BMJ  2006;332:905 (15 April), doi:10.1136/bmj.332.7546.905

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Calorie controlled diets reduce oxidative damage to DNA

Some evidence from experiments on laboratory animals shows that restricting calorie intake can prolong life. It's still unclear how, but researchers believe that a lower metabolic rate and reduced oxidative stress may have something to do with it. To find out if calorie restriction has similar effects in humans, researchers randomly assigned 48 overweight US volunteers to one of four diets for six months. One diet reduced calorie intake by 25%; the second combined 12.5% fewer calories with exercise designed to increase energy expenditure by 12.5%; the third contained only 890 calories a day; and the fourth, the control, supplied 100% of required calories.

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The groups that had lower intakes of calories lost significantly more weight than controls (10-14%). They also had greater reductions in two out of three accepted biomarkers for longevity in animals—core body temperature and serum concentration of insulin. The calorie controlled diets all caused energy expenditure to drop and were associated with less fragmentary DNA in blood cells compared with the control diet. Whether these changes prolong survival is unclear, and, even if they do, restricting calories is unlikely to be a realistic antidote to ageing for most people, says an editorial (pp 1577-8). But these kinds of metabolic experiment bring us one step closer to a more viable alternative.

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JAMA 2006;295: 1539-48[Abstract/Full Text]

Bioengineered bladders given to children with myelomeningocoele

For almost 100 years, scientists have been looking for a material to replace diseased bladder tissue. After testing and discarding skin, omentum, dura, peritoneum, placenta, and many more, they finally settled on segments of intestine. Bioengineering now offers a potentially less problematic solution—tissue grown from the patient's own bladder cells. It takes between seven and eight weeks to grow a decent sized bladder, which is then piggy backed on to the old diseased one.

The first seven patients were aged between 4 and 19 and had end stage bladder disease due to myelomeningocoele. Their new bladders improved urinary symptoms, such as incontinence, in a mean follow-up of four years This treatment is still evolving, however, and the technique for making and implanting the new bladder tissue changed twice during this short case series. Late modifications, such as improving the graft's blood supply with omental wrap, seemed to improve bladder function more than earlier attempts. Growing and implanting engineered bladders may be technically possible, but the technique is far from established as a safe and effective alternative to intestinal cystoplasty, a linked editorial says.

Lancet 2006 Apr 4 (www.thelancet.com) doi: 1016/S0140-6736(06)68438-9

Aggressive rosuvastatin treatment may shrink coronary atheroma

We know that statins can slow the progression of atherosclerosis in patients with coronary heart disease. Intensive treatment may even help the disease to regress, a study has shown. Five hundred and seven men and women with proved coronary atherosclerosis took the maximum permitted dose (40 mg a day) of rosuvastatin for up to two years. Intravascular ultrasound before and after showed a small but significant reduction in the percentage volume of atheroma blocking the target artery (from 39.6% to 38.6%). Rosuvastatin had similar or greater effects on other less stringent measures of atheroma volume. The drug reduced mean serum concentrations of low density lipoprotein cholesterol (the bad one) by a half from 3.4 to 1.6 mmol/l and increased serum concentrations of high density lipoprotein cholesterol (the good one) from 1.1 to 1.3 mmol/l.

The authors, supported by the drug's manufacturers, conclude that a potent statin can shrink atheroma if used at a high enough dose. At least two independent commentators remain unconvinced, however (pp 1583-4). The study had various weaknesses, including the lack of controls. The study's authors argue that it would have been unethical to offer less intensive statin treatment to controls with atherosclorosis.

JAMA 2006;295: 1556-65[Abstract/Full Text]

HPV vaccine protects for four years

A bivalent vaccine against human papilloma viruses (HPVs) 16 and 18 protects women against infection and its associated cervical lesions for four years, an extension of a randomised placebo controlled trial has found. The vaccine, which is given in three doses, remained 97% effective against new infections and 94-100% effective against persistent infections by the two viruses most commonly associated with cervical cancer. The vaccine also seemed to protect women (but to a lesser extent) against the third and fourth most common cancer causing viruses, HPVs 45 and 31.

Vaccinated women had high titres of antibody directed against HPVs 16 and 18 throughout the extended follow-up—133 times higher than controls who had been given a placebo vaccine. They also had far fewer abnormal cervical lesions, although numbers were small. The vaccine seems safe so far: in this trial, women in the placebo group reported most adverse events.

Lancet 2006 Apr 6 (www.thelancet.com) doi: 10.1016/S0140-6736(06)68439-0

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