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Postuar nga NS-6 datė 25 Maj 2007 - 00:50:

Could Early and Continuous HIV Therapy Achieve Eradication?

Cod. B25052007

one of the main reasons why HIV therapy fails is the persistence of the virus in unknown viral reservoirs. there are still unknown reservoirs , and the effect the drugs might have on these reservoirs is not well understood.however research continues to give new clues concerning these reservoirs and probable drug effect! the following article is a result of these efforts to eradicate this virus


The decay rate of the HIV reservoir in patients treated early in infection raises the question of whether eradication is possible with prolonged continuous therapy.

Eradication of HIV infection has not been possible, even with potent combination antiretroviral therapy (ART), because the virus persists in resting CD4 cells and other viral reservoirs. Estimates of the half-life of such viral reservoirs vary widely, but most of the relevant studies have involved patients who initiated ART during chronic infection.

Investigators from the NIH and the University of Washington now report results from a longitudinal study of seven patients who had initiated ART 0.3–4.4 months (mean, 2.7 months) after the onset of symptoms of primary HIV infection. The patients had received ART for 31.1–54.0 months (mean, 40.4 months) and had achieved maximal viral suppression. Throughout therapy, the researchers performed serial measurements on each patient to determine the number of circulating resting CD4 cells carrying replication-competent HIV.

The number of latently infected CD4 cells declined rapidly in each patient, with the half- life of the viral reservoir estimated to be 1.9–8.7 months (mean, 4.6 months). Assuming 106 latently infected CD4 cells at baseline, the projected time to complete elimination of HIV in the resting CD4-cell reservoir would be 3.1–14.5 years (mean, 7.7 years).

Comment: The short half-life of latently infected resting CD4 cells in this study raises the question of whether viral eradication is possible. However, if HIV populates reservoirs other than circulating CD4 cells early in infection, or if the decay rate slows over time, viral eradication might not be possible, at least until more-potent ART or new strategies to purge the reservoir are available.

— Daniel J. Diekema, MD, MS

Published in Journal Watch Infectious Diseases May 23, 2007

Postuar nga NS-6 datė 26 Maj 2007 - 10:23:

More Support for Fecal Immunochemical Testing

Cod. A26052007
one of the main,noninvasive test performed to find any suspect for colorectal masses is the guaiac test (a fecal occult blood detecting test). the problem with this test is that it is affected by many variables that may produce false positives and false negatives. the presence of non human hemoglobin, rehydration may produce false positives meanwhile hemoglobin degradation or vitamin C may produce false negatives. however the rate of these false results depend on the bleeding site. to prevent these false results,new methods are developed and their efficiency is getting analysed. the following article talks about one of these. it mainly concerns the usage of these methods in detecting colorectal cancers

also, i'd like to recommend you a review article present in the New England Journal of Medicine (NEJM 1999; 341: 38-46) that analysis the main fecal occult blood detecting test. i found it very interesting and i hope you find it the same

More Support for Fecal Immunochemical Testing

Immunochemical testing is emerging as superior to guaiac-based testing for colorectal cancer screening.

Many studies have indicated that immunochemical testing is superior to guaiac-based testing for detecting fecal occult blood. Adding to this evidence base is a French study, in which 10,673 average-risk adults completed both standard guaiac-based testing (nonrehydrated Hemoccult II) and quantitative immunochemical testing (Immudia/RPHA). Of the 886 study participants who had positive results on one or both tests, 644 underwent colonoscopy. Of these, 294 had adenomas or cancer.

The immunochemical test outperformed the guaiac-based test at every evaluated hemoglobin threshold. At the usual threshold of 20 ng/mL, the immunochemical test identified 50% more cancers and 256% more high-risk adenomas than did the guaiac-based test. However, the increased sensitivity resulted in lower specificity, such that 47 false-positive results would be required to detect 1 extra case of invasive colorectal cancer, and 2.2 false-positive results would be required to detect 1 extra advanced adenoma. With a threshold of 50 ng/mL, the immunochemical test detected 2.3 times as many advanced neoplasias as the guaiac-based test did, with no loss of specificity. At a threshold of 75 ng/mL, the overall rate of positive results on the immunochemical test was similar to that of the guaiac-based test (2.4%), with a 90% gain in sensitivity and an actual improvement in specificity (a 33% reduction in false positives).

