A dose-defining study of sumatriptan suppositories in the acute treatment of migraine

In this dose-ranging, randomised, multinational, multicentre, double-blind, placebo-controlled, parallel group study, 431 patients treated a single migraine attack with study medication: sumatriptan suppository 6 mg, 12.5 mg, 25 mg, 50 mg, 100 mg, or placebo. Patients were treated in the clinic with a single dose in suppository form. All doses of sumatriptan, except 6 mg, were significantly better than placebo (p < 0.004) and achieved similar rates of headache relief within two hours of dosing. The highest response rate was in the 25 mg group (72%) compared with placebo (37%) (p < 0.001). Fewer patients required rescue medication in the active groups (1% 100 mg to 13% 6 mg) compared with placebo (17%), and more patients were able to work and function normally two hours after dosing (41%, 100 mg; 20%, placebo). The overall incidence of adverse events was similar in the placebo, 6 mg and 12.5 mg groups (14-17%) but higher in the 25 mg, 50 mg and 100 mg groups (25%, 32% and 29% respectively). Analysis of plasma sumatriptan levels indicated rapid rectal absorption for all doses (median tmax = 1.0 hr). It is concluded that sumatriptan, in doses above 6 mg, is an effective and well tolerated treatment for acute migraine. From this study doses of 12.5 mg and 25 mg sumatriptan were identified as having the best efficacy/safety profile and were evaluated further.     

Graphology for the diagnosis of suicide attempts: a blind proof of principle controlled study

To evaluate the ability of two graphologists and two practising internists not trained in graphology to differentiate letters written by subjects who have attempted to commit suicide by self-poisoning and healthy volunteers, we performed a maximal blind controlled study vs. healthy volunteers. Forty fully recovered patients who had attempted to commit suicide and 40 healthy volunteers wrote and signed a short letter or story not related to the parasuicide or their mental health status. The evaluators classified the 80 letters as 'suicide' or 'no suicide' in an intention-to-treat analysis. Letters expressing sadness were subsequently excluded for a per-protocol analysis. Correct diagnosis of suicide and of healthy controls was made in, respectively, 32 of 40 and 33 of 40 letters by the graphologists and in 27 of 40 and 34 of 40 letters by the internists. After the exclusion of 12 letters expressing sadness, the sensitivity, specificity, positive predictive value and negative predictive value were, respectively, 73, 88, 81 and 82% for the graphologists and 53, 89, 80 and 71% for the internists. Both classified the letters with significantly more effectiveness than chance (p < 0.001) with no statistically significant difference between the two groups of evaluators. We concluded that graphological analysis is able to differentiate letters written by patients who attempt suicide from those written by healthy controls. This technique shows an acceptable degree of accuracy and could therefore become an additional discharge or decision-making tool in Psychiatry or Internal Medicine.     

Activity of megazol, a trypanocidal nitroimidazole, is associated with DNA damage

DNA damage associated with the trypanocidal activity of megazol [2-amino-5-(1-methyl-5-nitro-2-imidazolyl)-1,3,4-thiadiazole] was shown in experiments in which DNA repair-deficient RAD51(-/-) Trypanosoma brucei mutants were found to be hypersensitive to the drug. Parasites resistant to megazol were selected and showed modest cross-resistance to other trypanocides, although neither drug efflux nor changes to intracellular thiols correlated with resistance.     

Celecoxib is as efficacious as naproxen in the management of acute shoulder pain

This study compared the analgesic efficacy and safety of the cyclo-oxygenase-2 specific inhibitor celecoxib with the non-specific non-steroidal anti-inflammatory drug, naproxen, in patients with acute shoulder pain. Adult patients with shoulder pain, onset within the previous 14 days and shoulder pain of > or = 40 mm on a 100 mm visual analogue scale (VAS), were treated with oral doses of celecoxib or naproxen for 14 days and followed by a visit at day 42 in a double-blind, randomized study. The primary efficacy assessment was change in maximum pain at rest on a 100 mm VAS at day 14 compared with baseline. In addition, secondary efficacy pain and functional assessments were analysed at baseline, day 14 and day 42. A total of 202 patients were included in the trial (99 celecoxib 400 mg/day; 103 naproxen 1 g/day). The difference in change from baseline at day 14 in maximum pain at rest was not statistically significant between the two treatment groups, but was numerically higher for celecoxib than for naproxen (-47.9 +/- 2.5 versus -42.3 +/- 2.5, respectively). According to the limits of the 95% confidence interval of the difference between groups (-12.52; 1.38), celecoxib appeared to be at least as effective as naproxen. All secondary efficacy measures followed the same pattern, showing similarity between the two treatments with a trend in favour of celecoxib. The incidences of adverse events were similar for both groups. Fewer patients experienced epigastric pain with celecoxib (seven patients versus 14 with naproxen). This adverse event led to discontinuation in two patients receiving celecoxib and five receiving naproxen. Celecoxib 400 mg/day was at least as effective as naproxen 1 g/day in managing pain in this condition.     

Origins of U.S. Hispanics. Implications for diabetes

The purpose of this article was to characterize the origins of the United States Hispanic population and discuss the implications of these origins in the context of diabetes risk. Particular attention was focused on the genetic origins of the three major U.S. Hispanic groups, i.e., Mexican Americans, Puerto Ricans, and Cubans. The U.S. Census figures provided basic demographic information. Genetic marker data for ancestral populations were taken from a review of the literature and compendia. Genetic marker data for the Puerto Rican and Cuban populations were extracted from the literature. Genetic markers determined on approximately 1000 randomly selected Mexican Americans from Starr County, Texas, were taken as representative of the Mexican-American population. The Hispanic population is the second largest and fastest growing minority in the U.S. Estimates of the Hispanic population in 1988 indicated some 19.4 million residents, of whom 62% were classified as Mexican, 13% as Puerto Rican, and the remaining 25% as Cubans and others. Various lines of evidence can be used to characterize the Hispanic population and its origins. These include ethnohistory, self-assessment of ancestry, surname distributions, speech and cultural characteristics, quantitative traits, and genetic structure. Genetic data were used to estimate the contribution of putative ancestral populations to the contemporary gene pool. For Mexican Americans, 31% of the contemporary gene pool is estimated to be Native American derived, whereas 61 and 8% are Spanish and African derived, respectively. In Puerto Rico, the percentage of contributions of Spanish, Native American, and African admixture to the population are 45, 18, and 37%, respectively. For Cuba, the parallel estimates are 62, 18, and 20%. The high frequency of Native American-derived genes in the contemporary Hispanic population predict a higher frequency of non-insulin-dependent diabetes mellitus (NIDDM) under the assumption that genes are important in NIDDM etiology. Our results are consistent with the finding of the significant role of genes in determining risk.