Evaluating the therapeutic approach in pregnancies complicated by borderline glucose intolerance: a randomized clinical trial.

AIMS: Most studies relating minor gestational metabolic alterations to macrosomia refer to glucose intolerance classified on the basis of the National Diabetes Data Group or previous World Health Organization diagnostic thresholds. Our aim was to evaluate the consequences of very mild forms of gestational glucose intolerance, defined by an elevated 50-g glucose challenge test followed by a normal oral glucose tolerance test, using the more restrictive Carpenter and Coustan's criteria (Borderline Gestational Glucose Intolerance, BGGI). METHODS: Three hundred BGGI women were randomly assigned to: Group A (standard management), Group B (dietary treatment and regular monitoring). A control group (C) was also considered. Newborns were classified as macrosomic, large (LGA), or small for gestational age (SGA). RESULTS: The three groups were similar in age, body mass index and parity. Therapy in Group B significantly improved fasting (from 4.68 +/- 0.45 to 4.28 +/- 0.45 mmol/l) and 2-h postprandial glycaemia (from 6.01 +/- 0.57 to 5.13 +/- 0.68 mmol/l). Fasting glycaemia at delivery was significantly lower in B (4.20 +/- 0.38 mmol/l) than in A (4.84 +/- 0.45 mmol/l), and was also lower than in C (4.31 +/- 0.39 mmol/l). Significantly fewer LGA babies were born to Group B (6.0%) than Group A (14.0%) and Group C (9.1%). No difference was found in the SGA rate. The neonatal Ponderal Index was higher (P = 0.030) in group A (2.73 +/- 0.35) than in C (2.64 +/- 0.30) and B (2.64 +/- 0.24). CONCLUSIONS: Even very mild alterations in glucose tolerance can result in excessive or disharmonious fetal growth, which may be prevented by simple, non-invasive therapeutic measures.

Progesterone supplement in pregnancy: an immunologic therapy?

One of the most interesting functions of the placenta is the regulation of the maternal immune response such that the fetal semi-allograft is tolerated during pregnancy. Trophoblasts are presumed to be essential to this phenomenon because they lie at the maternal-fetal interface, where they are in direct contact with cells of the maternal immune system. Trophoblasts do not express classic major histocompatibility complex (MHC) class II molecules. Surprisingly, cytotrophoblasts express more HLA-G, a MHC class Ib molecule, as they invade the uterus. Progesterone plays an important role in postovulatory regulation of the menstrual cycle. If fertilization occurs, progesterone supports implantation of the ovum and maintains the pregnancy. Progesterone has been named the 'hormone of pregnancy', because in preparing the endometrium for embryo implantation and facilitating endometrial development, it is critical to the very survival of a pregnancy. In addition, this key hormone inhibits the rejection of T cell-mediated tissue and also decreases myometrial activity and sensitivity throughout pregnancy. The cellular actions of progesterone are mediated through intracellular progesterone receptors (PRs), which are well studied gene regulators, not express classic major histocompatibility complex. The more used paradigm is relative to the alteration of relationship TH1/TH2, but the complexity of the respective distributions of cytokines at the materno-fetal interface, strongly suggest that, as useful as it certainly was for a while, the Th1/Th2 paradigm must now be considered as an oversimplification. Rather, the existing data point to sequential windows and are suggestive of a system where an extreme complexity is allied to very precise timing and tuning. They also suggest that the materno-fetal relationship is not simply maternal tolerance of a foreign tissue, but a series of intricate mutual cytokine interactions governing selective immune regulation and also control of the adhesion and vascularization processes during this dialogue. However, as shifting the immune response toward the Th2 pattern (IL-4, IL-5, IL-6) may benefit the fetus, whereas development of proinflammatory Th1 cells (secreting IL-2, IFN g, TNF a) may be harmful. Now we are working to open comprise the precise behaviour of NK populations, with the hope of obtaining a diagnostic test of the condition of abortion from 'immunological causes'.

Efficacy of external cephalic version performed at term.

OBJECTIVE: To evaluate the efficacy and complications of external cephalic version in term (37 or more weeks) gestation. STUDY DESIGN: A case series from February 1990 until December 1994 studied 160 patients with term singleton breech presentation. External cephalic version (ECV) with prophylactic tocolysis was the method used. RESULTS: ECV was successful in 67% of the cases (107/160) overall, in 56% of the nulliparous (57/102) and 86% of the multiparous women (50/58). About 90% of those with successful ECV (96/107) had a vaginal delivery with a vertex presentation of the fetus. Emergency Caesarean section due to fetal distress was not required during or immediately after the procedure. No perinatal mortality or babies with an Apgar score less than 7 at 5 min were observed. CONCLUSIONS: ECV in term pregnancy seems to be useful and it is safe both for the mother and the fetus. It should be performed at term, with close monitoring of the fetus, and in an environment able to provide an emergency Caesarean section.

