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Biomedical subjects

H Heimpel

Publications and source records attributed to H Heimpel.

At least 217 records · Page 12Linked to original sources
PubMed1984

Low-dose Ara-C in the treatment of acute leukemia. Cytotoxicity or differentiation induction?

The differentiation inducing effect of low-dose Ara-C on human myeloid leukemic cells was studied in two patients with subacute myelocytic and subacute myelomonocytic leukemia in vivo and in vitro. By continuous i.v. administration of 10 mg Ara-C/m2 over 12 h daily for 12 or 20 days complete remissions were obtained in both patients with normalization of the incidence of the committed progenitor cells BFU-E and CFU-C in the marrow while the incidence of pluripotent CFU-GEMM remained subnormal. Parallel cultures of the patients' bone marrow cells in diffusion chambers (DC) implanted in mice demonstrated a clear cytotoxic effect of low-dose Ara-C. The greater increase of granulopoietic cells within DC in the Ara-C exposed group than in control mice after the end of drug administration is, in addition, an indication for differentiation induction by this kind of Ara-C therapy.

Adult↗
PubMed1984

Treatment of refractory chronic idiopathic thrombocytopenic purpura with high dose intravenous immunoglobulin.

Three patients with a history of chronic idiopathic thrombocytopenic purpura stretching back over 20 years are reported. Despite splenectomy and immunosuppressive therapy satisfactory control of their disease has not been achieved. They had remained refractory to all therapeutic manoeuvres with corticosteroids and immunosuppressives for years with thrombocyte counts between 5,000 and 25,000/microliters and the concommitant risk of bleeding. This report describes the treatment of bleeding complications in these patients with high dose intravenous immunoglobulin; the peripheral blood thrombocyte count increased in all three patients from subnormal towards normal, but 2 to 4 weeks later returned to its initial low value. During the therapeutically induced raised thrombocyte count a normal bleeding time and only a moderate inhibition of thrombocyte adhesion and aggregation was observed resulting in reasonable haemostasis. High dose intravenous immunoglobulin is therefore a practical method for the control of bleeding complications in patients with refractory chronic idiopathic thrombocytopenic purpura. A clear explanation for its mode of action has not been found - the lymphocyte subpopulations remained unchanged and immunoglobulin production in vitro during the course of treatment was only minimally decreased.

Antibody Formation↗
PubMed1984

The relationship of lytic effects against autologous and allogeneic PHA blasts induced in human mixed lymphocyte cultures.

In addition to the cytotoxic T lymphocytes (CTL) killer cells which lyse autologous PHA lymphoblasts are also generated in mixed lymphocyte cultures (MLC). By modifying various tissue culture conditions, we demonstrate that the generation of allospecific effectors can be reduced but not the lytic activity against autologous PHA lymphoblasts. Cold target inhibition experiments showed a cross reaction between autologous and allogeneic PHA lymphoblasts. No inhibition was seen with fresh lymphocytes. It seems, therefore, that the measured lytic activity of specific CTL generated in a MLC is in fact partially mediated by cytotoxic cells which kill also autologous PHA lymphoblasts.

Cytotoxicity, Immunologic↗
PubMed1984

Variations in the susceptibility to lysis of NK target cells.

Natural killer (NK) cell activity varied considerably from one subject to another and in the same subject tested on different occasions. In addition to the interindividual variations, considerable variation was also found in the susceptibility to lysis of cultured target cell lines. In this report it is shown that the susceptibility to lysis of NK target cells depends on the growth phase of these cells but is independent of the cell cycle. These results may be important for interpreting NK cell data, may have some implications for transplantation experiments in animals using cultured tumor cells and are in agreement with the data describing the sensitivity of tumor cells to radiation or chemotherapy.

Adult↗
PubMed1984

Intensified therapy in acute lymphoblastic and acute undifferentiated leukemia in adults.

