Hepatic effects of repeated oral administration of diclofenac to hepatic cytochrome P450 reductase null (HRN™) and wild-type mice

Hepatic NADPH-cytochrome P450 oxidoreductase null (HRN?) mice exhibit normal hepatic and extrahepatic biotransformation enzyme activities when compared to wild-type (WT) mice, but express no functional hepatic cytochrome P450 activities. When incubated in vitro with [¹⁴C]-diclofenac, liver microsomes from WT mice exhibited extensive biotransformation to oxidative and glucuronide metabolites and covalent binding to proteins was also observed. In contrast, whereas glucuronide conjugates and a quinone-imine metabolite were formed when [¹⁴C]-diclofenac was incubated with HRN? mouse liver, only small quantities of P450-derived oxidative metabolites were produced in these samples and covalent binding to proteins was not observed. Livers from vehicle-treated HRN? mice exhibited enhanced lipid accumulation, bile duct proliferation, hepatocellular degeneration and necrosis and inflammatory cell infiltration, which were not present in livers from WT mice. Elevated liver-derived alanine aminotransferase, glutamate dehydrogenase and alkaline phosphatase activities were also observed in plasma from HRN? mice. When treated orally with diclofenac for 7 days, at 30 mg/kg/day, the severities of the abnormal liver histopathology and plasma liver enzyme findings in HRN? mice were reduced markedly. Oral diclofenac administration did not alter the liver histopathology or elevate plasma enzyme activities of WT mice. These findings indicate that HRN? mice are valuable for exploration of the role played by hepatic P450s in drug biotransformation, but poorly suited to investigations of drug-induced liver toxicity. Nevertheless, studies in HRN? mice could provide novel insights into the role played by inflammation in liver injury and may aid the evaluation of new strategies for its treatment.     

Using Family Members as Medical Interpreters: An Explanation of Healthcare Practitioners’ Normative Practices in Pediatric and Neonatal Departments in Australia

ABSTRACT

Both international tourism and migration of people with low English proficiency (LEP) to Australia are increasing. Thus, health-care practitioners (HPs) increasingly use interpreters to communicate with patients with LEP. Although qualified interpreters are the most suggested and policy-endorsed mechanism for communicating with patients with LEP, family members (FMIs) are also used as interpreters. This study investigated (a) when do health professionals consider it appropriate to use FMIs and (b) what characteristics of family members health professionals believe make them suitable to act as FMIs. As part of a larger project examining the decision-making processes of HPs regarding interpreter use, 69 HPs from neonatal and pediatric departments in one hospital in Queensland Australia were interviewed. Results indicated HPs thought the appropriateness of using FMIs depended on the type of information, such that it was either completely acceptable (e.g., explaining some basic or non-medical information) or completely unacceptable (e.g., confidential information or consent). However, in an emergency, when no other options were available, FMIs were used. The characteristics of suitable FMIs included age, level of English proficiency and medical understanding, and the relationship between patient and FMI. Results were to some extent consistent with Queensland government policies but there were notable differences, including using children and regarding FMIs as first preference. Improving HP’s knowledge of policies may increase their confidence in their practice and appropriate use of FMIs, thereby improving their care delivery to patients and families with LEP.     

Nasal masks for domiciliary positive pressure ventilation: patient usage and complications.

BACKGROUND--Nasal mask discomfort is a major factor in compliance with treatment by nasal intermittent positive pressure ventilation (NIPPV) and nasal continuous positive airway pressure (CPAP). METHODS--A study of skin complications resulting from mask usage, with particular reference to predisposing factors, was carried out in 66 patients by means of a postal questionnaire. An effective means of managing ulceration at the nasal bridge while continuing therapy is described. RESULTS--Some disruption of treatment due solely to mask discomfort was experienced by 35 patients (53%), consisting of broken skin or open sores in 11 cases (17%). CONCLUSIONS-Although complications resulting from nasal mask usage are common, early identification of patients at risk of developing such complications and appropriate intervention will result in improved patient compliance.     

Antigenuria after immunization with Haemophilus influenzae oligosaccharide CRM197 conjugate (HbOC) vaccine

We tested the urine of 30 infants 6 weeks to 7 months of age after they received standard 10-micrograms (0.5-ml) doses of HbOC (HibTITER) Haemophilus influenzae b (Hib) conjugate vaccine for the presence of Hib antigenuria using a commercially available latex particle agglutination assay (Directigen). Urines were collected within 1 hour, from 1 to 3 hours, at 24 hours and at 3, 6 and 9 days after vaccine administration and reactions were quantitated from 0 to 3+. In contrast to previous studies in older children which showed little or no antigenuria following HbOC vaccination, our study shows that in infants intense Hib antigenuria is evident within 2 to 3 hours and persists 3 days after vaccine administration and that less intense antigenuria may be detected in some infants for several days. With efficacious vaccines now being used in 2- to 6-month-old infants, invasive Hib disease may soon be limited to infants of this age just before their seroconversion. It should be recognized that antigenuria occurs for several days after vaccination with Hib conjugate vaccines and that it could be erroneously interpreted as evidence of invasive Hib infection.