Psoriatic Arthritis List NEWSLETTER

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News & Views Newletter
edited by Jack Nicholas, cornishpro@aol.co

SORIATIC ARTHRITIS NEWS AND VIEWS
VOL. 3 ISSUE 5 April 1, 2003
PSORIATIC ARTHRITIS MEDICAL NEWS
INFECTION BEFORE ARTHRITIS?

PSORIATIC ARTHRITIS NEWS AND VIEWS
VOL. 3 ISSUE 6 April 25, 2003
PSORIATIC ARTHRITIS MEDICAL NEWS

INFLIXIMAB MAY BE EFFECTIVE IN TREATMENT OF POLYMYALGIA RHEUMATICA NEW YORK (Reuters Health) April, 2002

Infliximab may be a useful adjunct, and perhaps an alternative, for patients with steroid-resistant polymyalgia rheumatica (PMR), according to a report in the April issue of The Journal of Rheumatology.

Dr. Carlo Salvarani, of the Arcispedale S. Maria Nuova in Reggio Emilia in Italy, and colleagues examined whether treatment with infliximab had a steroid-sparing effect in four patients with relapsing PMR who were unable to reduce their dose of prednisone to less than 7.5 - 12.5 mg/day and had corticosteroid-related side effects.

The patients were given 3 mg/kg infliximab at weeks 0, 2, and 6, and were monitored for clinical signs and symptoms, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and interleukin-6 (IL-6) over 1 year.

The researchers report that 2 weeks after the first infusion, two patients had a complete response to infliximab. The patients had normal values of ESR and IL-6, and were able to stop prednisone. One patient had a complete and persistent clinical remission 2 weeks after the first infusion of infliximab. IL-6 remained elevated in this case, but ESR values were normalized during follow-up.

At the end of the 1-year follow-up, these three patients were free of symptoms and had normal ESR and CRP.

The fourth patient experienced continuous clinical activity. This was associated with elevated acute phase reactants during follow-up. However, compared to baseline, IL-6 levels were lower during follow-up, and the patient's prednisone dosage was reduced to 5 mg/day.

Dr. Salvarani and colleagues say these preliminary results are encouraging and point out that the sustained reduction in IL-6 is of particular interest, as it is "the main inducer molecule of the systemic acute phase reaction in PMR." They call for a controlled study to investigate further. J Rheumatol 2003;30:760-763.

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ARTHRITIS DRUGS CAN INCREASE CVD RISK IN HYPERTENSIVE PATIENTS NEW YORK (Reuters Health) April, 2003

Even the relatively small changes in systolic blood pressure associated with common arthritis medications can significantly increase the risk of cardiovascular disease (CVD), study findings suggest.

Corticosteroids and nonsteroidal anti-inflammatory can reduce the efficacy of anti hypertensive agents, Dr. Mason W. Russell and associates point out. Therefore, they recommend that clinicians consider the propensity of individual anti arthritis agents to increase blood pressure when prescribing for patients with hypertension and that they routinely monitor blood pressure.

Dr. Russell, of Medical Research International in Waltham, Massachusetts, and his team estimate the likelihood of CVD over 1 year among US adults with osteoarthritis and rheumatoid arthritis, based on data from the Third National Health and Nutrition Examination Survey and the Framingham Heart study.

For the 11.8 million individuals age 35 and older with hypertension and arthritis, an increase in systolic blood pressure of 1 mm Hg could cause approximately 7100 additional cases of ischemic heart disease and stroke annually, they report in the April issue of the Journal of Rheumatology. For an increase of 5 mm Hg, that rate would rise to 35,700, with associated healthcare costs of $569 million.

These figures are conservative since they do not take into account the added burden of congestive heart failure and angina, the authors note.

Some medications, such as indomethacin, are associated with greater hypertensive effects than others, points out Dr. Richard Day, of St. Vincent's Hospital and University of New South Wales, Sydney, Australia, in an editorial.

That risk is even higher when hypertension is present before the exposure, he adds, and it appears that cyclooxygenase-2 selective inhibitors do not appear to lower the risk.

"The co prescription of low-dose aspirin, beta-blockers, angiotensin-converting enzyme inhibitors, hypolipidemics, and other drugs relevant to CVD increasingly needs to be addressed and reviewed when advising and treating patients with rheumatic conditions," he writes. J Rheumatol 2003;30:642-645,714-719.

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CAN CELEBREX AND VIOXX TREAT PARKINSON'S - Blocking a key enzyme might help slow the progression of the disease By Jennifer Thomas - HealthScoutNews Reporter - April , 2003

Researchers have identified a brain enzyme that might contribute to the progression of Parkinson's disease. The good news is that arthritis drugs already on the market can block the activity of the enzyme, which means the finding could lead relatively quickly to a new Parkinson's treatment.

"As a clinician, I find the results very exciting," says Dr. Jay Van Gerpen, a neurologist and specialist in movement disorders at the Ochsner Clinic Foundation who was not involved with the research. "I am cautiously optimistic this could open up real treatment options in staving off the progression of Parkinson's disease."

The study appears in this week's issue of the Proceedings of the National Academy of Sciences.

Parkinson's disease is a degenerative disorder of the brain that affects about 1 percent of Americans over age 65. Symptoms include tremors, slowness of movement and muscle stiffness to the point of paralysis.

The cause of Parkinson's is not known. However, doctors do know Parkinson's results in a gradual destruction of the neurons that transmit the neurotransmitter dopamine. Dopamine is important in regulating movement.

Certain drugs, including levodopa, can reduce symptoms of Parkinson's disease by restoring dopamine levels. But no treatment has been proven to slow the progressive cell death, Van Gerpen says. As the cells continue to die, levodopa loses its effectiveness.

"Lots of people have been looking for something that could actually slow the progression of the cell death," he says.

In the current study, researchers may be getting closer. Researchers went looking for a particular enzyme, cyclooxygenase-2 (cox-2), in the brains of post-mortem Parkinson's patients and mice with a disease similar to Parkinson's.

Cox-2 is known to play a role in triggering the inflammation of osteoarthritis. Osteoarthritis can be effective treated with a relatively new class of drugs called cox-2 inhibitors, which help reduce the pain and swelling. These drugs include Celebrex and Vioxx, which are prescribed to people who can't tolerate aspirin or other painkillers.

