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Biomedical subjects

A R Spitzer

Publications and source records attributed to A R Spitzer.

At least 19 recordsLinked to original sources
PubMed2006

A study of the role of multiple site blood cultures in the evaluation of neonatal sepsis.

BACKGROUND: The optimal number of blood cultures needed to document sepsis in an ill neonate has undergone little critical evaluation. Multiple site cultures may improve pathogen detection if intermittent bacteremia occurs, or if a low density of bacteria is present in the blood. We hypothesized, however, that bacterial clearance is slower and bacteremia more continuous in septic neonates, so that a single site blood culture should be sufficient to accurately document true septicemia. OBJECTIVE: To determine the need for multiple site blood cultures in the evaluation of neonates for sepsis. DESIGN/METHODS: Clinical data were prospectively collected for 216 neonates who had 269 pairs of blood cultures taken from two different peripheral sites for the evaluation of possible sepsis. A minimum of 1 ml of blood was obtained from the two peripheral sites within 15-30 min of each other. Based on prior retrospective data, we determined that 203 infants would need to have two site blood cultures to demonstrate a significant improvement in pathogen detection at an alpha of 0.05 and a beta of 0.20 (80%) power. RESULTS: A total of 186 culture pairs were taken for evaluation of early-onset sepsis in 186 neonates, while 83 pairs were drawn for evaluation of late-onset sepsis in 43 neonates. In all, 21 neonates from the late-onset group were evaluated more than once, and 12 neonates were evaluated for both early- and late-onset sepsis. In all, 20 (9.2%) of 216 neonates had 22 episodes of culture-proven sepsis at a median age of 18 days. All neonates with positive cultures had the same organism with a similar sensitivity pattern obtained from the two different peripheral sites. The other 196 study neonates had negative blood cultures from both sites. The single episode of early-onset sepsis was caused by Listeria monocytogenes, while all remaining episodes were late-onset with the following organisms: Staphylococcus epidermidis (7), methicillin-resistant Staphylococcus aureus (MRSA) (3), combined MRSA and Candida albicans (2), Candida albicans alone (2), late-onset Group B beta-hemolytic Streptococcus (GBS) (2), Klebsiella pneumoniae (2), Enterococcus fecalis (1), Escherichia coli (1), and Serratia marcescens (1). Since no infant grew organisms from only one of the two sites, the data indicate that the diagnosis of sepsis would have been made correctly in all infants with a single site culture. CONCLUSIONS: Two site blood cultures for the initial evaluation of neonatal sepsis do not have a better yield in pathogen detection. Sepsis in neonates can be detected with no loss of accuracy with a single site blood culture with blood volume of>or=1 ml.

Bacteremia↗
PubMed2004

Diminished lung compliance and elevated surfactant lipids and proteins in nutritionally obese young rats.

Dietary-induced obesity is associated with increases in lung weight, lung volume, alveolar surface area, and number of lamellar bodies in alveolar epithelial type II cells. This suggests that alterations in lung compliance and surfactant content may also occur. The effects of dietary-induced obesity on lung function and surfactant composition were studied in newborn male rats raised in (1) small litters until weaning and then fed a high fat diet (Obese Group, n = 23) and (2) normal-sized litters until weaning and subsequently fed a normal rat diet (Control Group, n = 29). At age 8 weeks, lung function was measured in anesthetized, spontaneously breathing rats, and surfactant composition was analyzed in lung tissue and lavage fluid. The 8-week-old obese rats had a higher body weight (31%) and fat pad weight/body weight ratio (224%) than the Control Group. When compared with control animals, obese rats had an increased respiratory rate, reduced tidal volume, and decreased lung compliance (dynamic and specific). Disaturated phosphatidylcholine (DSPC) in lung tissue and surfactant pellets (large aggregates) and SP-A and SP-B levels in large aggregates were higher in obese than control rats. Phospholipid, DSPC, and triglyceride contents were also elevated in lung tissue in obese rats, suggesting intracellular lipid accumulation, but low relative to alveolar surface area. Thus, alterations in lung function and surfactant lipids and proteins occur in dietary-induced obesity in young rats. We speculate that intrapulmonary lipid deposition and possible surfactant deficiency relative to alveolar surface area may contribute to the reduction in lung compliance in obese rats.

Animals↗
PubMed2001

Synexin and GTP increase surfactant secretion in permeabilized alveolar type II cells.

