PubMed Health⌕ Search

Biomedical subjects

W J Cashore

Publications and source records attributed to W J Cashore.

At least 19 recordsLinked to original sources
PubMed2000

Bilirubin and jaundice in the micropremie.

Although it has been customary to treat neonatal jaundice at lower serum bilirubin levels in low-birth weight infants than in term infants, the threshold bilirubin levels and long-term benefits for early treatment of preterm infants have not been validated. This article summarizes and evaluates existing evidence and strategies for early treatment of bilirubin in micropremies and recommends a conservative but flexible approach to early monitoring and phototherapy for jaundice in extremely low-birth weight infants.

Bilirubin↗
PubMed1996

Attitudes about sibling visitation in the neonatal intensive care unit.

OBJECTIVE: To survey the attitudes and recommendations of staff members before and after the implementation of sibling visitation in a neonatal intensive care unit. DESIGN: Staff survey conducted before (1992) and after (1993) the implementation of sibling visitation. SETTING: A perinatal tertiary care center. PARTICIPANTS: Staff members including physicians, nurses, respiratory therapists, social workers, and unit clerks (n = 139 in 1992; n = 120 in 1993). MEASUREMENTS AND MAIN RESULTS: A 7-point Likert scale survey (1 = strongly disagree: 7 = strongly agree) was designed for the study. In both 1992 and 1993, the staff most strongly agreed that visitation requires special supervision, should have designated times, increases sibling knowledge, enhances sibling attachment to the baby, and increases family satisfaction. Wilcoxon rank sum tests comparing the staff across the 2 years indicated substantial attitudinal changes in favor of sibling visitation, including less perceived interference with nursing care and nursery routines (P < .01) and less concern about the infants' risk of respiratory infection and exposure to chickenpox (P < .05). There was greater attitudinal agreement between disciplines in 1993 than in 1992, suggesting better staff consensus about sibling visitation following its implementation. The recommended minimum age for visitation was 4.67 years and 4.05 years in 1992 and 1993, respectively. Brief visits of 10 to 15 minutes' duration were consistently recommended. Staff rated the sibling visitation program as successful (median = 6) on a scale ranging from 1 (very poor) to 7 (very successful). CONCLUSIONS: Staff members have concerns about sibling visitation that include increased risk of infection, organization, and supervision. A sibling visitation program that addresses these concerns can be successfully implemented and supported by staff, thereby fostering family-centered care in the neonatal intensive care unit.

Attitude↗
PubMed1995

Postnatal maturation of the blood-brain barrier for unbound bilirubin in newborn piglets.

The postnatal maturation of the blood-brain barrier (BBB) for unbound bilirubin was studied in 2-day- and 2-week-old piglets. Hyperbilirubinemia was induced by bolus infusion of bilirubin at 25 mg/kg followed by continuous infusion of 20 mg/kg/h for 3 h. During the study period, arterial blood pH and blood gas tensions, serum osmolarity, and mean arterial blood pressures were within the physiologic range. Brain bilirubin content and the brain/blood distribution ratio for bilirubin were higher in the 2-day-old than in the 2-week-old piglets. In both age groups, regional brain bilirubin concentration and brain/blood ratios were higher in subcortical regions (cerebellum and brainstem) than in the cerebral cortex. We conclude that in newborn piglets the blood-brain barrier for unbound bilirubin matures with increasing postnatal age and that irrespective of maturity the relative permeability of the BBB for bilirubin appears higher in subcortical than in cortical regions.

Aging↗
PubMed1995

Rates of bilirubin clearance from rat brain regions.

The mechanism for the preferential distribution of bilirubin to basal ganglia ('kernicterus') is unknown. We hypothesized that differences in bilirubin clearance rates between brain regions might explain this phenomenon. Bilirubin [30 mg/kg over 5 min, with 370-740 kBq (10-20 mu Ci) tritiated bilirubin] was infused into a peripheral vein in unanesthetized, young Sprague-Dawley rats (n=36, weight 149 +/- 15 g, mean +/- SD). After blood sampling, groups of rats were killed at 15, 30, 45, 60, 75, 180, and 360 min with an intravenous injection of pentobarbital. Brain vasculature was flushed in situ and brains dissected into seven regions, which were weighed, dissolved and scintillation counted. Blood was analyzed for bilirubin, albumin, and blood gases. Brain bilirubin concentrations were calculated after determining the specific activity of bilirubin in serum at the time of sacrifice. Bilirubin half-lives in serum and brain regions were (in minutes, mean +/- SD): serum 24.6 +/- 17.2, whole brain 18.5 +/- 21.5, cortex 17.6 +/- 19.3, hippocampus 19.0 +/- 21.5, striatum 17.1 +/- 18.5, midbrain 16.3 +/- 18.6, hypothalamus 17.4 +/- 21.0, cerebellum 21.6 +/- 33.8, medulla 20.0 +/- 24.1. There were no significant differences in bilirubin half-lives between regions. The half-life of bilirubin in brain reported here is appreciably shorter than the 1.7 h previously found in rats with opened blood-brain barriers, but appears compatible with data on auditory brainstem response reversibility following exchange transfusion in jaundiced infants. We conclude that bilirubin disappeares rapidly from brains with intact blood-brain carriers.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗
PubMed1994