Previous research had also implicated cox-2 in other neurodegenerative diseases, including Alzheimer's and amyotropic lateral sclerosis (ALS, or Lou Gehrig's disease), although the role in those diseases is not as well understood.

"Because we knew of the cox-2 inhibitors' effectiveness in treating other diseases where inflammation was a factor, and because we knew that cox-2 could somehow be involved in these other neurodegenerative diseases, we put two and two together," says Serge Przedborski, senior author of the study and a professor of neurobiology and pathology at Columbia University. "We thought it was a natural study to assess what could be the role of cox-2 in Parkinson's."

Researchers found elevated levels of cox-2 in human brains with Parkinson's, and in mice brains with a MPTP, a condition that mimics Parkinson's.

Next, researchers gave the mice cox-2 inhibitors. They found more dopaminergic neurons survived -- about 88 percent of the neurons endured while on the drug, compared to 41 percent without the drug.

But Przedborski and his colleagues were surprised when they delved further into the mechanism. They'd expected to find that cox-2 was involved with inflammation in the Parkinson's patients.

But when the mice were give cox-2 inhibitors, they saw no reduction in inflammation.Instead, researchers believe the cox-2 enzyme may hasten cell death by causing oxidative stress, a process that causes the production of free radicals that damage surrounding cells. After enough damage, the cells die. Previous researchers had linked Parkinson's with oxidative stress.

"There is a large body of literature supporting the idea that oxidative stress plays a role in Parkinson's, but there was nothing that showed the mechanism," Przedborski says. "Cox-2 may be involved." The next step will be trying the cox-2 inhibitors in human trials with Parkinson's patients. "We can argue about the intimate mechanism, but that is an issue for researchers rather than patients," he says. "The beauty of the study is that many cox-2 inhibitors are already on the market. They have a track record; they are known to be reasonably safe."

While the cox-2 inhibitors seem very promising, Przedborski said it will not be a cure. "We've started to realize that the death of neurons is probably not the result of a single factor, but probably of multiple factors that interact with each other to ultimately kill the cell," he says.

To read more about Parkinson's disease, visit the Parkinson's Disease Foundation or the National Institute of Neurological Disorders and Stroke.

SOURCES: Serge Przedborski, Ph.D., professor, neurobiology and pathology, Columbia University, New York City; Jay Van Gerpen, M.D., neurologist, Ochsner Clinic Foundation, New Orleans; April 7-11, 2003, Proceedings of the National Academy of Sciences Copyright © 2003 ScoutNews, LLC. All rights reserved.

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OBESITY STRONGLY LINKED TO CANCER DEATH
By Salynn Boyles - WebMD Medical News Reviewed By Brunilda Nazario, MD April, 2003

A major new study from the American Cancer Society offers the strongest evidence yet that being overweight increases your risk of dying from cancer. Researchers suggest that as many as 90,000 cancer deaths in the U.S. each year may be related to obesity and could be prevented.

The cancer deaths were not confined to malignancies with known links to excess body weight, such as breast and colorectal cancers. The study identified many cancers not previously associated with obesity, including stomach cancer and prostate cancer in men, multiple myeloma, non-Hodgkin's lymphoma, and cancers of the cervix, ovary, prostate, liver, and pancreas.

"There is no question that this research shifts our thinking about the relationship between overweight and obesity to cancer mortality in general," lead researcher Eugenia E. Calle, PhD, tells WebMD. "Most people don't understand that being overweight or obese is a risk factor for cancer, so we hope it will increase that awareness." Calle directs the analytic epidemiology program at the American Cancer Society (ACS).

The research is published in the April 24 issue of The New England Journal of Medicine. Calle and American Cancer Society colleagues identified 57,145 cancer deaths among 900,000 people followed for 16 years. None of the participants had cancer when they enrolled in the study.

Researchers found that 14% of all cancer deaths among men and 20% of all cancer deaths in women were associated with being overweight or obese. For almost all cancers, the risk of death increased as body mass did. The heaviest men and women in the study were 52% and 62% more likely to die of cancer, respectively, than men and women of normal weight.

The researchers concluded that 90,000 cancer deaths a year in the U.S. are related to excess body weight and could be prevented if people maintained a normal body weight throughout their lifetime. That compares with 170,000 annual deaths attributed to smoking.

"It seems quite clear now that after tobacco smoking, obesity is emerging as the second quantitatively most important cause of cancer, at least in western populations," epidemiologist Hans-Olov Adami, MD, tells WebMD. "This is yet another very important reason for people to keep their weight under control."

Adami, who wrote an editorial accompanying the study, admits he is not optimistic that the new evidence will greatly affect behavior. He is professor and chairman of the department of medical epidemiology and biostatistics at the Karolinska Institute in Stockholm, Sweden.

"We know that there is an epidemic of obesity in the United States, and it is a growing problem throughout the western world," he says. "As long as we make food available in excessive portions on every commercial street corner around the clock and, at the same time, systematically remove all natural incentives to energy expenditure, it is hard to see how this will change."

SOURCES: The New England Journal of Medicine, April 24, 2003. Eugenia E. Calle, PhD, director of analytic epidemiology, American Cancer Society, Atlanta. Hans-Olov Adami, MD, professor and chairman, department of medical epidemiology and biostatitics, Karolinska Institute, Stockholm, Sweden. © 2003 WebMD Inc. All rights reserved.

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INFLAMMATION: A NEW LINK TO DISEASE By Karen Collins April, 2002

Inflammatory substances in body may help cancer spread. Researchers say eating foods high in omega-3 fats, such as salmon, may help protect our bodies against inflammation and the resulting risk of cancer and other diseases.

One of the current "hot topics" in health research is how inflammation affects our risk of heart disease, stroke, diabetes and even cancer. Scientists are increasingly focused on a certain kind of inflammation - specifically, the form that takes place deep in our cells and tissues - and the important role it may play in the development of disease.

NORMALLY, INFLAMMATION is a good sign. When your thumb swells up after you accidentally bang it with a hammer, it tells you that your immune system is sending white blood cells and other, hormone-like substances to help start the healing process. But not every kind of inflammation is that easy to see, and it's the invisible kind that takes place throughout our body, over and over again, that is attracting so much attention.

