We know that people tend to lose muscle mass as they age. We know that sedentary lifestyles, hormonal changes, oxidative damage and infiltration of fat into muscles are common causes of the phenomenon.

But few of us know that age-related loss of muscle can be a profound cause of disability. The condition affects nearly 10% of people over the age of 60, and it has been estimated to account for at least $18.5 billion per year in direct medical costs.

A growing understanding of the economic costs of age-related muscle wasting has sparked renewed interest in the matter by scientists, pharmaceutical and food companies, and of course, by all those aging baby boomers.

Drug companies are searching for compounds other than the notoriously dangerous anabolic steroids that can build muscle or delay age-related muscle loss. Food conglomerates like Danone and Nestlé are looking for nutritional products that have the same effect.

For commercial enterprises like these to succeed, of course, the condition needs to be clearly defined. Call it creating a disease if you wish, but “if you are trying to sell drugs, you want to have a very clear criterion for diagnosing the problem and for endpoints to treat it,” UCSF’s Thomas Lang explained to the New York Times.

Lang and other scientists have settled on the term “sarcopenia” to describe the condition. Some prefer to think of the matter simply: sarcopenia is to muscle what osteoporosis is to bone. However, some studies have shown that strength, as manifested by gripping force, or muscular function, as measured by, say, walking speed, are better predictors of future problems for the elderly.

Meanwhile, experts agree that for now, exercise, especially resistance (weight) training is the best way to restore or maintain muscle mass. Adequate nutrition, particularly Vitamin D and perhaps protein intake, may also help. See you at the gym!

Plexxikon announced last week that its experimental drug shrank melanoma tumors in a whopping 81% of the patients who received it.

Scientists suggested that the positive results from this early-stage trial might represent a breakthrough in the treatment of a notoriously recalcitrant malignancy, even though the drug’s beneficial results were not permanent. The cancers began growing again in every patient but two after the course of treatment ended.

“Metastatic melanoma is a challenging disease to treat. There have been no significant therapeutic advances in the past 20 years,” Paul Chapman, senior author of the study told BurrillReport.

“We learned that half of melanomas are addicted to a mutated gene called BRAF; this new drug inhibits BRAF and shuts off these tumors,” added Chapman, who is an attending physician at the Melanoma and Sarcoma Service at Memorial Sloan-Kettering.

The BRAF mutation occurs in 40-60% of people with melanoma.

Berkeley-based Plexxikon’s experimental drug is called PLX4032. It appeared to shrink metastatic lesions in multiple locations including liver, bone and the small bowel.

Plexxikon has co-developed the drug with Roche under a license and collaboration agreement. Roche also plans to market a gene-based diagnostic tool that can identify melanoma patients who carry the genetic peculiarity that renders their cancers receptive to PLX4032.

Plexxikon has begun mid- and late-stage studies of its drug simultaneously in an effort to find out as quickly as possible whether it can improve survival in patients with melanoma.

A small study has linked multiple blows to the head, sustained during athletic competition, to a degenerative brain condition similar to Lou Gehrig’s disease.

In the study, Bob Cantu, a neurosurgeon at Boston University Medical Center and colleagues examined brain and spinal cord tissue from a dozen former athletes that had died. Three of them had been diagnosed with ALS before their deaths.

Each athlete had sustained multiple concussions. One of them had at least 10 concussions. The subjects were found to have protein deposits known as tau and TDP-43 in their brains and spinal cords. These proteins have previously been found in the brains, but not the spinal cords of patients with ALS.

The fact that similar proteins were found, but in a different distribution from “classic” ALS suggests that the neurodegenerative disorder associated with multiple head trauma is similar to, but distinct from the classic disease.

Repetitive head injuries include both full-blown concussions and less severe blows to the head, said Robert Stern, in an interview with the Wall Street Journal. The study co-author added that “concussions are really the tip of the iceberg.”

This doesn’t mean children shouldn’t participate in contact sports, cautioned Gerard Gioia, chief of pediatric neuropsychology at Children’s National Medical Center. “The benefits of kids’ activities in sports, in recreation, in physical exercise far outweigh the risks,” Gioia told the Journal. “But that doesn’t mean we ignore the risk.”

Previous studies have suggested that repetitive head trauma increases the risk of other degenerative brain disorders including Parkinson’s disease (think about Muhammad Ali) and Alzheimer’s disease.

The write-up appears in the Journal of Neuropathology and Experimental Neurology,

Last week, federal regulators gave the go-ahead for the nation’s first trial of embryonic stem cells in human beings. Geron Corporation will run the trial. It is designed to assess the safety of so-called GNROPC1 oligodendrocyte stem cells in treating spinal cord injuries.

Geron plans to begin testing by year-end. It will enroll about 10 patients over 2 years and follow them for 15 years after treatment. For safety reasons, Geron will space-out each enrollee by at least 30 days.

The primary purpose of the trial will be to determine whether GRNOPC1 is safe. Geron will assess efficacy as a secondary outcome.

