STUDY: Doctors recognizing new consequences of tick-borne illness

JOURNAL: Rheumatology

AUTHORS: Dr. Brian Fallon

ABSTRACT: More and more doctors are recognizing that Lymes can cause brain problems — including memory loss, fatigue, disorientation, even severe depression.

---

COMMENTARY: Researchers are trying to determine just how prevalent these problems are.

Dr. Brian Fallon of the New York State Psychiatric Institute at Columbia University said brain scans of people infected can show areas that appear to be damaged.

“There’s no doubt that there are people out there with significant neurologic or neuro-psychiatric problems who are quite impaired and who aren’t being recognized as having Lyme disease,” he said.

The number of Lyme disease cases reported in the United States is approaching 20,000 a year. Many experts think the actual number is 10 times that and climbing sharply. The biggest danger is at this time of year, when the ticks that carry the disease are most likely to be biting.

Lyme disease remains concentrated in the Northeast, Mid-Atlantic, Minnesota and Wisconsin. But cases have now been reported in almost every state.

One of the biggest problems is that symptoms vary widely. Most people bitten by an infected tick have either no symptoms or flu-like symptoms easily cured with antibiotics. About 10 percent get chronic pain in the joints and the best guess is that the brain problems occur in 10 percent to 15 percent of cases.

Treatment results vary too. Antibiotics can often help the joint pain and the brain problems, but not always.

The manufacturer of the only Lyme disease vaccine took it off the market citing poor sales following unproven allegations of side effects. So the only protection now is to avoid tick bites by wearing long clothing and applying insect repellent — cutting the risk of a disease that for some can have serious consequences.

STUDY: Large American Cancer Society Study Reinforces Evidence of Dangers of Being Overweight

JOURNAL: American Cancer Society’s Cancer Prevention Study

AUTHORS: Eugenia Calle, PhD,

ABSTRACT: Women who are overweight or obese after menopause have a greater risk of dying from breast cancer than women who maintain a normal weight.

---

COMMENTARY: Overweight and obesity were measured by body mass index (BMI), a measure of weight that is adjusted for height. Breast cancer mortality rates increased continually and substantially with increasing BMI, and were twice as high in obese women than in lean women. Based on the results of this study, the authors estimated that 30% to 50% of breast cancer deaths among postmenopausal women in the US may be attributed to overweight and obesity.

The good news is that unlike many risk factors for breast cancer, weight is modifiable. If women can avoid weight gain in adulthood and maintain a lean to normal weight throughout life , they will be at lower risk of dying from breast cancer.

Most previous studies of how weight affects a woman’s breast cancer risk have been unable to examine risk across a wide range of body mass , and few studies have looked at breast cancer mortality.

In addition, most studies have been too small to investigate potential differences between weight and breast cancer mortality in subgroups of women. CPS II included 424,168 postmenopausal women who were cancer-free when they enrolled in the study in 1982. After 14 years of follow-up, 2,852 women had died of breast cancer.

STUDY: Make sure your taking zinc

JOURNAL: ADA Annual Meeting: Abstracts 1644-P, 569-P.

AUTHORS: Rui Jiang

ABSTRACT: Eating nuts helps prevent the development of diabetes and that zinc supplementation in obese, insulin-resistant women improves insulin sensitivity, even in the absence of zinc deficiency.

---

COMMENTARY: Major constituents of nuts (unsaturated fatty acids, magnesium and fiber) have been inversely associated with risk of type 2 diabetes; however, the overall effects of nut consumption on risk of type 2 diabetes are not available but our results suggest that frequent nut consumption is associated with lower risk of type 2 diabetes in women.

In this offshoot of the Nurses' Health Study, the authors analyzed data from validated dietary questionnaires completed in 1980 by 83,818 women, aged 34 to 59 years, without a history of cardiovascular disease, cancer, or diabetes. During 16 years of follow-up, 3,206 women developed type 2 diabetes.



