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Biomedical subjects

A Martini

Publications and source records attributed to A Martini.

At least 379 records · Page 21Linked to original sources
PubMed1977

Antineoplastic activity and pharmacokinetics of adriamycin and daunomycin in tumor bearing mice.

In C57B1/6 mice bearing the intramuscular Lewis lung carcinoma, single intravenous doses of Adriamycin showed an higher antineoplastic effectiveness on the primary tumor and its lung metastasis than equal doses of its analog Daunomycin. The in vitro cell-binding of Daunomycin to these tumor cells was higher than that of Adriamycin, but no differences in cytotoxicity were found between the two agents. Pharmacokinetic studies revealed that Adriamycin (and/or its metabolites) accumulated in the neoplastic tissue more promptly, in significantly greater quantities and for longer periods than Daunomycin. The possible importance of these findings in explaining the greater therapeutic activity of Adriamycin in experimental animals is discussed.

Animals↗
PubMed1977

Studies in rats on the mechanism by which 6-mercaptopurine inhibits the anticoagulant effect of warfarin.

The observation in man that 6-mercaptopurine (6-MP) decreases the anticoagulant effect of warfarin could be simulated in male Wistar Lewis rats. This permitted a detailed study in animals on the mechanism of this drug interaction. It was found that 6-MP treatment (5 mg/kg at 12-hour dose intervals) neither affects the distribution nor increases the elimination rate of 14C-warfarin. The degradation rate of prothrombin complex activity (determined after blocking the synthesis of prothrombin complex activity by 15 mg/kg of warfarin sodium) was also not inhibited by 6-MP. When added to rat plasma in vitro, 6-MP had no effect on prothrombin times. It was evident, however, that 6-MP treatment produces a significant shortening of the prothrombin times of nonanticoagulated animals. This effect was completely reversible a few days after discontinuance of 6-MP treatment. Analysis of the activity of clotting factors II, V, VII, VIII, and X by one-stage assays using human deficient substrate plasma revealed that the increase in prothrombin complex activity during 6-MP treatment is mainly due to an increase in factor II activity. From these experiments it appears that 6-MP increases the synthesis and/or activation of prothrombin and thereby decreases the response to oral anticoagulant drugs.

Animals↗
PubMed1976

The enantiomers of phenprocoumon: pharmacodynamic and pharmacokinetic studies.

The pharmacodynamics and pharmacokinetics of the optical enantiomers of phenprocoumon were studied in 5 normal subjects and compared to the racemic mixture. Each subject received a single oral dose of 0.6 mg/kg of racemic, S(-), and R(+) phenprocoumon. S(-) phenprocoumon was 1.6 to 2.6 times as a potent as R(+) phenprocoumon when the area under the effect/time curve was used to quantify the total anticoagulant effect per dose. Comparing the plasma concentrations that elicited the same anticoagulant effect, S(-) phenprocoumon was 1.5 to 2.5 times as potent as R(+) phenprocoumon. The anticoagulant activity of the racemic mixture was between that of the enantiomers. There was no distinct difference in the rate of elimination between the enantiomers. The apparent volume of distribution and the plasma clearance for S(-) phenprocoumon were less than those for R(+) phenprocoumon. When the binding of the enantiomers to human serum albumin was compared, S(-) phenprocoumon was more highly bound than R(+) phenprocoumon. The protein binding of racemic phenprocoumon was between that of the enantiomers. The results show that S(-) phenprocoumon is more potent anticoagulant than R(+) phenprocoumon and that the pharmacokinetic differences between the enantiomers are due mainly to differences in their distribution.

Adult↗
PubMed1976

Importance of pharmacokinetic studies on cyclophosphamide (NSC-26271) in understanding its cytotoxic effect.

