Biomedical subjects
H G Lasch
Publications and source records attributed to H G Lasch.
Coagulation inhibitors in pulmonary cancer patients.
Pulmonary cancer patients are known to have an elevated risk to suffer from thromboembolic complications. Because hereditary deficiencies of coagulation inhibitors antithrombin III, protein C and protein S are known to cause thromboembolic events it was the aim of our study to search for acquired alterations of these proteins in pulmonary cancer patients. We could demonstrate antithrombin III and protein C to be within the normal range in patients suffering from pulmonary carcinoma. In contrast, in patients suffering from metastatic pulmonary carcinoma bound protein S was increased, while free protein S was significantly reduced. In some patients the decrease of free protein S was comparable to the diminution observed in hereditary protein S deficient patients. A high positive correlation was observed between C4b-binding protein and bound protein S, indicating C4b-binding protein to be a regulatory protein for the shift from free and anticoagulatory active to bound and anticoagulatory inactive protein S. In conclusion, the decrease of free protein S is one source for thromboembolic complications in pulmonary cancer patients. For interpretation of altered free protein S levels it is useful to measure C4b-binding protein.
Omega-oxidized leukotriene B4 detected in the broncho-alveolar lavage fluid of patients with non-cardiogenic pulmonary edema, but not in those with cardiogenic edema.
Leukotriene (LT) generation has been implicated in the pathogenesis of the acute respiratory distress syndrome, ARDS. In the present study, we analysed broncho-alveolar lavage fluids of patients on mechanical ventilation because of ARDS (17 samples taken from 9 patients) or because of cardiogenic edema (8 samples taken from 6 patients) and of healthy volunteers (10 samples from different donors). LTs were separated as methylated and non-methylated compounds using different HPLC procedures, and were identified by chromatographic mobility, on-line UV-spectrum analysis and post HPLC immunoreactivity. In the lavage samples of the healthy volunteers and the patients with cardiogenic edema, no LTs were detected by these techniques (detection limit congruent to 0.1-0.2 ng/ml lavage fluid). By contrast, in 15 out of 17 samples from patients with ARDS LTB4 or its metabolites 20-OH-LTB4 and 20-COOH-LTB4 were detected. The endproduct of omega-oxidation, 20-COOH-LTB4, represented the quantitatively predominant compound, detected in the range of 0.3-2.6 ng/ml perfusate. We conclude that the chemotactic agent LTB4 may be involved in the amplification of inflammatory events encountered in ARDS, and that the oxidized metabolites of LTB4 are particularly suitable for monitoring lung leukotriene generation under conditions of neutrophil efflux and oxidative stress.
Catecholamines and thrombocyte alpha 2-adrenoceptors in patients with acute myocardial infarction.
In 28 patients with first myocardial infarction plasma catecholamines and thrombocyte alpha 2-adrenoceptors were studied. The first determination (by HPLC and radioligand binding, respectively) was performed immediately after hospital admission and 6 weeks later. In the acute phase of myocardial infarction plasma adrenaline and noradrenaline levels were high. No significant differences in thrombocyte alpha 2-adrenoceptors and plasma concentrations of adrenaline and noradrenaline were observed between diabetic and non-diabetic patients. In three non-surviving patients only the affinity of the alpha 2-adrenoceptor to the radioligand was decreased (P less than 0.05), the relatively high catecholamine levels failed to reach statistical significance. Six weeks after hospital admission, adrenaline plasma levels were significantly decreased in diabetic and non-diabetic patients, while noradrenaline was only lowered in non-diabetic patients (P less than 0.05). Only in this group did the receptor number (BMAX) show a significant elevation 6 weeks after hospital admission. We conclude that, in acute myocardial infarction, alpha 2-adrenoceptors mainly interact with noradrenaline. Accordingly, no adrenoceptor alteration occurred in diabetic patients, who showed only a decrease in adrenaline but not in noradrenaline plasma concentrations 6 weeks following myocardial infarction. The different patterns in diabetic and non-diabetic patients suggest an alteration of catecholamine metabolism in diabetes mellitus.
