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Biomedical subjects

K Sankaran

Publications and source records attributed to K Sankaran.

At least 37 records · Page 2Linked to original sources
PubMed1995

Delayed interval delivery in quadruplets.

Prolonged interdelivery periods in preterm twin and triplet gestations have resulted in a good outcome for the fetus(es) remaining in utero. This is the second reported case of delayed delivery intervals in quadruplets who were born on 3 separate days. We report on a set of quadruplets following gonadotropin induction of ovulation, in which preterm delivery of the first infant occurred at 26 weeks' gestation. Active uterine contractions ceased and ultrasonography confirmed the remaining triplets to be in separate amniotic sacs with satisfactory heart rate tracings. With bed rest and tocolysis, the delivery of the second infant did not occur until 8 days later. After a further 36-h delay, placental abruption prompted cesarean delivery of the remaining twins. The first infant died of sequelae of prematurity at 7 months, while the remaining triplets survived and are neuro-developmentally normal 1 year after delivery. This report demonstrates the feasibility of prolonging the delivery interval of the fetus(es) in higher order multiple gestations, using tocolysis and watchful expectancy, after the preterm birth of one or more fetuses.

Adult↗
PubMed1995

Chronic lung inflammation in victims of toxic gas leak at Bhopal.

Bronchoalveolar lavage (BAL) studies in 20 patients at Bhopal, 1.3 +/- 0.4 yr and 2.7 +/- 0.6 yr after toxic gas exposure had revealed that the lower respiratory tract inflammation had progressed from initial macrophage alveolitis to macrophage-neutrophilic alveolitis. The interval between the two lavages was 1.4 +/- 0.6 yr. BAL studies in a new group of 24 patients 5.1 +/- 1.0 yr after exposure had confirmed chronic inflammation of the lower respiratory tract as evidenced by macrophage-neutrophilic alveolitis in these subjects as well. Clinical, radiographic and pulmonary function abnormalities were persistent in a proportion of subjects in both groups. Fibronectin (FN) levels were estimated in BAL fluid in 41 patients. Elevated FN levels were seen in 12 (29.3%) subjects and nine of these 12 had radiographic abnormalities. Severely exposed subjects (n = 30) had significantly higher BAL fibronectin levels compared to normal subjects and mild/moderately exposed subjects. Repeat FN estimations in BAL samples from 10 patients had revealed that five had abnormally high FN including three who had high FN on both occasions. The number of patients showing abnormal decline in pulmonary function was higher in patients with elevated FN than in patients with normal FN. Thus, persisting clinical, roentgenographic and ventilatory abnormalities, as well as macrophage-neutrophilic alveolitis along with abnormally elevated FN levels in a proportion of subjects, suggest the possibility that lung fibrosis can occur in subjects exposed to toxic gas at Bhopal.

Accidents, Occupational↗
PubMed1995

One-year outcome in 232 premature infants with birth weights of 750 to 1249 grams and respiratory distress syndrome randomized to rescue treatment with two doses of synthetic surfactant or air placebo. Canadian Exosurf Neonatal Study Group.

A randomized, double-blind, placebo-controlled trial was performed in 13 hospitals in Canada to assess whether two rescue doses of a synthetic surfactant (Exosurf Neonatal) would reduce mortality and morbidity rates in neonates with respiratory distress syndrome who weighed from 750 to 1249 gm. As part of the original trial design, double-blind follow-up evaluations were performed at 1-year adjusted age. A total of 118 patients who received air placebo and 114 patients who received synthetic surfactant were evaluated at 1 year. Growth and development in the two groups were equivalent. Scores on the Bayley Scales of Infant Development were within the normal range for both groups (mental development index, 90 +/- 22 vs 92 +/- 22; psychomotor development index, 81 +/- 19 vs 87 +/- 22 for the air placebo and synthetic surfactant groups, respectively). However, in both groups the proportion of infants with any impairment (air placebo group, 43 of 118 (36%); synthetic surfactant group, 41 of 114 (36%) and severe impairment (air placebo group, 29 of 118 (25%); synthetic surfactant group, 21 of 114 (18%)) was substantial. We conclude that two rescue doses of synthetic surfactant in infants with RDS who weighed 750 to 1249 gm had no detrimental effect on developmental outcome or late morbidity. No long-term benefits to 12-months corrected age were observed with the use of surfactant in this weight class. Larger studies or meta-analyses of existing trials will be required to determine if there are any late outcome advantages associated with rescue use of synthetic surfactant in infants weighing 700 to 1249 gm.

