F Van Lente

THE IMPACT OF ROUTINE MYCOPHENOLATE MOFETIL DRUG MONITORING ON THE TREATMENT OF CARDIAC ALLOGRAFT REJECTION

INTRODUCTION Mycophenolate mofetil (MMF) is a unique immunosupressive agent that has been shown to be efficacious in the treatment of cardiac allograft rejection. The utility of therapeutic drug monitoring on rejection prophylaxis and treatment is inconclusive. This study was undertaken to evaluate the incidence of rejection in relation to MMF trough level following heart transplantation. METHODS Between May 1998 and February 1999, we retrospectively analyzed the clinical outcome of 215 heart transplant patients who had routine monitoring of MMF trough level at the time of scheduled endomyocardial biopsy. Patients were divided into three groups according to the time interval post transplant, and were evaluated in relation to the MMF trough level. Group I, 104 patients within 6 months of transplant; Group II, 90 patients, 6-12 months post transplant; and Group III, 71 patients beyond one year of transplant. Fifty patients had samples in more than one group. Rejection was defined as Grade > or = 3A based on ISHLT criteria. Mean follow-up period was 179+/-52 days. RESULTS A significantly decreased incidence of rejection was noted in the samples with MMF trough level > or = mg/l compared to those with less than 2 mg/l inpatients evaluated within the first year of transplant (Group I: 8.8% vs. 14.9%, Group II: 4.2% vs. 11.3%, both P=0.05). In the presence of therapeutic cyclosporine (CSA) or tacrolimus (FK) blood levels, the incidence of rejection decreased significantly when MMF trough level was > or = 2 mg/l compared to samples with MMF trough level <2 mg/l (3.6% vs. 14.4%, P=0.005). No significant difference was noted in the presence of subtherapeutic CSA or FK levels (15.4% vs. 13.9%, P=NS). CONCLUSIONS Monitoring of MMF trough levels may play a role in the management of cardiac transplant recipients during the first year post transplant.

N-Terminal Prohormone Brain Natriuretic Peptide as a Predictor of Cardiovascular Disease and Mortality in Blacks With Hypertensive Kidney Disease: The African American Study of Kidney Disease and Hypertension (AASK)

Background— Higher levels of N-terminal prohormone brain-type natriuretic peptide (NT-proBNP) predict cardiovascular disease (CVD) in several disease states, but few data are available in patients with chronic kidney disease or in blacks. Methods and Results— The African American Study of Kidney Disease and Hypertension trial enrolled hypertensive blacks with a glomerular filtration rate of 20 to 65 mL · min−1 · 1.73 m−2 and no other identified cause of kidney disease. NT-proBNP was measured with a sandwich chemiluminescence immunoassay (coefficient of variation 2.9%) in 994 African American Study of Kidney Disease and Hypertension participants. NT-proBNP was categorized as undetectable, low, moderate, or high. Proteinuria was defined as 24-hour urinary protein–creatinine ratio >0.22. A total of 134 first CVD events (CVD death or hospitalization for coronary artery disease, heart failure, or stroke) occurred over a median of 4.3 years. Participants with high NT-proBNP were much more likely to have a CVD event than participants with undetectable NT-proBNP after adjustment (relative hazard 4.0 [95% confidence interval [CI] 2.1 to 7.6]). A doubling of NT-proBNP was associated with a relative hazard of 1.3 (95% CI 1.0 to 1.6) for coronary artery disease, 1.7 (95% CI 1.4 to 2.2) for heart failure, 1.1 (95% CI 0.9 to 1.4) for stroke, and 1.8 (95% CI 1.4 to 2.4) for CVD death. The association of NT-proBNP with CVD events was significantly stronger (Pinteraction=0.05) in participants with than in those without proteinuria. Higher NT-proBNP was not associated with renal disease progression. Conclusions— These results suggest that elevated NT-proBNP levels are associated with higher CVD risk among blacks with hypertensive kidney disease. This association may be stronger in individuals with significant proteinuria.

Serum prostate specific antigen, sex hormone binding globulin and free androgen index as markers of pubertal development in boys

Prostate specific antigen (PSA) expression in the prostate gland is regulated by androgens. Serum levels of PSA are undetectable by routine assays in normal boys. Measurable values could serve as a marker for pubertal development. In order to explore this question, we measured serum PSA levels in normal boys throughout puberty and examined the interrelationships with various hormonal and physical developmental changes.

Characterization of calcium phosphate powders by ESCA and EDXA

Calcium phosphate (CaP) materials can be well characterized by traditional methods such as wet chemistry and X-ray diffraction (XRD). These methods, however, offer limitations when non-destructive evaluation of CaP coatings on curved surfaces is required. Since the source powders for these coatings are generally commercially available CaP powders, careful characterization of the source powders may allow inferences to be made regarding the effects of plasma spraying on coating composition. Nine commercially available CaP powders were characterized by scanning electron microscopy, wet chemistry and XRD. These techniques showed that major differences exist between individual powders claiming to be hydroxyapatite. Analysis of these nine powders by electron spectroscopy for chemical analysis (ESCA) and energy dispersive X-ray analysis (EDXA) suggest that these techniques can provide the chemical composition of CaP in a non-destructive manner and thus may be of use in determining the composition of CaP in configurations (such as coatings on metal surfaces) not readily amenable to traditional methods. A calibration curve is required, however, to relate this surface chemical composition result to the materials bulk composition as determined by wet chemistry analysis. Errors of less than 10% can be obtained using ESCA and EDXA. These studies suggest that non-destructive chemical composition evaluation by EDXA and ESCA may also be applicable to CaP coatings.

Cholecystokinin (CCK) stimulated peak lipase concentrations correlate with pancreatic duct morphology

Cholecystokinin (CCK) stimulated peak lipase concentrations correlate with pancreatic duct morphology