Randomized, blinded, placebo-controlled trial of tissue factor pathway inhibitor in porcine septic shock.

This study tested the hypothesis that tissue factor pathway inhibitor (TFPI) would improve mortality and morbidity evoked by peritonitis-induced bacteremia in pigs. Secondarily, it sought to determine if TFPI treatment would attenuate cardiodynamic abnormalities produced by this septic model. 32 pigs were chronically instrumented with intracardiac transducers to measure left ventricular pressure and diameter, pulmonary and aortic pressures, and cardiac output. At least 5 days after surgery to implant transducers, basal cardiovascular readings and blood samples were obtained. Using a randomized, blinded study design, either purified, reconstituted TFPI (1 mg/kg bolus, 10 mg/kg/min for 48 h), placebo (arginine buffer), or saline was administered to pigs immediately after Escherichia coli 0111.B4 (3.0-11 x 10(9) colony-forming U/kg)-laden fibrin clots were implanted intraperitoneally, producing peritonitis and bacteremia. Pigs did not receive antibiotics or supportive therapy. No significant differences in primary or secondary endpoints were noted between the arginine and saline groups, so these data were combined into a control group (N = 20). 5 of 12 TFPI pigs survived (42%), while 5 of 20 control pigs survived (25%); this difference was not significant (p = .714, Fisher's exact test). TFPI treatment augmented cardiac output in surviving pigs, but did not affect any other cardiovascular performance variable (heart rate, % diameter shortening, or systemic and pulmonary vascular resistance). In controls, peritonitis induced rapid increase in plasma tumor necrosis factor-alpha (428 +/- 771 to 5,933 +/- 559 pg/mL at 2 h) and interleukin-8 (180 +/- 153 to 1,393 +/- 145 pg/mL at 2 h). TFPI treatment significantly attenuated cytokine responses to sepsis, reducing peak tumor necrosis factor-alpha to 2,103 +/- 813 pg/mL and reducing peak interleukin-8 levels to 534 +/- 211 pg/mL at 2 h (p < .05, Tukey test, two-way ANOVA). In conclusion, TFPI treatment attenuated important mediator components of the inflammatory response but did not provide significant survival benefit.

Chlormethiazole abuse.

This report describes 17 cases of chlormethiazole abuse or dependence. These include one case with symptoms and signs of withdrawal and two other similar cases where undoubted dependence was combined with excessive alcohol intake. Seven other patients with alcoholism who indulged in drug-seeking behaviour involving chlormethiazole are also reported, together with a further seven abusers of various other drug who were also discovered to be taking chlormethiazole.

Fetal exsanguination associated with antepartum hemorrhage.

Fetal bleeding in utero is infrequent. It is usually life-threatening but can be treated successfully in most cases if recognized early. Four cases are described and it is suggested that screening for fetal blood be done in all instances of antepartum hemorrhage.

Respiratory distress syndrome and the value of amniotic fluid phospholipids in predicting such complications before birth.

The amniotic fluid study of 80 samples from 40 patients, obtained by amniocentesis between 28 and 40 weeks of pregnancy, was carried out. It was noted that L/S (Lecithin/Sphingomyelin) ratio was significantly different at 36-38 weeks of pregnancy when compared with values in pregnancies of less than 36 weeks gestation (P less than 0001). No cases of RDS occurred when the L/S ratio was mature 4 or more. A brief review of recent developments in etiology of RDS are also presented.