Acute on chronic liver failure in a patient with sickle cell anaemia (HbSS).

A man in his late 40s with sickle cell anaemia (HbSS) presented to the emergency department with 2 weeks of diffuse oedema, increased abdominal girth and dyspnoea. His anasarca was thought to be indicative of an acute decompensation of his known liver cirrhosis with transfusion-induced haemosiderosis. While his anasarca improved with diuresis, his direct hyperbilirubinaemia suddenly worsened without any signs of haemolysis, biliary disease or obstruction. He also developed an acute worsening in serum creatinine (1.17-7.0 mg/dL in 7 days) despite subsequent treatment for presumed hepatorenal syndrome (HRS). Given his clinical decline, the patient's goals of care were transitioned to comfort measures only. His clinical presentation and rapid liver and renal deterioration were most typical of sickle cell intrahepatic cholestasis (SCIC). SCIC can lead to rapid deterioration in renal function and can be mistaken for HRS. When SCIC is suspected, consideration of exchange transfusions should be made early.

Minocycline improves recognition memory and attenuates microglial activation in Gunn rat: a possible hyperbilirubinemia-induced animal model of schizophrenia.

BACKGROUND: Accumulating evidence indicates that neuroinflammation plays a significant role in the pathophysiology of schizophrenia. We previously reported evidence of schizophrenia-like behaviors and microglial activation in Gunn rats. We concluded that the Gunn rat, which exhibits a high concentration of unconjugated bilirubin, may be useful as an animal model of schizophrenia. On the other hand, there have been numerous reports that minocycline is effective in treating schizophrenia. METHODS: In the present study, we investigated the effects of minocycline on performance of behavioral tests (prepulse inhibition (PPI) and novel object recognition test (NORT)) after animals received either 40mg/kg/d of minocycline or vehicle by intraperitoneal (i.p.) injection for 14 consecutive days. Furthermore, we examined the effects of minocycline on microglial activation in the hippocampal dentate gyrus of Gunn rats and Wistar rats. RESULTS: We found that administration of minocycline for 14days significantly increased the exploratory preference in retention sessions and tended to improve the PPI deficits in Gunn rats. Immunohistochemistry analysis revealed that microglial cells in the minocycline-treated Gunn rat group showed less expression of CD11b compared to vehicle-treated Gunn and Wistar groups. CONCLUSIONS: Our findings suggest that minocycline improves recognition memory and attenuates microglial activation in the hippocampal dentate gyrus of Gunn rats. Therefore, minocycline may be a potential therapeutic drug for schizophrenia.

Infants with bilirubin levels of 30 mg/dL or more in a large managed care organization.

OBJECTIVE: To describe the incidence, etiology, treatment, and outcome of newborns with total serum bilirubin (TSB) levels >or=30 mg/dL (513 micro mol/L). DESIGN: Population-based case series. SETTING: Eleven Northern California Kaiser Permanente Medical Care Program hospitals and 1 affiliated hospital. PATIENTS: Eleven infants with TSB levels of >or=30 mg/dL in the first 30 days after birth, identified using computer databases from a cohort of 111,009 infants born 1995-1998. OUTCOME MEASURES: Clinical data from the birth hospitalization, rehospitalization, and outpatient visits in all infants; psychometric testing at age 5 (N = 3), neurologic examinations by child neurologists at age 5 (N = 3), or primary care providers (N = 7; mean age: 2.2 years); Parent Evaluation of Developmental Status (N = 8; mean age: 4.2 years). RESULTS: Maximum TSB levels of the 11 infants ranged from 30.7 to 45.5 mg/dL (525 micro mol/L to 778 micro mol/L; mean: 34.9 mg/dL [597 micro mol/L]). Four were born at 35 to 36 weeks gestation, and 7 were exclusively breastfed. Two had apparent isoimmunization; the etiology for the other 9 remained obscure, although only 4 were tested for glucose-6-phosphate dehydrogenase deficiency and 1 was bacteremic. None had acute neurologic symptoms. All received phototherapy and 5 received exchange transfusions. One infant died of sudden infant death syndrome; there was no kernicterus at autopsy. Two were lost to follow-up but were neurologically normal when last seen for checkups at 18 and 43 months. One child was receiving speech therapy at age 3. There were no significant parental concerns or abnormalities in the other children. CONCLUSIONS: In this setting, TSB levels >or=30 mg/dL were rare and generally unaccompanied by acute symptoms. Although we did not observe serious neurodevelopmental sequelae in this small sample, additional studies are required to quantify the known, significant risk of kernicterus in infants with very high TSB levels.

"Safe" hyperbilirubinemia is associated with altered neonatal behavior.