COX-2 is an enzyme in our bodies that boosts the production of inflammatory chemicals. Normally, these proteins and hormone-like substances are churned out by our immune systems with no ill effects. Under certain conditions, however, they may actually help cancer cells multiply and spread. That's why one type of anti-inflammatory drugs, collectively called COX-2 inhibitors, are under study for a potential role in preventing or treating cancers of the colon, uterus, breast, prostate and other tissues.

DOES NUTRITION PLAY A ROLE? And now, scientists are investigating whether the way we eat could also influence the kind of chronic inflammation that might be linked to cancer risk and other health problems. Around the world, different researchers are focusing on different aspects of the issue. Some are looking at how two families of polyunsaturated fats may work together to play a protective role.

Omega-3 fats are found mainly in fatty fish such as salmon, mackerel, and albacore (white) tuna, but are also found in flaxseeds and flaxseed oil, walnuts and canola oil. Omega-6 fats are found in many common vegetable oils (corn, safflower, sunflower). All are considered heart-healthy because they don't raise blood cholesterol. But when omega-6 fats predominate over omega-3 fats, something else happens: our bodies seem to increase COX-2 levels and produce more of the hormone-like substances that promote inflammation. When omega-3 and omega-6 fats are more balanced in the diet, fewer of these inflammatory substances are produced.

This is why some scientists believe that if we boost omega-3 fats with regular consumption of naturally fatty fish or sources like flax, and reduce our excess use of vegetable oils, spreads and high-fat snacks made with them, we might make the COX-2 in our bodies less active, and decrease the amount of inflammatory hormones that might be associated with cancer risk.

INFLAMMATION AND OBESITY
Other scientists are seeking to determine if inflammation may be one reason that obesity has been linked to higher cancer risk. Research now suggests that the body's fat cells produce cytokines (proteins that promote low-grade inflammation) and that the distribution of body fat might also play a role. A study in the Journal of the American Medical Association shows that one measure of inflammation increased by more than 50 percent in obese women whose fat was mainly in their hips and thighs ("pear-shaped"), and by more than 400 percent in obese women with significant waistline fat ("apple-shaped").

Interestingly, some studies now show that regular exercise may have precisely the opposite effect on the immune system, and may reduce levels of inflammatory proteins. This might help to explain why research has linked regular physical activity with lower cancer risk.

RESEARCH ON PLANT-BASED DIETS
Still other scientists, including many sponsored by the American Institute for Cancer Research, are investigating how an overall plant-based diet might help keep inflammation in check. Antioxidant nutrients and phytochemicals in fruits and vegetables protect cells' DNA from damage that can lead to cancer; and some evidence now suggests they may also lower production of inflammation-promoting hormones. In fact, a wide variety of natural phytochemicals found in fruits and vegetables are under investigation for possible COX-2 lowering effects.

All of this evidence linking diet to the kind of chronic inflammation associated with cancer risk is still preliminary, however, and it would be premature to change our diets if this was the only reason to do so. Of course, it isn't the only reason - a plant-based diet with plenty of fruits and vegetables, maintenance of a healthy weight and regular exercise is already a strategy that is estimated to lower cancer risk by 30 to 40 percent. We know that it works - the incoming research about inflammation may soon help us get a better idea of some of the how and why. Nutrition Notes is provided by the American Institute for Cancer Research in Washington, D.C.

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MEDICATION SIDE EFFECTS STRIKE 1 IN 4

Doctors often ignore problem, study finds. Researchers say the problem of drug side effects is important, in part, because adverse symptoms may discourage patients from taking vital medicines.

Side effects from prescription medicines plague one in four patients, and when they surface, most doctors fail to act, U.S. researchers said Wednesday. The study findings sound an alarm to the millions of Americans who take prescription drugs each year. 'It's a problem that is common, in many cases the impact could be prevented or reduced, and it has a large impact on patients.' - TEJAL GANDHI, Internist at Brigham & Women's Hospital in Boston

SOME 3.34 BILLION prescriptions were dispensed in the United States in 2002, according to IMS Health, a provider of pharmaceutical and health care data.

"It's a problem that is common, in many cases the impact could be prevented or reduced, and it has a large impact on patients," said Tejal Gandhi, an internist at Brigham & Women's Hospital in Boston and the chief author of the study, published in this week's New England Journal of Medicine,

Previous estimates have suggested that nearly 5 percent of hospital admissions - over 1 million per year - are the result of drug side effects. But most of the cases are not documented. The findings of the Gandhi team are based on prescriptions given to 1,202 adults in four outpatient clinics in Boston.

MANY SIDE EFFECTS PREVENTABLE
"They found that adverse drug events were fairly frequent and usually mild, although potentially serious, and preventable events were more frequent than any patient or clinician would like (or should be willing to accept)," William Tierney of the Indiana University School of Medicine said in an editorial.

Among the side effects, 13 percent were serious, such as low blood pressure or internal bleeding, and 39 percent were preventable or potentially treatable, such as cases where a drug was given to a patient known to be allergic to it.

In preventable cases, patients were given the wrong drug 45 percent of the time, the wrong dose was prescribed in 10 percent of the cases, and patients were told to take it too frequently 10 percent of the time.

"A lot of problems were going on a long time that weren't being fixed, either because the patients didn't tell the doctor or the physicians didn't change the medication. That was what surprised us," Gandhi told Reuters.

In nearly two-thirds of the cases, the side effects persisted because the doctor failed to heed the warning signs. Patients who suffered in the remaining cases did so because they never told the doctor about their symptoms.

'PROBLEM WILL ONLY GET WORSE'
Gandhi said the problem is important, in part, because side effects may discourage patients from taking vital medicines, potentially worsening their health.

Tierney said the medical community needs to use a variety of techniques to reduce side effects, such as computer programs that check doses or a system where patients are routinely interviewed about possible drug-related symptoms while they wait for their appointment.

"With these 10-minute appointments, it's hard for the doctor to get into whether the symptoms are bothering the patients," Gandhi said.

"In the absences of such efforts ... given the increasing number of powerful drugs available to care for the aging population, the problem will only get worse," Tierney said.

