Tuesday, October 28, 2008

Liver Transplants

The pain is debilitating. The only option: smoking medical marijuana. That's the reality for many hepatitis C patients whose road to health includes a liver transplant. Although Canadian transplant centres are more willing than those in the United States, not everyone says yes to liver patients who smoke marijuana, and a University of Alberta researcher says that decision-making process is unacceptable.

Karen Kroeker, along with three other students at various universities, sent out surveys to a number of transplant clinics across the United States and Canada. Results found that the difference between the two countries were obvious in some patient groups: around 60 per cent of Canadian centres would either do the surgery or consider it for a liver transplant patient who smoked marijuana, while 70 per cent of U.S. transplant programs said absolutely not. Kroeker also found that patients in both countries, who have no social support - meaning they have no family, friends or a social worker - aren't likely to receive the organ they need.

The problem Kroeker has with these results: the lack of literature to support the surgeons' decision. As a result of her findings, which will be published in the November issue of Liver International, Kroeker says physicians need to determine eligibility criteria for liver-transplant patients that pertains directly to the likelihood of a patient rejecting the organ and is based only on empirical medical evidence.

When a patient is being reviewed for eligibility, whether they smoke marijuana shouldn't be a factor, she says. "If we have evidence to say the patients don't do well, then I think that's a reason to exclude people," Kroeker said.

She cites alcohol use as an example. When transplants first began to be performed, those who drank alcohol weren't eligible for a new liver. Kroeker's study found, however, that surgeons conducted studies on the topic of abstinence and liver health and, as a result of that research, transplant rules changed. If the patient has been sober for six months, 94 per cent of the clinics in North America will now consider transplantation.

The same goes for HIV-positive patients. "When they first started transplanting, HIV was an absolute contraindication. No one even considered transplantation because the disease was a death sentence at that time." Kroeker adds that's no longer the case and that there is research being conducted on post-transplant HIV-patients that will help determine the viability of transplants in HIV-positive patients.

In reference to her findings, Kroeker said, "I think there should be a large-scale study," because too-little research is available on post-transplant patients whose eligibility may currently be in question.

"Unless you actually perform transplants for those people, how would you know how they do?"

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Article adapted by Medical News Today from original press release.
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Source: Quinn Phillips
University of Alberta

Tuesday, October 7, 2008

Alcoholism and Genetics

ScienceDaily (Mar. 9, 2007) — A genetic variant of a receptor in the brain's reward circuitry heightens the stimulating effects of early exposures to alcohol and increases alcohol consumption, according to a new study by researchers at the National Institute on Alcohol Abuse and Alcoholism (NIAAA), part of the National Institutes of Health (NIH).

Conducted in rhesus monkeys, the study extends previous research that suggests an important role for a similar brain receptor variant in the development of human alcohol use disorders. A report of the findings is published in the March, 2007 issue of the Archives of General Psychiatry.

"Although the pathway to alcoholism is influenced by many factors, our findings affirm that individuals who possess this receptor variant may experience enhanced pleasurable effects from alcohol that could increase their risk for developing alcohol abuse and dependence," notes Markus Heilig, M.D., Ph.D., NIAAA Clinical Director and the study's senior author.

Molecules known as opioid peptides bind to opioid receptors in the brain to signal experiences of reward and reinforcement, as well as the euphoria and other positive subjective effects produced by alcohol. Previous studies have shown that, among the brain's various subtypes of opioid receptors, the mu-subtype is most likely responsible for transmitting alcohol's positive effects.

"We also know that there are several genetic variants of the human mu-opioid receptor," notes first author Christina Barr, V.M.D., Ph.D., a lead investigator in NIAAA's Laboratory of Clinical and Translational Studies and Laboratory of Neurogenetics. "One of these, designated 118G, has a greatly enhanced ability to bind opioid peptides. People who have this variant of the receptor have reported increased euphoria following alcohol consumption."

Drs. Barr, Heilig, and their colleagues note that recent studies have linked the 118G mu-opioid receptor with alcohol dependence in humans. In the current study, the researchers explored the link between genetic variants of mu-opioid receptors and alcohol-related behaviors in a group of 82 rhesus monkeys.

"A mu-opioid receptor variant that is functionally similar to the human 118G variant occurs in these animals," explained Dr. Barr. "That is, it also has a greatly enhanced ability to bind opioid peptides. We hypothesized that monkeys that had the gene for this receptor variant would experience enhanced alcohol stimulation and, therefore, consumption.

Groups of monkeys had access to both alcoholic and non-alcoholic solutions for one hour per day for a period of six weeks. Researchers measured the animals' alcohol intake and post-intake activity, and determined which monkeys carried the gene for the mu-opioid receptor similar to the human 118G receptor. Activity measures are commonly used in animal studies to assess alcohol's pleasurable effects.

As predicted, the researchers found that monkeys with the variant gene showed increased activity following alcohol consumption. They also found that male animals with the variant had a clear preference for the alcohol solution and consumed on average almost twice as much alcohol as other animals. Males with the variant also became intoxicated on almost 30 percent of testing days, while other animals did so only on an average of 8 percent of testing days.

"The male-restricted effect of this gene is interesting, and parallels other recent evidence that opioid transmission may play a greater role in alcohol problems among some males than among females," explained Dr. Heilig. This information also complements recent data suggesting that alcohol-dependent people with the gene for the 118G receptor have a better therapeutic response to medications that block opioid receptors. More broadly, the finding underscores the important role that the pleasurable and stimulating initial effects of alcohol play in the subsequent development of alcohol problems."