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Biomedical subjects

K Geissler

Publications and source records attributed to K Geissler.

At least 163 records · Page 9Linked to original sources

[Bone marrow transplantation in chronic myeloid leukemia--experiences in 16 patients].

Between January 1983 and December 1986 16 patients (8 f, 8 m, median age 31.5 years, 14-41) with chronic myelocytic leukaemia (CML) received bone marrow grafts from their HLA compatible sibling donors. 11 patients were in the chronic and 4 in the accelerated phase. 1 patient was in lymphatic blast crisis. The patients were pretreated with busulfan (n = 15, total dose: 100-1000 mg, median: 225), mitobromitol (1 pat.), hydroxyurea (2 pats.), pre-irradiation of the spleen with 800 rad (1 pat.) and one patient had received 3 cycles of vincristin and prednisolone. The conditioning regimen consisted of cyclophosphamide (120 mg/kg) and total body irradiation (1000 rad, lung 800 rad). The prophylaxis against graft versus host disease (GVH-D) consisted of methotrexate (MTX) in 14 patients and of MTX in combination with cyclosporin-A in 2. At present (January 15th 1987) 9 patients survive 30 to 1210 days (median 1009) post graft (6/11 grafted in chronic, 2 of 4 in accelerated phase and 1/1 grafted in blast crisis. The causes of death were interstitial pneumonitis (CMV-associated, 2 pats.), venoocclusive disease of the liver (2 pats.), acute GVH-D and septicemia (2 pat.) and relapse (1 pat.). The Karnovsky score of 8/9 survivors is 100%, one patient has a score of 70% due to chronic GVH-D. Bone marrow transplantation for CML bears a high risk of early mortality but offers the unique option of permanent eradication of leukaemic haemopoiesis with subsequent long term survival.

Adolescent↗

[Oral anticoagulant therapy--renaissance of an old therapy?].

Although the antithrombotic potential of oral anticoagulants is undisputed, bleeding complications constitute a serious problem. One of the main causes for these complications has been a lack of standardization of the prothrombin time. The introduction of the International Normalized Ratio (INR) has led to a better standardization of prothrombin time. Thus, the same level of anticoagulation can be reached using different reagents and therefore over- and undercoagulation can be avoided. Furthermore, the benefit/risk ratio can be improved by adapting the intensity of anticoagulation to the indication. The following clinical conditions are established indications for treatment with oral anticoagulants: Prevention of cardiac emboli in acute anterior myocardial infarction with atrial thrombus, in patients with atrial fibrillation with or without mitral valve disease, in patients with prosthetic heart valves and in patients with dilated cardiomyopathy. Furthermore, oral anticoagulants should be given to patients after femoropopliteal bypass. A relatively mild oral anticoagulant treatment (INR 2-3) is sufficient to prevent recurrences of venous thrombosis and pulmonary emboli. The duration of treatment in patients with venous thromboembolism depends on some clinical features and the results of clotting tests which indicate an increased tendency to thrombosis.

Administration, Oral↗

In vitro culture studies of granulocyte/macrophage and erythroid progenitor cells in lymphoproliferative disorders.

Granulocyte/macrophage progenitor cells (CFU-GM) and erythroid progenitor cells (BFU-E) have been assayed in peripheral blood (PB) and/or bone marrow (BM) from 12 patients with acute lymphocytic leukemia (ALL), 16 patients with chronic lymphocytic leukemia (CLL) and 31 patients with various forms of non-Hodgkin lymphoma (NHL) without BM involvement. Progenitor cell growth in PB and BM from the NHL patients did not differ statistically from controls (p greater than 0.1). CFU-GM and BFU-E per ml PB were markedly increased in ALL and CLL patients (p less than 0.001) while CFU-GM and BFU-E per plated BM cells from these patients were severely depressed (p less than 0.001). Lymphoblasts from one ALL patient failed to inhibit CFU-GM and BFU-E-derived colony growth from control PB mononuclear cells. The high levels of circulating progenitor cells in ALL and CLL patients clearly distinguish them from other cytopenic hematological malignancies, in which decreased progenitor cell levels have been demonstrated previously (acute myeloid leukemia, hairy cell leukemia). The cause of this finding and its pathophysiological implication still remains to be established.

Bone Marrow↗

Myeloid progenitor cells in the peripheral blood of patients with hairy cell leukemia and other "leukemic" lymphoproliferative disorders.

