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Biomedical subjects

J E Biskupiak

Publications and source records attributed to J E Biskupiak.

7 recordsLinked to original sources

Estimation of the cost savings resulting from the use of ursodiol for the prevention of gallstones in obese patients undergoing rapid weight reduction.

BACKGROUND: Morbidly obese patients enrolled in a rapid weight reduction program are at a high risk of developing gallstones. Two multicenter, placebo-controlled, randomized, double-blind trials have demonstrated that the prophylactic use of ursodiol in males and females 18 to 70 years of age is effective for the prevention of gallstone formation in this patient population. This study examines the cost consequences associated with the prophylactic use of ursodiol. METHODS: A medical decision analysis model for the prophylactic administration of ursodiol in morbidly obese patients undergoing rapid weight reduction by either gastric bypass surgery or very-low-calorie-diet, was developed through the use of data from two clinical trials and review of the related literature. The expert opinion of clinicians from the fields of internal medicine, gastroenterology and surgery were solicited. Financial data for the charges associated with cholecystectomies, physician fees and ursodiol were obtained from current financial databases. RESULTS: The model demonstrates that the prophylactic administration of ursodiol, in morbidly obese patients undergoing rapid weight reduction, results in cost savings. Sensitivity analysis was performed to illustrate that the cost savings achieved by the prophylactic use of ursodiol were valid over a realistic range of charges and assumptions. CONCLUSION: The decision model may allow health care decision makers to apply their own data to the model to determine the cost savings obtainable through the prophylactic use of ursodiol in patients undergoing rapid weight reduction.

Adult

Radiosynthesis of 6-[C-11]-D-glucose.

Availability of 6-[C-11]-D-glucose will permit positron emission tomography (PET) investigations of glucose utilization derived from the pentose shunt which supports biosynthesis in tissues. The first radiosynthesis of 6-[C-11]-D-glucose is described. As much as 1 mCi of 6-[C-11]-D-glucose, sufficient for animal studies, is obtained from [C-11]CO2 after 100 min with a 16% radiochemical yield (EOB). The radiosynthesis has many attractive features. The method uses [C-11]CH3I and combines a Wittig reaction and a stereoselective OsO4 catalyzed alkene hydroxylation. The OsO4 hydroxylation of the [C-11]-labeled alkene (9) is accomplished in less than 10 min with high stereoselectivity (94:6) in favor of the 6-[C-11]-D-gluco-isomer. HPLC purification (C-18) of the protected labeled sugar removes the undesired 6-[C-11]-L-ido-sugar at an early stage and avoids the use of an expensive low-capacity ion-exchange HPLC column. OsO4, a highly toxic reagent, is removed in the process by adsorption and inactivation on polymer-bound triphenylphosphine.

Carbon Radioisotopes

Characterization of iodovinylmisonidazole as a marker for myocardial hypoxia.

Misonidazole and related compounds are metabolically trapped in viable cells as a function of reduced cellular pO2. [18F]fluoromisonidazole has been used to detect hypoxia in the heart and in tumors noninvasively with positron emission tomography. The purpose of this study was to characterize the uptake of the iodinated misonidazole congener iodovinylmisonidazole (IVM) in ischemic myocardium. In six open chest dogs (Group 1), the left anterior descending (LAD) coronary artery was partially occluded and in four dogs (Group 2), demand ischemia was produced by the combination of atrial pacing and catecholamine infusion in the presence of a LAD stenosis. [131I]IVM (5-15 microCi/kg, i.v.) was given following the onset of ischemia. Tracer deposition was measured by postmortem tissue sampling 4 hr postinjection and compared to microsphere myocardial blood flow (MBF) measurements made at baseline and at 2 hr postinjection. In Group 1, regional IVM deposition in heart samples within the ischemic area was inversely related to MBF with maximum tissue:blood ratios of 3.2. For a given level of reduced blood flow, IVM uptake was higher in the subendocardium indicating a greater vulnerability of the subendocardium to reductions in oxygen delivery. In Group 2, enhanced IVM deposition was detected as a result of demand ischemia, even in some regions where absolute flow was normal or increased from baseline, indicating that flow per se is not the principal determinant of tracer uptake. We conclude that IVM is a promising marker for myocardial hypoxia with potential clinical application using gamma camera imaging.

Animals

Synthesis of an (iodovinyl)misonidazole derivative for hypoxia imaging.

Nitroimidazoles undergo a bioreduction in viable hypoxic tissue, resulting in trapping within these tissues, as demonstrated by misonidazole. A radioiodinated analogue of misonidazole (IVM, (E)-5-(2-Nitroimidazolyl)-4-hydroxy-1-iodopent-1-ene, 3) has been synthesized by halodestannylation, for evaluation as an imaging agent for hypoxia. A key step in the synthetic sequence involves the use of the Lewis acid BF3.Et2O to promote the nucleophilic ring opening of glycidyl tosylate with (E)-1-lithio-2-(tributylstannyl)ethylene. Direct comparison of IVM versus F-MISO (2) another misonidazole type hypoxic cell marker, in several in vitro cell culture studies, indicates that IVM behaves in analogous fashion to F-MISO and has promise as a hypoxia imaging agent for SPECT.

Animals