[Adriamycin-combination chemotherapy with or without immune stimulation by corynebacterium parvum in metastasizing carcinoma of the breast (author's transl)]. / Adriamycin-Kombinations-Chemotherapie mit oder ohne Immunstimulation durch Corynebacterium parvum beim metastasierenden Mammakarzinom. Ergebnisse einer prospektiven, randomisierten, multizentrischen Studie.

In a randomised, multicentre study the effect of changing the combined cytostatic treatment with VAC (vincristin, adriamycin, cyclophosphamide) to FMC (fluorouracil, methotrexate, cyclophosphamide) was tested, as well as the effect of active non-specific immune stimulation with Corynebacterium parvum, and compared with a control group. In 59 of 120 patients (49%) in whom the results could be analysed there was a measurable significant regression of tumour size to less than 50% of its initial value. The course was stabilized in a further 43 (36%) women. Further tumour-growth progression or death in the early phase of treatment occurred in only 18 women (15%). Average remission was 16 months. Median survival time from start of the study in all analysable patients averaged 22 months. Patients with an ulcer at the site of application of Corynebacterium parvum had a clearly prolonged survival time. In all, immune stimulation with Corynebacterium parvum was no better, either with regard to the remission rate, remission duration or survival time.

Proliferation characteristics of erythroblasts in chronic renal failure.

Proliferation of bone marrow erythroblasts in patients with chronic renal disease was studied by combined application of cytophotometric measurement of the DNA content and 3H-TdR labeling in vitro. A striking decrease of 3H-TdR labeling was found in most of the cases. The proportion of diploid (G0 + G1) as well as of tetraploid unlabeled cells (G2) was increased. The data suggest a disturbed induction of DNA synthesis of resting cells as well as an arrest of cells in G2 being responsable for ineffective cell production in this disease.

In vivo labeling of platelets with 75Se -- selenomethionine in patients with hepatic cirrhosis and thrombocytopenia.

Labeling of platelets in vivo by 75Se -- Selenomethionine (75Se-M) was performed in nine cases of hepatic cirrhosis and thrombocytopenia for evaluation of the kinetics of platelet maturation. Folic acid and vitamin B12 deficiency was excluded by pretreatment of the patients with these agents. The platelet maturation time -- time between the injection of the isotope and maximum radioactivity of separated blood platelets -- was shortened to 7.7 +/- 1.1 days (mean +/- SD) compared to the normal 9.1 +/- 1.4 days. For explanation a disturbance of megakaryocyte maturation and/or platelet release from the bone marrow is suggested.

In vivo study of platelet kinetics by 75Se-methionine in different haematological disorders.

Labeling of platelets in vivo by 75Se-methionine was performed in premalignant and malignant haematological disorders for evaluation of the kinetics of platelet maturation. The "normal" platelet maturation time (time between the injection of the isotope and maximum radioactivity of separated blood platelets) in eight non-haematological patients showing normal platelet counts was 9.1 days. A shortening of platelet maturation time of 5-7 days was observed in three of four cases with panmyelopathy (high bone marrow cellularity), in three of four cases with malignant lymphatic disorders (multiple myeloma, chronic lymphocytic leukaemia, lymphosarcoma), and in two of four cases with myeloproliferative syndromes. No correlation to the peripheral platelet counts was observed. For explanation of the premature platelet release from the bone marrow a disturbance of the megakaryocyte maturation is suggested.

Proliferation characteristics of lymphoid cells of human bone marrow in health and in chronic renal failure.

Proliferation of bone marrow lymphoid cells of 8 healthy subjects and 7 patients with chronic renal insufficiency was compared using the cytophotometric measurement of the DNA content combined with 3H-thymidine labelling in vitro. In renal insufficiency the cells showed a marked decrease of the proliferation activity. This is apparent from the impaired labelling indices and accumulation of diploid and unlabelled cells. The data suggest that the lymphoid cell proliferation is affected by the same pathophysiological mechanism as that leading to impairment of red cell production. By subclassification according to cytoplasmic basophilia, this proliferation disturbance could be related to the basophilic and not to the pale type of lymphoid cells.

Originalarbeiten.

In 5 cases of polycythaemia vera and 2 cases with other myeloproliferative disorders accompanied by thrombocythaemia (megakaryocytic myelosis), the megakaryocytes were differentiated and studied by use of the combined application of cytophotometric determination of the DNA content and autoradiography with tritiated thymidine (3H-TdR) in vitro. A shift to the right of the megakaryocyte series, occurence of high polyploidy cells at 64c and a decrease of the 3H-TdR-labeling indices were observed. The data suggest a disturbance of the rhythmical polyploidization of the megakaryocytes, consisting of an elevated proportion of rest cells at the different ploidy stages. The maturation capacity of megakaryocytes may be related more to the resting than to the DNA synthesizing cells.

Characterization of ineffective erythropoiesis in erythroleukaemia.

In 6 cases initially showing a symptomatology of erythroleukemia, the proliferation of erythroblasts was studied by combined Feulgen cytophotometry and autoradiography after labelling with 3H-TdR in vivo. A proliferation disturbance was observed consisting of an accumulation of diploid and unlabelled cells and a decreased proportion of cells in S. This defect occurred within the basophilic cell compartment in one case and within the early polychromatic cell compartment in all 6 cases. The results indicate the existence of out-of-cycle cells, which may be responsible for the inefficacy for erythropoiesis in this disease. The defect was present in all 4 cases with acute erythroleukaemia. In one of the two cases showing no deterioration of the physical and haematological condition over a period of years, an additional defect was observed, consisting of a striking accumulation of tetraploid unlabelled cells. Therefore, the technique used may be suitable as a diagnostic tool for evaluation of new types of ineffective erythropoiesis.