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Biomedical subjects

H D Waller

Publications and source records attributed to H D Waller.

At least 55 records · Page 3Linked to original sources
PubMed1987

Successful bone marrow transplantation from an unrelated donor in a child with AML in second remission.

In February 1986 we transplanted a 10-year-old girl with AML in second remission with the bone marrow of an unrelated donor. HLA-types were different for one A- and one B-antigen between patient and donor. Conditioning regimen consisted of 14 Gy total body irradiation with lung shielding, 8 X 3 g/m2 cytosin arabinoside and 90 mg/kg cyclophosphamide. GVHD-prophylaxis was performed with cyclosporin A, methotrexate and prednisolone. Only mild GVHD I of the skin could be observed after rapid engraftment. 100 days after transplantation the patient was in good clinical condition and GVHD-prophylaxis was discontinued without any reactivation of acute or chronic GVHD. Engraftment was documented by sex chromosome and blood group typing. 120 days after transplantation leukemic blasts were detected in the peripheral blood and the child died 130 days after BMT from relapse of the leukemia. Despite the negative outcome, this was the first successful bone marrow transplantation from a unrelated donor in Germany.

Bone Marrow Transplantation↗
PubMed1987

Philadelphia-positive chronic myelogenous leukemia with breakpoint 5' of the breakpoint cluster region but within the bcr gene.

We report on the first Philadelphia chromosome (Ph) positive chronic myelogenous leukemia (CML) characterized by a rearrangement within the 5' part of the bcr gene on chromosome 22, but outside the restricted breakpoint cluster region. In situ hybridization studies revealed a translocation of the c-abl oncogene to the Ph chromosome and Northern blot analysis identified a chimeric 8 kb bcr/abl RNA transcript in leukemic cells. These data suggest that 1. less bcr coding sequences than previously assumed may be essential for the putative transforming activity of the rearranged bcr/abl gene and 2. the bcr probes currently used for diagnostic purposes could miss Ph-positive CML cases.

Adult↗
PubMed1987

[Importance of HLA systems in the regulation of hematopoiesis].

Human hematopoiesis is known to be influenced by local microenvironments, as well as by a large number of specific soluble inhibitory or stimulatory mediators. It has been suggested that the HLA system plays an important role in the regulation of physiological and pathological hematopoietic cell proliferation and differentiation. The quality and quantity of HLA-antigen expression have been shown to influence interactions of colony-inhibitory factors with hematopoietic precursor cells. It is also assumed that HLA antigens mediate regulatory mechanisms of T-lymphocytes on the production of hematopoietic factors, as well as on hematopoietic cell proliferation and differentiation. The HLA antigens may thus participate in regulatory functions of the immune system in hematopoiesis.

Cell Differentiation↗
PubMed1987

[Pharmacokinetic aspects in the use of new cytostatic drugs].

A knowledge of pharmacokinetic data is essential for a rational treatment with cytotoxic drugs. The use of pharmacokinetics and insight into the metabolism make it possible to elucidate, predict or prevent toxicities after single and combined drug treatment. In addition, a careful monitoring in early clinical trials might help to find the optimal dose and schedule and to avoid less effective routes of application. This might improve the therapeutic range and efficacy of drug therapy in oncology.

Antineoplastic Agents↗
PubMed1987

Effect of free radical scavengers and metal ion chelators on hydrogen peroxide and phenylhydrazine induced red blood cell lipid peroxidation.

Desferrioxamine a well-known iron chelator was found to decrease hydrogen peroxide and phenylhydrazine induced lipid peroxidation of red blood cell membranes assessed by hydrocarbon gas release and loss of polyunsaturated fatty acids. Hydroxyl radical scavengers like mannitol and thiourea and proteins like albumin were unable to reduce peroxidative reactions to our system. Addition of uric acid (in an unphysiological concentration of 5 mM) to the incubation medium resulted in a slight reduction in H2O2/phenylhydrazine mediated break-down of arachidonic (20:4) and docosahexaenoic acid (22:6) in the erythrocyte membrane and consequently in a decreased alkane release and haemolysis.

Alkanes↗
PubMed1987

The relationship between lipid composition of red blood cells and their susceptibility to lipid peroxidation.

