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Biomedical subjects

V Bhandari

Publications and source records attributed to V Bhandari.

At least 19 recordsLinked to original sources
PubMed2006

Site-specific characteristics of infants developing bronchopulmonary dysplasia.

HYPOTHESIS: Site-specific variables that contribute to the pathogenesis of bronchopulmonary dysplasia (BPD) can be identified. OBJECTIVES: To evaluate the demographic, nutrition and growth characteristics of infants at risk for developing BPD at two neonatal intensive care units (NICUs: sites A and O). STUDY DESIGN: Records of 306 infants of < or = [corrected] 30 weeks gestational age (GA) who survived to at least 36 weeks postmenstrual age were retrospectively reviewed. Data were obtained for maternal and neonatal demographics, weights, total fluids, calories, carbohydrate, protein and fat intake at birth, 7, 14, 21 and 28 days of life. RESULTS: BPD rates were not different at the two sites. No statistical differences were noted in the incidence of maternal chorioamnionitis, pregnancy-induced hypertension or use of antenatal steroids among infants who developed BPD (n = 169) and those who did not (n = 137). White race, birth weight, respiratory distress syndrome requiring surfactant, sepsis and patent ductus arteriosus were significantly associated (all P < or =0.03) with BPD. After controlling for significant confounding variables, infants who developed BPD had significantly (P < 0.001) less weight gain, received less calories and fat in the first postnatal month. In the 26 to 28 weeks GA group, the odds of getting BPD were 5.4 (95%CI: 1.4 to 21.3) times greater for site A than site O (P = 0.017). CONCLUSION: Our analysis suggests that while some decrease in BPD can be achieved by focusing on ventilation/oxygen use, this approach is unlikely to impact on the youngest infants.

Black or African American↗
PubMed2004

Effect of antioxidants on apoptosis and cytokine release in fetal rat Type II pneumocytes exposed to hyperoxia and nitric oxide.

The response of the fetal rat Type II pneumocyte (FTIIP), the stem cell of the alveolar epithelium, to hyperoxia would be helpful to understand the effects of oxygen-induced injury to the developing lung. Our goals were to evaluate the effect of antioxidants (AO) on apoptosis and release of cytokines in freshly isolated FTIIP (day-19) in the presence of 95% O2 and/or nitric oxide (NO). There was increased apoptosis in FTIIP exposed to hyperoxia alone and in combination with NO; this was significantly attenuated (p < 0.01) in the presence of 3 AO, namely grape seed proanthocyanidin extract (GSPE), superoxide dismutase (SOD) and catalase. The anti-inflammatory cytokine IL-10 has been shown to have a role in ameliorating tissue damage owing to persistent inflammation. The release of IL-10 was significantly decreased (p < 0.01) in the presence of GSPE and catalase, compared to control. Addition of SOD led to increased IL-10 compared to GSPE or catalase (p < 0.01) or the combination of GSPE + SOD + catalase (p < or = 0.01). Thus, in our in vitro model of hyperoxic and NO mediated injury to FTIIP, protection from apoptotic cell death with the addition of AO was associated with varying levels of IL-10 release. Our data suggest that the use of SOD and/or IL-10 may decrease hyperoxic lung injury by decreasing apoptosis. Further studies are needed to understand the mode of protection from catalase and GSPE.

Aerobiosis↗
PubMed2003

The sy-fi study: a randomized prospective trial of synchronized intermittent mandatory ventilation versus a high-frequency flow interrupter in infants less than 1000 g.

OBJECTIVE: Mechanical ventilation has significantly decreased mortality for preterm infants with respiratory distress syndrome. However, the barotrauma associated with mechanical ventilation is responsible for the development of bronchopulmonary dysplasia (BPD) in 20% to 90% of these infants, depending on gestational age. Recent studies suggest that high-frequency ventilation is associated with better gas exchange and less barotrauma. The purpose of this study is to determine if high-frequency ventilation, using the flow interrupter, reduces the incidence of BPD in the ELBW infant. STUDY DESIGN: Parental consent was obtained prior to mechanical ventilation. Infants less than 1000 g without significant congenital anomalies were eligible for study entry. Infants were randomized, prior to the onset of mechanical ventilation, to receive either synchronized intermittent mandatory ventilation (SIMV) or high-frequency flow interruption. Both ventilator methods were obtained using the Infant Star Ventilator (Mallinckrodt, St. Louis, MO). Data were collected prospectively on all study entrants and analyzed using SigmaStat Software. RESULTS: Forty-six infants, from two centers, were enrolled in this study. There was no significant difference in the ventilator days or BPD, defined as oxygen requirement at 36 weeks postmenstrual age, between the high-frequency ventilation and SIMV groups.

