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Biomedical subjects

W Linkesch

Publications and source records attributed to W Linkesch.

At least 91 records · Page 5Linked to original sources

[Myelosarcoma of the ovary].

The case is reported of a patient with granulocytic sarcoma of the right ovary and infiltration of granulocytic precursor cells into abdominal lymph nodes without any evidence of acute leukaemia on examination of the blood and bone marrow. Removal of the tumour and subsequent polychemotherapy was followed by remission. A local recurrence was treated with radiation and high-dose polychemotherapy. The patient has now been in complete remission for seven years. Thus, granulocytic sarcoma may have a good prognosis if treated with aggressive therapy, including operation, radiation, and high-dosage polychemotherapy.

Adult↗

[Defects in the prostaglandin system. IX. Lipoxygenase defect of thrombocytes in a patient with polycythemia vera].

Patients with the myeloproliferative syndrome (MPS) often show morphological and functional platelet abnormalities and an increased incidence of lowered cyclooxygenase- and/or lipoxygenase activity. We present the case history of a 68-year-old male patient with polycythaemia vera in whom an absolute absence of platelet lipoxygenase activity has been detected for the first time in the literature.

Aged↗

Experimental treatment of chronic lymphocytic leukemia with extracorporeal photochemotherapy. Initial observations.

Based on the encouraging results obtained with extracorporeal photochemotherapy (EP) in the treatment of the exfoliative erythrodermic form of cutaneous T-cell lymphoma (CTCL), leukemic form, as well as other T-cell-mediated diseases we evaluated the therapeutic potential of EP in patients with chronic lymphocytic leukemia (B-CLL). Three patients with B-CLL were treated for a period of 1 year. Two patients showed stabilization of disease, as demonstrated by reduction in their peripheral white blood cell count, with one patient showing lymph-node resolution. A third patient with significant intolerance to previous chemotherapy did not respond within the observed period. No significant side effects of EP were observed. Our observations suggest that EP may have a positive effect on the course of B-CLL in selected patients. Additional clinical trials are warranted to further define the role of EP alone or in combination therapy in the management of B-CLL.

Adult↗

Impaired conversion of exogenous arachidonic acid by platelets to thromboxane B2 and correction of that deficiency by interferon-alpha.

In the course of an investigation of cyclooxygenase and 12-lipoxygenase activity in platelets of patients with myeloproliferative syndrome receiving treatment with interferon-alpha 2 patients showed unusual results which have not been reported so far. Both patients had thrombocytosis, in one case associated with polycythaemia. In platelets of both patients, a reduced conversion of exogenous 14C arachidonic acid to TXB2 was observed accompanied by a shift in conversion to PGE2 and 12-HETE in one patient and to 12-HETE alone in the other before therapy. These findings were paradoxically associated with evidence of enhanced platelet activation in vivo. Treatment of both patients with interferon-alpha resulted in reversal of the biochemical abnormalities and in clinical remission.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗

Effect of recombinant interferon-alpha2C on reticuloendothelial function in patients with thrombocytosis.

The aim of the study was to investigate the influence of recombinant interferon-alpha 2C (rIFN-alpha 2C) on the in vivo Fc-dependent phagocytic activity of the reticuloendothelial (RE) system. Fourteen patients with excessive thrombocytosis due to myeloproliferative disorders were studied before and 3 months after initiation of therapy. RE function was determined by measuring the clearance of autologous red blood cells (RBC) labeled with 51Cr and sensitized with anti-D antibody. Eleven of the 14 patients responded to rIFN-alpha 2 treatment (platelets, less than 440 X 10(9)/liter). Rather in contrast to a shortening of platelet half-life and an increase (trendwise) in platelet-bound IgG, rIFN-alpha 2 caused a significant impairment of RE function. Although this finding could in part be accounted for by the treatment-related decrease in splenic volume, statistical analysis revealed a direct influence of rIFN-alpha 2 on RBC clearance (p less than 0.01). Our study results might be explained by an interferon (IFN)-induced, intensified expression of Fc receptors on platelet (and leukocyte) surfaces, possibly enhancing unspecific binding of IgG to their cellular membranes. The subsequent increased platelet uptake may lead to an overloading of the RE system causing impaired reactions to additional stimuli such as IgG-coated RBC.

