Guest editorial: celebrating the 50TH anniversary of the introduction of chlorpromazine in North America and the advent of the psychopharmacology revolution.
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To test the safety and efficacy of tirilazad mesylate, a nonglucocorticoid 21-aminosteroid, in improving the outcome of patients with aneurysmal subarachnoid hemorrhage (SAH), 902 patients were enrolled in a prospective randomized, double-blind, vehicle-controlled trial at 54 North American neurosurgical centers. Five patients were excluded prior to receiving any study drug. Of 897 patients who received at least one dose of study medication, 300 received a placebo containing a citrate vehicle, 298 received 2 mg/kg per day tirilazad, and 299 received 6 mg/kg per day tirilazad, all administered intravenously beginning within 48 hours of the SAH and continuing through 10 days posthemorrhage. All patients were also treated with orally administered nimodipine. At 3 months post-SAH, there were no significant differences (p < 0.025) among the groups with regard to mortality rate, favorable outcome on the Glasgow Outcome Scale, or employment status. During the first 14 days after the SAH, there were no significant differences among the groups in the incidence or severity of clinically symptomatic or angiographically identifiable cerebral vasospasm. Mortality data stratified by gender and neurological grade on admission (assessed according to a modified World Federation of Neurological Surgeons scale) demonstrated that the men with Grades IV to V had a 33% mortality rate in the vehicle group, 52% in the 2 mg/kg per day tirilazad group (p = 0.29), and 5% in the 6 mg/kg per day tirilazad group (p = 0.03). Tirilazad was well tolerated at both dose levels. Tirilazad mesylate at dosage levels of up to 6 mg/kg per day for 8 to 10 days following SAH did not improve the overall outcome in patients with aneurysmal SAH in this trial. The differences in the efficacy of tirilazad in this trial and a previously reported trial in Europe, Australia, and New Zealand, in which dosage levels of tirilazad of 6 mg/kg per day reduced mortality rates and increased good recovery, may be a result of differences in admission characteristics of the patients and/or differences in management protocols, including the use of anticonvulsant medications.
We report new body mass estimates for the North American Eocene primate Omomys carteri. These estimates are based on postcranial measurements and a variety of analytical methods, including bivariate regression, multiple regression, and principal components analysis (PCA). All body mass estimation equations show high coefficients of determination (R2), and some equations exhibit low prediction errors in accuracy tests involving extant species of body size similar to O. carteri. Equations derived from PCA-summarized data and multiple regression generally perform better than those based on single variables. The consensus of estimates and their statistics suggests a body mass range of 170-290 g. This range is similar to previous estimates for this species based on first molar area (Gingerich, J Hum Evol 10:345-374, 1981; Conroy, Int J Primatol 8:115-137, 1987).
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The Meropenem Yearly Susceptibility Test Information Collection (MYSTIC) Program provides susceptibility data for participating medical centers where carbapenems are utilized. The activity of meropenem and nine broad-spectrum antimicrobial agents were assessed against 3,047 bacterial isolates collected during 2002 from 16 North American sites. The overall rank order of susceptibility of the 10 antimicrobial agents tested against Gram-negative isolates was: meropenem (98%) > imipenem (97%) > cefepime (95%) > tobramycin (93%) > piperacillin/tazobactam = gentamicin (92%) > ceftazidime (91%) > ciprofloxacin (87%) > aztreonam (86%) > ceftriaxone (74%). These results and those from previous years, demonstrate the continued excellent potency and spectrum of activity for meropenem. The utility of meropenem against Pseudomonas aeruginosa isolates has increased steadily with a rise in percent susceptibility each year from 78.2% in 1999 to a present rate of 93.1% susceptible. Conversely, we showed the susceptibility for ciprofloxacin against these same P. aeruginosa isolates has decreased from 82.9 to 72.3% susceptible over four years. Many medical centers have observed a decreased activity of some aminoglycosides, cephalosporins and fluoroquinolones due to increases in rates of extended-spectrum beta-lactamases, Amp C and other resistance mechanisms. Carbapenem resistance remains rarely documented and these beta-lactamase-stable agents appear to be an alternative treatment option for serious community-acquired or nosocomial infections in high risk patient populations.
The health consequences of an adverse body-fat distribution (e.g., android, upper-body, visceral) have only recently concerned the medical community. Ninety years ago, however, actuarial study demonstrated the relationship of body-fat distribution to the mortality experience of insured, North American men. Thirty-four insurance companies pooled their data on males issued life policies between 1870 and 1899. Special classes of risk were defined by weight for height at baseline or by the observation that abdominal girth exceeded the girth of the expanded chest (abdominal obesity). The mortality experience of each risk class was compared to an age-stratified, actuarial table of the period. We present new analyses of these historical data relating specifically to the mortality impact of abdominal obesity. Among 163,567 overweight men, the prevalence of abdominal obesity increased with age and with degree of overweight. Among moderately overweight men, those with abdominal obesity experienced 133% of the expected mortality rate compared to 112% of the expected mortality for those who were not abdominally obese. Severely overweight men with abdominal obesity experienced 152% of the expected mortality compared to 135% of the expected mortality for severely overweight men who were not abdominally obese. We believe this nineteenth-century, acturial study of waist and chest girths was the first demonstration that body-fat distribution can influence longevity. These early actuarial findings, taken with more recent reports, establish that abdominal enlargement, but not necessarily an 'upper-body' fat distribution, constitutes a major health hazard. Future research must establish which abdominal-obesity index best predicts disease outcomes.
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