After adjustment for age, body mass index (BMI), smoking, physical activity, family history of diabetes, alcohol, and total energy intake, nut consumption was inversely associated with risk of diabetes. Compared with women who almost never ate nuts, multivariate relative risk (RR) among women who ate nuts less than once weekly was 0.93 (95% confidence interval [CI], 0.86-1.01). RR was 0.84 (95% CI, 0.76-0.93) among those who ate nuts one to four times weekly, and RR was 0.72 (95% CI, 0.60-0.88) among those who ate nuts more than five times weekly (P<.0001 for trend).

The protective effect of nuts did not vary after further controlling for dietary factors, including intake of vegetables, fruits, and whole grain, and a composite diet score composed of trans fat, cereal fiber, glycemic load, marine omega-3 fatty acids, folate, and polyunsaturated fat-to-saturated fat ratio.



In a separate study by Dilina N. Marreiro and colleagues from Universidade de Sao Paulo-SP in Brazil, zinc supplementation enhanced insulin sensitivity in obese women who were not zinc-deficient.

In this prospective, double-blind, clinical interventional study, 56 obese women with normal glucose tolerance were randomized to treatment with zinc, 30 mg daily, or placebo for four weeks. At baseline, age was 25 to 45 years, mean BMI was 36.2 ± 2.3 kg/m2, and both groups were similar in clinical and laboratory parameters.

Insulin resistance as measured by a homeostasis model assessment did not change in the placebo group, but it decreased from 5.8 ± 2.6 to 4.3 ± 1.7 (P<.05) in the zinc-supplemented group. Insulin decreased from 28.8 ± 14.1 to 21.2 ± 8.1 mU/mL (P<.05) in the zinc group but was unchanged in the placebo group.



"A short time of zinc supplementation improved insulin sensitivity in obese insulin [resistant] women without zinc deficiency," the authors write.

STUDY:

JOURNAL: Journal of the National Cancer Institute 9/17, 2003.

AUTHORS: Dr. Philip R. Taylor

ABSTRACT: High blood levels of alpha-tocopherol, a form of vitamin E, may reduce a person's chances of getting stomach and esophagus cancer.

---

COMMENTARY: The findings, which are reported in the Journal of the National Cancer Institute, are based on a Chinese study in which participants took supplements containing vitamin E or used no supplements.

People who used the supplements were less likely to die from cancer than those who did not.



Further analysis revealed that the risk of esophagus cancer and a type of stomach cancer decreased as blood levels of alpha-tocopherol rose. In contrast, levels of gamma-tocopherol, another form of vitamin E, were not related to the risk of either cancer.

Surprisingly, high levels of alpha-tocopherol appeared to raise the risk of another type of stomach cancer called gastric noncardia cancer (GNCC).

The results "provide support for a role of alpha-tocopherol in the (cause) and prevention of" esophagus and stomach cancers, the investigators conclude.



Once again we see that balance is everything. Too much of a good thing may not be good.

STUDY:

JOURNAL: The British Medical Journal

AUTHORS: Rogier Hintzen

ABSTRACT: Stressful events, such as the death of a loved one, financial worries or job problems, can exacerbate symptoms of multiple sclerosis.

---

COMMENTARY: In a study reported in The British Medical Journal, researchers at the Erasmus Medical Center in Rotterdam found that stress was linked with double the risk of an increase in the severity of symptoms of the auto-immune disease.

"The knowledge that stressful events are associated with disease activity adds important information to the limited insight that patients and their caregivers have on this unpredictable disease," said Rogier Hintzen, a neurologist at the center.

MS is a chronic, progressive disease that occurs when immune system cells attack and destroy the myelin sheath that protects nerve cells in the brain and spinal cord. It affects about a million people worldwide.

Twice as many women as men suffer from MS, which can be difficult to diagnose because symptoms such as tingling, fatigue, loss of balance and slurred speech are intermittent.

The illness is more common in people living in colder climates and rare in Africa and Asia. Its cause is unknown and there is no cure.

Hintzen and his team, who questioned 73 MS patients, said they did not find any increase in infections after stressful events.