Aged↗

Interferon-alpha-induced morphological changes of megakaryocytes: a histomorphometrical study on bone marrow biopsies in chronic myeloproliferative disorders with excessive thrombocytosis.

Interferon(rIFN)-alpha, a successful therapeutic agent in the control of thrombocytosis, has been shown to suppress human megakaryopoiesis. We investigated bone marrow biopsies from 12 patients with thrombocytosis due to chronic myeloproliferative disorders. Prior to treatment as well as during rIFN-alpha-2c therapy, several morphometric parameters of megakaryopoiesis were evaluated. Megakaryocyte density decreased significantly in all patients, megakaryocyte size decreased in polycythaemia vera, agnogenic myeloid metaplasia, and essential thrombocythaemia, but increased in chronic myeloid leukaemia. The various changes observed during therapy indicate an inhibitory effect of rIFN-alpha-2c on megakaryopoiesis and suggest a selective influence on megakaryocytes at various stages of maturation. Increased numbers of pyknotic (bare) nuclei may reflect a shortening of megakaryocyte life-span. No remarkable changes were found in the fibre content of the bone marrow.

Aged↗

Long-term alpha-interferon therapy in myelodysplastic syndromes.

The myelodysplastic syndrome (MDS) is characterized by a high probability of leukemic transformation and frequently lethal infections or bleeding episodes. Up to now, no generally accepted form of therapy has been established for MDS. Previous trials with alpha-interferon (IFN-alpha) have shown some beneficial effects. We studied the effects of long-term application of IFN-alpha at higher dosages in patients with "low-risk" MDS. Ten patients were included in the study; eight were treated for a period of 6-36 months. IFN-alpha was administered at a median dosage of 9, 6, 4 mU/week during the first, second, and third year, respectively. Response was determined by the status of peripheral blood and bone marrow. Prolonged exposure to IFN resulted in a response rate of 3/10 (30%). In an additional case, disease progression was retarded during the third year of therapy. The incidences of infections and bleeding events subsided notably. After the withdrawal of IFN, hematological and clinical parameters rapidly deteriorated in some patients. The observed improvement of the patients' susceptibility to infections possibly prolongs their survival and seems to justify further trials on IFN treatment in patients with MDS.

Aged↗

[The cholesterol risk factor--initial results of a screening study in industries].

After the distribution of suitably informative leaflets all the employees of 2 companies were invited to participate in a screening programme with the aim of detecting elevated cholesterol levels. 238 out of 510 employees participated in the screening. Related to the age-adjusted Austrian recommendations for the upper limit of normal values, cholesterol was elevated in 73 people (30.7%). The percentage of smokers was slightly below the Austrian rate with 26% in company M and 30% in company H. All the participants were informed of their laboratory results within one week. Participants with a moderately or extremely increased risk were invited to a personal talk. Furthermore, a number of other previously undetected abnormalities were detected in 41 cases (17.2%), leading to subsequent clinical diagnosis and treatment. In addition, 3 plasma factor defects were discovered. These investigations served as a foundation for a more intensive planned programme. A continuation of this screening procedure is planned involving about 10,000 people per year.

Adult↗

[Cholesterol screening in a bank for the detection of a risk population].

In October 1987 voluntary screening for cholesterol war performed in a bank. After preceding information had been issued to the participants 25 ml blood were drawn on 4 days from 667 employees (48.9% males, 51.1% females) for determination of the blood lipids and other parameters. The mean age (range 19 to 60) was 39 +/- 9 years; 29.2% were smokers. The mean cholesterol level amounted to 212 mg/dl. According to age- and sex-related normal values 42% exhibited an increased risk, whereby the percentage was particularly high (55%) in the age group under 30 years.

Adult↗

Long-term interferon therapy for thrombocytosis in myeloproliferative diseases.

31 patients with thrombocytosis associated with myeloproliferative disorders were included in a prospective trial of long-term interferon therapy. 6 patients (19%) had side-effects which required withdrawal of interferon within one year. 22 patients (71%) achieved and maintained a complete response (platelet count less than 440 x 10(9)/l) for at least twelve months, with reduction or abolition of symptoms associated with thrombocytosis and a significant fall in bone-marrow megakaryocytes. At twelve months, 25 patients were randomly allocated to maintenance or withdrawal of interferon. Thrombocytosis recurred rapidly when treatment was stopped, but a second remission could be achieved by resumption of interferon therapy.

