Giftung und Entgiftung von Parathion und Paraoxon

Summary 1. In experiments on rats and mice, paraoxon (E 600) was found to be less effective on intraperitoneal than on intramuscular injection: on intraperitoneal injection, the lethal dose (LD₅₀) as well as the dose causing 50% inhibition of the brain cholinesterase (ED₅₀) were about four times higher than on intramuscular injection (detoxication by passage through the liver).2. Parathion (E605), on the other hand, was less effective on intramuscular than on intraperitoneal injection: on intramuscular injection, the LD₅₀ as well as the ED₅₀ were nearly twice as high as on intraperitoneal injection (toxification by passage through the liver).3. The anticholinesterase agent 217-AO lost only little of its effectiveness by passing the liver following an intraperitoneal injection. In vivo, 217-AO was more effective than paraoxon, although 25 times higher concentrations are needed to inhibit the cholinesterase in vitro.The results suggest that paraoxon is detoxicated by the liver so quickly that only a small fraction of the injected amount becomes effective, and that the toxification of parathion in the liver takes place more quickly than the detoxication of the paraoxon formed.4. Dopamine was destroyed in the liver so quickly (monoamino-oxydase) that the intraperitoneal injection of a dose was ineffective which, on intramuscular injection, caused a strong rise in blood pressure.5. Hexobarbital (Evipan) was destroyed in the liver so slowly (enzymes in the microsomes) that intraperitoneal and intramuscular injections were equally effective.The different behaviour of the last two substances shows that it depends on the velocity of the inactivation in the liver whether or not there is a difference in effectiveness between intraperitoneal and intramuscular injections.

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Herrn Professor Dr. W. S. Loewe, Salt Lake City, zum 75. Geburtstag gewidmet.     

Beitrag zur Klinik und Pathogenese der Hyalinosis cutis et mucosae (Lipoid-Proteinose Urbach-Wiethe)

Zusammenfassung 1. Es werden 3 Fälle von Hyalinosis cutis et mucosae (Lipoid-Proteinose Urbach-Wiethe) beschrieben.2. Bei einem dieser Patienten finden sich intrakranielle Verkalkungen, die in Verbindung mit epileptischen Anfällen und einer gewissen Debilität auf eine Miterkrankung des Gehirnes hinweisen.3. Aus dem familiären Auftreten und der deutlichen Häufung von Blutsverwandtschaft bei den Eltern läßt sich auf einen recessiven Erbgang schließen.4. Die histologischen und histochemischen Untersuchungen sowie Fettanalysen im Gewebe und Blut machen die Annahme, daß es sich bei der Hyalinosis cutis et mucosae um eine Fettstoffwechselstörung (phosphatidige Lipoidose Urbach) handelt, wenig wahrscheinlich. Eher wäre auf Grund des histologischen Bildes und der elektrophoretisch nachgewiesenen Verschiebungen der Eiweißzusammensetzung des Serums an eine Eiweißstoffwechselstörung zu denken, vielleicht im Zusammenhang mit einer endokrinen Dysregulation. Diese Annahme schließt nicht aus, daß eine Störung der terminalen Strombahn an der Entstehung und der Lokalisation dieses Krankheitsbildes mitbeteiligt ist.Mit 20 Textabbildungen.Herrn Prof. A. Stühmer zu seinem 65. Geburtstage gewidmet.     

Effectiveness of different intervention measures in children and adolescents with hypertension and lipid metabolism disorders

141 children and adolescents (7-21 years, mean age 14.2 years) showed values of blood pressure, total cholesterol and triglycerides greater than or equal to 90 percentile and HDL-cholesterol values less than or equal to 10 during an examination of 639 children of parents with distinct coronary risk factors or early percentile infarction. By randomization they were subdivided into two groups. (A and B) and underwent intervention measures of different intensity. While group B got only a unique recommendation concerning the preventive measures, in group A a regular, non medicamentous individual treatment was performed. After one year a decrease of blood pressure could be proved in the two groups. A significant decrease of total and HDL cholesterol was found only in group A. While the blood pressure was most clearly reduced in 7-13-year-old children, the most distinct lipid changes were shown in 14-17-year-old adolescents. An influence on body-weight and triglycerides could not be established. Our results confirm the possibilities and also the limits of preventive measures in childhood and adolescence. Apart from the intended decrease of blood pressure and total cholesterol the simultaneous decrease of HDL-cholesterol refers to open questions in the conception of the primary prevention, particularly in children.     

Dose-reduced antihypertensive agents--use in complex nonmedicamentous therapy of hypertension

In order to estimate the influence of a non-medicamentous therapy (CNT) on the consumption of medicaments and coronary risk in high blood pressure 73 hypertensives of a medicamentously stabilized CNT-group were examined in comparison to a group of the same size of patients with hypertension who were managed exclusively medicamentously for behaviour of blood pressure, need of antihypertensive drugs and changes of hypertension-associated risk factors. After an exactly controlled 6-month treatment hypertensives with additionally recommended far-reaching CNT showed an economization of medicaments by scarcely the half in comparison to the reference group. By means of suitable control methods a causal non-medicamentously conditioned decrease of blood pressure could be excluded. A different need of antihypertensive drugs was simulated by the exacter intake of medicaments in the index-patients. Notwithstanding the metabolic effects of the additional therapy have induced a positive change of atherogenic lipids. The examinations indicate in general the difficulty of the judgement of efficacy of non-medicamentous therapeutic measures in connection with a rational dose-reduced long-term therapy with antihypertensive drugs.     

Nifedipine therapy in uncomplicated essential hypertension and hypertensive problem cases

In altogether 54 patients with high blood pressure of the clinical degrees of severity I-IV the blood pressure-reducing effectiveness of the calcium antagonist nifedipine was investigated both in the framework of an oral long-term therapy and especially in problematic situations of high blood pressure. According to the results of own treatment nifedipine is particularly suited for the antihypertensive combination therapy with beta-receptor blockers. Monotherapeutically favourable possibilities of application exist in hypokinetic types of the regulation of circulation as well as in elderly hypertensives. Therapy-resistant as well as crisis-like developments of high blood pressure react with excessive, well tolerable and persisting reductions of blood pressure. Above all with regard to this still little considered indication in the meantime nifedipine represents an unavoidable enrichment in the therapeutic basis spectre of the hypertonus.