But one stressful event during a period of four weeks was associated with double the risk of exacerbation within the next week.

STUDY:

JOURNAL: Journal of the National Cancer Institute

AUTHORS: Everett Vokes, M.D

ABSTRACT: Cancer patients who travel more than 15 miles for treatment appear to survive longer than patients who live closer to their treatment center, even after controlling for factors such as disease stage and economic status, concludes a study conducted at the University of Chicago and published in the Journal of the National Cancer Institute.

---

COMMENTARY: Patients who traveled at least 15 miles for care had one-third the risk of dying during the trial and follow-up period as those living closer.

For every 10 miles that a patient traveled for care, the risk of death decreased by 3.2 percent. A similar pattern was seen with progression-free survival.

"This does not mean that time on the highway is curative," insists Everett Vokes, M.D., professor of medicine and chief of hematology/oncology at the University of Chicago and senior author of the study. "It does suggest that distance is a good marker for some unmeasured resource such as access to health care options, personality traits like compliance or motivation, or a supportive social network, that we don't yet know how to assess."

The results confirm something oncologists "have long appreciated," note the authors. Patients who explore therapeutic options and expend the resources to receive those therapies seem to "fare better than those who end up at the closest place," even if their diseases and treatments are the same.

The study, conducted by Vokes, a specialist in head and neck cancers, Elizabeth Lamont, M.D., (formerly at Chicago and now at the Massachusetts General Hospital Cancer Center in Boston) and colleagues, involved 110 patients with advanced (stage-IV) head and neck cancer who were enrolled in one of four phase II clinical trials at the University of Chicago Hospitals from 1993 to 2000.

All four trials involved aggressive treatment intended to eradicate the cancer. Patients received five cycles of combined chemotherapy plus twice-daily radiotherapy. Despite advanced disease, more than 60 percent of the patients enrolled in these trials go on to survive at least five years.

Although patients from near and far were comparable in terms of disease severity, those who traveled 15 miles or more tended, on average, to have higher incomes and more education and were more likely to be white. Patients who within 15 miles of the hospital were more likely to have had laryngeal cancer, which has a relatively favorable prognosis, and to be African American, also an advantage.

Unlike many previous studies, African Americans did better in these trials. "When treatment was standardized and health factors, social resources, and neighborhood effects were rigorously accounted for," the authors remarked, African Americans had "better survival outcomes than white patients."

STUDY:

JOURNAL: Gut, October 2003

AUTHORS: Dr. K. C. H. Fearon

ABSTRACT: Dietary supplements enriched in omega-3 fatty acids, a component of fish oil, may help cancer patients gain weight, new research suggests.

---

COMMENTARY: Weight loss and muscle deterioration are common problems for people with advanced cancer. In animal studies, omega-3 fatty acids have been shown to protect against this problem, also known as cachexia.

The current findings, reported in the medical journal Gut, are based on a study of 200 patients with pancreatic cancer who received a diet supplement containing omega-3 fatty acids or a similar supplement lacking these fatty acids for 8 weeks. The subjects were instructed to consume two cans per day of the assigned supplement.

In the overall analysis, both supplements were equally effective in stopping the loss of body weight and muscle tissue.

However, on average, patients only consumed 1.4 cans per day of supplement--well below the recommended dose of 2 cans per day.

When the data was reanalyzed taking this into account, the authors found that as the amount of the omega-3 supplement consumed went up, so did weight and muscle gain. In contrast, this effect was not seen with the supplement lacking omega-3 fatty acids.

The team also found that only weight gain with the omega-3 supplement was actually tied to an improved quality of life.

STUDY: Back to Genes

JOURNAL: Journal of the National Cancer Institute

AUTHORS: Zvi Livneh

ABSTRACT: Israeli researchers said they had identified a naturally produced compound that may explain why only some smokers get lung cancer.

---

COMMENTARY: Smokers with low levels of the enzyme were five to 10 times more likely to develop lung cancer than smokers with the highest levels, the team at Israel's Weizmann Institute found.