[Ethical questions at the bedside].
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[Pulmonary function parameters of shock lung patients--results of a follow-up study].
In seventeen patients out of a total of 219 survivors who had received long-term ventilation for pulmonary failure, an examination was carried out to clarify the question as to late pulmonary sequelae. The following sequelae were detected: 1. a diffusion disturbance in five cases, 2. load-dependent pulmonary hypertension in four cases, and 3. a considerable reduction in compliance.
"Haemostasis time", a modified bleeding time test and its comparison with the Duke and Ivy/template bleeding times. II. Application in bleeding disorders.
"Haemostasis time" (HT), the occlusion time of a Butterfly 25 short cannula inserted into the cubital vein, is a bleeding time modification comparable to the skin bleeding times according to Duke and Ivy/Mielke. It also measures platelet function and is not influenced more than the latter tests by clotting factors. In HT, subendothelium is replaced by a standard artificial surface. The technique was investigated in patients with haemophilia A and B, von Willebrand's disease (vWD), and defects of factors VII and XI. HT was prolonged in 9/16 patients with haemophilia A/B, but did not correlate with the factor VIII:C/IX:C values. However, it reflected the different bleeding tendencies in those patients as represented by early or late onset of bleeding symptoms and occurrence of spontaneous haemarthroses. Of the vWD patients, not classified by multimeric analysis, 15/31 had prolonged Simplate II bleeding times, 14/31 prolonged HTs. Only 20/31 patients had corresponding normal or prolonged bleeding times with both techniques. HT correlated significantly with the Duke bleeding time (p = 0.011), ristocetin cofactor activity (p = 0.003) and von Willebrand factor antigen (p = 0.022), while no correlations were found between these parameters and the Simplate II method. Statistical evaluation shows, that in vWD, HT can replace the less precise Duke bleeding time but not the non-related Ivy/Simplate techniques.
[The progress of a fibrinolytic therapy with streptokinase, urokinase and warfarin in a thoroughbred with intermittent lameness with special reference to resonance thrombography].
A thoroughbred horse, suffering from intermittent lameness was treated with streptokinase, urokinase and warfarin. The appearing fibrinolytic changes in coagulation were exhibited in a resonance thrombogram. In attendant coagulation studies fibrinogen- and fibrin-degradation products were demonstrated. The stallion does not show any lameness since the end of the treatment and is standing in a breeding station since March 1988.
[Intensive care medicine 1986].
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[Principles of drug prevention of thrombosis].
The most important reasons of venous thrombosis are injuries of the vessel wall, hypocirculation (stasis) and hypercoagulability of the blood (Virchow-Trias). The prophylaxis of thrombosis is based on the inhibition of the plasmatic coagulation system and on the improvement of circulation. In general surgery the onset of venous thrombosis can be reduced from 28% to about 9% by low-dose heparin prophylaxis.
[Changes in the coagulation system in shock].
Disorders of the coagulation system in shock are caused by injuries of the endothelium, influx of thromboplastic material into the blood and stasis. In this way, the intrinsic and the extrinsic system is activated. Fibrin is generated in the blood stream and forms high molecular complexes together with fibrinogen (hypercoagulability). With progress of the shock fibrin can deposit in the small vessels with the consequence of impaired circulation. Finally clotting factors and inhibitors (e.g. antithrombin III) are consumed by disseminated intravascular coagulation. This results in a bleeding tendency (consumption coagulopathy). In this survey particular shock formes (endotoxin induced, cardiogenic, traumatic, hemorrhagic) are discussed with regard to the reflections of the blood coagulation. The therapy of shock-induced disorders of blood coagulation are focused on treatment of primary disease, prevention or elimination of microthrombi, substitution of blood respective plasma components.
Mechanisms of altered myocardial contractility during hemodialysis: importance of changes in the ionized calcium to plasma potassium ratio.