Bronchopulmonary Dysplasia↗
PubMed2003

Pulmonary hypoplasia and persistent pulmonary hypertension in the newborn with homozygous alpha-thalassemia: a case report and review of the literature.

The survival of infants with homozygous alpha-thalassemia, once considered a lethal diagnosis, is now possible through in utero and postnatal diagnostic and therapeutic interventions. We report the survival of a newborn with homozygous alpha-thalassemia complicated by pulmonary hypoplasia and persistent pulmonary hypertension, an association not previously reported.

Diagnosis, Differential↗
PubMed2002

Release of cytokines and apoptosis in fetal rat Type II pneumocytes exposed to hyperoxia and nitric oxide: modulatory effects of dexamethasone and pentoxifylline.

The response of the fetal rat Type II pneumocyte (FTIIP), the stem cell of the alveolar epithelium, to hyperoxia would be helpful to understand the effects of oxygen-induced injury to the immature lung. In such a scenario, the presence of nitric oxide (NO) may have a protective or detrimental effect. Our goals were to evaluate the release of cytokines and apoptotic cell death in freshly isolated FTIIP (19-day) in the presence of 95% O(2) and/or NO. The effects of dexamethasone and pentoxifylline on the FTIIP cytokine response were also studied. There was no significant difference in the levels of IL-1beta and IL-10 from FTIIP, in room air, hyperoxia and/or NO at 2, 6 and 24 h. However, IL-6 release was significantly higher, when measured over time, after 2, 6 and 24 h of exposure to hyperoxia and NO. Dexamethasone in the presence of hyperoxia and/or NO increased the release of IL-10 at 24 h. There was increased apoptosis in FTIIP exposed to hyperoxia alone and in combination with NO; this was significantly attenuated in the presence of dexamethasone and pentoxifylline. We speculate that the cytoprotective effects of dexamethasone in the immature lung may, in part, be mediated via IL-10.

Animals↗
PubMed2002

Hyperoxia and nitric oxide reduce surfactant components (DSPC and surfactant proteins) and increase apoptosis in adult and fetal rat type II pneumocytes.

Nitric oxide (NO) alone or in conjunction with hyperoxia can have protective or detrimental effects on the lung. Our hypothesis was that hyperoxia in conjunction with NO would result in increased cellular dysfunction and apoptotic cell death in adult and fetal Type II pneumocytes (TIIP) in a dose-dependent manner. The TIIP were obtained from adult and 19-day fetal rat lungs. The TIIP were then exposed to 100, 200 and 500 micro M of the NO-donor, Glyco-SNAP-2, alone or in conjunction with 95% oxygen for 24 h. While low-dose NO exposure alone did not increase cytotoxicity, in conjunction with hyperoxia, there was a significant dose-dependent increase in apoptotic cell death of adult TIIP as well as fetal TIIP. Choline incorporation into disaturated phosphatidylcholine was markedly decreased in adult TIIP while the fetal TIIP had similar values as controls. However, the mRNAs of surfactant proteins A, B and C as well as iNOS were significantly reduced in fetal TIIP. Exogenous peroxynitrite also increased nitrotyrosine formation in fetal TIIP as did hyperoxia and NO. The effect of hyperoxia and NO could be abrogated with catalase and superoxide dismutase. These findings may have significant clinical implications in the use of NO in premature infants.

Animals↗
PubMed2001

A prospective controlled trial of albuterol aerosol delivered via metered dose inhaler-spacer device (MDI) versus jet nebulizer in ventilated preterm neonates.

