A Virus moves West

(and North, and South....) | By Janet Ginsburg

	Click to view a PDF of the virus' spread across the U.S. (244K)

Humans, birds, and mosquitoes propelled the spread of West Nile Virus in the US from coast to coast in less than four years. Various secondary cycles played a part as well. (see West Nile: The Virus that Came to Stay)

Map adapted from Centers for Disease Control and Prevention data; other information compiled by Janet Ginsburg (jgstories@yahoo.com).

The Evolution of Varicose Vein Treatment

William H. Pearce, MD, FACS

William H. Pearce, MD, FACS, Northwestern University Feinberg School of Medicine

Drugs Blocking the Renin-Angiotensin System Offer Advantages Beyond Lowering Blood Pressure
Using antihypertensive agents to decrease blood pressure (BP) is of clinical benefit, but drugs that block the renin-angiotensin system offer advantages in addition to reduced BP, according to the conclusion of a new review article. Peter Sleight, MD, John Radcliffe Hospital, Oxford, United Kingdom, and Salim Yusuf, MD, DPhil, Hamilton Health ...Full Story

• Painful diabetic peripheral neuropathy relieved with use of oral topiramate (South Med J - DGReview)
• Current and future aims of lipid-lowering therapy: changing paradigms and lessons from the heart protection study on standards of efficacy and safety (Am J Cardiol - DGReview)
• NAMS: Increased Risk of Dementia in Postmenopausal Women on Hormone Therapy (DGDispatch)
• Atrial Fibrillation in the Elderly (Curr Treat Options Cardiovasc Med - DGReview)
• NAMS: Hormone Therapy May Need to be Used Cautiously in Patients Taking Rosiglitazone (DGDispatch)
• Who should be treated with combination therapy as initial treatment for hypertension? (J Clin Hypertens (Greenwich) - DGReview)
• RAAS Escape: A Real Clinical Entity that May Be Important in the Progression of Cardiovascular and Renal Disease (Curr Hypertension Rep - DGReview)
• Evaluation of long-term safety of the anti-IgE antibody, omalizumab, in children with allergic asthma (Ann Allergy Asthma Immunol - DGReview)
• ICAAC: Amoxicillin Remains Treatment of Choice in Children with Middle-ear Infections (DGDispatch)
• ICAAC: Amoxicillin/Clavulanate May Be Better than Azithromycin for Acute Otitis Media in Children (DGDispatch)

• New evidence on the importance of the renin-angiotensin system in the treatment of higher-risk patients with hypertension (J Hypertens - DGReview)
• Randomized double-blind study comparing 3- and 6-day regimens of azithromycin with a 10-day amoxicillin-clavulanate regimen for treatment of acute bacterial sinusitis (Antimicrob Agents Chemother - DGReview)
• The changing model of insulin use in type 2 diabetes (Postgrad Med - DGReview)
• Antiproteinuric efficacy of losartan in comparison with amlodipine in non-diabetic proteinuric renal diseases: a double-blind, randomized clinical trial (Nephrol Dial Transplant - DGReview)
• Selective serotonin reuptake inhibitors combined with venlafaxine in depressed patients who had partial response to venlafaxine: four cases (Prog Neuropsychopharmacol Biol Psychiatry - DGReview

Drug halts progress of "mad cow disease" in UK man

Last Updated: 2003-09-26 15:14:36 -0400 (Reuters Health)

By Alex Richardson

BELFAST (Reuters) - An experimental treatment given to a Northern Irish teenager has halted the progress of brain damage caused by the human form of mad cow disease, medical experts studying his case said on Friday.

Jonathan Simms, 19, from Belfast, is the first person to have pentosan polysulphate (PPS) injected into his brain in an attempt to slow the damage caused by variant Creutzfeldt-Jakob Disease (vCJD).

"Here we have a kid who had gone down and down and down, now he's put all the weight he had lost back on, his heart rate is back up to normal," said Stephen Dealler, a consultant microbiologist at the Royal Lancaster Infirmary in England.

"It is one case, and you can't go round saying we have the answer, but it has justified large amounts of work to go ahead to find out what was really going on, to find out why the drug appeared to have such an effect and which way to go from here."

He was speaking after experts from several countries gathered at a Belfast hotel for a case conference organised by the teenager's father Don Simms to discuss whether PPS has been effective in stabilising Jonathan and prolonging his life.

Although Jonathan remains confined to bed with limited ability to move or interact with those around him, Don Simms said he had seen "small but significant" improvements since winning the right to give his son the experimental treatment.

"He's not dead, that's the most significant thing. His swallow has increased, so that he can deal with his own secretion of saliva, which is a big thing for CJD sufferers," he told Reuters.

"He's living 10 months longer than the average, I was told he had a year by two experts, in two different countries."

