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Biomedical subjects

E Kurrle

Publications and source records attributed to E Kurrle.

At least 55 records · Page 3Linked to original sources

[Blood clotting factor XIII substitution in acute leukaemia: result of a randomized and controlled study].

A randomized and controlled study was undertaken to test whether substitution with factor XIII concentrates influences the clinical course in patients with acute leukaemia and acquired factor XIII deficiency (less than or equal to 60%). A control group of 31 patients was compared with a factor XIII-treated group of 29 patients. Partial factor XIII deficiency was successfully corrected by substitution. On the other hand, there was no statistically significant difference between the two patient groups in the frequency and severity of bleeding complications, transfusion requirements, and the number of remissions. Undesirable side-effects as a result of substitution treatment were not observed.

Acute Disease↗

Infection prophylaxis in acute leukaemia patients: comparison of selective and total antimicrobial decontamination of the gastrointestinal tract.

In a retrospective study, total antimicrobial decontamination with strict reverse isolation (ITD) and selective decontamination without isolation (SD) were compared as means of preventing infection in patients with acute leukaemia. Thirty patients were treated with ITD and 34 patients with SD. The surveillance cultures indicated that aerobic gram-negative bacilli and yeast could be equally eliminated effectively in both the groups. The anaerobic flora was only minimally influenced by SD. The incidence of acquired infections was 1.17 per patient in group ITD as compared to 0.85 in group SD. In group ITD, acquired bacterial infections were mostly caused by gram-negative bacilli (63%) whereas in the group SD these microorganisms accounted only for 25% of the infections. In group SD the total number of fever days was significantly lower and the mean duration of pyrexial episodes was substantially shorter. The results indicate that SD is an effective and inexpensive method for preventing gram-negative infections and might be at least as effective as ITD.

Acute Disease↗

Risk factors for infections of the oropharynx and the respiratory tract in patients with acute leukemia.

The pathogenicity of microorganisms isolated by surveillance cultures, the neutrophil count in the peripheral blood, and the interaction of the two factors were analyzed as risk factors for infections of the oropharynx and the respiratory tract in patients with acute leukemia being treated in strict reverse isolation under antimicrobial modulation. A statistical method was developed for the identification of bacteria, the presence of which was correlated with an increased risk of infection. A significantly increased risk was found mainly for species of Klebsiella, Enterobacter, Proteus, and Pseudomonas. The degree of neutropenia was significantly correlated with the risk of infection, which was influenced by the microbiologic state of the oropharynx. Thus, patients with gram negative bacilli had significantly more days with infection at all levels of neutropenia than patients without gram-negative bacilli. These two risks factors were additive but did not potentiate each other.

Acute Disease↗

The efficiency of strict reverse isolation and antimicrobial decontamination in remission induction therapy of acute leukemia.

The efficiency of strict reverse isolation and antimicrobial decontamination in remission induction therapy of acute leukemia was studied retrospectively in 47 patients who were treated with a standardized aggressive chemotherapy of daunorubicin and cytosine arabinoside. Twenty-two patients were treated in strict reverse isolation with antimicrobial decontamination and 25 patients in the open ward without any measures against infections. In the patients in isolation the incidence of new infections per patient was 0.77 compared to 1.42 in the control group. The rate of complete remissions was 77% in the patients in isolation vs. 56% in the control patients.

Acute Disease↗

Culture of human haemopoietic cells in diffusion chambers. I. Growth of normal peripheral blood cells.

Growth of mononuclear cells from human peripheral blood from 10 normal individuals was tested in diffusion chamber culture over a period up to 17 or 21 days. After an initial decrease during the first few days an increase of the total cell number was observed with maximal values on day 13. In all individuals growth of undifferentiated blast cells, lymphocytes, plasma cells, immature and mature granulopoietic cells, macrophages, and megakaryocytes occurred. In all individuals the different cell types had similar growth patterns in diffusion chamber culture. The considerable numerical variations which were seen in the granulopoietic cells were probably due to different stem cell concentrations in the peripheral blood of the investigated individuals. The results indicate that the diffusion chamber technique is a valuable method for the detection of haemopoietic stem cells and the culture of lymphocytic cells in man.

Adult↗

Beneficial effect of granulocyte transfusions in patients with defects in granulocyte function and severe infections.