The objective of this study was to identify the most efficient and cost-effective nebulizer device for delivery of albuterol aerosol as a bronchodilator in ventilated preterm infants. Bronchodilators are frequently used as part of the therapeutic regimen of ventilated preterm infants. This can be delivered by different types of nebulizers like the Jet or metered dose inhaler (MDI) spacer device. Fifty-three premature infants being ventilated for RDS (24 to 34 weeks of gestation) were studied just prior to extubation. Twenty-four of them received standard doses of albuterol aerosol via Jet nebulizer and 29 via MDI-spacer. Heart rate, respiratory rate, oxygen saturation, lung compliance, and airway resistance were monitored prior and 15 minutes after albuterol delivery. There were significant changes in the parameters studied between pre- and postnebulizer treatment. In both groups, there was a significant improvement in lung function as evidenced by 13-24% decreased airway resistance (RAWE) and 3-7% increased lung compliance (CDYN). There was also a beneficial clinical response as demonstrated by increased oxygen saturations. These findings suggest that both MDI-spacer and Jet nebulizer are equally effective in delivering the albuterol aerosol to the lower respiratory tract. Since a small dose of albuterol delivered via the MDI-spacer improved lung function as effectively as a higher dose via the Jet nebulizer, the MDI-spacer would be the preferred mode of aerosol administration, especially because it takes only 2 minutes to deliver it. Furthermore, it was also cost-effective as one MDI-spacer treatment costs 2 cents, while a Jet treatment costs 10 cents in our neonatal intensive care unit (NICU).

Administration, Inhalation↗
PubMed2001

Clinical correlations in infants in the neonatal intensive care unit with varying severity of gastroesophageal reflux.

BACKGROUND: Gastroesophageal reflux (GER) is frequently a benign condition in infancy with spontaneous resolution. In the neonatal intensive care unit (NICU), however, it can add to neonatal morbidity if not adequately diagnosed and treated. The objective of the current study was to analyze factors associated with GER in infants in the NICU and correlate them with the severity of the disease. METHODS: All infants in the NICU (n = 150; born November 1994 through April 1999) who were evaluated by a five-channel pH study to rule out GER were included in the study. Infants were grouped as normal, with a reflux index (RI) of less than 6 (n = 66); mild, with RI of 6 to 14 (n = 42); and severe, with RI of more than 14 (n = 42). Maternal and neonatal data were obtained. Clinical GER was defined as the presence of feeding problems (significant gastric residue or emesis) and medical improvement with antireflux measures and medications. RESULTS: There was no difference in birth weight, gestational age; incidence of patent ductus arteriosus, intraventricular hemorrhage, necrotizing enterocolitis, or chronic lung disease; and treatment with aminophylline or caffeine among the groups. Infants with mild and severe GER (RI 6-14 and >14) had significantly more clinical GER than the normal group (P = 0.0001). Additionally, infants with RI more than 14 had significantly more respiratory distress syndrome, lower hematocrits at the time of study and longer length of stay than those with no or mild GER (P = 0.02). CONCLUSION: Infants with severe GER had lower hematocrits despite receiving more blood transfusions and iron therapy. Infants with severe GER also had prolonged hospital stays. Early diagnosis and aggressive management of GER may decrease neonatal morbidity and result in earlier discharge from the NICU.

Cohort Studies↗
PubMed2001

A prospective randomized, controlled trial comparing synchronized nasal intermittent positive pressure ventilation versus nasal continuous positive airway pressure as modes of extubation.

