men recently diagnosed with epilepsy who began treatment with carbamazepine13. These patients had increased serum SHBG levels, reduced dehydroepiandrosterone sulfate, and a decreased free-androgen index. Results from other studies in individuals without epilepsy showed that low levels of free testosterone and elevated concentrations of SHBG are both associated with ED14-16.

Given that oxcarbazepine does not induce hepatic metabolism17, it should have fewer deleterious effects on SHBG than carbamazepine. The results from Rtty et al. suggest that, unlike with carbamazepine, serum testosterone, gonadotropins, and SHBG concentrations were normal in men receiving low doses of oxcarbazepine (

The cases presented here support research findings on the influence of AEDs on sex hormone levels and erectile function. In 3 of the 4 patients, testosterone levels were measured during oxcarbazepine therapy to ensure levels were within the normal range. However, testosterone levels were not measured prior to switching therapy from carbamazepine to oxcarbazepine; such data would have been interesting to have to confirm a hormonal basis for the ED experienced with carbamazepine. Oxcarbazepine and carbamazepine are clinically distinctly different medications, and oxcarbazepine may be preferred for the treatment of men with epilepsy to avoid the potential risk of ED17. More formal studies are needed to evaluate the precise mechanisms involved in anticonvulsant-induced sexual dysfunction, specifically ED and decreased libido.

Acknowledgment

This case study report was supported by an unrestricted educational grant from Novartis Pharmaceuticals.

References

1. Tecoma ES. Oxcarbazepine. Epilepsia 1999;40(Suppl 5):S37-S46

2. Isojarvi JI, Repo M, Pakarinen AJ, Lukkarinen O, Myllyla W. Carbamazepine, phenytoin, sex hormones, and sexual function in men with epilepsy. Epilepsia 1995;36:366-70

3. Herzog AG, Drislane FW, Schomer DL, Pennell PB, Bromfield EB, Kelly KM et al. Differential effects of antiepileptic drugs on sexual function and reproductive hormones in men with epilepsy: interim analysis of a comparison between lamotrigine and enzyme- inducing antiepileptic drugs. Epilepsia 2004;45:764-8

4. Suva HC, Carvalho MJ, Jorge CL, Cunha Neto MB, Goes PM, Yacubian EM. Sexual disorders in epilepsy. Results of a multidisciplinary evaluation [in Portuguese]. Arq Neuropsiquiatr 1999;57:798-807

5. Leris AC, Stephens J, Hines JE, McNicholas TA. Carbamazepinerelated ejaculatory failure. BrJ Urol 1997)79:485

6. Dam M, Ekberg R, Loyning Y, Waltimo O, Jakobsen K. A double- blind study comparing oxcarbazepine and carbamazepine in patients with newly diagnosed, previously untreated epilepsy. Epilepsy Res 1989;3:70-6

7. Reinikainen KJ, Keranen T, Halonen T, Komulainen H, Riekkinen PJ. Comparison of oxcarbazepine and carbamazepine: a doubleblind study. Epilepsy Res 1987; 1:284-9

8. Rtty J, Turkka J, Pakarinen AJ, Knip M, Kotila MA, Lukkarinen O et al. Reproductive effects of valproate, carbamazepine, and oxcarbazepine in men with epilepsy. Neurology 2001;56:31-6

9. Isojarvi JI, Pakarinen AJ, Rautio A, Pelkonen O, Myllyla W. Serum sex hormone levels after replacing carbamazepine with oxcarbazepine. Eur J Clin Pharmacol 1995;47:461-4

10. Pommerville P. Erectile dysfunction: an overview. Can J Urol 2003;10(Suppl l):2-6

11. Lambert MV. Seizures, hormones and sexuality. Seizure 2001;10:319-40

12. Brunei M, Rodamilans M, Martinez-Osaba MJ, Santamaria J, To- Figueras J, Torra M et al. Effects of long-term antiepileptic therapy on the catabolism of testosterone. Pharmacol Toxicol 1995;76:371-5

13. Rtty J, Pakarinen AJ, Knip M, Repo-Outakoski M, Myllyla W, Isojarvi JI. Early hormonal changes during valproate or carbamazepine treatment: a 3-month study. Neurology 2001;57:440-4

14. Ahn HS, Park CM, Lee SW. The clinical relevance of sex hormone levels and sexual activity in the ageing male. BJU Int 2002;89:526-30

15. Aversa A, Isidori AM, De Martino MU, Caprio M, Fabbrini E, Rocchietti-March M et al. Androgens and penile erection: evidence for a direct relationship between free testosterone and cavernous vasodilation in men with erectile dysfunction. Clin Endocrinol 2000;53:517-22

16. Alexopoulou O, Jamart J, Maiter D, Hermans MP, De Hertogh R, De Nayer P et al. Erectile dysfunction and lower androgenicity in type 1 diabetic patients. Diabetes Metab 2001;27:329-36

17. Schmidt D, Elger CE. What is the evidence that oxcarbazepine and carbamazepine are distinctly different antiepileptic drugs? Epilepsy Behav 2004;5:627-35

CrossRef links are available in the online published version of this paper:

http://www.cmrojournal.com

Paper CMRO-2946_4, Accepted for publication: 03 May 2005

Published Online: 03 June 2005

doi: 10.1185/030079905X50561

Rajesh Sachdeo(a) and Revathi R. Sathyan(b)

a Clinical Professor of Neurology, University of Medicine and Dentistry of New Jersey; Director, NJ Comprehensive Epilepsy Center, Saint Peter’s University Hospital, New Brunswick, NJ, USA

b Research Assistant, University of Medicine and Dentistry of New Jersey, New Brunswick, NJ, USA

Address for correspondence: Rajesh Sachdeo, MD, Director, NJ Comprehensive Epilepsy Center, St. Peter’s University Hospital, 254 Easton Avenue, CARES Building, 4th floor, New Brunswick, NJ 08903, USA. Tel.: +1 (732) 565-5478; Fax: +1 (732) 745-2980; email: [email protected]

Copyright Librapharm Jul 2005

Key words: Cryptosporidium parvum * Giardia lamblia * Nitazoxanide * Persistent diarrhea

ABSTRACT

Despite advances in the management of diarrheal disorders, diarrhea is the second most frequent illness in the world. Persistent diarrhea, common in community pediatrics, is often caused by organisms such as Giardia lamblia, Cryptosporidium parvum and, less frequently, Cyclospora, Isospora belli, and Clostridium difficile. Identifying the causative organism is often challenging, and diagnostic tests may be inaccurate and expensive and, thus, of limited benefit. Consequently, carefully chosen empiric therapy guided by a physician’s clinical impressions may be a useful and cost-effective option in children with persistent diarrhea, particularly those whose signs and symptoms suggest a protozoal etiology. This article discusses the empiric use of anti-infective nitazoxanide, a thiazolide compound, in three case reports of children with persistent diarrhea, and presents an overview of the diagnostic and therapeutic issues associated with this disorder and the pharmacodynamics and pharmacokinetics of the drug.

Introduction

Diarrhea is the second leading cause of death among children worldwide and is responsible for approximately 2 million deaths annually’. In the United States, diarrhea is a frequent presenting complaint among children, accounting for 10% of office visits for children younger than 3 years of age2. In a substantial number of patients of all ages, acute diarrhea (≤ 14 days duration) develops into persistent diarrhea (> 14 days duration) without associated findings, such as abdominal pain or weight loss, and poses a significant challenge in terms of effective treatment. Diarrhea that lasts > 30 days is classified as chronic3. Although diarrhea is known to be caused by viruses, bacteria, and parasites, identifying the causative organism is often problematic; laboratory studies may be more costly than clinical impressions, physical examinations, and the outcome of empiric therapy, and may yield false-negative results. A thorough history and physical examination provide the basis for determining whether the child needs further diagnostic tests or consultation with a gastroenterologist. However, if the child with persistent diarrhea is otherwise healthy, empiric therapy may be a reasonable consideration. Fortunately, medications for the treatment of persistent diarrhea are available, effective and inexpensive.

Antiprotozoal agents used in the management of persistent diarrhea include metronidazole (Flagyl*) and, more recently, nitazoxanide (Alinia[dagger]). The following case studies illustrate how the early use of nitazoxanide can effectively manage persistent diarrhea before costly and time-consuming tests are performed to identify the cause.

Case reports

The efficacy of empiric nitazoxanide in children with chronic or persistent diarrhea is undergoing evaluation at the Children’s Center for Digestive Health Care in Atlanta, Georgia, and will be the subject of future publications. Nitazoxanide has been approved by the US Food and Drug Administration as a suspension for the management of diarrhea caused by Giardia lamblia and Cryptosporidium parvum in children aged 1 to 11 years and as a tablet for the management of diarrhea caused by G. lamblia in children and adults aged 12 years and older3. The following case reports derive from patients clinically evaluated and treated by the author as outpatients in this subspecialty practice.

