Biomedical subjects
Publications and source records attributed to F Zimmermann.
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Two of our own patients with Boerhave's syndrome are reported. A disturbance of the vomiting process with abrupt increase of pressure in the esophageal lumen combined with a circumscribed constitutional weakness of the esophageal wall appears to be the decisive factor in the etiology of atraumatic complete esophageal rupture. The clinical picture is characterized by vomiting and painful sensations in the abdomen and thorax in addition to subsequent acute epigastric symptomatology. A water-soluble contrast medium is very useful in the radiological diagnosis. Thoracotomy with suture and drainage is recommended as the treatment of choice. Operative treatment treatment has a mortality of 38% compared with more than 60% with drainage alone.
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Tadpoles of Rana temporaria (size 5-7 mm) were kept in solutions of D-penicillamine (DPA), beta-aminopropionitril (betaAPN), and L-thyroxine at different concentrations for 18 days. The influence of the substances on metamorphosis was investigated. In low concentrations (1 or 10 mg/100 ml) D-penicillamine accelerates the process of metamorphosis. At these concentrations investigated skeletal malformations could not be observed. A content of 100 mg of DPA/100 ml is toxic. After 8 days of exposure only 4 of the 15 test animals had survived. In all concentrations investigated, beta-aminopropionitril has a toxic action. In low concentration (1 mg/100 ml) deformities are found which could be described as bending of the femur and twisting of the whole hind limb. The animals are non-viable, they die shortly after termination of metamorphosis. Higher concentrations (10 or 100 mg/100 ml) are lethal within the first 10 days. L-thyroxine (0.01 mg/100 ml) shows the wellknown metamorphosis-accelerating effect.
In order to study the influence of D-penicillamine (DPA) and beta-aminopropionitrile (BAPN) as well as of a combination of both substances (proportion by weight 1:1) on the collagen of skin, aorta, and femoral epiphysial cartilage, the mechanical properties of these fibrous organs were examined, after having performed tests on onset and dissipation of action, measured by the decrease of ultimate load of excised strips of skin using the two individual compounds. The action of 320 mg/kg of DPA sets in within 7 days reaching a maximum value after 14 days. After discontinuance of the substance the control values are reached within 15 days. BAPN shows its maximal effect on the 18th test day. After discontinuance of treatment the control value is not reached within 35 days. DPA and BAPN show organo-specific actions: DPA has a considerably stronger influence on the collagen of skin than on the collagen of the aorta; under the present test conditions it does, however, not affect the collagen of the distal femoral epiphysial cartilage. As compared to DPA, BAPN exerts a less pronounced influence on the collagen of the skin, similar influence on the collagen of the aorta, and a strong influence on the collagen of the distal femoral epiphysial cartilage. If both substances are administered together, the organospecific actions of DPA on the one hand and BAPN on the other hand are maintained. It is discussed whether the different chemical compositions of the collagen (Type I--IV) may be connected with the organospecific effects of the test substances.
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Male albino rats are treated with high doses of D-penicillamine (2000 mg/kg/day orally), paramethasone (50 mu-g/kg/day orally), and with a combination of equal doses of D-penicillamine and paramethasone for a period of 4 weeks. At the end of treatment the mechanical properties of dorsal skin and aorta of the experimental animals are determined. 4 weeks of treatment with D-penicillamine or paramethasone, respectively, leads to a decrease in the skin thickness of the experimental animals. With simultaneous administration of both substances the decrease in skin thickness is about the same. Load resulting in rupture is considerably reduced by D-penicillamine, while only a slight decrease is seen with paramethasone. Simultaneous administration of both substances results in considerable decrease in load resulting in rupture, similar to the effect produced by D-penicillamine. Tensile strength which is not influenced by paramethasone treatment, decreases after treatment with D-penicillamine as well as after simultaneous administration of D-penicillamin and paramethasone. Load resulting in rupture of the aorta remains uninfluenced under the experimental conditions. Comparison of the groups shows that simultaneous administration of D-penicillamine and paramethasone leads to the same results as those which may be obtained with sole administration of D-penicillamine. This suggests that the effect of D-penicillamine on the mechanical properties of the rat skin is not influenced by an additional high dose of paramethasone under the experimental conditions chosen.
In acute pharmacological experiments, D-betta,betta-dimethylcysteine (D-penicillamine, Metalcaptase) stands out for its good oral and intravenous tolerance. In case of high dosage, slight analgesic and anti-inflammatory effects can be found. The influence on newly formed connective tissue is not uniform. While the wet and dry weights of granulomata are not influenced, D-penicillamine causes a retardation of the healing process in standardised burns. Mechanical properties of connective tissue such as the resistance of cut wounds, the tearing strength of excised dorsal skin strips or of the capsule of the knee-joint show after long-term treatment with D-penicillamine a dose-dependent change in the sense of a decrease of the data obtained. After discontinuation of the test substance, the data reach standard values within a few days.
Two experiments were carried out to determine the period of time for a) the decrease of the load resulting in rupture of excised dorsal skin strips of the rat induced by daily oral treatment with D-beta, beta-dimethylcysteine (D-penicillamine, Metalcaptase) and b) the effect produced by D-penicillamine treatment to subside after discontinuation of the substance. 1. On the 5th day of treatment (320 mg/kg/day), the load resulting in rupture of excised dorsal skin strips of rats from an animal group decreased from 3480 p (initial value) to 2350 p. On the 9th day of treatment, the value for the load resulting in rupture dropped to 1790 p. Further decrease of the load resulting in rupture cannot be obtained even after a 2 weeks' treatment with 320 mg/kg D-penicillamine. 2. An animal group was treated with 320 mg/kg D-penicillamine for 7 days. At the end of this period of treatment, the load resulting in rupture of excised dorsal skin strips amounts to 1400 p. After discontinuation of the medication, the load resulting in rupture of the dorsal skin is determined at intervals of several days. 6 days after discontinuation of the test substance, a marked rise was observed and after 15 days, no difference was found between the initial value of non-treated animals and previously treated animals. Thus, it takes a few days only to induce a decrease of the load resulting in rupture by D-penicillamine and its recovery after discontinuing the medication.
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Physico-chemical, spectroscopic (UV, IR, NMR, mass), chromatographic (GLC, TLC) properties and synthesis of 1,3-bis(2-ethylhexyl)-5-amino-5-methyl-hexahydropyrimidine (hexetidine) are reported and discussed. Moreover, the difference between commercial and purified hexetidine is demonstrated.
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