Air↗
PubMed1995

Double-blind, randomized, placebo-controlled Canadian multicenter trial of two doses of synthetic surfactant or air placebo in 224 infants weighing 500 to 749 grams with respiratory distress syndrome. Canadian Exosurf Neonatal Study Group.

In a multicenter, double-masked, placebo-controlled rescue trial conducted at 12 Canadian hospitals, two 5 ml/kg doses of a synthetic surfactant or air placebo were administered to 224 infants with birth weights of 500 to 749 gm who had established respiratory distress syndrome and an arterial/alveolar oxygen tension ratio of less than 0.22. The first dose was given between 2 and 24 hours of age; the second dose was given 12 hours later to the infants continuing to receive mechanical ventilation. Infants were stratified at study entry by birth weight and gender. Infants receiving synthetic surfactant showed significant improvements in alveolar-arterial oxygen tension gradient, arterial/alveolar oxygen tension ratio, and oxygen and ventilator requirements through day 7. In the group randomized to synthetic surfactant, significant improvements were seen in oxygen requirements at the first time point measured (2 hours; p = 0.02), in the alveolar-arterial oxygen tension gradient by the second time point measured (6 hours; p = 0.03), and in mean airway pressure after 6 hours. Overall mortality at 28 days was not significantly different in the two groups (50% vs 46%, air placebo group vs synthetic surfactant group; p = 0.586). Similarly, neither the incidence of bronchopulmonary dysplasia (37% vs 30%, air placebo group vs synthetic surfactant group; p = 0.089) nor the incidence of survival without BPD through 28 days (17% vs 26%, respectively; p = 0.070) was significantly different in the two groups. No significant differences in the incidence of safety-related outcomes or in adverse effects such as apnea or pulmonary hemorrhage were noted. These findings indicate that rescue therapy with synthetic surfactant results in physiologic improvements in very tiny premature infants, but improvements in overall mortality or other complications of respiratory distress syndrome were not documented in the sample evaluated.

Air↗
PubMed1995

Structure-function relationship of bacterial prolipoprotein diacylglyceryl transferase: functionally significant conserved regions.

The structure-function relationship of bacterial prolipoprotein diacylgyceryl transferase (LGT) Has been investigated by a comparison of the primary structures of this enzyme in phylogenetically distant bacterial species, analysis of the sequences of mutant enzymes, and specific chemical modification of the Escherichia coli enzyme. A clone containing the gene for LGT, lgt, of the gram-positive species Staphylococcus aureus was isolated by complementation of the temperature-sensitive lgt mutant of E. coli (strain SK634) defective in LGT activity. In vivo and in vitro assays for prolipoprotein diacylglyceryl modification activity indicated that the complementing clone restored the prolipoprotein modification activity in the mutant strain. Sequence determination of the insert DNA revealed an open reading frame of 837 bp encoding a protein of 279 amino acids with a calculated molecular mass of 31.6 kDa. S. aureus LGT showed 24% identity and 47% similarity with E. coli, Salmonella typhimurium, and Haemophilus influenzae LGT.S. aureus LGT, while 12 amino acids shorter than the E. coli enzyme, had a hydropathic profile and a predicted pI (10.4) similar to those of the E. coli enzyme. Multiple sequence alignment among E. coli, S. typhimurium, H. influenzae, and S. aureus LGT proteins revealed regions of highly conserved amino acid sequences throughout the molecule. Three independent lgt mutant alleles from E. coli SK634, SK635, and SK636 and one lgt allele from S. typhimurium SE5221, all defective in LGT activity at the nonpermissive temperature, were cloned by PCR and sequenced. The mutant alleles were found to contain a single base alteration resulting in the substitution of a conserved amino acid. The longest set of identical amino acids without any gap was H-103-GGLIG-108 in LGT from these four microorganisms. In E. coli lgt mutant SK634, Gly-104 in this region was mutated to Ser, and the mutant organism was temperature sensitive in growth and exhibited low LGT activity in vitro. Diethylpyrocarbonate inactivated the E. coli LGT with a second-order rate constant of 18.6 M-1S-1, and the inactivation of LGT activity was reversed by hydroxylamine at pH 7. The inactivation kinetics were consistent with the modification of a single residue, His or Tyr, essential for LGT activity.

Amino Acid Sequence↗
PubMed1995

The umpA gene of Escherichia coli encodes phosphatidylglycerol:prolipoprotein diacylglyceryl transferase (lgt) and regulates thymidylate synthase levels through translational coupling.