A 3-year-old boy (patient A) with a congenital and a 24-year-old man (patient B) with an acquired granulocyte function defect received supportive granulocyte transfusions for the management of severe infections. The boy had suffered from recurrent infections since bith. His granulocytes showed in vitro almost no chemotactic responsiveness, an impaired phagocytosis and reduced intracellular killing of Candida albicans. Family studies suggested that it was an inherited autosomal recessive defect. The child developed a Pseudomonas pneumonia at the age of 3 years, which did not respond to antibiotic therapy. Granulocyte transfusions were then started and soon after the fever and pneumonia disappeared. Patient B showed the haematological signs of a preleukaemic state. He had 3 recurrent episodes of furunculosis which led each time to cellulitis and septic temperatures accompanied by symptoms of an enterocolitis. Tests of granulocyte function in vitro showed reduced intracellular killing of Staphylococcus aureus. Granulocyte transfusions were started, since no clinical improvement could be attained by antibiotics. With transfusion therapy, fever, cellulitis and enterocolitis disappeared each time.

Adult↗

[Effectiveness of gnotobiotic measures in the treatment of acute leukemia: the results of a prospective randomized clinical study].

60 adult patients with acute leukemia (AL) previously untreated or in relapse received induction chemotherapy with different types of supportive care. Group A was decontaminated by nonabsorbable antibiotics in strict reverse isolation, group B was isolated only and group C was treated under routine hospital conditions. There were less infections in group A and B compared with group C. 76% of patients in group A achieved remission, in contrast to 57% in group B and 59% in group C. Late evaluation three years after termination of the study showed that all patients were dead except four patients being in first remission after discontinuation of maintenance treatment. Three patients were treated in group A, one patient in group C. However, the differences of survival and remission rates were not significant. Failure to demonstrate significant advantage of isolation and decontamination in treatment of AL was caused by insufficient suppression of microbes by the applied antimicrobial measures. Thus, it is suggested to investigate better antimicrobial treatment before gnotobiotic care is accepted as routine supportive treatment in AL.

Acute Disease↗

Increase of proliferative activity of leukaemic blast cells from human peripheral blood in liquid culture.

The proliferative behaviour of leukaemic cells from the peripheral blood of 12 patients suffering from acute leukaemia was investigated in short term liquid culture. In 3 cases of AML an increase of the blast cell number was observed exceeding the initial value whereas in 9 other cases the cell number decreased more or less rapidly. In 9 of these patients the proliferation kinetics of the cultured leukaemic blast cells were studied with 3H-thymidine labelling. In all these cases the labelling index increased during the first days of culture, in 3 cases to values of 48%, 45% and 38% on day 3. Only in 5 cases, however, did an absolute increase of the blast cells incorporating 3H-thymidine occur. Here the doubling times of the proliferating leukaemic blast cells were estimated to be 12, 13, 14, 28 and 55 h. Since a doubling time of 12 to 14 h seems to be too short to be explained only by an exponential growth of the initially proliferating cells it is postulated that leukaemic blast cells in a G0- or long G1-phase were present in the peripheral blood of these patients and that these entered the cell cycle during liquid culture.

Adolescent↗

Evidence for differentiation of human leukemic blood cells in diffusion chamber culture.

Peripheral blood cells of 21 patients with different forms of acute leukemia were cultured in diffusion chambers (5 x 10(5) cells/chamber) implanted intraperitoneally in 650 R preirradiated host mice over a period of up to 21 days. In patients with acute myeloid leukemia (AML), acute erythroleukemia (AEL), or acute myelomonocytic leukemia (AMMoL), the total number of cells which developed during this culture period exceeded the implanted value and also the values for normal peripheral blood cells from ten controls. In acute undifferentiated leukemia (AUL), two out of six patients showed considerable growth whereas the others, and also two patients with acute lymphoid leukemia (ALL), had poor growth. Differential counts revealed that the rise in total cells was due mainly to proliferation of blast cells and formation of granulopoietic cells. The latter exceeded the numbers from normal peripheral blood cells in 9 out of 13 patients with AML, AEL, or AMMoL and in 2 out of 6 patients with ALL. The production of granulopoiesis was not restricted to proliferating cells, but included mature cells which were of abnormal morphology in some cases. From the amount of granulopoiesis and the time of its development it was assumed that they were at least partly derived from leukemic blast cells. Chromosome analyses to decide whether the granulopoietic cells were of leukemic or normal cell origin are in progress.

