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Biomedical subjects

W Oh

Publications and source records attributed to W Oh.

At least 217 records · Page 12Linked to original sources

Effect of serum hyperosmolality on opening of blood-brain barrier for bilirubin in rat brain.

The effect of hyperosomolality on the blood-brain barrier for bilirubin was studied in rats. Hyperbilirubinemia was induced in the chronically catheterized rat by infusion of bilirubin at a rate of 30 mg/kg/h for three hours. After two hours of bilirubin infusion, three levels of hyperosmolality were induced by bolus of urea at three different doses: 50, 75, and 100 mmol/kg, respectively. The serum osmolality rose from 297 mosm/L in the control group to 345, 383, and 400 mosml/L in the three respective groups. No significant differences were found between the groups in levels of total or free serum bilirubin, serum albumin, blood pH, and blood gases. A significant dose relationship was found in both brain bilirubin and brain albumin content with reference to the serum hyperosmolality. The results indicate that hyperosmolality causes opening of the blood-brain barrier for bilirubin in the rat. It may be speculated that this adverse phenomenon (hyperosmolality) may play a role in the pathogenesis of kernicterus in infants whose serum bilirubin levels are below the range of saturated bilirubin binding capacity.

Animals↗

Validity of Doppler measurements of anterior cerebral artery blood flow velocity: correlation with brain blood flow in piglets.

Continuous wave Doppler ultrasonography through the anterior fontanel has recently been used to assess changes in cerebral blood flow in human neonates. There has been controversy concerning whether measurements of Doppler blood flow velocity indeed correlate with brain blood flow. An in vivo correlation was performed between brain blood flow as measured by the microsphere method and Doppler flow velocity measurements of the cerebral arteries via an artificial fontanel in young piglets. The peak systolic velocity (r = .76, P less than .001), end diastolic velocity (r = .72, P less than .001) and area under the velocity curve (r = .86, P less than .001) all showed significant positive correlations with brain blood flow. The pulsatility index did not correlate with brain blood flow. Although continuous wave Doppler flow velocity measurements of the anterior cerebral artery cannot quantitatively assess cerebral blood flow, this methodology can be used to correlate changes in cerebral blood flow and provide a meaningful trend analysis following physiologic or pharmacologic perturbation of the cerebral circulation.

Animals↗

Infants with bronchopulmonary dysplasia. Growth pattern and neurologic and developmental outcome.

We evaluate neurodevelopmental and growth outcomes of low-birth-weight infants with bronchopulmonary dysplasia (BPD). Twenty-six cases of BPD (group A) were diagnosed from 244 neonatal survivors with a low birth weight (less than or equal to 1,500 g) born in 1975, 1976, and 1977. During the same period, BPD did not develop in eight infants with a comparable neonatal course (group B) (received oxygen therapy greater than or equal to 21 days). Twenty-five infants who received O2 therapy five or fewer days had a mild clinical course and were considered controls (group C). The BPD infants suffered more asphyxia, respiratory distress syndrome, acidosis, and longer parenteral alimentation and hospitalization than group C infants. Compared with groups B and C, the BPD infants had more respiratory morbidities at 4 and 12 months (P less than .005) and more severe neurodevelopmental sequelae at 2 years.

Bronchopulmonary Dysplasia↗

Fatty acid synthesis in rat fetuses with intrauterine growth retardation.

The effect of uterine artery ligation at 17 days of gestation to induce intrauterine growth retardation (IUGR) on fetal fatty acid synthesis was studied in pregnant rats. Significant impairment in fatty acid synthesis was observed in fetal liver and lung tissues. The specific activity of fatty acids at 19 days of gestation in the liver was lower in the IUGR rats, as compared to controls, 44.6 +/- 13 versus 87.9 +/- 10 cpm/mumol fatty acids (p less than .05). At 21 days of gestation, the specific activity of fatty acids was 40.6 +/- 7.8 as compared to 75.8 +/- 9.8 cpm/mumole in the IUGR and control fetuses, respectively (p less than .05). In lung, the specific activity of fatty acids was 25.7 +/- 5.4 cmp/mumole in IUGR fetuses as compared to 46.6 +/- 9 cpm/mumole in control littermates at 19 days (p less than .05). This difference persisted at 21 days since the specific activity was 32.2 +/- 2.4 in experimental fetuses as compared to 42.6 +/- 3.0 cpm/mumole in controls (p less than .05). Brain and placental tissues demonstrated no statistically significant differences in specific activity at either time in gestation. The total fatty acid content per organ for both liver and lung was also reduced in the IUGR group. Decreased substrate transfer from mother to fetus during placental insufficiency may account for decreased lipogenesis in the IUGR fetus. Brain and placental tissues are spread despite significant compromises in liver and lung capabilities for fatty acid synthesis.

