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Biomedical subjects

R Seitz

Publications and source records attributed to R Seitz.

At least 73 records · Page 4Linked to original sources
PubMed1989

The disturbance of hemostasis in septic shock: role of neutrophil elastase and thrombin, effects of antithrombin III and plasma substitution.

In 42 patients with septic shock, 29 of whom underwent substitution with antithrombin III concentrate and fresh frozen plasma for coagulation disorders, the proteinase-inhibitor complexes thrombin-antithrombin III and neutrophil elastase-alpha 1 proteinase inhibitor, were elevated on admission. On admission, the elastase complex was significantly higher in the patients receiving substitution (p = 0.0039), but at the endpoint it was higher in the non-survivors (p = 0.0040). The elastase decrease was confined to the substitution group with the thrombin complex decreasing in both groups. Initially the thrombin complex correlated with prothrombin times and factor XIII, while the elastase complex correlated with creatinine, thrombocyte count and prothrombin times in the late stages. Hemostatic disturbance, thrombin generation and neutrophil elastase release were favorably influenced by substitution. Furthermore, in this uncontrolled pilot study, the survival rate was higher in the treated (16 of 29) than in the untreated (1 of 13) patients, although the treated patients initially had pronounced hemostatic disturbances.

Adolescent↗
PubMed1989

High-dose chemotherapy with autologous bone marrow support in advanced malignant melanoma.

Eight patients with advanced malignant melanoma were treated with high-dose melphalan (80-90 mg/m2) and BCNU (600-800 mg/m2). In all patients autologous bone marrow preservation was performed prior to therapy. Bone marrow was stored for 48 h in a refrigerator at 10 degrees C and reinfused 48 h post-therapy. Three patients had a complete response (CR), 1 a partial response and 4 patients no response. Two patients with CR died 4 and 5 months after therapy. One had an interstitial pneumonitis and 1 patient died from unknown cause. The third patient had a relapse 12 months after therapy. Major side effects were severe nausea/vomiting and a mild mucositis. Two patients suffered from BCNU-related encephalopathy. All patients had a full hematologic reconstitution after 6 weeks. High-dose chemotherapy with autologous bone marrow support achieves a high response rate. Long-term disease-free survival, however, was not seen with this approach.

Adult↗
PubMed1989

Influence of various concentrations of cefotiam and ceftizoxime on the phagocytosis of gonococci by polymorphonuclear granulocytes.

Both cefotiam and ceftizoxime stimulate the uptake of gonococci by polymorphonuclear granulocytes in vitro as can be seen by light microscopy. Although this already holds true of antibiotic concentrations lower than the minimum inhibitory concentration (MIC: 1/4 x) this effect is much more marked at concentrations highly exceeding the MIC (4000 x). As light microscopic investigation allows the analysis of large numbers of cells but no final judgement on actual bacterial engulfment definite phagocytosis is demonstrated by electron microscopy.

Cefotiam↗
PubMed1989

Reduced fibrinolytic capacity and its restoration by plasminogen substitution in acute renal failure.

A common finding in acute renal failure, particularly if it is caused by septic shock, consists of fibrin deposits in the intrarenal blood vessels. In a study of fibrinolytic parameters in 82 patients with severe bacterial infections, a significant negative correlation between plasminogen plasma concentration and serum creatinine was found. On admission the plasminogen levels were lower than the alpha 2-antiplasmin concentrations, which means a reduction of the fibrinolytic capacity due to a preponderance of the inhibitor. Preliminary experience with a replacement therapy is here reported. In 9 patients with an acute renal failure due to septicaemia or other serious diseases with shock, a substitution with fresh frozen plasma and antithrombin III concentrate was carried out in order to stop disseminated coagulation. A considerable increase of urine excretion was observed in 5 of these patients in close connection with the additional administration of a plasminogen concentrate.

Acute Kidney Injury↗
PubMed1988

Granulocyte-platelet interactions and platelet fibrinogen receptor exposure.

