The month in research
Respiratory medicine
Antibiotics for sinusitis?
Lancet 2008;371:908-14
A new meta-analysis of the effects of antibiotics in people with possible sinusitis reports a number needed to treat of 15.
That means one extra person would be cured for every 15 people treated with antibiotics. Are antibiotics justified? Probably
not, say the authors and a linked comment (p 874). The confidence intervals around this figure were very wide, and the upper
limit included the possibility that antibiotics do not harm compared with placebo (one fewer patient cured for every 190 given
antibiotics).
Patients with relatively severe or long lasting symptoms were no more likely to benefit from antibiotics than anyone else.
Patients with a purulent nasal discharge took longer to get better, but antibiotics did not reliably speed their recovery
in this analysis. Symptoms such as face pain, tooth pain, and pain on bending did not help identify patients likely to have
a bacterial infection that would respond to antibiotics. The authors conclude that watchful waiting and symptomatic treatments
are enough for most adults with symptoms of sinusitis. Most trials, however, excluded people with a high fever, periorbital
swelling, erythema, or intense facial pain. (This item was first published in the BMJ, 2008;336:636.)
Endocrinology
Encouragement to lose weight
JAMA 2008;299:1139-48
Losing weight is hard enough, but keeping it off is an even greater challenge, say researchers. All the successful slimmers
in their recent trial gradually regained weight. Those left to their own devices regained significantly more than those who
had regular telephone and face to face support, but the difference was disappointingly modest—at 30 months controls had regained
5.5 kg, whereas those given personal support had regained 4 kg (P=0.01).1
Adjusted weight change by treatment group
A third group had access to an interactive website where they could set goals, plot their progress, and learn how to keep
motivated. This group did better than controls for about two years, but had regained as much weight as controls by the end
of the 30 month follow-up.
All 1032 participants were overweight or obese with a high risk of cardiovascular disease at the start of the trial. They
lost a mean of 8.5 kg in a six month run-in period before randomisation. Weight regain is likely to be even more of a problem
in unselected populations without a good track record.
All three groups kept control of their calorie intake during follow-up. Exercise was more of a problem. Participants managed
an extra 48 minutes a week during the six month weight loss phase, but couldn’t maintain it after randomisation. (This item
was first published in the BMJ, 2008;336:636.)
Surgery
Non-polypoid colorectal lesions
JAMA 2008;299:1027-35
Colorectal polyps are a well known and common precursor to invasive cancer. The epidemiology of flat or depressed lesions
is less clear, particularly in Western developed countries.
Researchers recently found 170 non-polypoid tumours in 1819 adults (mostly men) who had a colonoscopy at one hospital in California
between July 2003 and June 2004. That is an overall prevalence of 9.3%. Non-polypoid lesions were more likely to contain in
situ or submucosal carcinoma than polyps of a similar size found in the same cohort (odds ratio 9.78, 95% confidence interval
3.93 to 24.4). They are hard to find with traditional colonoscopy techniques, and missed non-polypoid lesions may account
for at least some of the interval cancers that develop between screening rounds, says an editorial (p 1068). These researchers
used a special technique—highlighting flat or depressed abnormalities with indigo carmine spray. They found the highest prevalence
in people attending for routine surveillance because of a personal or family history of colorectal cancer (15.4% (101/654),
12.8% to 18.4%).
These findings are in line with previous work from Japan, where flat or depressed lesions of the colonic mucosa are common
and ominous. (This item was first published in the BMJ, 2008;336:582-3.)
Endocrinology
Insulin from embryonic stem cells
Nat Biotechnol 2008;26:443-52; doi: 10.1038/nbt1393
Human embryonic stem cells may one day be used to treat diabetes. This depends on a renewable supply of β islet cells from
implanted pancreatic tissue.
In an important step towards this, researchers have found that pancreatic endoderm derived from human embryonic stem cells
efficiently generated endocrine cells that were responsive to glucose upon implantation into mice. Human insulin and C peptide
were detected in mice sera at concentrations similar to those in animals transplanted with about 3000 human islets.
Molecular testing showed that these engrafted stem cells exhibited many properties of functional β cells, including expression
of appropriate critical transcription factors, processing of proinsulin, and the presence of mature endocrine secretory granules.
Also, in a test of therapeutic potential, researchers were able to show that implantation of pancreatic endoderm protects
against hyperglycaemia induced by streptozotocin. These findings, the researchers argue, help to confirm the putative therapeutic
roles of human embryonic stem cells to treat insulin dependent diabetes.
Medical genetics
Fixing fragile X?
Nat Chem Biol 2008;4:256-63; doi: 10.1038/nchembio.78
Fragile X syndrome is caused by the functional loss of fragile X mental retardation 1 (FMR1) gene. Loss of the corresponding
gene (Fmr1) in Drosophila shows many of the phenotypes associated with the syndromes in humans.
Researchers have confirmed that this loss of the Fmr1 gene is caused by glutamate toxicity during embryogenesis and possibly
afterwards because mutants reared on a diet that contained excess glutamate died early during embryonic development.
Using this model, researchers screened a chemical library of 2000 compounds and identified nine molecules that rescue animals
from glutamate toxicity, including three that implicate the GABAergic inhibitory pathway. In addition, the inhibition of glutamate
excitation provided by treatment with γ-aminobutyric acid (GABA) resulted in improvement of several anomalies seen in flies
with Fmr1 mutations, including abnormal behaviour in courtship and somatic defects.
Also, researchers have found that muscarinic cholinergic receptors may also have a role in the genesis of fragile X syndrome,
parallel to the GABAergic pathway. Further exploration along these lines, researchers add, might provide effective therapeutic
approaches to treating mental retardation caused by specific chromosomal defects.
Student BMJ 2008;16:217 | 17
