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Selected AbstractsEffects of protein A immunoadsorption in patients with advanced chronic dilated cardiomyopathy,JOURNAL OF CLINICAL APHERESIS, Issue 4 2009Andreas O. Doesch Abstract Objectives: The objective of this study was to investigate functional effects of immunoadsorption (IA) in severely limited study patients with chronic nonfamilial dilated cardiomyopathy (DCM), and to analyze the prevalence of Troponin I (TNI) autoantibodies. Background: Immunoadsorption (IA) has been shown to induce early hemodynamic improvement in patients with nonfamilial DCM. Methods: We performed IA using Immunosorba columns on five consecutive days in 27 patients with chronic DCM, congestive heart failure of NYHA class ,II, left ventricular ejection fraction below 40%, and mean time since initial diagnosis of 7.2 ± 6.8 years. Results: Immediately after IA, IgG decreased by 87.7% and IgG3 by 58.5%. Median NT-pro BNP was reduced from 1740.0 ng/L at baseline to 1504.0 ng/L after 6 months (P = 0.004). Mean left ventricular ejection fraction (LVEF) was not significantly improved overall (24.1 ± 7.8% to 25.4 ± 10.4% after 6 months, P = 0.38), but LVEF improved ,5% (absolute) in 9 of 27 (33%) patients. Bicycle spiroergometry showed a significant increase in exercise capacity from 73.7 ± 29.4 Watts to 88.8 ± 31.1 Watts (P = 0.003) after 6 months while VO2max rose from 13.7 ± 3.8 to 14.9 ± 3.0 mL/min kg after 6 months (P = 0.09). Subgroup analysis revealed a higher NT-pro BNP reduction in patients with shorter disease duration (P = 0.03) and without TNI autoantibodies at baseline (P = 0.05). All 9 patients with an absolute increase of LVEF of ,5.0% were diabetic (P = 0.0001). Conclusions: In this study, on severely limited heart failure patients with nonfamilial DCM, IA therapy moderately improved markers of heart failure severity in a limited subgroup of patients. This may be due to the selected study population with end-stage heart failure patients and the lower reduction of IgG3 compared to previous studies. Future blinded multicenter studies are necessary to identify those patients that benefit most. J. Clin. Apheresis 2009. © 2009 Wiley-Liss, Inc. [source] Pharmacokinetics and bioavailability of trimethoprim-sulfamethoxazole in alpacasJOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 5 2002J. Chakwenya The pharmacokinetics and bioavailability of trimethoprim-sulfamethoxazole (TMP-SMX) were studied in six healthy male-castrate alpacas (Lama pacos) after intravenous (i.v.) or oral (p.o.) drug administration of 15 mg/kg TMP-SMX using a crossover design with a 2-week washout period. After 90 days one group (n = 3) was given a p.o. dose of 30 mg/kg TMP-SMX and the other group (n = 3) was given a p.o. dose of 60 mg/kg TMP-SMX. After i.v. administration of 15 mg/kg of TMP-SMX the mean initial plasma concentration (C0) was 10.75 ± 2.12 ,g/mL for trimethoprim (TMP) and 158.3 ± 189.3 ,g/mL for sulfamethoxazole (SMX). Elimination half-lives were 0.74 ± 0.1 h for TMP and 2.2 ± 0.6 h for SMX. The mean residence times were 1.45 ± 0.72 h for TMP and 2.8 ± 0.6 h for SMX. The areas under the respective concentration vs. time curves (AUC) were 2.49 ± 1.62 ,g h/mL for TMP and 124 ± 60 ,g h/mL for SMX. Total clearance (Clt) for TMP was 21.63 ± 9.85 and 1.90 ± 0.77 mL/min kg for SMX. The volume of distribution at steady state was 2.32 ± 1.15 L/kg for TMP and 0.35 ± 0.09 L/kg for SMX. After intragastric administration of 15, 30 and 60 mg/kg the peak concentration (Cmax) of SMX were 1.9 ± 0.8, 2.6 ± 0.4 and 2.8 ± 0.7 ,g/mL, respectively. The AUC was 9.1 ± 5, 25.9 ± 3.3 and 39.1 ± 4.1 ,g h/mL, respectively. Based upon these AUC values and correcting for dose, the respective bioavailabilities were 7.7, 10.5 and 7.94%. Trimethoprim was not detected in plasma after intragastric administration. These data demonstrate that therapeutic concentrations of TMP-SMX are not achieved after p.o. administration to alpacas. [source] Assessment of fetal liver volume and umbilical venous volume flow in