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Biomedical subjects

K Sankaran

Publications and source records attributed to K Sankaran.

At least 19 recordsLinked to original sources

Pulmonary hemorrhage in premature infants after treatment with synthetic surfactant: an autopsy evaluation. The American Exosurf Neonatal Study Group I, and the Canadian Exosurf Neonatal Study Group.

In an across study analysis of five multicenter, placebo-controlled trials of the synthetic surfactant, Exosurf Neonatal in infants weighing at least 700 gm, the incidence of clinical pulmonary hemorrhage was 1.9% in treated infants and 1.0% in control infants. To investigate whether a similar increase was also present histologically at postmortem examination, a blinded retrospective review of all autopsy reports from infants dying during these five trials was conducted. Pulmonary hemorrhage was present in 55% of 159 infants undergoing autopsy; the incidence was not different in infants treated with surfactant or air placebo. Birth weight was inversely related to the incidence of pulmonary hemorrhage in both groups. Pulmonary pathologic findings significantly associated with pulmonary hemorrhage included pulmonary interstitial emphysema and necrotizing laryngotracheitis in both groups. In the surfactant group, patent ductus arteriosus, intraventricular hemorrhage, and pneumothorax were significantly more frequent among those who developed pulmonary hemorrhage. In contrast to clinical diagnosis, pathologic diagnosis of pulmonary hemorrhage at autopsy was not more common in infants treated with Exosurf Neonatal.

Autopsy

Sedative/hypnotic effects of chloral hydrate in the neonate: trichloroethanol or parent drug?

Although the metabolism and pharmacokinetics of chloral hydrate (CH) have been reported, there have been no attempts to correlate CH or its metabolite, trichloroethanol (TCE) with the sedative or hypnotic effects. In order to determine whether plasma concentrations of CH or TCE reflect the sedative/hypnotic effects, a sedation/agitation scale was developed. Based on the results of the present study, the sedative/hypnotic effects of TCE cannot be ruled out completely. However, in the neonate, the parent drug CH seems to have a more important role than has been previously suggested from human research.

Chloral Hydrate

Pulmonary eosinophilia in pulmonary tuberculosis.

Three radiologically and bacteriologically confirmed pulmonary tuberculosis patients had eosinophilic pneumonia, as demonstrated by BAL. In two patients, pulmonary eosinophilia was present only at the site of the lesion and the third had eosinophilia in both peripheral blood and lung. There was complete elimination of the eosinophilic inflammatory process in two patients who had successfully completed antituberculosis treatment.

Adult

Tropical eosinophilia: clinical and physiological response to diethylcarbamazine.

Fifty patients with tropical eosinophilia were studied clinically and physiologically, before and after a standard 3-week course of diethylcarbamazine. Before treatment the main physiological abnormality was a reduction in the carbon monoxide transfer factor. One month after the start of treatment most patients had shown a marked symptomatic improvement, but peripheral blood eosinophilia persisted in 52%, radiographic abnormalities in 44%, cough in 22% and chest signs in 8%. Significant improvement was noted in almost all aspects of lung function including blood gases, but the mean values for forced expiratory volume in one second, forced vital capacity, transfer factor and transfer coefficient continued to be significantly lower than predicted values. This study demonstrates the incomplete reversal of clinical, haematological, radiological and physiological changes in tropical eosinophilia one month after starting a 3-week course of diethylcarbamazine.

Adolescent

Effect of diethylcarbamazine on the alveolitis of tropical eosinophilia.

Bronchoalveolar lavage studies in 33 patients with acute untreated tropical eosinophilia have demonstrated intense eosinophilic alveolitis. Following treatment with a standard 3-week course of diethylcarbamazine, there was a significant fall in lung eosinophils (p less than 0.001). However, a mild alveolitis characterised by hypercellular lavage fluid due to a significant increase in absolute alveolar macrophages (p less than 0.001) and due to an increase in both the absolute number (p less than 0.01) and percentage of eosinophils (p = 0.02) was persisting at 1 month despite treatment. Long-term follow-up is essential to know the fate of alveolitis.

Acute Disease

Correlation of lower respiratory tract inflammation with changes in lung function and chest roentgenograms in patients with untreated tropical pulmonary eosinophilia.