One hundred seventy adult patients with acute lymphoblastic leukemia (ALL) or acute undifferentiated leukemia (AUL) were entered into a prospective multicenter therapy trial at 25 hospitals. The aim of the trial was to improve remission duration by using a modified form of an intensified induction regimen that was successful in childhood ALL, to define immunologic subtypes of ALL by use of cell-surface markers, and to extract other possible prognostic factors. The overall complete remission rate was 77.8%. The median overall survival time was 26 months, being 4 months for nonresponders and 32 months for responders. The median remission duration for the 126 patients with complete remission was 20 months. Prognostically favorable factors for remission duration were response to chemotherapy within 4 weeks, age less than 35 years, a low initial leukocyte count, and the immunologic subtypes c-ALL with early response to therapy and T-ALL, where 61% and 58%, respectively, are still in complete remission at 3 years. An adverse influence on remission duration was observed for the subtype null-ALL, with a median survival of 13 months, and for patients with a delayed response to induction therapy, independent of phenotype.

Acute Disease↗
PubMed1983

Antimicrobial prophylaxis in acute leukaemia: prospective randomized study comparing two methods of selective decontamination.

In a prospective study the efficacy of two regimens for selective decontamination of the digestive tract was studied in patients with acute leukaemia during remission induction therapy. Seventy-eight patients were randomized to receive either a combination of cotrimoxazole, polymyxin B and nystatin (group A) or a combination of nalidixic acid, polymyxin B, neomycin and nystatin. With both regimens the gastrointestinal tract could be decontaminated equally effectively from potential pathogens. In the oropharyngeal region the decontamination from Enterobacteriaceae was significantly better in group A (P less than 0.01). In both groups less than 10% of the acquired infections were caused by gram-negative bacilli and no gram-negative septicaemia occurred in either group. The median time interval until the first acquired infection was 17 days in group A and 36 days in group B, respectively (P less than 0.05). It is concluded that regimen A might be more effective than regimen B though both regimens prevent reliably severe gram-negative infections.

Acute Disease↗
PubMed1983

Adjuvant chemo(immuno-)-therapy of primary breast cancer with adriamycin-cyclophosphamide (and levamisole)--six-year evaluation.

In a phase II-type study 52 patients with no signs of metastases but with a high risk of recurrence were treated with 6 courses of adriamycin-cyclophosphamide as adjuvant systemic therapy following modified radical mastectomy of primary breast cancer. Half of the patients were randomized to receive additional immunotherapy with levamisole for 2 yr. The scheduled dose and time regimen could be achieved in over 90% of patients. A comparison of the actuarial disease-free and overall survival with data reported in the literature indicates a similar positive effect of adjuvant systemic therapy as described in adjuvant studies using polychemotherapy regimens. Immunotherapy with levamisole has no effect on disease-free and overall survival but added to general toxicity. Particular attention was paid to psychological consequences of adjuvant systemic therapy; consistent attention by one specifically trained physician during the whole therapy and follow-up period was effective in coping with the emotional problems. The difficulties in treating recurrences after adjuvant therapy became apparent. A high rate of loco-regional recurrences and of cerebral metastases was noted.

Breast Neoplasms↗
PubMed1983

The evaluation of serial measurements of the NK cell activity in man.

Studies on the NK cell activity require extensive controls because it is known that a series of variables can influence both the quality of effector cells and of target cells. This known variation of the susceptibility to lysis in one target cell line or even in sublines requires "standards", if separately performed experiments should be compared. In some laboratories, the experiments have been controlled for the variation of the target cell's susceptibility to lysis; others control for the differences of NK cell activities among subjects or for the variation of the NK cell activity in individuals from day to day. Each of these methods concentrates the main point of control to a particular variable. To demonstrate the power of several variables in relation to an induced and expected variation of the NK cell activity, we describe in this paper the results of a factorial analysis of variance testing PB-MNC from healthy donors against two target cells. The in vitro treatment of PB-MNC by IFN was chosen as induced variation of NK cell activity. As variables of the system, we defined subjects, days, target cells, and the effect of IFN. It is shown that the induced variable (IFN-treatment) counts for the most powerful variance component (32% of the total variance). Other large variance components are the differences of NK cell activities among subjects (20%), the day to day variation of the subjects' NK cell activities (13%), and the day to day variation of the susceptibility of target cells to lysis (13%). Since it is almost impossible to control for all variables in an experiment, some variables have to be selected which should be controlled for. The quantification of the variables, which is possible by a factorial analysis of variance, is useful for that purpose. This method of data analysis allows to estimate further the relevance of a particular expected effect if several variables, as in NK cell tests, influence the result of the experiment.