We have previously suggested that synexin (annexin VII), a Ca(2+)-dependent phospholipid binding protein, may have a role in surfactant secretion, since it promotes membrane fusion between isolated lamellar bodies (the surfactant-containing organelles) and plasma membranes. In this study, we investigated whether exogenous synexin can augment surfactant phosphatidylcholine (PC) secretion in synexin-deficient lung epithelial type II cells. Isolated rat type II cells were cultured for 20-22 h with [(3)H]choline to label cellular PC. The cells were then treated with beta-escin, which forms pores in the cell membrane and releases cytoplasmic proteins including synexin. These cells, however, retained lamellar bodies. The permeabilized type II cells were evaluated for PC secretion during a 30-min incubation. Compared with PC secretion under basal conditions, the presence of Ca(2+) (up to 10 microM) did not increase PC secretion. In the presence of 1 microM Ca(2+), synexin increased PC secretion in a concentration-dependent manner, which reached a maximum at approximately 5 microg/ml synexin. The secretagogue effect of synexin was abolished when synexin was inactivated by heat treatment (30 min at 65 degrees C) or by treatment with synexin antibodies. GTP or its nonhydrolyzable analog beta:gamma-imidoguanosine-5'-triphosphate also increased PC secretion in permeabilized type II cells. The PC secretion was further increased in an additive manner when a maximally effective concentration of synexin was added in the presence of 1 mM GTP, suggesting that GTP acts by a synexin-independent mechanism to increase membrane fusion. Thus our results support a direct role for synexin in surfactant secretion. Our study also suggests that membrane fusion during surfactant secretion may be mediated by two independent mechanisms.

Animals↗
PubMed2001

The timing of neonatal discharge: An example of unwarranted variation?

UNLABELLED: Discharge from an intensive care nursery should be dependent on the infant's clinical and social condition and independent of the day of the week. OBJECTIVE: To evaluate admission and discharge dates of 5272 neonates cared for in 5 major metropolitan regions in the United States and managed by a national disease management company for the distribution of the day of the week. STUDY DESIGN: All infants discharged to home between July 1, 1996 and September 30, 1998 are included. Data are represented as a percentage of total discharges or admissions for each weekday assignment. Using the normal approximation to the multinomial distribution, we tested for proportional differences on each weekday. RESULTS: The data demonstrate that the timing of nursery discharge has an uneven distribution across the days of the week, with weekend (Saturday and Sunday) discharge rates that are significantly lower than weekday discharge rates. This uneven distribution exists in both the term and preterm subgroups as well. There is also an uneven distribution of births among the days of the week, with a pattern that reveals fewer weekend births than weekday births in the entire population studied, as well as in both the term and preterm subgroups. Normalizing these weekend discharges to the previous weekday could generate potential saving of $1 569 405 in charges for the total population and 627 days of hospitalization. The average length of stay of infants discharged on Mondays is longer than for those infants discharged on Saturday or Sunday. CONCLUSIONS: We speculate that changes in discharge planning could decrease the variation in day of discharge, shorten length of hospitalization, and potentially reduce cost.

Benchmarking↗
PubMed2000

Coordinate packaging of newly synthesized phosphatidylcholine and phosphatidylglycerol in lamellar bodies in alveolar type II cells.

Methylamine, a weak base, inhibits packaging of newly synthesized phosphatidylcholine (PC) in lamellar bodies in 20-22 h cultured alveolar type II cells, suggesting a role for acidic pH of lamellar bodies. In this study, we tested if (i) the packaging of PC is similarly regulated in freshly isolated type II cells and (ii) methylamine also inhibits the packaging of other surfactant phospholipids, particularly, phosphatidylglycerol (PG). The latter would suggest coordinated packaging so as to maintain the phospholipid composition of lung surfactant. During the short-term metabolic labeling experiments in freshly isolated type II cells, methylamine treatment decreased the incorporation of radioactive precursors into PC, disaturated PC (DSPC), and PG of lamellar bodies but not of the microsomes, when compared with controls. The calculated packaging (the percentage of microsomal lipid packaged in lamellar bodies) of each phospholipid was similarly decreased (approximately 50%) in methylamine-treated cells, suggesting coordinated packaging of surfactant phospholipids in lamellar bodies. Equilibrium-labeling studies with freshly isolated type II cells (as is routinely done for studies on surfactant secretion) +/- methylamine showed that in methylamine-treated cells, the secretion of PC and PG was decreased (possibly due to decreased packaging), but the phospholipid composition of released surfactant (measured by radioactivity distribution) was unchanged; and the PC content (measured by mass or radioactivity) of lamellar bodies was lower, but the PC composition (as percentage of total phospholipids) was unchanged when compared with control cells. We speculate that the newly synthesized surfactant phospholipids, PC, DSPC, and PG, are coordinately transported into lamellar bodies by a mechanism requiring the acidic pH, presumably, of lamellar bodies.

