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Biomedical subjects

R P Verma

Publications and source records attributed to R P Verma.

12 recordsLinked to original sources
PubMed2006

Risk factors and clinical outcomes of pulmonary interstitial emphysema in extremely low birth weight infants.

OBJECTIVE: We studied the ante- and postnatal risk factors and clinical outcomes associated with pulmonary interstitial emphysema (PIE) in extremely low birth weight infants (ELBW, <1000 g at birth) in the present era of tocolytics, antenatal steroid and postnatal surfactant administration. STUDY DESIGN: This was a retrospective case-controlled study of all ELBW admitted consecutively during a designated study-period in a level III nursery. Data were analyzed by performing univariate and multivariate analysis as applicable. RESULTS: Infants with PIE had lower 1 and 5 min Apgar scores (P=0.04 and 0.003 respectively), increased surfactant utilization (P=0.004), higher maximum inspired oxygen concentration (P=0.04) and mean airway pressure administration (P=0.02) during the first week of life, and increased neonatal mortality (P=0.01). They received higher antenatal doses of magnesium sulfate (MgSO(4)) (P=0.02). 56% of infants with PIE were exposed to more than 10 g of MgSO(4) (Mg10), compared to 15% in non-PIE group (P=0.01). The multivariate logistic regression analysis including significant co-variates revealed an independent association between Mg10 and PIE (P=0.01, Odds ratio 19.8, 95% CI 1.5-263). CONCLUSION: Pulmonary interstitial emphysema is associated with increased mortality in ELBW infants. Mg10 is an independent risk factor for PIE in this population.

Apgar Score↗
PubMed2005

Inhibition of neutrophil elastase and thrombin activity by caffeic acid esters.

Natural and synthetic caffeic acid esters were assayed for their enzymatic activity versus neutrophil elastase (EC 3.4.21.37) and thrombin (EC 3.4.21.5). Lipophilic caffeic acid esters inhibited neutrophil elastase activity and the inhibition rate was enhanced with increasing length of the aliphatic chain of the alcohol component. The geometry of the chain seems to be more important than the number of carbon atoms. The most inhibitory compound was n-octylcaffeic acid ester with an IC50 value of 1.0 microM. Thrombin activity was only weakly inhibited by the caffeic acid esters thus demonstrating a specificity for neutrophil elastase. Because of its critical role in inflammatory processes, inhibition of neutrophil elastase by caffeic acid esters might be of importance in the treatment of inflammation.

Caffeic Acids↗
PubMed2002

QSAR: then and now.

In this review, the evolution of QSAR is traced from the insightful observations of Crum-Brown and Frazier to Hammett's critical equations and finally Hansch's seminal contributions on hydrophobicity and modelling of biological activity based on extrathermodynamic principles. Today's QSAR models can stand alone, augment other graphical approaches or be examined in tandem with equations of a similar mechanistic genre to truly reveal the power of the paradigm. This review will focus on the three standard classifications routinely used in QSAR analysis electronic, hydrophobic, and steric, as well as topological indices. Electronic parameters will focus on Hammett sigma constants and their numerous variations. Dipole moments, hydrogen bond descriptors and quantum chemical indices as well as applications of their utilization will be described. The hydrophobicity parameter will be examined by tracing its early history, its operational definition and its determination by either experimental methods or computational calculations. Steric parameters, which run the gamut from size to shape, will be described by Taft's, Hancock's, Charton's, Fujita's, Verloop's and Simon's contributions. Topological effects, delineated by connectivity indices, kappa shape and electrotopological indices of Kier and Hall are also described. Examples of QSAR models incorporating most of these parameters are reviewed. In cases where the 95% confidence intervals of variables are available, they are listed in parentheses. A brief Comparative QSAR analysis of non-nucleoside reverse transcriptase inhibitors (NNRTI's) is outlined and various models obtained by different groups examining 4, 5, 6, 7-tetrahydro-5-methylimidazo [4, 5,1-j,k][1,4] benzodiazepin-2(1H)-ones (TIBO) and 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)-thymine (HEPT) derivatives are compared for mechanistic insight that could be useful in the process of inhibitor design.

