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Biomedical subjects

R Bhat

Publications and source records attributed to R Bhat.

At least 73 records · Page 4Linked to original sources

Effect of exogenous surfactant on the development of bronchopulmonary dysplasia in a baboon hyaline membrane disease model.

To test the effect of exogenous surfactant on the evolution of histopathologic changes of bronchopulmonary dysplasia (BPD), we conducted a study in a premature baboon hyaline membrane disease model. One hundred mg/kg bovine surfactant sonicated in saline or 3 ml/kg saline placebo was instilled via the trachea at about 10 min of age. The clinical status and physiologic changes were monitored for 9 days, and pulmonary histopathology was evaluated after death. Compared to the control, the surfactant-treated animals showed a significant improvement in arterial/alveolar oxygen ratio and pulmonary compliance, facilitating rapid weaning from assisted ventilation. Lung histology revealed that pulmonary parenchyma expanded 70% to 95% without features of early BPD. Dysplastic maturation, air trapping, or cellular atypia was not seen. In contrast, lung histology in the control group revealed alveolar expansion less than or equal to 50%, basal cell hyperplasia in the bronchial and bronchiolar epithelium, dysplastic maturation with cellular atypia, extensive epithelial erosion, and type II cell hyperplasia, all features of early BPD. The results of this study suggest that in the premature baboon model, exogenous surfactant therapy improves pulmonary functional abnormalities and lessens the histologic features of BPD, perhaps because of rapid weaning and reduced barotrauma.

Animals↗

Effect of single dose surfactant on pulmonary function.

Sequential changes in pulmonary mechanics in response to single dose exogenous surfactant instillation were studied in 15 preterm neonates who had hyaline membrane disease (HMD). The infants were part of a larger double-blind national study. Birth weight ranged from 0.88 to 1.55 kg, and gestational age was between 27 to 32 wk. There were six infants in the surfactant group and nine in the placebo group. Pulmonary mechanics were studied before and at 2, 24, 60, and 96 h after surfactant or sham instillation using a pneumotachometer and an esophageal balloon catheter. The variables studied were dynamic compliance (Cdyn), pulmonary resistance, work of breathing, tidal volume, and minute ventilation. Infants in the surfactant group showed an immediate and significant (p less than .05) improvement in gas exchange ratio, decreased mean airway pressure (9.7 +/- 0.9 to 7.9 +/- 0.4 cm H2O) and airway resistance (133 +/- 6.3 to 92 +/- 14.9 cm H2O/L.sec) (p less than .05). Changes in Cdyn were noted only at 24 h after surfactant instillation. In the control group, gradual improvement occurred after the initial deterioration. The findings suggest that the immediate improvement in oxygenation after surfactant instillation is the result of factors other than changes in lung compliance, such as improved ventilation/perfusion and better capillary stability with decreased leakage of fluid into alveoli.

Airway Resistance↗

Chest radiographic course after exogenous surfactant therapy in baboons with respiratory distress syndrome.

Exogenous surfactant materials have been used under a variety of treatment protocols in cases of neonatal respiratory distress syndrome (RDS). To evaluate the differences in radiologic changes that follow either an early or late therapy with exogenous bovine surfactant, we reviewed 189 serially obtained chest radiographs from 48 premature baboons with RDS studied under different treatment regimen. Twenty-six animals were controls (100 chest films), and 22 received 100 mg/kg bovine surfactant instilled via the trachea in three study protocols (89 chest films). Surfactant was given within 10 min of birth in one group and at 2 h of age in the other. In 25/26 controls, radiologic evidence of severe RDS was seen by 2 h of age; these changes persisted in 15 animals at 24 h. By contrast, a rapid clearing of radiologic features of RDS was seen following surfactant instillation in all 22 (100%) animals within 4 h, but one (4.5%) of these 22 deteriorated at 9 h of age. Pulmonary interstitial emphysema (PIE) was seen in 9/26 (34.6%) and pneumothorax in 5/26 (19.2%) control animals, while 1/22 (4.5%) surfactant-treated animals developed PIE, and none had pneumothorax. The presence of a shunt via the patent ductus arteriosus did not affect radiographic findings in 20 animals studied by contrast injection. Therapy for patent ductus arteriosus (PDA) also had no substantial influence on the radiographic findings, or with regard to the pulmonary course. Radiographic clearing of RDS occurred approximately 18 to 20 h prior to the improvement in pulmonary compliance.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Structural studies of lipid A from Pseudomonas aeruginosa PAO1: occurrence of 4-amino-4-deoxyarabinose.