Ammonium Chloride↗
PubMed2000

Group B streptococcal infection early onset disease controversies in prevention guidelines, and management strategies for the neonate.

Group B streptococcus (GBS) has been a major pathogen that is particularly devastating to the newborn for more than two decades. Initial guidelines were promoted by the AAP in 1992 to help deal with this organism, but these recommendations were poorly accepted and not widely used. In 1996-1997 the AAP, CDC, and ACOG created new guidelines for the management of the mother and infant at risk for GBS. Though usually in agreement, these three sets of recommendations still have some differences that may be confusing to the pediatrician. This paper looks at the acquisition, intrapartum treatment, and postnatal management of GBS, along with some of the controversies associated with the management of this disease.

Female↗
PubMed1998

Cardiac malposition, redistribution of fetal cardiac output, and left heart hypoplasia reduce survival in neonates with congenital diaphragmatic hernia requiring extracorporeal membrane oxygenation.

OBJECTIVE: To evaluate cardiac position, left ventricular (LV) mass, and distribution of fetal cardiac output in infants with congenital diaphragmatic hernia (CDH) who required extracorporeal membrane oxygenation (ECMO), and in control subjects. STUDY DESIGN: Echocardiograms were performed on 23 neonates with CDH shortly after birth, and repeated within 5 days of repair on ECMO in 21 infants,aand on 12 infants receiving ECMO for other diagnoses, and on 10 healthy, term neonates. Cardiac angle between the midline saggital plane and the interventriculak septum was measured, and deviation from normal (45 degrees) was determined. The ratio of cross-sectional areas (proportional to flows) across the pulmonary (PV) and aortic (AV) valves was determined (PV2/AV2) in 19 infants with CDH and in the healthy control subjects. RESULTS: Thirteen (57%) infants with CDH survived and 10 (43%) died, with no difference in cardiac deviation before surgical repair (35 +/- 13 degrees vs Cardiac deviation persisted after repair in nonsurvivors (27 +/- 14 degrees vs 800.01 and LV mass was significantly less (1.68 +/- 0.39 vs 3.05 +/- 1.20 gm/kg, p00.0005). Neonates requiring ECMO for other diagnoses and well term babies did not have cardiac angle deviations; both these groups had a greater LV mass than did the infants with CDH. The PV2/AV2 flow ratios were higher in infants with CDH (median, 1.73; range, 1.25 to 16.50) compared with those of the healthy infants (0.96, 0.79 to 1.69, p < 0.0002). CONCLUSIONS: Cardiac malposition persisted despite CDH repair in nonsurvivors with low LV mass, and fetal cardiac output was redistributed away from the left ventricle. Lung hypoplasia with reduced pulmonary flow returning to the left atrium and altered left atrial hemodynamics may result in LV hypoplasia

Abnormalities, Multiple↗
PubMed1998

Adverse neurodevelopmental outcome after extracorporeal membrane oxygenation among neonates with bronchopulmonary dysplasia.

OBJECTIVE: The relationship between bronchopulmonary dysplasia (BPD) and neurodevelopmental outcome after extracorporeal membrane oxygenation (ECMO) has not been extensively reported. We compared the outcomes in a large series of infants with and without BPD after ECMO. STUDY DESIGN: Hospital charts and follow-up records of 145 infants treated with ECMO (1985 through 1990) were reviewed. Complete long-term respiratory and follow-up outcome data were available in 64 infants. BPD occurred in 17 survivors; the remaining 47 did not have BPD. RESULTS: Babies with BPD were more likely to have had respiratory distress syndrome. Mean (+/- SD) age at ECMO initiation was later for the BPD group (127+/-66 vs 53+/-39 hours, p < 0.001), and the duration of ECMO treatment was longer (192+/-68 vs 119+/-53 hours, p < 0.001). Bayley Scales of Infant Development scores at <30 months were lower in infants with BPD (p < 0.001), as were three of four Mullen Scales of Early Learning scores (> or = 30 months, p < 0.001 or p = 0.01). At 57+/-16 months 11 (64%) patients with BPD had mild neurologic disabilities, and 3 (18%) had severe disabilities. At a similar age (53+/-16 months, p = NS) 16 (34%) patients without BPD had mild disabilities, whereas 2 (4%) had severe disabilities (p < 0.01). CONCLUSIONS: The occurrence of BPD after ECMO is associated with adverse neurodevelopmental outcome. Patients with BPD after ECMO merit close long-term follow-up.