The treatment involves injecting the stem cells into the spinal cord of injury victims 1-2 weeks after the injury occurs.

The FDA originally accepted Geron’s study application in January, 2009. It subsequently held things up after Geron reported that mice treated with GRNOPC1 had developed tiny cysts on their spines. According to Geron, many patients with spinal cord injuries develop larger cysts as the injury heals. Geron also reported that the cysts were not observed in a second animal study.

Oligodendrocyte stem cells mature into myelin-producing oligodendrocytes. Myelin forms a sheath around nerve cells that protects them and facilitates conduction of impulses via the nerves from the brain to the muscles, skin and internal organs. The hope is that the GRNOPC1 stem cells will facilitate healing of damaged spinal cord tissue and restore normal nerve conduction.

Embryonic stem cell research is controversial because in some cases, the cells are obtained from aborted human embryos. In 1996, Congress prohibited federal funds from being used to support stem cell research. Six years later, President Bush relaxed the ban by allowing federal funds to be used for research on stem-cell lines already in existence. In March, 2009, President Obama lifted the ban altogether.

Surgeons at UC San Diego have removed a woman’s gallbladder through her mouth. The procedure, known as natural orifice translumenal endoscopic surgery (NOTES), was performed as part of a prospective multicenter clinical trial designed to compare it with laparoscopy.

Soon after laparoscopy was introduced in the 1980s, it became the technique of choice for gallbladder removal (cholecystectomy), because it was associated with reduced costs and morbidity.

Typically, laparoscopic cholecystectomy requires creating 3-5 incisions in the abdominal wall. In contrast, NOTES involves accessing the gallbladder through the mouth and a subsequent a hole created in the stomach (the so-called transgastric approach). An alternative NOTES procedure accesses the gallbladder through the vagina (the transvaginal approach).

“What is unique about this trial is that we will not only evaluate the safety and efficacy of NOTES compared to laparoscopy but will also assess and compare pain levels, cosmetic outcomes, operative costs and logistical outcomes,” said Santiago Horgan a principal investigator in the study and chief of minimally invasive surgery at UCSD Health System. Horgan has performed more than 70 NOTES surgeries.

Horgan said that traditional laparoscopy is highly effective, but suggested the newer approach might reduce post-operative infection, hernia, scarring and pain.

“We hypothesize that NOTES procedures may reduce pain and infection by eliminating abdominal wall incisions altogether,” Horgan explained. “Post-operatively, many patients experience pain while walking or coughing due to contraction of the abdominal muscles. This discomfort is absent following the natural orifice approach.”

The trial is designed to perform 70 NOTES cases (35 transgastric and 35 transvaginal) and 70 laparoscopic cases. The UCSD site plans to enroll 20 patients.

Cholecystectomy is one of the most common surgeries in the US. Nearly 750,000 patients undergo the procedure each year.

The dream of an effective vaccine against the AIDS virus may have moved one step closer to reality, according to federal scientists.

The scientists identified 2 naturally occurring antibodies that destroy nearly 90% of all strains of HIV, the virus that causes AIDS. They say their finding could hasten development of new HIV treatments as well as a vaccine.

HIV is deviously mutable. Frequent mutations in its DNA change the composition of surface proteins on the virus, allowing it to escape an immune response. This enables the virus to continue infecting cells even after antibodies targeting it have appeared — it has thus been able to avoid vaccines developed against it so far.

There are hundreds of variants of the HIV virus around the world. Finding so-called broadly neutralizing antibodies that can kill the majority of these strains has been the goal of HIV researchers for 2 decades.

To date, the best researchers have been able to do is find antibodies that block about 40% of the known HIV strains. Key to a breakthrough in this regard is to isolate antibodies that attack relatively unchanging parts on the surface of the HIV virus. And that’s what may just have been accomplished.

“I am more optimistic about an AIDS vaccine at this point in time than I have been probably in the last 10 years,” Gary Nabel of the National Institute of Allergy and Infectious Diseases told the LA Times. Nabel headed the project reporting the breakthrough. The write-up appears in Science.

Nabel’s team isolated antibodies from a 60-year-old African American man that had been infected with HIV. Using new imaging and analytical techniques, the team isolated 2 antibodies, known as VRC01 and VRC02, which are directed against a protuberance on the surface of the HIV virus. The spike facilitates binding to something called the CD4 binding site on white blood cells of humans. When an antibody binds to to the spike, it prevents the virus from entering the cell.

The HIV virus relies exclusively on this receptor to enter human white blood cells, so it can’t infect them when antibodies are attached to the spike.

Nabel’s team is currently testing a synthetic version of the spike as a possible vaccine in animals. They hope to begin human testing fairly soon.

The NIH has rejected a request to approve several dozen colonies of human embryonic stem cells for use by federally funded researchers. The lines were created by Reproductive Genetics Institute, a private infertility clinic based in Chicago. They contain mutations thought to be linked to several diseases including cystic fibrosis, muscular dystrophy and Huntington’s disease.