Comment: The time has come to replace guaiac-based testing for colorectal cancer with fecal immunochemical testing wherever possible. One powerful advantage of the quantitative testing method is that the performance characteristics can be adjusted to meet the goals of specific screening programs by altering the threshold level for a positive test.

— Douglas K. Rex, MD

Published in Journal Watch Gastroenterology May 25, 2007


Guittet L et al. Comparison of a guaiac based and an immunochemical faecal occult blood test in screening for colorectal cancer in a general average risk population. Gut 2007 Feb; 56:210-4.

Postuar nga NS-6 datė 03 Qershor 2007 - 12:30:

Reducing the Intensity of Treatment in Mild Asthma

Cod. B03062007

Two randomized trials demonstrate the feasibility of step-down therapy in patients whose asthma is well controlled.

Many patients with mild asthma take standard daily doses of inhaled corticosteroids indefinitely. Two new industry-supported, placebo-controlled, randomized trials — each with about 500 participants whose mild asthma was controlled with twice-daily inhaled steroids — show that "step-down" therapy may be reasonable for such patients.

One study compared twice-daily inhaled steroid therapy with once-daily oral or inhaled alternatives. Patients received one of three treatments: inhaled fluticasone (Flovent Diskus, 100 µg), twice daily; combined fluticasone/salmeterol (Advair Diskus, 100/50 µg), once daily in the evening; or oral montelukast (Singulair), once daily. At 16 weeks, treatment failure (an endpoint that included several clinical and spirometric outcomes) had occurred in 20% of patients in each inhaled-therapy group and in 30% of montelukast patients, a significant difference. This difference reflected primarily spirometric outcomes, and not differences in need for systemic steroids or urgent asthma care.

The second study examined the relatively novel idea that as-needed inhaled steroids might be as effective as daily maintenance therapy. Patients received one of four treatments: twice-daily inhaled beclomethasone (250 µg) with as-needed albuterol; twice-daily combined beclomethasone/albuterol, with as-needed albuterol; the same beclomethasone/albuterol combination, but only as needed; and as-needed albuterol only. At 6 months, the primary outcome — morning peak expiratory flow rate — was similar in the twice-daily beclomethasone and the as-needed beclomethasone/albuterol groups, and was significantly higher in both groups than in the as-needed albuterol group. Both twice-daily beclomethasone and as-needed beclomethasone/albuterol were associated with fewer exacerbations than as-needed albuterol.

Comment: These important trials demonstrate the feasibility of step-down therapy in patients whose mild persistent asthma is well controlled with standard twice-daily inhaled corticosteroids. An objective of this research is to minimize cumulative lifetime exposure to inhaled steroids, which may have systemic effects after years of use. The first trial shows that once-daily montelukast or a once-daily combination of an inhaled steroid plus salmeterol are both reasonable alternatives (although treatment failures occurred somewhat more frequently with montelukast). In the second trial, symptom-driven inhaled corticosteroids worked as well as daily therapy in patients with mild asthma.

— Allan S. Brett, MD
the studies mentioned in the article have been published in the New England Journal of Medicine. if any of you have any access or need to browse those articles for any interest,here are the citations :

-The American Lung Association Asthma Clinical Research Centers. Randomized comparison of strategies for reducing treatment in mild persistent asthma. N Engl J Med 2007 May 17; 356:2027-39.

-Papi A et al. Rescue use of beclomethasone and albuterol in a single inhaler for mild asthma. N Engl J Med 2007 May 17; 356:2040-52.

Postuar nga NS-6 datė 27 Qershor 2007 - 00:43:

Stimulating Platelet Production

the progress in understanding the way stem cells get transformed in blood cells brought to life the concept of growth factors synthesis.they can play the same role as the factors produced by the body. this concept may bring great benefit in diseases where there is placelet destruction or lack of production increasing so the risk of hemorrhages due to lack of placelets. the following article considers the recent progresses in this research and analysis the benefit of the new placelet production stimulators (NS-6)

New megakaryocyte-stimulating agents might allow patients with thrombocytopenia to avoid drug toxicity.

Three classes of agents that stimulate platelet production are being developed. These all bind to and stimulate the thrombopoietin (TPO) receptor: TPO peptide mimetics (e.g., AMG 531), TPO nonpeptide mimetics (e.g., AKR-501, eltrombopag), and TPO-agonist antibodies (genetically modified to create small bivalent fragments called minibodies; Blood 2007; 109:4607). All of the agents raise platelet counts in animal models; two, AMG 531 and eltrombopag, are currently in clinical development. AMG 531, when injected weekly for 6 weeks, significantly increased platelet counts in 12 of 16 patients with immune thrombocytopenic purpura (ITP; N Engl J Med 2006; 355:1672).

