Relative effects of antepartum and intrapartum maternal blood glucose levels on incidence of neonatal hypoglycemia.

OBJECTIVE: The objective of this study was to compare the relative effects of both antepartum and intrapartum maternal plasma glucose concentrations on neonatal plasma glucose levels. STUDY DESIGN: This was a prospective, nonrandomized study. Two hundred thirty-three pregnant insulin-requiring patients with diabetes received intensive diabetic treatment aimed at maintaining the 2-hour postprandial plasma glucose level < 150 mg/dl and the intrapartum plasma glucose level < 100 mg/dl. The neonatal plasma glucose level was monitored during the first 48 hours of life and the incidence of neonatal hypoglycemia was compared with the average antepartum and intrapartum maternal plasma glucose concentrations. RESULTS: The lowest incidence of neonatal hypoglycemia occurred, as expected, among infants of patients who had the lowest mean antepartum and intrapartum plasma glucose levels. However, the intrapartum plasma glucose concentration had a stronger association with decreased neonatal hypoglycemia than the antepartum plasma glucose levels. CONCLUSIONS: Even in the presence of poor antepartum diabetic control tight regulation of the intrapartum plasma glucose levels will significantly reduce the incidence of neonatal hypoglycemia.

Effects of maternal dexamethasone therapy on fetal lung development in the rhesus monkey.

A large body of evidence demonstrates that antenatal glucocorticoids can accelerate fetal lung maturation. The purpose of this study was to delineate the optimal dose of dexamethasone and to determine whether a single- or multiple-injection regimen of the same total dexamethasone dosage was more effective in accelerating pulmonary development. Pregnant rhesus monkeys were injected with varying doses of dexamethasone or vehicle as either a single-bolus injection or as four separate injections, each spaced 12 hours apart. All maternal treatments were begun exactly 72 hours prior to delivery, and all fetuses were delivered by cesarean section at 135 +/- 1 days gestation. When a single injection of dexamethasone was used, fetal liver weight increased in a dose-related fashion. Fetal and maternal cortisol and fetal blood glucose concentrations were also influenced by increasing dexamethasone dosages. Fetal pulmonary phospholipids, however, were unchanged at all steroid doses examined. Multiple injections of dexamethasone generally produced more pronounced effects, even though the total dexamethasone dose remained the same. Thus, liver weight and fetal and maternal cortisol, glucose, and insulin levels were significantly influenced by the multiple administration of dexamethasone. In addition, total lung phosphatidylcholine, surfactant phosphatidylcholine, the surfactant-phosphatidylcholine-to-total-phosphatidylcholine ratio, and the surfactant-disaturated-phosphatidylcholine-to-total-lung-disaturated- phosphatidylcholine ratio were elevated after the multiple-injection regimen. A total dose of 0.5 mg dexamethasone/kg maternal body weight given in four separate injections appeared to produce the most beneficial results. These data suggest that low-dose, antenatal glucocorticoid treatment can effectively accelerate the biochemical maturation of the fetal lung.

[Homozygote CB deficiency revealed by recurrent Neisseria meningitidis infections in an adolescent]. / Déficit homozygote en C8 révélé par des infections récidivantes à Neisseria meningitidis chez un adolescent.

BACKGROUND: Meningococcal infections associated with late complement component deficiency are rarely severe and usually occur during adolescence and adulthood. We report severe manifestations in a boy in whom the first episode appeared early. CASE REPORT: A 14 year-old gypsy boy was admitted because of a febrile meningococcal meningitis that was complicated by a rapidly extensive and necrotic purpura, obnubilation and clotting abnormalities without hemodynamic anomalies. The patient was given symptomatic therapy and a 12-day course of antibiotics that resulted in rapid and complete recovery. Medical history of this patient showed that he had been admitted at the age of 3 years for a severe febrile purpura with septic shock and clotting abnormalities followed by rapid and complete recovery after symptomatic and antibiotic therapy. No germ had been then isolated. The complement system was studied 3 weeks after the second hospitalization: total hemolytic complement activity could not be detected and C2, C3 and C4 were normal. Examination of the terminal pathway-revealed total C8 deficiency. The patient received meningococcal vaccine and was discharged on oral penicillin prophylaxis. He remained healthy during the ensuing 4 years. CONCLUSIONS: Meningococcal infections associated with late complement component deficiency are generally uncomplicated but they remain potentially severe. Early screening for this late complement component deficiency should be considered after severe clinical manifestations.

Molecular effects of T lymphocytes on the regulation of keratin gene expression.

