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

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.

© 2003 Reuters Limited. All rights reserved.

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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.

SOURCES: Journal of the American College of Nutrition, April 2003. © 2003 WebMD Inc. All rights reserved.

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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
Issue 2003 4/24/03 -6