Dose-effect relationship of bilirubin on striatal synaptosomes in rats.

The uptake of tyrosine as precursor of dopamine in striatal nerve endings was studied in rat striatal synaptosomes to evaluate the role of different bilirubin concentrations on this mechanism of synaptic neurotransmission. Freshly prepared striatal synaptosomes obtained from adult male Sprague-Dawley rats (200-300 g) were homogenized in about 25 vol of 0.32 M sucrose and 5 nM Hepes at pH 7.4 and centrifugated at 12,000-16,000 rpm for 20 min. 14C tyrosine was evaporated under N2 and resuspended in tyrosine 100 microliters/ml. Different concentrations of crystalline bilirubin ranging from 70 to 140 microM at 10-min intervals were prepared. Eighty microliters of synaptosomes were added to 5 microliters of the different bilirubin concentrations and 20 microliters of 14C tyrosine. The results of this study show a statistically significant correlation between bilirubin levels and tyrosine uptake in rat synaptosomes (p < 0.05) supporting the hypothesis that the effect of bilirubin on neuronal excitability is dose-dependent.

Animals↗
PubMed1993

Endotoxemia and brain bilirubin in the rat.

To investigate the possible role of sepsis with endotoxemia in kernicterus, we studied the effect of endotoxin on accumulation of bilirubin and albumin in rat brain. Male Sprague-Dawley rats were given Escherichia coli endotoxin i.v. After 150 min 10 microCi 125I-bovine serum albumin was given intravenously, followed by a 1-hour bilirubin infusion. Brain bilirubin was significantly higher in the endotoxin group than in the controls (1.34 +/- 0.47 vs. 0.83 +/- 0.31 microgram/g, p < 0.05). However, the difference between the ratios of brain bilirubin to total serum bilirubin at the time of sacrifice were not significant. Total and unbound bilirubin values were significantly higher in the endotoxin-treated group at 165 min. Endotoxemia increased the net accumulation of bilirubin in rat brain, but this increase was probably secondary to an increase in total and unbound bilirubin, rather than an increase in the transfer per se of bilirubin across the blood-brain barrier.

Albumins↗
PubMed1992

Changes in piglet auditory brainstem response amplitudes without increases in serum or cerebrospinal fluid neuron-specific enolase.

We studied the relationship between changes in auditory brainstem responses (ABR) and serum and cerebrospinal fluid levels of neuron-specific enolase (NSE) in hyperbilirubinemic 2- to 8-d-old piglets. Infusion of a stabilized solution of bilirubin resulted in serum bilirubin levels of 571.1 +/- 48.8 mumol/L (mean +/- SEM) after 6 h. ABR were obtained at baseline and then hourly until the piglets were killed. We measured peak amplitudes and latencies for waves I-V, as well as latency for the post-V trough. Changes in amplitudes and latencies were analyzed as slopes because of heterogeneous variances. Over time, a significant reduction was observed in peak II-V amplitudes of bilirubin-infused piglets, but not in those of corresponding controls. No change was observed in latencies. NSE was analyzed by RIA. Serum NSE remained stable throughout the experiment (means 5.1-6.6 micrograms/L) and did not differ between the groups. Cerebrospinal fluid NSE values also remained stable, and no differences that could be ascribed to hyperbilirubinemia were detected. We conclude that hyperbilirubinemia induced significant changes in piglet ABR amplitudes without concomitant evidence of severe neuronal compromise, as might have been indicated by significant increases in serum and/or cerebrospinal fluid NSE levels. This provides further support to the clinical impression that early ABR changes during hyperbilirubinemia may be reversible.

Animals↗
PubMed1990

The neurotoxicity of bilirubin.

Recent clinical and research findings on kernicterus and bilirubin toxicity are reviewed. Bilirubin binds to cell membranes and appears to interfere with the metabolism, depolarization, and transmitter functions of neurons. The neurobehavioral and clinical findings associated with bilirubin encephalopathy and low bilirubin kernicterus are presented and evaluated. Cardiorespiratory stabilization, avoidance of displacing drugs, and preventive use of phototherapy appear to have decreased the incidence of low bilirubin kernicterus in high-risk newborns.

