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Biomedical subjects

H Mönig

Publications and source records attributed to H Mönig.

At least 55 records · Page 3Linked to original sources
PubMed1993

Effect of whole-body irradiation on phagocytic cells in mouse blood measured by chemiluminescence.

In investigations with mice the influence of an X-irradiation on the chemiluminescence yield of granulocytes from the peripheral blood was measured. The measurements were carried out with diluted freshly drawn blood by adding luminol as chemiluminogenic substance. The granulocytes were stimulated by zymosan. The following dependencies were investigated: dose from 1 to 8 Gy and time twelve hours to 32 days after a whole-body irradiation. In general the chemiluminescence yields from blood of irradiated animals are reduced in dependence of dose compared with the findings in controls. In unirradiated animals (controls) there exists a good correlation between the numbers of granulocytes and the chemiluminescence. This correlation is diminished after an irradiation. For the fourth day after a whole-body irradiation the chemiluminescence shows an exponential dose dependence. If chemiluminescence counts are related to the number of granulocytes (relative chemiluminescence) an increased chemiluminescence per single granulocyte is recorded up to the eighth day after an irradiation with 1 Gy. It may be assumed that subpopulations of granulocytes with enhanced ability to form oxidative metabolic products are responsible for this effect.

Animals↗
PubMed1993

[Evaluation of underexposed conventional x-ray films following digitization].

Inadequate exposure of analogue radiographs is reported in the literature to occur in 5-25% of cases. Therefore, the present study was performed to test whether selective image processing after digitization could reveal diagnostic details on underexposed radiographs. In addition, the minimal exposure values required for diagnostic purposes after adequate image processing were studied. Phantom studies, organ preparations and measurements of physical parameters with decreasing exposure values were performed. The detection of anatomic and pathologic (nondisplaced fracture lines, microcalcification and renal stones) structures were evaluated by 12 readers. Radiographs with exposure values 20-40% lower than "ideal" values can provide adequate diagnostic images after digital processing. The diagnostic information is significantly impaired with values under 50% of the correct exposure values. In conclusion, this method is adequate to save underexposed radiographs for diagnostic purposes and to avoid repeated examinations.

Analog-Digital Conversion↗
PubMed1992

The effect of endotoxin on preirradiated mice.

Adult male mice were given a whole body irradiation with non-lethal doses of 2.5 or 5 Gy. Unirradiated animals served as controls. The animals (including controls) received a single injection of endotoxin (LPS from Salmonella abortus equi) with doses of 100, 200 or 400 micrograms one day up to one year after irradiation. Twelve, 24 or 48 hours after lipopolysaccharide (LPS) application the animals were killed and dissected. Animals which died spontaneously were also examined. Liver, lung, kidney, small intestine, and stomach were histologically investigated. The histological findings showed, that differences exist between irradiated and unirradiated mice and that the cause of death is also different for animals dying spontaneously. The investigations have shown that after irradiation phases of different degrees of sensitivity with regard to the endotoxin response exist. This behaviour can be observed by different lethality rates or in the light of the histological results. Moreover, the histological findings have shown, that distinct regenerative changes occur first of all in the liver, in the mucosa of small intestine, and the gastric mucosa, in which the number of differentiated cells compared with the mitotic active cells is reduced. It can be ascertained, that a whole body irradiation with 2.5 to 5 Gy enhances an additional injury by endotoxin weeks to months later. Contrary to this a preirradiation a few days before endotoxin application leads to a "protection" against the efficacy of endotoxin. These findings can be explained by modes of action described in literature, according to which endotoxins induce the formation of highly active mediators especially the tumor necrosis factor.

Animals↗
PubMed1991

Pharmacokinetics of encainide in patients with cirrhosis.

The pharmacokinetics of encainide were investigated in 10 patients with cirrhosis and 10 matched controls following single intravenous (IV, 25 mg), single oral (so, 25 mg), and multiple oral (mo, 25 mg thrice daily over 5 days) dosing. The hepatic oxidative drug-metabolizing enzyme capacity and its inducibility were assessed by antipyrine elimination and 6-beta-hydroxycortisol excretion. Eight controls and nine patients were of the extensive metabolizer phenotype (EM), as assessed by the sparteine metabolic ratio. Statistics was performed in EM only. The antipyrine half-life was significantly longer and clearance was significantly lower in patients with cirrhosis. Following IV administration, no significant differences in encainide half-life clearance, volume of distribution, or the area under the plasma concentration time curve (AUC) were observed between patients and controls. Following so and mo, there was a fourfold reduction in the oral clearance in cirrhotics. Thus, encainide bioavailability was increased in cirrhosis. Whereas the AUC of encainide was significantly higher in patients, no differences were observed in its active metabolites, O-desmethyl-encainide (ODE) and 3-methoxy-O-desmethylencainide (MODE). Plasma concentrations of encainide and its metabolites after 3 and 5 days of mo suggested steady-state conditions after 3 days of oral dosing. No change in antipyrine elimination and 6-beta-hydroxycortisol excretion following mo occurred. There was no relationship between parameters of encainide and antipyrine elimination. In conclusion, even though the elimination of encainide was reduced in patients with cirrhosis, plasma levels of the pharmacologically active metabolites, ODE and MODE, were comparable.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

The effects of frusemide and probenecid on the pharmacokinetics of phenprocoumon.