The enzyme is called OGG1 or 8-oxoguanine DNA glycosylase 1. The enzyme fixes damage done to DNA by smoking and other environmental stresses and is one of a large group of repair compounds in the body.

Writing in the Journal of the National Cancer Institute, Zvi Livneh and colleagues said 40 percent of the 68 lung cancer patients they tested had low levels of OGG1 activity, in contrast to 4 percent of a healthy group of 68 people.

Nonsmokers with the lowest levels of OGG1 also had a higher risk of lung cancer, although their overall risk of cancer was much lower than that of the smokers.

Lung cancer is by far the biggest cancer killer in the world, killing a million people every year worldwide and nearly 160,000 a year in the United States.

Up to 90 percent of all lung cancer patients are smokers, but only 10 percent of heavy smokers develop lung cancer. Smoking is also a major cause of heart disease and stroke.

STUDY:

JOURNAL: British Medical Journal 8/03

AUTHORS:

ABSTRACT: Pregnant women who take certain types of painkillers, including aspirin, are up to 80 percent more likely to miscarry.

---

COMMENTARY: But paracetamol is not a risk, regardless of how often it is used during pregnancy.

Researchers in California interviewed more than 1,000 women shortly after they became pregnant and asked them about their reproductive history and their use of painkillers.

They found that use of aspirin and other non-steroid based anti-inflammatory drugs (NSAIDs) increased the risk of miscarriage by 80 percent.

The risk was much higher when NSAIDs were taken close to the time of conception.

Paracetamol, aspirin, and other NSAIDs such as ibuprofen, all suppress fatty acids which are needed for the successful implantation of an embryo in the womb.

But NSAIDs act on the whole body, paracetamol acts only on the central nervous system, which may explain why it has no effect on pregnancy, the researchers said.

Meanwhile, it may be prudent for physicians and women who are planning to be pregnant to be aware of this potential risk and avoid using NSAIDs around conception.

STUDY: Vitamins a good thing

JOURNAL: The Journal of nutrition.; 2003 Aug;133(8) p45304

AUTHORS: Holmquist C; Larsson S; Wolk A; De Faire U;

ABSTRACT: Epidemiologic data relating multivitamin supplement use to the risk of

---

cardiovascular disease are sparse and inconsistent. We examined the association

between self-selected use of low dose multivitamin supplements and the

risk of myocardial infarction (MI).

COMMENTARY: Our results are based on data from a large population-based, case-control study of subjects aged 45-70 residing in Sweden, a country in which consumption of fruits and vegetables is relatively low and foods are not fortified with folic acid.

The study included 1296 cases (910 men, 386 women) with a first nonfatal MI and 1685 controls (1143 men, 542 women) frequency-matched to the cases by sex, age and hospital catchment area. Odds ratios (OR) and 95% CI were calculated from unconditional logistic regression models.

Among controls, 57% of the women and 35% of the men used dietary supplements; corresponding figures for the cases were 42 and 27%, respectively. Of those taking supplements, 80% used multivitamin preparations. After adjustment for major cardiovascular risk factors, the OR of MI comparing regular users of supplements with nonusers were 0.79 (95% CI 0.63-0.98) for men and 0.66 (95% CI 0.48-0.91) for women.

This inverse association was not modified by such healthy lifestyle habits as consumption of fruits and vegetables, intake of dietary fiber, smoking habits and level of physical activity, although never smoking appeared to outweigh the association in women.

Findings from this study indicate that use of low dose multivitamin supplements may aid in the primary prevention of MI.

STUDY: Interesting End Option

JOURNAL: J Am Coll Surg. 2003;197:s91

AUTHORS: Robert E. Weiss

ABSTRACT: Brachytherapy is found to be beneficial for treating prostate cancer that recurs after external beam radiotherapy.

---

COMMENTARY: Retrospective record review identified 20 consecutive patients from 1998 to the present who were treated with radioactive seed implantation. All patients had biopsy-proven recurrent localized prostate cancer and had a staging evaluation negative for imageable disease.