Bronchopulmonary Dysplasia↗
PubMed1998

Earlier discharge of infants from neonatal intensive care units: a pilot program of specialized case management and home care. Delaware Valley Child Health Alliance.

A multidisciplinary approach using a neonatology independent physicians association, affiliated hospitals, a pediatric home care company, and a health maintenance organization was designed to promote earlier safe discharge of infants from intensive care. This pilot project involved 43 infants who received case management and early discharge home with home oxygen, monitoring, intravenous antibiotics, gavage feedings, phototherapy, or nutritional management for poor weight gain. A staff neonatologist remained the primary physician until the patient would have been discharged according to standard criteria. Two patients had unscheduled readmissions and all infants survived. This approach resulted in an estimated savings of 456 hospital days and $329,982; 89% of parents rated the care as good to excellent, and 83% were satisfied with the program and outcome. This study suggests that a prospectively designed program can be designed to promote safe earlier discharge of infants in intensive care.

Case Management↗
PubMed1998

Volutrauma, PaCO2 levels, and neurodevelopmental sequelae following assisted ventilation.

Today it is essential that we define care practices in neonatology that not only increase survival but also produce optimal pulmonary and neurodevelopmental outcomes for our patients. Assisted ventilatory care continues to be influential at all three levels. In this article, the authors discuss current understanding of the possible mechanisms for pulmonary and neurologic injury, or benefits associated with ventilation at both low and high PaCO2 levels, as well as evidence for neurodevelopmental sequelae with various ventilator strategies.

Barotrauma↗
PubMed1997

Activation of protein kinase C by 1,4-dihydro-2,6-dimethyl-5-nitro-4-[2-(trifluoromethyl)-phenyl]-3-py rid ine carboxylic acid methyl ester (Bay K 8644), a calcium channel agonist, in alveolar type II cells.

A role for calcium channels in the regulation of surfactant secretion is suggested by the observation that endothelin-1-stimulated surfactant secretion is inhibited by calcium channel blockers. 1,4-Dihydro-2,6-dimethyl-5-nitro-4-[2-(trifluoromethyl)-phenyl]-3-pyridi ne carboxylic acid methyl ester (Bay K 8644), a dihydropyridine derivative, stimulates voltage-dependent and non-voltage-dependent calcium channels in a number of cell types. This study demonstrates that Bay K 8644 increased phosphatidylcholine (PC) secretion in isolated lung epithelial type II cells in a time- and concentration-dependent manner with an EC50 of 100 +/- 8 nM (mean +/- SEM, N = 6). The secretagogue effect of Bay K 8644 was independently decreased in the absence of external calcium, or in the presence of nifedipine, a calcium channel antagonist, or inhibitors of protein kinase C (PKC). Bay K 8644 increased intracellular calcium from 130 +/- 8 to 230 +/- 14 nM (N = 6, P < 0.05), an effect that was blocked by nifedipine. Bay K 8644 also increased the membrane-associated PKC activity in a concentration-dependent manner. In the membranes from Bay K 8644-stimulated cells, the increase in calcium-dependent PKC was greater than that in the calcium-independent PKC, suggesting preferential translocation of calcium-dependent PKC to the membranes. We suggest that both elevated calcium and activation of PKC are required for calcium agonist Bay K 8644-induced surfactant secretion in type II cells.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1997

Calcium-dependence of synexin binding may determine aggregation and fusion of lamellar bodies.

Synexin (annexin VII) is a member of the annexin family of calcium and phospholipid binding proteins that promote calcium-dependent aggregation and fusion of lipid vesicles or secretory granules. We have previously suggested that synexin may be involved in membrane fusion processes during exocytosis of lung surfactant since it promotes fusion in vitro of lamellar bodies with plasma membranes. In this study, we characterized calcium-dependency of synexin binding to lamellar bodies and plasma membranes, since such binding is the initial, and, therefore, may be the rate-limiting step in membrane aggregation and fusion. The binding of biotinylated synexin to lamellar bodies and plasma membranes increased in a calcium-dependent manner reaching a maximum at approx. 200 microM Ca2+. Binding to lamellar bodies was completely inhibited by unlabelled synexin. Gel-overlay analysis showed that synexin bound to an approx. 76 kDa protein in the lamellar body and plasma membrane fractions. The calcium kinetics were noticeably similar for synexin binding to lamellar bodies and plasma membranes, aggregation of lamellar bodies, and fusion of lamellar bodies with lipid vesicles. At low calcium concentrations, aggregation of lamellar bodies could be increased with increasing synexin concentration, and arachidonic acid increased all three parameters (binding, aggregation, and fusion) in a similar manner. The effects of calcium and arachidonic acid on these three parameters suggest that synexin binding to lamellar bodies may be a rate-determining step for fusion during surfactant secretion. Furthermore, at near physiological calcium levels, the membrane fusion may be enhanced by elevated concentrations of synexin and polyunsaturated fatty acids.