OBJECTIVE: To determine whether synchronized nasal intermittent positive pressure ventilation (SNIPPV) would decrease extubation failure compared with nasal continuous positive airway pressure (NCPAP) in preterm infants being ventilated for respiratory distress syndrome (RDS). METHODS: Infants who were </=34 weeks' gestational age and who were ventilated for RDS were randomized to either SNIPPV or NCPAP after extubation. The criteria for extubation were peak inspiratory pressure of </=16 cm H(2)O, positive end expiratory pressure of </=5 cm H(2)O, intermittent mandatory ventilation rate of 15 to 25, and fraction of inspired oxygen </=0.35. Pulmonary function tests (PFT) were obtained before extubation. After extubation, blood gases were monitored for a minimum of 72 hours. Success was defined as remaining in the selected mode of treatment or demonstrating improvement (switching to oxyhood/nasal cannula/room air) by 72 hours. RESULTS: Thirty-two (94%) of 34 infants were extubated successfully with the use of SNIPPV versus 18 (60%) of 30 with the use of NCPAP (P <.01). There was no difference in apnea/bradycardia episodes in the 2 groups during the 72-hour study period. Among 55 infants who had PFT, 80% (8 of 10) with dynamic lung compliance of >/=0.5 mL/kg/cm H(2)O and expiratory airway resistance of </=70 cm H(2)O/L/s were extubated successfully. In infants with poor lung function (dynamic lung compliance: <0.5 mL/kg/cm H(2)O; expiratory airway resistance: >70 cm H(2)O/L/s), successful extubation was seen in 93% (27 of 29) in the SNIPPV group and 60% (15 of 25) in the NCPAP group. When weight was controlled for at the time of extubation, the odds of success in the SNIPPV group were 21.1 times higher (95% confidence interval: 3.4, 130.1) than that of the NCPAP group. CONCLUSIONS: SNIPPV is more effective than NCPAP in weaning infants with RDS from the ventilator. PFT may be useful in predicting successful extubation.

Female↗
PubMed2000

Hyperoxia causes an increase in antioxidant enzyme activity in adult and fetal rat type II pneumocytes.

It is well known that exposure to hyperoxia results in lung inflammation and damage, which leads to the development of chronic lung disease. Previous studies have shown increased activities of antioxidant enzymes (AOE) in lung tissue from animals exposed to hyperoxia. We propose the hypothesis that the fetal type II pneumocytes (TIIP) would be resistant to oxygen toxicity by virtue of increasing AOE activity on exposure to hyperoxia. The aim of this study was to measure the activities of catalase, glutathione reductase, glutathione peroxidase (GPX), and cytosolic superoxide dismutase (SOD) in cultures of adult and fetal rat TIIP exposed to 95% oxygen for 24 h. Control cells were incubated in room air. Hyperoxia exposure resulted in 53.4 +/- 1.2% of control viability (mean +/- S.E.M.; p = 0.001) in the adult TIIP with a significant threefold increase in the activities of all the AOE. The fetal TIIP were more resistant to hyperoxia (99.4 +/- 6.1% of control viability). However, in the fetal TIIP, only SOD and GPX levels were significantly increased (fourfold and 2.3-fold, respectively) compared with fetal controls. We conclude that fetal TIIP are more resistant to hyperoxia than adult TIIP in terms of viability; other protective antioxidant factors might account for the better survival of fetal TIIP in hyperoxia.

Animals↗
PubMed1999

Potential biochemical growth markers in premature infants.

Identification of a biochemical marker of growth in low birth weight (LBW) infants would be of benefit to rapidly assess the effects of illness and/or therapeutic intervention. The aims of the present study were (1) to measure serially the C-terminal fragment of type I procollagen (PICP), bone-specific alkaline phosphatase (BSAP), and osteocalcin (OC) in LBW infants during the first 6 weeks of life; (2) to correlate the changes in PICP, BSAP, and OC with the changes in weight; and (3) to evaluate PICP levels as a marker for bronchopulmonary dysplasia (BPD). Premature neonates (< or =36 weeks of gestation) had cord blood and then weekly blood samples taken from up to 6 weeks after birth. Daily changes in weight were recorded. Measurements of serum PICP, BSAP, and OC were done in duplicate by immunoassay. In a subset population (25-30 weeks), PICP levels in the first 4 weeks of life were evaluated as a marker for subsequent development of BPD. A total of 77 infants had serum PICP and BSAP measured. The mean (+/- SEM) gestational ages of all the infants were 30.4 (+/-0.3) weeks and birth weights 1477 (+/-55) g. Fifteen infants also had measurements of OC done. In these 15 infants, change in weight was correlated significantly with PICP (p<0.0001), but not with either BSAP (p = 0.8) or OC measurements (p = 0.9). In appropriate for gestational age (AGA) infants (n = 66), the PICP values decreased from the cord blood values to the week 1 measurement, coinciding with the fall in weight over the same time period. BSAP values, on the other hand, continued to increase from birth onwards. Over the first 6 weeks of postnatal life in these infants, change in weight had a stronger positive correlation with PICP (R2 = 0.43, p<0.0001) than BSAP (R2 = 0.03, p<0.01). In the subset population, PICP levels at week 4 were significantly lower (p<0.04) in those infants who subsequently developed BPD. PICP measurements are correlated with somatic growth in premature infants and could be used as a biochemical marker in infants who develop BPD.

