Thursday, August 02, 2007

Standard anaesthetic practice harmful

Nitrous oxide, better known as laughing gas, is the cornerstone of anaesthesiology but a landmark Australian study has questioned its routine use in major surgery. The study of more than 2000 adult surgical patients worldwide found removing nitrous oxide from the anaesthetic cocktail significantly reduced the risk of major post-operative complications. Researchers reported a lower incidence of fever, pneumonia, wound infection, severe nausea and vomiting in patients undergoing major surgery where nitrous oxide was avoided.

The study, published in the August edition of Anaesthesiology, is expected to trigger fierce debate in the profession given nitrous oxide has been used for more than 150 years. "It would be fair to say all anaesthetists will read this Australian study with great interest across the world," said Brisbane specialist Patrick See, director of the St Andrew's Medical Institute. "It will be a landmark article that will stimulate a lot of discussion."

An estimated one million Australian patients and more than 10 million in the US are administered nitrous oxide annually. But the study's chief investigator Paul Myles, head of anaesthesia at the Alfred Hospital in Melbourne, expects that to plummet on the basis of the findings. "I think this study is going to reduce the use of nitrous oxide by about five to tenfold right now," Professor Myles said. "Our bottom line is that we should stop using nitrous oxide routinely in major surgery involving adults. "Some anaesthetists stopped using it a number of years ago because they had concerns about it but we've now got hard data."

Professor Myles stressed the results did not apply to patients having minor surgery, women in labour, dental procedures or operations involving children. All patients in the study were at least 18 and underwent surgery lasting two hours or more. They were randomly assigned to receive a nitrous oxide-based anaesthetic or one free of laughing gas.

The study authors reported slightly more heart attacks and deaths in the nitrous oxide group but Professor Myles said follow-up research was needed to back up those findings. "The numbers are too small for us to make any firm conclusions," Professor Myles said. The research team has already launched another study of 7000 patients with a $2.8 million grant from the National Health and Medical Research Council.

Dr See, who was not involved in the research, said he had started using nitrous oxide on fewer patients "some years ago" because of emerging concerns. Nevertheless, Dr See expects the Australian study to raise eyebrows among some anaesthetists.


Hope for MS: Genetics progress

The first genetic advance in multiple sclerosis research in three decades has opened new approaches to treating the neurological disorder, scientists said yesterday. Research has identified two genetic variants that each raises a person's risk of developing MS by about 30 per cent, shedding new light on the origins of the autoimmune disease that could ultimately lead to better therapies. The two genes are the first to be linked conclusively to MS since the mid-1970s, when the only other gene that is known to contribute to the condition was found.

Their discovery is particularly promising as both are involved in managing the activity of T-cells, the "infantry" of the immune system that sometimes mistakenly attack healthy tissue to cause autoimmune conditions. In MS, the immune system starts to destroy the fatty myelin sheaths that insulate nerve cells, leading to progressive neurological damage.

Both genes, which control receptors that T-cells use to find their targets, are potential targets for new drugs to control MS. They were found in a major study of the genetics of MS published in the New England Journal of Medicine, and the significance of one has been confirmed in two separate papers published in Nature Genetics.

Scientists said that the genes would have important implications for understanding the disease and ultimately for treating it. Margaret Pericak-Vance of the University of Miami, a senior member of both research groups, said: "They give us a new way of looking at the biology of the disease, and could be targets for therapeutic development." Stephen Hauser, Professor of Neurology at the University of California, San Francisco, said of one of the genes, the interleukin-7 receptor (IL-7R): "I believe that this receptor and its interaction with regulatory T-cells will now become a major focus of research on MS."

While MS is not directly inherited or caused by a single gene, it is known to be partly inheritable: people with close relatives who have the condition are at higher risk. Since the 1970s, however, only one gene that contributes to a raised risk has been identfied. A variant of this gene, known as HLA-DRB1, seems to make the body worse at recognising its own tissue, and increases an individual's chances of developing MS by up to four times.