There were no major complications. At about one to two weeks after treatment, transient adverse effects included irritative bladder symptoms in 35% and erectile dysfunction in 25% of those who were potent before brachytherapy.

Although these symptoms were similar to those who have undergone primary brachytherapy, a higher proportion of patients (55%) developed urinary obstructive symptoms, including one patient who needed a long-term catheter.

Based on normalization of prostate-specific antigen (PSA) levels, four-year actuarial disease-free survival was 70%. Gleason grade, initial stage, and pre- and postimplant PSA levels were associated with better odds of biochemical disease-free survival.

"Transperineal fluoroscopic-guided and biplane ultrasound-guided salvage prostate brachytherapy provides a potentially curative treatment modality for patients with recurrent localized prostate cancer after 3-D conformal external beam therapy,".

STUDY: Make sure to get enough iron early in pregnancy

JOURNAL: Am J Clin Nutr. 2003;78:773-781

AUTHORS: Laurie Barclay, MD

ABSTRACT: Early supplementation of iron to nonanemic, initially iron-replete pregnant women significantly improves birth outcomes, according to the results of a randomized controlled trial published in the American Journal of Clinical Nutrition.

---

COMMENTARY: Between June 1995 and September 1998, this study enrolled 513 low-income women before the 20th week of gestation. Of the 513 women, 275 had a hemoglobin concentration greater than 110 g/L and a ferritin concentration greater than 20 µg/L and were randomized to treatment with capsules containing either 30 mg ferrous sulfate or placebo until the 28th week of gestation.

At the 28th week and at the 38th week of gestation, women with a ferritin concentration of 12 to less than 20 µg/L or < 12 µg/L received 30 and 60 mg iron/day, respectively. Nearly all subjects received some prenatal iron supplementation. Infant birth weight and gestational age at delivery were determined for 117 and 96 of the 146 and 129 women randomized to receive iron and placebo, respectively.

Compared with placebo, iron supplementation from enrollment to 28 weeks of gestation did not significantly affect the overall prevalence of anemia or the incidence of preterm births. However, this regimen was associated with higher birth weight (206 ± 565 g; P = .010), lower incidence of low-birth-weight infants (4% vs. 17%; P = .003), and lower incidence of preterm low-birth-weight infants (3% vs. 10%; P = .017).

"Prenatal prophylactic iron supplementation deserves further examination as a measure to improve birth weight and potentially reduce health care costs," the authors write. "In contrast to the US Preventive Services Task Force and Institute of Medicine recommendations, our study provides evidence that infants may benefit substantially from maternal iron supplementation beginning early in gestation."

The authors report no conflicts of interest.

In an accompanying editorial, Kathleen M. Rasmussen and Rebecca J. Stoltzfus, from Cornell University in Ithaca, New York, note that these findings were unexpected: "The effect on birth weight was relatively large, much larger than nearly all the effects reported in [previous] iron-supplementation trials.... More surprising still, the benefit to birth weight occurred without demonstrable improvement in maternal iron status."

STUDY: Chinese remedy Tripterygium wilfordii Hook F (TWHF) extract offered benefit to patients with refractory rheumatoid arthritis.

JOURNAL: Arthritis Rheum. 2002;46:1735-1743

AUTHORS: Xuelian Tao, MD

ABSTRACT: The Chinese remedy Tripterygium wilfordii Hook F (TWHF) extract was well tolerated and offered benefit to patients with refractory rheumatoid arthritis, according to the results of a double-blind, placebo-controlled trial reported in the July issue of Arthritis & Rheumatism.

---

COMMENTARY: Extracts of TWHF have been widely used in China to treat a broad spectrum of autoimmune and inflammatory diseases. Results from most of the clinical trials of TWHF have claimed significant therapeutic benefit, although nearly all of the trials were uncontrolled, as mandated by Chinese custom.

