Hannah Wunsch

Cocaine use transiently increases heart-attack risk

According to the results of a new study, for 1 hour after its use cocaine is “associated with a large abrupt and transient increase in the risk of a myocardial infarction in patients who are otherwise at relatively low risk”. This research, from Murray Mittleman (Harvard Medical School, Boston, MA, USA) and colleagues, is the first to quantify the myocardial infarction risk associated with cocaine use. The researchers interviewed 3946 patients at 64 medical centres who fulfilled specific criteria identifying them as having had an acute myocardial infarction. Patients, who were interviewed within a few days of the event, were asked about time, place, and quality of the myocardial infarction pain, frequency of exposure to potential triggers, and cocaine use in the previous year. Those admitting cocaine use were also asked when they had last used the drug (Circulation 1999; 99: 2737‐41). Of the patients interviewed, 38 (1%) reported cocaine use in the 12 months before the infarction, and nine reported use within 60 minutes before the onset of symptoms. The researchers used a case-crossover study design, in which control information for each patient was based on their own past exposure experience, to analyse these data. They report that in the first hour after cocaine use, myocardial infarction risk was 23·7 (95% CI 8·5‐66·3) times greater than the baseline risk during periods of non-exposure to cocaine. Because of the difficulty of getting people to admit to drug use, the risk increase calculated may even be an underestimate. “We were doing a large study

Myoblast transplants challenged in muscular dystrophy

Myoblast transplants challenged in muscular dystrophy T investigation of myoblast transplantation therapy, a treatment for muscular dystrophy being tested by the Cell Therapy Research Foundation (CTRF; Memphis, TN, USA), was designated a US FDA “Fast Track development program” on Oct 16 and phase III clinical trials are planned. But new results throw doubt on to the technique. UK and US scientists say they can find no evidence for donor-derived dystrophin in a boy who received CTRF’s treatment. The new data, they say, challenge the validity of the therapy. In myoblast transplantation therapy missing or non-functional dystrophin in the muscles of patients with muscular dystrophy is replaced by injecting muscle cells from an unrelated donor into the patient. According to the technique’s proponents, these wild-type cells fuse with the patient’s muscle cells and supply functional dystrophin. By staining biopsy material with antibody specific for dystrophin, the treated muscle can be tested for expression of functional, donor-derived protein. However, patients can express some endogenous, albeit mutant dystrophin, in their muscles, and this might be mistaken for donor dystrophin if biopsy samples are stained with only one antibody. Concerned that the dystrophin that has been found in patients who have had myoblast transplantation therapy was in fact endogenous mutant protein, Terry Partridge (MRC Clinical Sciences Centre, London, UK) and colleagues obtained biopsy samples from a patient who had had the treatment and stained his cells with multiple antibodies for dystrophin. 10–15% of the muscle fibres stained positively with an antibody specific for peptides encoded by exons 57–60 of the dystrophin gene. Antibody staining was similarly positive for all other dystrophin regions tested, except those encoded by exons 27–28 and 40–41. These antibodies did not stain the patient’s cells at all, but did stain normal muscle cells from an unrelated control. There was no difference in amounts of dystrophin in the myoblast-injected muscle and a sham-injected muscle in the same patient. The authors conclude that the dystrophin detected in the patient’s biopsy must be his own mutant protein, not protein expressed from the grafted myoblasts (Nat Med 1998; 4: 1208–09). About 120 children have been treated by CTRF at a cost of about US

Drug combinations best in acute asthma attacks

150 000 per child, but there are many critics who argue that clinical trials are premature. “A lot of scientists have done myoblast trials and all have been resoundingly negative, except for the CTRF trials”, says Eric Hoffman (University of Pittsburgh, PA, USA), one of the authors of the Nature Medicine letter. “I think it would be sensible to go through all the [treated] children where dystrophin is found and see whose it is”, adds Partridge. CTRF filed a lawsuit against Hoffman and Partridge earlier this year, claiming that CTRF had been injured by intentionally defamatory statements made by the scientists.

Bed rest for sciatica and lower-back pain may not be the best option

O corticosteroids are the drugs given most often during acute asthma attacks. But the results of a randomised control trial suggest that the addition of inhaled corticosteroids can reduce the number of relapses after discharge from emergency departments. Brian Rowe (University of Alberta, Edmonton, Canada) and colleagues studied 188 patients with acute asthma who visited a community teaching hospital emergency department. Patients who had taken oral or inhaled corticosteroids during the previous week were excluded from the study. All participants were discharged with a 7-day course of oral prednisone (50 mg/day). In addition, 94 patients were given 1600 mg/day of inhaled budesonide for 21 days; the other 94 participants were given a placebo inhaler. After 21 days, 12 (12·8%) patients given inhaled corticosteroid had had a relapse compared with 23 (24·5%) patients given placebo (p=0·049). Patients given inhaled corticosteroid used 2-agonists less often than did control patients. They also reported fewer symptoms and a better quality of life during the 21-day study. Based on their results, the authors conclude that as few as nine patients with acute asthma would need to be given inhaled corticosteroids in order to prevent one relapse (JAMA 1999; 2 8 1 : 2119–26). Patients already taking inhaled corticosteroids were excluded from the trial, but Mark Fitzgerald (University of British Columbia, Vancouver, Canada) notes that among all the patients attending the emergency room with an acute asthma attack (1006 during the study), only 37% were already using inhaled corticosteroids. “Here is a very high-risk population and we would expect close to 100% using inhaled corticosteroids”, he says. Thus, the study highlights the low general use of these drugs in asthma. “The bottom line is that the combination therapy works better than prednisone alone” to treat acute asthma, says Rowe. But, he adds, this study does not indicate how long to give the therapy, which dose to use, or which combination is best.

COX provides missing link in mechanism of aspirin in colon cancer

D a recent claim to the contrary, the beginnings of human language and the speech capacity of Neanderthals “remain open questions”, says David DeGusta (University of California, Berkeley, CA, USA). Researchers previously suggested that Neanderthals could talk when they found that the hypoglossal canals from fossils of five early men were within the modern human-size range. The researchers assumed a correlation between canal size and hypoglossal nerve size which, in turn, determines tongue function. But when DeGusta and co-workers measured the hypoglossal canal in 32 non-human primate species and in 104 modern human skulls, they saw a “large overlap” in canal size between monkeys and man (Proc Natl Acad Sci U S A 1999; 9 6 : 1800–04). “More than 50% of monkeys had hypoglossal canals in the human-size range”, says DeGusta. And, in skulls from five human cadavers, there was no correlation between the size of the hypoglossal canal and of the hypoglossal nerve. “It was a nice idea, but it just doesn’t work”, says DeGusta. “The anatomy of the hypoglossal canal is more complicated than it seemed, which precludes us from making a simple equation between its size and speech.”