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.”

In an innovative effort to find new uses for existing drugs, pharmaceutical giant Pfizer has struck a deal with the Washington University School of Medicine enabling the University’s scientists to access information regarding over 500 pharmaceutical compounds in Pfizer’s archives.

The 5-year agreement also calls for Pfizer to contribute $22.5 million to the University. Proprietary information will be shared for drugs that are currently on the market and those that failed during  testing. The deal is believed to be the first of its kind in the industry.

The parties expect the partnership can reduce the time-to-market for drugs that are found to have new applications, because the time consuming, pre-clinical (safety) studies have already been performed on these compounds.

“There are two realities in drug discovery,” Don Frail told BurrillReport. The chief scientific officer of Pfizer’s Indications Discovery Unit explained that “the majority of candidates tested in development do not give the desired result, yet those drugs that do succeed typically have multiple uses. By harnessing the expertise at this academic medical center, the collaboration seeks to discover new uses for these compounds in areas of patient need that might otherwise be left undiscovered.”

To foster collaboration, Pfizer developed a web portal that permits Washington University scientists to access clinical and preclinical data regarding Pfizer’s proprietary compounds. An oversight committee composed of scientists from both organizations will evaluate research proposals that have been co-authored by researchers from the University and Pfizer.

Pfizer’s Indications Discovery Unit will move its laboratories closer to the Washington University campus to further promote idea exchange.

“This is a tremendous opportunity for both partners,” Jeffrey Gordon, director of the University’s Center for Genome Sciences told Burrill. “It leverages the complementary strengths and interests of both Washington University and Pfizer.”

Most of us know we can expect to feel a burning sensation when we consume jalapenos or other hot peppers. But few peope know that such spicy fare might also increase body temperature via a mechanism that burns calories just as effectively as exercise.

At least that’s what scientists at the UCLA Center for Human Nutrition seem to have discovered during a recent trial involving 34 volunteers who were trying to peel off some pounds.

The tongue-scorching effects of spicy peppers comes from capsaicin, a chemical produced by plants to discourage animals from turning them into dinner. These same plants also produce a milder tasting analogue known as dihydrocapsiate (DCT).

The UCLA scientists randomized the study subjects to receive either DCT or a placebo with their meals. They subsequently measured the subjects’ energy expenditure and found it to be highest among the cohort that had received DCT. In fact, it was nearly twice as high as in those receiving the dummy pill, and the phenomenon was associated with increased fat burning as well.

The scientists warn however that their findings are preliminary, since their subjects were placed on a low-calorie liquid diet, and it’s not clear the same results would be seen among people on a normal diet. The researchers also said the energy-burning effects of DCT might not be seen in folks who are of normal weight to begin with.

The findings were presented during an April meeting of a conference known as the Experimental Biology 2010 meeting, which was held in  in Anaheim.

Rejection of the donor organ is a frequent and sometimes life-threatening complication of heart transplantation. It is best handled if caught early, and since early rejection is typically asymptomatic, physicians had heretofore been required to perform regular biopsies to screen for rejection of the transplanted heart.

The biopsy is expensive and not without risk however, so scientists have long searched for a non-invasive alternative to diagnose rejection.

That search may have yielded results. In a presentation at last month’s meeting of the International Society for Heart & Lung Transplantation, Michael Pham and colleagues from Stanford University showed that a genetic test reduced the need for biopsies in selected patients.

The gene test is known as Allomap. It is marketed by XDx and has been used on 7,000 transplant recipients so far. It costs about $3,000, or 25-40% less than the biopsy.

The study by Pham’s team included 602 transplant recipients. It showed that Allomap was as effective as routine biopsies in preventing serious episodes of transplant rejection like heart failure, the need for a re-transplant or death.

The study was limited to patients who were at low risk for rejection and had undergone the procedure at least 6 months prior to enrollment. Nineteen months after randomization, 14.5% of patients that were followed with the genetic test and 15.3% of those followed with routine biopsies suffered a major complication.

“You’re not going to harm patients by reducing the number of biopsies,” Pham told the Wall Street Journal.

Pham noted that his team’s findings could not be extrapolated to patients that had received a transplant within the last 6 months or to those at high risk for rejection.

The study appears in the New England Journal of Medicine.

When Viagra first hit the market, there was hope it might work in women as well as men, giving a pharmacological boost to those with low levels of sexual arousal (referred to clinically as “female sexual dysfunction” or “female sexual arousal disorder”).

With the possible exception of woman who experience loss of libido as a side-effect of antidepressant drugs, that hasn’t turned out to be the case.

But now scientists at Pfizer, the company that markets the little blue pill, claim to have made an advance that could eventually lead to a female version of the wonder drug.

Their rather dry write-up is titled “UK-414,495, a selective inhibitor of neutralendopeptidase, potentiates pelvic nerve-stimulated increases in female genital blood flow in the anaesthetized rabbit.” It appears in the British Journal of Pharmacology.

Ironically, the subjects of their research were rabbits, whose reputation suggests they don’t need much help in the breeding department, but whatever.

According to the scientists, UK-414,495 enhances blood flow to a female rabbit’s clitoris and vagina after its pelvic nerve is stimulated. It does this by blocking destruction of VIP, a neurochemical that dilates blood vessels.

Viagra, in contrast, works by increasing nitric oxide availability in the small blood vessels of the penis…a completely different mechanism from UK-414,495. No wonder it doesn’t do diddly for women!

Although the experimental drug in this study isn’t fit for human use, the Pfizer scientists say their work may unlock the door to other compounds that are.

Even if that were the case, they add that “the translation of results obtained in the rabbit to humans is unknown, especially since the link between blood flow and subjective arousal remains controversial.”  Apparently however, some studies do suggest that women with arousal disorders are helped by enhanced genital blood flow.