The drugs that posed the greatest risk of side effects were the serotonin-reuptake inhibitor class of antidepressants, the non-steroidal anti-inflammatory drugs often given for joint pain, and calcium-channel blockers used to treat high blood pressure.

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VITAMIN D + CALCIUM = GOOD BONES
By Jeanie Lerche Davis - WebMD Medical News Reviewed By Brunilda Nazario, MD

April, 2003 -- We need calcium for good bones, but vitamin D is equally important -- it helps the body with calcium absorption. In fact, calcium supplements plus vitamin D can increase calcium absorption by up to 65%.

The finding appears in the latest Journal of the American College of Nutrition.

It points to the increased need for people to take daily vitamin D supplements, says lead researcher Robert P. Heaney, MD, of Creighton University in Nebraska. Americans up to age 50 are advised to take 200 IU (international units) of vitamin D daily. From age 51 to 70, the advised dose is 400 IU. For people over age 70, it's 600 IU.

Vitamin D is also made in the skin when it is exposed to sunlight. However, concern about skin cancer has caused many people to limit their time in the sun. In addition, during the winter across the northern half of the U.S., there is an insufficient amount of the sun's rays reaching the skin to stimulate production of vitamin D, a news release states.

To look at this issue, Heaney and colleagues conducted two studies in the spring, one year apart, each involving 34 postmenopausal women with apparently normal blood levels of vitamin D.

In the first study, the women were first pretreated with a dose of .02 mg of vitamin D -- on alternative days, for three weeks -- to quickly increase their blood levels of vitamin D.

On the "study day," their blood was tested before breakfast. Then, they were given 500 mg calcium supplements -- but no vitamin D supplement -- to mimic a standard low-calcium breakfast. They were also given a low-calcium lunch a bit later. Their blood was tested before breakfast and at frequent intervals for 10 to 12 hours afterward to determine calcium absorption.

In the second study, women did not receive the pretreatment with vitamin D. They were simply given calcium supplements plus 200 IU of vitamin D supplements on the study day, plus a low-calcium lunch, and their blood was tested at similar intervals through the day.

The first study's results showed the positive effects of extra vitamin D over the long haul -- the women's blood showed from 45% to 65% greater levels of calcium.

Along with calcium supplements, people should take vitamin D to promote calcium absorption, Heaney states.

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SMOKING BOOSTS MEN'S RISK OF RHEUMATOID ARTHRITIS
NEW YORK (Reuters Health) March, 2003

Smoking may double the risk of rheumatoid arthritis in men, but it does not seem to affect women's risk of the disease, a new study from Finland suggests.

Researchers suspect that hormones such as estrogen may help explain why smoking does not seem to raise the risk of the disease in women, although they stress that more study is needed to understand the different effects of smoking in men and women.

Although the cause of rheumatoid arthritis is not very well understood, research suggests that age, smoking, obesity and genetic factors appear to play a role in the development of the disease, they explain.

In the current study, 1095 male and female Finnish patients previously diagnosed with rheumatoid arthritis were compared with 1530 healthy adults. The study was conducted by a team led by Dr. Eswar Krishnan of Stanford University in Palo Alto, California. A doubling of risk for rheumatoid arthritis was seen in men with a past history of smoking compared with men who had never smoked, Dr. Krishnan's team reports in the journal Arthritis Research and Therapy.

But the smoking-related risk was only seen among men who tested positive for rheumatoid factor. Dr. Krishnan's team points out that past research has shown that smoking boosts the production of these antibodies.

No relationship between smoking and increased risk of rheumatoid arthritis was seen in women, suggesting that estrogen or other sex differences may counteract the effects of smoking, according to the researchers. They propose that the menstrual cycle may help block the effect of smoking on rheumatoid factor and rheumatoid arthritis. But, they note that there were not enough data on the female participants' menopausal status to address this issue.

Overall, "data presented in this report suggest that factors related to the sex of an individual modify the effect of smoking on the risk of rheumatoid arthritis," the authors conclude. Arthritis Res Therapy 2003;5:158-162.

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INVESTIGATIONAL FIBROMYALGIA DRUG SUCCESSFUL IN PHASE II STUDY NEW YORK (Reuters Health) March, 2003

Cypress Bioscience Inc.'s milnacipran, a norepinephrine serotonin reuptake inhibitor, significantly reduced pain intensity and improved overall pain in a phase II study of fibromyalgia syndrome, lead investigator Dr. Daniel Clauw reported Friday.

Dr. Clauw, director of the University of Michigan's Chronic Pain and Fatigue Research Program, presented the results at the 22nd Annual Scientific Meeting of the American Pain Society. He is also chairman of Cypress' Rheumatology Advisory Board.

San Diego-based Cypress had released much of the data in February, but Dr. Clauw gave new information on pain intensity.

In the double-blind study, 125 patients were randomized to placebo or milnacipran once or twice daily. The patients had fibromyalgia syndrome for 5-to-7 years on average, Dr. Clauw said. The dose was escalated over the first 4 weeks to a plateau dose maintained for 8 weeks.

Patients who received the twice-daily dose had a statistically significant improvement in pain. Thirty-seven percent reported at least a 50% reduction in pain intensity compared with 14% of placebo patients. Seventy percent of all milnacipran-treated patients reported overall improvement compared with 36% of placebo patients.

The most commonly reported adverse event was nausea. About 27% of patients overall dropped out of the study, but that was no higher than expected, he said.

Cypress hopes to begin phase III studies late this year.

There are no approved drug therapies for fibromyalgia, but it is usually treated with tricyclic antidepressants. Milnacipran is currently approved to treat depression in 22 countries, including France and Japan.

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My sincere apologies to all our members for the delay in my April 15th issue. Our personal life was hit with the sudden illness and death of my brother from cancer. He fulfilled two roles in my life: brother, and best friend. I will miss him.

You may be only one person in the world, but you may also be the world to one person.

Good Health to All,

Jack Nicholas
Newsletter Editor
Cornishpro@aol.com<br>

Issue 2003 4/24/03 -6
INFECTIONS COMMONLY PRECEDE EARLY ARTHRITIS SYMPTOMS

NEW YORK (Reuters Health) - Patients with early arthritis often present with a history of recent infections, and such patients may be more likely to experience remission within 6 months of diagnosis, according to a report in the March issue of The Journal of Rheumatology.