Lipid A derived from Pseudomonas aeruginosa PAO1 contains a biphosphorylated 1-6-linked glucosamine disaccharide backbone. The reducing glucosamine has an unsubstituted glycosidically linked phosphate at C-1. The nonreducing glucosamine has an ester-bound phosphate at C-4' which is nonstoichiometrically substituted with 4-amino-4-deoxyarabinose. Induction of 4-amino-4-deoxyarabinose was dependent on cultural conditions. No pyrophosphate groups were detected. Acyloxyacyl diesters are formed by esterification of the amide-bound 3-hydroxydodecanoic acid with dodecanoic acid and 2-hydroxydodecanoic acids in an approximate molar ratio of 2:1. Dodecanoic and 3-hydroxydecanoic acids are esterified to positions C-3 and C-3' in the sugar backbone. All hydroxyl groups of the glucosamine disaccharide except C-4 and C-6' are substituted. Lipopolysaccharide chemical analyses measured glucose, rhamnose, heptose, galactosamine, alanine, phosphate, and glucosamine. The proposed lipid A structure differs from previous models. There are significant differences in acyloxyacyl diesters, and the proposed model includes an aminopentose substituent.

Amino Sugars↗

Thermodynamics of some nucleic acid bases and nucleosides in water, and their transfer to aqueous glucose and sucrose solutions at 298.15 K.

The partial molar heat capacities and volumes of some of the constituents of nucleic acids have been determined in water and 1 molal aqueous glucose and sucrose solutions in order to elucidate the nature of interactions occurring between various nucleic acid bases, nucleosides and the sugar (glucose and sucrose) molecules. The results have been explained in terms of the contributions from hydrophobic interactions, hydrophilic interactions and the hydrogen bonding between the solute and solvent molecules. The results have also been compared with those of amino acids and peptides in aqueous glucose and sucrose solutions.

Adenine↗

Surfactant therapy and spontaneous diuresis.

The effect of artificial surfactant therapy on renal function and the onset of spontaneous diuresis was prospectively evaluated in 19 infants with hyaline membrane disease in a double-blind, controlled study. Twelve infants were in the surfactant group; seven infants received placebo (0.9% saline solution). There was no difference in the time of onset of spontaneous diuresis (as defined by output greater than or equal to 80% of intake). The glomerular filtration rate, determined by endogenous creatinine clearance, was also similar in the surfactant- and placebo-treated infants during the first 3 days of life. The fractional excretion of sodium was significantly higher in the placebo group at 24 hours and 36 hours. Infants in the placebo group had a higher negative sodium balance than those in the surfactant group. Ventilatory status improved significantly soon after surfactant treatment, as evidenced by improvement in the alveolar/arterial oxygen pressure ratio and by a lower mean airway pressure. These data suggest that ventilatory status can be improved without diuresis; the factors that regulate diuresis are multiple and not fully understood.

Blood Gas Analysis↗

Maternal insecurity and failure to thrive in Asian children.

Four Asian babies were investigated because they failed to thrive. In all four cases the failure to thrive was a result of the mother's social isolation and inability to communicate, and to the father's refusal to accept that there was a problem in the family.

Anxiety↗

Treatment of patent ductus arteriosus after exogenous surfactant in baboons with hyaline membrane disease.

The effect of early treatment of patent ductus arteriosus (PDA) on the acute course of hyaline membrane disease was tested in a primate model, after intratracheal administration of 100 mg/kg exogenous bovine surfactant phospholipids at mean ages between 2.3-2.4 h. Twenty-two premature baboons were divided into four groups: seven animals were controls (group A); five were treated with surfactant but PDA was not intervened (group B); in five surfactant treatment was followed by three doses of 0.2 mg/kg intravenous indomethacin beginning at a mean age of 5.5 h (group C); and in five surfactant treatment was followed by a surgical ligation of PDA between 5-5.5 h of age. After surfactant instillation in groups B, C, and D, a prompt and sustained improvement was noted in a/APO2, mean airway pressure, ventilator efficiency index and pulmonary compliance. However, no consistent differences were found in the respiratory variables within the surfactant treated groups during the 72-h experiment: the respiratory course in the animals treated for PDA (groups C and D) was generally similar to the animals in which PDA was not treated (group B). In animals treated with surfactant and indomethacin (group C) the mean aortic blood pressure was maintained more optimally as compared to the other three groups. These findings suggest that although a significant early ductal shunting does occur after exogenous surfactant therapy in this animal model, the expected pulmonary deterioration does not occur, and an early abrupt interruption of PDA does not seem to provide additional advantage to the immediate course of hyaline membrane disease.

Animals↗

Response to bovine surfactant (surfactant TA) in two different HMD models (lambs and baboons).

