Bradykinin B2 receptor antagonism with LF 18-1505T reduces brain edema and improves neurological outcome after closed head trauma in rats

BACKGROUND: We evaluated the effect of LF 18-1505T, a novel nonpeptide bradykinin type-2 receptor antagonist, on brain edema and neurologic severity score (NSS) after closed head trauma (CHT). METHODS: There were 132 rats anesthetized and assigned for sham or CHT; infusion of saline or LF 18-1505T (0.3, 1, 3, 10, or 30 microg x kg x min); and determination of neurologic outcome (brain water content and NSS) or physiologic variables (blood pressure, glucose concentration, etc.). RESULTS: Post-CHT brain water content was less with LF 18-1505T doses of 3 and 10 microg x kg x min (80.1 +/- 3.8 through 81.6 +/- 2.6%, mean +/- SD) than in the untreated group (84.6 +/- 1.9%, p < 0.01). Post-CHT NSS improved with doses of 3, 10, and 30 microg x kg x min (median, 7; range, 0-12 through median, 10; range, 8-18) as compared with that in the untreated group (median, 17; range, 14-23; p < 0.05). LF 18-1505T with or without CHT did not significantly alter physiologic variables. CONCLUSIONS: LF 18-1505T decreased brain edema and improved neurologic status after CTH in rats without significantly altering physiologic values.     

Congenital paravertebral arteriovenous fistula: a case report

Congenital paraspinal arteriovenous fistulae are rare and usually diagnosed after neurologic or cardiovascular manifestations. They may be discovered unexpectedly in children during clinical examination, which reveals the presence of a vascular murmur. The association with multicystic kidney is exceptional. We report 1 case with thoracic localization of a congenital paraspinal arteriovenous fistula associated with a multicystic kidney in a 3-year-old boy who was treated by endovascular embolization.     

International integrated database for the evaluation of severe sepsis and drotrecogin alfa (activated) therapy: analysis of efficacy and safety data in a large surgical cohort

BACKGROUND: The International Integrated Database for the Evaluation of Severe Sepsis and Drotrecogin alfa (activated) Therapy includes an extensive cohort of surgical patients (1659/4459; 37%). This database broadens the experience reported on a comparatively small set of surgical patients from the pivotal Protein C Worldwide Evaluation in Severe Sepsis trial to examine issues of safety and efficacy in a much larger cohort. METHODS: We conducted a retrospective analysis of prospectively defined outcomes from 5 integrated clinical studies of severe sepsis. Multivariable analyses incorporated propensity scores, treatment, and significant baseline risk factors as independent variables in logistic regression models for 2 outcomes: serious adverse events that were observed during infusion and 28-day, all-cause mortality rates. Adjusted odds ratios were calculated for clinically important strata. Multiple subcategories of serious bleeding-event rates are presented. RESULTS: Although surgical patients who were treated with drotrecogin alfa [activated] (DrotAA) experienced a greater proportion of serious bleeding events during the infusion period, most of the patients were treated without fatal consequence. A 10.7% absolute all cause mortality risk reduction (adjusted odds ratio, 0.66; 95% CI, 0.45-0.97) was observed for DrotAA-treated, high-risk (Acute Physiology and Chronic Health Evaluation II, >or=25) surgical patients. We could not demonstrate a survival benefit in DrotAA-treated, low-risk (Acute Physiology and Chronic Health Evaluation II, <25) surgical patients. When surgical patients were stratified by number of organ dysfunctions, absolute risk reductions were observed in both categories: multiorgan (4.3%) and single (4.5%). CONCLUSION: International Integrated Database for the Evaluation of Severe Sepsis and Drotrecogin alfa (activated) Therapy analyses affirmed the favorable benefit/risk profile of DrotAA for surgical patients. The serious adverse event rate that was experienced by surgical patients during the study drug infusion period was 7.5% in the DrotAA-treated group versus 6.3% in the placebo-treated group (odds ratio, 1.41; 95% CI, 0.89-2.25). The clinical benefit of DrotAA therapy paralleled baseline risk of death and substantiated findings from the Protein C Worldwide Evaluation in Severe Sepsis study. Future analyses are needed to evaluate the special relationships among sepsis severity, bleeding management, and the postoperative timing of DrotAA administration.     

Transplacental effects of nitrosamines in Syrian hamsters. III. Dimethyl- and dipropylnitrosamine.

The aliphatic nitrosamines dimethylnitrosamine (DMN), diethylnitrosamine (DEN), dipropylnitrosamine (DPN), and dibutylnitrosamine (DBN) reached fetal tissue in quantitatively measurable amounts after subcutaneous administration to pregnant Syrian hamsters. The compounds were present for at least 2 h in maternal blood, placenta, fetus, and amniotic fluid; DBN was still measurable after 6 h. Only a weak or borderline transplacental effect was seen when incidences and latencies of neoplasms in the respiratory and digestive tracts of the F1-generation were compared with those of the P-generation after exposure to a single dose of DMN or DPN. However, some tumor types occurred at relatively high rates in the young, but were seen only occcasionally in their mothers or in this hamster colony in general.     

Untersuchungen über Perchloräthylen-Emanationen an zwei Typen von offenen Metallreinigungsapparaten

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