Optimal dosing of penicillin G in the third trimester of pregnancy for prophylaxis against group B Streptococcus.

OBJECTIVE: We wanted to determine the optimal dose of intravenous penicillin (PCN) in the third trimester of pregnancy for the prophylaxis of group B Streptococcus. STUDY DESIGN: Healthy women in the third trimester with a singleton pregnancy were recruited. Eligibility included no previous penicillin or cephalosporin allergy and no history of renal disease. We obtained a baseline 24-hour urine collection for total protein concentration and creatinine clearance. Two intravenous catheters were placed, and 1 million units of penicillin G (PCN G) sodium was infused through one catheter. Serial blood samples were obtained through the second catheter at 1, 5, 15, 30, 60, 90, 120, 150, 180, 210, and 240 minutes. Serum was stored at -80 degrees C until assays were performed. Reverse-phase high-performance liquid chromatography was used to determine serum concentrations. RESULTS: Fifteen patients met the requirements for eligibility. The average 24-hour urine sample for total protein concentration was 187 mg/dL (range, 11-252), and creatinine clearance was 191 mL/min (range, 137-245). Average maximum serum concentration (C(max)) was 67 microg/mL (range, 34-132) and was reached within 5 minutes. Average serum PCN concentration was 12 microg/mL (range, 9-25) after 4 hours of urine collection. CONCLUSION: The C(max) was 67 microg/mL (670 x minimum inhibitory concentration). One million units of intravenous PCN G exceeds MIC in the treatment of GBS. The dosing interval should be 4 hours to ensure anti-GBS activity in all patients. More frequent dosing does not increase activity. Current recommendations for GBS prophylaxis which use PCN G should be modified pending future studies of neonatal PCN concentrations.

The diagnosis and management of preterm labor.

Accurate diagnosis of preterm labor remains a problematic issue. New techniques such as transvaginal cervical sonography and fetal fibronectin are increasingly important in diagnosis and intervention planning. Neither test can, at present, be recommended for screening of the general population since there is no effective intervention for a positive test. Future directions in research include development of new tocolytic agents such as COX-2 inhibitors and clarification of the best use of adjunctive therapies such as betamethasone for lung maturity.

The Preterm Prediction Study: prediction of preterm premature rupture of membranes through clinical findings and ancillary testing. The National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network.

OBJECTIVE: Our objective was to determine the relative importance of demographic characteristics, clinical risk factors, and ancillary screening tests in the prediction of preterm birth as a result of premature rupture of membranes. STUDY DESIGN: A total of 2929 women were evaluated in 10 centers at 23 to 24 weeks' gestation. Demographic and clinical characteristics were ascertained. Cervicovaginal fetal fibronectin and bacterial vaginosis were evaluated. Cervical length was measured by vaginal ultrasonography. Patients were evaluated for spontaneous preterm birth caused by preterm premature rupture of membranes at <37 and <35 weeks' gestation. Multivariate analyses were performed separately for nulliparous women and multiparous women. RESULTS: Premature rupture of membranes at <37 weeks' gestation complicated 4.5% of pregnancies, accounting for 32.6% of preterm births. Univariate analysis revealed low body mass index, pulmonary disease, contractions within 2 weeks, short cervix (

Ambulatory management of preterm labor.

The care of women with preterm labor has focused predominantly on inpatient therapy: tocolysis, antibiotics, and steroid administration. The emphasis is slowly but surely shifting to secondary prevention and outpatient therapy. Our goal should be toward primary prevention of preterm labor in all women. Then and only then will a true reduction in spontaneous prematurity rates be seen.

Placental villous glucose metabolism and hormone release respond to varying oxygen tensions.

