July, August, September
2001 Therapeutics Letter

July / August / Bruce H. Woolley, PharmD, Editor Vol. 8, No. 7
September 2001 Kenneth J. Hunt, Associate Editor

CAD | Testosterone | Cancer | Ginseng |Osteoarthritis | Lung Cancer | Linezolid

Predictors of CAD and Stroke in Diabetics

Data from a recent prospective community-based study demonstrated that in patients with type 2 diabetes mellitus, several factors are independently associated with the development of coronary artery disease and cerebrovascular disease. Researchers at the Mayo clinic reported that quantitative measurements for cholesterol, triglycerides, glucose, and lipoprotein(a) were obtained from 449 patients between 1968 through 1982. All patients were free of CAD and cerebrovascular disease but had type 2 diabetes mellitus.

More than 200 coronary events and 115 cerebrovascular events occurred over a mean follow-up of 13 years. On statistical analysis, significant predictors of future CAD events included age, fasting glucose levels, smoking, and triglycerides. Significant predictors of future cerebrovascular events included age, hypertension, fasting glucose levels, and smoking. The investigators remarked that more medical attention should be directed toward altering the classic risk factors and the nonclassic risks, especially hyperglycemia and diabetic dyslipidemia.

Haitham S et al. Mayo Clin Proc 2001;76:707-712.

Testosterone Supplementation Improves Cognition

According to a recent article in the July issue of Neurology, short-term testosterone supplementation improves spatial functions and verbal memory in healthy older men. Researchers from the University of Washington Medical School in Seattle randomized 25 healthy men, 50 to 80 years of age, to receive a 6-week course of weekly placebo or 100 mg testosterone injections. Total testosterone levels increased by 130% and 116% after 3 and 6 weeks of treatment in the treatment group compared with baseline levels. There was also a 77% and 73% increase in estradiol levels at the same time intervals.

Spatial memory, spatial ability and verbal memory were significantly improved in the testosterone group compared with their baseline cognitive function and the cognitive function of the placebo group. The investigators point out that the improvements were not apparent for all cognitive domains, such as selective attention or language. They suggest that increases in serum testosterone or estradiol may have selective or specific effects on memory and spatial abilities.

The authors also note that it is unclear whether these improvements in cognition are attributable to increased testosterone or estradiol levels, or both. They call for further studies to examine the relative contribution of testosterone versus estradiol on cognition in men.

Neurology 2001;57:80-88.

New Drug May Help With Resistant Cancers

An experimental treatment for advanced myelodysplastic syndrome may help to prevent cancer patients from building up a resistance to chemotherapy drugs. In laboratory studies on ovarian and colon cancer cells scientists at the Beatson Laboratories at Glasgow University found that the drug decitabine, produced by US pharmaceutical company SuperGen Inc., made the cells more sensitive to chemotherapy drugs.

Researchers who lead the project, along with SuperGen, are planning to do clinical trials to see if the drug will have the same effect on human tumors. They recently presented this research at the Genomic Regulation and Cancer conference in Glasgow .

The research team discovered that key genes were turned off in chemotherapy-resistant cancer cells in a process called DNA methylation. Decitabine reverses the process and may be able to restore the cells' sensitivity to the toxic drugs. "This may be the tip of the iceberg" say the researchers. Recent advances in the way we study DNA methylation in the human genome are important in determining genes that may be targets for these types of drugs.

Ginseng Found to Have No Psychological Benefit

Researchers have found that the use of popular herbal remedy ginseng is not associated with any psychological benefit. A study published in the June 2001 issue of the Journal of the American Dietetic Association denounced the wide belief that the ginseng root has a number of psychological benefits, including combating stress-related physical and mental fatigue and boosting mood performance.

Study coordinators, based out of the sport and exercise psychology laboratory at the Oregon State University in Corvallis, Oregon, report that there is no benefit in taking the ginseng supplement in relationship to taking a sugar pill. The researchers examined 83 healthy individuals with an average age of 25.7 years, and divided the 40 women and 43 men into 3 groups: 2 groups were given 200 mg (the recommended dose) and 400 mg of ginseng, and the third group received a placebo.

Dosage and quality of the ginseng was determined at an independent research lab in Sweden to ensure that it was pure ginseng supplement and had no additives. They quantified participants' psychological variables such as total mood disturbance (depression and anxiety), as well as positive and negative feelings both before and at the end of the 8-week trial.