Red blood cells from 31 healthy donors were examined for the cholesterol content, the fatty acid composition, and the susceptibility to lipid peroxidation induced by either hydrogen peroxide or phenylhydrazine. Lipid peroxidation was monitored by the release of pentane and ethane. In addition, plasma fatty acids were measured in order to find out, whether plasma and red cell fatty acids were correlated. In experiments with hydrogen peroxide, a significant positive correlation was found between the proportion of arachidonic acid (C 20:4n - 6; r = 0.57, p less than 0.01) and docosahexaenoic acid (C 22:6n - 3; r = +0.71, p less than 0.01), and the release of pentane and ethane, respectively. A significant negative correlation was found between the membrane cholesterol content and the pentane release (r -0.44, p less than 0.05). In experiments performed with phenylhydrazine, red cell membrane lipid composition did not influence the susceptibility of red cells to lipid peroxidation. A close correlation was found between plasma and red cell fatty acids (palmitic acid, r = +0.46, p less than 0.01; linoleic acid, r = +0.41, p less than 0.05; arachidonic acid, r = +0.59, p less than 0.01; docosahexaenoic acid, r = +0.67, p less than 0.01). The results demonstrated that the degree of peroxide-induced oxidation of erythrocyte lipids depends on the content of polyunsaturated fatty acids in the membrane, which on the other hand, is determined by plasma fatty acids. It is suggested that dietary variations may influence the susceptibility of red cells to lipid peroxidation.

Adult↗
PubMed1987

Pregnancy after bone marrow transplantation for severe aplastic anemia.

Two women suffering from severe aplastic anemia were treated by bone marrow transplantation (BMT). They became pregnant 17 and 40 months after the procedure. During the first 20 weeks of pregnancy, one of them continued to receive cyclosporin A (CSA) to prevent graft-versus-host disease. Her CSA serum levels during these first 4 months ranged from 35 to 280 ng/ml. The course of pregnancy was uneventful and a healthy boy was delivered at term by Cesarean section. The other patient was shown to have rejected the transplanted marrow 4 months after BMT; autologous regeneration had occurred. During the last 2 months of her pregnancy, the hemoglobin and platelet numbers decreased again. Nevertheless, a healthy girl was delivered at term. Three months after delivery this patient's hematologic parameters are almost back to normal.

Anemia, Aplastic↗
PubMed1986

Plasma and red cell lipids in alcoholics with macrocytosis.

The cholesterol and phospholipid content and the fatty acid composition in plasma and red cell membranes was determined in 10 alcoholics with macrocytic erythrocytes. None of the patients had anemia. Red cells exhibited macrocytosis up to 108 fl in all patients. Bilirubin, albumin, prothrombin, and cholinesterase were in the normal range, whereas transaminases and gamma-glutamyl transpeptidase activities in serum were elevated in most of the patients. The molar ratio cholesterol/phospholipids in red cells was not altered in alcoholics. An abnormally high ratio of saturated/unsaturated fatty acids was found in plasma as well as in red cell phospholipids from alcoholics. Linoleic acid was substantially decreased in plasma of alcoholics (controls 32.3%, alcoholics 21.8%). This fatty acid abnormality was reflected by a decrease of linoleic acid in red cell phosphatidylcholine. The present data may suggest that fatty acid changes taking place in membranes of macrocytes were a consequence of changes in the plasma and reflect plasma/membrane exchanges rather than direct effects of ethanol on red cell membranes. Lipid alterations of red cell membranes may be involved in the development of macrocytosis in chronic alcoholism.

Adult↗
PubMed1986

Lipid abnormalities in plasma and red cell membranes of chronic alcoholics.

The fatty acid composition of plasma and red cell membranes was determined in alcoholics without liver dysfunction upon admission for withdrawal therapy and after a 4-week period of abstinence, and in normal subjects. Fatty acid analysis of plasma by capillary gas chromatography showed a higher proportion of saturated fatty acids in alcoholics on admission than in normal subjects. Other major differences in plasma fatty acids in alcoholics were the reduction of linoleic acid and the increase in palmitic acid. Similar abnormalities were measured in red cell membranes of alcoholics. Although there were less polyunsaturated fatty acids in red cells of alcoholics, the degree of hydrogen peroxide or phenylhydrazine-induced lipid peroxidation was the same as in controls. Membrane tolerance to ethanol was attributed to adaptive membrane alterations (increase of saturated fatty acids in membranes). However, the here reported changes in plasma and red cell lipids suggest that alterations in red cell membrane lipids reflect abnormalities in plasma lipids due to equilibrium exchanges rather than signify adaptive changes of the red cells to ethanol.