Drug Stability↗
PubMed2000

Toxicology of benzyl alcohols: a QSAR analysis.

There is an evidence that benzyl alcohols may exhibit toxicity via a radical mechanism. To test this possibility, we studied the toxicity of para substituted benzyl alcohols on rapidly dividing cancer cells (L1210 leukemia). This system has previously found utility in studying the apparent radical toxicity of a variety of phenols. However, no evidence could be found for an electronic effect and the cellular toxicity was associated primarily with hydrophobicity. Comparison of this quantitative structure-activity relationships (QSAR) with others for the reactions of benzyl alcohols in diverse systems provides insight into mechanisms of action. A QSAR for the interaction of benzyl alcohols with protozoa yields an equation that is dependent on both hydrophobicity and acidity of the OH group versus a mixture of bacteria and fungi, the critical dependence on hydrophobicity prevails with a small dependence on a resonance-stabilized, radical mediated electronic effect. The chloramphenicols provide an instructive example, where the radical mediated electronic effect overshadows the hydrophobic contribution to bacterial toxicity. These various QSAR for benzyl alcohols indicate that mechanisms of growth inhibition in vitro vary depending on cell/organism type, the strength of the bond and lability of the hydrogen, and the strength of the initiating radical reagent.

Animals↗
PubMed1996

Vitamin A deficiency and severe bronchopulmonary dysplasia in very low birthweight infants.

Preterm infants often have abnormally low serum vitamin A concentrations. Persistence of vitamin A deficiency for a prolonged postnatal period may contribute to the development of bronchopulmonary dysplasia. We retrospectively analyzed data from 22 infants with birthweight < or = 1250 g who had hyaline membrane disease requiring mechanical ventilation with oxygen and in whom serum vitamin A concentrations had been measured at the onset of enteral feeding and every 2 weeks thereafter. Thirteen infants (low serum vitamin A group) had one or more serum vitamin A concentrations < or = 11 mcg/dL at > 10 days of age. In 9 infants (higher serum vitamin A group) all serum vitamin A concentrations were > 11 mcg/dL at > 10 days of age. Mean birthweight, mean gestational age, sex, race, incidence of antenatal maternal glucocorticoid treatment and ventilatory support on the first day of life were similar for the two groups. Severe bronchopulmonary dysplasia was as defined as characteristic radiographic changes and either discharge from the hospital with supplemental oxygen or death from respiratory failure at > 28 days of age following mechanical ventilation with oxygen since birth. The incidence of severe bronchopulmonary dysplasia was significantly higher in the low serum vitamin A group (11/13, 3 deaths vs. 1/9, no deaths; p=0.001). The incidence of pulmonary air leak, the number of ventilator days, the number of days of postnatal glucocorticoid treatment for chronic lung disease, the number of episodes of suspected sepsis and the number of days of antibiotic treatment also were higher in the low serum vitamin A group. Low serum vitamin A group infants were older at the onset of enteral feeding (21 days vs. 8 days; p = 0.001) and during feeding their average daily enteral intake of vitamin A was lower (713 IU vs. 1255 IU; p = 0.001) when compared with infants in the higher serum vitamin A group. Our retrospective analysis of data from these infants confirms earlier reports from other workers that persistent marked vitamin A deficiency in very low birthweight infants is associated with a high incidence of severe bronchopulmonary dysplasia, delayed onset of enteral feeding and low enteral intake of vitamin A.

Bronchopulmonary Dysplasia↗
PubMed1995

Respiratory distress syndrome of the newborn infant.