Prevalence of fetal left ventricular hyperechogenic foci in a low risk population.

OBJECTIVE: To ascertain the prevalence and clinical significance of small hyperechogenic foci detected in the fetal left ventricle in routine ultrasound screening of pregnant women attending our hospital. POPULATION AND METHODS: From April 1994 to April 1995, 1135 consecutive pregnant women examined at the obstetric ultrasound unit of our hospital were studied prospectively. A postnatal cardiologic examination was performed when signs of cardiopathy were observed at the prenatal ultrasound investigation or the neonatal examination. RESULTS: Congenital heart disease was detected in 10/1148 infants born (0.9%); eight diagnoses were made prenatally (detection rate 80%). The prevalence of left ventricular hyperechogenic foci was 3.2% (37/1148 fetuses). In 35 cases (94.6%) the foci were no longer observed at the routine third trimester examination. Only in two cases (5.4%) did foci persist at the postnatal examination but without clinical signs of cardiopathy or karyotype anomalies. No association was observed between foci and major structural abnormalities. The foci were single in 32 cases (86.5%). Four foci (10.8%) were located at the interventricular septum, five (13.5%) bilaterally at the papillary apparatus of the mitral valve, and the others at the ventricular wall. No focus was associated with incompetence of the affected valve, whereas five (13.5%) were associated with a fetal disorder. CONCLUSIONS: The prevalence of intracardiac hyperechogenic foci in our general population considered at low risk was more than five times greater than that reported in the literature. Foci were not associated with structural heart defects or chromosomal abnormalities. Persistence during the third trimester and postnatal life was rare and without evident signs of heart disease.

Pharmacokinetics of MDL 63,246, a new semisynthetic glycopeptide antibiotic, in the rat.

Following intravenous administration in the rat, the concentration of MDL 63,246 in plasma was high and long-lasting. Concentrations fell with an apparent three-exponential decay. MDL 63,246 was distributed in a high volume and was cleared quite slowly. The pharmacokinetics of MDL 63,246 in the rat appear to be dose proportional in the dose range of 20 to 50 mg/kg of body weight. When administered subcutaneously, MDL 63,246 was slowly absorbed from the injection site, and the extent of availability was good, being 70.1%. MDL 63,246 was eliminated slowly by both renal and fecal excretion. MDL 63,246 is rapidly and extensively distributed into the tissues. At 0.5 h after drug administration, radioactivity was detected in all organs examined. At 24 h after administration, the total concentrations of radioactivity still increased in some organs which represent a slowly equilibrating compartment, but only the kidneys and liver showed a higher total concentration of radioactivity than plasma. Between 24 and 192 h after treatment, total concentrations of radioactivity decreased very slowly, and finally, apart from brain, all tissues showed higher concentrations than plasma, indicating a very high affinity of MDL 63,246 for tissues. The ratio of the concentration of radioactivity in blood to that in plasma ratio was 0.58, indicating that MDL 63,246 does not diffuse into erythrocytes and that binding to the erythrocyte membrane does not occur. All of these findings appear to correlate with the excellent in vitro and in vivo activities of the compound, suggesting that MDL 63,246 could be therapeutically efficacious at lower dosages and longer treatment intervals than those currently used for vancomycin and teicoplanin.

High-performance liquid chromatographic determination of rifapentine and its metabolite in human plasma by direct injection into a shielded hydrophobic phase column.

A simple high-performance liquid chromatographic method for determination of rifapentine, a cyclopentyl semisynthetic analogue of rifamycin belonging to the class of piperazinyl hydrazone derivatives of 3-formylrifamycin SV, and its metabolite, 25-desacetylrifapentine, in human plasma was developed using direct injection of the sample onto a Supelco LC HISEP column. The mean recovery was 100.3% for rifapentine and 99.7% for the metabolite and the precision of the assays was 3% and 7%, respectively. The limit of determination was 0.2 micrograms/ml and the method was validated for concentrations up to 64 micrograms/ml for rifapentine and 32 micrograms/ml for the metabolite. The results correlated well with those of the microbiological assay with Sarcina lutea as test organism.