Animals↗

Hemodynamic responses to asphyxia in spontaneously breathing newborn term and premature lamb.

The comparative effects of asphyxia were studied in spontaneously breathing premature and full term newborn lambs. The premature lambs exhibited significantly higher baseline blood flow to several organs. Asphyxia induced similar changes in regional organ blood flow in preterm and term newborn lambs. Regional differences were found in baseline brain blood flow with an increase from cephalad to caudad. Asphyxia resulted in preferential increases in blood flow to the lower brain structures (cerebellum, medulla, midbrain, and spinal cord). Blood flow to most organs returned to baseline 140 min after recovery from asphyxia.

Animals↗

Autoregulation of brain blood flow in the newborn piglet: regional differences in flow reduction during hypotension.

The potential use of a piglet as a model for investigation of brain blood flow was evaluated by assessing the presence of autoregulation in 11 spontaneously breathing newborn piglets. Blood pressure was altered by phlebotomy. When the mean arterial blood pressure was greater than 50 mm Hg, no significant change in brain blood flow (microsphere technique) occurred (r = 0.04), indicating the presence of autoregulation. When the animals became hypotensive a pressure passive relationship exists between brain blood flow and mean arterial blood pressure. However, since the piglets breathed spontaneously and hyperventilated during hypotension, both the mean arterial blood pressure and PaCO2 fell and both correlated with brain blood flow. Thus, it cannot be determined which factor is responsible for the reduction in flow. The blood flow to the specific regions of the brain (cerebrum, cerebellum, brainstem) and mean arterial blood pressure also showed no correlation when the latter was greater than 50 mm Hg. During hypotension, each region demonstrates pressure passive relationships, but the reduction in blood flow is most pronounced in the cerebrum, less in the cerebellum, and least in the brainstem (mean +/- S.E., 64 +/- 8%, 41 +/- 13%, 32 +/- 13% reductions from control respectively, P less than 0.05). The study indicates that a newborn piglet may serve as an appropriate model for the study of brain hemodynamics particularly with regard to autoregulation. Furthermore, during hypotension, preferential protection of vital regions of the brain (cerebellum and brainstem) occur which may have important implications in interpreting the effect of hypotension on the newborn central nervous system.

Animals↗

Cerebral blood flow velocity in infants with polycythemia and hyperviscosity: effects of partial exchange transfusion with Plasmanate.

To determine if there are significant changes in cerebral blood flow velocity and vascular resistance in neonates with polycythemia and hyperviscosity, 11 such infants were studied before and after partial exchange transfusion with Plasmanate. Seven matched control infants were also studied. Blood flow velocity of the anterior cerebral artery was measured with a bidirectional continuous waveform Doppler velocimeter. Blood flow and vascular resistance were calculated from the velocity tracings, using the area under the velocity curve and the Pulsatility Index. Reduction in hematocrit and viscosity produced significant increases in blood flow velocity and a reduction in vascular resistance. The postexchange values were similar to those of the control group. These results indicate that infants with polycythemia and hyperviscosity have decreased cerebral blood flow velocity and increased vascular resistance which normalize after partial Plasmanate exchange transfusion.

Blood Pressure↗

Glycemic response to lipid infusion in the premature neonate.