We assayed granulocyte-macrophage committed progenitor cells (CFU-GM), erythroid committed progenitor cells (BFU-E) and pluripotent hemopoietic progenitor cells (CFU-MIX) in the peripheral blood of patients with hairy cell leukemia (HCL), acute lymphocytic leukemia (ALL) and chronic lymphocytic leukemia (CLL). In 8 HCL patients retaining their spleens, the number of circulating CFU-GM, BFU-E and CFU-MIX were under the lower limits of normal controls in 6, 6 and 5 cases, respectively, and were in the lower normal ranges in the remaining cases. Six splenectomized HCL patients had generally more circulating progenitor cells than their nonsplenectomized counterparts. In the peripheral blood of 2 patients with ALL and 3 patients with CLL, progenitor cells of all types were markedly increased compared to their respective values in the blood of control subjects. Hairy cells from 2 HCL patients failed to inhibit CFU-GM, BFU-E and CFU-MIX derived colony growth from control peripheral blood mononuclear cells. In 3 HCL patients previously low circulating progenitor cells did not rise 5-7 months after RC-alpha 2-IFN treatment despite normalization of peripheral blood counts. Our results suggest that a reduction of the committed and pluripotent progenitor cell compartment might be at least in part responsible for the pancytopenia in the majority of patients with HCL.

Adult↗

Treatment of severe aplastic anemia with combined immunosuppression (antithymocyte globulin and high-dose methylprednisolone).

Fifteen patients with transfusion-dependent severe aplastic anemia (SAA) were treated with combined immunosuppression consisting of horse-antithymocyte globulin (ATG; Atgam, Upjohn) and high-dose 6-methylprednisolone (MP). Oxymetholone was scheduled for 2 years but was discontinued in 7 patients after 10-385 days due to liver toxicity. Serious side effects usually seen in ATG monotherapy were rare during combined immunosuppression. Currently 12 of 15 patients are alive 110-1,275 days (median 475.5) after start of treatment. One patient has received too short treatment to be evaluated. All the others are transfusion-independent. Three patients died; two from septicemia before hemopoietic recovery could be expected and one after relapse. Our results confirm that the addition of high-dose MP abrogates the side effects of ATG monotherapy, and the addition of MP does not counteract, but rather enhances the beneficial effect of ATG in SAA. We recommend combined immunosuppressive treatment with ATG and high-dose MP as a highly feasible, safe and effectful therapy for patients with transfusion-dependent SAA.

Anemia, Aplastic↗

Circulating committed and pluripotent haemopoietic progenitor cells, in infants.

Circulating CFU-GM, BFU-E and CFU-MIX were assayed in 21 infants aged between 1 day and 44 weeks. Compared to 15 adults, progenitor cells of all types were increased until 10 weeks following birth and approached the respective ranges of adults thereafter. The mean increases of progenitor cells in infants aged between 1 day and 10 weeks were 26-fold for CFU-GM, 7-fold for BFU-E and 5-fold for CFU-MIX. Our results demonstrate that not only committed progenitor cells (CFU-GM, BFU-E), but also early progenitor cells with the capacity for self-renewal (CFU-MIX), are increased in early infancy. These data further support the hypothesis that high levels of blood progenitor cells in very early stages of life reflect the colonization process of developing bone marrow by circulating progenitor cells and demonstrate the terminal phase of this process during the first 10 weeks after birth.

Adult↗

[Antibodies against ds-DNA in systemic lupus erythematosus--value for diagnosis and determination of activity].

The specificities and sensitivities of 3 methods for detection of anti-ds-DNA-antibodies were investigated in 32 SLE-patients and 95 control patients with ANA greater than or equal to 1:100. The sensitivities of CL-IF-assay, filter-RIA and EIA were 47%, 78% and 87%, respectively. The according specificities were 96%, 88% and 84%. In contrast to the CL-IF-assay, the filter-RIA as well as the EIA are of major clinical importance in monitoring SLE-patients.

Antibodies, Antinuclear↗

Aplastic anemia: assessment of myeloid progenitor cells in the bone marrow and blood provides prognostic information.

