Drotrecogin alfa (activated) in patients with severe sepsis presenting with purpura fulminans, meningitis, or meningococcal disease: a retrospective analysis of patients enrolled in recent clinical studies.

INTRODUCTION: We report data from adult and pediatric patients with severe sepsis from studies evaluating drotrecogin alfa (activated) (DrotAA) and presenting with purpura fulminans (PF), meningitis (MEN), or meningococcal disease (MD) (PF/MEN/MD). Such conditions may be associated with an increased bleeding risk but occur in a relatively small proportion of patients presenting with severe sepsis; pooling data across clinical trials provides an opportunity for improving the characterization of outcomes. METHODS: A retrospective analysis of placebo-controlled, open-label, and compassionate-use trials was conducted. Adult patients received infusions of either DrotAA or placebo. All pediatric patients (<18 years old) received DrotAA. 189 adult and 121 pediatric patients presented with PF/MEN/MD. RESULTS: Fewer adult patients with PF/MEN/MD met cardiovascular (68.3% versus 78.8%) or respiratory (57.8% versus 80.5%) organ dysfunction entry criteria than those without. DrotAA-treated adult patients with PF/MEN/MD (n = 163) had an observed 28-day mortality rate of 19.0%, a 28-day serious bleeding event (SBE) rate of 6.1%, and an intracranial hemorrhage (ICH) rate of 4.3%. Six of the seven ICHs occurred in patients with MEN (three of whom were more than 65 years old with a history of hypertension). DrotAA-treated adult patients without PF/MEN/MD (n = 3,088) had an observed 28-day mortality rate of 25.5%, a 28-day SBE rate of 5.8%, and an ICH rate of 1.0%. In contrast, a greater number of pediatric patients with PF/MEN/MD met the cardiovascular organ dysfunction entry criterion (93.5% versus 82.5%) than those without. DrotAA-treated PF/MEN/MD pediatric patients (n = 119) had a 14-day mortality rate of 10.1%, an SBE rate of 5.9%, and an ICH rate of 2.5%. DrotAA-treated pediatric patients without PF/MEN/MD (n = 142) had a 14-day mortality rate of 14.1%, an SBE rate of 9.2%, and an ICH rate of 3.5%. CONCLUSION: DrotAA-treated adult patients with severe sepsis presenting with PF/MEN/MD had a similar SBE rate, a lower observed 28-day mortality rate, and a higher observed rate of ICH than DrotAA-treated patients without PF/MEN/MD. DrotAA-treated pediatric patients with severe sepsis with PF/MEN/MD may differ from adults, because all three outcome rates (SBE, mortality, and ICH) were lower in pediatric patients with PF/MEN/MD.

Wild squirrel monkey (Saimiri sciureus) "caregiver" calls: Contexts and acoustic structure.

A field study of the vocal behavior of 22 wild adult female squirrel monkeys (Saimiri sciureus) in Parque Nacional del Manu, Peru, found that 21% of vocalizations were "caregiver" calls. Caregiver calls are brief, low frequency calls, often with numerous harmonics, that are addressed by caregivers to their own infants in three contexts: 1) prenurse, signalling the caregiver's location and willingness to nurse; 2) nurse, while nursing; and 3) end nurse, indicating the end of the nursing bout. Three measures (start, end, and peak frequency) of the acoustic structure of the fundamental frequency of the caregiver calls significantly differed across the contexts. Duration of caregiver calls, however, was not distinguished by context. Compared to other primate taxa, the specificity and importance of caregiver calls in squirrel monkey vocal behavior appears unusual, if not unique. That S. sciureus caregiver calls are highly developed and employed so extensively probably follows from an unusual combination of ecological and life history factors. These factors include delayed weaning and large infant body size, high levels of indirect foraging competition which encourages spatial separation, susceptibility to predation, and specialization on a densely foliated, branch-end microhabitat in which visual contact is often impeded. © 1995 Wiley-Liss, Inc.

Male residence and association patterns in Costa Rican squirrel monkeys (Saimiri oerstedi).

A model is developed to interpret the evolution of the unusual pattern of male residence and social structure in the Costa Rican squirrel monkey (Saimiri oerstedi). Observations of a wild population document that males 1) maintain close spatial and social associations with other males, especially other males in their birth cohort, but not females and infants; 2) exhibit negligible within-troop male-male aggression, high levels of antipredator vigilance, and frequent predator deterrence; 3) cooperate in aggressive olfactory investigation of females; and 4) maintain residence in their natal troop with their male birth cohort, eventually succeeding to reproductive positions in their natal troop. Less commonly, male age-cohorts leave the troop well past reproductive maturity and usurp the reproductive male cohort in another troop. We suggest that this divergence from the social structure typical of male squirrel monkeys in Peru (males transient between troops, weak male-male bonds, high within-troop male aggression, little investment in anti-predator behavior) arose because female S. oerstedi in Costa Rica are not philopatric. In Costa Rica, long term reproductive cooperation is likely advantageous to males, because of the frequent movement of female S. oerstedi between troops; the potential costs of inbreeding are reduced. Male S. oerstedi of all ages residing in the same troop, but especially those of the same age cohort, are predicted to have a much higher degree of genetic relatedness than adult females. © 1994 Wiley-Liss, Inc. This article is a US Government work and, as such, is in the public domain in the United States of America.

An evaluation of semen characteristics in men 45 years of age or older after daily dosing with tadalafil 20mg: results of a multicenter, randomized, double-blind, placebo-controlled, 9-month study.

OBJECTIVES: Assess the effects on spermatogenesis of daily tadalafil 20mg over three spermatogenesis cycles in men >or= 45 yr. METHODS: In this double-blind, placebo-controlled, noninferiority study, healthy men (or with mild erectile dysfunction) were randomized to receive tadalafil 20mg (n=125) or placebo (n=128) for 9 mo followed by a 6-mo, treatment-free period. Semen and serum samples were provided at baseline and every 10-12 wk. The primary outcome was the proportion of subjects with >or= 50% reduction in sperm concentration at end point. Secondary outcomes included sperm concentration, number per ejaculate, motility and morphology; serum concentrations of testosterone, luteinizing and follicle-stimulating hormones; and tolerability. RESULTS: Of 253 men enrolled, 191 (75%) completed treatment phase: 2 of 96 (2.1%, placebo) and 12 of 95 (12.6%, tadalafil) subjects had >or= 50% reduction in sperm concentration. Tadalafil was noninferior to placebo because the upper 95% confidence interval for the difference in proportions of tadalafil and placebo subjects with a >or= 50% reduction in sperm concentration was 17.5%, significantly less than the prespecified noninferiority margin of 20% (p=0.015). Ninety-four percent (179 of 191) of men completed the 6-mo, treatment-free period: Baseline sperm concentration levels were restored in 8 of 12 (tadalafil) and 1 of 2 (placebo) men. There were no significant differences between groups in secondary end points. Common treatment-emergent adverse events were headache, back pain, dyspepsia, gastroesophageal reflux disease, and myalgia. Twelve (9.6%) tadalafil and seven (5.5%) placebo subjects discontinued because of adverse events. CONCLUSIONS: This study demonstrated no deleterious effects of 9 mo of daily tadalafil 20mg on spermatogenesis or hormones related to testicular function in men >or= 45 yr.