Previous studies investigating the role of infections in arthritis have been inconclusive, the authors explain, and there is little information regarding the prognosis of arthritis associated with a prior infection.

Dr. Maria Soderlin from Vaxjo Central Hospital in Vaxjo, Sweden, and colleagues examined the prevalence of prior infection in 71 patients with arthritis of less than 3 months' duration and sought to determine whether prior infection influenced the clinical outcome after 6 months.

Overall, 32 patients (45%) had a prior infection verified either by positive serology and/or infection history, the authors report.

The most common infection in the 27 patients with reactive arthritis was involved Campylobacter jejuni, the report indicates, and 2 of 15 patients with rheumatoid arthritis had verified recent infections.

Remission rates were common after 6 months, the researchers note, with 22 of the 32 recently infected patients (69%) experiencing remission, compared with 15 of 39 patients (38%) without recent infections. One third of the patients with rheumatoid arthritis were in remission at the 6-month follow-up.

"In all, 45% of the patients in this study had an infection preceding the arthritis," the authors report, "indicating the importance of systematic surveillance for infections in patients presenting with early arthritis."

"It is clear that no overwhelming evidence exists to link any single known infectious agent with rheumatoid arthritis," Dr. Sara M. Carty from University Hospital of Wales in Cardiff, UK, and colleagues counter in a related commentary. "Studies need to be designed to examine specific models of interaction between rheumatoid arthritis and infection, addressing variables such as attack rate, delay in onset, and persistence of infection."

"The need for further study should not close our eyes to the possibility that rheumatoid arthritis is unrelated to infection," the commentators conclude.

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Barbara K. Hecht, Ph.D. and Frederick Hecht, M.D., Medical Editors for MedicineNet.com believe there are factors within the preceding article that needed further examination and comment. They therefore asked for an expert opinion from William C. Shiel, Jr., MD, who is an experienced practicing Rheumatologist (and Chief Editor of MedicineNet). Dr. Shiel responded as follows:

Firstly, "reactive arthritis" is a specific form of arthritis that has, for some decades now, been known to follow a number of infections. If these researchers are including cases of reactive arthritis in their study, then the study is simply not generalizable to patients with rheumatoid arthritis, an entirely different form of joint disease. Also, identifying specific organisms in patients with reactive arthritis can sometimes lead to cure with antibiotics. This is distinctly different from patients with rheumatoid arthritis.

Secondly, it is well appreciated already by practicing rheumatologists (arthritis specialists) that patients with rheumatoid arthritis have somewhat altered immune systems, making them more susceptible to infections, either before or after the onset of their arthritis. So noting infections prior to the onset of the arthritis condition is not breaking news.

And lastly, we must use extreme caution before accepting the idea that the cause of rheumatoid arthritis is directly related to infection. For years, researchers have been looking for single microorganisms to treat in order to eradicate the disease. To date, none has been identified. Nevertheless, aggressive research is yet underway as to the many possible causes of the disease, including aging immune cells, genes that are inherited, environmental exposures, and a variety of infections. Therefore, I completely agree with the final sentence at the conclusion of this report ("The need for further study should not close our eyes to the possibility that rheumatoid arthritis is unrelated to infection") and I would add that we should keep a close watch on upcoming reports. WILLIAM SHIEL, MD, FACP, FACR, CHIEF MEDICAL EDITOR

Dr. Shiel received a Bachelor of Science degree with honors from the University of Notre Dame. After graduating from St. Louis University School of Medicine, he completed his Internal Medicine residency and Rheumatology fellowship at the University of California, Irvine. He is board-certified in Internal Medicine and Rheumatology. He is a Fellow of the American Colleges of Physicians and Rheumatology.

Dr. Shiel is in active practice in the field of rheumatology in south Orange County, California. He is currently an active Associate Clinical Professor of Medicine at University of California, Irvine. He has served as chairman of the Department of Internal Medicine at Mission Hospital Regional Medical Center.

He served on the Medical and Scientific Committee of the Arthritis Foundation, and is currently on the Medical Advisory Board of the Lupus Foundation of America. Dr. Shiel is proud to have served as Chief Editor for MedicineNet.com since its founding in 1996.

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TEMPORARY DEFERRAL RECOMMENDED FOR HEART PATIENTS VOLUNTEERING FOR SMALLPOX VACCINATION

The Centers for Disease Control and Prevention took the precautionary step of adding a temporary medical deferral to the smallpox vaccination program for persons who have been diagnosed with heart disease. CDC is investigating whether there is any association between smallpox vaccination and reports of heart problems in seven health care workers who have been vaccinated.

CDC added the temporary measure to the existing list of deferral criteria based on information from its real-time monitoring system, which showed a small number of heart-related incidents among health care workers following smallpox vaccination. It is not clear whether this number is greater than would be expected normally in this population, CDC scientists said.

"We promised to closely monitor this program and to put safety first, so we are exercising exceptional caution," said Julie Gerberding, M.D., CDC director. "If our investigation shows this precautionary measure should become permanent or the need for other changes or enhancements in the civilian smallpox vaccination program, we will take immediate action." "We continue to believe that it is important and necessary to vaccinate health care workers to prepare our nation in the event we have to respond to a smallpox outbreak," Dr. Gerberding said.

CDC is recommending that persons with known cardiac disease - such as cardiomyopathy, previous heart attack, history of angina, or other evidence of coronary artery disease - be temporarily deferred from receiving smallpox vaccination. CDC will provide states with simple questions about heart p roblems to use in screening people volunteering for smallpox vaccination.

In pursuing its promise of safety, last week CDC asked the Advisory Committee on Immunization Practices' (ACIP) Smallpox Vaccine Safety Review Board to examine reports of heart-related adverse events occurring in connection with the smallpox vaccination program. CDC is also beginning research projects aimed at identifying and understanding any associations that may exist between smallpox vaccine and heart-related problems.

"A major part of our monitoring program involves regularly sharing information about adverse events with experts such as those on the ACIP. They can help assess whether the smallpox vaccine is, indeed, associated with the medical conditions described in the adverse event reports," said Walter Orenstein, M.D., director of CDC's National Immunization Program.

