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.     

The development of a research human milk bank.

Although there are well-established clinical human milk banks in the United States, there are no milk banks specifically intended to foster research on human milk. The authors' goal was to establish a milk bank with a core data set to support exploratory and hypothesis-driven studies on human milk. Donations to the Cincinnati Children's Research Human Milk Bank are accepted within the context of ongoing, hypothesis-driven research or on an ad hoc basis. Donors must give informed consent, and scientists wishing to use the samples must have Institutional review board approval for their use. Development of more research human milk banks can potentially provide resources for multidisciplinary collaboration and advance the study of human milk and lactation.     

The effect of diaper type and overclothing on fecal contamination in day-care centers

Fecal coliform contamination of environmental surfaces and hands in the day-care center is common. This study evaluated the effect of two diaper types on fecal contamination. Ten rooms in four day-care centers containing 141 children were studied in a prospective, randomized, crossover study. A total of 2946 samples were cultured during the 9-week study. Fecal coliforms were isolated from 307 inanimate objects (15%), 73 toy balls (46%), and 131 hands (17%). The number of contaminated inanimate objects was significantly less in rooms where paper diapers were worn when compared with that in rooms where double cloth diapers with plastic overpants were worn and in rooms where clothes were worn over diapers. Inanimate object cultures had more contamination in rooms in which diarrhea had occurred. Containment of feces by overclothes and diaper type may be important in decreasing transmission of enteric pathogens in day-care environments.     

N-terminal brain natriuretic peptide in scleroderma-associated pulmonary arterial hypertension: reply

We read with interest the comments of Mathai and Hassoun, andagree that caution is required in using an NTproBNP level of     

Attitudes Toward Transplantation in U.K. Muslim Indo-Asians in West London

The worldwide shortage of organs for transplantation makes it important to understand why some oppose donation. Attitudes vary with religion and ethnicity. Accordingly, we undertook a qualitative study of the attitudes of 141 U.K. Muslim Indo-Asians to organ donation. Participants were observed, focus group discussions held and in-depth individual interviews conducted. We identified a high level of alienation from the health care system in general. With respect to organ donation in particular, its importance was generally discounted, often in deference to authority figures within the community who appeared negatively disposed. The culture-specific issues arguing against donation included a sense of the sacredness of the body, a fatalistic approach to illness, a belief that organs took on an independent role as 'witnesses' to an individual's life on Judgement Day and an anxiety that the donor would have no control of the probity of the recipient of an organ. We believe these data suggest a need to improve in a culturally sensitive fashion the provision of health information provided to this community.     

Intraperitoneal therapy for ovarian cancer: analysis of fluid distribution by computerized tomography.

Nineteen patients with ovarian cancer and minimal residual or persistent disease who were treated with cisplatin or carboplatin-based intraperitoneal (IP) regimens had distribution studies of IP contrast and computerized tomography prior to and during treatment. The distribution pattern was assessed retrospectively and scored for the presence of contrast in each of eight regions: the under surface of right and left diaphragms, the right and left paracolic gutters, the lesser omental sac, the intramesenteric region and the true and false pelvis. Assigning a point to each region with adequate distribution, we classified 10 patients to an excellent pattern (greater than or equal to 7 of 8 regions), 6 to a good pattern (5 to less than 7 regions), and 3 to an inadequate distribution pattern (less than 5 regions). Serial studies were performed in 8 patients after more than 4 cycles of IP therapy. In these patients, all of whom were tolerating treatment without progression, the distribution remained virtually unchanged for those with excellent distribution. One of three with good distribution manifested inadequate distribution on repeat study, and one of two with inadequate distribution improved to show a good pattern. In this small study there was no correlation of distribution patterns with plasma CA-125 at onset of IP treatment and prior surgical procedures or placement of the catheter tip. However, three patients with unsatisfactory patterns had procedures consisting of catheter placement only rather than formal reassessment laparotomies for ovarian cancer. Since satisfactory IP distribution may be required for obtaining a therapeutic advantage from IP therapy, methods for its assessment must be developed.(ABSTRACT TRUNCATED AT 250 WORDS)