Alkaline Phosphatase↗
PubMed1999

Pulmonary hemorrhage in neonates of early and late gestation.

Our objectives in this study of pulmonary hemorrhage (PH) were to define common characteristics of infants who develop PH, identify factors associated with PH and report the outcome. Neonates (42/2980 admissions) with PH and matched controls were identified. Early gestation (< or = 35 weeks) infants with PH [EGPH] (n = 34; 12 survived) had occurrence of PH at 3.6 +/- 1.1 (mean +/- sem) days and were significantly associated with multiple births (p = 0.03), RDS (p < 0.01) and use of Survanta (p < 0.02). Among EGPH, small for gestational age (SGA) infants (n = 7) had a 100% mortality rate. Late gestation (> or = 36 weeks) infants with PH [LGPH] (n = 8; 6 survived) had occurrence of PH at 0.7 +/- 0.3 days and were significantly associated with low 1 minute (p = 0.04) and 5 minutes (p = 0.01) Apgar scores. All infants were managed with increases in mean airway pressure (MAP) and/or use of cocaine/epinephrine through the endotracheal tube. We have identified 2 groups of neonates with distinct factors associated with PH; use of 1:10,000 epinephrine (0.1 ml/kg) and/or 4% cocaine (4 mg/kg) may be useful adjuncts to increases in MAP for management of PH.

Biological Products↗
PubMed1999

Current incidence of retinopathy of prematurity, 1989-1997.

OBJECTIVE: To report the current incidence and the need for surgery for retinopathy of prematurity (ROP) in neonates (22-36 weeks' gestational age [GA], July 1, 1989 through June 30, 1997). STUDY DESIGN: Retrospective analyses using computerized perinatal database kept on all admissions, a review of patient charts, and eye examination log books. SETTING: Level 3 regional referral NICU. PATIENTS: A total of 2528 infants <37 weeks' GA were admitted during this time. Of these infants, 950 met the criteria for eye examination beginning at 4 to 6 weeks of age and repeated every 2 weeks until complete vascularization of the retina or death or discharge. RESULTS: The incidence of ROP was (202/950) 21.3% for any stage and 4.6% (44/950) for stage 3 ROP or greater. No ROP was noted in infants born at >32 weeks' GA. No infant born at >28 weeks needed retinal surgery. Using birth weight (BW) criteria, stage 3 ROP was not noted in infants with BWs >1500 g; retinal surgery was not needed in infants with BWs >1000 g. A number of perinatal factors were associated with ROP on univariate analysis. However, using multiple logistic regression analyses of these factors, only GA and days on supplemental oxygen therapy were associated significantly with the development of ROP. Despite increased survival of extremely low BW infants, we found a considerable reduction in incidence and severity of ROP compared with reports from an earlier chronological period. However, infants <28 weeks' GA or with BWs <1000 g were still at considerable risk for retinal surgical treatment for ROP. CONCLUSION: We conclude that the incidence and severity of ROP have decreased significantly in the present era of surfactant therapy.

Analysis of Variance↗
PubMed1998

Physical and functional interactions between receptor-like protein-tyrosine phosphatase alpha and p59fyn.