No psychological benefits were found after eight weeks of ginseng supplementation, at either the clinically recommended level (200 milligrams) or at twice that level. The investigators report that the study offers more evidence that a physician or a registered dietitian should provide input in the decision to initiate herbal therapy.

Ginseng has been revered as a product with medicinal property and is used more selectively in Asia. A major problem in ginseng supplement studies done in the West is that they are relatively short-term studies focused on a young and healthy population. Many studies done in China have reportedly shown ginseng's beneficial effect in older persons and persons who are sick or physically and mentally weak.

Researchers caution that more studies are needed to see whether the findings hold in other populations. In the meantime, skepticism about the claims made by both sides on ginseng is probably warranted.

Bradley J. et al. J Am Diet Assoc vol. 101, Number 6; June 2001

NIH and Drug Companies Battle Osteoarthritis

The NIH and four pharmaceutical companies recently launched a combined initiative to gather critical information about osteoarthritis in a bid to hasten the development of a cure. There is currently a lack of good data about osteoarthritis, principally regarding the disease's early physiological signs and symptoms. Current information about the disease available for use is poorly organized, making it difficult for scientists to develop a uniform standard that they can use to find a cure for osteoarthritis.

Physicians currently monitor the disease through X-rays and blood tests. Researchers are finding that those methods are not adequate to properly evaluate potential new drugs. The blockage in drug development now exists because researchers have not identified early markers of the disease.

The Osteoarthritis Initiative will collect data from 5,000 people at high risk of developing the disease. Public funding for the initiative has been estimated at $8 million per year from the NIH, GlaxoSmithKline, Merck, Novartis and Pfizer to establish up to six clinical trials. ® Scientists will be working to determine early markers of osteoarthritis risk. Pharmaceutical companies will then use the data to design drugs that can slow or eradicate osteoarthritis in high risk and affected individuals.

Survival After Lung Cancer Resection

For patients who have undergone high-risk operations for cancer, postoperative mortality rates are often lower at hospitals where more of these procedures are performed. Researchers recently carried out a population-based study to estimate the extent to which the number of procedures performed at a hospital (hospital volume) is associated with survival after resection for lung cancer.

The study, published in the July 19 New England Journal of Medicine indicates that people who receive surgery to treat lung cancer live longer and have fewer complications if they are treated at a teaching hospital that performs a lot of these surgeries. Data from 2,118 patients treated at 76 hospitals between 1985 and 1996 were studied. Five years after surgery, 44% of the people treated at the two medical centers that performed the most lung cancer surgeries (between 67 and 100 procedures) a year survived at least 5 years, compared to 33% of people treated at the 34 hospitals that did fewer than nine such surgeries a year.

The study suggests that hospital characteristics around the time of surgery, and not patient factors, were the reason for the difference in outcome, according to the researchers. These findings should not be used to determine the status of a particular hospital, but to learn more about why these differences in care occur between patients receiving what is essentially the only treatment for lung cancer.

Bach, PB et al. New Eng. J Med. Volume 345(3):181-188 July 19, 2001

Linezolid Resistance to Staphylococcus Aureus Identified

An 85-year-old man undergoing peritoneal dialysis appears to be the first reported case of linezolid resistance to Staphylococcus aureus, researchers report in the July 21 edition of Lancet. This is reportedly the first clinical isolate of methicillin-resistant Staphylococcus aureus (MRSA) found that is resistant to the new antimicrobial agent linezolid. Physicians from Massachusetts General Hospital, in Boston, noted that during the clinical trials there have been reports of resistance to linezolid in vancomycin-resistant enterococci. Staph areus, however, is a far more virulent pathogen.

This article comes at a time when the CDC has launched an initiative to reduce the use of vancomycin among hospitalized patients. Vancomycin is the only other drug except for linezolid that can be used to treat MRSA. Luckily for the patient who was the subject of this article, the strain of Staphylococcus aureus that was resistant to linezolid was susceptible to other more commonly used antibiotics. This is unlike most other MRSA isolates.

Researchers believe that the key is that clinical laboratories and physicians are aware that resistance can occur and that there should be routine testing of Staphylococcus and enterococcal isolates for resistance to linezolid. Pharmacia, the manufacturer of linezolid, notes in a company statement that they were aware that resistance to Staphylococcus aureus could develop and they have already made these data available to the medical community.

The article adds that no other cases of linezolid-resistant S aureus have been reported, despite the fact that more than 80,000 patients have been treated worldwide with linezolid in the US and 15 other countries.

Tsiodras S et al., Lancet 2001;358:207-208.

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