Many scientists believe that studies using these lines will reveal new information about the diseases, and perhaps lead to new treatments, but NIH Director Francis Collins nixed the proposal on grounds that the acquisition of the new lines violated his organization’s strict ethical guidelines.

The new stem cell lines were obtained from embryos donated by couples that were receiving treatment for infertility. The company decided against using them after tests revealed the genetic defects.

An NIH advisory panel tasked by Collins to evaluate the situation found however, that the consent forms used by RGI to secure the lines included unacceptably broad language and required couples to give up their right to sue the clinic for any cause.

Collins’ decision will limit research on the valuable cell lines to scientists who have secured private funding. The new NIH director did approve 8 other new stem cell lines, meaning that federally funded scientists have 75 different lines they can use for research.

“The NIH guidelines for reviewing stem cell lines for federal funding were set up to adhere rigorously to the well-established norms for informed consent,” Collins said in a statement. “It was painful for my advisory committee to recommend against approval of additional lines from RGI because of a consent problem, but rigorous guidelines are only meaningful if they are rigorously applied.”

Short stature is associated with a 50% greater risk of coronary heart disease, according to Tuula Paajanen and colleagues, who reported their findings in the European Heart Journal.

To reach these conclusions, the scientists performed a meta-analysis on 52 relevant articles on the subject, which were found during a systematic search of MEDLINE, PREMEDLINE and All EBM reviews. Together, the studies included a bit more than 3 million individuals.

For the purposes of their study, the scientists defined “short” as being below 5’5″ in males and below 5’0″ in females. They defined “tall” as being above 5’10″ in men and above 5’6″ in women.

Analysis of the combined studies revealed that individuals in the shortest cohort had a 46% greater likelihood of sustaining a cardiovascular event than those in the tallest cohort.

The scientists concluded that since short children tend to become short adults, their findings might help physicians select shorter kids and teens for early intervention programs designed to reduce cardiovascular risk. 

The study is believed to be the first to confirm the association, which had been debated for at least 50 years. It must be remembered that this study has shown a correlation, but does not prove that short stature actually causes cardiovascular disease. Randomized controlled trials would be required to prove causality, but of course they are impractical in the current instance.

Allopurinol, for 40 years a mainstay in the treatment of gout, has been shown to work for angina too, according to scientists at the University of Dundee.

To reach this surprising conclusion, Awsan Noman and colleagues enrolled 65 patients with chronic stable angina pectoris and angiographically proven coronary artery disease into a randomized, controlled trial of high-dose allpurinol (600 mg per day) vs. placebo.

The scientists found that patients randomized to receive allopurinol increased the median time to ST depression (a sine qua none of coronary ischemia) from 232 seconds to 298 seconds, whereas in placebo-treated subjects that statistic increased from 232 seconds to 249 seconds, a significant difference.

Allopurinol also increased total exercise time and the time before onset of chest pain. There were no adverse treatment effects.
 
Noman’s group suspects the beneficial effects of Allopurinol are caused by its ability to inhibit an enzyme known as xanthine oxidase. This in turn reduces myocardial oxygen (energy) consumption for a particular stroke volume.
 
Next up for the scientists is to determine how best to use allopurinol in the management of chronic stable angina. They were optimistic in this regard, noting that compared with nitrates and beta blockers allopurinol does not reduce blood pressure or heart rate, or trigger headaches and tiredness, which commonly accompany standard drug treatments.

They also noted that allopurinol may be quite useful in developing countries where the incidence of coronary artery disease is exploding and access to more expensive drugs and invasive therapies is limited.

The article appears in Lancet.

Most people are born with 4 wisdom teeth, which normally descend below the gum line between the ages of 17 and 25. Wisdom teeth are believed to have been important to our hunter-gatherer ancestors, whose coarse diet caused teeth to grind down and wear out.

The jaws of our hunter-gatherer ancestors were much larger than ours however, and for many of us there isn’t enough room in our mouths to accommodate the late-comers.

In these cases, wisdom teeth can become impacted (trapped in the jawbone) or erupt through the gum line only partially—a situation that predisposes to bacterial infections of the jaw, periodontal disease and tooth decay.

Of course, most people experience none of these complications, and the prophylactic surgical procedure designed to remove these risks can cause complications of its own. These include infections, postoperative bleeding and even perforated sinuses or nerve damage.

So how does one decide whether to have wisdom teeth removed, even if they are causing no problems? It turns out the scientific literature contains almost no guidance on the matter.

The American Dental Association for example, has not published guidelines for dealing with wisdom teeth. It prefers to let care givers decide on a case-by-case basis.

Thankfully, the NIH recently launched a study that might shed light on the subject. The study, led by Greg Huang of the University of Washington, will record the reasons given by general dentists when they suggest either pulling or keeping wisdom teeth, and then track patient outcomes for 2 years.

Meanwhile, Chevy Chase dentist Steven Kahan, who has dealt with the problem for 40 years, told the Washington Post, “It is the kind of thing where all of us make a somewhat educated guess.”