OBJECTIVE: The effects of varying oxygen tensions on tissue metabolic behavior are not well understood, yet many intracellular pathways are influenced by them. In the placenta, optimal in vivo oxygen tension at the villous level is unknown. The purpose of this study was to determine effects of varying oxygen tensions on glucose metabolism and hormone release from perifused placental villous explants. METHODS: Placentas from term normal pregnancies (n = 8) were individually minced into villous fragments, placed into three parallel chambers for each placenta, and continuously perifused for 6 hours with nonrecirculating medium aerated with either 0%, 20%, or 95% oxygen yielding mean oxygen tensions of 76 mmHg, 167 mmHg, and 543 mmHg respectively. Outflow medium was removed at regular intervals and compared to the inflow medium to determine oxygen and glucose consumption as well as lactate, lactate dehydrogenase, hCG, estradiol, and progesterone release. RESULTS: Oxygen consumption was directly proportional to oxygen tension. Glucose consumption was lowest at low oxygen tension, while both lactate and LDH release were lowest at high oxygen tension. Both hCG and progesterone release rates were lowest at high oxygen tensions. Estradiol release demonstrated a trend similar to that of the other hormones although there was no statistically significant difference among the three different levels of oxygen tension. CONCLUSION: Varying oxygen tensions affect placental villous glucose metabolism and hormone release. Under lower oxygen tensions, glucose is metabolized through glycolysis rather than through oxidative phosphorylation and is associated with higher lactate release. Exposure to higher oxygen tensions results in reduced hCG and progesterone release. Higher oxygen tensions may be associated with tissue toxicity.

Intravillous eicosanoid compartmentalization and regulation of placental blood flow.

OBJECTIVE: To determine the roles of the eicosanoids thromboxane and prostacyclin, and their compartmentalization, in the regulation of placental blood flow. METHODS: First, the sites of production of thromboxane and prostacyclin were determined within the placental villus using immunohistochemical staining for thromboxane and prostacyclin synthetase. Second, the production of both eicosanoids was studied in cultured trophoblasts and compared with that in the villous core by measuring the metabolites thromboxane B2 and 6-keto-prostaglandin F 1 alpha. Finally, eicosanoid production was assessed in intact villi after stimulation by an acute change in oxygen content, 5% to 95%. RESULTS: Immunohistochemical staining showed that thromboxane production was primarily within the trophoblasts, whereas prostacyclin production was localized to the endothelial cells within the villi. In culture, we found preferential production of prostacyclin by the villous core cells and increased production of thromboxane by trophoblasts. Perifusion of intact villi demonstrated increased production of thromboxane by trophoblasts in response to an increase in oxygen content. Prostacyclin levels were too low to be detected. CONCLUSIONS: Placental blood flow appears to be regulated by compartmentalized eicosanoids, with thromboxane affecting primarily the maternal side of the placental circulation and prostacyclin affecting primarily the fetal side.

The effect of immediate intraperitoneal carboplatinum on wound healing.

The effect of introducing intraperitoneal carboplatinum on wound healing immediately after wound closure was studied using a rat model. All animals were opened through a midline incision. A bowel anastomosis was then performed in a single-or two-layer fashion using 6-O suture. Immediately after closing the abdominal wall, each animal was percutaneously injected with either normal saline for controls (n = 11), or carboplatinum, 3 (n = 8), 9, (n = 19, or 12 mg/kg (n = 4). Abdominal and skin incisions were closed separately using 4-O silk suture. Animals were sacrificed 7 days postoperatively. Adhesions were blindly assessed on the following scale: 0 (no adhesions), 1 (filmy adhesions), 2 (firm adhesions), and 3 (dense adhesions). Anastomoses were assessed for leakage. Three centimeters of the incision were harvested to evaluate wound breaking strength. Analysis of abdominal wound breaking strengths showed control = 1320 g +/- 220, 3 mg = 1055 g +/- 155, 9 mg = 891 g +/- 127, and 12 mg = 594 g +/- 165 (P < 0.025). Evaluation for dense adhesions resulted in control = 27%, 3 mg/kg = 50%, 9 mg = 63%, and 12 mg = 100% (P < 0.0001). Immediate instillation of intraperitoneal carboplatinum had a significant effect on wound healing with a decrease in abdominal tensile strength directly related to the dose instilled. It also had a significant effect on adhesion formation with a higher dose leading to a higher incidence of adhesion formation. Based on animal model data, it appears that the immediate instillation of intraperitoneal carboplatinum at the time of laparotomy incision closure could lead to significant problems with wound strength and adhesion formation.