Animals↗
PubMed1989

Influence of drugs on albumin and bilirubin interaction.

Twenty-eight drugs, including cephem antibiotics and anti-inflammatory agents currently used or considered potentially useful in neonatal intensive care nurseries in Japan, were examined to determine their influence on albumin and bilirubin interaction by means of a glucose oxidase - peroxidase method, using an automated analyzer (Arrows) for unbound bilirubin (U.B.). The apparent binding constant for drugs to the high-affinity site on albumin (KD) was determined. Of cephem antibiotics, latamoxef sodium (LMOX) and cefazolin sodium (CEZ) were found to displace bilirubin from albumin (KD = 5.9 x 10(3) M-1 and 4.5 x 10(3) M-1, respectively) as strongly as Na salicylate (KD = 6.8 x 10(3) M-1). Mephenamate and indomethacin, which are used for medical closure of patent ductus arteriosus in premature infants, were also found to be stronger bilirubin displacers (KD = 1.3 x 10(5) M-1 and 1.2 x 10(5) M-1, respectively) than sulfisoxazole (KD = 1.6 x 10(4) M-1). Maximal displacement factors (MDF's) were also estimated in reference to protein binding (%) and effective serum concentration (M) of each drug in human adults. Of these drugs, mephenamate showed a higher risk of bilirubin displacement (MDF = 3.79) than sulfisoxazole (MDF = 2.58) and LMOX had a higher risk of displacement (MDF = 1.97) than Na salicylate (MDF = 1.85). On the other hand, indomethacin and CEZ showed minimal effects on displacement at therapeutic levels (MDF = 1.03 and 1.00, respectively). At therapeutic serum levels, mephenamate and LMOX may possess the potential for displacing bilirubin from albumin and increasing the risk of bilirubin encephalopathy, in a manner similar to sulfisoxazole.

Albumins↗
PubMed1989

Permeability of the blood brain barrier for 125I-albumin-bound bilirubin in newborn piglets.

Permeability of the blood brain barrier (BBB) for bilirubin and 125I-albumin was studied in 2-d- and 2-wk-old piglets. 125I-albumin was given by bolus at the beginning of each study. Hyperbilirubinemia was produced by an initial bolus infusion of bilirubin and sustained at a plasma bilirubin:albumin molar ratio of approximately 1.0 by continuous infusion of bilirubin for 3 h. During the study period, arterial pH and blood gas tensions, serum osmolarity, and mean arterial blood pressure were within the physiologic range for age in both groups. Serum albumin and serum total and unbound bilirubin concentrations were higher in the 2-wk-old piglets. Brain bilirubin concentrations and permeability (P.S product) of the BBB for bilirubin were higher in the 2-d-old than in the 2-wk-old piglets, but the values of P.S for albumin were not different between the two groups. In 2-d-old piglets, regional brain bilirubin concentrations and permeability of the BBB were higher in subcortical regions (cerebellum and brainstem) than in the cerebral cortex. Regional brain albumin concentrations and BBB permeability to albumin in 2-d-old piglets were higher only in the cerebellum. In all regions, the bilirubin:albumin molar ratio was higher in the brain tissues than in the blood. In 2-wk-old piglets, the brain concentrations and P.S products for bilirubin were lower and the regional differences were less marked than for 2-d-old animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗
PubMed1988

The effects of brain bilirubin deposition on auditory brain stem evoked responses in rats.

Auditory brain stem evoked responses (ABR) in newborn infants are altered by elevated serum bilirubin levels and may be used as an indicator of bilirubin toxicity. The hypothesis of our study was that hyperbilirubinemia may affect ABR's because of bilirubin deposition in the brain stem. We examined this hypothesis by studying 21 male adult rats divided into three groups: group A, control (n = 8); group B, low bilirubin (n = 6); and group C, high bilirubin (n = 7). Each experimental group was studied over 150 min. The control group received a buffer solution. The low bilirubin group received a low dose bilirubin bolus of 50 mg/kg followed by continuous infusion of 20 mg/kg/h. The high bilirubin group received a bolus of 100 mg/kg bilirubin followed by continuous infusion of 40 mg/kg/h. All groups received sulfisoxazole (50 mg/kg X 3) during the second hour of the study. Auditory evoked potentials were recorded at 0 and 150 min. At the end of the study, the brains were analyzed for bilirubin content. Bilirubin deposition in the 3 groups was 0.6 +/- 0.28 micrograms/g, 0.93 +/- 0.07 micrograms/g and 3.2 +/- 2.2 micrograms/g for the control, low bilirubin and high bilirubin groups, respectively. Bilirubin deposition in the brain was associated with a significant amplitude reduction of Wave I and III, but had no effect on absolute latencies and interpeak latencies. Very high brain bilirubin concentrations were associated with absence of Waves I and IV. Wave I was also significantly reduced in the low bilirubin group where there was slightly increased bilirubin deposition in the brain. We conclude that ABR changes in the form of wave amplitude reduction were associated with brain stem and cerebellum bilirubin deposition. We speculate that previously reported observations of abnormal ABR changes in hyperbilirubinemic newborn infants are associated with bilirubin deposition.