Adult↗
PubMed1983

Cytogenetic studies in chronic myeloproliferative disorders.

Cytogenetic studies were performed on 113 patients with the clinical diagnosis of a chronic myeloproliferative disorder: 70 were classified as chronic myelocytic leukemia (CML), 8 as polycythemia vera (PV), 10 as osteomyelofibrosis/sclerosis (OMS), and 15 as unclassified myeloproliferative disorder (UMPD). 2 patients, 1 with UMPD and 1 with subacute leukemia, were reclassified as CML after the cytogenetic study. In the group comprising PV, OMS, and UMPD, 28% (9/32) had a chromosomally abnormal clone. The chromosomes affected involved those reported to show nonrandom alterations in myeloproliferative disorders, namely the chromosomes, 1, 7, 8, and 9.4 patients exhibited a loss of the Y-chromosome.

Adult↗
PubMed1983

[Recruiting patients and results of a preliminary study on the therapy of acute lymphatic leukemia and acute undifferentiated leukemia in adults].

The aim of the study was to improve remission quality through application of an intensified induction therapy successful in childhood ALL; in a modified form for patients of 15-35 years and in a reduced form for patients of greater than 35-65 years with ALL or AUL. The 8-week induction therapy consists of two phases. In phase I, prednisone, vincristine, daunorubicin, and L-asparaginase are given and in phase II, cyclophosphamide, cytosine-arabinoside, and 6-mercaptopurinee. As CNS-prophylaxis, intrathecal methotrexate, and CNS-irradiation with 24 Gy are used. After 3 months a re-induction therapy similar to the induction therapy is given with dexamethasone and adriamycin instead of prednisone and daunorubicin and without L-asparaginase. Maintenance therapy with 6-mercaptopurin and methotrexate follows over a period of 2 years. Since the formation of the study group in 1979 up to 30.06.81, 170 patients from 25 hospitals with newly diagnosed ALL or AUL were treated according to the protocol. Up to 30.11.81, 162 patients had completed treatment and were evaluable. Of these, 77.8% achieved complete remission, 80.7% in the age group 15-35 years and 68.3% in the age group greater than 35-65 years. The median survival time for all patients was 24 months and for the 126 patients with complete remission the median has not yet been reached (last observation 31 months). The median remission duration is 20 months. Prognostic factors for remission duration are (1) the number of chemotherapy courses required to reach complete remission, (2) the immunological subtype, (3) age and (4) initial leukocyte count.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1982

[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↗
PubMed1982

[Drug induced agranulocytosis].

Drug-induced agranulocytosis comprises a severe selective neutropenia in a hypersensitive individual. The compelling problem in a single case to determine the etiology of agranulocytosis results from multiple drug consumption, use of composed preparations and the unknown relative risk of most of the incriminated drugs. Immune and toxic mechanisms may be involved, however, the underlying pathomechanism does not correlate with typical hematological and clinical features of agranulocytosis. Prognosis is associated with the infectious state of the patient and the duration of the neutropenic phase which reflects the degree of impairment of bone marrow hemopoiesis. After withdrawal of all potentially hazardous drugs treatment of agranulocytosis follows the therapeutical approach in severe neutropenias due to cytostatic drug exposure.

Agranulocytosis↗
PubMed1982

Critical analysis of granulocyte function in 154 patients wtih different diseases.

Several granulocyte functions were analyzed in vitro in 154 patients with chronic or recurrent infections, as well as in a variety of disorders known or suspected to affect host resistance. Only a few specific abnormalities were diagnostic and occurred in congenital, hereditary disorders. Opposed to these permanent changes are those which were probably acquired or transient and are often multifactorial in origin. In the majority of these patients, an inconstant and nonspecific pattern emerged which is not helpful in the diagnosis of underlying disease. In selected patients, however, and as research procedures, these and related tests should be helpful in elucidating the basic functions of granulocytes and may implicate therapeutical approaches.

Adolescent↗