In a phase 1 dose-finding study of eltrombopag, conducted by industry employees, the drug (range, 5–75 mg) was given orally once daily for 10 days to 73 healthy men. Plasma samples were collected through day 28. Platelet counts increased by more than 20% above baseline in 6 of 9 men who received 30 mg, and in all 19 men who received 50 mg or 75 mg. The largest increase, 50% above baseline, was seen in men who received 75 mg daily. The platelet count began rising by day 8, peaked at day 16, and returned to baseline by day 22. The half-life of the drug was longer than 12 hours, and drug accumulated in the plasma at the higher dose levels. No consistent clinical or laboratory adverse effects were noted.

In a meeting abstract from a previous study of eltrombopag in patients with ITP, researchers reported that 86% of patients had increases in platelet counts to greater than 50,000/µL at a daily dose of 75 mg for 6 weeks. A trend toward less bleeding was seen, and no significant adverse effects manifested (Blood 2006; 108:abstract 475).

Comment: Most of the treatments that are recommended for patients with ITP (steroids, splenectomy, anti-D antibodies, cytotoxic agents, and, more recently, rituximab) are directed toward limiting the platelet destruction that occurs in this disease. However, although marrow megakaryocytes usually are increased in patients with ITP, they might not be producing platelets maximally. As demonstrated by these trials of megakaryocyte-stimulating agents, additional platelet production to raise platelet counts can be achieved in some of these patients. This new approach could allow patients to avoid some of the more toxic drugs that currently are prescribed for ITP. Furthermore, these agents could be useful in the management of thrombocytopenia that occurs in some patients with myelodysplasia, in whom megakaryocytes are present but platelet production is suboptimal. Some experts speculate that one or more of these new agents will be clinically available by the end of 2008. Whether these agents are indicated mainly for patients with refractory thrombocytopenia or also as a first-line therapy is still unclear.

— David Green, MD, PhD

(June 25, 2007)


Jenkins JM et al. Phase 1 clinical study of eltrombopag, an oral, nonpeptide thrombopoietin receptor agonist. Blood 2007 Jun 1; 109:4739-41.

Postuar nga NS-6 datė 07 Korrik 2007 - 00:19:

Mending Broken Hearts (part 1)

Cod. A07072007

By Jennifer Kahn
Foto: Robert Clark

As heart disease reaches epidemic proportions worldwide, researchers are moving away from the old "clogged-pipes" model to search for triggers lurking in our genes.

Cheeseburgers, smoking, stress, the rise of the couch potato: These are the usual suspects on the list of risk factors for heart disease, a malady reaching global epidemic proportions. Now discoveries about genetic triggers may help us spot trouble before it starts.

Gloria Stevens is lying on her back, sedated but alert, staring at an image of her own beating heart. Metaphorically, Gloria's heart is the very core of her emotional self—not to be worn on the sleeve, much less displayed on an overhead monitor. More literally, it is a blood-filled pump about the size of a clenched fist whose rhythmic contractions have kept Gloria alive for 62 years, and with a little tinkering will keep her going for an indeterminate number more.

At this moment, her doctor is threading a thin catheter up through her femoral artery from an incision in her groin, on into the aorta, and from there into one of the arteries encircling Gloria's heart. At the tip of the catheter is a small balloon. The doctor gently navigates the tip to a spot where plaque has narrowed the artery's channel by 90 percent. With a quick, practiced movement he inflates the balloon to push back the artery wall, deflates the balloon, then inserts an expandable stent—it looks like a tiny tube of chicken wire—that will keep the passage open. As Gloria watches on the monitor, the crimp in her artery disappears, and a wide laminar flow gushes through the vessel, like a river in flood.

The procedure is over. It has lasted only half an hour. In all likelihood, Gloria will be able to go home the next day. So will a few thousand other patients in the United States undergoing such routine angioplasty—more than a million of them a year. Pipe fixed, patient cured, right?


Because of her treatment, Gloria's quality of life will likely improve. She'll breathe easier and maybe live longer. But she is hardly cured. Her coronary atherosclerosis—a hardening and narrowing of the arteries that supply the heart with oxygen-rich blood—still leaves her vulnerable to future blockages and coronary heart disease.