The interactions between lymphocytes and the epidermis are very important in autoimmune skin diseases. Mutual interaction between keratinocytes and T cells is effected both by soluble peptides and by direct cell-to-cell contact. We investigated the possibility that direct cell-to-cell contact with T cells may also play a role in the regulation of keratin gene expression. We have transfected human epidermal keratinocytes with the constructs containing promoters of keratin genes and then cocultured them with the HUT78 strain of human T cells. We found that T cells induce transcription of K5, K6, K14 and K16 genes, as well as the RSV viral promoter, but not K17, K10 or the SV40 viral promoter controls.

[Acute heart insufficiency in an 8-month-old infant presenting with hypocalcemia and Epstein-Barr virus infection: acute myocarditis? Or primary hypokinetic dilated cardiomyopathy?]. / Insuffisance cardiaque aiguë chez un nourrisson de huit mois preésentant une hypocalcémie et une infection à virus d'Epstein-Barr: myocardite aiguë? Ou myocardiopathie dilatée hypokinétique primitive?

An eight-month-old was admitted for acute congestive heart failure with fever. The respective parts played by hypocalcemia (due to vitamin-D deficiency rickets) and acute Epstein-Barr virus infection are discussed. Hypocalcemia was sufficiently marked to induce heart failure per se but replenishment of calcium stores was followed by only partial improvement in cardiac manifestations. Initial management was difficult because of the risks associated with concomitant administration of calcium and digitalis. After eighteen months during which the patient's status remained stable, evaluation showed that clinical features were consistent with sequelae of acute viral myocarditis. The possibility of primary hypokinetic dilated cardiomyopathy was then considered. Esterified carnitine levels were found to be increased leading to further investigations which outruled mitochondrial cytopathy.

[Mitral valve prolapse and Willebrand disease. Study of 16 cases of Willebrand disease]. / Prolapsus valvulaire mitral et maladie de Willebrand. Etude sur seize cas de maladie de Willebrand.

We studied mitral valve morphology and kinetics in 16 children aged 3 to 15 years with documented von Willebrand disease. Mitral valve prolapse was demonstrated in four cases (25%); this result is consistent with findings of similar studies in adults. This non-random association between mitral valve prolapse and von Willebrand disease, as well as embryologic evidence and reports of other conditions found in patients with von Willebrand disease, suggest that mesenchymal dysplasia is the underlying anomaly. Patients with von Willebrand disease and mitral valve prolapse may be at increased risk for cerebrovascular events.

Reflex sympathetic dystrophy: electronic thermography as an aid in diagnosis.

Reflex sympathetic dystrophies can be distressing conditions for patients as well as physicians. In the full-blown case, the diagnosis is easy to make; however, many more subtle forms of reflex sympathetic dystrophy exist. In the full-blown case, diagnosis may be quite simple when the physical findings are present. In the more subtle forms, however, one must have a high index of suspicion in order to make the diagnosis. Clinical testing, such as stellate ganglion blocks, may or may not be helpful. Electronic infrared thermography emerges as a helpful tool in the aid to diagnosis. We have presented several cases in order to illustrate this.

Fetal lung development in male and female nonhuman primates.

Indices of lung maturation were assessed in 58 rhesus fetuses at five gestational ages during the last trimester of nonhuman primate pregnancy to determine whether fetal sex influences lung maturation. In addition to analysis of whole lung phospholipids, glycogen, protein, DNA, and pressure-volume curves surfactant fraction phosphatidylcholine (PC) was quantitated following isolation by sucrose gradient centrifugation and a combination of predictors were assessed by all possible subsets regression to attain a composite "maturity index." For the total population, there was a uniform progression in physical growth characteristics, lung destensibility and stability and phospholipids with advancing gestation. The quantitative change in surfactant fraction PC concentration for both sexes was considerably greater than that observed for whole lung PC between 135 days gestation and term. Further, the increase in surfactant PC occurred in association with improving lung destensibility and deflation stability prior to maximum changes in the whole lung PC or disaturated PC concentration. There were no statistically discernible differences in biochemical or physiological assessment between sexes at any gestational age. These data in nonhuman primates suggest that documented differences in survival from the respiratory distress syndrome between males and females do not result from a discordance in lung maturation as a function of time throughout the last trimester of gestation.

Discordance between male and female deaths due to the respiratory distress syndrome.