Pharmacokinetic studies on cyclophosphamide (CP) and its alkylating metabolites produced by hepatic biotransformation have been performed in vivo in animals and in vitro in the perfused liver. CP levels were determined by a gas-chromatographic method combined with mass-spectrometry, and production of alkylating metabolites was assayed by the 4-(4-nitrobenzyl)pyridine reaction for alkylating compounds. Differenes in serum drug levels between normal rats and rats bearing Walker 256 carcinosarcoma were observed in vivo and were confirmed by the liver-perfusion technique. Pharmacokinetic parameters and enzyme kinetic data both in normal and in tumor-bearing animals will be presented. The disappearance of CP and the corresponding formation of CP metabolites was significantly modified when (a) CP was given after previous treatment with a compound which alters its biotransformation (ie, phenobarbital, an inducer of microsomal metabolism), (b) CP was given after previous treatment with CP (which inhibits microsomal metablism), or (c) CP was given with competitive substrates of aldehyde oxidase or dehydrogenase (glyceraldehyde, chloral hydrate, and disulfiram). Results obtained in animals or in the perfused liver will be discussed. The significance of this modified CP metabolism in influencing its cytotoxic effect will be discussed and correlations between drug levels and activity will be presented.

Animals↗
PubMed1976

Studies on the disposition of cyclophosphamide (NSC-26271) in tumor-bearing mice by means of gas chromatography-chemical ionization-mass fragmentography.

The disposition of cyclophosphamide (CP) in mice bearing Lewis lung tumor has been studied by chemical ionization-mass fragmentography using isophosphamide as the internal standard. The drugs were analyzed as their N-trifluoroacetyl derivatives in order to increase sensitivity and to avoid column adsorption and decomposition phenomena. The minimum detectable amount was 500 pg/injection. Linearity was found up to microgram amounts of the substance without any interference of endogenous compounds.

Acetylation↗
PubMed1976

[Results of nerve repair on the upper limbs].

This paper concerns the clinical results of microsurgical repair to nerve injuries on the upper extremities of 66 patients, who had sustained a total of 126 nerve injuries. The majority of these cases involved lesions of the sensory nerves, occurring in the area of the palmar surface of the hand and flexor surface of the fingers (102 nerves and 24 injuries involving the nerve trunks of the median and ulnar nerves). -- Fifty-five percent of the cases were treated primarily, 25% secondarily, and the remaining 20% required nerve transplants. Forty percent involved crush injuries and 87% had sustained associated injuries. -- Tests for tactile gnosis were performed by means of "blindfold" tests. The analysis of the results was carried out according to accepted methods; the "Sedon" method was adapted in order to be able to judge the sensibility from a more functional aspect. -- The repair to sensory nerves is more successful than that carried out on the motor nerves. The degree of success is dependent upon the age of the patient, the nature of the wounds, and the associated injuries. -- Results of primary nerve suture are considerably better than those resulting from nerve transplants even in cases of unfavorable soft issue conditions. Thus, our opinion is that an experienced hand surgeon trained in the field of microsurgery should not be afraid of undertaking primary repair procedures as long as the technical and administrative requirements are adequate.

Hand↗
PubMed1975

[Results of flexor tendon injuries. A comparative study of primary suture and secondary grafting].

This work describes the results of 75 flexor tendon repairs with all injuries involving the flexor tendons of the fingers either in the palm or in "no-man's land". Of these 75 cases, primary repair was performed in half the cases with flexor tendon grafts. Comparisons were made between these two varying methods of treatment, bearing in mind the nature and circumstances of the injury. In the group of primary tendon repairs, 60% of the patients showed good to very good results; in the grafted group, only 42% showed equally good results. From this study it is felt that primary tendon repair, when technically feasible, is the prefered procedure within the palm or the digits. Associated nerve and bone injuries were not found to be a contraindication to such an approach.

Finger Injuries↗
PubMed1975

[Construction of a finger substitute with sensation following the loss of all fingers].

On a patient with traumatic loss of all of the fingers a light but satisfactory grip was obtained by the construction of an opposition post with sensation. This was achieved by a tubed abdominal pedicle flap containing iliac bone graft. A neurovascular cross-finger flap was transfered from the uninjured hand in such a way that an anastomosis to a branch of the nerve of the injured hand was possible, allowing for the development a satisfactory sensation.

Abdominal Muscles↗