15 patients with aplastic anemia were prospectively followed after having measurements of myeloid progenitor cells in bone marrow and blood. Treatment included androgens, low or high dose steroids and standardized supportive care. The median length of survival was 5.8 months. When patients were grouped according to the numbers of myeloid progenitor cells present in their blood and bone marrow, we found that the survival length of aplastic patients with higher progenitor cell numbers was prolonged when compared to that of patients with lower numbers of these cells. The prognostic information obtained from such in vitro cultures was particularly indicative when the patients were grouped according to 'growth' and 'no growth': the absence of colony-forming myeloid stem cells was associated with survival times significantly shorter than those of patients whose cells maintained their colony-forming capacity. Besides initial numbers of myeloid progenitor cells, only initial numbers of granulocytes were related to survival length. Thus, the measurement of myeloid progenitor cells in bone marrow and blood can be of prognostic value in patients with aplastic anemia.

Aged↗

[Clinical experiences with high-dose methotrexate].

40 patients with various forms of malignant disease, who had already been subjected to conventional regimens of treatment, were treated between 1976 and 1981 at the Department of Chemotherapy, Vienna University, with high-dose methotrexate (MTX) as sole therapeutic agent. 18 patients received MTX in moderately high doses of 250 mg/m2 to 750 mg/m2 at 10-day intervals. 19 patients were treated with high doses of 5 to 15 g MTX at 10-day intervals. In 2 cases of severe malignant non-Hodgkin's lymphoma one patient received 2 X 1 g MTX with an interval of 19 days between doses and the other received a single dose of 5 g MTX by infusion. One patient with alveolar soft part cell sarcoma was given ultra-high therapy, with a cumulative dose of 205 g. None of the patients in the group given moderately high-dose MTX therapy, whereas three in the high-dose group had an objective remission. Objective remission was obtained neither in the two lymphoma patients nor in the ultra-high-dose treated case. Complications such as leucopenia and/or thrombopenia were found in 9%, reversible transaminase activity increases in 45%, as well as a decrease in creatinine clearance in 10% of the cases. Irreversible severe kidney insufficiency was found in none of the cases. One patient with lymphoma died as a result of severe toxic epidermiolysis with involvement of the gastrointestinal mucosa, whilst the other suffered from pulmonary complications in the form of the respiratory distress syndrome. On the basis of our experience the use of high-dose MTX therapy as an alternative method following trials of all conventional regimens is not recommended.

Female↗

Tic-tac-toe.

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Artifacts↗

Foreign affairs.

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Artifacts↗

Influence of purified recombinant human macrophage colony stimulating factor in mice.

The endotoxin-resistant strain of mouse, C3H/Hej, was assessed for hematological responsiveness to multiple injections of high dosages of purified recombinant human macrophage colony stimulating factor (rhu-M-CSF). Mice were administered the rhu M-CSF i.p. at dosages of 40 micrograms per injection, 2 or 3 times per day for 4 days. This resulted in significant increases in circulating leukocytes compared to control mice given sterile pyrogen-free saline. Assessment of the marrow and spleen of these mice on the 5th day noted a significant reduction in the numbers of marrow hematopoietic progenitor cells, with no change in their cycling rates. In contrast, splenic granulocyte-macrophage and erythroid progenitor cell numbers were markedly increased and the cycling rates of these progenitors plus those of multipotential progenitors were significantly enhanced. Marrow and splenic early myeloid cells (blasts, promyelocytes, and myelocytes) and macrophages were increased, while marrow and splenic PMN were decreased. The results suggest that multiple injections of high dosages of rhu-M-CSF to previously untreated mice for a short period of time has a modest enhancing effect on blood leukocyte levels. This is associated with a shift of hematopoietic cell activity from the marrow to the spleen.

Animals↗

[Antibodies against ds-DNA and nucleoprotein in systemic lupus erythematosus--comparison of various determinative methods].

Five methods for the detection of antibodies against ds-DNA and nucleoprotein were compared with respect to their usefulness for the diagnosis and monitoring of SLE: filter radio-immunoassay (filter RIA), enzyme immunoassay (EIA N) and Crithidia lucilia assay (CL-IF) for detecting anti-ds-DNA antibodies as well as enzyme-immunoassay (EIA NP) and a latex test (LE test NP) for detecting anti-NP antibodies. In testing 32 SLE patients we obtained the following sensitivities: filter RIA 78%, EIA N 87%, CL-IF 47%, EIA NP 73% and LE test NP 25%. Among 95 patients having ANA greater than or equal to 1:100 in their sera, but who had no clinical signs of SLE, anti-ds-DNA antibodies were detectable in 12% (filter RIA), 16% (EIA N) and 4% (CL-IF) as well as anti-NP antibodies in 35% (EIA NP) and 4% (LE test NP). Only filter RIA and EIA N were of significant value in differentiating active from inactive SLE.

Autoantibodies↗