We have examined the in vivo activity of receptor-like protein-tyrosine phosphatase alpha (PTPalpha) toward p59(fyn), a widely expressed Src family kinase. In a coexpression system, PTPalpha effected a dose-dependent tyrosine dephosphorylation and activation of p59(fyn), where maximal dephosphorylation correlated with a 5-fold increase in kinase activity. PTPalpha expression resulted in increased accessibility of the p59(fyn) SH2 domain, consistent with a PTPalpha-mediated dephosphorylation of the regulatory C-terminal tyrosine residue of p59(fyn). No p59(fyn) dephosphorylation was observed with an enzymatically inactive mutant form of PTPalpha or with another receptor-like PTP, CD45. Many enzyme-linked receptors are complexed with their substrates, and we examined whether PTPalpha and p59(fyn) underwent association. Reciprocal immunoprecipitations and assays detected p59(fyn) and an appropriate kinase activity in PTPalpha immunoprecipitates and PTPalpha and PTP activity in p59(fyn) immunoprecipitates. No association between CD45 and p59(fyn) was detected in similar experiments. The PTPalpha-mediated activation of p59(fyn) is not prerequisite for association since wild-type and inactive mutant PTPalpha bound equally well to p59(fyn). Endogenous PTPalpha and p59(fyn) were also found in association in mouse brain. Together, these results demonstrate a physical and functional interaction of PTPalpha and p59(fyn) that may be of importance in PTPalpha-initiated signaling events.

Amino Acid Sequence↗
PubMed1998

Respiratory tract colonization with mycoplasma species increases the severity of bronchopulmonary dysplasia.

There is controversy regarding the role of mycoplasmas (MP) colonizing the neonatal respiratory tract in the development of bronchopulmonary dysplasia (BPD). To determine the association of respiratory MP colonization and BPD. Retrospective analysis of neonates (26-32 weeks of gestation) intubated for respiratory insufficiency. Tracheal aspirate cultures were obtained for MP if the lung disease was not improving by 7-10 days or there were radiographic changes suggestive of inflammation. Of 63 infants who had tracheal aspirates sent, 17 had positive MP cultures. We found no significant difference in the gestational ages (27.6 +/- 0.4 vs 27.8 +/- 0.2 weeks) or birth weights (1097 +/- 86 vs 997 +/- 42 grams) in MP positive vs negative infants. No differences were noted in antenatal or postnatal steroid use, gender, race, sepsis, RDS, PDA, air leaks, NEC, GER, days on positive pressure ventilation or days on oxygen. There were significantly (p = 0.04) more infants with severe BPD (defined as oxygen requirement at 36 weeks corrected post menstrual age) among MP positive (n = 14; 82%) versus MP negative (n = 25; 54%) infants. Presence of MP in the tracheal aspirates is associated with an increased likelihood of developing severe BPD.

Bronchopulmonary Dysplasia↗
PubMed1997

Actin depolymerization is developmentally regulated in rat type II cells exposed to terbutaline.

The type II alveolar epithelial cell synthesizes and secretes pulmonary surfactant. Terbutaline enhances phospholipid release from adult and fetal type II cells. Our hypothesis is that the actin network of microfilaments regulates the secretory activity of the type II cell. To examine the developmental regulation of the changes in actin subfractions associated with secretory activity, cultures of type II cells derived from adult and 19-d fetal rat lung were incubated with or without 10 microM terbutaline for 1, 30, and 60 min. Dose-response effects of terbutaline were examined in adult type II cells. Effects of phorbol ester were also examined Globular (G-actin) and filamentous (F-actin) fractions were extracted from the cells and analyzed separately. Specified cellular equivalent volumes of each subfraction were analyzed by Western blotting, visualized by a color reaction, and quantified by densitometry. There was a decrease in the cytoskeletal F-actin pool along with an increase in the G-actin fraction within I min in adult type II cells exposed to terbutaline, indicating that depolymerization of F-actin occurs. Values returned to control levels by 60 min. In contrast, the decrease in F-actin, with a concomitant increase in G-actin, was maximal at 60 min in fetal cells exposed to terbutaline. There was a dose-dependent increase in actin depolymerization with maximal effects at 10 microM terbutaline. Phorbol ester also caused an increase in actin depolymerization. Depolymerization of the actin microfilament network may regulate transport and exocytosis of lamellar bodies in type II cells. We speculate that there is an early secretory mechanism that involves depolymerization of actin microfilaments and a late, actin-independent secretory mechanism present in adult type II cells. The timing of the response of the actin-dependent pathway is developmentally regulated. This may explain the developmental differences in the secretion of surfactant that we have previously shown.

Actins↗