Hemodialysis is associated with alterations in myocardial contractility, but duration and precise determinants responsible for these changes are unknown. We investigated the effect of several variables, established to influence left ventricular (LV) contractility, which normally changed during dialysis: the plasma concentrations of ionized calcium, potassium, bicarbonate, and magnesium and the removal of uremic toxins. The influence of three different isovolemic bicarbonate-dialysis procedures in 16 patients with normal (group 1) and hypertrophied myocardium (group 2) was assessed by echocardiography prior to and up to 44 h following each dialysis. During the first procedure, ionized calcium and potassium concentration decreased, but LV performance remained unchanged in both groups. The second procedure with increased ionized calcium and decreased potassium concentration resulted in an improvement of mean circumferential fiber shortening (VCF from 1.15 to 1.56 circ/s (P less than 0.001) in group 1 and from 1.05 to 1.16 circ/s (P less than 0.05) in group 2. The positive inotropic effect declined gradually up to 12 h (group 1) and 2.5 h (group 2) respectively. In the third procedure when ionized calcium was increased and potassium concentration remained unchanged contractility did not improve. Removal of uremic toxins, decrease in magnesium, and increase in bicarbonate concentrations were comparable during each procedure. These results suggest that the ionized calcium to potassium ratio is the important determinant of dialysis-related augmentation in LV contractility. In LV hypertrophy the expected contractile response is diminished indicating a depressed inotropic state.
[Pathophysiology of the microcirculation].
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[Indications for coagulation-active treatment in intensive care stations in hospitals without and with coronary angiography].
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Comparison of sympathomimetic amines with collagen, calcium ionophor and adenosine diphosphate in their effects on thromboxane formation of human platelet rich plasma.
Platelet rich plasma (PRP) was stimulated by addition of epinephrine, norepinephrine, dopamine, dobutamine, ADP, collagen or A 23187 in various concentrations. Before, during and after aggregation the levels of thromboxane B2 (TxB2) were measured by radioimmunoassay. After addition of collagen or A 23187 a strong stimulation of thromboxane synthesis was observed, beginning with the early aggregation phase. TxB2 values after complete aggregation amounted to 110-220 ng/ml and up to 500 ng/ml, respectively. After ADP, epinephrine and norepinephrine the thromboxane formation took place mainly in the late aggregation phase and reached levels of 37-51 ng TxB2/ml PRP. Dopamine and dobutamine in concentrations up to 50 microM failed to stimulate platelet's thromboxane synthesis and induced only small changes of optical density of PRP.
Influence of fluid removal rate during hemodialysis on left ventricular performance and exercise tolerance in patients with coronary artery disease.
The effect of hemodialysis (HD) on left ventricular (LV) function and exercise tolerance were measured at rest and during exercise using gated equilibrium radionuclide ventriculography in seven patients with confirmed coronary artery disease (CAD). To separate the effects of fluid removal rate on LV function in CAD, we investigated the same patients with identical overall volume loss of 4 liters during two different treatment times (4 hr and 2 hr). HD significantly increased resting LV ejection fraction (EF) from 55.7 +/- 8% to 64.7 +/- 8% (P less than 0.01) during the 4 hr HD and from 58.1 +/- 9 to 68.1 +/- 10 (P less than 0.05) during the 2 hr HD. Indicating ischemia, EF decreased at pre- and postdialysis peak exercise without differences between both treatments. HD also resulted in an improved segmental wall motion score. Exercise duration as well as S-T segment depression and angina score improved during HD, whereas heart rate, blood pressure and double product remained unchanged. We conclude that HD improves global and regional resting LV function and exercise tolerance in patients with CAD. The degree of interdialytic hydration and not the degree of fluid removal per time affects LV performance in CAD. Since LV function is the major prognostic factor in CAD, those patients require volume restriction and/or shorter interdialytic phases.
[Problems in the education of physicians in the Federal Republic of Germany. Address delivered at the opening of the Angiology Congress 1982].
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[Blood coagulation and the lung].
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