We have studied the pharmacokinetics of phenprocoumon with and without co-administration of frusemide and probenecid in two groups of 17 healthy volunteers. Frusemide 40 mg b.i.d. for 7 days did not interact with phenprocoumon to a significant extent. Probenecid 500 mg q.i.d. for 7 days significantly accelerated the overall elimination of phenprocoumon, as indicated by a decrease in AUC from 295 to 157 micrograms.h.ml-1, and a reduction in the fraction of the dose excreted by the kidneys. The data are consistent with inhibition of the glucuronidation of phenprocoumon by probenecid. Its accelerated elimination may be a consequence of the increased formation of hydroxylated metabolites.

Administration, Oral↗
PubMed1990

Effect of oral contraceptive steroids on the pharmacokinetics of phenprocoumon.

1. The effect of chronic administration of oral contraceptive steroids (OCS) on the pharmacokinetics of the oral anticoagulant phenprocoumon was investigated in seven healthy females. 2. Plasma concentrations of phenprocoumon and the urinary recovery of unchanged as well as conjugated drug were measured following a single oral dose of 0.22 mg kg-1. A group of seven non-smoking, drug-free women matched for age and body weight served as controls. 3. Administration of OCS was associated with a significant increase in the clearance of phenprocoumon from 1.6 +/- 0.7 to 2.0 +/- 0.7 ml min-1 kg-1 (P less than 0.05). The urinary recovery of phenprocoumon glucuronide was significantly higher in OCS users (21.0 +/- 16 vs 14.0 +/- 10 (% of dose); P less than 0.05). No difference in plasma protein binding of phenprocoumon was observed, being 99.2 +/- 0.07 in both groups. 4. The accelerated glucuronidation of phenprocoumon in OCS users suggests the need for careful monitoring of the anticoagulatory response in these subjects, especially when the OCS are withdrawn.

4-Hydroxycoumarins↗
PubMed1990

Prolonged radioprotective activity of WR-2721 linked to dextran.

The radioprotective agent WR-2721 was linked to dextran and poly(glutamic acid) respectively, to obtain a prolonged radioprotective ability. Male mice were administered these water soluble polymer conjugates one to 72 hours prior to a whole body irradiation with X-rays. A prolongation of radioprotective efficiency was achieved with two dextran-(WR-2721)-conjugates. For a period of 24 hours between administration, and irradiation dose reduction factors of 1.14 +/- 0.04 and 1.10 +/- 0.03 respectively were found. After 72 hours, no protective effect was observed. Histopathological investigations of the liver for formation of tumors 200 to 600 days after irradiation seems to indicate that a protective effect is not produced by the dextran-(WR-2721)-conjugates.

Amifostine↗
PubMed1989

[Probenecid affects liver metabolism].

The effect of probenecid on the pharmacokinetics of phenprocoumon (PPC) given as a single oral or intravenous dose, on the vitamin-K-dependent protein-C-antigen, and on the pharmacokinetics of antipyrine and 6 beta-hydroxycortisol was determined in 14 healthy volunteers. Probenecid caused a 75% decrease in urinary excretion of PPC and PPC-glucuronide and shortened the plasma half-life of PPC significantly (by about 35%). The results after oral and intravenous administration of PPC did not differ significantly. Plasma protein-C-antigen concentrations following intravenous PPC were significantly increased by probenecid. The plasma half-life of antipyrine after 7 days of probenecid therapy was significantly diminished. Accordingly, urinary excretion of 6 beta-hydroxycortisol was significantly increased. These data appear for the first time to reveal enzyme-inducing properties of probenecid, which may be responsible for the shortening of PPC plasma half-life when probenecid is given simultaneously. In addition, the influence of probenecid on plasma protein-C-antigen concentrations may indicate further effects of probenecid on liver metabolism.

4-Hydroxycoumarins↗
PubMed1989

[Defibrination syndrome after snake bites].

A defibrination syndrome developed in two men (aged 51, and 29 years old) within two hours of having been bitten by vipers Echis carinatus and Agkistrodon halys, respectively. In both the syndrome was characterized by afibrinogenemia with prolongation of the thrombin time, presence of fibrin monomers and split products of fibrinogen. Haemorrhagic signs included oral mucosa bleeding and macrohematuria. Specific serum was administered 9 and 16 hours, respectively, after the bite and achieved normalization of all clotting values within 48 hours.