General neonatal mortality statistics and those for the respiratory distress syndrome (RDS) were examined for the State of Wisconsin from 1979 through 1982. The objectives were to ascertain whether there are differences in total neonatal mortality related to sex and birth weight, to determine the veracity of reported gender differences in deaths due to RDS, and to assess the contribution of other risk factors for neonatal mortality to overall and sex-specific deaths occurring secondary to RDS. Additionally, a prospective analysis was performed at one perinatal center during a 5-year period in attempts to determine whether gender remained a significant factor in deaths due to RDS after adjusting for incidence. Overall, the most frequent diagnoses in those who died were RDS (15.6%), deaths due to complications of pregnancy (8%), immaturity (4.2%), and asphyxia (3.4%). The majority of fatalities for both sexes occur in neonates weighing less than 1 kg and the percentage of deaths attributable to RDS is greatest between 1 and 1.5 kg. The difference between sexes is also maximal in the latter weight group. Deaths secondary to RDS are greater for males regardless of Apgar score at one and five minutes, mode of delivery, maternal age, or ancillary diagnosis. These data suggest that deaths secondary to RDS are consistently greater in male neonates and that delivery within a limited "window" of time during gestation increases male susceptibility to fatal RDS.

An experimental model for studies of fetal maldevelopment in the diabetic pregnancy.

Values for plasma glucose and serum insulin in fasting conditions and glucose disappearance rates during an intravenous glucose tolerance test were obtained from 54 adult female rhesus monkeys. Some of these animals were subsequently made diabetic by intravenous infusion of streptozotocin (STZ). A single treatment with STZ (47.5 mg/kg) was consistently effective in ten animals for inducing severe hyperglycemia and diminished insulin response to glucose infusion. One of four additional animals became significantly glucose intolerant after a single treatment with STZ (30 mg/kg) and three of three animals became glucose intolerant after two treatments at this dosage. The greater effectiveness of STZ for inducing severe diabetes mellitus in the present study compared with previous investigations using nonhuman primates was attributed to rapid mixing and infusion of STZ with proven diabetogenic activity. Severely diabetic animals have been successfully maintained by daily subcutaneous injections of a combination of NPH and regular insulin. Fetuses of monkeys treated with STZ before conception were hyperglycemic and hyperinsulinemic, and four of these six fetuses were large for gestational age. Preliminary data suggest that fetal lung glycogen concentrations were elevated in these animals compared with controls at 145 days of gestation. It is concluded that the rhesus monkey treated with STZ before pregnancy represents a useful model for studies of fetal maldevelopment in pregnancies complicated by varying degrees of maternal diabetes.

Developmental aspects of lung lipids.

From this review, it is evident that multiple maternal/fetal endogenous or completely exogenous factors have been associated with the complex process regulating fetal lung development. Recent in vitro experiments with human fetal lung explants are especially noteworthy and may establish a perspective for future research. Snyder et al (108) and Medelson et al (74) have found that lung explants from 16-22-week abortuses show differentiated type II cells and augmented PC synthesis within 4 days of culture, rather than the minimum 10- to 15-week period expected in utero. Such a phenomenon is reminiscent of the usual time for clinical recovery from uncomplicated RDS (34). Thus, although expression of the genes influencing lung surfactant phospholipid synthesis and related biochemical processes normally occurs relatively late in gestation, the potential for biochemical differentiation is clearly present in earlier stages. It appears then that the "programming" of the fetal lung for maturation is not absolute but may be altered under certain influences. Whether the advent of lung biochemical maturation occurs as a result of release from inhibition, as the human lung explant data imply, or occurs in response to stimuli, as suggested by exogenous corticosteroid effects, remains to be clarified and is a very challenging scientific problem. It will also be of great interest to define further other biochemical regulators, such as fibroblast pneumocyte factor, that may play an important role in fetal lung maturation.

Saturated phospholipids in amniotic fluid of normal and diabetic pregnancies.

To assess fetal lung maturation in normal and diabetic pregnancies, the authors studied two phospholipids that are more specific for pulmonary surfactant than total phosphatidylcholine (lecithin), namely saturated phosphatidylcholine and phosphatidylglycerol. Results indicated that saturated phosphatidylcholine concentrations normally increase from 10 to 20 nmol/mL before 34 weeks to as high as 150 nmol/mL at term. Although the absolute concentration of saturated phosphatidylcholine could not be used to reliably identify pregnancies leading to respiratory distress syndrome, a saturated phosphatidylcholine level greater than 50% of total phosphatidylcholine was associated with satisfactory neonatal pulmonary function, whereas RDS often occurred in premature infants when less than half the phosphatidylcholine was saturated. Carefully regulated diabetic pregnancies at 36 to 42 weeks of gestation were not different from matched control subjects with respect to total phosphatidylcholine, its ratio to sphingomyelin, saturated phosphatidylcholine, or phosphatidylglycerol. Respiratory distress syndrome did not occur in any infant of the 40 diabetic mothers studied, nor were there any congenital anomalies or cases of symptomatic hypoglycemia.