Although hearts suffer many maladies—valves leak, membranes become inflamed—coronary heart disease, which can lead to heart attack and ultimately to heart failure, is the number one killer of both men and women in the United States, where 500,000 die annually. Worldwide, it kills 7.2 million people every year. Exacerbated by the export of Western lifestyle—motorized transport, abundant meat and cheese, workdays conducted from the comfort of a well-padded chair—incidence of the disease is soaring.

To help stem this lethal tide, cardiologists can prescribe such cholesterol-lowering drugs as statins to help keep arteries clear. They can advise patients to change their habits, or they can operate to fix an immediate problem. Angioplasty is one procedure, and surgery to bypass the diseased arteries is another—each year more than 400,000 bypasses are performed in the U.S. Transplants can replace severely damaged hearts, and artificial ones can keep people alive while they wait for a donor heart. But in the face of an impending global epidemic, none of these stopgap measures addresses the essential question: Who gets heart attacks and why?

The human heart beats 100,000 times a day, propelling six quarts of blood through 60,000 miles (97,000 kilometers) of vessels—20 times the distance across the U.S. from coast to coast. The blood flows briskly, surging out of a ten-ounce (0.3 kilograms) heart so forcefully that large arteries, when severed, can send a jet of blood several feet into the air. Normally the relentless current helps keep blood vessels clean. But where an artery bends, tiny eddies form, as in a bend in a river. This is where bits of sticky, waxy cholesterol and fat can seep into the artery wall and oxidize, like butter going rancid. Other matter piles up too. Eventually, the whole mass calcifies into a kind of arterial stucco, or plaque.

Until recently, cardiologists approached heart disease as a plumbing problem. Just as mineral deposits restrict the flow of water through a pipe, an accretion of plaque impedes the flow of blood through an arterial channel. The more crud in the system, the greater likelihood that a dammed artery will trigger a heart attack. Doctors now dismiss this "clogged-pipes model" as an idea whose time has passed. It's just not that simple.

Most heart attacks are caused by plaque embedded within the artery wall that ruptures, cracking the wall and triggering the formation of a blood clot. The clot blocks the flow of blood to the heart muscle, which can die from lack of oxygen and nutrients. Suddenly, the pump stops pumping.

Contrary to the clogged pipes model, heart attacks generally occur in arteries that have minimal or moderate blockage, and their occurrence depends more on the kind of plaque than on the quantity. Scientists have been struggling to figure out what type is most responsible. Paradoxically, findings suggest that immature, softer plaques rich in cholesterol are more unstable and likely to rupture than the hard, calcified, dense plaques that extensively narrow the artery channel. But understanding the root cause of the disease will require much more research. For one thing, human hearts, unlike plumbing fixtures, are not stamped from a mold. Like the rest of our body parts, they are products of our genes.

Postuar nga NS-6 datė 07 Korrik 2007 - 00:21:

Mending Broken Hearts (part 2)

Don Steffensen was putting duck-hunting decoys out on a small lake one fall afternoon in southwestern Iowa when his heart attack hit. The infarction was massive and unexpected. It's likely that Steffensen survived only because a buddy was carrying nitroglycerin tablets and quickly slipped one under his friend's tongue. Nitroglycerin is used to make dynamite; in the body, a heavily diluted form releases nitric oxide, which signals the smooth muscle cells in veins and arteries to relax, dilating the vessels.

The Steffensen clan is enormous: more than 200 relatives spread over three generations, many of the youngest are now dispersed from Iowa to New York and beyond. Although heart trouble is common in the family, it had never struck anyone as unusual. "I attributed it to diet," shrugs Tina, a slim 38-year-old and the family's only vegetarian.

It was a reasonable conclusion. The Steffensens were raised on the kind of farm food that the state is famous for—ham balls, meatloaf, pie, macaroni and cheese—and still popular even as careers have moved indoors. Driving north through cornfields to meet some of the family in Buffalo Center, I dined at a restaurant offering deep-fried sandwiches. A single ham and cheese hoagie—dunked in hot fat and served sizzling—seemed capable of stopping a heart all on its own.

But could the high incidence of heart trouble among the Steffensens be related to something else besides high-fat diets? Eleven years after Don's attack, his wife, Barbara, happened to overhear a doctor describing a study about the genetics of heart attacks.