Case 1

A 14-month-old (10.5kg) male previously treated with amoxicillin for bilateral otitis media presented with a 1-month history of diarrhea that persisted despite the implementation of a lactose- free diet. The patient’s history was negative for risk factors for persistent diarrhea (Table 1), and the results of physical examination were unremarkable. Bowel movements were loose, mucoid, and occurred three to eight times daily. Stools were negative for blood, white blood cells, bacterial pathogens, Clostridium difficile toxins, yeast, and ova and parasites. The patient was treated with nitazoxanide suspension 100mg bid (9.52mg/kg bid) for 3 days. Symptoms resolved with therapy, and treatment was well tolerated with only mild bloating.

Case 2

A 12-month-old, 9.5kg male with a history of eczema and gastroesophageal reflux presented with a 3- to 4-week history of diarrhea and vomiting. The mother reported that the infant had three to five large, loose stools daily. The patient’s hypoallergenic formula was lactose-free, and the only medication he was taking was a proton pump inhibitor. The child was afebrile and showed no abnormalities on physical examination. Results of a complete blood cell count and tissue transglutaminase values were within normal limits. Stool culture and examination were negative for ova and parasites and fungi or other pathogens; the stool was also negative for blood and leukocytes. The infant was treated with nitazoxanide suspension 100mg bid (10.5mg/kg bid) for 3 days. Over the next 4 days, symptoms resolved, stool consistency improved, and the number of bowel movements decreased. The treatment was well tolerated with no adverse reactions. The patient remained well.

Table 1. Risk factors for diarrhea in children

Case 3

An 8 -year-old, 30.7kg male presented with a 2-week history of intermittent diarrhea, abdominal discomfort, malodorous stools, anorexia and weight loss. Prior to the onset of the diarrhea, the patient had received amoxicillin/clavulanic acid for culture- confirmed group A streptococcal pharyngitis. Although the family had a septic system, their water was supplied by the city. The patient’s medical history was unremarkable except for surgery to correct transposition of the great vessels at 8 days of age. Guaiac testing revealed trace amounts of blood in the stool; C. difficile toxins were not detected by immunoassay. The stool was negative for bacterial pathogens, ova and parasites, and fungi. The patient was prescribed nitazoxanide suspension 200 mg bid (6.5mg/ kg bid) for 3 days. The treatment was well tolerated with no adverse reactions. His symptoms improved within 2 days, and he remained well thereafter.

Discussion

In case 1, the patient was evaluated after the primary care physician had failed to find a pathogen through standard diagnostic tests. Although the patient’s treatment with an earlier antibiotic suggested the possibility of an opportunistic infection, stools were negative for C. difficile toxin and smear for yeast. Alteration of this patient’s diet indicated that lactose intolerance, a common cause of diarrhea in the United States4, was not responsible for this patient’s diarrhea. The choice was to continue performing potentially diagnostic studies and possibly delay treatment or initiate a 3-day presumptive course of nitazoxanide, which would be more costefficient, with the knowledge that if the patient did not respond we could quickly proceed with the additional diagnostic tests. Initiating therapy with nitazoxanide resolved diarrheal symptoms and obviated the need for additional laboratory testing. Thus, this therapeutic intervention saved the patient and his family from a comprehensive workup for other causes of prolonged diarrhea that would have been unrevealing.

Case 2 demonstrates the efficacy and safety of nitazoxanide, administered as recommended by the manufacturer, for a child who met the criteria of the Infectious Diseases Society of America for persistent diarrhea. The probability of common noninfectious causes for the patient’s symptoms was decreased by a careful history, physical examination, and limited laboratory studies. However, the duration of symptoms and their prompt resolution after treatment suggest that the diarrhea had an infectious etiology or that nitazoxanide is effective for persistent diarrhea for which no cause could be identified at this time.

As in case 1, the history of the patient in case 3 certainly suggests the possibility of infection with C. difficile. The patient had received broad-spectrum antibiotic therapy within the previous month, but the immunoassay of the stool for C. difficile toxins A and B was negative. Although the immunoassay for the toxin is not as sensitive as cytotoxicity in a cell culture system, the patient was not believed to have antibioticassociated diarrhea or colitis. In addition, information from the manufacturer indicates that C. difficile is sensitive to nitazoxanide3. As in the previous cases, empiric nitazoxanide therapy was effective. Further testing still may have failed to demonstrate the etiology of the patient’s gastrointestinal manifestations while adding cost and time.

As demonstrated by these cases, the evaluation and effective management of diarrhea characterized by a duration of 14 days or longer is clinically challenging. Although the differential diagnosis is broad, a clinical history is invaluable in guiding physicians toward the appropriate evaluation of each patient with diarrhea. When treating patients with persistent diarrhea, it is important to rule out common noninflammatory disorders56. Patients with diarrhea of 2 to 3 days duration rarely necessitate a workup unless they present with fever, bloody diarrhea, or severe abdominal pain. However, there are a substantial yet ill-defined number of patients whose diarrhea becomes persistent witho\ut associated findings, such as abdominal pain and weight loss. As demonstrated in all three cases, a complete history, including a dietary and medication history as well as a detailed description of the patient’s diarrhea, describing the color, consistency, and frequency of elimination of the stools, is important in evaluating patients with persistent diarrhea. Patients with persistent diarrhea may be infected with parasites such as Giardia and Cryptosporidium, or less common parasites such as Entamoeba histolytica, Cyclospora, and Isospora belli. C. difficile is a potential, common causative pathogen for diarrhea that persists beyond 3 days in hospitalized patients and patients who have recently taken broad-spectrum antibiotics, such as the patient in case 3(7).

Identifying the causative organism

The causes of persistent diarrhea typically differ from those of acute or chronic diarrhea. The probability that persistent diarrhea is caused by a non-dysenteric organism increases significantly after excluding the following from the diagnosis: postinfectious or primary lactose intolerance, chronic nonspecific diarrhea, and the prodromal manifestations of other chronic diarrheal states (i.e., celiac syndrome, inflammatory bowel disease).

Of the parasites associated with persistent diarrhea, Giardia is the most frequently diagnosed in public health laboratories in the United States8. Illness caused by infection with C. parvum has been linked to water from swimming pools, fountains, public water supplies, and institutions such as hospitals9. Blastocystis hominis is a protozoan parasite commonly identified in stool specimens. There is ongoing debate about the pathogenicity of this organism10. Some studies suggest that it is an etiologic agent of persistent diarrhea, whereas others are unable to demonstrate an association between symptoms and the presence of the organism in the stool11- 13.

Diagnostic testing

For patients with persistent diarrhea, attempts to identify the responsible organism, guide treatment, and help contain healthcare costs can be problematic. Common tests include stool examination for ova and parasites; immunofluorescence and enzyme immunoassay for Giardia and Cryptosporidium; acid-fast stains for Cryptosporidium, Cyclospora, and lsospora; polymerase chain reaction for Cryptosporidium; acid-fast stains or culture for Mycobacterium avium complex; and chromotrope or other stains for Microsporidia7. The most common laboratory test for diagnosing C. difficile mediated disease is an enzyme immunoassay that detects toxins A and B. This test provides results within 2 to 6 hours with a specificity of 93% to 100% and a sensitivity of 63% to 99%’4. The majority of combination enzyme immunoassays have a sensitivity of 85% to 95%15.

While it is not within the scope of this paper to discuss diagnostic testing at length, many diagnostic laboratories are unable to identify the organisms associated with persistent diarrhea. According to studies, the detection rate for Giardia is 67% in a single specimen submitted for microscopic ova and parasite examination, and 85% when three specimens are submitted on 3 separate days16,17. Thus, even under the best circumstances, this pathogen is not detected in approximately one of every six patients. Importantly, the performance of most of these tests relies on skill sets not available in all laboratories, and the accuracy of the results depends on other factors such as proper collection and delivery. If stools are not placed in preservatives or examined immediately, the sensitivity can fall. Moreover, the turnaround time and reporting of test results may delay therapy.

Empiric therapy as a diagnostic tool

Although the acceptance of empiric therapy is not universal among physicians, it is counterproductive to delay treatment in a patient who is ill (and unable to work or attend school) while waiting for the results of diagnostic testing; this often leads to diagnostic evaluations with poor positive predictive values. Separating pediatrie patients whose diarrhea is self-limiting from patients infected with Giardia or Cryptosporidium also may support the role for empiric therapy. Although the Infectious Diseases Society of America guidelines recommend empiric therapy in patients who have traveler’s diarrhea and febrile diarrhea, the role of empiric therapy in patients with other types of diarrhea is still unclear7. However, as demonstrated in all three of the cases described here, particularly case 1, the use of empiric therapy enables physicians to initiate treatment based on clinical impressions – a comprehensive history and clinical examination – of the patient, thus obviating the need for invasive testing that may increase the cost of care.