The new genetic variants affect a different part of the immune system, the control receptors on T-cells that act as receiving antennae for interleukins - proteins that summon these killer cells to attack invaders. Each has less effect on MS than HLA-DRB1, raising the risk by about 30 per cent, but both are common. Some 72 per cent of white Europeans have the most damaging version of the interleukin-2 receptor (IL-2R) gene, while 56 per cent have the most damaging variant of the IL-7R gene. This indicates that these genes are far from the only contributors to MS - the overwhelming majority of people who carry the risky variants are healthy. Many other genes, as well as environmental factors, are involved.

David Hafler, Professor of Neurology at Harvard Medical School in Boston, who led one of the research teams, said: "Each gene contributes only a small amount of risk. The big question is, how do they interact with each other, and are they in common pathways? A major effort to understand the full complement of genes involved in MS will be necessary to completely understand the disease." A fuller knowledge of how the genes raise risk, however, will still be useful in designing new drugs. It may even prove possible to correct the inter-leukin signalling pathways to stop the condition from developing.

Simon Gregory, of Duke University in North Carolina, who contributed to the research, said: "Our finding is very important because the genetic factors that are already known to be associated with multiple sclerosis only explain less than half of the total genetic basis for the disease."

The discovery that IL-2R is linked to MS is also significant because previous research has suggested it also contributes to two other autoimmune conditions, type 1 diabetes and autoimmune thyroid disease. "Scientists are increasingly finding genetic links between autoimmune diseases that affect different tissues in the body, including type 1 diabetes and rheumatoid arthritis," Professor Hafler said. "This study will likely spur further research into the connection between these seemingly separate conditions."

The findings have emerged from two slightly different approaches to gene-hunting that have become possible because of advancing technology and the mapping of the human genome. The most important was a genome-wide association study, which scanned more than 500,000 genetic variations from more than 13,000 people to find associations between particular mutations and MS. "People have been looking for genes involved in MS for 30 years," Professor Hafler said. "Why weren't they found? The answer is you couldn't do it without the sequence of the human genome."

Lee Dunster, of the MS Society, said: "One of the great unknowns about MS is what causes it and this looks like a welcome breakthrough in getting to grips with the genetics behind the disease. People with MS often worry about what caused it, and particularly whether it will affect their children, so a better understanding of the role of certain genes is good news. These latest findings will be of great interest to researchers trying to develop future treatments."



Just some problems with the "Obesity" war:

1). It tries to impose behavior change on everybody -- when most of those targeted are not obese and hence have no reason to change their behaviour. It is a form of punishing the innocent and the guilty alike. (It is also typical of Leftist thinking: Scorning the individual and capable of dealing with large groups only).

2). The longevity research all leads to the conclusion that it is people of MIDDLING weight who live longest -- not slim people. So the "epidemic" of obesity is in fact largely an "epidemic" of living longer.

3). It is total calorie intake that makes you fat -- not where you get your calories. Policies that attack only the source of the calories (e.g. "junk food") without addressing total calorie intake are hence pissing into the wind. People involuntarily deprived of their preferred calorie intake from one source are highly likely to seek and find their calories elsewhere.

4). So-called junk food is perfectly nutritious. A big Mac meal comprises meat, bread, salad and potatoes -- which is a mainstream Western diet. If that is bad then we are all in big trouble.

5). Food warriors demonize salt and fat. But we need a daily salt intake to counter salt-loss through perspiration and the research shows that people on salt-restricted diets die SOONER. And Eskimos eat huge amounts of fat with no apparent ill-effects. And the average home-cooked roast dinner has LOTS of fat. Will we ban roast dinners?

6). The foods restricted are often no more calorific than those permitted -- such as milk and fruit-juice drinks.

7). Tendency to weight is mostly genetic and is therefore not readily susceptible to voluntary behaviour change.

8). And when are we going to ban cheese? Cheese is a concentrated calorie bomb and has lots of that wicked animal fat in it too. Wouldn't we all be better off without it? And what about butter and margarine? They are just about pure fat. Surely they should be treated as contraband in kids' lunchboxes! [/sarcasm].

Trans fats:

For one summary of the weak science behind the "trans-fat" hysteria, see here. Trans fats have only a temporary effect on blood chemistry and the evidence of lasting harm from them is dubious. By taking extreme groups in trans fats intake, some weak association with coronary heart disease has at times been shown in some sub-populations but extreme group studies are inherently at risk of confounding with other factors and are intrinsically of little interest to the average person.


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