Curious, Don and 20 of his relatives each sent a vial of blood to the Cleveland Clinic, where the research was being conducted. Eric Topol, a cardiologist and genetics researcher at the clinic, spent a year studying their DNA. Each person's genome comes with millions of individual variations, but Topol was looking for something distinctive—and shared only by the members of the clan with heart trouble. The mutation he and his team finally spotted, in a gene called MEF2A, produced a faulty protein. "We knew we had something," Topol says. "But the question was: How does this sick protein, present at birth, lead to heart attacks 50 years later in life?"

Topol himself is as lean as a greyhound and weathered in a cowboyish way. He talks slowly and eats minimally: salads for dinner and high-fiber cereal for breakfast. He doesn't eat lunch at all. Like almost every cardiologist I've talked to, he takes statins preventively, and his cholesterol count is a low 135. His children, 22 and 25, also eat uncommonly well for their ages. "People have looked at the cadavers of men in their 20s who died in car accidents or as casualties of war, and nearly all had arterial cholesterol deposits," Topol said as we walked to his lab. "This disease starts much earlier than people realize."

Using endothelial cells (which line the inside of the artery wall) grown in culture, Topol set about figuring out what the MEF2A mutation does. He and his coworkers created some cells carrying the Steffensen variant, and others with the normal form of the protein. Both cell proteins were tagged fluorescent green so their locations could be visualized on a computer screen. The resulting images revealed a striking difference.

In a normal cell, all the MEF2A protein was inside the nucleus; on the screen, the cell resembled a fried egg with a fluorescent green yolk. But in the cells carrying the mutated version, the nucleus did not glow; instead the cell membrane was edged by a thin, luminous green line: a layer of MEF2A protein, trapped where it cannot serve its usual purpose. Topol believes that this defect affects the integrity of the coronary artery walls, rendering them more vulnerable to cracking when the plaque embedded in them ruptures. And each crack brings an increased chance of a heart attack.

Since this discovery, the Steffensens have become famous, appearing on shows like 60 Minutes II. Their mutant gene turns up in a Robin Cook novel titled Marker, about a health insurance company in New York that secretly screens patients for the MEF2A mutation and then kills them to preempt future medical-care payouts. Lively reading, but the Steffensen gene is an unlikely target for an insurance company, in part because it is an uncommon genetic defect.

Topol's study did find that although dysfunctional MEF2A is very rare, the chance of heart disease in those carrying it may approach 100 percent. Most other genetic variations identified thus far increase the risk by much less. As it turns out, Topol himself carries a bum gene: apoE4, which affects inflammation in the arteries. Unlike MEF2A, it is common; every fourth person has it.

"Heart disease is not a one- or two-gene problem," says Steven Ellis, a Cleveland Clinic cardiologist who oversees a 10,000-person genetic study known as GeneBank that collects DNA samples from patients who enter hospitals with atherosclerosis. Ellis, like most cardiac researchers, suspects that dozens of genes end up contributing to a predisposition: Some affect arterial integrity, others inflammation (which both causes and exacerbates arterial cracks), and still others the processing of lipids (the fats and cholesterol that turn into plaques). Of the several dozen genes, each may contribute just one percent to a person's total risk—an amount that may be compounded, or offset, by outside factors like diet. As one doctor told me, any person's heart attack risk is "50 percent genetic and 50 percent cheeseburger."

The point of tracking down all these small mutations, Ellis explains, is to create a comprehensive blood test—one that could calculate a person's genetic susceptibility by adding up the number of risky (and, eventually, beneficial) variables. Combined with other important factors, such as smoking, weight, blood pressure, and cholesterol levels, doctors could decide which patients need aggressive treatment, such as high-dose statins, and which ones are likely to benefit from exercise or other lifestyle changes. Some genes already can predict whose cholesterol level will respond strongly to dietary changes and whose won't. Assessing risk is crucial, Ellis says, because heart disease is often invisible. In fact, 50 percent of men and 64 percent of women who die of heart disease die suddenly, without experiencing any previous symptoms.

Although standard tests can detect atherosclerosis, they aren't foolproof. They may reveal plaques, but give no indication whether or not they are life-threatening. Tests like angiography, for example, where doctors inject a dye into the bloodstream and track it with x-rays, can show how much blood is flowing through an artery, but not discern the plaques embedded inside the artery wall—often the culprit in a heart attack.

