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Biomedical subjects

O Richter

Publications and source records attributed to O Richter.

At least 37 records · Page 2Linked to original sources

Simplified microvascular suture techniques for rat liver transplantation as a microsurgical model with arterial blood supply.

The methods for liver transplantation in the rat mainly used do not include reconstruction of the arterial blood supply to the liver. Furthermore, to ensure a short anhepatic phase these methods almost all entail specially developed cuff anastomoses in the recipient operation instead of the conventional microvascular suture technique. Thus an acceptable survival rate can be attained in the experimental animals. This detailed description of simplified microvascular suture techniques is intended to present an alternative to the cuff anastomoses used almost exclusively. In the donor operation with this method, the liver is dissected with an arterial pedicle including the abdominal segment of the aorta, and the liver is flushed in situ not only via the portal vein, but also via the hepatic artery. The organ is implanted in the recipient animal using simplified microvascular suture reconstruction of the arterial blood supply to the liver. Use of telescopic spectacles with 2-fold magnification has proven to be adequate for the entire procedure. With mastery of this method of rat liver transplantation, the average duration of the anhepatic phase is about 20 min, substantially below the 30-min limit which is critical for the survival of the experimental animals. The donor operation requires about 60 min, and the recipient operation 70 to 80 min. With this method, the spectrum of investigations on liver transplantation which are possible in the rat is substantially extended in that clinical conditions can be reproduced very much more exactly by combination of portal and arterial in-situ flushing in the donor operation and rearterialization of the transplant in the recipient operation, as compared to the transplanted rat liver being supplied only with portal venous blood.

Anastomosis, Surgical↗

Future research directions and data requirements for developing ambient ozone guidelines or standards for agroecosystems.

The ambient air quality in Central Europe appears to have the potential to adversely affect the productivity of the agroecosystems in that geographic area. Therefore, there is a need to develop, validate, and apply air pollutant exposure-plant response models to explain the relationships between the stochastic chemical climate and ecosystem responses. Such models will have to include numerical terms for the effective air pollutant exposure regime to account for the fluxes of matter, energy and information within the ecosystem and its components. The structure and function of the ecosystem which are influenced by the air pollutant flux can be described by a combination of empirical and mechanistic models. A discussion of such an approach is presented in this paper.

Journal Article↗

Partition of serum lipoproteins in a polyethylene glycol/dextran two-phase system.

Aqueous two-phase systems containing polyethylene glycol (PEG) and dextran as phase forming polymers were used for the partition of unmodified and hypochlorite modified lipoproteins. Low density lipoprotein (LDL) was separated from high density lipoprotein (HDL) by sequential ultracentrifugation from human plasma. In agreement with the higher electrophoretic mobility, high density lipoprotein shows a higher value of the partition coefficient in contrast to low density lipoprotein. An increase in the concentration of chloride ions reduces the enrichment of lipoprotein in the top phase and favours the accumulation of aggregated material at the interface. The partition coefficient strongly depends on the age of the lipoprotein sample. Differences in the value of the partition coefficient could be obtained for the lipoprotein fractions HDL-2 and HDL-3. Hypochlorite modified LDL shows higher values of the partition coefficient due to the higher negative charge of the modified lipoprotein particle.

Chemical Phenomena↗

Modification of low density lipoproteins by sodium hypochlorite.

Human low density lipoproteins (LDL) were incubated with increasing amounts of sodium hypochlorite. A decrease of the number of free amino groups on the LDL surface starts only upon addition of 30-40 moles NaOCl per mole apoB, whereas all detectable SH groups are oxidized after addition of nearly 17-20 moles NaOCl. All hypochlorite-modified LDL samples have a higher electronegative surface charge compared with native LDL as revealed by agarose gel electrophoresis and partition of LDL in an aqueous polyethylene glycol/dextran two-phase system. The more NaOCl is used to alter LDL, the higher is the electrical surface charge. Changes in surface charge are found already at low NaOCl concentrations where no decrease of amino groups is detected. It is assumed that changes in surface charge are caused by the formation of monochloramines and especially at low degrees of modification by a further unknown contribution. An effect on the primary structure of apoB or peroxidation-like changes in NaOCl-altered LDL could not be found under our experimental conditions. The results are discussed with respect to such modifications under in vivo conditions by hypochlorous acid generated in stimulated phagocytosing cells.