We have examined the interaction of human granulocyte elastase with human platelets. Incubation of human platelets with human granulocyte elastase exposed active fibrinogen-binding sites as evidenced by 125I-labeled fibrinogen binding and spontaneous fibrinogen-induced platelet aggregation. The aggregation of platelets by fibrinogen occurred at low concentrations of human granulocyte elastase (0.5-1 microgram/ml). Platelets pretreated with human granulocyte elastase exposed an average of 10,500 fibrinogen binding sites per platelet, i.e., about one-third the number of binding sites exposed by optimal concentrations of ADP. With the use of a polyclonal antiplatelet membrane antibody, the glycoproteins IIb (GPIIb), IIIa (GPIIIa), and a 60,000-Da (60 kDa) protein (66 kDa in a reduced system) derived from GPIIIa were immunoprecipitated from the surface of detergent extracts of human 125I-radiolabeled platelets pretreated with increasing concentrations of human granulocyte elastase. Experiments performed by immunoblotting with use of polyclonal and monoclonal antibodies directed to GPIIIa showed that pretreatment of human platelets with granulocyte elastase resulted in the appearance of an additional proteolytic derivative of GPIIIa migrating with an apparent molecular mass of 120 kDa in a nonreduced system. GPIIIa appears to be the preferred substrate of elastase, since GPIIb was not degraded by human granulocyte elastase. We conclude that 1) the proteolytic action of human granulocyte elastase on platelet GPIIIa results in the formation of two major hydrolytic products, and 2) human granulocyte elastase exposes active fibrinogen-binding sites associated with the GPIIb/GPIIIa complex, resulting in direct platelet aggregation by fibrinogen.

Adenosine Triphosphate↗
PubMed1987

[Significance of the thrombin-antithrombin III complex in the diagnosis of pulmonary embolism and deep venous thrombosis--comparison with fibrinopeptide A, platelet factor 4 and beta-thromboglobulin].

In 22 patients with suspected pulmonary embolism and 19 patients with suspected deep vein thrombosis, thrombin-antithrombin III complex (TAT) as an indicator of thrombin activation was measured using a newly developed ELISA. For comparison fibrinopeptide A (FPA), as a marker of an activated coagulation, as well as platelet factor 4 (PF4), and beta-thromboglobulin (beta-TG), as markers of platelet activation, were determined. In all patients in whom pulmonary embolism was confirmed by perfusion lung scan and in 15 of 16 patients in whom deep vein thrombosis was confirmed by phlebography, TAT exceeded the upper limit of normal (3.0 ng/ml). FPA was increased in 71% of the pulmonary embolism patients, PF4 in 53%, and beta-TG in 59%. The data for the patients with deep vein thrombosis were comparable. PF4 and beta-TG were increased in more than 25% of the normal controls, FPA in 17%, and TAT in 9%. TAT is very sensitive in detecting an activation of the coagulation system in patients with suspected thromboembolic events. The test, however, is not specific for thromboembolism; it only indicates an activation of the coagulation system. Acute pulmonary embolism or deep vein thrombosis would appear to be unlikely if TAT is normal. The measurement of TAT is easier and less susceptible to disturbances than that of FPA, PF4, and beta-TG.

Antithrombin III↗
PubMed1987

Possible interaction of platelets and adrenaline in the early phase of myocardial infarction.

It is known that in most cases of transmural acute myocardial infarction a platelet clot originates within a coronary artery. In acute myocardial infarction patients increased levels of the plasma catecholamines adrenaline and noradrenaline as well as the platelet release proteins platelet factor 4 and beta-thromboglobulin have been reported. In this study, significantly higher values were found of platelet factor 4 (P less than 0.0001) and beta-thromboglobulin (P less than 0.002) in 17 acute myocardial infarction patients as compared to 17 control patients (on intensive care due to non-cardiac disorders), while the plasma levels of adrenaline and noradrenaline were not different. Positive correlations were obtained between the two catecholamines and the platelet products in the control group and between adrenaline and both platelet factor 4 (r = 0.715, P less than 0.01) and beta-thromboglobulin (r = 0.547, P less than 0.05) in the acute myocardial infarction patients. The data suggest that a stimulation of the platelets by adrenaline may facilitate in vitro activation during sampling in patients with high catecholamine load. On the other hand, a "preactivation" of the platelets by an increase of adrenaline might be of significance for thrombus formation in acute myocardial infarction.

Adult↗
PubMed1987

Studies of local anesthetic action on natural spike activity in the aortic nerve of cats.