There is no cure for vCJD, which is fatal and has been linked to eating meat from cattle infected with Bovine Spongiform Encephalopathy (BSE), also known as mad cow disease.

LEGAL BATTLE

Doctors began giving Jonathan the drug, commonly used to treat cystitis, after his family won a legal battle last December. Health officials needed court permission as the treatment had not been tested on humans and the disease had left Jonathan incapable of deciding for himself.

"I'm not a salesman for PPS, that's entirely up to other families," said Simms, when asked if he thought the drug should be made available to other sufferers.

"But the information we have now - no one had that - and I don't want those other families, if they wish to have the compound, to have to jump the same hurdles as we did."

Doctors and scientists at Friday's conference said more research was needed to confirm PPS as a treatment for vCJD, but believed it should be given to more sufferers.

"I am absolutely convinced, as a scientist, that if Jonathan had been treated earlier we would not see Jonathan in as poor a state as he is now," said Chris Pomfrett, a lecturer in neurophysiology at Manchester University, in northern England.

"The delay that happened with Jonathan must not be allowed to happen to others."

Jonathan's family doctor, Mark McClean, said he was frustrated the drug had not been administered when his family first requested it in March 2002.

"Given the choice between certain death in a matter of weeks or months, and treatment, albeit experimental, which could have even a one-in-a-million chance of halting the disease, there's no choice. I would choose the treatment," he said.

"In our study, of one, admittedly, against all the experts advice we proved it has been safe... and it has been effective in halting the disease, and perhaps improving his state of mind."

Britain destroyed 3.7 million cattle in the 1980s and 1990s because of BSE. There have been nearly 120 confirmed or probable deaths in Britain from vCJD.

Diabetes and cancer: an unexpected link

Antidiabetes drugs may also help in the treatment of some forms of cancer | By Andrea Rinaldi

An intriguing study in the September 24 Journal of Biology—published by BioMed Central, a sister company of The Scientist—suggests there could be a previously unrecognized anticancer benefit from treatment with some common antidiabetic drugs. Simon A. Hawley and colleagues at the University of Dundee show how the tumor suppressor protein kinase LKB1 is linked to AMP-activated protein kinase (AMPK), the target enzyme for several drugs commonly used to treat type 2 diabetes (Journal of Biology, 2:28, September 24, 2003).

AMPK acts as a "metabolic master switch," reducing glucose levels and inhibiting biosynthetic pathways and cell proliferation. A lack of, or a mutation in, the LKB1 gene gives rise to Peutz-Jeghers syndrome, an autosomal dominant human disorder in which the risk of developing malignant tumors in some tissues is 15-fold higher than normal. Both the activation pattern of AMPK and the LKB1 substrate have been poorly understood, but recent observations suggest that the latter is associated with a group of accessory proteins known as STRADα/β and MO25α/β, which increase the kinase activity of LKB1.

Hawley et al. purified two forms of AMPK from rat liver and observed that both fractions contained LKB1, STRADα, and MO25α and that the AMPK activity could be immunoprecipitated using anti-LKB1 antibodies. Recombinant LKB1–STRADα/β –MO25α/β complexes fully activated AMPK in cell-free assays, providing further support for the idea that the link between AMPK and LKB1 has a functional background. In addition, the authors demonstrated that LKB1-mediated activation of AMPK also takes place in vivo in HEK-293T cells, but not in HeLa cells (which don't express LKB1 and therefore represents a natural knockout cell line). In HeLa cells, activation was achieved by stably expressing recombinant LKB1. This suggests that the tumor-suppressing properties of LKB1 may depend on its ability to activate AMPK.

"Our findings provide strong evidence that LKB1–STRAD–MO25 complexes represent the major upstream kinases acting on AMPK, although they do not rule out the possibility that the complex might contain additional components," conclude the authors.

Having established the LKB1–AMPK connection, Hawley et al. attempted to verify if antidiabetic drugs targeting AMPK by increasing its enzymatic activity could be affected by LKB1 in vivo. They observed that metformin—the most widely used diabetes drug in the world—could not activate AMPK in HeLa cells, presumably since they lack LKB1, and that expression of recombinant LKB1 restored the ability of HeLa cells to respond to the drug. The authors speculate that metformin, and possibly other diabetes drugs, may work by directly activating LKB1, which in turn activates AMPK, leading to glucose sequestration—with immediate benefits for those with diabetes—and to inhibition of cell growth and division, which ultimately prevent tumor development and proliferation.

New birth control to limit women's periods

By Amy Cox
and Christy Feig
CNN
Monday, September 8, 2003 Posted: 1:21 PM EDT (1721 GMT)

Seasonale, approved by the Food and Drug Administration on Friday, would reduce the number of women's periods to four a year by taking the hormones generally found in conventional birth control pills, but for longer spans of time.

Seasonale would be another alternative for women seeking birth control, said an official with the pill's manufacturer, Barr Laboratories.