In this trial, 35 patients with refractory, longstanding rheumatoid arthritis were randomized to treatment with placebo, low-dose extract (180 mg/day), or high-dose extract (360 mg/day) for 20 weeks, followed by an open-label extension period. Of patients who completed at least four weeks of treatment, eight of 10 in the high-dose group, four of 10 in the low-dose group, and none of 12 in the placebo group met criteria for clinical response, defined as 20% improvement in disease activity according to American College of Rheumatology criteria.

Of patients enrolled in the open-label extension, five of seven receiving high-dose extract, four of seven receiving low-dose extract, and two of four receiving placebo met criteria for clinical response.

Of 35 patients initially enrolled in the trial, 21 completed the 20-week study; one patient from each group withdrew because of adverse effects. The most common adverse effect was diarrhea. No patients withdrew because of adverse events during the open-label extension.

Despite study limitations and the need for larger trials, the authors noted that TWHF extract at 360 mg/day appears to be safe in rheumatoid arthritis patients. The symptoms and signs of inflammation and the physical functioning of most of the patients in the trial improved.

STUDY: When is low too low

JOURNAL: European College of Neuropsychopharmacology

AUTHORS: Dr Y. Kim

ABSTRACT: A new study has found evidence that depressed patients with low cholesterol levels may be more likely to commit suicide.

---

COMMENTARY: Low levels of cholesterol in patients suffering from depression have previously been linked to suicide and violence.

The team compared cholesterol levels in 149 patients with major depression who were admitted to an emergency room after suicide attempts with those of 149 patients who were also depressed but who did not attempt suicide. There were also 251 healthy controls in the study.



Dr Y. Kim told the Prague meeting that depressed patients with blood cholesterol levels of less than 160 milligrams per deciliter appeared to be at increased risk.

STUDY:

JOURNAL: Neurology, September 23, 2003.

AUTHORS: Dr. admin M. Meyer

ABSTRACT: Menopause is not associated with significant memory loss, new study findings indicate.

---

COMMENTARY: Previous studies have suggested an increase in forgetfulness reported by women during menopause, Dr. admin M. Meyer and colleagues note in the current issue of Neurology.

The researchers, based at Rush-Presbyterian-St. Luke's Medical Center in Chicago, initiated a long-term study in 1996, which included 803 women between 42 and 52 years old. All of the subjects were premenopausal or in the early stages of menopause at the start of the study. Each year, the women were tested for working memory and perceptual speed.

During an average follow-up of 2.1 years, the authors observed small but significant improvements in both cognitive scores with aging, after adjusting the data for ethnicity, education, income and self-reported health. Meyer's group suggests that learning effects may explain the improvement over time.

The investigators note that more refined analysis of the study data is forthcoming. They hope that additional analysis of risk factors and other psychosocial measures, such as depression and stress, will help identify predictors of cognitive change during menopause.

STUDY:

JOURNAL: the Environmental Working Group

AUTHORS:

ABSTRACT: - Several American mothers nursing their infants had high levels of potentially toxic flame retardant chemicals in their breastmilk.

---

COMMENTARY: The chemicals are bromine-based fire retardants and are used in a wide range of products including furniture, computers, television sets, automobiles, copy machines and hair dryers to make them less likely to catch fire.

They can build up in the body over years.

Brominated fire retardants impair attention, learning, memory, and behavior in laboratory animals at surprisingly low levels.

The most sensitive time for toxic effects is during periods of rapid brain development.

The average level of bromine-based fire retardants in the milk of 20 first-time mothers was 75 times the average found in recent European studies.

Milk from two study participants contained the highest levels of fire retardants ever reported in the United States, and milk from several of the mothers in EWG's study had among the highest levels of these chemicals yet detected worldwide.

These results confirm recently published findings from University of Texas researchers, as well as other U.S. studies, that American babies are exposed to far higher amounts of fire retardants than babies in Europe, where some of these chemicals have already been banned.

In the United States, only California and Maine have acted to restrict the use of these chemicals.

The group stressed that women should not stop breastfeeding. No study links intake of the chemicals from breastmilk with any problems in children.

Any health effects probably take place while the children are still in the womb.



Albemarle Corp. of Richmond, Virginia, one of the companies that makes the flame-retardant chemicals, said it was working to find out if the chemicals are dangerous.