Common antiprotozoal agents

The most common antiprotozoal agents used in persistent diarrhea are metronidazole and nitazoxanide, both of which are effective in the management of giardiasis in children aged 2 to 11 years. Both treatments have been well tolerated18. While therapeutic equivalence between these two drugs is important, other distinguishing features may make nitazoxanide the better choice. For example, it may be advantageous to use a drug such as nitazoxanide, which is approved for both children and adults and covers both Cryptosporidium and Giardia. There are no data supporting the use of metronidazole in the management of Cryptosporidium. Also, metronidazole is associated with a potential risk of genotoxicity7,19,20. Other factors to consider are that nitazoxanide can be dosed twice daily whereas metronidazole requires three-times-daily dosing, and nitazoxanide is available in a strawberryflavored oral suspension, which may impact compliance in pediatrie patients. Also, because the length of therapy for nitazoxanide is shorter than for metronidazole (3 vs. 5 days), there may be cost benefits to using the former. Recommended nitazoxanide dosage and administration are shown in Table 2(21).

Table 2. Nitazoxanide dosage and administration21

Nitazoxanide

Mechanism of action

The antiprotozoal activity of nitazoxanide appears to result from interference with the pyruvate-ferredoxin oxidoreductase (PFOR) enzyme-dependent electron transfer reaction, which is essential to anaerobic energy metabolism (Figure I)22. Studies have shown that the PFOR enzyme from G. lamblia directly reduces nitazoxanide by a transfer of electrons in the absence of ferredoxin. The DNA-derived PFOR protein sequence of C. parvum appears to be similar to that of G. lamblia, accounting for the activity of nitazoxanide against both pathogens23’24. Because of its selectivity, nitazoxanide does not appear to be mutagenic22.

Pharmacokinetics

Following oral administration, nitazoxanide is rapidly hydrolyzed to the active metabolite, tizoxanide (desacetyl-nitazoxanide). Tizoxanide undergoes conjugation, primarily by glucuronidation. Tizoxanide has no significant inhibitory effect on cytochrome P450 enzymes. The parent drug nitazoxanide is not detected in plasma following oral administration. Maximum plasma concentrations of the active metabolites tizoxanide and tizoxanide glucuronide are observed within 2 to 4 hours of administration. In plasma, > 99% of tizoxanide is bound to protein. Pharmacokinetic parameters of tizoxanide and tizoxanide glucuronide are shown in Table 3(21).

Figure 1. Pyruvate-ferredoxin oxidoreductase (PFOR)-dependent metabolic pathway. Adapted from Dunne et al.22 CoASH, reduced coenzyme A; Fd(ox), ferredoxin oxidised; Hyd, hydrogenase; Fd(red), ferredoxin reduced; CoA, coenzyme A; RNO^sub 2^, prodrug metronidazole.

Tizoxanide is excreted in the urine, bile, and feces, and tizoxanide glucuronide is excreted in the urine and bile. Nitazoxanide oral suspension is not bioequivalent to the tablet. The relative bioavailability of the suspension is 70% compared with the tablet23″26.

Clinical studies

Nitazoxanide is safe and generally well tolerated27’28. In the course of 31 clinical studies, 2983 children were exposed to the drug3. In controlled and uncontrolled studies in 613 children treated with nitazoxanide oral suspension, the most commonly reported adverse events were abdominal pain (48/613 patients; 7.8%), diarrhea (13/613 patients; 2.1%), vomiting (7/613 patients; 1.1%), and headache (7/613 patients; 1.1%)3. All events were mild and transitory. The administration of nitazoxanide was not associated with a significant effect on hematologie parameters, clinical chemistry values, or urinalysis test results. In placebo-controlled clinical studies in children treated at the recommended doses, the rates of occurrence of adverse events did not differ significantly between nitazoxanide and placebo3.

Table 3. Pharmacokinetic parameters of tizoxanide and tizoxanide glucuronide21

Table 4. Spectrum of activity of nitazoxanide in preclinical studies

Safety and efficacy

Nitazoxanide has been shown to be both safe and effective in the treatment of children with giardiasis29, cryptosporidiosis4-28, and blastocystosis (personal communications, J.-F. Rossignol, Romark Institute for Medical Research). Studies demonstrate high efficacy rates (> 80%) for nitazoxanide compared with placebo; rates as high as 86% for C. parvum30 and 85% for G. lamblia29 have been reported. Studies by the manufacturer indicate that nitazoxanide is also safe and effective when used against a number of other parasites that may cause persistent diarrhea (Table 4)24’3U33. In fact, the drug has shown activity against some diarrhea-causing bacterial pathogens, including C. difficile31.

Conclusion

In selected situations, following a careful history and physical examination, some patients may be better served by empiric therapy than by extensive diagnostic evaluations. Certainly, in pediatrie patients with persistent diarrhea without serious symptoms such as fecal blood or leukocytes, a therapeutic trial with an appropriate antiprotozoal agent would be wor\thwhile. The broad efficacy of nitazoxanide against organisms responsible for persistent diarrhea and its favorable safety profile provide a foundation for the rational use of empiric therapy in this population. Moreover, as supported by the case studies reported herein, the apparent success of nitazoxanide against diarrhea for which no cause has been identified suggests an infectious etiology for the disorder or a broad spectrum of efficacy for the drug. Because persistent diarrhea continues to be a huge public concern worldwide, the potential of nitazoxanide in the management of lower gastrointestinal tract pathogens warrants further investigation and may lead to the earlier clinical use of this agent or its use as a diagnostic measure.

Acknowledgement

Declaration of interest: The author received a grant in 2005 from Romark Pharmaceuticals (Tampa, FL), the manufacturer of nitazoxanide.

The author is also grateful for the assistance provided by Medesta Publications in the preparation of this manuscript, funded by Romark Pharmaceuticals.

* Flagyl is a trade name of Pharmacia Corporation, Chicago, IL

[dagger] Alinia is a trade name of Remark Laboratories, Tampa, FL

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27. Rossignol JF, Ayoub A, Ayers MS. Treatment of diarrhea caused by Giardia intestinalis and Entamoeba histolytica or E. dispar: a randomized, double-blind, placebo-controlled study of nitazoxanide. J Infect Dis 2001;184:381-4

28. Amadi B, Mwiya M, Musuku J, et al. Effect of nitazoxanide on morbidity andmortality in Zambian children with cryptosporidiosis: a randomised controlled trial. Lancet 2002;360:1375-80

29. Ortiz JJ, Chegne NL, Gargala G, et al. Comparative clinical studies of nitazoxanide, albendazole and praziquantel in the treatment of ascariasis, trichuriasis and hymenolepiasis in children from Peru. Trans R Soc Trop Med Hyg 2002;96:l-4

30. Rossignol JF, Hidalgo H, Feregrino M, et al. A ‘double- blind’ placebo-controlled study of nitazoxanide in the treatment of cryptosporidial diarrhoea in AIDS patients in Mexico. Trans R Soc Trop Med Hyg 1998;92:663-6

31. McVay CS, RolfeRD. In vitro and in vivo activities of nitazoxanide against Clostridium difficile. Antimicrob Agents Chemother 2000;44:2254-8

32. Megraud F, Occhialini A, Rossignol JF. Nitazoxanide, a potential drug for eradication of Helicobacter pylori with no crossresistance to metronidazole. Antimicrob Agents Chemother 1998;42:2836-40

33. Sisson G, Goodwin A, Raudonikiene A, et al. Enzymes associated with reductive activation and action of nitazoxanide, nitrofurans, and metronidazole in Helicobacter pylori. Antimicrob Agents Chemother 2002;46:2116-23

CrossRef links are available in the online published version of this paper: http://www.cmrojournal.com

Paper CMRO-2949_4, Accepted for publication: 29 April 2005

Published Online: 24 May 2005

doi: 10.1185/030079905X50534

Stanley A. Cohen

Children’s Center for Digestive Health Care, Atlanta, GA, USA

Address for correspondence: Dr Stanley A. Cohen, Children’s Center for Digestive Health Care, 993 D Johnson Ferry Road, #440, Atlanta, GA 30342, USA. Tel.: +1-404-257-0799; Fax: +1-404-503- 2280; email: [email protected]

Copyright Librapharm Jul 2005

Although peripheral arthritis is the most common extra- intestinal manifestation of inflammatory bowel disease, it is very rarely addressed in the orthopaedic literature. The overwhelming majority of patients with inflammatory bowel disease present with gastrointestinal symptoms and do not have any joint involvement until much later. We present the case of a patient who had joint pain and swelling but lacked any sign of gastrointestinal involvement. After five months of work-up, the patient was diagnosed with Crohn disease and the joint symptoms improved with appropriate medical treatment. We believe that inflammatory bowel disease should be considered in the differential diagnosis of joint pain and swelling. Our patient was informed that data concerning the case would be submitted for publication.

