Prevention of preterm delivery with vaginal progesterone in women with preterm labour (4P): randomised double-blind placebo-controlled trial.

OBJECTIVE: To evaluate the effectiveness of 200 mg of daily vaginal natural progesterone to prevent preterm birth in women with preterm labour. DESIGN: Multicentre, randomised, double-blind, placebo-controlled trial. SETTING: Twenty-nine centres in Switzerland and Argentina. POPULATION: A total of 385 women with preterm labour (24(0/7) to 33(6/7) weeks of gestation) treated with acute tocolysis. METHODS: Participants were randomly allocated to either 200 mg daily of self-administered vaginal progesterone or placebo within 48 hours of starting acute tocolysis. MAIN OUTCOME MEASURES: Primary outcome was delivery before 37 weeks of gestation. Secondary outcomes were delivery before 32 and 34 weeks, adverse effects, duration of tocolysis, re-admissions for preterm labour, length of hospital stay, and neonatal morbidity and mortality. The study was ended prematurely based on results of the intermediate analysis. RESULTS: Preterm birth occurred in 42.5% of women in the progesterone group versus 35.5% in the placebo group (relative risk [RR] 1.2; 95% confidence interval [95% CI] 0.93-1.5). Delivery at <32 and <34 weeks did not differ between the two groups (12.9 versus 9.7%; [RR 1.3; 95% CI 0.7-2.5] and 19.7 versus 12.9% [RR 1.5; 95% CI 0.9-2.4], respectively). The duration of tocolysis, hospitalisation, and recurrence of preterm labour were comparable between groups. Neonatal morbidity occurred in 44 (22.8%) cases on progesterone versus 35 (18.8%) cases on placebo (RR: 1.2; 95% CI 0.82-1.8), whereas there were 4 (2%) neonatal deaths in each study group. CONCLUSION: There is no evidence that the daily administration of 200 mg vaginal progesterone decreases preterm birth or improves neonatal outcome in women with preterm labour.

Differential effects of ouabain and 2,4-dinitrophenol on contractile tension of and on sodium and calcium efflux from frog heart ventricular strips.

1 The efflux, from heart ventricular strips of Rana pipiens, of sodium ((22)Na) and calcium ((45)Ca) was measured simultaneously.2(22)Na efflux could be resolved into two first order kinetic components: k(I) = 0.105 min(-1), thought to represent efflux from the extracellular space, and k(II) = 0.0182 min(-1) representing efflux from the cells.3(45)Ca efflux was also resolved into an extracellular component, k(I) = 0.1216 min(-1); and an intracellular one, k(II) = 0.0102 min(-1). (45)Ca k(II) was greatly increased by 2,4-dinitrophenol (DNP), but unchanged by caffeine. This suggests that it represents a mitochondrial calcium compartment.4(22)Na k(II) was not changed by DNP. This indicates that, at the time of DNP addition, (22)Na was passively bound to undefined intracellular components.5 Ouabain (10(-6) M) decreased (45)Ca efflux (k(II)) initially but at later periods slightly increased it. The former effect is thought to be due to an action at the plasma membrane level, while the latter probably represents an increased exchangeability of mitochondrial calcium. The same effects were always found when ouabain was applied at different times of strip superfusion.6 Ouabain (0.25 to 4 muM) did not decrease the k(II) of (22)Na efflux. Kinetic reasons are presented which indicate that, in this preparation, the activity of the sodium pump may be too fast to be measured by means of (22)Na efflux, therefore these findings do not necessarily mean that ouabain does not inhibit active sodium transport.7 The time course of the inotropic effect of ouabain was also studied in ventricular strips of Rana pipiens heart that were stimulated at 0.2 Hz with biphasic, 2 ms pulses of supramaximal intensity, and incubated in Ringer solution containing 1.1 mM calcium, or in ;calcium-free' Ringer (residual calcium: 5.2 muM), or in ;calcium-free' Ringer with 0.1 mM of the calcium chelator ethyleneglycol bis (beta-aminoethylether) N,N'-tetraacetic acid (EGTA).8 In Ringer, the inotropic effect of ouabain was already observed at 5-10 s after steroid addition, even with the lowest concentration tested (0.25 muM), while signs of toxicity appeared only after 15 min in 4 muM ouabain, the highest concentration used.9 When the strips were incubated in ;calcium-free' Ringer solution, force of contraction decayed to 1-2% of that in 1.1 mM calcium. Addition of 4 muM ouabain to these hypodynamic strips led to a progressive increase in contractile force of up to 300%, that started after a 50 s latency period. No signs of toxicity were observed.10 Incubation of the strips in EGTA-Ringer also reduced contractile force to about 2% of that in Ringer, and 4 muM ouabain also increased force of contraction by approximately the same amount as seen in ;calcium-free' Ringer, but the effect began after a 10 min latency period. The concentration of calcium ion (Ca(2+)) in the extracellular space of strips incubated in EGTA-Ringer, was approximately 800 fold lower than in Ringer, and 60 fold lower than in ;calcium-free' Ringer solution.11 Caffeine (20 mM) induced, in strips previously incubated for 1 h in 4.4 mM calcium Ringer solution plus 10(-6) M ouabain, a marked initial contracture, that relaxed spontaneously, and was followed by slow waves of contracture. This was not observed if the strips were incubated, prior to caffeine, in 4.4 mM calcium Ringer without ouabain, or in 1.1 mM calcium Ringer solution that contained 10(-6) M ouabain.12 Based on these findings, a hypothesis that can explain the inotropic effect of cardioactive steroids is presented.

[Evaluation of the tuberculin reaction in health occupation students] . / Evaluación de la respuesta a la tuberculina en estudiantes del área de la salud.

A cross-sectional study was done at the University of Antioquia, MedellIn, Colombia, to evaluate the response to a tuberculin skin test among students in undergraduate health programs (medicine, odontology, nursing, and bacteriology) as compared to undergraduate students in nonhealth programs. The study included students from the beginning, middle, and end of the university's academic programs. The sample of 490 students included 273 from health programs and 217 from nonhealth programs. Participants were randomly selected using lists provided by the university registrar, for the second semester of 1998. The presence of a BCG vaccination scar was determined, and all the participants were also questioned about TB-related risk factors. Tuberculin skin test reactivity was evaluated by the size of induration 72 hours after intradermal injection of two tuberculin units of purified protein derivative RT 23. There were no differences in tuberculin reactivity between students from the health programs and from the nonhealth programs, irrespective of the academic level. However, there was a significantly higher proportion of positive skin tests among students with a BCG scar. These results suggest that undergraduate health students do not have extensive contact with TB patients or with clinical samples from such patients. Nevertheless, the results do not rule out TB as an occupational risk for health personnel.