Single dose cefazolin prophylaxis for postcesarean infections: before vs. after cord clamping.

The objective of this study was to test the hypothesis that 1 g of cefazolin administered preoperatively is no more effective than the same dose administered after cord clamping in preventing postcesarean infectious morbidity. Ninety consecutive laboring subjects undergoing cesarean delivery at > or = 37 weeks gestation were randomized by computer to receive 1 g of cefazolin intravenously preoperatively or after cord clamping in a double-blinded, placebo-controlled study. The 2 groups were compared for differences in maternal and neonatal demographics, and intrapartum and operative characteristics associated with postcesarean infection. Primary maternal outcome variables were endometritis or wound infection. Secondary outcomes included intra-abdominal abscess formation, septic pelvic thrombophlebitis, pneumonia, or urinary tract infection. Neonatal outcomes included sepsis screens, sepsis, pneumonia, and meningitis. Subjects were followed 6 weeks postoperatively for late complications. Subjects receiving cefazolin preoperatively or after cord clamping had similar maternal and neonatal demographics, and intrapartum and operative characteristics. One patient in the former group experienced both endometritis and wound infection. In the latter group, 2 wound infections and 1 case of endometritis occurred (P = 0.35). There were no secondary maternal infections. Two infants treated for pneumonia and 2 other infants readmitted with febrile illnesses were born to mothers receiving cefazolin preoperatively. Overall, 8 neonates were evaluated for suspected sepsis and all had negative studies. Six of these infants' mothers received cefazolin preoperatively (P = 0.28). In conclusion, 1 gram of cefazolin preoperatively is no more effective than the same dose administered after cord clamping in preventing postcesarean infectious morbidity, but is associated with a trend toward increased suspected sepsis in the newborn. However, this trend may be related to differences between the study groups' risk factors for infection.

Butyrate modulates surfactant protein mRNA in fetal rat lung by altering mRNA transcription and stability.

We examined the effects of Na butyrate, a known regulator of gene expression, on surfactant protein mRNA concentration, transcription, and degradation. Exposure of explants of 18-day fetal rat lung to Na butyrate resulted in a decrease in surfactant protein A (SP-A) mRNA concentration to 7% of control after 6 h and to 18% of control after 24 h. The reduction in SP-A mRNA concentration was associated with decreased mRNA transcription and stability at both these times. The effects on SP-B mRNA were similar to those on SP-A, but quantitatively less. In contrast, butyrate had a biphasic effect on SP-C mRNA concentration. There was an initial decrease to 30% of control at 6 h, followed by an increase to control levels by 24 h. Transcription of SP-C was increased at both these times, whereas degradation was enhanced at 6 h, but not at 24 h. The level of surfactant protein mRNA after butyrate treatment therefore depends on the balance between induced changes in transcription and degradation. Butyrate had no effect on gamma-actin mRNA concentration in this system. Circulating levels of butyric acid analogues are elevated in the mothers and fetuses in diabetic pregnancies. Some of these fetuses have delayed lung maturation and decreased amniotic fluid SP-A levels. We speculate that butyric acid analogues partially mediate the changes in pulmonary maturation induced by maternal diabetes.

Surfactant protein C: hormonal control of SP-C mRNA levels in vitro.

We have studied hormonal regulation of the surfactant protein C (SP-C) in fetal 18-dah rat lung explants. SP-C mRNA was detected in Northern blots with a specific rat SP-C cDNA probe and quantified by densitometry. Treatment of the explants with dexamethasone resulted in a dose-dependent increase of the SP-C mRNA level. Transcriptional assays have shown that the regulation of SP-C mRNA by dexamethasone involves a transcriptional step. Administration of the cAMP analogues, 8-bromoadenosine 3',5'-cyclic monophosphate (8-BrcAMP) or dibutyryl adenosine 3',5'-cyclic monophosphate (DBcAMP), produced a dose-dependent increase of SP-C mRNA levels, with maximum stimulation observed at 200 microM. The thyroid hormone T3 had no effect on SP-C mRNA levels, whether administered alone or in combination with dexamethasone. Variation in the effects of the above hormones on three surfactant protein mRNAs, SP-A, SP-B and SP-C, indicates that the hormonal regulation of the surfactant proteins is a complex process and that each gene is, in part, differentially regulated.

Hormonal effects on the surfactant protein B (SP-B) mRNA in cultured fetal rat lung.

Glucocorticoids, triiodothyronine (T3), and cyclic adenosine monophosphate (cAMP) have been shown previously to modulate phosphatidylcholine and surfactant protein A (SP-A) synthesis in fetal rat lung explant cultures. In this report, we have examined the hormonal regulation of the rat surfactant protein B (SP-B) mRNA to determine whether SP-B expression is coordinately regulated with the surfactant phospholipids or with SP-A. Dexamethasone (1 to 200 nM) and cAMP (200 microM) had a stimulatory effect on SP-B mRNA levels, whereas T3 tended to inhibit the accumulation of SP-B mRNA. In combination experiments, treatment with dibutyryl-cAMP (200 microM) and dexamethasone (100 nM) resulted in about a 22-fold increase, whereas dexamethasone or dibutyryl-cAMP alone produced 18- and 2-fold increases, respectively. When the cAMP analogue 8-bromo-cAMP (200 microM) was used in combination with dexamethasone, there was no significant difference between the combined effect and that of dexamethasone alone. T3 treatment, however, resulted in a significant reduction of the dexamethasone-induced stimulation from about a 22-fold to a 14-fold increase. Tissue in situ hybridization showed that dexamethasone stimulated the levels of SP-B mRNA in cells from both the alveolar and bronchiolar epithelium. These data indicate that there are differences in the hormonal regulation of the components of surfactant, suggesting that they are independently regulated.

Regulation of surfactant protein A mRNA by hormones and butyrate in cultured fetal rat lung.

We have previously shown that dexamethasone, triiodothyronine (T3) and dibutyryl adenosine 3',5'-cyclic monophosphate (cAMP) stimulate phosphatidylcholine (PC) synthesis in fetal rat lung explants in culture. There are also additive interactions between these agents with regard to PC synthesis. In this study we examined the regulation of surfactant protein A (SP-A) mRNA in fetal rat lung in culture. Dexamethasone increased SP-A mRNA in the explants in a dose-dependent fashion (1-200 nM), but T3 did not. Whereas 8-bromo-cAMP increased SP-A mRNA, a decrease was observed with dibutyryl cAMP. These findings support the view that at least some of the genes involved in the synthesis of the various components of surfactant are independently regulated. Since we observed differences in the effects of a cAMP analogue which contained butyrate and one that did not, explants were then cultured with Na butyrate, a known regulator of gene expression. A significant decrease in SP-A mRNA was observed at mM concentrations. Exposure of the explants to alpha-aminobutyric acid, a butyric acid analogue which is elevated in the blood of infants of diabetic mothers, resulted in a significant decrease in SP-A mRNA at a concentration 1/25 of that required for Na butyrate. This observation raises the question of whether the decreased SP-A levels reported in fetuses of diabetic mothers may, at least in part, be related to this metabolite.