Case Report

A twenty-two-year-old male active-duty sailor in the United States Navy presented with a six-week history of right knee pain following a twisting injury that he had sustained while climbing a ladder on a ship; the knee twisted as the trunk rotated on the planted ipsilateral foot. At the time of the initial orthopaedic evaluation, the patient reported that pain and swelling in the right knee had failed to respond to a course of anti-inflammatory medication and activity modification. There was no history of clicking, catching, locking, or snapping. A review of systems was negative for fevers, chills, nausea, vomiting, recent sexual contact, recent weight loss, loose stools, abdominal pain, or a history of other joint pain or swelling.

Physical examination of the knee revealed a moderate effusion, normal appearance of the skin, mild warmth to touch, and decreased range of motion from 0 to 100 secondary to pain and swelling. There was diffuse tenderness of the anterior fat pad but no tenderness at the joint line. Provocative testing of the knee in varus and valgus, the Lachman test, the McMurray test, and the drawer tests all revealed negative results. Strength and sensation in the lower extremity were normal. At this point, the patient was treated nonoperatively with anti-inflammatory medications, activity modification, and a directed course of physical therapy.

At the four-week follow-up visit, the patient still had pain, swelling, and persistent effusion of the right knee. Aspiration of the right knee yielded 10 mL of bloody fluid that revealed an inflammatory effusion with a large amount of red blood cells (165,000), and some white blood cells (22,000). A gram stain revealed polymorphonuclear leukocytes without organisms, and an analysis of the synovial fluid showed no crystals. Because of the persistence of pain, warmth, and effusion but lack of mechanical symptoms, the differential diagnosis included pigmented villonodular synovitis, traumatic knee injury (meniscal tear or ligament injury), and advanced patellofemoral pain syndrome.

A magnetic resonance imaging scan demonstrated intact cruciate and collateral ligaments and normal menisci. A moderate joint effusion was evident along with thickening of the synovium that was consistent with synovial hyperplasia, but no pigmented villonodular synovitis was seen (Figs. 1-A and 1-B). The patient underwent arthroscopy of the knee for the performance of partial synovectomy. On arthroscopic examination, the synovium was found to be markedly hypertrophic, especially in the anterior and medial and lateral gutters of the knee (Figs. 2-A and 2-B). Histologic examination of the synovitic material demonstrated acute and chronic inflammation, granulation tissue, histiocytes, subsynovial multinucleated giant cells, fibrin deposition, and microscopic hemosiderin deposition. However, despite the hemosiderin deposition, there was no nodular or villonodular proliferation consistent with pigmented villonodular synovitis (Fig. 3). Laboratory data obtained at this time demonstrated a microcytic anemia (hemoglobin level of 12.1 g/dL [121 g/L], hematocrit of 36.3% [0.363], mean corpuscular volume of 71 fL, an erythrocyte sedimentation rate of 51 mm/hr, and a C-reactive protein level of 15.7 mg/dL [0.16 mg/L]). Due to the inflammatory nature of the findings, additional laboratory data were obtained, including phenotyping for HLA B-27 (human leukocyte antigen B-27) and testing for antinuclear antibody (ANA) titers and rheumatoid factor, all of which revealed negative results. Additional physical therapy was prescribed, and a rheumatologic consult was obtained.

Figs. 1-A and 1-B T1-weighted (Fig. 1-A) and T2-weighted (Fig. 1- B) sagittal magnetic resonance images of the right knee, demonstrating moderate effusion and synovitis. There is a large collection of fluid in the knee; however, there are no characteristic findings of pigmented villonodular synovitis.

Approximately six weeks after surgery, the patient presented with similar symptoms in the contralateral knee. The rheumatologic work- up demonstrated a similar inflammatory knee effusion and a worsening microcytic anemia (the results of iron studies were consistent with iron deficiency), and an anteroposterior radiograph of the pelvis demonstrated sclerosis and early erosive changes of the sacroiliac joints without ankylosis. An upper gastrointestinal series with small-bowel follow-through was ordered. (With this test, the patient drinks barium and then radiographs are made as the contrast medium empties out of the small intestine and into the large intestine. Although the test is not specifically used to study the colon, pathological processes can be visualized as the contrast medium travels through the colon.) The small-bowel follow-through revealed a cobblestone mucosal pattern of the entire colon with absence of the haustral pattern and likely backwash ileitis with narrowing of the ileocecal valve. A colonoscopy demonstrated focal chronic and active colitis with microabscesses and granulomatous inflammation with necrosis throughout the colon. The ulcerations, the focal nature of the changes, the granulomatous inflammation, and the extension of the inflammation below the mucosa were consistent with a diagnosis of Crohn disease, a chronic inflammatory gastrointestinal disease of unknown etiology.

Figs. 2-A and 2-B Arthroscopic view from the lateral portal, demonstrating marked synovitis in the medial (Fig. 2-A) and lateral gutters as well as in the suprapatellar pouch (Fig. 2-B).

Fig. 3

Photomicrograph of the synovial biopsy specimen, demonstrating acute and chronic inflammatory cells, granulation tissue, multinucleated giant cells, and microscopic hemosiderin deposition without nodular or villonodular proliferation (hematoxylin and eosin, 10).

Soon thereafter, the patient began to have multiple loose stools, with cramping, each day, arthralgia in the left hip and right wrist, episcleritis in the right eye, and approximately ten deep, pus- filled ulcers on the anterior aspect of the leg. The ulcers each were approximately 1 cm in diameter and were confirmed by biopsy to be pyoderma gangrenosum. These new clinical findings, together with the findings of inflammatory arthritis of the knee and sacroiliitis, further supported the diagnosis of Crohn disease. The patient was treated with sulfasalazine, high-dose prednisone, azathioprine, and iron. The knee pain and swelling, diarrhea, episcleritis, synovitis, anemia, and pyoderma gangrenosum all resolved, and the patient was able to taper off the oral corticosteroid medication over a two- month period. He returned to full military duties, without recurrent effusion or pain in either knee.

Discussion

Acute knee injuries are common in young adults. We describe the case of a young man with no pre-injury joint symptoms who presented with a low-energy injury to the knee along with diffuse swelling, effusion, and loss of motion that persisted despite rest, physical therapy, and anti-inflammatory medications. A magnetic resonance imaging scan was ordered to help narrow the differential diagnoses to either trauma or synovitis. Although there were no gastrointestinal symptoms, the patient’s rheumatologist suspected that the diagnosis was inflammatory bowel disease on the basis of the findings of anemia, oligoarthritis, and asymptomatic sacroiliitis; however, it was not until the colonoscopy was performed that Crohn disease was confirmed.

Musculoskeletal manifestations of inflammatory bowel disease include peripheral arthritis, granulomatous monarthritis, sacroiliitis, and ankylosing spondylitis1, with peripheral arthritis being the most common manifestation2. The knees are the most commonly affected joints2,3, followed by the ankles, elbows, wrists, and shoulders1. The symptoms include pain, swelling, tenderness, and a decreased range of motion1,2. As the inflammation in one joint abates, another joint often becomes affected. The arthritis usually resolves within one to three months after the onset of symptoms and is self-limited, with approximately 90% of the episodes lasting four weeks or less4. Joint erosion is rare. In one series, 71% of thirty- four cases of peripheral arthritis that occurred with Crohn disease were oligoarticular4. Extra-articular manifestations are rare in patients with Crohn disease. In one study3 of patients with Crohn disease, the rate of pyoderma gangrenosum was 1.1% (five of 449) and the rate of iritis or uveitis was 6.4%(twenty-nine of 449) but there were no cases of hemolytic anemia. However, when cutaneous or ocular symptoms are seen in addition to articular manifestations, abdominal disease should be suspected.

The link between inflammatory bowel disease and peripheral arthritis has been established. Several studies have described the prevalence of peripheral arthritis in patients with Crohn disease to be 11% (seventeen of 160) to 16% (eighty-four of 521)5,6. Crohn disease does not seem to affect one gender more than the other; one study4 showed that 13% (eight) of sixty-three men and 14% (fifteen) of 104 women had peripheral arthritis.

Peripheral arthritis usually is manifested only after the inflammatory bowel disease has been diagnosed for some time6. The case of our patient reflects the rare presentation of peripheral arthritis prior to the onset of gastrointestinal symptoms. The severity of the arthritis usually mimics the activity of the bowel disease, and the arthritis usually abates with medical treatment3, underscoring a direct relationship between intestinal exacerbations and joint symptoms2,3. Extraintestinal manifestations are most frequently encountered with ileocolitis (28% to 61% of cases), then colitis (range, 26% to 47% of cases), and then ileitis (13% to 19% of cases)2,3,6. Surgery of the affected joint probably does not influence the natural history of peripheral arthritis; rather, medical management is the mainstay of therapy because the disease is due to a systemic process.