The effect of lipid infusion on glucose homeostasis in the preterm newborn infant was evaluated. Seven infants were given a test dose of 0.25 gm/kg/hour of lipid emulsion. Their response was characterized by :(1) a two fold increase in serum free fatty acid concentrations, (2) a small, transient rise in insulin values, and (3) a sustained increase in serum glucose concentration (mean increment in serum glucose was 24% over baseline). Nine infants received a test dose of 0.5 gm/kg/hr of lipid. Their response was similar to that in the lower infusion group, but of a greater magnitude: an eightfold increase in free fatty acids, sustained increase in serum insulin concentration, and a mean increment in serum glucose values of 65% over baseline. Increased lipid availability in the low-birth-weight newborn infant plays a significant role in promoting an increase in serum glucose concentrations.

Blood Glucose↗

The effects of different rates of plasmanate infusions upon brain blood flow after asphyxia and hypotension in newborn piglets.

Brain blood flow was determined in 21 spontaneously breathing, awake, newborn piglets during control, asphyxia, superimposed hypotension, and subsequent volume expansion (15 ml/kg of plasmanate). The piglets were divided into three groups based upon the rate of volume expansion: rapid infusion group-piglets received plasmanate in three minutes; slow infusion group-piglets received plasmanate in 30 minutes: the noninfused group-piglets did not receive plasmanate. The results showed comparable increases in brain blood flow among each group during asphyxia, and similar reduction to preasphyxia values during superimposed hypotension. Although pressure-passive changes occurred, the rate of volume expansion did not influence the magnitude of change in brain blood flow. Significantly lower arterial blood pressure and brain blood flow were observed in those piglets who did not have a plasmanate infusion. Intracranial hemorrhages were not observed at autopsy in any of the study subjects. These data indicate that rapid or slow infusion of plasmanate for volume restoration did not influence the pattern of brain blood flow and that in these relatively mature brains, intracranial bleeding was not observed. Both plasmanate infused groups had higher brain blood flows at study completion (when compared to controls), reflecting compensation for anemia to maintain adequate oxygen delivery. Furthermore, regional differences in blood flow were found during asphyxia and superimposed hypotension (brain-stem greater than cerebellum greater than cerebrum), probably reflecting compensatory protection of vital portions of the central nervous system.

Animals↗

Unbound bilirubin and kernicterus in low-birth-weight infants.

Unbound bilirubin, bilirubin binding capacity, and bilirubin binding affinity were determined by the horseradish peroxidase method at the time of maximum hyperbilirubinemia and/or before exchange transfusions in 13 preterm infants who later died and had autopsies performed. Five of the 13 infants had kernicterus at autopsy. There were no significant differences in weight, gestational age, highest indirect bilirubin level, albumin concentration, severity of acidosis, use of assisted ventilation, sepsis, or other major clinical complications between the five infants with kernicterus and the eight infants without kernicterus. Compared with the eight nonkernicteric infants, the five kernicteric infants had significantly higher unbound bilirubin concentrations (13 +/- vs 27 +/- 9 nmoles/liter, respectively, P less than .05) and significantly lower bilirubin binding capacity and affinity. The data suggest an association between low bilirubin binding capacity and affinity, increased unbound bilirubin, and kernicterus in preterm infants with severe clinical complications.

Bilirubin↗

Transcutaneous carbon dioxide monitoring in the newborn period.

One hundred ninety-one simultaneous PtcCO2 and PaCO2 values were recorded from 20 neonates using a heated CO2 sensor. Gestational age and birth weight ranged from 30--44 weeks and 1.22--3.4 kg, respectively. An overestimation of PaCO2 was consistently found. Regression analysis revealed a slope of 1.29, an intercept of 18 mm Hg and a correlation coefficient of 0.85 (p less than 0.001). The PtcCO2 sensor has multiple potential uses in the sick neonate but further experience is necessary to provide adequate correction factors.

Carbon Dioxide↗

Increased erythropoiesis and elevated erythropoietin in infants born to diabetic mothers and in hyperinsulinemic rhesus fetuses.

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.

Animals↗

Rapid glucose disappearance in infants with infection.