Animals↗
PubMed1987

The in vivo effect of bilirubin and sulfisoxazole on cerebral oxygen, glucose, and lactate metabolism in newborn piglets.

Bilirubin inhibits in vitro oxidative phosphorylation and glycolysis. This study investigated the in vivo effect of bilirubin on cerebral oxygen, glucose, and lactate uptake in newborn piglets. Seventeen 2- to 4-day-old piglets were divided into three groups and examined as follows: group 1 = control (C); group 2 = control with sulfisoxazole; and group 3 = experimental, given bilirubin with sulfisoxazole. In the experimental group, bilirubin was infused for 4 h. The cerebral bilirubin content in the bilirubin-infused group was 11.0 +/- 1.4 nmol/g of cerebral cortex (mean +/- SEM), consistent with levels found in infants with kernicterus. However, this level of brain bilirubin had no major, acute effects on cerebral uptake of oxygen, glucose, or lactate despite producing lethargy and ataxia which were consistent with bilirubin intoxication. This suggests that mitochondrial changes may not be involved in vivo in acute bilirubin encephalopathy.

Animals↗
PubMed1985

Effects of bilirubin on transepithelial transport of sodium, water, and urea.

Urinary concentrating defects and renal salt wasting have been described in the hyperbilirubinemic Gunn strain strain of rat. Homozygous animals demonstrate significant reductions in renal medullary urea and sodium ion concentrations. These observations are consistent with possible bilirubin associated disorders in the transepithelial transport of water and solute. To test this hypothesis, measurements of active sodium transport and passive water and urea fluxes were made in hemibladders isolated from the Dominican toad, Bufo marinus. Tissues were exposed to amphibian bicarbonate Ringer's solution containing 0.1 mM bilirubin with 0.05% bovine serum albumin (BSA) or BSA alone. Vasopressin-stimulated sodium transport, as reflected by short circuit current (SCC), was inhibited by 18 +/- 6% in the presence of bilirubin (N = 10; P less than 0.02). Cyclic AMP (p-Cl-phenylthio cAMP 10(-5) M) stimulated SCC was inhibited to a similar degree in the presence of bilirubin. The inhibition was noted only when bilirubin was in the serosal bath, and it could be abolished with BSA 0.5%. Bilirubin had no effect on the increase in SCC induced by higher concentrations of cyclic AMP (10(-4) M), aldosterone, or amphotericin B. Furthermore, bilirubin had no effect on the hydro-osmotic response to vasopressin and vasopressin-induced changes in urea permeability. These findings show that short-term exposure to bilirubin exerts a tissue-specific effect on the vasopressin-stimulated active transport of sodium but has no effect on the vasopressin-induced fluxes of water and urea.

Aldosterone↗
PubMed1985

Brain bilirubin deposition and brain blood flow during acute urea-induced hyperosmolality in newborn piglets.

Acute hyperosmolality-induced blood brain barrier breakdown has been demonstrated to increase the permeability of sucrose, which is similar in molecular weight to bilirubin, independently of changes in regional brain blood flow. We studied three groups of piglets given continuous bilirubin infusions to maintain serum bilirubin concentrations at approximately 8 mg/dl. Normal serum osmolality was maintained throughout the study in control animals. Two experimental groups were made hyperosmolar (330 and 375 mosmol/liter) with bolus urea infusions during the last hour of the study. Regional brain bilirubin concentrations were elevated in the 375 mosmol/liter hyperosmolal experimental group, but not in the 330 mosmol/liter group. Regional brain albumin concentrations also were increased over the control group in the 375 mosmol/liter animals. There were no differences in regional brain blood flows to account for the increases in brain bilirubin concentrations. Our results show that brain bilirubin deposition occurs following breakdown of the blood brain barrier by acute, severe hyperosmolality (375 mosmol/liter) and that the deposited bilirubin is derived from both bound and unbound fractions. The bilirubin deposition occurs independently of changes in regional brain blood flow; however, regional differences in the blood brain barrier permeability to albumin also occur.

Animals↗