Various theories have been proposed with regard to the method in which inflammatory bowel disease causes peripheral arthritis. One such theory suggests that the gastrointestinal tract acts as a protective barrier between the gut and the serum until inflammation in the bowel causes an increase in gut permeability, which leads to transfer of bacterial antigens from the gut to the serum. Additionally, there may be cross-reactivity between antigens in the intestine, synovium, skin, eyes, and biliary tree7. Furthermore, the bacterial products lead to activation of immunoregulatory cells, complement, and proinflammatory cytokines7,8. The synovial fluid and tissue show nonspecific inflammatory changes2; however, several case reports have demonstrated noncaseating granulomas of the synovium9- 11.

The primary care provider is usually the first to diagnose an inflammatory bowel condition and is therefore more likely to be alert to the extra-articular manifestations of these conditions3. However, on occasion, the orthopaedic surgeon may be the first physician to evaluate a patient with persistent joint pain and swelling and thus should be aware of the extraarticular systemic causes of joint pain and swelling.

References

1. Levine JB. Extraintestinal manifestations of inflammatory bowel disease. In: Kirsner JB, editor. Inflammatory bowel disease. 5th ed. Philadelphia: Saunders; 2000. p 397-409.

2. Resnick D. Enteropathic arthropathies. In: Resnick D, Niwayama G, editors. Diagnosis of bone and joint disorders. 2nd ed. Philadelphia: Saunders; 1988. p 1219-30.

3. Veloso FT, Carvalho J, Magro F. Immune-related systemic manifestations of inflammatory bowel disease. A prospective study of 792 patients. J Clin Gastroenterol. 1996;23:29-34.

4. Munch H, Purrmann J, Reis HE, Bertrams J, Zeidler H, Stolze T, Miller B, Korsten S, Cremers J, Strohmeyer G. Clinical features of inflammatory joint and spine manifestations in Crohn’s disease. Hepatogastroenterology. 1986; 33:123-7.

5. Salvarani C, Vlachonikolis IG, van der Heijde DM, Fornaciari G, Macchioni P, Beltrami M, Olivieri I, Di Gennaro F, Politi P, Stockbrugger RW, Russel MG; European Collaborative IBD Study Group. Musculoskeletal manifestations in a population-based cohort of inflammatory bowel disease patients. Scand J Gastroenterol. 2001;36:1307-13.

6. Palm O, Moum B, Jahnsen J, Gran JT. The prevalence and incidence of peripheral arthritis in patients with inflammatory bowel disease, a prospective population-based study (the IBSEN study). Rheumatology (Oxford). 2001;40:1256-61.

7. Levine JB, Lukawski-Trubish D. Extraintestinal considerations in inflammatory bowel disease. Gastroenterol Clin North Am. 1995;24:633-46.

8. Wollheim FA. Enteropathic arthritis: how do the joints talk with the gut? Curr Opin Rheumatol. 2001;13:305-9.

9. Al-Hadidi S, Khatib G, Chhatwal P, Khatib R. Granulomatous arthritis in Crohn’s disease. Arthritis Rheum. 1984;27:1061-2.

10. Toubert A, Dougados M, Amor B. Erosive granulomatous arthritis in Crohn’s disease. Arthritis Rheum. 1985;28:958-9.

11. Hermans PJ, Fievez ML, Descamps CL, Aupaix MA. Granulomatous synovitis and Crohn’s disease. J Rheumatol. 1984;11:710-2.

BY LIEUTENANT MARIUSZ A. OLSZEWSKI, MD, MEDICAL CORPS, UNITED STATES NAVAL RESERVE, COMMANDER RICHARD E. MANOS, MD, MEDICAL CORPS, UNITED STATES NAVAL RESERVE, COMMANDER PETER J. WEIS, MD, MEDICAL CORPS, UNITED STATES NAVAL RESERVE, AND LIEUTENANT COMMANDER MATTHEW T. PROVENCHER, MD, MEDICAL CORPS, UNITED STATES NAVAL RESERVE

Investigation performed at the Departments of Orthopaedic Surgery and Rheumatology, Naval Medical Center San Diego, San Diego, California

Lieutenant Mariusz A. Olszewski, MD, Medical Corps, United States Naval Reserve

Commander Richard E. Manos, MD, Medical Corps, United States Naval Reserve

Commander Peter J. Weis, MD, Medical Corps, United States Naval Reserve

Lieutenant Commander Matthew T. Provencher, MD, Medical Corps, United States Naval Reserve

Departments of Orthopaedic Surgery (M.A.O., R.E.M., and M.T.P.) and Rheumatology (P.J.W.), Naval Medical Center San Diego, 34800 Bob Wilson Drive, Suite 112, San Diego, CA 92134-1112

The authors did not receive grants or outside funding in support of their research or preparation of this manuscript. They did not receive payments or other benefits or a commitment or agreement to provide such benefits from a commercial entity. No commercial entity paid or directed, or agreed to pay or direct, any benefits to any research fund, foundation, educational institution, or other charitable or nonprofit organization with which the authors are affiliated or associated.

The views expressed in this article are those of the authors and do not reflect the official policy or position of the Department of the Navy, the Department of Defense, or the United States government.

doi:10.2106/JBJS.D.01822

Copyright Journal of Bone and Joint Surgery, Inc. Aug 2005

‘INFERTILITY time-bomb warning”; “infertility on the rise”; “women can’t ‘have it all'” – the news can make grim reading forwomen in their thirties who have not yet started a family. This week, the fertility specialist Lord Winston declared that youngerwomen should be encouraged to take time out of their careers to have children, to avoid the heartache of leaving it too late.

Yet the facts belie this dismal picture. The truth is that for a woman in her late thirties who wants to have a baby, the odds are still in her favour. The number of babies born to women over 35 has doubled in the past decade. A new book, Conception and Pregnancy over 35, seeks to cater for this growing constituency. Professor Lesley Regan, head of obstetrics and gynaecology at St Mary’s Hospital, Imperial College, London, writes in the foreword that “conceiving in the late thirties will probably, but not necessarily, take a bit longer” and that “most couples are successful eventually”. But why does it take longer? And is there anything you can do to speed things up?

1How likely am I to experience problems conceiving?

Women over 35 experience a decline in fertility as a result of a decrease in the number and health of their eggs, an increasing likelihood of medical problems such as diabetes and hypertension, and less frequent sex. They may also experience unrecognised miscarriages as a result of chromosomal problems. Also, ageing affects the uterus by, for example, increasing the chance of fibroids (growths of fibrous tissue), making it more difficult for fertilised eggs to implant.

According to Dr Laura Goetzl, an American specialist in high- risk pregnancy and the principal author of Conception and Pregnancy over 35, that does not mean you should assume the worse.

While you may have a longer conception time, “it is best to assume that you will become pregnant within a year or so and confidently make plans to achieve conception”. Most couples conceive within a year.

2Why is 35 such an important age?

Thirty-five is “a bit of an oldfashioned definition”, according to Dr Richard Kennedy, a consultant obstetrician and gynaecologist at Walsgrave hospital, Coventry.

“There’s no magical definition at which it’s more difficult to conceive, ” he says. “However, the risks are raised the closer you are to 40, particularly with first babies.”

Sheena Young, Scottish spokeswoman for the Infertility Network, adds that some women will experience no noticeable decline in their fertility at 35;

indeed, it is “not unusual” for women to be fertile in their forties and a few remain so in their fifties.

3If I already have children, am I less likely to have problems?

If you have had a baby at 33 and are then trying to have another by the same man at 37, then the chances of having difficulties are probably less than if you were trying for the first time at 37, according to Dr Kennedy.

4What can I do to assist my chances of conceiving?

Stay healthy. Healthy eating can help your chances of conceiving by boosting your general health and hormonal balance. Eat a wellbalanced diet, containing all the main food groups. Go for complex carbohydrates and remember to drink plenty of water. Folic acid is an important nutrient pre-conception and many women take it in supplement form. It decreases the risk of neural tube birth defects which affect the brain and spinal cords and occur in the first month after conception. Maintain a sensible body weight: being very overweight is associated with lower fertility, while underweight women may not ovulate regularly. It is also worth establishing a good exercise programme before you conceive when you still have plenty of energy. Strength training, especially of the abdominals, will help prevent back pain during pregnancy.

Discuss any pre-existing medical conditions with your doctor.

5Do I have to give up drinking and smoking?

Avoid binge-drinking. You should avoid smoking, as it has been linked to decreased fertility.

6My wife and I are planning to start a family. Is there anything I can do to boost our chances of conceiving?

Apart from the obvious, you should avoid binge-drinking or smoking very much. In addition, the Infertility Network advises that men should try to keep the area around the scrotum cool.

7Do I have to have “timed sex” with my partner?

Some doctors, including DrGoetzl, advocate “timed sex” – in other words, having sex around times when the woman is at hermost fertile. Methods of predicting this include calculating your ovulation period and monitoring fluctuations in body temperature.