Adult↗
PubMed1986

Natural killer cell activity against a thymoma cell line Thy 121 in bone marrow transplant recipients.

Twenty-one patients with acute and chronic leukemia or severe aplastic anemia were studied for NK activity against a thymoma cell line (Thy 121) before and after allogeneic bone marrow transplantation. The means of the pretransplant and post-transplant levels did not differ from the mean of 134 NK determinations in 67 healthy donors. There was no correlation between pretransplant NK levels and the appearance of graft-versus-host disease. Three weeks following bone marrow transplantation, pretransplant NK levels were observed. The sensitivity of NK cells to interferon was the same as in normal donors both before and after bone marrow transplantation. In contrast to methotrexate, cyclosporin A inhibited NK activity in patients and controls in vitro. In vivo cyclosporin A treatment, however, did not decrease NK levels in bone marrow recipients.

Adolescent↗
PubMed1986

TAD-induction therapy for 175 adults with acute myeloid leukemia, followed by consolidation and maintenance therapy. The joint study of Ulm and Tübingen.

175 patients with acute myeloid leukemia were treated between February 1980 and March 1985 with a TAD-induction therapy, three intensified consolidation cycles (COAP, COAP, AD), and a two-year mild maintenance therapy. The median age of the patients was 44 years, range 15-68 years. 62.3% of all patients attained complete remission and 13.7% partial remission. The median duration of remission was 10 months and the median survival time of patients in complete remission was 20 months. Patients older than 50 years had a higher early death rate (17.6) than younger patients (8.9%), but no difference was found in remission rates or in the median duration of remission and of survival. These results are in line with those of comparable studies.

Adolescent↗
PubMed1986

[Serum lipids of alcoholics before and following abstinence. Significance for coronary risk].

Cholesterol, triglycerides, and lipoproteins were studied in 23 alcoholics on admission for withdrawal therapy and after 4 weeks of abstinence. Lipoproteins were estimated quantitatively by lipoprotein electrophoresis. The results were used for the prediction of the risk of coronary heart disease. Half of the alcoholics had "high" or "elevated coronary risk" on admission for withdrawal. Abstinence resulted in decreased HDL-cholesterol concentrations in serum. Concurrently, the number of alcoholics with elevated coronary risk increased. This was mainly caused by high LDL-cholesterol levels on admission and after abstinence.

Adult↗
PubMed1985

The fatty acid composition of red cells deficient in glucose-6-phosphate dehydrogenase and their susceptibility to lipid peroxidation.

Oxidant damage to red cell membranes could play a part in the pathogenesis of acute and chronic haemolysis in glucose-6-phosphate dehydrogenase deficiency. Therefore, we studied the substrate for red cell membrane lipid peroxidation, i.e. the content of various polyunsaturated fatty acids in ghosts, and the susceptibility of red cells to lipid peroxidation in normal subjects and in subjects deficient in glucose-6-phosphate dehydrogenase. The fatty acid composition of red cell membranes and plasma was analysed by capillary column gas chromatography. The sensitivity of red cells to lipid peroxidation was evaluated after hydrogen-peroxide-induced oxidant stress. The degree of lipid peroxidation was monitored by measuring the release of pentane and ethane formed during the breakdown of n-6 and n-3 fatty acids. The red cell sensitivity to lipid peroxidation was found to be higher in subjects with glucose-6-phosphate dehydrogenase deficiency than in normal subjects. In the former, saturated fatty acids, in particular palmitic and stearic acid, were found to be decreased, whereas the proportion of arachidonic acid showed a clear increase. Fatty acid analysis of plasma did not reveal significant abnormalities in enzyme-deficient patients, which could explain the alteration of membrane fatty acids. Our results suggest that the increased content of substrate for lipid peroxidation, particularly arachidonic acid, in red cell membranes of subjects deficient in glucose-6-phosphate dehydrogenase, should be considered in an evaluation of an enhanced sensitivity to red cell lipid peroxidation.

Erythrocyte Membrane↗