Dextrans↗

[Residues of active substances after consumption of contaminated food: status report on the evaluation of residues with examples of two drugs].

Pharmacokinetic models are presented for the computation of time courses of blood levels of drugs in man following the consumption of contaminated food. Mathematically, two linear systems of differential equations are set up for the donor organism (e.g., trout) and for the recipient, (e.g., man), where the first system generates the initial conditions for the second. Models of this kind are applied to the transfer of chloramphenicol to man via carp and trout (which had previously been administered this drug) and to the transfer of theophylline to infants via breast milk. Limiting concentration profiles are computed by constructing the most favourable and most adverse combinations of parameters with respect to drug elimination in both the donor and recipient organism.

Animals↗

[Analysis of decay curves with biphasic kinetics].

Medication of trout and carps with chloramphenicol and sulfadimidine results in tissue residues which best fit by a biexponential decay curve. The analysis of residues does not reveal any systematic deviations of the data from the model. On the basis of this model half lives for the fast and slow drug elimination phases can be estimated. For the assessment of withdrawal times it is necessary to compute confidence limits for the decay curves. A withdrawal time may be defined by the intersection of recommended maximal concentrations with the upper confidence limit. This analysis does not include any metabolites. This model is also suited for monitoring purposes. It is recommended to apply the procedure to all chemicals exhibiting biexponential decay kinetics.

Animals↗

Pharmacokinetic data analysis of alfentanil after multiple injections and etomidate-infusion in patients undergoing orthopedic surgery.

The pharmacokinetics of Alfentanil, a new short acting analgesic, and Etomidate, a very short acting hypnotic compound, were studied in patients undergoing orthopedic surgery. Anesthesia was induced by bolus i.v. injection of Alfentanil and Etomidate, whereas the maintenance was performed by continuous infusion of Etomidate and repetitive i.v. injections of Alfentanil. The kinetics of the analgesic can be described by a two-compartment model; the elimination half-life has a mean value of 64.8 +/- 38.5 min. No cumulation of the drug was seen in spite of multiple injections. Concerning Etomidate it is not clear whether one or two compartments are needed. The mean elimination half-life is 29.4 +/- 6.2 min. The results suggest a possible shortening of the half-life of Etomidate in the presence of Alfentanil.

Adult↗

[Pharmacokinetics and pharmacodynamics of proxyphylline in asthmatic children].

In 15 asthmatic children and 3 healthy adult volunteers the pharmacokinetics and pharmacodynamics of proxyphylline under oral treatment, and the pharmacokinetics after intravenous administration were determined. The concentration-time-courses after intravenous application could best be fitted to an open 2-compartment model whereas the pharmacokinetics after oral treatment followed an open 1-compartment model. Under oral administration great inter- and intraindividual variances of the serum levels occurred. These differences which showed no age-dependency were suggested to be due to variations of the absorption velocity and the elimination half-lifes. In order to evaluate the curative efficacy of proxyphylline on lung function parameters all children had to undergo a whole body-plethysmography. No significant antiobstructive effects on the relevant baseline ventilation parameters could be observed. The protective efficacy of proxyphylline was determined in asthmatic children who developed an exercise induced asthma after a 7 minutes run. Only in 3 of 11 children a significant reduction of the enhanced airway resistance occurred. No correlation between serum levels and the protective effects was found. The present results show that there is no positive association between pharmacokinetics and pharmacodynamics of proxyphylline in asthmatic children. A safe antiobstructive therapy appears to be impossible within the dose range recommended so far.

Administration, Oral↗

The relationship between pharmacodynamics and pharmacokinetics in asthmatic children receiving a sustained-release formulation of theophylline.

