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Biomedical subjects

R Bhat

Publications and source records attributed to R Bhat.

At least 109 records · Page 6Linked to original sources

Critical care problems in neonates. Colloid osmotic pressure in healthy and sick neonates.

Clinical usefulness of colloid osmotic pressure (COP) measurements in adults has been well established. However, data in healthy and sick neonates are sparse. The present study established the COP changes in healthy term and preterm infants and in critically ill neonates. COP in healthy term (16.9 +/- 1.9 mm Hg) and preterm (15.4 +/- 1.3) infants was significantly lower than adults (21.6 +/- 3.6). Even in sick neonates, COP correlated with gestational age (n = 78, r = 0.63, p less than 0.001 , birth weight (r = 0.58, p less than 0.001) and total protein (n = 71, r = 0.58, p less than 0.001). Critically ill preterm infants with hyaline membrane disease had the lowest COP (11.5 +/- 1.2). Administration of 10% albumin failed to increase the COP significantly. In critically ill preterm infants who survived, the COP increased during the first postnatal week, whereas in nonsurvivors COP decreased significantly to less than 10 mm Hg.

Blood Proteins↗

Simultaneous tissue pH and transcutaneous carbon dioxide monitoring in critically ill neonates.

Clinical usefulness and factors affecting transcutaneous CO2 (PtcCO2) monitoring were studied in 22 critically ill neonates. In 10 of 22 infants, both tissue pH (pHt) and PtcCO2 were monitored simultaneously using Roche pHt and CO2 electrodes. Arterial blood gases were obtained from umbilical artery catheter. The effect of variations in blood pressure, oxygenation, arterial pH (pHa) pHt, and medications on PtcCO2 were studied. There was a linear correlation between pHt and pHa (n = 108, r = 0.85, slope 1.08), PtcCo2 and PaCO2 (n = 188, r = 0.85, slope 1.49). The pHt changes correlated better with PtcCO2 than with arterial CO2 (r = 0.78, slope 1.35). The major factors affecting the PtcCO2 relationship were (a) hypoxia and (b) acidosis. When PaO2 less than 40 torr, PtcCO2 correlated poorly to PaCO2 (n = 23, r = 0.48, slope 0.72) whereas, during normoxia (PaO2 greater than 40 torr), it correlated well, r = 0.85, slope 1.51 similarly. When pHt was greater than 7.30, PtcCO2 correlated better with PaCO2 (r = 0.88, slope 1.37) than during tissue acidosis (r = 0.71, slope 1.51). Mean blood pressure down to 30 mm Hg and administration of dopamine and tolazoline did not affect the PtcCO2 to PaCO2 relationship (n = 69, r = 0.86, slope 1.6). Clinically, both continuous pHt and PtcCO2 were found to be very useful in the management of critically ill neonates.

Acidosis↗

Neonatal abdominal aortic thrombosis.

Thromboembolism of abdominal aorta and its branches after umbilical artery catheterization has been previously reported. In the past, total occlusion of the abdominal aorta and its major branches was associated with high mortality. Successful aortic thrombectomy in the neonatal period has been reported only once in English literature. The successful management of 2 infants described here shows the need for early diagnosis and aggressive approach, including surgical thrombectomy when indicated. Thromboembolism of abdominal aorta and iliac arteries can be diagnosed by noninvasive methods, such as 2-dimensional echoaortography and Doppler blood flow measurement.

Aorta, Abdominal↗

Indomethacin metabolism in isolated neonatal and fetal rabbit hepatocytes.

Metabolism of indomethacin was examined in freshly isolated hepatocytes prepared by liver collagenase perfusion of fetal (28) and neonatal rabbits of 3, 5, 10, 12, and 25 days of age. Initial cell viability was more than 90% and linear rates of metabolism were observed for up to 2 hr of incubation. Deacylation of indomethacin to desbenzoyl indomethacin showed a rapid increase early in postnatal development while microsomal O-demethylation to desmethyl indomethacin was increased significantly only in the hepatocytes from 25-day-old rabbits. Glucuronide conjugates of indomethacin and indomethacin metabolites accounted for less than 8% of the total metabolites in hepatocytes from 25-day-old rabbits. The maturational development of indomethacin in metabolism may account for previously reported gestational dependent half-life of the drug in the premature infant (9). However, the factors that regulate development of indomethacin metabolism appear to be under more that one control system.

Animals↗

A comparison of oral and intravenous indomethacin dispositions in the premature infant with patent ductus arteriosus.