Treatment of neonatal jaundice is currently recommended for higher bilirubinemia levels than before. Using the Brazelton Neonatal Behavior Assessment Scale, we found that a series of 28 healthy, untreated, term neonates with moderate bilirubinemia scored significantly less than an equal number of appropriately matched controls with low bilirubinemia for visual and auditory items, both inanimate and animate. Also, a greater lability of state, a lower self-quieting ability and more frequent tremors were found in the jaundiced group. We conclude that hyperbilirubinemia per se, even in the concentration range where phototherapy is not currently recommended, can give rise to alterations in neonatal behavior.

Moderate hyperbilirubinemia induces a transient alteration of neonatal behavior.

OBJECTIVE: To investigate the behavioral changes induced by moderate hyperbilirubinemia in the otherwise healthy, untreated newborn infant. METHODS: Fifty term neonates (23 boys) with untreated moderate hyperbilirubinemia (median: 14.3 mg/dL; range: 13.2-20 mg/dL) and 50 matched control subjects with lower bilirubin concentrations (median: 9.1 mg/dL; range: 5.3-12 mg/dL) were administered the Brazelton Neonatal Behavioral Scale at 87 hours of life (range: 72-110 hours). A subgroup analysis was also performed at 104 hours of life (range: 96-134 hours) and at 3 weeks of age. RESULTS: At the first examination, all behavioral clusters were significantly altered in the group with moderate hyperbilirubinemia. The visual and auditory capabilities of the hyperbilirubinemic infant were especially compromised. Although social-interactive cluster scores significantly correlated both with serum bilirubinemia and birth weight, the former accounted for 8.7% of the variance and the latter accounted for only 4.7%. The moderate hyperbilirubinemia neonates' scores also showed a negative correlation with the autonomic system and more frequent presence of tremors. After 24 hours, a decrease in serum bilirubin within the moderate hyperbilirubinemic group was associated with improved scores. At 3 weeks of age, the behavioral assessment of the 2 groups did not show significant differences. CONCLUSIONS: Untreated moderate hyperbilirubinemia is associated with a transient and apparently reversible alteration of neonatal behavior, particularly in the social-interactive area.

Longitudinal outcome for low birth weight infants: effects of intraventricular hemorrhage and bronchopulmonary dysplasia.

This study addresses the mental and motor development of 78 low birth weight infants (LBW) classified into five groups according to early medical complications: (1) respiratory distress syndrome (RDS); (2) intraventricular hemorrhage (IVH Grades I-II); (3) IVH (Grade III); (4) IVH (Grade IV) with hydrocephalus; and (5) bronchopulmonary dysplasia (BPD) with or without IVH. Each child received an assessment of mental and motor development at 6, 12, 24 and 36 months of age. Results of mental scores revealed clear effects of group and age, but no interaction of group and age. The RDS and IVH (Grades I-III) groups generally had higher scores on indices of mental development than did IVH (Grade IV) and BPD infants with or without IVH. Although most groups had higher mental scores at the older ages, rates of growth were essentially parallel across the five groups. There was some support for differential rates of motor development, with the IVH (Grade IV) group showing acceleration between 24 and 36 months of age while the BPD group continued to show motor delay at 36 months. These results call into question the common practice of correcting psychology test scores of LBW infants for gestational age.

Open-field behavior of rats previously subjected to short-term hyperbilirubinemia with or without blood-brain barrier manipulations.

The aim of this study was to investigate (i) whether bilirubin encephalopathy with lasting sequelae could be created in a rat model, and (ii) putative differences in brain toxicity between bound and unbound bilirubin. Hyperbilirubinemia was produced by infusing bilirubin 20 mg/kg/h during 3 h into 6-week-old male Sprague-Dawley rats. In addition to the hyperbilirubinemia, different groups were created by exposing the rats to hyperosmolality, hypercarbia, and sulfisoxazole. Three weeks after the infusion the rats were studied in an open-field apparatus during 10 daily sessions of 15 min duration. A data collection program was used to study the following measures of activity: crossings in cage, peeks, rearing, latency to enter field, crossings in middle and in outer field, and time outside cage. The data were subjected to multivariate analyses of variance (MANOVA). Generally, the level of activity was higher in the bilirubin-treated rats as compared to the control animals. The difference in activity between bilirubin-treated and control rats changed systematically both between and within sessions. The data show that both unbound and albumin-bound bilirubin are neurotoxic, but they indicate a more pronounced effect of unbound bilirubin. The sequelae of bilirubin brain toxicity appear to include changes in stimulus processing. This is compatible with findings from neuropsychological tests of children who have had significant neonatal hyperbilirubinemia.