Dr Kennedy, however, counsels caution. He says: “For a couple who are having regular sex, two to three times a week, their chances are as good as having timed intercourse.”

Timed sex has downsides, particularly in terms of changing the dynamic of the sexual relationship. According to Dr Kennedy, it may be more beneficial for people who are having sex infrequently.

8It is disheartening to find you’re still not pregnant month after month. Can stress and worry make things worse?

It is hard to prove conclusively, but the anecdotal evidence is strong.

Stress can get tied up in a vicious cycle with fertility problems – it can impare ovulation, making conception more difficult, which in turn creates more stress. If it helps to try alternative therapies, then do so. Dr Goetzl advises planning a “fertility holiday”where you and your partner are not trying to conceive.

9If we do have trouble, what sort of tests and treatments can we have?

Your partner’s sperm can be tested and a questionnaire and blood tests carried out to make sure you are ovulating. If all is normal, you may be given an examination to see if your fallopian tubes are open or to look at your uterus. Treatments vary. In women with polycystic ovary disease, fertility pills may be enough. If not, the next step is a combination of hormone injections and assisted fertilisation, in which your doctor introduces a sample of your partner’s sperm into your uterus. If your partner’s sperm count is low, your fallopian tubes are blocked, or other treatments fail, you will probably be offered in vitro fertilisation. IVF involves combining your eggs with your partner’s sperm in a petri dish in the lab. If there are problems with your partner’s sperm, a single sperm can be injected into your eggs – intra cytoplasmic sperm injection (ICSI) – and the healthy embryos returned to the uterus.

10 When should I seek help?

If you are over 35, have followed advice relating to diet, exercise and body weight and have not conceived within sixmonths, you should “touch base”with your family doctor to discuss possible tests, according to Dr Kennedy.

After one year, he recommends specialist referral. The age cut- off for assisted conception (IVF and ICSI) in Scotland is 38. Sheena Young says: “With waiting lists being what they are, the age of the female partner is crucial.”

The National Infertility Awareness Campaign has welcomed an indication by the Scottish Executive yesterday that it will consider a waiting time target for infertility treatment. There are huge variations Scotland-wide.

Lorraine Sloan: “I thought I’d never have a family” There are plenty of high-profile women who have conceived and given birth in their late thirties or forties. Madonna, 47 this month, gave birth to Lourdes at 38 and Rocco just before her 42nd birthday while Cherie Blair had Leo, now five, at the age of 45. Celebrities benefit from the attentions of personal nutritionists, trainers and others to help them stay fit, but many women over 35 have happy stories of trouble-free conceptions and pregnancy – sometimes against the odds.

Lorraine Sloan, 37, was 35 when she got pregnant. The pregnancy was unplanned and all the more unexpected as she had a hormone imbalance, polycystic ovary syndrome and endometriosis. She was prescribed drugs and originally medics thought she would neither work again nor have a family. Now successfully running her own business as an alternative therapist, the Angel Sanctuary in Clydebank, she has defied predictions on both fronts. She says:

“They had diagnosed me with polycystic ovary syndrome and wanted to take my ovaries out at 24.

“I just consoled myself that I would not have a family.”

Lorraine decided not to rely on drugs, but turned to alternative therapies instead, such as Reiki.

Then the unexpected happened.

“I was feeling a bit sick and I knew there was something happening to me inside, ” she says. She remembers detecting a change in herself the first week of her pregnancy, a sensitivity she puts down to being attuned to her own body through practising alternative therapies. She went on to have Jack, who is now coming up for two.

Even without such problems to overcome, few women over 35 take pregnancy for granted.

Elaine Bell, 38, mother of Murray, one, says that she was surprised to get pregnant at 36 “pretty much immediately”.

“I never thought I would get pregnant so quickly, ” she says. “All the literature says that fertility drops as you get older, that highpressure jobs have an impact and so on.

“But most of my friends conceived first time, too.”

THE BABY BOOM

Births among women aged 35+ in Scotland as a percentage of overall births

35-39 40-44 45+

1976-80 4.4 0.9 0.0

1986-90 5.8 0.9 0.0

1994 8.7 1.2 0.0

1999 12.8 2.0 0.1

2004 6.5 3.0 0.1

Results of common laboratory tests must be interpreted with care in older adults. Laboratory results that vary with age are presented, along with possible causes and interpretations of results.

John Doe, 83 years old, comes to the clinic complaining of increasing fatigue and weakness. His past medical history includes diabetes mellitus, chronic anemia, and hypertension. The 5’10” man is thin (148 pounds) with small muscle mass. His skin color is pale pink. A battery of diagnostic tests reveals the following: hemoglobin 11.2 g/dL, hematocrit 40%, white blood cells 5,000/ml, fasting blood sugar 183 mg/dL, blood urea nitrogen 30 mg/dL, serum creatinine 1.9 mg/dL, and serum albumin 2.3 g/dL. The nurse is uncertain which laboratory values are significant in considering Mr. Doe’s care plan.

This case illustrates the difficulty in interpreting laboratory values for older adults, which is a complex task with varied opinions about what is normal. Multiple confounding factors make interpretation and use of laboratory results in older patients challenging. Some of the factors include (a) physiologic changes associated with aging, (b) the high prevalence of chronic conditions, (c) changes in nutrition and fluid consumption, (d) lifestyle changes, and (e) pharmacologie regimes (Brigden & Heathcote, 2000). Laboratory test results also may be affected by many factors other than aging. Influencing factors may include gender, body mass, alcohol intake, diet, and stress (Fischbach, 2004). Technical factors such as collection site, collection time, tourniquet application, and specimen transportation also can affect results but usually can be controlled by following standardized laboratory procedures (Brigden & Heathcote, 2000).

Results of diagnostic testing in older adults may have different meanings from the results found in younger individuals. Nurses should recognize that no general trend exists for the direction of change in laboratory values for older adults. For some tests, older adults have higher than normal values and for others, lower values; some remain unchanged. Changes in laboratory values can be classified in three general groups: (a) those that change with aging; (b) those that do not change with aging; and (c) those for which it is unclear whether aging, disease, or both influence the values (Tripp, 2000). Common laboratory tests with interpretations for older adults are presented.

Interpreting Reference Ranges

The accepted, normal ranges of values typically reported may not be applicable for older adults. Reference ranges may be more appropriate. Normal ranges are obtained by determining the mean of a random sample of healthy individuals, usually ages 20 to 40 years, in order to identify two standard deviations on either side of the mean. The concept of normal range, however, is not useful in determining age-related norms for older adults (Luggen, 2004).

Reference ranges or reference values are preferred concepts. Reference ranges or reference values are those intervals within which 95% of the values fall for a specific population (Lab Tests Online, 2001). For example, geriatric reference ranges are those intervals within which 95% of values for persons over 70 years of age would fall. It must be cautioned, however, that some researchers recommend not using reference ranges for laboratory test parameters pertaining to older adults because it is difficult to differentiate whether results are a sign of a disease or are related to normal aging (Luggen, 2004). However, reference ranges are useful in some situations. The use of reference ranges allows for recognition of the special needs of the population in question. Reference ranges are calculated not just for older adults, but also for neonates (especially low-birthrate infants), adolescents, and pregnant women. In addition, specific reference ranges are known for tests for other special populations (for example, serum erythropoietin in adult athletes such as marathon runners).

Laboratory values falling outside the normal ranges may indicate benign or pathologic conditions in the older adult (Fischbach, 2004). Values within the expected normal reference ranges, however, may also indicate new or progressing pathologic conditions in certain older adults. Nurses working with older adults should consider the total assessment rather than simply relying on laboratory diagnostic testing. For example, goals of management of diabetes should be individualized. The principal goal would be to enhance quality of life without undue risk of hypoglycemia. It usually is best to achieve fasting blood glucose levels of less than 140 mg/dl. However, in the frail elderly, it is best to avoid fasting or bedtime plasma glucose levels of less than 100 mg/dl if the patient is on insulin or sulfonylurea treatment (Reed & Mooradian, 1998).

Serum creatinine is a second example of a laboratory test in which results may be within the specified reference range and yet indicate pathology for the older adult. Creatinine is a product of creatine phosphate, used in skeletal muscle contraction. Endogenous creatinine production is constant as long as muscle mass remains constant (Pagana & Pagana, 2002). The mechanisms that regulate the older individual’s serum creatinine levels within the accepted reference range tend to overestimate renal functioning as a measure of glomerular filtration rate. Serum creatinine and blood urea nitrogen (BUN) levels in the high-normal category may represent significant renal dysfunction in the older adult who has inadequate protein intake (Daniels, 2002).