Pulmonary immaturity, including deficiency in the surfactant system, incomplete structural/functional development of lungs and high chest wall compliance contribute to the pathogenesis of respiratory distress syndrome (RDS). Pulmonary edema and overperfusion, resulting from a patent ductus arteriosus, may further worsen the respiratory failure, and aggravate the surfactant deficiency. Infants born prematurely present with respiratory distress within the first few minutes of life. This quickly becomes life-threatening, and may result in death from severe respiratory failure if appropriate respiratory and general supportive therapy are not immediately instituted. The oxygenation deficit in RDS is secondary to V/Q mismatch and right-left shunting of blood via pulmonary and extrapulmonary routes. Hypoxemia induced pulmonary vasoconstriction further contributes to V/Q mismatch and R-L shunting. Hypoventilation in RDS is due to decreased tidal volume, increased dead space ventilation, and finally, decreased minute ventilation. Characteristically, pulmonary compliance, both static and dynamic, are greatly reduced resulting in a high work of breathing, whereas airway resistance is normal or only slightly increased. This combination of abnormal pulmonary mechanics results in lower respiratory time constant in respiratory units, and helps in achieving ventilation and oxygenation by using low inspiratory time in the ventilator. Management of RDS starts with prenatal identification of the risk, prolongation of pregnancy by tocolysis and prenatal administration of pharmacological agents, like betamethasone. These agents increase the pulmonary gas exchange surface area and induce endogenous pulmonary surfactant in the fetus. Advances in ventilatory and general management techniques have strikingly improved the outcome and prognosis of children suffering from RDS since the 1960s. Recent advancements in the prevention and treatment of RDS, e.g., acceleration of lung development by prenatal pharmacological manipulations and postnatal provision of exogenous surfactant, have significantly contributed to the decrease in mortality from RDS. Pharmacological induction of lung maturation by drugs in combination, and improved technology in lung ventilation are expected to further improve the course and outcome of the disease in future.

Diagnosis, Differential↗
PubMed1994

Maturational response of colonic and renal Na+,K(+)-ATPase activity to K+ load and betamethasone in preterm rats.

Preterm human infants demonstrate high fecal K+/Na+ ratio that is inversely related to maturation. Renal and colonic basolateral membrane-located Na+,K(+)-adenosine triphosphatase (Na+,K(+)-ATPase) governs K+ excretion and is enhanced by both steroid administration and K+ loading. However, the response of premature kidney or colon to these stimuli is not well studied. We measured basal as well as stimulated levels of renal and colonic Na+,K(+)-ATPase activity in response to betamethasone and K+ load given separately and betamethasone given after K+ load in premature, mature, and 4-day-old Sprague-Dawley rats. Although preterm rats showed a higher basal level in the kidneys (p < 0.004), an increase in enzyme activity in response to the stimuli was achieved only in the colon (p < 0.001 for betamethasone, p < 0.0001 for K+ load, and p < 0.0007 for the combination). At term and at 4 days of postnatal age, however, the kidneys showed much higher levels than the colon in response to stimuli (p < 0.0001 for all) except for betamethasone at term. The response of colonic tissue of preterm and term rats to betamethasone given 4 days after a K+ load was less marked than response to betamethasone or K+ load given separately (p < 0.001). The stimulated levels achieved in the preterm colon were higher than the basal preterm renal values (p < 0.001). The tissue K+ content increased in response to K+ load in only the preterm colon (p < 0.05). We have demonstrated a tissue specificity in the development of Na+,K(+)-ATPase activity in K+ excretory organs of rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMedDate not supplied

Body electrolytes in bronchopulmonary dysplasia and the effects of diuretic therapy.

Body electrolytes and their regulatory hormones were studied in preterm infants who suffered from bronchopulmonary dysplasia under two groups: those who were not treated with diuretics (Group II), and those who were treated with diuretics (Group III). The values were compared with a group of matched healthy controls (Group I). Lower serum Na levels, a need of higher Na intake, and higher urinary Na concentrations and urinary specific gravity were found in Group II infants. FeNa was normal and the urinary flow rate was lower than the controls. These data suggest an inability of these infants to dilute urine. Group III infants who were treated with diuretics showed higher serum Na levels and lower urinary specific gravity than Group II infants. These values, as well as water and Na intake/output ratios, were all similar to the control values. Serum aldosterone level was highest in Group II but did not reach significance. Intracellular K concentration was not different between the groups indicating an optimum total body K balance. A significant negative correlation between serum Na and aldosterone levels was found in Group II infants, which was not noted in the controls. Significant correlations were also found between FeNa and plasma aldosterone level in the BPD groups, unlike the controls. The control group of infants showed significant positive correlation between Na balance and serum Na levels. Our results suggest that inability to dilute urine appropriately might be the reason for the BPD patients to retain body water. Water restriction and diuretic therapy therefore are reasonable therapeutic approaches in such cases.

