Science and Reason: Readings: health and medicine, 20 October 2007

The text following each item is quoted material, except for editorial comments, which are in color.

BubR1 Protein: A Key Regulator of Aging: Hoping to find a way to help people maintain their independence and quality of life as they grow older, Jan van Deursen, Ph.D., and a team of collaborators are investigating the relationship between common aging-associated diseases and the protein BubR1. He became interested in aging-related research after observing that mice deficient in the protein BubR1 age faster than normal mice. They say BubR1 deficient mice may hold the key to preventing or delaying disorders such as cataracts, muscle weakness and cardiovascular disease.
Aging and the Growth Hormone Crash: What Comes First?: "If pituitary hormones were released like water from a faucet into a bathtub, there'd be a constant slow filling of the tub in proportion to its size and whether or not the drain was open — you could solve that with high school physics," explains Dr. Veldhuis. "One of the complexities is that the pituitary squirts out a pulse of hormones at random times."

The pituitary gland, a pea-sized structure located at the base of the brain, regulates many key functions in the body. It secretes seven hormones in response to commands from the hypothalamus of the brain. Dr Veldhuis is interested in observing the pituitary response for its influence on aging. He is most interested in its secretion of the growth hormone (GH), which stimulates protein synthesis and cell division in cartilage and bone tissue. GH has a tendency to remove intra-abdominal fat, which is associated with diabetes and heart disease (metabolic syndrome).
Hormone dilemma, 5 years on: Five years ago this month, a landmark study dashed the belief that hormone treatment is the key to keeping women of a certain age sexy, healthy and young.

On the contrary, maintaining estrogen and progestin at abnormally high levels after menopause was shown to be risky for their hearts, brains, breasts and blood vessels.

The government study abruptly transformed the use of hormone therapy - and, in the ensuing years, has undermined the idea that women who don't get long-term treatment are doomed to decrepitude. ...

The landmark research remains bitterly controversial, its findings incredibly complex. In recent months, reanalyses of the data have found that while hormones raise heart risks for women long past menopause, they pose no such danger - and may have cardiac benefits - for recently menopausal women.

Critics of the study - known as the Women's Health Initiative - have argued for five years that it overstated the heart risks for younger women.

While the science is still evolving, hormones have been firmly reestablished in a limited role: to relieve the passing discomforts of dwindling estrogen.

And yet the risk of breast cancer from estrogen therapy has been reaffirmed in recent studies – under certain circumstances. But uncertainties still remain. See here, here, and here.
Can Fat Be Fit?: Two years ago Katherine M. Flegal, a researcher at the Centers for Disease Control and Prevention, did a new statistical analysis of national survey data on obesity and came to a startling conclusion: mildly overweight adults had a lower risk of dying than those at so-called healthy weights. ...

Stampfer cites the Flegal study as a prime example of the errors the critics make. The reason being overweight seemed to reduce mortality is because Flegal used the wrong comparison group, he says. The lean group in her study included smokers and people with chronic illnesses—both of whom have increased mortality risks, but not because they are slim. “When you get sick, you lose weight, and you die,” Stampfer says. Compared with those who are smokers or chronically ill, people who are overweight come out looking better than they should.
Eating Made Simple: Studies focusing on one nutrient in isolation have worked splendidly to explain symptoms caused by deficiencies of vitamins or minerals. But this approach is less useful for chronic conditions such as coronary heart disease and diabetes that are caused by the interaction of dietary, genetic, behavioral and social factors. If nutrition science seems puzzling, it is because researchers typically examine single nutrients detached from food itself, foods separate from diets, and risk factors apart from other behaviors. This kind of research is “reductive” in that it attributes health effects to the consumption of one nutrient or food when it is the overall dietary pattern that really counts most.
Cutting Cholesterol, an Uphill Battle: About 85 percent of the cholesterol in your blood is made in your body. The remaining 15 percent comes from food. But by reducing dietary sources of saturated fats and cholesterol and increasing consumption of cholesterol-fighting foods and drink, you can usually lower the amount of harmful cholesterol in your blood. My college roommate, for example, recently adopted a mostly vegetarian-and-fish diet, minus cheese but with occasional meat and chicken, and lowered her total cholesterol from 240 to 160 milligrams.
Deadly Inheritance, Desperate Trade-Off: Mrs. Platt is part of a study aimed at preventing pancreatic cancer in people who are at high risk for it, by finding precancerous growths and removing all or part of the pancreas to get rid of them. So far, about 20 people have had the preventive surgery at Johns Hopkins, and a small number of others have undergone it at other centers.

