Unfractionated heparin (UFH) is widely used in the treatment and prophylaxis of thrombosis. The anticoagulant effect of UFH is monitored according to activated partial thromboplastin time (APTT). However, there are reports of cases in which hemorrhagic complications develop despite APTT being maintained within the therapeutic range. This indicates there are problems with the monitoring method using APTT during UFH treatment. To assess the actual anticoagulant effect in UFH therapy using APTT as a monitoring method, we investigated changes in APTT and thrombin generation (TG) potential in vitro with the addition of UFH to samples from 10 healthy adults. There were large individual differences in the degree of APTT prolongation with the addition of UFH to samples from healthy adults. Furthermore, individual differences in the degree of TG change exceeded those in APTT in 7 subjects with comparable APTT changes caused by UFH (coefficients of variation: 2–5% for APTT, 10–50% for TG potential). Thus, with UFH treatment, there are large individual differences in the degree of TG inhibition even when APTT is within the appropriate range for coagulation control. These findings provide invaluable information for resolving the problem of hemorrhagic complications during UFH treatment based on the current APTT method.
Abstract High-frequency oscillatory ventilation (HFOV) at frequencies of approximately 15 Hz is associated with optimal CO 2 excretion. Higher frequencies using a nitrogen–oxygen gas mixture worsen CO 2 excretion. An in vitro experiment using HFOV and a helium–oxygen gas mixture showed a significant increase in CO 2 transport, which increased with increases in ventilation frequency. We hypothesised that in HFOV, the change in the arterial partial pressure of CO 2 (PaCO 2 ) would be greater at frequencies above 15 Hz when combined with helium–oxygen gas mixture administration. We tested this hypothesis in a hypoventilated healthy rabbit model by administering a helium–oxygen gas mixture at 15, 25, 35, and 45 Hz frequencies. One-way repeated measures ANOVA showed a significant decrease in PaCO 2 among the four ventilation frequency groups. Post-hoc analysis showed significant differences between 15 and 35 Hz frequencies and between 15 and 45 Hz frequencies. The mean (standard error) decrease of PaCO 2 was 10.8 (2.2), 14.1 (2.3), 21.3 (3.3), and 23.1 (2.5) mmHg at 15, 25, 35, and 45 Hz, respectively. Combination therapy of helium–oxygen gas mixture and high-frequency oscillation using ultra/very high frequencies (35–45 Hz) was associated with a greater PaCO 2 decrease than that using the standard frequency (15 Hz).
We used a time-dependent input rate function in the two-compartment model to simulate drug plasma concentrations after an oral administration. The input rate term has a Gaussian-like structure with two parameters, time to maximum absorption rate (tm) and measure of the duration of the absorption process (s). This structure corresponds to the scenario in which the absorption rate of the drug into the central compartment changes unimodally with respect to time after administration with a single peak at time tm. We demonstrate the applicability of this formulation in the simulation of plasma concentration of didanosine after oral administration in two Japanese hemophiliacs. We found that we were able to simulate the time courses of the didanosine plasma concentrations in both patients using the theoretical equation with the input term included, and that we were able to determine the six parameters in the equation by the least squares estimation. Pharmacokinetic values derived from the best-fit curve were almost comparable to those reported in other literature except that the Cmax and AUC0-infinity seemed to be slightly higher than those reported elsewhere. Although we are unable to verify the accuracy of this formulation because of the lack of sufficient Japanese data, we are able to demonstrate its efficacy and convenience in the application presented here.
Bisbenzylisoquinoline alkaloids of Stephania cepharantha have been used for various clinical purposes and recently reevaluated as stimulators of interleukin secretion in tissues. We analyzed molecular structures of bisbenzylisoquinoline alkaloids by determining their molecular weights using the 252Cf-plasma desorption mass spectrometry (PDMS) . The spectra were accumulated for 500000 fission events. The acceleration voltage used here was 15kV. Samples were analyzed using nitrocellulose-coated sample targets. Of the 5 alkaloids studied here, cepharanthine gave a main peak of molecular weight of 606.1 for the theoretical molecular weight of 606.7. The other minor peaks were considered to be demethylated fragment ions.252Cf-PDMS should be quite useful in studying structure, metabolism and pharmacokinetics of various drugs with extremely low coefficients of variation.
1. INTRODUCTION. The latest statistics how that Japanese hemophilia patients infected with HIV-through clotting factor concentrates may survive more than 10 years after HIV-infection without showing an onset of AIDS [1]. Unfortunately, however, results of the recent surveillance have revealed that about half of hemophilia patients had also been infected with the hepatitis C virus (HCV) [2]. Therefore, some hemophilia patients might suffer from hepatocellular carcinoma triggered by HCV after some latent periods. In the present study, we computed the life time expectancy of hemophilia patients with two risks of HIV-and HCV infections. 2. METHOD. We used the Weibull hazard function h(t) for the hazard rate from AIDS after infection with HIV-1. In order to describe the hazard rate arising from hepatocellular carcinoma after HCV infection, we utilized the theoretical function c(t) with two parameters that were obtained previously by ourselves from a case-controlled study on hepatocellular carcinoma patients infected with HCV through blood transfusion [3]. Substituting necessary parameters estimated for Japanese hemophilia patients into h(t), the life time expectancy t was computed by the following integration; tau=integral of exp(-integral of h(t')+c(t¿) dt') dt, where t' means the time after HIV-infection, and t¿ is a variable composed of tU and times of HIV-and HCV infections. 3. RESULTS AND DISCUSSION. Without hepatocellular carcinoma, the life time expectancy tau of the patients infected with HIV-1 at the age of 20 was computed as 15.0 years. On the other hand, for the same patients with the risk of hepatocellular carcinoma through HCV infection at the age of 10, 15, 20 and 25 years old, values of tau were computed at 12.2, 13.3, 14.1 and 14.4 years, respectively. Especially noticeable was the reduction of tau in cases of HCV infection was prior to HIV-infection. In the present computation, the two risks from HIV-1 and HCV infections were assumed to be additive because no explicit interaction between them has been reported yet. Various long term effects have been found with the development of HIV/HCV therapies; that should also take into account the survival estimation and therapy planning for HIV-1 infected patients in the coming years.
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