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Richard H Moseley

Publications and source records attributed to Richard H Moseley.

12 recordsLinked to original sources
PubMed2006

Effect of thiazolidinediones on bile acid transport in rat liver.

The thiazolidinedione derivatives, troglitazone, rosiglitazone, and pioglitazone, are novel insulin-sensitizing drugs that are useful in the treatment of type 2 diabetes. However, hepatotoxicity associated with troglitazone led to its withdrawal from the market in March 2000. In view of case reports of hepatotoxicity from rosiglitazone and pioglitazone, it is unclear whether thiazolidinediones as a class are associated with hepatotoxicity. Although the mechanism of troglitazone-associated hepatotoxicity has not been elucidated, troglitazone and its major metabolite, troglitazone sulfate, competitively inhibit adenosine triphosphate (ATP)-dependent taurocholate transport in isolated rat canalicular liver plasma membrane vesicles mediated by the canalicular bile salt export pump (Bsep). These results suggest that cholestasis may be a factor in troglitazone-associated hepatotoxicity. To determine whether this effect is 1) limited to canalicular bile acid transport and 2) is specific to troglitazone, the effect of troglitazone, rosiglitazone, and ciglitazone on bile acid transport was examined in rat basolateral (blLPM) and canalicular (cLPM) liver plasma membrane vesicles. In cLPM vesicles, troglitazone, rosiglitazone, and ciglitazone (100 microM) all significantly inhibited ATP-dependent taurocholate transport. In blLPM vesicles, these three thiazolidinediones also significantly inhibited Na(+)-dependent taurocholate transport. Inhibition of bile acid transport was concentration dependent and competitive in both cLPM and blLPM vesicles. In conclusion, these findings are consistent with a class effect by thiazolidinediones on hepatic bile acid transport. If hepatotoxicity is associated with this effect, then hepatotoxicity is not limited to troglitazone. Alternatively, if hepatotoxicity is limited to troglitazone, other mechanisms are responsible for its reported hepatotoxicity.

Animals↗
PubMed2006

What effect does physician "profiling" have on inpatient physician satisfaction and hospital length of stay?

BACKGROUND: 2002 marked the first time that the rate of hospital spending in the United States out-paced the overall health care spending rate of growth since 1991. As hospital spending continues to grow and as reimbursement for hospital expenses has moved towards the prospective payment system, there is still increasing pressure to reduce costs. Hospitals have a major incentive to decrease resource utilization, including hospital length of stay. We evaluated whether physician profiling affects physician satisfaction and hospital length of stay, and assessed physicians' views concerning hospital cost containment and the quality of care they provide. METHODS: To determine if physician profiling affects hospital length of stay and/or physician satisfaction, we used quasi-experimental with before-versus-after and intervention-versus-control comparisons of length of stay data collected at an intervention and six control hospitals. Intervention hospital physicians were informed their length of stay would be compared to their peers and were given a questionnaire assessing their experience. RESULTS: Nearly half of attending pre-profiled physicians felt negative about the possibility of being profiled, while less than one-third of profiled physicians reported feeling negative about having been profiled. Nearly all physicians greatly enjoyed their ward month. Length of stay at the profiled site decreased by an additional 1/3 of a day in the profiling year, compared to the non-profiled sites (p < 0.001). CONCLUSION: A relatively non-instrusive profiling intervention modestly reduced length of stay without adversely affecting physician satisfaction.

Adult↗
PubMed2005

Hepatic injury in a patient taking rosiglitazone.

We describe a 52-year-old man with type 2 diabetes mellitus who developed cholestatic hepatitis in association with rosiglitazone use. Liver biopsy findings included dilated canaliculi, inspissated bile, intrahepatocellular bile pigment deposits, and enlarged xanthomatous Kupffer cells. The form of liver injury reported in this case differs markedly from those reported previously for rosiglitazone.

Biopsy↗
PubMed2004

Sepsis and cholestasis.

Sepsis-associated cholestasis should always be considered as part of the differential diagnosis of jaundice in the hospitalized or critically ill patient. The development of a disproportionate elevation of serum bilirubin in comparison with serum alkaline phosphatase and serum aminotransferases should be considered an early warning sign of an underlying infection, even in the absence of fever,leukocytosis, or other signs or symptoms. Prompt recognition and appropriate medical and surgical intervention may reduce morbidity and mortality.

Cholestasis↗
PubMed2003

A cohort study of the incidence of serious acute liver injury in diabetic patients treated with hypoglycemic agents.

BACKGROUND: The incidence of acute liver failure or serious liver injury in diabetic patients is needed to evaluate the safety of hypoglycemic drug therapy. METHODS: We conducted a retrospective cohort study of 5 health maintenance organizations. Study patients were 171,264 health plan members 19 years or older when they received oral hypoglycemic drugs or insulin between April 1, 1997, and June 30, 1999. We searched for hospital discharge diagnoses and procedures potentially indicative of acute liver injury and reviewed the full-text medical records. Acute liver failure was defined as acute liver disease and (1) hepatic encephalopathy, (2) prothrombin time prolongation greater than 3 seconds or international normalized ratio greater than 1.5, and (3) a total bilirubin level greater than 3.0 mg/dL (>51 micro mol/L). Acute liver injury was diagnosed in individuals who did not meet 1 or more of the criteria for acute liver failure but had alanine transaminase or aspartate transaminase levels greater than 500 U/L. RESULTS: We identified 35 cases of acute liver failure or injury not clearly attributable to a known cause other than use of hypoglycemic agents. The age- and sex-standardized incidence per 1000 person-years was 0.15 for insulin users, 0.08 for sulfonylurea users, 0.12 for metformin users, and 0.10 for troglitazone users. The incidence was higher (on the order of 0.3 per 1000) during the first 6 months of exposure to all hypoglycemic agents. CONCLUSIONS: Acute liver failure or injury not clearly attributable to other known causes occurred on the order of 1 per 10,000 person-years among diabetic patients treated with oral hypoglycemic drugs or insulin.

Acute Disease↗