In essence, these patients are trading the risk of cancer for the reality of diabetes, and their willingness to do it is a measure of the fear and desperation that pancreatic cancer provokes.

“With pancreatic cancer you don’t have much opportunity to save lives, and we are, with this approach,” said Dr. Canto, the director of endoscopy at Johns Hopkins.
Electric fields have potential as a cancer treatment: Yoram Palti, of the Technion–Israel Institute of Technology in Haifa, and his colleagues have demonstrated another way to disrupt cell division: alternating electric fields with intensities of just 1–2 V/cm. The fields they use, with frequencies in the hundreds of kilohertz, were previously thought to do nothing significant to living cells other than heating them. But Palti and colleagues have conducted a small clinical trial showing that the fields have an effect in slowing the growth of tumors.
Science begins at home: Chemotherapy drugs, like most medicines, reach cells by slipping through narrow spaces in the walls of blood vessels that crisscross the body.

But all blood vessels are not alike.

The abnormal, leaky vessels that supply cancer cells have openings up to 100 times larger than those found in healthy vessels -- it's like comparing a soccer ball with a Goodyear blimp.

In a way, this biological quirk was the reverse of the problem he faced in seeking a molecular petroleum sieve.

Instead of creating a mesh, he wanted to bulk medicines up so their molecules wouldn't pass through the wall of normal blood vessels. At the same time, they needed to remain small enough to fit through pores of vessels feeding cancerous cells.

One anecdotal example of the difficulties of developing new and better drug therapies.
Mysteries of autoimmune diseases unravel: Scientists say immune disorders, which range from common diseases such as juvenile diabetes or lupus to some so unusual that many doctors have never heard of them, are among the most mysterious of ailments, genetically complex and so diverse that estimating their true prevalence is a guessing game. But with major advances in genetics and exponential growth of knowledge about the immune system, scientists say important discoveries are tantalizingly within reach. ...

Immune system disorders often cluster in families and within an individual, says Virginia Ladd, president of the American Autoimmune Related Diseases Association. "Once you have one, you have others. Some patients say if you live long enough, you can collect them."
Visualizing the Molecules that Cause Infectious Disease: Seeing with Supercomputers: CAMDL specializes in developing computer simulated models aimed at the discovery of new treatments for infectious diseases and cancer. It is one of few labs conducting advanced research in computational, medicinal, synthetic and combinatorial chemistry under one roof.

The laboratory houses supercomputing hardware and software used to process highly complex biological data, and develop comprehensive databases of three-dimensional molecules. Dr. Pang has adapted his imaging concepts from the small computer screen to a large wall screen where visitors are drawn into a three-dimensional, sub-microscopic world. Researchers can examine and study, in simulation, microsecond-scale proportions of proteins and enzymes associated with malaria, avian flu and severe acute respiratory syndrome (SARS). This ability has led to significant discoveries in the lab that Dr. Pang says will impact the prevalence and spread of infectious diseases.
Small-Scale Solutions: Chemists first invented lab-on-a-chip devices to analyze gases in the 1970s, but the effort to make practical microfluidics tools for biological studies has gained traction only in the past decade. One major advance, led by George Whitesides at Harvard University in the late 1990s, was to fabricate the chips from cheap, flexible rubber rather than the expensive, stiff silicon used to manufacture computer chips. In a method dubbed "soft" lithography, Whitesides and his colleagues started with the same photographic processes that computer-chip companies use to cast an integrated-circuit blueprint in a single wafer of silicon, but they poured rubber into the chip-making molds instead.
Vaccines and Their Promise Are Roaring Back: By the mid-1990s, however, innovation in vaccines had virtually come to a halt. Only a handful of companies even tried to develop new ones, compared with 25 in 1955.

But in a stunning reversal, innovators today are chasing dozens of vaccines, stimulated by some recent high-profile successes. ...

The allure of the silver bullet — of wiping out an entire class of related diseases with a single injection — remains a powerful symbol of technological advance.