CDC has received several reports of heart-related problems among the 25,645 people who have been vaccinated in the civilian program. The seven cases prompting today's precautionary action include three cases of myocardial infarction (heart attack), one of which resulted in death; two cases of angina (chest pain); and two cases of myopericarditis (inflammation of the heart muscle or sac surrounding the heart). In each case the individual's medical history, including risk factors for heart disease, is being studied.

Cases of heart inflammation following smallpox vaccination were reported in the 1960s and 1970s. However, the information from these reports does not provide any information about the types of people who may be at higher risk for heart-related problems following smallpox vaccination.

CDC protects people's health and safety by preventing and controlling diseases and injuries; enhances health decisions by providing credible information on critical health issues; and promotes healthy living through strong partnerships with local, national, and international organizations.

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LIFE EXPECTANCY IN THE U.S. RISES

In 2001, life expectancy reached a new high of 77.2 years, up from 77 years in 2000. The increase applied to men and women as well as blacks and whites, according to a report.

The increase may be due to the continued progress, including fewer deaths, in the country's top three killers--heart disease, cancer and stroke. According to the report, the national age-adjusted death rate decreased from 869 deaths per 100,000 people in 2000 to 855 deaths per 100,000 in 2001.

Life expectancy for men reached 74.4 years in 2001, as compared to 74.3 years in 2000. For women, life expectancy increased from 79.7 years in 2000 to 79.8 years in 2001. Among white men and black men and women, record-high life expectancies were seen.

Among the nation's leading causes of death, mortality from heart disease decreased almost four percent, deaths from cancer two percent, stroke almost five percent, and accidents/unintentional injuries close to two percent. Deaths from influenza/pneumonia showed the biggest decrease among leading causes of death, decreasing more than seven percent.

The report includes a new sub-category for homicide--deaths from terrorism--that was added after the September 11 attacks. Overall, the U.S. homicide rate increased almost 17 percent from 2000 to 2001, however the increase is due to the many deaths of the September 11 attacks. The rate of non-terrorism homicide actually decreased slightly from 2000 to 2001.

Although HIV is the sixth leading cause of death among people aged 25 to 44 years, and a leading cause of death among African Americans in this age group, the age-adjusted death rate from HIV/AIDS declined almost four percent between 2000 and 2001.

This decline continues the decreasing trend that has been seen for HIV/AIDS deaths since 1995. From 1987 to 1994, mortality from HIV increased some 191 percent. However, from 1995 to 2001, mortality from HIV has declined nearly 70 percent.

There were some increases in mortality from several leading causes of death. Mortality from kidney disease increased 3.7 percent, deaths from hypertension increased three percent, and deaths from Alzheimer's disease went up five percent. Also, the infant mortality rate--6.9 infant deaths per 1,000 live births--remained the same from 2000 to 2001.

Researchers say that while the report highlights some encouraging progress, more needs to be done to address diseases that disproportionately affect certain racial and ethnic groups. From the Center For Disease Control - 2003

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HEART DISEASE MOST COSTLY CONDITION By Jennifer Warner WebMD Medical News Reviewed By Brunilda Nazario, MD

Treating heart disease cost Americans $58 billion in 1997, making it the single most expensive item on the country's health care bill, followed by cancer, trauma, and mental disorders.

In a new report, researchers analyzed the cost of health care for some of the most common medical problems and came up with the top 15 costliest conditions for the 1997 calendar year. They found that although lung disorders like asthma affected the most Americans (41 million), the cost of treating lung conditions only ranked fifth on the list at $29 billion.

In comparison, the 17 million people diagnosed with heart disease spent $58 billion, 9 million cancer patients spent $46 billion, 37 million who suffered a traumatic injury spent $44 billion, and 20 million with mental disorders shelled out $30 billion.

Not surprising, researchers say the study found that many of the conditions in the top 15 are chronic diseases that require long-term care. Their findings appear in the current issue of Health Affairs.

Rounding out the top 15 were the following conditions (listed with their annual associated price tag and number of Americans affected):
Diabetes, $20 billion, 10 million people
Hypertension (high blood pressure), $18 billion, 27 million people
Stroke-related conditions, $16 billion, 2 million people
Osteoarthritis, $16 billion, 16 million people
Pneumonia, $16 billion, 4 million people
Back problems, $13 billion, 13 million people
Kidney disease, $10 billion, 2 million people
Endocrine disorders, $10 billion, 18 million people
SKIN DISORDERS, $9 BILLION, 20 MILLION PEOPLE (Well, we finally have been recognized and counted.)
Infectious diseases, $6 billion, 16 million people

Researchers Joel W. Cohen and Nancy A. Krauss at the Agency for Healthcare Research and Quality say private insurance paid for about 35% of the expenses for the top five conditions, and Medicare covered nearly 45% of heart disease expenses, 20-25% of cancer costs, and 16% of expenses related to treating mental disorders.

Out-of-pocket expenses were highest for high blood pressure, for which sufferers paid about 30% of their own costs -- largely due to prescription drug expenses. SOURCE: Health Affairs, Vol. 22 No. 2, 2003. © 2003 WebMD Inc. All rights reserved.

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NEW CLUES ABOUT PSORIATIC ARTHRITIS

SCIENTISTS FIND MOLECULAR FACTORS BEHIND DEVELOPMENT OF DISABLING DISEASE

(HealthScoutNews) -- Scientists at the University of Rochester Medical Center have identified the molecular factors that cause bone damage in people with psoriatic arthritis, a disease that affects as many as 1 million people in the United States.

Their study, which appears in the March 15 issue of the Journal of Clinical Investigation, found that people with psoriatic arthritis have an abundance of a type of cell that specializes in dissolving bone.

In addition, their joints contain high amounts of a protein that persuades th ese bone-dissolving cells to settle into joints and cause damage.

The discovery of this one-two molecular punch may help doctors understand why people with psoriatic arthritis are responding so well to new medicines. The study also provides information that may help develop new ways to treat the disease.

The study included 30 people with psoriatic arthritis and 12 healthy people. The researchers analyzed blood samples and examined cells from the synovium. That's the joint lining that normally nourishes a joint but turns invasive and destructive in people with psoriatic arthritis.