Bronchopulmonary Dysplasia↗
PubMedDate not supplied

Fecal sodium and potassium losses in low birth weight infants.

We measured 24-hour fecal losses of sodium (Na) and potassium (K) in immediate post natal period of preterm neonates to determine the role of this route in the electrolyte imbalances seen in such infants. The values from preterm infants were compared to a group of age matched term infants. Eleven studies were done on unfed extremely low birth weight infants (group I, birth weight < 1200 gms), seven on fed preterm infants (group II, birth weight 1201-2500 gms) and nine on fed term infants (group III, birth weight 2501-4000 gms). Measured and derived variables compared between the groups were 24 hour fecal volume, total fecal electrolyte contents, Na or K lost per kg of body weight and per gm. of stool and Na or K losses as percent of intake. Although 24 hour fecal volume was lowest in group I, none of the variables related to Na differed between groups I and II whereas all of them were significantly lower in group I when compared with group III. Groups II and III differed only in terms of Na loss/gm stool which was lower in the previous group. Conversely K loss/gm of stool was significantly higher in group I when compared with both groups II and III and the only variable that differed between groups II and III was a higher fecal K content as fraction of intake. Fecal K/Na ratio was highest in group I, and decreased progressively with advancing gestational age, whereas creatinine clearance was lowest in group I and increased along with gestational age.(ABSTRACT TRUNCATED AT 250 WORDS)

Feces↗
PubMedDate not supplied

Myocardial calcification in an extremely low birth weight infant with chronic renal failure and secondary hyperparathyroidism.

Myocardial calcification has been rarely described in premature infants after myocardial infarction and myocarditis with coxsackievirus B1. In adults and older children, metastatic myocardial calcification has been reported in chronic renal failure. We report a case of myocardial calcification in a 680-gm preterm infant after a prolonged course of renal failure complicated by secondary hyperparathyroidism. Subclinical myocardial injury was evidenced by a high serum creatine phosphokinase MB band concentration, which probably provided a susceptible substrate for the deposition of calcium crystals, because the multiplication product of serum calcium and inorganic phosphorus levels transiently exceeded 75 mg x mg/100 ml, indicating serum saturation during the course of secondary hyperparathyroidism. We report this case as an unusual complication of renal immaturity in extremely low birth weight infants and an indication of a relatively intact parathyroid glandular function in them. Hypoxia, myocardial dysfunction, and renal failure are common complications in such infants, and in the presence of renal failure, the serum levels of calcium and inorganic phosphorus should be maintained below the pathologic level to avoid ectopic calcification of the tissues, including the myocardium.

Calcinosis↗
PubMedDate not supplied

Early neonatal urinary tract infection: a case report and review.

We report the earliest case of urinary tract infection (UTI) so far described in term uncomplicated newborn infants. The unusual features of this case included early massive hematuria as the only presenting symptom and a host with no risk factors for either sepsis or localization of infection in the genitourinary tract. Reports of urinary analysis, urine cultures, renal ultrasound, and renal scan established the diagnosis of UTI. Massive hematuria in this case was probably precipitated by mild renal venous thrombosis. Ampicillin-resistant Escherichia coli was cultured from the urine, which responded promptly to appropriate treatment. A urine culture was done because of the predominantly urinary signs and symptoms. Although urine culture analysis is not routinely performed for the evaluation of possible sepsis before 72 hours of age, this investigation may be important in critically ill neonates who present with predominantly genitourinary signs and symptoms.

Ampicillin↗