Specific Laboratory Tests

Hemoglobin (HGB). While the results of studies of the effects of aging on the hematologic system vary (Brigden & Heathcote, 2000; Nilsson-Ehle, Jagenburg, Landahl, & Swanborg, 2000), research does indicate that older individuals may have changes in hemoglobin and erythrocyte synthesis caused by changes in iron and vitamin B12 absorption (Giddens, 2004). Impaired erythrocyte production, blood loss, increased erythrocyte destruction, or a combination of conditions have also been identified as causes for lowered hemoglobin (Giddens, 2004). Kee (2002) defines hemoglobin as abnormal if less than 13.5 gm/dl for males and 12.0 gm/dl for females. Recent studies with older adults, however, suggest lower levels may be acceptable. The currently reported lowest acceptable value for older adults is 11.5 gm/dl for males and 11.0 gm/dl for females (Brigden & Heathcote, 2000) (see Table 1).

Hemoglobin may be lower in older adults due either to normal aging changes or illnesses such as anemia. Manson and McCance (2004) identify impaired erythrocyte production, blood loss, increased erythrocyte destruction, or a combination of conditions as causes for anemia. Most instances of anemia are associated with chronic conditions such as renal insufficiency or gastric bleeding (Giddens, 2004). Anemia may be a serious condition because it places the older individual at greater risk for circulatory and oxygenation problems (Tripp, 2000). A reduction of hemoglobin can result in a decrease in oxygen content and an increase in fatigue. Signs of anemia may not be noticed if the anemia is mild, but some individuals may present with shortness of breath, fatigue, and paresthesia (Manson & McCance, 2004). A combination of vague symptoms and an unclear clinical picture may lead the health care provider to attribute the symptoms to “old age” and not to a treatable condition.

Hematocrit (HCT). Changes in hematocrit may reflect fluid and/or nutritional status in the older adult (Fischbach, 2004; Giddens, 2004). An increase in the hematocrit may signal volume depletion, while a decrease may be a result of conditions accompanied by fluid overload or dietary deficiencies. Hematocrit, the percentage of total blood volume that represents erythrocytes, may be normal if values are 30% to 45% for older males and 36% to 65% for older females (Desai & Isa-Pratt, 2002) (see Table 1).

Table 1.

Geriatric Laboratory Values and Interpretations of Hematology

White blood cells (WBC). Whether total leukocyte count is affected by aging is controversial. However, there are definite changes in that the T cells are less responsive to infection (Fulop et al., 2001; Sester et al., 2002). Immunity gradually declines after age 30 to 40 years (Rybka et al., 2003) (see Table 1). A decreased WBC value may result from specific disease (myeloma, collagen vascular disorders), infection or sepsis (pneumonia, urinary tract infections), or medications (cytotoxic agents, analgesics, phenothiazides), and should not be attributed to advancing age (Fischbach, 2004). This lowered WBC count in a healthy individual may result in an absence of elevated white blood cells in the presence of severe infection. Medications such as steroids also may influence the immune response (Giddens, 2004). Because of the slower immune response, common symptoms of infections, such as enlarged lymph glands, fever, or pain, may be decreased in severity or absent in the older adult (Beers & Berkow, 2000). Nurses should be vigilant in efforts to detect other signs of infections in the older adult, such as confusion. Because of the concern for serious undetected infection, nurses should educate older adults about infection prevention techniques, such as hand washing and timely vaccination for influenza and pneumonia.

Platelets (Pit). Aging usually causes a decl\ine in bone marrow function, which may contribute to lowered platelet counts and decreased platelet function (Luggen, 2004). Studies also suggest that platelet adhesiveness increases with age, with no changes in numbers (Thibodeau & Patton, 2004). The ability of the older adult’s body to respond to major blood loss by regenerating platelets may be inadequate, leading to inadequate clotting (Beers & Berkow, 2000) (see Table 1). The patient also must be assessed for potential or hidden blood losses, such as occult blood in stools and emesis.

Table 2.

Geriatric Laboratory Values and Interpretations of Erythrocyte Sedimentation Rate, Iron Metabolism, and Vitamin B12

Erythrocyte sedimentation rate (ESR). Brigden (1999) noted that the erythrocyte sedimentation rate increases with age, but the cause of this increase is unknown. ESR measures the rate at which red blood cells (RBCs) settle in 1 hour. An annual rate of increase in time of sedimentation rate for older adults has been quantified at 0.22 mm/hour/year from age 20 years (Duthie & Abbasi, 1991). An elevated ESR may indicate the presence of inflammation. Inflammation causes an alteration in blood proteins, making the RBCs heavier and causing them to settle faster (Fischbach, 2004). The acceptable reference range for the older adult is 40 mm/hour for males and 45 mm/hour for females (Brigden & Heathcote, 2000) (see Table 2). Because a slight elevation may or may not reflect the presence of an underlying inflammation, confirmation of a clinical problem may be difficult. Nurses should rely on other assessment factors, such as visible inflammation, pain, or fever, to determine a possible clinical condition.

Serum iron. Serum iron is decreased in many older adults, resulting in iron deficiency anemia as the most common form of anemia seen in older adults (Tripp, 2000) (see Table 2). One possible explanation is an agerelated decrease in hydrochloric acid (HCl) in the stomach (Beers & Berkow, 2000). HCI is important for facilitating iron absorption in the intestines. Serum iron, total iron-binding capacity, and iron stores decrease with age (Daniels, 2002). When there is a decrease in iron stores, serumferritin increases and serum transferrin decreases. The decrease in transferrin levels may indicate a decrease in liver synthesis (Lab Tests Online, 2004). Decreased iron storage and irondeficiency anemia, however, commonly are caused by inadequate dietary intake of iron or loss of iron through chronic or acute blood loss (Beers & Berkow, 2000). Nursing assessment should include a dietary assessment for reduced intake of iron-containing foods and assessment of occult bleeding from the gastrointestinal tract.

Table 3.

Geriatric Laboratory Values and Interpretations of Serum Proteins

Vitamin B12. Brigden and Heathcote (2000) report that serum vitamin B12 levels may decrease slightly with age (see Table 2). The deficiency in B12 may be due to chronic atrophie gastritis, an immune dysfunction that occurs more often in older adults, or from a deficiency of HCl, both leading to insufficient intrinsic factor and insufficient absorption of vitamin B12 (Beers & Berkow, 2000). The low end of the reference range for vitamin B12 is 150 pg/mL in the older adult as opposed to 190 pg/mL in a younger adult (Brigden & Heathcote, 2000) (see Table 2). Assessment for pernicious anemia, including checking for neuropathies, such as weakness, difficulty walking, and numbness or tingling, should be considered whenever anemia is present.

Total protein and albumin. Some serum protein levels, such as albumin and total protein, decline in older adults (Beers & Berkow, 2000). Changes in protein may reflect decreased liver functioning or inadequate nutritional intake (Beers & Berkow, 2000). While all serum proteins are reduced, albumin is the most significantly influenced by aging (Beers & Berkow, 2000). Albumin levels decrease each decade over the age of 60, with a marked decrease over 90 years of age (Daniels, 2002). In addition to being an indicator of disease or malnutrition, low serum albumin is the most common cause of a low serum calcium level in older adults, because most serum calcium is protein-bound (Beers & Berkow, 2000) (see Table 3).

Renal function. As mentioned previously, relying on commonly accepted laboratory values in determining renal function in the older adult is difficult. The age-related 30% to 45% decrease in functioning renal tissue and the glomerular filtration rate (GFR) leads to a decline in the creatinine clearance (Brigden & Heathcote, 2000). Commonly occurring reduction in lean body mass, decreased dietary protein intake, or decreased hepatic function may lead to decreases in the end products of metabolism, BUN, and creatinine (Brigden & Heathcote, 2000). BUN and creatinine levels overestimate renal functioning, as measured by GFR or creatinine clearance, because of the changes in body composition (Engelberg, McDowell, & Lovell, 2000; Luggen, 2004). A decrease in the lean body mass, relatively common in older adults, results in reduced protein degradation and nitrogen byproducts of metabolism (BUN). The decline in muscle mass also results in less creatinine production; serum creatinine values thus remain within normal limits despite diminished renal clearance capacity (Brigden & Heathcote, 2000) (see Table 4).

When considering age-related changes, most physicians and advanced practice nurses question the adequacy of BUN and creatinine as indicators of renal function (Kennedy-Malone, Fletcher, & Plank, 2004). Therefore, measurement of urinary creatinine clearance takes on special significance in the older adult. Serum creatinine is affected by both decreased GFR and body mass, while urinary creatinine clearance is affected only by glomerular filtration (Lewis et al., 2004). Determining renal function by creatinine clearance examination is especially useful when treating the older adult with medications because of the potential for the development of drug toxicity, even with usual doses (Daniels, 2002). Because it may be difficult to perform a creatinine clearance on the older patient, a formula can be used to estimate creatinine clearance values. For men, the formula is shown in Table 5 (Brigden & Heathcote, 2000). For women, the value determined from the formula is multiplied by 0.85. Normal ranges for creatinine clearance are 104 to 140 ml/minute for men and 87 to 107 ml/minute for women (see Table 4). Nurses should not assume that all changes in renal function are due to aging. Chronic urinary tract infections, benign prostatic hypertrophy, prostatic tumors, and diabetic neuropathy are also causes and should be ruled out (Lewis et al., 2004).