STUDY: We have know this for years

JOURNAL: FDA

AUTHORS:

ABSTRACT: The United States Food and Drug Administration (FDA) announced significant updates to the labeling of products containing lindane (hexachlorocyclohexane) to include additional warnings about the potential risks associated with its use and misuse, according to a recent report released by the FDA.

---

COMMENTARY: Lindane lotions and shampoos are used in the treatment of lice and scabies but may have toxic side effects if not used appropriately.

The new labeling on lindane products will include a boxed warning that anyone weighing less than 110 pounds (50 kg) use them with caution and that infants should not be treated with them at all.

Other label changes will include a warning of potential adverse reactions in people with compromised immune systems or in those taking antidepressant medications.

Toxicity of lindane lotion appears to be higher than that of lindane shampoo. Due to the potential toxic effects, the FDA states that lindane products should only be used if all other treatments for lice have failed.

Other natural treatments may be an effective, safer way to treat lice.

One study showed that applying a shampoo (by Nature’s Sunshine Products) containing 0.5% paw paw (Asimina triloba), 0.5% tea tree oil (Melaleuca alternifolia), and 1% thyme oil (Thymus vulgaris) was 100% effective in removing head lice from 16 infected children. The treatment regimen used was a single application, repeated every eight days, for a total of three applications. The shampoo was left in the children’s hair for 30 minutes for the first treatment and then 60 minutes for the subsequent treatments before rinsing.

Physicians recommend that parents examine their children regularly and start treatment as soon as possible once a child becomes infected.

STUDY: Look for alternatives

JOURNAL: Seminars in Nephrology

AUTHORS: Abhijit V. Kshirsagara

ABSTRACT: Despite a multitude of investigation over the last 2 decades, the treatment of membranous nephropathy remains both controversial and suboptimal.

---

COMMENTARY: Recent progress in the molecular pathways of inflammation and immunologic regulation holds the promise of offering futuristic alternatives and/or supplements to the standard regimen of glucocorticoids and alkylating agents.

Several potential points of intervention along the path of disease development and expression have been identified: modulation of the immune response to the pathogenetic antigen; inactivation of the inflammatory pathways responsible for B and T cell activation; blockade of pathogenetic antibody formation by B and T cells; blockade of the complement cascade; blockade of lipid peroxidation of glomerular basement membrane components; and blockade of renal fibrosis resulting from proteinuria, lipiduria, and/or inflammation.

These points of intervention form the basis of such varied potential therapies for membranous nephropathy.

STUDY:

JOURNAL: Pharmacology, biochemistry, and behavior.; 2003 Jun;75(3) p15451

AUTHORS:

ABSTRACT: A high soya diet improved memory and frontal lobe function in young volunteers, and since soya isoflavones are agonists at estrogen receptors, they may improve these functions in postmenopausal women.

---

COMMENTARY: Thirty-three postmenopausal women (50-65 years) not receiving conventional

hormone replacement therapy (HRT) were randomly allocated in a double-blind

parallel study to receive a soya supplement (60 mg total isoflavone equivalents/day) or placebo for 12 weeks.

They received a battery of cognitive tests and completed analogue rating scales of mood and sleepiness, and a menopausal symptoms questionnaire before the start of treatment and then after 12 weeks of treatment. Those receiving the isoflavone supplement showed significantly greater improvements in recall of pictures and in a sustained attention task.

The groups did not differ in their ability to learn rules, but the isoflavone supplement group showed significantly greater improvements in learning rule reversals. They also showed significantly greater improvement in a planning task.

There was no effect of treatment on menopausal symptoms, self-ratings of mood, bodily symptoms or sleepiness. Thus, significant cognitive improvements in postmenopausal women can be gained from 12 weeks of consumption of a supplement containing soya isoflavones that are independent of any changes in menopausal symptoms, mood or sleepiness.

STUDY:

JOURNAL: Int J Cancer 2003;106:856-862.