Researchers have been working to solve this problem with scanners that provide pictures of the arterial wall itself, but it's a tricky task. Normal cardiac artery walls are about a millimeter thick. Coronary arteries move with every beat of the heart, 70 times a minute. It's tough to get a clear image of something so small in constant motion.

Difficult, but not impossible. As I walk through the basement of the Cleveland Clinic, I pass a room containing a large, blue, plastic doughnut as tall as I am, with a woman's legs sticking out of the middle. The doughnut is a computed tomography (CT) scanner, a kind of three-dimensional x-ray machine that's also used for imaging tumors. The scanner, aided by medications that reduce a patient's heart rate and an injectable dye that highlights the arteries, can produce startlingly clear pictures.

Postuar nga NS-6 datė 07 Korrik 2007 - 00:22:

Mending Broken Hearts (part 3)

Scrolling through images on his computer monitor, Mario Garcia, the clinic's director of cardiac imaging, retrieves one that looks like a black-and-white landscape photographed from a plane, with a single, large river running through it. As Garcia zooms in on the river, a series of white lumps appears on the bank—hard plaques bright with calcium. But there is also a tiny black smudge. "That's the type we believe causes a heart attack," he says with satisfaction, pointing to the smudge of soft plaque. "It's a rare opportunity to see that."

Scrolling through images on his computer monitor, Mario Garcia, the clinic's director of cardiac imaging, retrieves one that looks like a black-and-white landscape photographed from a plane, with a single, large river running through it. As Garcia zooms in on the river, a series of white lumps appears on the bank—hard plaques bright with calcium. But there is also a tiny black smudge. "That's the type we believe causes a heart attack," he says with satisfaction, pointing to the smudge of soft plaque. "It's a rare opportunity to see that."

As compelling as the CT scan is, it's still an imperfect tool for predicting heart disease. It's expensive, for one, and the dose of radiation from the x-rays makes it ill suited for use in healthy-patient annual exams. And although it sees arterial plaques, even soft plaques inside arterial walls, it can't reveal whether those plaques are likely to crack and cause a heart attack.

Postuar nga NS-6 datė 07 Korrik 2007 - 00:24:

Mending Broken Hearts (part 4)

Until there are tests, genetic or otherwise, that give a clearer measure of risk, everyone would be advised to exercise, watch their diet, and take statins for elevated cholesterol—the same advice doctors gave when the clogged-pipes model of heart disease reigned unchallenged.

At the Cleveland Clinic, cardiologist Stephen Nissen has conducted several studies on statins such as Lipitor, which reduce the amount of LDL ("bad" low-density lipoprotein) cholesterol made by the liver. Nissen is an advocate of lowering cholesterol by any means necessary. Does he take a statin? "You bet!" he says. "I have no intention of dying of the disease I treat." His LDL level is a paltry 51. Of eight cardiologists I spoke with, all but one were taking the medication. (Some studies now seem to show that lowering even normal cholesterol levels has a protective effect.) HDL ("good" high-density lipoprotein) cholesterol is another story. Nissen calls it the "arterial-wall garbage barge" because of its ability to remove cholesterol from clogged arteries. Not all HDL can do this; some is dysfunctional. But tests have shown that raising the HDL level in genetically engineered lab mice can shrink their arterial plaques.

A drug that could raise functional HDL levels in humans would likely become the next multibillion-dollar blockbuster, and a few are in various stages of testing. However, the trial of a Pfizer drug called torcetrapib ended in failure. Torcetrapib had been shown, in combination with Lipitor, to raise HDL levels 44 to 66 percent with a once-a-day pill. But the increase was not necessarily in functional HDL, and the drug was also associated with elevated blood pressure. In December, when data showed a 60 percent higher death rate in patients taking torcetrapib with Lipitor than in those taking Lipitor alone, Pfizer abruptly ended the trial.

It's not clear whether the problem lay with one drug or an entire class of drugs. Until further research is completed, the several different statins on the market will remain the most prescribed class of drugs in the world, with 11.6 million prescriptions filled monthly in the U.S. alone. Pfizer's Lipitor may be the best-selling drug ever made, with 12 billion dollars in annual worldwide sales.

But statins, like any drug, carry the risk of side effects: Muscle aches are a well-known effect, and periodic blood tests to check liver function are recommended. The fact is, many of us just like to eat cheeseburgers, watch television, and get around in cars. And it's hard, says Leslie Cho, director of the Cleveland Clinic's Women's Cardiovascular Center, for a person to worry about a disease that hits ten years down the road—particularly since heart patients, unlike cancer patients, can't easily observe the progress of their disease. "You've done damage over years, and it will take years to undo that damage," she says. "That's a very hard thing to sell to Americans. We do what we can, but then people go home."

