Biomedical subjects

David W Holt

Publications and source records attributed to David W Holt.

39 records · Page 3Linked to original sources

PubMed2002

Monitoring mycophenolic acid.

The immunosuppressive agent mycophenolate mofetil is a prodrug for the active compound mycophenolic acid. Following organ transplantation, it is used mostly in combination with other immunosuppressive drugs, but it has also been used as primary therapy. Although in the pivotal clinical studies the drug was given in fixed doses, there has been substantial interest in the measurement of mycophenolic acid in plasma as a guide to optimizing therapy. Data have emerged which indicate that the metabolism of the compound is more complex than was originally thought and that variability in exposure to the drug, assessed by area under the time-concentration curve, is an important determinant of efficacy. This article highlights basic pharmacokinetic and pharmacodynamic data for mycophenolic acid, which underlie the rationale for its measurement. These data are then set in the context of providing a routine service for the measurement of the drug with either of the analytical techniques currently available--immunoassay or high-performance liquid chromatography. There are a number of issues regarding the clinical interpretation of mycophenolic acid measurements which are yet to be resolved. Centres contemplating the introduction of such a service will need to keep abreast of a rapidly evolving literature.

Clinical Trials as Topic↗

PubMed2002

Cardiac troponin T and creatine kinase MB content in skeletal muscle of the uremic rat.

BACKGROUND: The assertion that creatine kinase MB (CK-MB) and the developmental isoforms of cardiac troponin T (cTnT) are expressed by skeletal muscle in some clinical settings is an extrapolation from nonuremic rodent studies. We studied the content of CK-MB and cTnT in skeletal muscle of the renal-insufficient rat. METHODS: Skeletal muscles (gastrocnemius) were collected from both five-sixths nephrectomized rats (n = 11) and sham-operated controls (n = 11). cTnT content was analyzed by Elecsys (Roche), immunoblotting, and immunohistochemistry with antibodies M7 and M11-7 (Roche). CK isoenzymes were analyzed electrophoretically. RESULTS: Trace concentrations of cTnT were detected in some of the skeletal muscle samples [controls (3 of 11) and uremic rats (1 of 11)] at concentrations <0.01% of that detected in heart. By contrast, positive staining appeared in both groups with M11-7 by immunoblotting and immunohistochemistry. No immunoreactivity was detected in skeletal muscle using M7 in the immunoblot format, although immunoreactivity was detected by immunohistochemistry in all samples. The median percentages of CK-MB were 6.0% and 4.1% for the skeletal muscle from control and uremic rats, respectively. CONCLUSION: The detection of cTnT and CK-MB in skeletal muscle does not differ for uremic rats compared with sham-operated controls. cTnT isoforms detected by qualitative methods are not detected with the cTnT immunoassay. Observations with rodents should not necessarily be extrapolated to humans.

Animals↗

PubMedDate not supplied

Cardiopulmonary bypass in the cat.

OBJECTIVE: To assess the physiologic response to, and acute survival of, cats undergoing cardiopulmonary bypass (CPB) and to evaluate the efficacy of a commercial human pediatric oxygenator system on cats weighing less than 6 kg. STUDY DESIGN: Experimental study. ANIMALS: Six intact male cats METHODS: Cats were placed on cardiopulmonary bypass by cannulating the cranial and caudal vena cavae and the carotid artery. The pediatric CPB circuit was primed with 150 mL of a balanced crystalloid solution. Venous drainage was enhanced by a controlled, vacuum-assist system. A cross-clamp was placed on the ascending aorta and cardiac arrest was induced by antegrade infusion of a cold cardioplegia solution. After 45 minutes of arrest time, the cross-clamp was removed and the cats were weaned off bypass and decannulated. No blood products were administered. Heart rate, mean arterial pressure (MAP), central venous pressure, arterial blood gas, hematocrit (HCT), total plasma protein concentration (TP), serum electrolyte concentrations, and activated clotting time (ACT) were measured at baseline period (BL), during CPB, 60 minutes after CPB (CPB 60) and 90 minutes after CPB (CPB 90). A complete blood count (CBC), blood chemistry profile, and urinalysis were performed at BL, during CPB, and CPB 90. Cats were euthanatized after CPB 90. RESULTS: Cardiopulmonary bypass resulted in a significant (P <.05) decrease in mean HCT (18.0%) and TP (2.3 gm/dL) at CPB 90 when compared to BL (30.5% and 6.0 gm/dL, respectively). The MAP at CPB 90 (54 mm Hg) was decreased from BL (94 mm Hg). The ACT increased from a mean of 124 seconds to > 400 seconds with heparinization and was reversed to 300 seconds with protamine. Mean platelet counts decreased from BL (369,000 /microL) to CPB 90 (94,500 /microL). Mean white blood cell counts decreased from 13,200 /microL at BL to 2,200 /microL at CPB 90. Upon reperfusion, 1 cat fibrillated but was successfully defibrillated. CONCLUSIONS: Cardiopulmonary bypass was performed successfully in 6 cats weighing less than 6 kg. Acute survival to 90 minutes after CPB was achieved in all 6 cats CLINICAL RELEVANCE: The ability to perform CPB in the cat may allow intracardiac repair of various heart defects in this species.

Animals↗