Forty-one patients with untreated tropical pulmonary eosinophilia (TPE) were studied to determine whether there was any relationship between lower respiratory tract inflammation and either changes in lung function or abnormalities in chest roentgenograms. Total number of inflammatory cells in bronchoalveolar lavage (BAL) fluid, consisting of alveolar macrophages, lymphocytes, eosinophils and neutrophils had significant negative correlations with transfer factor (TLCO) (r = 0.519, p less than 0.001), transfer coefficient (KCO) (r = 0.312, p less than 0.05) and total lung capacity (TLC) (r = 0.352, p less than 0.05). The absolute count of eosinophils in BAL fluid had a significant negative correlation with TLCO (r = 0.430, p less than 0.01) and KCO (r = 0.300, p = 0.05), but not with forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1) or TLC. However, the absolute count of alveolar macrophages had a significant negative correlation with FVC (r = 0.343, p less than 0.05), FEV1 (r = 0.341, p less than 0.05) and TLC (r = 0.305, p less than 0.05), but not with TLCO or KCO. The total number of lymphocytes had a negative correlation with TLC (r = 0.315, p less than 0.05). There was no correlation between the types of cells recovered in BAL fluid and changes in chest radiographs as assessed by the ILO classification for occupational lung diseases. These data suggest that there may be a dissociation of pulmonary pathophysiological changes produced by different inflammatory cells in the lower respiratory tract. Macrophages and lymphocytes may produce more harm to the lung, as evidenced by significant negative correlations of these cells with lung volumes.

Adolescent

Chloral hydrate disposition following single-dose administration to critically ill neonates and children.

Although the metabolism and pharmacokinetics of chloral hydrate (CH) have been studied in healthy adults, no comprehensive studies have been done in neonates and young infants. Major physiological differences between these groups could greatly affect drug disposition. In this study the patient population (22 patients) was divided into three groups according to postconceptual age: group 1 = preterm infants (31-37 weeks), group 2 = fullterm infants (38-42 weeks) and group 3 = toddler-child patients (57-708 weeks). After receiving one 50 mg/kg oral dose of CH, the parent drug and its metabolites were determined by gas chromatography utilizing an electron capture detector. CH, contrary to what has been reported in the adult, was detectable for several hours after oral administration to patients in all three groups. A highly significant negative correlation was observed amongst the three groups for the half-life (t1/2) and area-under-the-curve for 0 to infinity values for trichloroethanol (TCE), the active metabolite responsible for the sedation effect. The t1/2 value for TCE in group 3 (9.67 h) was similar to that reported for the adult population, but in the less mature subjects it was approximately three (group 2: 27.8 h) to four times (group 1: 39.8 h) greater. Trichloroacetic acid had a remarkably long residence time in the study population after a single dose of CH. The concentration of this metabolite failed to decline even 6 days after dose. These issues should be carefully considered when CH administration is contemplated for clinical use in neonates, infants and children.

Administration, Oral

Determination of chloral hydrate metabolism in adult and neonate biological fluids after single-dose administration.

A simple, rapid and sensitive electron-capture gas chromatographic method has been developed for the simultaneous determination of chloral hydrate, trichloroethanol and trichloroacetic acid in biological fluids. The described method is applicable to single-dose pharmacokinetic studies of chloral hydrate in the adult. The method also meets the important requirement of using very small sample volumes and is sufficiently sensitive and reliable for disposition studies in the neonate.

Adult

Tyrosine hydroxylase in secretory granules from bovine adrenal medulla. Evidence for an integral membrane form.

Intact secretory granules isolated from bovine adrenal medulla express tyrosine hydroxylase (TH) activity. Granule-associated TH sediments on continuous sucrose gradients with dopamine beta-hydroxylase, a marker for granule membranes, indicating that TH is associated with chromaffin granules. Membranes prepared from lysed granules retain TH, whereas granule contents are free of the enzyme. TH immunoreactivity was detected in granule membranes by immunoblot analysis using a polyclonal antiserum against TH. TH immunoreactivity cannot be removed from membranes by washes in high ionic strength buffers and is only partially removed from membranes by treatment with either urea or Na2CO3. TH can be removed from granule membranes by the detergents Nonidet P-40, Triton X-100, and 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate. Treatment of membranes with a phosphatidylinositol-specific phospholipase C did not remove TH, ruling out the possibility of a glycosyl phosphatidyl anchor. Fractionation of granule membranes by temperature-induced phase separation in Triton X-114 revealed that TH is recovered in phases in which integral (detergent phase) and hydrophobic (phospholipid phase) membrane proteins are typically found. By contrast, TH from adrenal cytosol fractionated exclusively into the aqueous phase along with other soluble proteins. Digestion of granules with various protease enzymes revealed that TH is resistant to degradation, suggesting that the enzyme is embedded within membranes. TH becomes phosphorylated when intact granules are exposed to the catalytic subunit of the cAMP-dependent protein kinase, indicating that at least the N-terminal region of TH is exposed on the cytoplasmic surface of granules. These results establish that a fraction of TH is an integral component of bovine granule membranes. The association of TH with granule membranes may play a role in coordinating TH activity and catecholamine release.

Adrenal Medulla

Pulmonary function in healthy young adult Indians in Madras.