pregnancies complicated by insulin-dependent diabetes mellitusBJOG : AN INTERNATIONAL JOURNAL OF OBSTETRICS & GYNAECOLOGY, Issue 11 2003Simona M. Boito Objectives To determine fetal liver volume and its relation with umbilical venous volume flow and maternal glycosylated haemoglobin (HbA1c) in pregnancies complicated by diabetes mellitus type I. Design A cross sectional matched control study. Setting Obstetric out patient clinic, Erasmus MC,University Medical Centre, Rotterdam. Population Data from fetuses of diabetic women (n = 32; 18,36 weeks) were compared with data from normal controls (n = 32) matched for gestational age. Methods Umbilical venous cross sectional area (mm2) and time-averaged velocity (mm/s Doppler) were determined for calculation of volume flow (mL/min) and flow per kilogram fetal weight (mL/min/kg). Umbilical artery pulsatility index was determined. Fetal liver volume measurements were obtained using a Voluson 530-D. Main outcome measures Fetal liver volume, umbilical venous volume flow and downstream impedance. Results A statistically significant difference between fetuses of diabetic women and normal controls was found for liver volume (mean [SD]: 45.9 [34.0] vs 38.3 [28.7] mL), abdominal circumference (22.2 [6.6] vs 21.3 [5.6] cm), estimated fetal weight (1162 [898] vs 1049 [765] g) and fetoplacental weight ratio (0.22 vs 0.19) and liver volume/estimated fetal weight ratio (4.13% [0.007] vs 3.62% [0.009]). Umbilical venous volume flow (mL/min) and umbilical artery pulsatility index were not essentially different between the two study groups, but umbilical venous volume flow per kilogram fetal weight was lower (P < 0.05) in the diabetes group (94.3 [26.1] mL/min kg) compared with normal controls (109.5 [28.0] mL/min/kg). A positive correlation existed between fetal liver volume and maternal HbA1c (P = 0.002). Conclusions Measurement of fetal liver volume by three-dimensional ultrasound may play a role in identifying fetal growth acceleration in diabetic pregnancies. Fetal liver volume increase is positively related to maternal HbA1c levels reflecting degree of maternal glycemic control. Fetal liver volume normalised for estimated fetal weight is significantly higher in the fetuses of diabetic women. In the present study, umbilical venous volume flow and fetoplacental downstream impedance are not different between diabetic and normal pregnancies. [source] Pharmacokinetics of diclofenac in rats intoxicated with CCL4, and in the regenerating liverBIOPHARMACEUTICS AND DRUG DISPOSITION, Issue 8 2007Karina Reyes-Gordillo Abstract The pharmacokinetics of an intravenous and oral diclofenac dose of 3.2 mg/kg was studied in male Wistar rats under control conditions, 1 and 3 days after liver damage and regeneration induced by an oral injection of CCl4. One day after CCl4 administration, indicators of necrosis (alanine aminotransferase), cholestasis (,-glutamyl transpeptidase) and regeneration (,-fetoprotein) were significantly increased; these effects were reversed after 3 days. In nonintoxicated rats, t1/2 was 43.83 ± 4.95 min, Vd was 0.37 ± 0.04 l/kg, Cl was 129.21 ± 9.20 ml/min kg, AUCi.v. was 25.62 ± 1.45 µg/min ml, and AUCp.o. was 20.21 ± 1.03. One day after intoxication, when the liver was damaged and regenerating, the metabolism was decreased: diclofenac t1/2 was increased to 258.21 ± 30.80 min but Vd did not change significantly, therefore Cl was reduced to 32.81 ± 3.38 ml/min kg. By day 3 after intoxication, liver function, regeneration and pharmacokinetics returned to normal. The results show that liver damage and regeneration increases the bioavailability by decreasing elimination. The present observations suggest that reduction of the pharmacokinetic parameters may lead to drug accumulation in the regenerating-damaged liver with an attendant possible increase in toxic effects. The results in rats, also suggest that once hepatic injury is finished and regeneration is complete, diclofenac can be administered normally. Copyright © 2007 John Wiley & Sons, Ltd. [source] | ||||||||||