Tacrolimus Pharmacokinetics and Dose Monitoring After Lung Transplantation for Cystic Fibrosis and Other Conditions

In cystic fibrosis (CF), absorption of tacrolimus through the gastrointestinal tract may be impaired due to fat malabsorption. The aim of this pilot study was to compare tacrolimus pharmacokinetics and inter- and intrasubject variability of exposure in stable lung transplant recipients with and without CF, and to determine the best single-time predictors of exposure. The study included 11 lung transplant recipients with CF and 11 without CF who received tacrolimus twice daily. Blood samples were obtained predose and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8 and 12 h postdose on 3 separate days within 1 week. Tacrolimus pharmacokinetics and inter- and intrasubject variability of exposure were similar in the two groups, though exposure-per-milligram-dose was approximately 50% lower in CF patients. Tacrolimus trough concentration did not accurately predict the area under the concentration curve (AUC(0-12)), but the concentration measured 3 h postdose (C(3)) was tightly correlated with the AUC(0-12) in both CF (r(2)= 0.86) and non-CF (r(2)= 0.92) patients. In summary, patients with CF have a higher tacrolimus oral clearance, but nonsignificant differences in short-term inter- and intrasubject variability of exposure compared to patients without CF. C(3) is tightly correlated with AUC(0-12) in lung transplant recipients with and without CF.     

Characterization of normal and infarcted rat myocardium using a combination of small-animal PET and clinical MRI.

The combination of small-animal PET and MRI data provides quantitative in vivo insights into cardiac pathophysiology, integrating information on biology and morphology. We sought to determine the feasibility of PET and MRI for the quantification of ischemic injury in the rat model. METHODS: Fourteen healthy male Wistar rats were studied with 18F-FDG PET and cine MRI. Myocardial viability was determined in a transmural myocardial infarction model in 12 additional rats, using 18F-FDG PET and delayed-enhancement MRI with gadolinium-diethylenetriaminepentaacetic acid. All PET was acquired with a dedicated small-animal PET system. MRI was performed on a 1.5-T clinical tomograph with a dedicated small-animal electrocardiographic triggering device and a small surface coil. RESULTS: In normal rats, 18F-FDG uptake was homogeneous throughout the left ventricle. The lowest mean uptake of the 18F-FDG was found in the apical regions (79% +/- 6.0% of maximum) and the highest uptake was in the anterior wall (93% +/- 4.3 % of maximum). Myocardial infarct size as determined by histology correlated well with defects of glucose metabolism obtained with 18F-FDG PET (r = 0.89) and also with delayed-enhancement MRI (r = 0.91). Left ventricular ejection fraction in normal rats measured by cine MRI was 57% +/- 5.4% and decreased to 38% +/- 12.9% (P < 0.001) in the myocardial infarction model. CONCLUSION: Integrating information from small-animal PET and clinical MRI instrumentation allows for the quantitative assessment of cardiac function and infarct size in the rat model. The MRI measurements of scar can be complemented by metabolic imaging, addressing the extent and severity of ischemic injury and providing endpoints for therapeutic interventions.     

Aortocoronary collateral

We performed noninvasive coronary angiography using 64-slicecomputed tomography (CT) in a 65-year-old man with onset ofatypical angina pectoris and detected a chronic     

Non-HIV-Related Progressive Multifocal Leukoencephalopathy (PML): A Tertiary Cancer Center Experience

In the course of 1 year at a tertiary cancer center, 3 patients (2 men; 1 woman; age 51-75 years) were seen in neurological consultation (1.5% of all consultations). Clinical course in all patients was of a progressive neurologic disorder not consistent with either a primary or secondary malignancy. Magnetic resonance (MR) imaging was most informative with respect to diagnosis and subsequent management. Brain biopsy was performed in all patients to assist in both diagnosis and prognostication. All patients were determined to have progressive multifocal leukoencephalopathy (PML) by brain biopsy.     

Changes in snoring characteristics after 30 days of nasal continuous positive airway pressure in patients with non-apnoeic snoring: a controlled trial.

BACKGROUND--A study was performed to evaluate the effect of discontinuation of nasal continuous positive airway pressure (NCPAP) treatment on snoring characteristics. METHODS--Eighteen non-apnoeic snoring subjects were randomly allocated to either a no treatment control group or an NCPAP treatment group. The control group was studied twice (baseline and day 30 of follow up). In the NCPAP group the level of NCPAP that abolished snoring was determined and part abolished snoring was determined and patients were placed on NCPAP every night for one month. A sleep study was performed on the first night without NCPAP after completing 30 days of treatment (follow up 1). A fourth polysomnographic study was performed 8-10 days after NCPAP was stopped (follow up 2) in six subjects. RESULTS--In both groups total sleep time (TST) and sleep architecture remained unchanged at the different visits. Baseline snoring characteristics in the two groups were similar. In the control group the mean (SE) number of snoring episodes/hour of sleep (snoring index) and the percentage of TST > 60 decibels (dB) were 380 (36)/h and 11.1 (2.0)% TST respectively at baseline, and was unchanged at follow up. In the NCPAP group the snoring index decreased from 387 (50)/h to 320 (57)/h after NCPAP therapy, but the % TSTS > 60 dB decreased from 10.3 (1.8)% to 7.4 (1.5)%. The snoring index and intensity returned to baseline values at follow up 2 (374 (74)/h, 9.8 (2.1)% TST). Changes in snoring characteristics could not be explained by changes in body position between the different sleep studies. CONCLUSIONS--NCPAP improves snoring but this effect is lost soon after stopping treatment.