Forced vital capacity, forced expiratory volume in one second, functional residual capacity, residual volume, total lung capacity, and single breath diffusing capacity measurements (effective alveolar volume, carbon monoxide transfer factor, and transfer coefficient) were measured in 247 young healthy adults (130 male, 117 female) aged 15-40 years living in Madras. Subjects were of Dravidian stock, living at sea level with rice as their staple diet. Regression equations were derived for men and women for predicting normal pulmonary function for young adults in South India. The values were similar to those reported for subjects from Western India and lower than those reported for North Indians and caucasians.

Adolescent

Pulmonary membrane diffusing capacity and capillary blood volume in tropical eosinophilia.

Pulmonary membrane diffusing capacity (Dm) and pulmonary capillary blood volume (Vc) measurements were carried out in 21 patients with untreated tropical eosinophilia and 21 healthy controls matched for age, sex, height, and smoking habit. The mean single breath transfer factor (Dco) and the mean membrane diffusing capacity were significantly lower (p less than 0.001) in patients with tropical eosinophilia compared with control subjects. However, the mean capillary blood volume was not significantly different (p greater than 0.2). The positive correlations between Dm and transfer factor (r = 0.825), between Dm and effective alveolar volume (VA) (r = 0.721), and between Dco and VA (r = 0.774) were also highly significant (p less than 0.001) in study patients prior to treatment. These data suggest that reduction in single breath transfer factor in untreated tropical eosinophilia may be due to a reduction in membrane diffusing capacity, which in turn may be due to a reduction in area of membrane available for diffusion, as evidenced by the significantly reduced VA (p less than 0.001) in these patients. Since pulmonary capillary blood volume was normal, the pulmonary perfusion was within normal limits. Following three weeks of treatment with diethylcarbamazine citrate, although there was a significant rise in single breath transfer factor (p less than 0.001) and membrane diffusing capacity (p less than 0.05), both Dco (p less than 0.01) and Dm (p less than 0.01) continued to be significantly lower than those of control subjects. However, pulmonary capillary blood volume did not show any change (p greater than 0.2).

Adult

Diurnal rhythm of beta-endorphin in neonates.

In an attempt to prove whether beta-endorphin diurnal rhythm existed in neonates, 17 infants with a mean (+/- SD) gestational age of 31.7 +/- 4.8 weeks and a birth weight of 1,790 +/- 898 g were studied at a mean postnatal age of 3.3 +/- 0.5 days. Plasma samples were obtained from a pre-existing umbilical arterial line at 09.00 h, noon and 15.00 h. Mean plasma concentrations of beta-endorphin were 68.3 +/- 27.7, 54.5 +/- 13.7, and 45.1 +/- 10.8 pg/ml, respectively. Highly significant (p = 0.0002) variation of plasma beta-endorphin concentration was observed in these neonates suggesting the presence of a diurnal rhythm of beta-endorphin in neonates. It is important to specify the time of collection of blood samples for determination of opiates in neonates.

Asphyxia Neonatorum

Immediate and late ventillatory response to high and low O2 in preterm infants and adult subjects.

The differences in the immediate (30 sec or 1 min) and late (5 min) ventilatory response to high and low O2 have not been quantitated in preterm infants and adult subjects using the same methods. It was thought that these differences might explain the paradoxical ventilatory response to CO2 at various O2 concentrations in preterm infants (12). Thus, 9 preterm infants and 10 adult subjects were given 21% O2 to breathe and then 100 or 15% O2 for 5 min each. Adults also breathed 15% O2 before 100% O2 or 12% O2 in order to make their resting arterial PO2 more comparable to those of infants breathing 21% O2. The ventilatory response to 100% O2 was the same in preterm infants and adult subjects, but the late response to 15% O2 remained paradoxical, ventilation decreasing at 5 min by 18% in infants and increasing by 19% in adults. The authors conclude: 1) the traditional concept of the ventilatory response to 100% O2 being different in infants and adult subjects is false; 2) the notion that the response to low O2 is paradoxical in infants is correct; and 3) the data do not explain why the response to CO2 under various background concentrations of O2 in infants is the reverse of that in adult subjects, but the depressed ventilatory response to hypoxia in infants may justify, at least in part, their flatter response to CO2 during low O2 breathing.

Adult

Effect of sleep state on chest distortion and on the ventilatory response to CO2 in neonates.

In 10 preterm and 10 term infants, the effect of sleep state on chest distortion and on the ventilatory response to CO2 was assessed. It was found that chest distortion and ventilatory response to CO2 were independent of sleep state. Chest distortion, however, was more frequent in preterm than in term infants. The authors suggest that the increased prevalence of chest distortion in preterm infants is related to their highly compliant chest wall rather than to differences in sleep state.

Carbon Dioxide