The good news is that genetic research continues to thrive. Should we want to, we will soon be able to know the state of our hearts—and our genes—in ever growing detail. That knowledge, and what we do with it, could make the difference between dying at 65 and living until 80. The choice, increasingly, will be ours.

(National Geographic)

Think Again

Postuar nga NS-6 datė 26 Korrik 2007 - 15:25:

A Controlled Clinical Trial of Steroids for Bronchiolitis

Cod. C26072007

One dose of oral dexamethasone was no different from placebo.

Bronchiolitis is the leading cause of hospitalization of infants in the U.S. Use of steroids for infants with bronchiolitis remains controversial because of the lack of high-quality, sufficiently powered studies. In a multisite, double-blind clinical trial, researchers randomized 600 infants (age range, 2–12 months) who presented to the emergency department with no prior history of wheezing and a clinical picture consistent with moderate-to-severe bronchiolitis to receive either a single dose of oral dexamethasone (1 mg/kg) or placebo. The primary outcome was hospitalization 4 hours after drug administration.

The admission rate was virtually identical in the steroid and placebo groups (39.7% and 41.0%, respectively). No differences emerged in subgroup analyses of infants who were positive for respiratory syncytial virus, those younger than 6 months, or those with a history of eczema or a family history of asthma. Mean length of stay for hospitalized infants and subsequent admissions during the 7 days after the intervention were similar in the two groups.

Comment: This study likely represents the definitive study on the use of steroids for infants with bronchiolitis in the ambulatory care setting — steroids convey no benefit. However, infants with a prior history of wheezing were excluded. I am sure some clinicians will continue to administer steroids to infants who are admitted with bronchiolitis despite the lack of compelling evidence. I do not believe that steroids have a role in the treatment of bronchiolitis.

— Howard Bauchner, MD

Published in Journal Watch Pediatrics and Adolescent Medicine July 25, 2007


Corneli HM et al. A multicenter, randomized, controlled trial of dexamethasone for bronchiolitis. N Engl J Med 2007 Jul 26; 357:331-9.

Postuar nga NS-6 datė 06 Shtator 2007 - 23:03:

FDA Approves Novel Antiretroviral Drug

Cod. A07092007

August 6, 2007

The U.S. Food and Drug Administration (FDA) today approved maraviroc, an antiretroviral drug for use in adult HIV patients. Maraviroc, sold under the trade name Selzentry, is the first in a new class of drugs designed to slow the advancement of HIV and received priority review by the FDA.

Maraviroc is approved for use in combination with other antiretroviral drugs for the treatment of adults with CCR5-tropic HIV-1, who have been treated with other HIV medications and who have evidence of elevated levels of HIV in their blood (viral load). Rather than fighting HIV inside white blood cells, maraviroc prevents the virus from entering uninfected cells by blocking the predominant route of entry, the CCR5 co-receptor. CCR5 is a protein on the surface of some types of immune cells. Among patients who have previously received HIV medications, approximately 50 percent to 60 percent have circulating CCR5-tropic HIV-1. "This is an important new product for many HIV-infected patients who have not responded to other treatments and have few options," said Steven Galson, M.D., M.P.H., director of FDA's Center for Drug Evaluation and Research.

The product label includes a boxed warning about liver toxicity (hepatoxicity) and a statement in the Warnings/Precautions section about the possibility of heart attacks. The FDA's approval of maraviroc is based on safety and effectiveness data from two double-blind, placebo-controlled studies. The 1,076 clinical trial participants were selected because they still showed evidence of HIV-1 in their blood, despite treatment with other HIV medications. A blood test for CCR5 tropic HIV-1 was used during clinical trials to identify patients appropriate for treatment with maraviroc.

The safety and effectiveness of maraviroc have not been established in adult and pediatric patients who have never been treated with any other HIV drug. Additionally, the drug has not been tested or studied in pregnant women. The FDA recommends that HIV positive women should not breast feed, whether or not they are on antiretroviral medications.

The most common adverse events reported with maraviroc were cough, fever, upper respiratory tract infections, rash, musculoskeletal symptoms, abdominal pain, and dizziness.

Maraviroc is distributed by New York-based Pfizer Inc.

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