The aortic nerve was used to study the blocking action of procaine and bupivacaine on natural spike activity. In anesthetized cats, a segment of the aortic nerve was placed in a perfusion chamber and exposed to increasing drug concentrations, varying pH, while temperature remained constant. Total nerve activity was recorded continuously, and its change was related to drug concentration. The half-time of recovery following drug wash-out was also determined. At pH 7.4, the minimal blocking concentration was 0.5 X 10(-3) mol/l for procaine and 0.05 X 10(-3) mol/l for bupivacaine, the half-times of recovery 1.4 and 3.0 min, respectively. Procaine and bupivacaine reversibly blocked natural spike activity at the same concentrations as they blocked electrically evoked activity. The aortic nerve, whose physiologic spike traffic can be followed continuously for hours, may be used to advantage for studying the long-term effects of local anesthetics in vivo.

Action Potentials↗
PubMed1987

Participation and interactions of neutrophil elastase in haemostatic disorders of patients with severe infections.

The prognosis of septicaemia depends on the occurrence of complications such as shock and coagulation defects. The damage to haemostasis is usually explained by the action of the main coagulation and fibrinolysis enzymes, thrombin and plasmin. This paper presents data concerning the role of a third protease, granulocytic elastase. 82 patients who had been admitted to our hospital with suspected septicaemia were examined. Septicaemia was proven in 22 patients by the growth of microorganisms in blood cultures, and was clinically diagnosed in 9 patients. The plasma levels of neutrophil elastase-like protease complexed to a1antitrypsin (a1AT-ELP) were measured by zone immunoelectrophoresis assay (ZIA). The a1AT-ELP values were significantly increased in the 31 septic as compared to the 51 non-septic patients. In patients with complicated septicaemia, negative correlations of a1AT-ELP with factor XIII and the coagulation inhibitor antithrombin III were demonstrable. Among the patients with septic complications, the 3 who survived exhibited a dramatic decrease of a1AT-ELP, whereas in the other 16 patients who died the levels remained elevated. It might be of therapeutic significance that in 9 patients receiving fresh plasma and AT III-concentrate substitution for DIC the a1AT-ELP levels dropped, whereas they remained high in the other septicaemia patients. There were no correlations between a1AT-ELP and the a2antiplasmin-plasmin complexes (a2AP-P1), but strong correlations with signs of coagulation. The data suggest an interaction of coagulation and elastase release, probably involving the Hageman factor.

Anti-Bacterial Agents↗
PubMed1986

Impaired fibrinolysis and protein C increase after cadaver kidney transplantation.

Severe rejection crises occurred in 13 out of 20 cadaver kidney recipients; removal of the graft was inevitable in 10 cases. The plasminogen levels were found to be lower (76.5 +/- 2.9%) in the 13 patients with impaired graft acceptance (group B) than in the 7 patients experiencing only moderate rejection (group A, 93.7 +/- 5.2%, p less than 0.01) or the 41 patients with chronic renal disease (group C, 88.2 +/- 2.3%, p less than 0.01). Since alpha 2-antiplasmin was found to be enhanced, the alpha 2-antiplasmin/plasminogen ratio was high (1.56 +/- 0.07) in group B as compared with group A (1.19 +/- 0.05, p less than 0.002) and group C (1.11 +/- 0.04, p less than 0.001). The fibrinolytic capacity, which was assessed by a "reversed fibrin plate" assay, declined significantly after transplantation, and was lower in group B greater than 20 days after grafting. The neoantigen alpha 2-antiplasmin-plasmin complex was not detected in any patient; thus hyperfibrinolysis is unlikely to be responsible for the plasminogen decrease. Protein C rose above preoperative values (group A 117.1 +/- 8.7%; group B 133.7 +/- 9.0%) and reached higher levels in group A (221 +/- 24.1%) than in group B (157.4 +/- 14.8%, p less than 0.05) between days 11 and 20 after transplantation. No constant alterations were found with respect to antithrombin III and fibrinogen. Fibrin deposits, which reduce perfusion, can be found in the vessels of rejected kidney grafts. An impaired fibrinolytic capacity and a subsequent inability to remove these clots may be significant for the outcome of transplantation.

Adult↗