Table 4.

Geriatric Laboratory Values and Interpretations of Selected Renal Function Tests

Table 5.

Estimating Creatinine Clearance Values for Men

Table 6.

Geriatric Laboratory Values and Interpretations of Hepatic Enzymes

Table 7.

Geriatric Laboratory Values and Interpretations of Blood Lipids

Table 8.

Geriatric Laboratory Values and Interpretations of Glucose, Selected Electrolytes

Hepatic enzymes. The aging process does not significantly influence most hepatic laboratory test values (for example, bilirubin, ammonia, and lipids.) While lactic dehydrogenase (LDH) is not affected by aging, the enzymes gamma-glutamyl-transferase (GGT), serum aspartate aminotransferase (AST, SCOT), and alkaline phosphatase are affected (Brigden & Heathcote, 2000). GGT levels increase with aging (Tietz, Shuey, & Wekstein, 1997). AST increases slightly for individuals 60 to 90 years of age to 18 U/L to 30 U/L (Tietz et al., 1997). Serum alanine aminotransferase (ALT, SGTP) levels peak about 50 years of age and gradually fall to levels below those of younger adults by age 65 (Kelso, 1990). Alkaline phosphate (AP) increases with age to a level of 30 U/L to 140 U/L and is associated with age-related malabsorption, bone disorders, or decreased liver or renal functioning (Brigden & Heathcote, 2000) (see Table 6).

Table 9.

Geriatric Laboratory Values and Interpretations of Selected Blood Gases

Lipid profile. Lipid-related changes in aging adults younger than 70 years old are initially noted as increases in cholesterol, high- density lipoproteins (HDL), very low-density lipoprotein (VLDL), and triglycerides. Serum cholesterol increases as much as 40 mg/dl by age 60 in men and age 55 in women (Brigden & Heathcote, 2000). No increase is seen in adults over 90 years old; in fact, some very old adults will have decreased cholesterol levels (Tietz et al., 1997). The mean HDL increases 30% in men but decreases 30% in women between ages 30 and 80 (Brigden & Heathcote, 2000). Triglyceride levels increase by 30% in men and 50% in women between the ages of 30 and 80 years (see Table 7).

Glucose. Serum glucose levels increase slightly but steadily with age in parallel with a decrease in glucose tolerance. The normal reference range for serum glucose is broader for older adults, from 70 mg to 120 mg/100 ml (Tripp, 2000) (see Table 8). Older individuals may have lower glucose levels, reflecting poor nutritional status or overall loss in body mass (Kennedy-Malone et al, 2004). However, higher serum insulin levels are more commonly seen in older adults and may suggest insulin resistance, which is responsible for impaired glucose tolerance in 25% of individuals over age 75 (Kennedy-Malone et al., 2004). If insulin receptors do not respond to the same fasting level of glucose in old age as they did when the patient was younger, glucose intolerance without insulin-secretion changes could be the explanation. A reference value for the 2-hour postprandial glucose tolerance blood sugar test (PPBS) is calculated with the following formula (Brigden & Heathcote, 2000):

* 2-hr PPBS (mg/dl) = 100 + age in years (for patients over age 40)

Serum electrolytes. In most reports, electrolyte values remain well within the standard reference values \for older adults. Calcium levels increase in older patients (ages 60 to 90) but decrease in the very old over age 90 (Martin, Larsen, & Hazen, 1997). The initial increase can be explained by a decrease in serum pH and an increase in parathyroid hormone levels found in older individuals (Tietz et al., 1997). If the individual has a low serum albumin, however, the serum calcium level will most likely be low as mentioned previously. Serum potassium has been reported to increase slightly with age (Kennedy-Malone et al., 2004); however, most researchers use the same reference values as for younger adults (see Table 8).

Arterial blood gases (ABGs). Reference values for ABGs differ in older adults from those of younger adults. Stiffening of the elastic lung structures, decreased number of functioning alveoli, and decreased strength of the diaphragm are age-related changes that decrease respiratory functioning (Martin et al., 1997). The decreased respiratory functioning results in a decrease in the partial pressure of arterial oxygen tension (PaO^sub 2^). The arterial pressure decreases approximately 5/6 every 15 years starting at age 30 (Brigden & Heathcote, 2000). A formula (Brigden & Heathcote, 2000) has been devised to estimate arterial oxygen in older adults:

Table 10.

Geriatric Laboratory Values and Interpretations of Thyroxine, Triiodothyronine, Prostate-Specific Antigen

* PaO^sub 2^ (mmHg) = 100.1 – (0.325 X age in years)

Additionally, a corresponding increase in the carbon dioxide pressure (pCO^sub 2^) of approximately 2% per decade occurs after age 50. The bicarbonate-ion concentration also increases with age, balancing out the pO^sub 2^ and maintaining a normal blood pH (Brigden & Heathcote, 2000) (see Table 9).

Thyroid function tests. Changes in thyroid function in the older adult may be the most challenging problem for nurses as they try to separate disease from aging changes. Hypothyroidism is seen in 2% to 6% of the general population over age 70 (Kennedy-Malone et al., 2004). Free thyroxine (FT4) levels decrease progressively with age (Kennedy-Malone et al., 2004). Triiodothyronine (T3) shows substantial decreases in ages 30 to 80 years. Typically, a 20% change in T3 occurs during the lifetime of the older adult (Beers & Berkow, 2000) (see Table 10).

Prostate-specific antigen (PSA). Relevance of PSA values to support aggressive treatment is controversial (National Cancer Institute, 2004). Because an elevation in the PSA could be indicative of benign prostatic hypertrophy or prostate cancer, results from this test alone should not drive therapy. Because of false positives and false negatives, the agerelation variation of PSA increases difficulty in treatment decisions. Reference ranges for PSA with age are (a) 60 to 69 years: 0.0 to 5.0 ng/ml, and (b) 70 to 79 years: 0.0 to 6.3ng/ml. Men who have had a radical prostatectomy are expected to have values of 0.0 to 0.3 ng/ml (Daniels, 2002) (see Table 10).

Implications

Laboratory test results inform health care providers of a patient’s changing condition. The presence of multiple diseases, as well as the incidence of polypharmacy, may be a source of confusion in the clinical interpretation of laboratory results. Often, nurses must ask, “What test results are significant and suggest the presence of disease? Which results suggest changes in patient conditions that require further assessment or interventions?” Greater understanding of how to interpret laboratory test values in relation to the clinical picture for the older adult allows nurses to provide age-appropriate assessments and interventions.

Mr. Doe’s laboratory reports illustrate the confusion surrounding evaluating laboratory data for the older adult. Are his diagnostic test results helpful in explaining his fatigue and weakness? What really is happening with him? Perhaps the slightly elevated renal function tests indicate normal changes of aging. However, they also might be due to protein malnutrition, which is suspected because of his low body weight and recent weight loss. Obtaining serum protein and urinary creatinine studies as well as a thorough nutritional assessment might assist in defining the diagnosis.

Interpretation of laboratory test results allows nurses to rule out diagnoses that are not pertinent, but also assists in the examination of a broad spectrum of possibilities. Each laboratory may have variations in the reference ranges due to techniques and equipment. Nurses must work closely with laboratory personnel and pathologists to be informed about changes in reference ranges for older adults in a specific laboratory. Nurses also should educate other health care professionals about age-related variations in acceptable laboratory values. Better understanding of interpretation of diagnostic test results in older adults will allow nurses to feel confident about the care they provide.

References

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Luggen, A. (2004). Laboratory values and implications for the aged. In P. Ebersole & R Hess (Eds.), Toward healthy aging: Human needs and nursing response (6th ed.) (pp. US135). St. Louis: Mosby.

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Sester, M., Sester, U., Alarcon, S.S., Heine, G., Lipfert, S., Gerndt, M., et al. (2002). Age-related decrease in adenovirus- specific T cell responses. Journal of Infectious Diseases, 185(10), 1379-1387.

Thibodeau, G., & Ration, K. (2004). Structure and function of the body (12th ed.). St. Louis: Mosby.

Tietz, N.W., Shuey, D.F., & Wekstein, D.R. (1997). Clinical laboratory values in the aging population. Pure & Applied Chemistry, 69, 51-53.

Tripp, T. (2000). Laboratory and diagnostic tests. In A. Lueckenotte (Ed.), Gerontologic nursing (2nd ed.), pp. 405-424. St. Louis: Mosby.

Nancy Edwards, PhD, RN,C, is an Associate Professor, Purdue University School of Nursing, West Lafayette, IN.

Carol Baird, DNS, APRN, BC, is an Associate Professor, Purdue University School of Nursing, West Lafayette, IN.

Copyright Anthony J. Jannetti, Inc. Aug 2005