Adult↗
PubMed1988

Influence of nitrendipine and verapamil on plasma levels, urinary excretion, and beta-blocking effect of metoprolol.

Following randomized allocation eight healthy volunteers were treated for 1 week each with metoprolol alone (100 mg twice daily), verapamil 80 mg three times a day plus metoprolol 100 mg twice daily, and with nitrendipine 20 mg twice daily. Plasma levels and urinary recovery of the beta-blocker, antipyrine clearance, and heart rate on exercise were measured. Verapamil and nitrendipine slightly prolonged elimination half-life of metoprolol. The urinary recovery of the parent beta-blocker and of its alpha-hydroxy metabolite was elevated by both calcium antagonists (verapamil and nitrendipine). Exercise tachycardia (150 beats/min without drugs) was inhibited more pronounced on the combination therapies than under metoprolol administration alone. Results of the present study indicate that calcium antagonists enhance inhibition of exercise tachycardia caused by metoprolol, possibly due to their binding to myocardial beta-adrenergic receptors which is known from the literature. As both calcium antagonists did not increase plasma levels of metoprolol, in the present study a kinetic interaction between the beta-blocker and the calcium channel blockers investigated does not appear to be responsible for the pharmacodynamic effects observed.

Adult↗
PubMed1988

Selective inhibition of drug oxidation after simultaneous administration of two probe drugs, antipyrine and tolbutamide.

The effects of sulphaphenazole, cimetidine and primaquine on the disposition of antipyrine and tolbutamide in healthy volunteers have been investigated. The model substrates were administered simultaneously in order more clearly to define any selective effects of the potential inhibitors. Sulphaphenazole produced a significant increase in the half-life of tolbutamide (7.10 to 21.50 h) and a corresponding decrease in its clearance (0.260 to 0.084 ml.min-1.kg-1). Clearance to hydroxytolbutamide (OHTOL) and carboxytolbutamide (COOHTOL) was also significantly decreased. In contrast, sulphaphenazole had no effect on the disposition of antipyrine. Administration of cimetidine did not significantly alter the disposition of either model drug. However, a 1.6-times higher dose of cimetidine did increase the half lives both of tolbutamide and antipyrine (6.21 to 9.04 h and 14.2 to 19.2 h, respectively) and decrease their clearance (0.226 to 0.148 and 0.50 to 0.31 ml.min-1 kg-1, respectively). Clearance to OHTOL and hydroxymethylantipyrine (HMA) was reduced. A single dose of primaquine had no demonstrable effect on tolbutamide disposition whereas the half-life of antipyrine was increased (12.1 to 15.0 h) and its clearance decreased (0.63 to 0.38 ml.min-1.kg-1). The partial clearance to HMA, 4-hydroxyantipyrine (OHA) and norantipyrine (NORA) was also significantly reduced. The two main inferences are first, that tolbutamide and antipyrine are metabolised by different forms of cytochrome P-450, and second that a battery of model substrates is needed to investigate the inhibitory effects of a drug in man.

Adult↗
PubMed1988

Comparative effects of rifabutin and rifampicin on hepatic microsomal enzyme activity in normal subjects.

The comparative enzyme inducing effects of rifabutin and the chemically related drug rifampicin have been investigated in 8 normal subjects. Rifampicin 600 mg daily for 7 days caused considerable shortening of the antipyrine half-life and a marked increase in antipyrine clearance, associated with an increased rate of conversion to norantipyrine and, to a lesser extent, 4-hydroxyantipyrine and 3-hydroxymethylantipyrine. The urinary excretion of 6-beta-hydroxycortisol was also markedly increased, while plasma GGT activity showed only a slight albeit statistically significant elevation. In the same subjects, rifabutin in the proposed therapeutic dosage (300 mg daily) for 7 days also enhanced the metabolic elimination of antipyrine, with preferential stimulation of the demethylation pathway, and increased the excretion of 6-beta-hydroxycortisol, but the magnitude of the effects was significantly less than after rifampicin. No significant change in plasma GGT was seen. The results indicate that, contrary to the findings in animals, rifabutin does have enzyme inducing properties in man, although at the dosages assessed they were considerably less than those of rifampicin.

Adult↗
PubMed1988

[Effect of the new x-ray ordinance on x-ray diagnosis].

A report is made on the new German X-ray regulations that come into force on 1 January 1988 and their effect on X-ray diagnostics. The main points of the new regulations are constant quality control in order to decrease exposure to radiation, an improvement in image quality, and the introduction of new dose limitations for occupational exposure.

Germany, West↗