While less known than rheumatoid arthritis, psoriatic arthritis can be just as crippling. It usually strikes people who have psoriasis. About 10 percent to 15 percent of people with psoriasis develop psoriatic arthritis, which usually strikes people in their 20s and 30s.

People with the disease usually suffer pain, swelling and inflammation as the disease eats away at their joints. Some bones or digits such as fingers shrink or even disappear. The disease also causes disfiguring or disabling bone growth in the hands, feet, spine and other joints. SOURCE: University of Rochester Medical Center, news release, March 14, 2003

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CAFFEINE MAY HINDER RHEUMATOID ARTHRITIS DRUG
By Amy Norton - NEW YORK (Reuters Health)

The caffeine provided by less than two cups of coffee a day might be enough to dull the effects of the drug methotrexate in people with rheumatoid arthritis, a small study suggests.

Israeli researchers found that among 39 adults with rheumatoid arthritis, those with the highest caffeine intake--comparable to about one-and-a-half cups of coffee or more per day--showed a weaker response to methotrexate than did patients with the lowest caffeine intake.

According to the researchers, caffeine may interfere with methotrexate's ability to fight rheumatoid arthritis because caffeine acts on cell receptors called adenosine receptors. It's not yet clear why methotrexate helps rheumatoid arthritis, but one theory is that it increases adenosine production, which in turn reduces the inflammation that marks rheumatoid arthritis.

The investigators, led by Dr. Gideon Nesher of Shaare-Zedek Medical Center in Jerusalem, call for larger studies to look at the possible interaction between methotrexate and caffeine in people with rheumatoid arthritis.

Their report appears in the February issue of the journal Arthritis & Rheumatism.

"I think the findings are intriguing," Dr. John Klippel, medical director of the Atlanta-based Arthritis Foundation, told Reuters Health.

Klippel pointed out that "one has to be cautious" in interpreting the results of such a small study.

But he also said rheumatoid arthritis patients on methotrexate "might want to consider" easing up on caffeine.

"It might be time to start thinking about limiting caffeine intake," Klippel said.

He noted that earlier research in animals had suggested a caffeine-methotrexate connection, and this latest study has "taken the next step" by finding a relationship in people with rheumatoid arthritis.

All of the study participants were recently diagnosed with rheumatoid arthritis and were started on 7.5 milligrams (mg) of methotrexate a week. Their symptoms and daily diets were followed for three months, and patients were analyzed in three groups based on their caffeine intake.

Nesher's team found that by the end of the study, participants with the highest caffeine consumption showed less improvement in morning stiffness and joint pain compared with the lowest-intake group.

According to the researchers, their findings suggest that a daily intake of more than 180 mg of caffeine dulls the effects of methotrexate compared with caffeine doses of less than 120 mg per day.

A typical cup of brewed coffee contains around 120 mg of caffeine.

Klippel said that it's difficult to make specific dietary recommendations based on these findings. However, he noted, rheumatoid arthritis patients on methotrexate who want to watch their caffeine intake might try limiting themselves to one cup of coffee a day.

SOURCE: Arthritis & Rheumatism 2003;48:571-572. (Reuters Health)

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ANAKINRA BENEFICIAL IN RHEUMATOID ARTHRITIS UNRESPONSIVE TO METHOTREXATE NEW YORK (Reuters Health)

Treatment with anakinra, a human recombinant form of interleukin I receptor antagonist, rapidly improves functional status in patients with persistent active rheumatoid arthritis (RA) despite treatment with methotrexate, according to a report in the February issue the Journal of Rheumatology.

Dr. Stanley B. Cohen, of St. Paul Medical Center, Dallas, Texas, and colleagues examined the effect of treatment with anakinra on the functional status of 419 such patients. In addition to methotrexate, the patients were randomly assigned to receive placebo or 0.04, 0.1, 0.4, 1.0, or 2.0 mg/kg of anakinra once a day for 24 weeks.

The researchers used the Health Assessment Questionnaire (HAQ) to evaluate functional status at baseline and every 4 weeks. "A weighted sum of the scale scores is the HAQ disability index (HAQ-DI)," they explain.

Patients taking anakinra showed dose-dependent improvements in the HAQ-DI. About half of the patients experienced sizable improvements by week 4 and two-thirds had improvements by week 8.

Those taking the two highest doses of anakinra showed significant improvements in the HAQ-DI by week 4 compared to those in the placebo group. These improvements were considered clinically important. The investigators note that some patients improved to a point where no functional impairment was reported.

Dr. Cohen and colleagues note that longer studies are under way, planned for up to 20 years duration. These should show if anakinra affects radiological progression of rheumatoid arthritis, and whether improvements in functional status are sustained.

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TNF INHIBITOR LABELING ON RISK OF LYMPHOMA SHOULD CAUTION AGAINST COMPARISONS BETWEEN AGENTS - FDA Advisory Committee Hearings

Tumor necrosis factor inhibitor labeling regarding the risk of lymphoma should include a statement that standardized incidence ratios cannot be compared between agents, FDA's Arthritis Advisory Committee recommended March 4.

FDA indicated that Abbott's Humira labeling is being considered as a template for revisions to warnings in the labeling for Amgen's Enbrel and Centocor's Remicade.

Humira labeling includes a warning that "lymphomas have been observed in patients treated with TNF blocking agents including Humira. In clinical trials, patients treated with Humira had a higher incidence of lymphoma than the expected rate in the general population."

The adverse reactions section for Humira includes the rate seen in clinical trials and the standardized incidence ratio (the observed cases over the adjusted expected incidence in the general population).

CBER Division of Clinical Trial Design & Analysis Karen Weiss, MD, noted that the agency had more information for adalimumab, as the newest anti-TNF agent, based on its experience with Enbrel (etanercept) and Remicade (infliximab). Amgen and Centocor are in discussions with FDA over labeling revisions.

Much of the committee discussion centered on whether or not to include SIRs (standardized incidence ratio). Representatives from Abbott, Amgen and Centocor argued that including SIRs would be confusing and cause misleading comparisons.

The background SIR for rheumatoid arthritis should be included in labeling, the committee agreed. Both RA and immunosuppression are thought to be associated with lymphoma.