Pharmacodynamic response as well as serum and saliva concentrations of theophylline were monitored in 15 children under a long term theophylline treatment. Respiratory parameters, such as vital capacity and total bronchial resistance all related to bronchodilatation, were measured by use of a bodyplethysmograph. Measurements were performed before treatment and during the steady state with respect to serum levels. Due to small differences between peak and trough concentrations, no correlations between serum concentrations and respiratory parameters were found during the steady state. However, some important respiratory parameters exhibit considerable differences with respect to pretreatment values. In conclusion, one can state that during the steady state, theophylline exerts a constant influence on bronchodilatation which depends only slightly on the concentration range achieved.

Adolescent↗

The kinetics of bupivacaine (Carbostesin) plasma concentrations during epidural anesthesia following intraoperative bolus injection and subsequent continuous infusion.

Plasma levels of bupivacaine were measured in 25 patients undergoing major abdominal surgery. The pharmacokinetic analysis of these data shows: (1) under a short term treatment, i.e. in the initial phase where multiple injections are given, the kinetic properties are in accordance with linear kinetic theory. The data can best be fitted to a two-compartment-model. (2) under a longterm treatment, i.e. infusion for more than 50 h, a very high accumulation occurs in contradiction to this theory. Therefore, the calculation of plasma levels from initial kinetic data is not feasible.

Adult↗

Essential laboratory determinations for monitoring high-dose methotrexate treatment with citrovorum factor rescue.

The use of high-dose methotrexate (HDMTX) with citrovorum factor rescue (CFR) has considerably improved the prognosis of some pediatric malignancies. Massive doses of methotrexate (mtx) may lead to severe or even lethal toxicity. Safe administration of this regimen requires a wide pattern of laboratory tests as well as clinical supervision. One hundred and eighteen courses of HDMTX (12 gm/m2 over 6 hours iv) with CFR administered to 12 patients were analysed for changes of routine laboratory tests 0, 6, 24, 48, and 72 hours following infusion. Hgb, WBC, and platelets on average showed no change during the 72 hours follow-up period. Serum SGOT and SGPT were elevated with a maximum 24 hours following infusion and slowly returned to normal. The increase of serum LDH values were less marked and reached a maximum at 48 hours; changes of serum y-GT values were not significant. Evaluation of the elimination of mtx from serum in each individual patient throughout 14 sequential mtx courses gave no evidence of a prolonged serum half life due to impaired renal mtx clearance. There was also no evidence of enzyme induction in the liver resulting in a shortened serum half-life. Changes of serum enzymes also were not increasing throughout treatment. Careful monitoring of serum mtx levels is mandatory when HDMTX with CFR treatment is administered. Elevation of blood urea nitrogen and creatinine levels within 24 hours following mtx treatment identify the patient at risk for slow mtx elimination and severe toxicity requiring salvage by adequate doses of citrovorum factor.

Adolescent↗

Pharmacokinetics of dexamethasone in children.

A pharmacokinetic data analysis of plasma level data for dexamethasone obtained from children with various diseases and healthy adults was performed. A total of 33 subjects participated in the study. The results show: The pharmacokinetics of dexamethasone can be described satisfactorily within the frame of classic linear pharmacokinetic theory. The variance of important pharmacokinetic parameters is large. Therefore, if a close relationship between drug levels and therapeutic and adverse effects exists, which still has to be proved, optimal individual dosage regimens have to be calculated, guided by drug-level monitoring. When treating newborns, one should be aware that high drug levels are likely to occur, possibly necessitating a dose reduction.

Adolescent↗

[Developing a dose-administration schedule for drug therapy in childhood].

For the application of a target concentration strategy for the assessment of dosage regimens pharmacokinetic parameters and their variances must be known. Since pharmacokinetic parameters like the elimination constant or the volume of distribution undergo considerable changes during the perinatal period until early childhood, the application of standard dosage regimens may lead to serious under- or overtreatment. Based on kinetic data of children from the literature and own studies, it is demonstrated, how changes of the volume of distribution and of the elimination constant influence the optimal dosage regimen. The optimal dosage regimen is evaluated using a special criterion of optimality.

Age Factors↗