Acute Disease↗

Growth and differentiation of rat bone marrow stem cells in diffusion chamber culture.

The growth of granulopoietic progenitors (CFU-C) and morphologically identifiable haemopoietic cells from rat bone marrow was studied in intraperitoneal diffusion chambers over a 6-day period. The aim of this study was to investigate whether stem cells preceding the granulopoietic progenitors are able to restore and to maintain depleted compartments of CFU-C and immature granulopoietic cells under the conditions of diffusion chamber culture. After treatment of rats with repeated doses of hydroxyurea (HU) a bone marrow cell suspension could be obtained wherein proliferating haemopoietic cells were reduced to a very low level and CFU-C to undetectable levels. During culture in diffusion chambers, growth of CFU-C, immature granulopoietic cells and macrophages could be observed from this HU-treated bone marrow. It is concluded that in diffusion chamber culture stem cells preceding CFU-C are able to rebuild functioning compartments of granulopoietic progenitors and morphologically identifiable haemopoietic cells.

Animals↗

Re-entry of resting leukaemic blood cells into proliferation in human acute leukaemia during diffusion chamber culture.

From 17 patients with different forms of acute leukaemia, mononuclear blood cells were cultured in diffusion chambers (DC) implanted intraperitoneally into pre-irradiated mice. In 14 patients, growth of blast cells could be observed during the culture period of up to 21 days. To question whether this growth of blast cells was due only to proliferation of the initially proliferating fraction or whether a re-entry of resting leukaemic cells into proliferation was involved, various 3H-thymidine (3H-TdR) labelling studies were carried out. The absolute increase of blast cells in EC showed no correlation with the fraction of leukaemic blast cells in DNA-synthesis in the implanted cell suspension as measured by 3H-TdR labelling in vitro. Furthermore, in 2 patients where the kinetic behaviour of initially labelled leukaemic blast cells was followed during DC culture, the increase in total blast cells could only be attributed to a small extent to proliferation of those cells initially in the cell cycle. Lastly, "in vivo" labelling during the culture period showed that in one case 25% and in another case 60% of the blast cells in DC were proliferating. The conclusion is that, owing to the stimulation of the diffusion chamber milieu and possibly also due to removal of an in vivo inhibition, in most cases of acute leukaemia resting leukaemic blast cells can apparently re-enter the active cell cycle. This has relevance for an understanding of the self-maintenance of the leukaemic cell population and may also be a reason for relapse of leukaemia after the usual cytostatic drug treatment which affects mainly the proliferating leukaemic cells.

Acute Disease↗

Experimental analysis of developing hemopoiesis in fetal bone marrow.

1. We have used fetal rats to study the following aspects of the development of hemopoiesis: (a) content of hemopoietic stem cells in fetal bone marrow, liver, and peripheral blood and (b) origin of hemopietic cells in the developing mammalian bone marrow. 2. In the studies we utilized the diffusion chamber technique to study the content of stem cells committed to granulopoiesis. The number of myelopoietic stem cells in liver peripheral blood and in "bone marrow" of 18-day-old rats is nearly identical. Since in "bone marrow" a considerable number of peripheral blood cells are present in the vessels at that time, whereas extravascular cells consist only of mesenchymal cells, one might assume that these peripheral blood cells give rise to granulocytic precursors in the cultures. Morphologically these cells are "blast" cells and lymphocytes. 3. Based on cell labeling indices of radioautograms, derived from continuous infusion of pregnant rats with [3H]thymidine, it could be shown that in the perichondral area mesenchymal cells of the fetus and newborn have a slow rate of DNA turnover whereas "bone marrow" cells are in an active state of profileration. 4. In further support of this it was also shown that injections of hydroxyurea (an agent which destroys cells in DNA synthesis) has vitrually no effect on perichondral mesenchymal cells whereas "bone marrow" cells were completely blocked in their ability to support myelopoietic differentiation in the diffusion chamber implants. 5. The conclusions would therefore be that (a) local perichondral cells, i.e., mesenchymal cells, do not contribute to marrow hemopoiesis, (b) matrix cells of the developing bone marrow cannot reconstitute hemopoiesis, and (c) hemopoietic bone marrow cells develop from migrating peripheral "stem cells", one of the sources being the liver.

Animals↗