Asphyxic disease of the neonatal kidneys.
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Biomedical subjects
Publications and source records attributed to D B Singer.
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The pathogenesis of the increased erythrocytosis and extramedullary erythropoiesis observed in infants of diabetic mothers (IDM) has been obscure. In the present studies, IDM were found to have elevated umbilical plasma erythropoietin (Ep) concentrations by radioimmunoassay. 22 of 61 IDM (36%) had levels above the range of 28 nonasphyxiated, appropriately grown normal infants. In 16 controls and 20 IDM, plasma Ep correlated directly with plasma insulin (P less than 0.001, r = 0.73). To investigate this relationship further, a chronic rhesus model was studied with continuous fetal hyperinsulinemia for 21 d in utero in the last third of pregnancy. In five experimental fetuses, plasma insulin levels averaged 4,210 microU/ml at delivery, whereas plasma Ep was above the range of six controls. In addition, the experimental fetuses had elevated reticulocyte counts in umbilical cord blood. The mechanism for the increased plasma Ep associated with hyperinsulinemia in the fetus is unexplained but may be mediated by fetal hypoxia.
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Placentae from 20 pregnancies complicated by diabetes mellitus were, by morphometric analyses, similar to 20 placentae from normal patients. Since the average gestation in this study was 1.5 weeks less in the PDM group, accelerated maturity rather than retarded villous development may be inferred. Based on maternal HbAIC determinations, neonatal morbidity and macrosomia, the morphometric similarities of PDM to control placentae in this series do not appear to be explained by normalization of maternal blood glucose levels in the diabetic group.
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The total creatine phosphokinase (CPK) activity and the levels of activity of its MM, MB and BB isoenzymes were measured in sera obtained within four hours after birth from 32 newborn infants. The total CPK level and activity of its MM, MB, and BB isoenzymes increased significantly with increasing acidosis. In addition, statistically significant correlations were found between the total CPK level in infants' sera and their one-minute Apgar scores. The infants' birth weight, gestational age, and mode of delivery did not correlate significantly with the serum total CPK activity. Infants who died within ten days after birth from causes related to asphyxia had significantly higher total CPK activity levels in their sera in comparison with the survivors. The data suggest that perinatal asphyxia with acidosis may result in the leakage of CPK and its isoenzymes from the damaged cells into the circulation and that a marked elevation of their values may indicate a poor prognosis for survival.
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A case of advanced idiopathic arterial calcification occurred in a macerated male fetus, 29 weeks' gestational age, delivered of a 22-year-old primigravida. The aortic valve, aorta, coronary arteries, ductus arteriosus, and pulmonary, mesenteric, periadrenal, and renal arteries were calcified and were detected on postmortem roentgenogram. Myocardial calcification and endocardial fibroelastosis were also present. The mother's calcium, phosphorus, and alkaline phosphatase levels were normal. Vitamin D intake was not excessive. A maternal febrile illness at 18 to 19 weeks' gestation was the only untoward event during pregnancy.
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Hyperinsulinemia was produced in fetal rhesus monkeys for 21 days in the last third of gestation by subcutaneous pork insulin injected at 19 U a day. Plasma insulin concentrations in treated fetuses (N = 4) were 3525 microU/ml. There was no difference in paired pre- and post-treatment fetal plasma glucose concentration. Activity of the hepatic enzymes that promote glucose utilization (glucokinase and hexokinase) and glycolysis (phosphofructokinase, pyruvate kinase, and pyruvate dehydrogenase) was unaffected. Similarly, glycogen metabolism enzymes (active and inactive synthase and phosphorylase) were unaltered. Two gluconeogenic enzymes (PEPCK and glucose-6-phosphatase) were diminished in the treated group compared with controls. Fetal hyperinsulinemia enhanced lipogenic and NADPH-producing enzyme activities, as evidenced by a twofold increase in fatty acid synthase and in citrate cleavage enzyme activity. Malic enzyme was absent. Hyperinsulinemia with euglycemia (1) increases the activity of enzymes that participate in lipogenesis, (2) decreases some of those controlling gluconeogenesis, and (3) has no effect on the enzymes of glycolysis.
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Red blood cell ghost preparations are often cited as providing unequivocal or convincing evidence for the active transport of solutes from a solution of low concentration across a membrane to a solution of higher concentration. Electron microscopic examination of the more widely used ghost preparations show that a considerable quantity of cytoplasmic macromolecules (including hemoglobin) remain within the treated red blood cells. That is, many of the ghost preparations are not hollow membrane perparations. It is concluded that the problem of active solute transport in red blood cell ghost preparations should be reexamined. Furthermore, experiments with ghost preparations purporting to demonstrate active transport should include electron photomicrographs of the preparation utilized.
Acquired monosaccharide intolerance is characterized by the malabsorption of all carbohydrates, resulting in profuse acidic diarrhea. Five infants with this syndrome, ranging from two to six months of age, were studied by measuring their ability to absorb glucose given by intestinal perfusion. Jejunal biopsies obtained at the time of perfusion were studied by light and electron microscopy, and surface area measurements were obtained. Glucose absorption and surface area were significantly decreased (P less than 0.005) during the acute phase of the disease and improved during convalescence. A linear correlation (r = 0.8757) was observed between the ability to absorb glucose and intestinal surface area. It is concluded that the loss of absorptive surface is a major cause of the reduced carbohydrate absorption and consequent diarrhea.
Localization of fluorescein-conjugated heat-aggregated IgG (FA IgG) was demonstrated by immunofluorescence in renal glomeruli of 16 of 69 patients with glomerulonephritis. FA IgG bound more frequently in kidney biopsies from patients with diffuse glomerulonephritis and depressed renal function, and localized selectively in glomeruli that contained heavy deposits of IgM, C3, and C4. The factors that caused FA IgG to bind were specifically reactive with the Fc piece of the IgG molecule and were resistant to 56 degrees C heat for 30 minutes. Localization of FA IgG in the kidney did not correlate with the presence of soluble immune complexes or detectable antiglobulin antibodies in the sera. Binding of FA IgG was also seen in glomeruli and arteries of 18 of 21 kidney allografts studied at the time of impending rejection. But the factors responsible for binding FA IgG in the allografts were heat labile and thus could have been C1q. Although the role of these "antiglobulins" in the immunobiology of glomerulonephritis remains unknown, the fact that they occurred mainly in patients with relatively severe glomerular injury suggests that they could play some part in promoting renal glomerular injury.
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