Type I collagen from calf skin, collagen modified by pepsin treatment, methylation, succinylation or deamidation, as well as the alpha-chains and cyanogen bromide peptides of the alpha1-chain were ...investigated with respect to their capacity to induce aggregation of human platelets. These preparations permitted an evaluation of the efficacy of the amino acid sequence, triple conformation,and various fibrillar structures in platelet aggregation. All collagens in dissolved in dissolved form (collagen dissolved at acid pH, pepsin-treated, methylated, deamidated, and succinylated collagen) induced platelet aggregation only after fibril formation. The arrangement of molecules within fibrils is of secondary importance. Modification of the side chains of amino acid residues affects primarily the formation of fibrils. The effect of these side chains on platelet aggregation is masked by the overwhelming potency of the fibrillar forms.
5 patients suffering from von Willebrand's syndrome were treated with DDAVP administered intravenously or intransally. The concentration of F. VIII-related activities (F. VIII:C, F. VIII R:AG, F. ...VIII R:WF), as well as the mobility of F. VIII R:AG in crossed immunoelectrophoresis and the alterations of bleeding time were continuously monitored. DDAVP induced both quantitative and qualitative changes of F. VIII-related properties. The bledding time was markedly reduced for some hours. The therapy was well tolerated and should be submitted to further clinical trials as a possible way to avoid the disadvantages connected with the transfusion of blood components.
Biochemical modulation of 5-fluorouracil (5-FU) by folinic acid (FA) increases the response rate in patients with metastatic colorectal cancer compared to 5-FU alone. Phase II trials also ...demonstrated increased efficacy when interferon was added to 5-FU. In two consecutive trials, 76 patients were treated on days 1-5 with FA 200 mg/m2 plus interferon 5 x 10(6) U/m2 and 5-FU 350 mg/m2 as intravenous bolus injection (n = 33, regimen A) or 5-FU 500 mg/m2 as 2-hour infusion (n = 43, regimen B), repeated every 3 weeks with individual 5-FU dose escalation in steps of 50 (regimen A) or 100 mg/m2 (regimen B). In regimen A 5-FU dose reduction to 300 mg/m2 due to toxicity was necessary in 49% of the patients; in regimen B a 5-FU dose of 600 mg/m2 or above was tolerated by 70% of the patients. Dose-limiting toxicity was severe mucositis and/or diarrhea. Objective responses were observed in 5 of 33 patients (15%) in regimen A (3-28%, 95% confidence interval) and 7 of 41 patients (17%) in regimen B (5-29%, 95% confidence interval). Median time to progression was 4.7 and 4.8 months, and median survival 9.9 and 11.4 months for regimens A and B, respectively. Prolonged 5-FU administration over 2 h allows the administration of a higher 5-FU dose compared to bolus injection with no apparent improvement in antineoplastic efficacy. The addition of interferon to the combination of 5-FU plus FA in this dose and schedule does not seem to improve the response rate but appears to increase treatment toxicity.
Blood samples were taken for haemostatic analysis from 225 patients with angina pectoris who were admitted to hospital for coronary angiography. beta thromboglobulin, platelet factor 3, platelet ...factor 4, factor VII:C, factor VIII:C, von Willebrand factor antigen, activated partial thromboplastin time, fibrinogen, antithrombin III, protein C:Ag, plasminogen, and antiplasmin were measured before angiography. Patients who had had a myocardial infarction in the two months before the investigation were excluded from the study. Multiple linear regression analysis showed that none of the haemostatic variables contributed independently to the prediction of an angiographic score that indicated the extent of coronary atherosclerosis. History of myocardial infarction, male sex, worsening of angina pectoris, serum triglycerides, and ejection fraction were independently associated with the angiographic score. There were some significant correlations between haemostatic variables and conventional risk factors for coronary heart disease. Thus data obtained from haemostatic analyses of peripheral venous blood do not permit the presence or the extent of atherosclerosis in coronary arteries to be predicted.
One hundred and fifty-nine patients with chronic myelogenous leukemia have been treated in six studies during 10 years at Hannover Medical School University Center. The prognosis of 111 patients ...without pretreatment has been improved compared to conventional therapy with a median survival of 5.7 years. Cytogenetic remissions have been induced in all studies followed for a longer time. The most pronounced improvement of prognosis has been observed in these patients.
Several conclusions can be drawn on the basis of the results on the different treatment concepts: 1. Patients with pretreatment have an unfavourable response to interferon. 2. There is a likely effect of the dose of Interferon alpha on the frequency of cytogenetic remissions. 3. The combination of Interferon alpha and interferon gamma has been toxic and ineffective in a pilot study. 4. The combination of interferon and cytosine arabinoside has a positive impact on the frequency of cytogenetic remissions. A continuous parallel application of both drugs seems to be most effective in this respect. An ongoing trial has been initiated to compare a fixed combination of Interferon alpha and cytosine arabinoside and with hydroxyurea respectively. Additionally the feasibility of autologous peripheral blood stem cell transplantation will be studied in patients with insufficient response to the interferon treatment.
Scanning microscopic investigations show the interaction of Leukocytes and Erythrocytes with fibrillar and aggregating type I and type III collagens in vitro. Leukocytes, in the presence of collagen, ...form loose aggregates within a minute and these aggregates, after 15 to 30 minutes, coalesce and become compact. The close association of the fibrillar collagens to the leukocyte surfaces is shown. Fibrillar collagen and collagen in solution with erythrocytes form only loose aggregates. Qualitative differences between the various collagen preparations were not found. The pathogenetic implications of these observations are briefly discussed.
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