Committee members also recommended that additional data on anti-TNF-associated lymphoma should be collected from larger, long-term patient registries.

Although each company has ongoing registries, committee members felt they drew too heavily from clinical trial populations, and that there should be greater standardization. One committee member said a national registry would be appropriate.

The committee also debated whether class labeling for congestive heart failure was needed. Enbrel carries a precaution and Remicade has a warning against use in patients with CHF based on failed clinical trials, and the committee members suggested that evidence warrants adding a statement for Humira. FDA is in discussions with all three manufacturers about CHF revisions.

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TOP SCIENTIST WARNS OF "SICKNESS" IN U.S. HEALTH SYSTEM Tim Radford, Science Editor of the Guardian - Denver

The US health system is itself sick and needs a national commission to get it back on the road to recovery, Floyd Bloom, president of the American Association for the Advancement of Science, told the association's annual meeting last week.

Dr Bloom is the head of neuropharmacology at the Scripps Research Institute, La Jolla, California. He was editor in chief, until 2000, of the journal Science, and he once headed the neuropharmacology laboratory at the National Institutes of Health. That an architect of modern neuroscience chose to open the largest single public science conference in the United States to make his point suggests more than just a cautionary diagnosis.

Dr Bloom warned of soaring health premiums, shortages of expertise in a number of specialties, paperwork burdens, and archaic methods of information management. And he had more immediate problems in mind. "The threat of war and the imposition of mass casualties from any new acts of terrorism could prove calamitous for the US medical community's ability to care for the ill," he said.

He listed specific problems. Communication was difficult. The number of drugs available to treat an increasingly elderly population had passed the 10 000 mark. Many of these drugs had covert interactions between them. Patients were seeing several doctors, who did not know about each other and who were prescribing drugs that may be mutually antagonistic or toxic.

"So there is a great need for stepping back from this crisis situation and finding ways to re-examine the decisions that we have made and the choices that we have in the future," he said. "Unless we do something now, all of the doubling of the NIH's [National Institutes of Health] research resources . . . will have a difficult time making it through the pipeline to reach the bedsides of the patients," he said. Genomic research was unlikely to provide any dramatic benefits for many years, but it distracted from the problems multiplying right now.

He also raised the problems that stress in infancy might impose in later life for millions of Americans. "Stress is the name we give to a natural reaction our bodies generate when we encounter a situation that is unbeknownst to us," he said. "We activate our autonomic nervous system, and as a result our blood pressure goes up, our heart rate goes up, our blood glucose goes up, and our blood lipids go up. All of which is a great advantage if you are trying to flee from a threatening situation.

"But if stress is maintained, what results is a change in our metabolism which permanently results in hyperglycemia, down-regulation of insulin receptors, deposits of lipids from those high lipids in the bloods into the endothelial cells of the capillaries. And prolonged stress of itself is a major factor in the onset of type 2 diabetes, hypertension, cardiovascular illness, and various problems of modern society."

He then turned his attention to what he described as the "reactive" health system in the United States.

"We wait until somebody is sick, and then we try to do something about it. Preventive medicine has a great deal to offer. Socioeconomic status has important proclivities for a host of illnesses in our country, including osteoarthritis. The lower you are in the socioeconomic status scale, the more likely you are to have osteoarthritis, or asthma, or other kinds of pulmonary illnesses," he said.

"We can't declare poverty to be gone. But we can recognize what the factors are and try to apply what we have today-instead of waiting for molecular discoveries to tell us how we might tailor drugs at some point in the future."

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AVENTIS ARAVA LABELING DOES NOT NEED TO BE UPDATED FDA Advisory Committee Meeting

Aventis Arava labeling does not need to be updated to add any increased warning about liver toxicity, members of FDA's Arthritis Advisory Committee recommended at its March 5 meeting.

The current labeling for the rheumatoid arthritis agent, which warns about potential increases of liver enzymes, is "satisfactory," committee consultant James Lewis, MD, Georgetown University Medical Center, said.

In addition, Lewis and other committee members said a "Dear Doctor" letter should not be required to communicate information concerning reports of liver toxicity and failure with Arava (leflunomide) received by FDA's Adverse Event Reporting System.

Committee Acting Chair Steven Abramson, MD, concurred that no change in Arava labeling or "Dear Doctor" letter are necessary, noting that data presented by the company and by FDA from clinical trials and health plan databases showed no increase in hepatotoxicity with Arava.

However, FDA Anti-inflammatory, Analgesic & Ophthalmic Drug Products Division Director Lee Simon, MD, indicated that FDA believes Arava labeling "needs to be changed slightly" to communicate more information about potential hepatotoxicity. He also expressed interest in issuing a "Dear Doctor" letter.

The advisory committee voted unanimously that Arava's benefits in RA outweigh its potential risks. The committee concluded that Arava's risks were no greater than other disease-modifying antirheumatic drugs.

Lewis reviewed case reports from the AERS database and found that none of the reported cases of liver injury or death could be definitively tied to Arava. FDA has received 16 post-marketing reports of possible Arava-related acute liver failure and labeled two of them as having a "probable" association with Arava.

At the open public hearing of the meeting, Public Citizen Health Research Group Director Sidney Wolfe, MD, accused FDA of trying to hide reviewer dissent because two Office of Drug Safety reviewers did not make presentations at the meeting.

In a Nov. 7, 2002 memo, Drug Risk Evaluation Division Safety Evaluator Renan Bonnel, MD, and ODS Associate Director of Science David Graham, MD, recommended that Arava be withdrawn from the market due to the possible liver toxicity findings. HRG prompted the investigation into Arava's safety with a citizen's petition seeking the product's withdrawal in March 2002.

The committee also voted 11 to 0 with two abstentions that Arava should be approved for a claim of improvement in physical function.

Aventis conducted one-year extension studies of its three NDA pivotal trials of Arava and showed continued improvements over placebo on the Health Assessment Questionnaire, which assesses physical function in activities of daily living, and other function measures.

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Life is not measured by the number of breaths we take, but by the moments that take our breath away.

Good Health to All,

Jack Nicholas
Newsletter Editor
Cornishpro@aol.com
Issue 2003 4/01/03 -5