AUTHORS: Dr. Johannes V. Swinnen

ABSTRACT: Epigallocatechin-3-gallate (EGCG), a component of green tea, seems to induce apoptosis of prostate cancer cells by inhibiting fatty acid synthase (FAS), an enzyme that is overexpressed in a variety of human malignancies.

---

COMMENTARY: Although numerous reports have indicated an anticancer effect for EGCG, the exact mechanisms involved were unclear.

Several synthetic compounds have been shown to inhibit FAS and induce cancer cell apoptosis. Recently, however, researchers showed that EGCG, a natural compound, could inhibit FAS in chicken liver extracts. Therefore, it is possible that EGCG's anticancer effects are due to its ability to block FAS.

To investigate, Dr. Johannes V. Swinnen and colleagues, from the Catholic University of Leuven, evaluated EGCG's effects in cultured prostate cancer cells and in normal fibroblasts.

EGCG caused dose-dependent inhibition of FAS in the cancer cells that coincided with a decrease in cell growth and induction of apoptosis. In contrast, epicatechin, a chemical similar to EGCG that does not block FAS, did not inhibit cancer cell growth or induce apoptosis.

EGCG slowed the growth rate, but did not induce apoptosis of normal fibroblasts--cells with low levels of FAS activity. This provides further evidence that EGCG's anticancer effects are mediated by FAS inhibition, the researchers note.

"It may be concluded that EGCG-medicated FAS inhibition is undoubtedly one of the mechanisms that merit consideration when trying to explain the cancer chemopreventive and chemotherapeutic potential of this green tea polyphenol," the authors state.

STUDY:

JOURNAL: American Neurological Association

AUTHORS: Dr. John Weiss

ABSTRACT: Glutamate produces more disruptive free radicals in motor neurons than in other spinal neurons, according to a preclinical study of spinal neuron/astrocyte cultures.

---

COMMENTARY: The finding strengthens the hypothesis that excess oxygen free radicals, stimulated by elevated levels of extracellular glutamate, promote the loss of motor neurons and nerve cells in patients with amyotrophic lateral sclerosis (ALS).

In healthy nerve cells, glutamate pumps in surrounding astrocytes successfully clear the molecule from the extracellular environment, according to Dr. Weiss. Yet when the pumps break down, the level of glutamate rises.

The excess glutamate floating outside motor neurons consequently trigger a feed-forward cycle, in which the glutamate outside the neurons induces the neurons to increase free radical production.

The cell cultures have provided a baseline to help examine how the relationship between glutamate and astrocyte may work.

STUDY:

JOURNAL: IDSA 41st Annual Meeting: Abstract LB-10. Presented 2003.

AUTHORS: Steven J. Reynolds, MD, MPH

ABSTRACT: Results of a prospective cohort study of 2,298 Indian men suggests that circumcision is associated with a "profound 8-fold reduction in HIV-1 risk.

---

COMMENTARY: Steven J. Reynolds, MD, MPH, a postdoctoral fellow in infectious diseases at Johns Hopkins University School of Medicine in Baltimore, Maryland, said the study results "not only add to the developing body of knowledge on circumcision and HIV transmission, but they also lend great support to studies now underway Uganda, Kenya, and South Africa."

Compared with uncircumcised men, circumcised men had an adjusted risk of HIV-1 infection of 0.12, which was significant (P = .003). The incidence of HIV-1 infection in uncircumcised men was 5.5%, while it was just 0.7% among the circumcised men.

At an IDSA press conference where the circumcision study was discussed, Cynthia Sears, MD, professor of medicine at Johns Hopkins, said most men in India are not circumcised. "That is also true in parts of sub-Saharan Africa where there are high rates of HIV transmission. In some instances there will be cultural and religious barriers to considering circumcision.

But where it is appropriate, then this is another measure that can help to reduce the rate of transmission," Dr. Sears said. "But [circumcision] does not obviate the need to use condoms," she added. Dr. Sears was not involved in the study.

The important implication in this study is the likelihood that circumcision has some protective efficacy against HIV transmission.