[Suprasternal echocardiography in the diagnosis of lung embolism].
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Biomedical subjects
Publications and source records attributed to T Meinertz.
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The investigation includes the area of facialis in Erinaceus europaeus, Talpa europaea, Pachyura indica and Sorex araneus. It is indicated that the topography of muscles diverges considerably from the equal conditions in Rodentia, Carnivoar and Ungulata . The dorsal length musculature thus is almost an undivided mass of muscles by the 4 species investigated as also the laterally and ventrally situated musculature at certain points diverges from the conditions within other above mentioned animal groups.
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The pathogenesis of local skin necroses after intramuscular injection of various drugs such as phenylbutazone (Embolia cutis medicamentosa, Nicolau's syndrome) is not clear. In an attempt to simulate this clinical feature experiments were performed on the rabbit ear lobe. A 20% phenylbutazone solution was injected paraarterial, intraarterial and paraarterial after perforation of the vessel. The drug produced a violent inflammation with all kinds of application. The local inflammation induced by paraarterial injection resulted in a fine scarring. Both other kinds of application produced necroses or even perforations. The histological examinations in these cases revealed massive destructions of the inner arterial wall. In control-experiments necroses or perforations were nerve observed. From these data the following conclusions on the etiology of Nicolau's syndrome can be drawn: Phenylbutazone injected into the vascular or perivascular tissue causes an obligatory inflammation. After lesion of an artery complete destruction of the vessel followed by necrosis of the skin may occur. It seems obvious that this secondary effect can not completely be avoided.
The effect of cholestyramine (12 gm/day divided into 3 doses) on the pharmacokinetics and pharmacodynamics of a single intravenouse dose (30 mg) of phenprocoumon was studied in 6 normal subjects. Cholestyramine treatment led to an increase in the rate of elimination of phenprocoumon in all. Total clearance increased 1.5- to 2-fold. The total anticoagulant effect per dose was considerably reduced during treatment with cholestyramine. Binding studies in vitro showed that phenprocoumon is strongly bound to cholestyramine and that at a given cholestyramine concentration the percentage of phenprocoumon bound remained constant over a large concentration range of phenprocoumon. The results suggest that phenprocoumon undergoes extensive enterohepatic recycling in man which can be effectively interrupted by cholestyramine.
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The effects of papaverine on cyclic AMP (c-AMP), 45 calcium uptake and force of contraction were studied in electrically stimulated left guinea-pig auricles. Papaverine (2 x 10(-6) - 2 x 10(-5)M produced a concentration-dependent positive inotropic effect which was not affected by 10(-7) M propranolol. Papaverine (10(-5)M increased cyclic AMP; this effect developed faster than the increase in twitch tension. Papaverine (10(-5)M) enhanced 45calcium uptake. These results are taken to support the idea of a causative series of interactions between a papaverine induced increase in c-AMP, calcium uptake and force of contraction.
Three aspects of treatment with oral anticoagulant drugs are discussed: 1. Drug interactions which can lead to changes in the elimination or distribution of oral anticoagulant drugs with special emphasis on the time course of the augmentation of the anticoagulant effect. 2. Pharmacokinetic factors responsible for inter- and intrasubject differences in the response to oral anticoagulant drugs. 3. Treatment of overdosage and intoxication with oral anticoagulant drugs. Besides symptomatic treatment with vitamin K and prothrombin complex concentrate the interruption of the enterohepatic recycling by cholestyramine is demonstrated as a useful method for enhancing the elimination of phenprocoumon and warfarin from the body.
The effect of repeated administration of tolbutamide on the elimination and anticoagulant action of a single oral dose of dicoumarol 600 mg was studied in four healthy male subjects using a crossover design. In all subjects the plasma concentration of dicoumarol in the postabsorptive phase was lower during concomitant tolbutamide treatment. However, the subjects differed with respect to the elimination kinetics of dicoumarol and the effect of tolbutamide on some of the measured pharmacokinetic paramaters. In two subjects dicoumarol was eliminated by apparent first-order kinetics. Tolbutamide led to a pronounced increase in the elimination rate and a shift in the plasma concentration-response relationship towards a lower concentration of dicoumarol. The total hypoprothrombinaemic effect per dose of dicoumarol was not affected. The decline in the dicoumarol concentration in plasma in the other two subjects was concentration-dependent. Apparent first-order kinetics were observed only at plasma concentrations below 10 mg/L. Tolbutamide treatment did not markedly affect the slope of the terminal portion of the plasma concentration vs. time curve, but diminished the area under the total curve. The plasma concentration-response relationship of dicoumarol was not affected by tolbutamide, but there was a small decrease in the area under the anticoagulant effect vs. time curve. The plateau level of tolbutamide in plasma increased considerable in all subjects after administration of one dose of dicoumarol. Thus, simultaneous administration of tolbutamide and dicoumarol to man often causes no changes in the anticoagulant activity of dicoumarol, but this is due not to lack of interaction of the drugs but to the complexity of their interactions, involving processes that may counteract each other.
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.
The effect of dibutyryl cyclic AMP (DB-c-AMP; 3 X 10(-4)-3 X 10(-3) M) on electrically induced twitch and high potassium (142.4 mM KCl)-induced contracture tension was studied in papillary muscles from normal and reserpinized cats ([Ca]0 1.8 mM; 25 degrees C; pH 7.4). In both groups of preparations, the increase in twitch tension evoked by DB-c-AMP was accompanied by an abbreviation of the time to peak force and of relaxation time. In the same preparations, the high potassium contracture was markedly depressed by DB-c-AMP in a concentration-dependent manner. Similar results were obtained with the N6-monobutyryl derivative of cyclic AMP. The relaxing effects of the cyclic nucleotides on KCl contractures did not appear to be due to possible non-cyclic breakdown products: adenosine, 5'-AMP and sodium butyrate did not attenuate contracture tension at concentrations up to 3 X 10(-3) M. The same applies to ATP and non-cyclic N6-2'-0-3'-0-tributyryl-adenosine-monophosphate. Theophylline (10(-2) M) was found to prolong the relaxation time of the twitch and to enhance the high KCl contracture. It is concluded that cyclic AMP may be capable of modulating the relaxation process of mammalian heart and that not only the positive inotropic but also the relaxant effects of catecholamines on myocardium described before may be mediated by the cyclic AMP system. The relaxant effects of cyclic AMP derivatives on intact myocardial preparations are attributed to a stimulation by cyclic AMP of the calcium transport of the sarcoplasmic reticulum (SR) and are interpreted to be a corollary to the effects of cyclic AMP previously obtained on isolated SR preparations.
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This study supplements earlier works on the topography of the mammalian heart. The material comprises the hearts of 25 species, 12 of which have not been examined previously. The general morphology of the hearts is briefly dealt with. V. cava cranialis sinistra is preserved in Phascolomys and Macropus. It is presumably present in all Ruminantia, where it has been reduced to the sinus coronarius cordis in Perissodactyla. A particular emphasis is laid on the fact that the paired A. carotides and Aa. subclaviae originate from a single common stem, truncus brachio-cephalicus, in Rangifer, Ovibos, Cervus axis, Bos banteng, Okapi, the Perissodactyla, and in Dicerorhinus sumatrensis and Viscacia. A common origin of the carotids and the A. subclavia dextra is frequently found in most other groups. The fusion seems occur through wandering of the vessels towards the right - i.e. towards A. subclavia dextra. Separate origins of the 4 beffore-mentioned stems occur rarely and only incompletely. Sinus coronarius is of a typical shape. Most probable V. anonyma is always present.