Using a combination of biochemical, physical, and genetic techniques, we have shown that the umpA gene of Escherichia coli is allelic with the lgt (phosphatidylglycerol:prolipoprotein diacylglyceryl transferase) of Salmonella typhimurium. These genes are essential for the viability of the respective organism and exhibit 92.8% sequence identity at the amino acid level. In E. coli, lgt and thyA (thymidylate synthase) form an operon. Thymidylate synthase levels are regulated by transcription from the lgt promoter and by translational coupling.

Amino Acid Sequence↗
PubMed1995

Prospective, randomized, controlled evaluation of a gentamicin loading dose in neonates.

A prospective, randomized, controlled evaluation comparing a 4-mg/kg loading dose (LD) of gentamicin to the standard regimen of 2.5 mg/kg every 12, 18 or 24 h was conducted in critically ill neonates. The objective of the study was to compare the time required to achieve a therapeutic peak serum concentration (i.e. the number of dosing intervals) and to compare the number of serum concentrations outside the therapeutic range as an indicator of potential toxicity between the treatment groups. Eighteen of 26 patients, 5 of 13 in the control group and 13 of 13 in the LD group (p = 0.012) achieved an initial peak concentration of > or = 5 micrograms/ml following the first gentamicin infusion. There were no significant differences between the control and LD group in the number of potentially toxic serum concentrations. When patients were subdivided according to gestational age (GA), patients of < or = 34 weeks had significantly lower initial peak concentrations. A LD of 4 mg/kg in neonates, particularly those of < or = 34 weeks GA, produced a therapeutic peak concentration following the initial dose. There is a minimal risk of attaining serum concentrations commonly associated with toxicity providing the dosage interval is adjusted based on serum creatinine determinations. Based on this study, infants of > 34 weeks GA generally achieve therapeutic peak concentrations after the first dose with conventional dosing; however, in younger infants an appropriate LD is required to reach therapeutic concentrations early in therapy.

Aging↗
PubMed1994

Lipid modification of bacterial prolipoprotein. Transfer of diacylglyceryl moiety from phosphatidylglycerol.

The peptide, MKATKLVLGAVILGSTLLAGCSSN, corresponding to the N-terminal 24 amino acids of Braun's prolipoprotein, was used to study the lipid modification of prolipoprotein in Escherichia coli by measuring the rate of incorporation of either [2-3H]glycerol or [9,10-3H]palmitate from the corresponding labeled phosphatidylglycerol into the peptide. Using E. coli strains containing varying levels of prolipoprotein diacylglyceryl modification activities due to mutations in or overexpression of the gene involved in diacylglyceryl modification (lgt), we have shown that the activities based on the peptide assay correlated well with the prolipoprotein-based assay. Further, we have followed the fate of the lipid substrate, phosphatidylglycerol, during the modification reaction and found that lipid modification of prolipoprotein involves the transfer of diacylglyceryl moiety from phosphatidylglycerol to the sulfhydryl group of the cysteine residue with the concomitant formation of sn-glycerol 1-phosphate. This mechanism is contrary to the previously proposed two-step mechanism of an initial glyceryl transferase followed by O-acyl transfer (Chattopadhyay, P.K., and Wu, H.C. (1977) Proc. Natl. Acad. Sci. U. S. A. 74, 5318-5322). Accordingly, the enzyme that catalyzes this activity has been named phosphatidylglycerol-prolipoprotein diacylglyceryl transferase. The revised pathway for the lipoprotein biogenesis in bacteria consists of three successive reactions catalyzed by prolipoprotein diacylglyceryl transferase, signal peptidase II, and apolipoprotein N-acyltransferase.

Amino Acid Sequence↗
PubMed1993

Isolation and characterization of a temperature-sensitive mutant of Salmonella typhimurium defective in prolipoprotein modification.

A temperature-sensitive (ts) mutant of Salmonella typhimurium that accumulated unmodified murein prolipoprotein at 42 degrees C but not at 30 degrees C was identified. In vivo and in vitro studies of the biosynthesis of Braun's lipoprotein revealed that this mutant (SE5221) was defective in the glyceryl modification of prolipoprotein. The ts mutation was mapped to 60.6 min of the S. typhimurium chromosome and was linked to argA and cysH. A clone with a 1.4-kilobase S. typhimurium DNA insert that complemented the ts mutation and restored the prolipoprotein modification activity both in vivo and in vitro was isolated. DNA sequencing of the complementing region revealed an open reading frame encoding a protein with 291 amino acids lacking NH2-terminal signal sequence. This open reading frame is immediately 5' to the thyA gene and is allelic to umpA of Escherichia coli. Wild-type strains harboring the cloned gene exhibited elevated levels of prolipoprotein modification activity. At the non-permissive temperature, the mutation affected both growth and viability, and the mutant cells exhibited anomalous cell morphology. The ts phenotype was suppressed by the introduction of a lpp::Tn10 mutation. These results suggest that the cloned gene encodes prolipoprotein glyceryl transferase (lgt), and in the wild-type background, this prolipoprotein modification enzyme is essential for the growth and viability of S. typhimurium.

