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Biomedical subjects

J Scholle

Publications and source records attributed to J Scholle.

8 recordsLinked to original sources

Late conversion from steroids to azathioprine in cyclosporin-treated renal graft recipients.

In renal graft recipients primarily treated with cyclosporin and low-dose methylprednisolone, withdrawal of the long-term steroid medication increases the likelihood of developing rejection episodes. In order to determine the predictive value of clinical parameters and routine prewithdrawal graft biopsies for the risk of rejection, the authors studied 141 kidney recipients from whom steroids were withdrawn 7-9 months after transplantation in a clinically stable situation. Both the quality of the HLA-match and the results of prospective graft biopsies were found to correlate significantly to the occurrence of acute rejection. In order to investigate the influence of additional azathioprine medication on the incidence of acute rejections in recipients not receiving steroids, immunosuppression was continued with cyclosporin monotherapy in 88 patients and with cyclosporin plus azathioprine in 53 patients. The risk of developing rejection episodes was significantly reduced from 48% after 1 year on monotherapy to 28% after the addition of azathioprine medication.

Azathioprine↗

Kinetics of the redistribution phenomenon after extracorporeal elimination.

Evaluation of the efficiency of extracorporeal elimination is rendered difficult by the rebound phenomenon which may occur in plasma concentrations after hemodialysis, hemoperfusion, or plasma exchange. The term clearance, derived from the extraction rate, has the drawback that it is often based on the incompatible terms plasma concentration and blood flow. To avoid these difficulties, clearance may be calculated from kinetics of plasma concentrations. But this approach will lead to an overestimation of the eliminative efficiency, because plasma concentrations may decline faster than tissue levels, which will be indicated by the rebound phenomenon. The rebound is due to a redistribution from tissue into plasma and follows 2-compartment kinetics. However, the amount removed by extracorporeal elimination reflects the redistribution phenomenon and, simultaneously, can be used to evaluate the absolute efficiency. The amount removed can be derived from 1-compartment kinetics if redistribution can be neglected, and from 2-compartment kinetics if a redistribution takes place. The amount removed can also be evaluated using model- independent approaches, which may be applied even if sustained absorption or proliferation must be assumed. According to these approaches, the removed amount is given by graphic extrapolation, and it can be calculated from extracorporeal clearance and from concentrations in the removed fluid, or it can be eluted from the extracorporeal device.

Extracorporeal Circulation↗

Elimination kinetics of plasma exchange.

Interest in the therapeutic use of plasma exchange for various diseases is growing. The two different effects of plasma exchange are elimination and activation. The kinetics are linear for elimination by plasma exchange, but not for activation. Plasma exchange is performed intermittently and can be described by intermittent kinetics. According to intermittent kinetics, plasma exchange removes 50% to 75% of a substance in plasma within 1-2 h, corresponding to an elimination half-life of 30-40 min. Hybrid kinetics, a mixture of actually intermittent but theoretically continuous elimination by plasma exchange, can however also be applied. Hybrid kinetics are more convenient and more reliable than intermittent kinetics. This is because hybrid kinetics are based solely on the concentrations before each plasma exchange; hybrid kinetics also reflect removal from the entire body and not just from the plasma compartment. According to hybrid kinetics, the amount of a substance in the body removed within 3-4 days is 50% of the difference between the initial and the final plasma concentration, depending on the intensity of plasma exchange. The intensity may well contribute at least in part to the beneficial effect of plasma exchange in various diseases.

Antibodies↗

First-pass effect: nonlinear concept comprising an explicit solution of integrated Michaelis-Menten equation.

The first-pass effect results from metabolism during the first liver passage of a drug given by mouth. The metabolism is described by the Michaelis-Menten equation, but the integrated form of the Michaelis-Menten equation has no explicit solution for concentration and its handling requires a computer. However, the presented nonlinear equation of the first-pass effect is an explicit integration of the Michaelis-Menten equation and involves only general mathematics. However, the problem of evaluating the Michaelis-Menten constants Vm and Km is not resolved. Therefore, linear equations are also derived, which correspond to previous clearance models.

Biological Availability↗

Membrane plasma exchange in Goodpasture's syndrome.

We report two cases with Goodpasture's syndrome successfully treated by membrane plasma exchange. In both patients, pulmonary infiltrations and hemoptysis had already resolved after the first pulse methylprednisolone dose (1000 mg IV). Following plasma exchange, renal function did not further deteriorate in one patient and returned to normal in the other patient. From the clinical course of our patients and a review of the literature, we conclude that membrane plasma exchange is effective in preventing deterioration of renal function in Goodpasture's syndrome. Analysis of the literature shows that patients who respond to plasma exchange have significantly fewer crescents and lower plasma creatinine, while non-responders are more often oliguric or anuric and require dialysis at the time of plasma exchange.

Adult↗