Altered carbohydrate metabolism has been reported during episodes of neonatal infection. To document that there is more rapid glucose disappearance during infection, intravenous glucose tolerance tests (IVGTT) and serial plasma growth hormone and insulin levels were determined in eight full-term neonates during the first three days of an acute episode of infection and during convalescence, 5 to 15 days later. Eight healthy infants were each studied once using the same study protocol. Glucose disappearance rates, measured as K1 of glucose, were increased (p less than 0.01) during both the acute septic period (3.7 +/- 0.3% disappearance/min; mean +/- S.E.M.) and convalescent period (2.5 +/- 0.2% min) when compared with values in control infants (1.3 +/- 0.3%/min). Gram-negative, gram-positive, and viral infections were all associated with rapid glucose disposal. The abnormality in carbohydrate homeostasis persisted for at least 5 to 15 days after treatment was begun. Baseline and stimulated (20-minutes post bolus glucose infusion) plasma insulin and growth hormone levels did not differ among the groups. Thus, there is no evidence that hyperinsulinism produced the rapid glucose disappeared rate and enhanced glucose utilization. The reason for the disturbed carbohydrate metabolism in neonatal infections remains unknown.

Age Factors↗

Hyperviscosity in the newborn lamb produces pertubation in glucose homeostasis.

We studied the effect of hyperviscosity on plasma glucose concentration, endogenous glucose production, and plasma insulin concentration in 12 term mixed breed newborn lambs. After a 7-hr fast, 0.45% saline was infused at a constant rate for 6 hr during which time hourly plasma glucose and 3-hourly plasma insulin concentrations were determined. A glucose turnover determination by the prime-constant infusion technique using 3H6 radiolabeled glucose was performed at a steady state. An exchange transfusion was then carried out using maternal packed red blood cells in six lambs to produce hyperviscosity and using maternal whole blood in six other lambs to maintain normoviscosity. After the exchange transfusion, a second study identical to that in the pre-exchange period was carried out. There was no significant difference in the mean plasma glucose concentration (mg/dl; mean +/- S.E.) between groups during the first turnover period (pre-exchange transfusion) [103 +/- 4.9 (normoviscous) versus 96 +/- 4.8 (Hyperviscous)], but during the postexchange transfusion turnover period, the plasma glucose concentration was lower in the hyperviscous than in the normoviscous group [89 +/- 4.3 (Normoviscous) versus 76 +/- 4.0 (Hyperviscous)] (P less than 0.05.) Endogenous glucose production declined from the first to the second glucose turnover determination in both groups, but there was no significant difference between the normoviscous and hyperviscous groups. Plasma insulin concentrations were similarly low in both groups suggesting suppression in the fasted state. The data suggest that the hyperviscosity acts as an independent variable to depress plasma glucose concentration, the mechanism of which is still undefined.

Animals↗

Glycohemoglobin in postpartum women.

As women giving birth to large for gestational age (LGA) infants are at risk for glucose intolerance during pregnancy, fasting plasma glucose (FPG) and glycohemoglobin levels (Hb AIc) were studied in the immediate postpartum period (less than 10 days). These laboratory tests, in addition to infant birth weights and perinatal histories in a group of 146 women whose infants were above the 95th percentile for gestational age, were compared with those of a group of women whose infants were appropriate for gestational age (AGA: above the 25th percentile but below the mothers 75th percentile) as well as with those of a group of control mothers without diabetic risk factors. Mean Hb AIc and FPG were elevated in the mothers of the LGA infants. When either the LGA group alone or all 3 groups together were analyzed by linear regression, significant relationships were observed for maternal Hb AIc versus FPG (P less than .001); maternal Hb AIc versus birth weight corrected for gestational age (P less than .001); and maternal FPG versus birth weight corrected for gestational age (P less than .001). In addition, infant weight correlated with maternal prepregnancy weight (r = .36), maternal weight gain in pregnancy (r = .23), and maternal height (r = .17), but not with any of the paternal anthropometric features studied. Twenty-six women with LGA infants underwent postpartum oral glucose tolerance tests before discharge. Four had abnormal results and all had Hb AIc values above SD of the nonrisk control values (5.8% total Hb). Of the 16 mothers of LGA infants with FPG levels greater than 85 mg/dl (above SD of the nonrisk control values), 7 (44%) also had Hb AIc levels of more than 5.8%. Moreover, on retrospective analysis, the LGA infants manifested increased perinatal morbidity (P less than .05) compared to the combined control groups.

Birth Weight↗