"For women who desire prevention of pregnancy and are comfortable taking a hormonal contraceptive, then this gives them an option," says Dr. Carole Ben-Maimon, president and COO of Barr Research. "We see it as a [choice] for those wanting the convenience."

First introduced in the 1960s, the most common birth control pills combine the hormones estrogen and progestin for use for three weeks followed by a week of placebos to allow a woman to have her period. Seasonale, however, uses the same types of hormones but for 12 weeks straight before a week of placebos.

Not having as many periods -- and the medical problems surrounding them -- has some women intrigued.

Kelley Barclay joined more than 1,400 women in a clinical trial of Seasonale because her monthly period plagued her with cramps, mood swings and pain.

"My mood swings were not at all like they had been before, not at all severe, and my pain was not at the level that it had been before I started Seasonale," she explains.

Almost 39 million women in the United States use some kind of birth control, according to the Kaiser Family Foundation. The most common reversible method is oral contraceptives, in use by an estimated 25 percent of women who use birth control.

The technique of taking birth control pills continuously to keep from having a period isn't new.

For instance, Dr. Carolyn Westhoff, an obstetrician-gynecologist at Columbia Presbyterian Medical Center in New York, has been using regular packs of birth control pills back-to-back to skip her period for about 10 years.

"It's really terrific not to have the bleeding, not to have the cramps, not to have some of those symptoms that lead up to a period," she says. "And I think many women will be really eager to trade in 14 a year for four a year."

Westhoff, not associated with the clinical trials, had said she would prescribe Seasonale to her patients if it won FDA approval.

"Using Seasonale, ... I think mainly is going to add a lot of convenience for women and freedom from the symptoms they have with their periods."

But Dr. Susan Rako -- author of "No More Periods?" -- argues that there are good medical reasons for a woman to have a period.

"Bleeding is the only way our bodies can rid themselves of excess stored iron, and excess stored iron is another risk factor for heart attack and strokes," Rako says. "And that's why in their menstrual years, women have fewer heart attacks and strokes than men."

Rako said other issues are raised, too, when considering period suppression.

"We're not just talking about doing away with menstruation," she says. "We're talking about doing away with women's normal hormonal menstrual cycle, which is really responsible for what fundamentally makes a woman a woman."

Barr's Ben-Maimon says that Seasonale is as effective at preventing pregnancy as other oral contraceptive products. The failure rate for traditional birth control pills is around 1 to 2 percent with perfect use, according to the FDA.

Some women should not use birth control pills, including those who smoke cigarettes, particularly if they're older than 35. There is a slight increase in risk for blood clots and high blood pressure

Venous thrombosis risk lower with transdermal rather than oral ERT

Last Updated: 2003-09-26 12:30:05 -0400 (Reuters Health)

By Megan Rauscher

NEW YORK (Reuters Health) - Unlike transdermal estrogen replacement therapy (ERT), oral ERT induces activated protein C (APC) resistance, a risk factor for venous thromboembolism, and activates blood coagulation, according to a randomized study conducted in France.

"This randomized trial highlights the importance of the route of estrogen administration in prescribing postmenopausal hormone therapy," Dr. Emmanuel Oger from Dandenong Hospital in Victoria, Australia, told Reuters Health.

Oral ERT is known to raise the risk of venous thromboembolism (VTE), but less is known about the effects of transdermal estrogen, he and his colleagues write in the September issue of Arteriosclerosis Thrombosis and Vascular Biology: Journal of the American Heart Association.

To investigate, they randomly assigned 196 postmenopausal women to placebo or to oral estradiol (1 mg/d) or transdermal estradiol (50 µg/d), both combined with oral micronized progesterone (100 mg/d) for 6 months.

Oral but not transdermal ERT significantly altered the effect of APC on thrombin generation (ETP-based assay), "leading to an acquired APC resistance," the team reports.

Moreover, after 6 months, plasma prothrombin fragment 1+2 levels, a marker of coagulation activity, were significantly higher in the oral estrogen arm than in the transdermal or placebo arms and were positively and significantly correlated with changes in ETP-based assay.

"Taken together, these data provide a plausible biologic mechanism to the clearly demonstrated association between oral estrogen and venous thrombosis," the team writes.

Furthermore, Dr. Oger said, the study adds to a "strong body of biological evidence that suggests a lower risk for venous thrombosis, if any, among users of the [estrogen] skin patch."

For example, in a case-control study published in The Lancet in August, current oral ERT users were 4 times more likely to develop VTE than current transdermal ERT users (See Reuters Health report Aug. 7, 2003).

"Whether transdermal ERT is a safe option for the relief of severe climacteric symptoms needs further investigation that our study might well stimulate," Dr. Oger and colleagues conclude.

Arterioscler Thromb Vasc Biol 2003;23:1671-1676.