The responses of Surfactant TA instillation in two groups of premature lambs (Group I, 124.8 +/- 1.1 days and Group II, 132.2 +/- 1.2 days, mean +/- SD) and one group of premature baboons (140 +/- 1.6 days) were compared to study the effectiveness of the same surfactant in different animal models. The treatment group received Surfactant TA 100 mg/kg surfactant lipid at 1 to 2 h of age. Control lambs and baboons did not receive surfactant. Sequential measurements of arterial blood gas tension, acid base status, mean airway pressure (MAP) and oxygen requirement (FiO2) were carried out for 8 h after surfactant instillation. The results show that the Group I surfactant-treated lambs improved significantly following instillation. The a/APO2 improved from 0.08 +/- 0.02 before treatment to 0.31 +/- 0.12, and the MAP decreased from 15.8 +/- 0.9 cm H2O to 13.3 +/- 1.3 cm H2O 2.5 h after treatment. At 5.5 h after treatment, the lambs given surfactant deteriorated. Group II treated lambs showed sustained improvement throughout the study period, and improvement in the treated group was not significantly different from Group II control lambs. The surfactant-treated baboons, however, showed sustained and significant improvement in a/APO2 from the time of instillation to the end of the study. These data suggest that the differences in response to the same surfactant therapy between the lamb and baboon models were due to related differences in species, lung maturation, and the differences in response to surfactant, i.e., alveolar leak of protein.

Animals↗

Early and late surfactant treatments in baboon model of hyaline membrane disease.

Because the issue of optimal time for artificial surfactant therapy for hyaline membrane disease has not been established, the effects of treatment with a reconstituted bovine surfactant (surfactant TA) were compared at two time periods in a hyaline membrane disease model in a premature baboon. The baboons were delivered by cesarean section at 75% of gestation (139.5 +/- 1.5 days, mean +/- SD). One group was treated with surfactant TA within ten minutes after birth (ultraearly), another group was treated at two hours of age (late) and a third (comparison group) did not receive the surfactant. Both treatment groups had significantly higher compliance and ratio of arterial to alveolar Po2 ratio and lower mean airway pressure and oxygen requirement (Fio2) than the comparison group. At autopsy, the largest residual volume and hysteresis in pulmonary pressure-volume curves were noted in the ultraearly group, intermediate values were found in the late group, and least values were found in the comparison group. These data indicate that early surfactant therapy for hyaline membrane disease results in greater improvement in lung mechanics than delaying treatment, even for two hours. Delivery room treatment with surfactant of infants at risk for hyaline membrane disease is perhaps better than therapy for established hyaline membrane disease.

Animals↗

Double-blind controlled trial of single-dose treatment with bovine surfactant in severe hyaline membrane disease.

In a double-blind clinical trial the effects of a single dose of reconstituted bovine surfactant ('Surfactant TA') were assessed in 30 premature infants (birthweight 751-1750 g) with severe hyaline membrane disease. 17 infants had a sonicated saline suspension of 100 mg/kg surfactant phospholipid instilled into the trachea at 5.0 (SD 0.7) hours of age and 13 infants received saline by the same route at 4.3 (1.1) hours of age. In the surfactant-treated group there was early improvement in oxygenation and ventilation. Haemodynamically significant patent ductus arteriosus occurred more often in the surfactant group; pneumothorax and pulmonary interstitial emphysema occurred less often. The combined incidence of death and severe bronchopulmonary dysplasia was significantly lower in the surfactant group (3/17) than in the placebo group (9/13).

Animals↗

Effect of calcium chloride on the conformation of proteins. Thermodynamic studies of some model compounds.

Partial molar heat capacities (CP2 degrees) and volumes (V2 degrees) for some amino acids and peptides were measured in 1 M aqueous calcium chloride solutions at 298.15 degrees K using a Picker flow microcalorimeter and an oscillating-tube digital density meter. Using the data for these amino acids and peptides in water, the corresponding partial molar heat capacities of transfer (CP2,tr degree) and volumes (V2,tr degree) from water to 1 M aqueous calcium chloride were deduced. These thermodynamic parameters are significantly positive, indicating that strong interactions occur between the ions of calcium chloride and the charged centres of these amino acids and peptides. A comparison has been made with a similar transfer of these compounds to sodium chloride solutions. The thermodynamic parameters of the transfer of peptide group (-CONH) are much more positive in calcium chloride than in sodium chloride solutions. The implication of this result for the ability of calcium chloride to act as a stronger destabilizer of protein conformation is discussed.

Amino Acids↗

Effect of hepatic cytosol on postnatal drug metabolism.

Postnatal maturation for indomethacin O-demethylation in freshly isolated hepatocytes and 10,000 g liver homogenates of rabbit was found to be significantly different from that observed in rabbit hepatic microsomes. Addition of hepatic cytosol (100,000 g supernatant) from day 10 postnatal rabbits significantly inhibited indomethacin O-demethylation by hepatic microsomes from adult rabbits. Kinetic studies demonstrated that the inhibition was competitive and consistent with the concentration of cytosol. The pattern of postnatal maturation for hepatic microsomal drug metabolism may in part be related to changes in the concentration of endogenous cytosolic inhibitors.

Animals↗