Alleles↗
PubMed1993

Reference values and prediction equations for maximal expiratory flow rates in non-smoking normal subjects in Madras.

Maximal Expiratory Flow Rates such as Peak Expiratory Flow Rate (PEFR), rates at 25%, 50% and 75% of forced vital capacity (V max 25%, V max 50% and V max 75%) and forced expiratory flow during the middle half of forced vital capacity (FEF 25-75%) were measured in 273 healthy non-smoking adults (144 males, 129 females) aged 15-63 years living in Madras. Regression equations were derived for men and women for predicting maximal expiratory flow rates for adults in South India. Expiratory Flow Rates at lower lung volumes in men were similar to those reported for caucasians, but higher than those reported for western Indian Subjects. However, in women the flow rates were similar to those of western Indians and lower than those of caucasians, probably due to indoor air pollution since childhood. These data may suggest that expiratory flow rates at lower lung volumes may not show ethnic variability.

Adolescent↗
PubMed1993

Prediction equations for maximal voluntary ventilation in non-smoking normal subjects in Madras.

Maximal voluntary ventilation (MVV) was measured in 256 healthy non-smoking adults (132 males, 124 females) aged 15-63 years living in Madras. The mean MVV (+/- SD) in males was 126.7 +/- 31.9 and in females 77.7 +/- 16.4. Regression equations were derived for men and women for predicting maximal voluntary ventilation for adults in South India. MVV in South Indians were similar to those reported for other Indian subjects, but lower than those reported for caucasians.

Adolescent↗
PubMed1993

Plasma beta-endorphin concentration and xanthine treatment in apnea of prematurity.

Apnea of prematurity is a common problem in neonatal intensive care nurseries. Xanthines are used to treat apnea, but their mechanism of action is not clearly understood. To determine whether xanthines stimulated beta-endorphin (beta-ED) release in preterm infants, plasma beta-ED concentrations were measured in 27 infants with apnea of prematurity. These infants had a mean (+/- SD) birthweight of 1560 +/- 487 g, gestational age 31 +/- 2.5 weeks, and a postnatal age of 7.3 +/- 4.6 d. Twenty-five of the infants were treated with I.V. aminophylline 2.5 mg/kg/dose 4 times daily and 2 were treated orally with caffeine (10 mg/kg). Blood samples were collected prior to and 30 min after treatment with xanthines. Apneic spells greater than 15 sec were recorded and reviewed every 24 h using a Hewlett-Packard Merlin Monitor (Waltham, MA.) system. Infants were then stratified into responders (Group 1, n = 14) and nonresponders (Group 2, n = 13), with responders defined as showing more than 50% decrease in the frequency of apneic spells in the first 24 h of treatment. beta-ED were measured as previously described using a radioimmunoassay technique. In group 1, plasma beta-ED concentration increased significantly, (p = 0.0496) from pre-xanthine (24.4 +/- 12 pg/ml) to post xanthine (34.6 +/- 24 pg/ml) treatment, whereas in Group 2 the concentrations remained the same (23.3 +/- 5 pg/ml) and (22.6 +/- 4 pg/ml). Birthweight, gestational age, postnatal age, and diagnoses in both groups were compared and no significant differences were observed. Interestingly, xanthine treatment caused increased plasma beta-ED release when apneas decreased.

Apnea↗
PubMed1993

Effect of treatment on maximal expiratory flow rates in tropical eosinophilia.

Maximal expiratory flow rates such as peak expiratory flow rate (PEFR), rates at 25%, 50% and 75% of vital capacity (VE max 25%, VE max 50%, VE max 75%) and forced expiratory flow during the middle half of forced vital capacity (FEF 25-75%) were recorded in 23 patients with tropical eosinophilia (TE) before and after treatment. The mean values of all flow rates were significantly lower (P < 0.001) in untreated TE patients compared to predicted values. After three weeks' treatment with diethylcarbamazine, although there was a significant rise in the mean values of all expiratory flow rates (P < 0.05) except VE max 75% (P > 0.2), all flow rates continued to be significantly lower (P < 0.01) at one month than predicted values.

Diethylcarbamazine↗
PubMed1992

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↗
PubMed1992

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↗