Plasma concentrations of indomethacin were studied in 18 premature infants exhibiting significant patent ductus arteriosus (sPDA) after either intravenous or oral drug administration. Oral absorption of indomethacin was prolonged and bioavailability, based on area under the curve (AUC), was less than 20%. The mean volume of distribution for indomethacin was 0.36 l/kg and showed only a small variation between subjects. The drug elimination half-life ranged from 10-25 hours and demonstrated a significant correlation with gestational age. There was no evidence to support dose-dependent clearance or enterohepatic circulation in this study. Side effects of indomethacin were limited in one infant. No significant changes were observed in hematocrit, platelet count, and serum creatinine. The results from this study support the continued use of intravenous sodium indomethacin trihydrate at doses of 0.2 mg/kg and intervals of 18-24 hours for pharmacological treatment of sPDA.

Administration, Oral↗

Structural changes induced in glycogen phosphorylase b by the binding of glucose and caffeine.

The allosteric inhibitors glucose and caffeine cause significant structural alterations in glycogen phosphorylase b (1,4-alpha-D-glucan:orthophosphate alpha-D-glucosyltransferase, EC 2.4.1.1). Both cause a masking of two sulfhydryl groups and a reduction of binding affinity for AMP. Caffeine produces an alteration in the microenvironment of the binding site for 1-anilin-naphthalene-8-sulfonate, resulting in a decrease of quantum yield of fluorescence and a change in spectral distribution. The binding of glucose is exothermic with an enthalpy of binding of -6.0 kcal/mol. Glucose causes a change in the molecular ellipticity in the pyridoxal-5'-phosphate region. The implications of these results are discussed.

Adenosine Monophosphate↗

Continuous tissue pH monitoring in critically ill neonates.

Continuous tissue pH was measured using a minaturized glass electrode in 21 sick term and preterm infants. Tissue pH correlated well with arterial (r = 0.87) and capillary pH (r = 0.90) during the steady state. However, tpH was lower than arterial pH during hypoperfusion and state of shock. Improvement in tissue perfusion resulted in improvement in tpH and good correlation with arterial pH. The electrode was also sensitive to changes in carbon dioxide tension and adminitration of buffer. The good correlation with arterial pH and the feasibility of continuous recording of tissue pH makes it a useful instrument for monitoring the acid-base status of critically ill neonates.

Acid-Base Equilibrium↗

Pharmacokinetics of oral and intravenous indomethacin in preterm infants.

The pharmacokinetic profile of indomethacin administered either orally or intravenously in 13 preterm infants with significant patent ductus arteriosus (PDA) is reported. 9 infants received oral indomethacin and 4 received intravenous therapy. Plasma half-life was significantly prolonged as compared to adult values and demonstrated significant correlation with gestational age. Mean half-life in neonates less than 32 weeks gestation was 17.2 (0.8) vs. 12.5 (0.5) h for neonates greater than 32 weeks gestation. Bioavailability of the oral dosage based on AUC was 13% but no difference was observed in the plasma protein binding or distribution volume of drug as compared to adult values. No serious complications could be attributed to the use of indomethacin at these dose levels in the premature infant.

Administration, Oral↗

Ligand binding and self-association of phosphorylase b.

The mutual influence of ligand binding and self-association has been examined for phosphorylase b in the presence of a series of small ligands. The stepwise equilibrium constants describing the mutual dependence have been evaluated and discussed in terms of possible molecular mechanisms.

Adenosine Monophosphate↗

Gestational age and indomethacin elimination in the neonate.

The disposition of oral indomethacin was studied in 9 premature infants with significant patent ductus arteriosus (sPDA) with birth weights ranging from 800 to 1,960 gm and gestational ages of 28 to 36 wk. Peak plasma concentrations in most of the subjects were not observed until 3 to 4 hr after administration and ranged from 0.027 to 0.31 microgram/ml. Plasma half-life (t1/2) of indomethacin ranged from 11 to 20 hr and correlated with gestational age. Plasma protein binding studies, in samples from the premature infant using radiolabeled indomethacin, showed no difference in binding from values obtained with adult plasma (greater than 98%). Absorption of orally administered indomethacin appears to be incomplete and plasma clearance much longer than in the adult.

Blood Proteins↗

Disposition of indomethacin in preterm infants.

Indomethacin is currently used for the pharmacologic closure of PDA in preterm infants with respiratory distress syndrome. However, the response to the drug has been variable and the disposition of the drug in preterm infants is not well understood. We studied the pharmacokinetics of indomethacin in nine preterm infants with birth weights ranging from 800 to 1,960 gm and gestational ages of 28 to 36 weeks. Three different dose schedules (0.1, 0.25, 0.3 mg/kg dose) were used. The plasma half-life of indomethacin ranged from 11 to 20 hours. Peak levels were achieved within four hours and ranged from 0.027 to 0.310 microgram/ml. The half-life in infants less than 32 weeks' gestation was significantly prolonged compared to that in infants greater than 32 weeks. Protein-binding studies with 14C indomethacin showed that 98% of indomethacin was protein bound. Absorption of orally administered indomethacin appears to be poor and incomplete. No immediate major complications could be correlated to indomethacin therapy in this study.

Birth Weight↗