Aryl hydrocarbon receptor-independent toxicity of weathered crude oil during fish development

Polycyclic aromatic hydrocarbons (PAHs), derived largely from fossil fuels and their combustion, are pervasive contaminants in rivers, lakes, and nearshore marine habitats. Studies after the Exxon Valdez oil spill demonstrated that fish embryos exposed to low levels of PAHs in weathered crude oil develop a syndrome of edema and craniofacial and body axis defects. Although mechanisms leading to these defects are poorly understood, it is widely held that PAH toxicity is linked to aryl hydrocarbon receptor (AhR) binding and cytochrome P450 1A (CYP1A) induction. Using zebrafish embryos, we show that the weathered crude oil syndrome is distinct from the well-characterized AhR-dependent effects of dioxin toxicity. Blockade of AhR pathway components with antisense morpholino oligonucleotides demonstrated that the key developmental defects induced by weathered crude oil exposure are mediated by low-molecular-weight tricyclic PAHs through AhR-independent disruption of cardiovascular function and morphogenesis. These findings have multiple implications for the assessment of PAH impacts on coastal habitats.     

Physicians' willingness to report impaired colleagues

We surveyed physicians to determine what factors were associated with their reporting of impaired colleagues to Physician Health Programs (PHPs). We conducted a cross-sectional mail survey of 1000 randomly selected practicing physicians in the United States. A survey instrument asked the physicians whether they would report 10 hypothetical impaired colleagues to a PHP. The results show that a majority of the physicians would report physicians to PHPs, but were more likely to report hypothetical physicians involved in substance abuse than those who were emotionally or cognitively impaired (p<0.001). Respondents who felt they had a societal obligation as opposed to an obligation to protect the rights of the individual (p=0.006) were more likely to report hypothetical physicians. Those respondents who stated they knew of guidelines on reporting impaired physicians had more frequently reported impaired colleagues (p<0.001). We conclude that physicians should be educated on the availability and functioning of PHPs and the ethical and legal obligations of assisting impaired colleagues.     

The role of enteral nutrition in the reversal of parenteral nutrition-associated liver dysfunction in infants

Background

Liver dysfunction in children dependent on parenteral nutrition (PN) is well established, and the extent of hyperbilirubinemia has been shown to correlate with morbidity and mortality. The aim of this study was to assess whether increasing provisions of enteral nutrition can improve PN-associated hyperbilirubinemia over time.

Methods

A retrospective review was conducted on infants in our institution's Short Bowel Syndrome Clinic from 1999 to 2004. Inclusion criteria included PN duration more than 1 month, serum direct bilirubin more than 3 mg/dL while on PN, and tolerance of full enteral nutrition with eventual discontinuation of PN. Paired t tests were used for statistical analyses.

Results

Twelve infants were identified with a PN duration of 5 ± 1 months. Five patients underwent liver biopsy while on PN, and histological evidence of cholestasis was found on all specimens. Peak total and direct bilirubin levels were 10.5 ± 1.9 and 7.0 ± 1.6 mg/dL, respectively, and occurred at time of PN discontinuation. Only 2 patients had improvement in serum bilirubin levels before initiation of full enteral nutrition. After initiation of full enteral nutrition and discontinuation of PN, all patients achieved permanent normalization of bilirubin levels by 4 months (P < .05) after a 1-month plateau phase. Alkaline phosphatase levels approached reference range within this time but were not significant.

Conclusion

These data demonstrate for the first time that although PN-dependent infants can achieve normalization of marked hyperbilirubinemia with enteral nutrition, the improvement in liver function usually begins only after full enteral nutrition is tolerated and PN is withdrawn. These findings support the aggressive weaning of PN to enteral nutrition in infants with short bowel syndrome.     

Accuracy of computed tomographic intravenous cholangiography (CT-IVC) with iotroxate in the detection of choledocholithiasis

To determine the accuracy of computed tomographic intravenous cholangiography (CT-IVC) for detection of choledocholithiasis. Sixty-five patients undergoing endoscopic retrograde cholangiography (ERC) underwent CT-IVC prior to ERC, using a single detector helical CT following intravenous infusion of 100 ml iotroxate. Patients with bilirubin levels >3 times normal were excluded. ERC was indeterminate in three patients (4.7%) and CT-IVC in four (6.3%). Twenty-three patients had ductal calculi at ERC, and CT-IVC was positive in 22, with two false positives and one false negative: sensitivity 95.6%, specificity 94.3%. Stones were multiple in nine and solitary in 14. Of the 14 solitary stones, ten were 5 mm and eight were 4 mm. The bilirubin level in positive cases was within normal in 20. Maximum intensity projection (MIP) reformats showed stones in only 27% of cases and surface rendered (SR) reformats in none. CT-IVC is highly accurate for detection of ductal calculi, including single small calculi, with a normal or near normal serum bilirubin. Axial images should be used for interpretation rather than MIP or SR reformats.