Animals↗
PubMed1997

Pulmonary sequelae in infants treated with extracorporeal membrane oxygenation.

The decision to place an infant on extracorporeal membrane oxygenation (ECMO) is based on predictions of expected morbidity and mortality. One unknown factor is the relationship between pre-ECMO pulmonary dysfunction and on barotrauma and post-ECMO pulmonary sequelae. To determine whether placement of infants on extracorporeal membrane oxygenation (ECMO) early is associated with less subsequent pulmonary dysfunction than placing infants on EMCO later, we evaluated pulmonary function in 25 neonates prior to ECMO, when the infants had come off EMCO, and at the time of nursery discharge. Pulmonary resistance (R) and compliance (CL) were determined by a pneumotachograph and esophageal manometry, and functional residual capacity (FRC) was determined by a helium dilution method. Maximal expiratory flow (VmaxFRC) was determined by thoracic compression at the time of discharge. Infants were assigned to an early ECMO group (< 36 hours of age, n = 12), or a late ECMO group (> 36 hours of age, n = 13). When first evaluated, the early group had a higher oxygenation index than the late group (mean value, 63 versus 48), but initial pulmonary function measurements were not different between the two groups. In the early group mean CL increase from 0.20 to 0.36 ml/cmH2O/kg, FRC increased from 7 to 20 ml/kg, and mean R decreased from 107 to 61 cmH2O/L/sec between the initial study and immediately after ECMO. In the late group, only FRC increased from a mean of 8 to 20 ml/kg. CL and FRC increased from post-ECMO to discharge in both groups (mean CL from 0.36 to 0.76 ml/cmH2O/kg in the early group, and from 0.30 to 0.79 in the late group). Mean FRC increased from 20 to 26 ml/kg in the early group, and from 20 to 25 ml/kg in the late group. VmaxFRC was lower in the late than the early group at discharge (mean, 1.14 versus 1.58 L/sec; P < 0.05). While both groups of infants had minimal pulmonary dysfunction at discharge, the infants placed on ECMO early had evidence of slightly less airway dysfunction despite a higher initial oxygenation index than the infants placed on ECMO late.

Airway Resistance↗
PubMed1997

Ionic regulation of proton chemical (pH) and electrical gradients in lung lamellar bodies.

This study investigated the pH (chemical) and electrical gradients in lamellar bodies, the acidic surfactant-secreting organelles of lung epithelial type II cells, by following the uptake of a weak fluorescent base, quinacrine, and a membrane potential-sensitive dye, bis-(3-phenyl-5-oxoisoxazol-4-yl)pentamethine oxonol (oxonol V). In isolated lung lamellar bodies, the ATP-dependent uptake of both agents could be inhibited by bafilomycin A1, a reportedly specific inhibitor of vacuolar-type H(+)-ATPase (V-ATPase) and could be dissipated by a protonophore, carbonyl cyanide p-(trifluoromethoxy)phenylhydrazone, suggesting that the V-ATPase generates an electropositive interior. A closely linked uptake of Cl- neutralizes the positive electrical potential and increases the proton pump activity. The uptake of quinacrine, but not oxonol V, was decreased by Na+. This effect of Na+ could be prevented by dimethylamiloride, suggesting the presence of electroneutral Na+/H+ exchanger in lamellar body membranes. The initial rates of quinacrine and oxonol V uptake were increased by bumetanide, but only in the presence of Na+, K+, and Cl-, suggesting that the lamellar bodies also contain an outwardly directed electroneutral Na(+)-K(+)-2Cl- cotransporter. Thus three ion transporters, H(+)-translocating V-ATPase, Na+/H+ exchanger, and Na(+)-K(+)-2Cl- cotransporter, appear to determine the chemical and electrical gradients across the lamellar body membrane.

Animals↗