Aged↗

Giant hemangioma of the liver (Kasabach-Merritt syndrome): successful suppression of intravascular coagulation permitting surgical removal.

The clinical course of a patient presenting with thrombocytopenia (86 X 10(3)/L) and signs of intravascular coagulation (prothrombin time, 45%; partial thromboplastin time, 49 s; fibrinogen, 40 mg/dl; antithrombin III, 85%; factor X, 73%; plasminogen, 42%) due to a giant hemangioma of the liver (Kasabach-Merritt syndrome) is reported. Treatment with i.v. heparin, fibrinogen, and fresh-frozen plasma led to significant elevation of fibrinogen (156 mg/dl) and antithrombin III (102%) without changing the decreased activities of the procoagulant factors. Similarly, the signs of hyperfibrinolysis persisted (fibrinogen degradation products, 50 micrograms/dl; plasminogen, 43%; alpha-2 antiplasmin, 74%). The hemangioma was completely removed by excision of the left lobe of the liver. Subsequently, all coagulation parameters returned to normal, indicating a complete reversibility of the coagulation disorder.

Adult↗

Effect of cell growth and cell differentiation on 1-beta-D-arabinofuranosylcytosine metabolism in myeloid cells.

Resistance of leukaemic blasts to 1-beta-D-arabinofuranosylcytosine (ara-C) has been shown to be associated with changes in the metabolism of this drug. However, effects of cell growth and maturation stage on ara-C metabolizing enzymes have to be excluded as a possible cause of different enzyme activities in leukaemic blasts between nonresponders and patients achieving complete remission. We evaluated the effects of cell cycle phase and cell differentiation on the activity of cytidine deaminase, deoxycytidylate deaminase and deoxycytidine kinase in myeloid cell lines. Our data indicate that different enzyme profiles in nonresponders might not only be caused by the emergence of mutator phenotypes but may also reflect the growth and maturation stage of leukaemic blasts.

Cell Cycle↗

Amsacrine, cytarabine and thioguanine (AAT) versus daunorubicin, cytarabine, thioguanine (DAT) in adults with untreated acute non-lymphoblastic leukemia (ANLL). Austrian-German results.

69 patients (median age 53 years, 19-79 years old) with untreated acute non-lymphoblastic leukemia (ANLL) were randomized to receive either a regimen of amsacrine, cytarabine, thioguanine (AAT) or daunorubicin, cytarabine, thioguanine (DAT). AAT consisted of amsacrine 200 mg/m2/day x 5, thioguanine 100 mg/m2/12 h p.o. x 10; DAT was daunorubicin 50 mg/m2/day x 3, cytarabine 200 mg/m2/day x 5, thioguanine 100 mg/m2/12 h p.o. x 10. After one or two induction courses the patients subsequently received 2 consolidation courses. 17 patients were not assessable for response to therapy due to exitus during induction treatment. Complete remission could be obtained in 14/24 (58%) of DAT patients respectively. Patients less than 60 years of age achieved CR in 63% (AAT) vs 65% (DAT), whereas patients greater than or equal to 60 years obtained a CR in 50% (AAT) vs 13% (DAT). Toxicity appears not to be increased significantly with amsacrine. These data indicate that amsacrine could replace daunorubicin in remission induction regimens of ANLL containing cytosin arabinoside and thioguanine without decreasing the response rate.

Adolescent↗

In vivo tracing of indium-111 oxine-labeled human peripheral blood mononuclear cells in patients with lymphatic malignancies.

The in vivo migration of [111In]oxine-labeled peripheral mononuclear cells (PMNC) was studied in 20 patients with various lymphatic malignancies and palpable enlarged lymph nodes. The maximal labeling dose of 10 microCi (0.37 MBq) [111In]oxine/10(8) PMNC was found not to adversely influence either cell viability or lymphocyte proliferation in vitro. For in vivo studies, 1.5 X 10(9) PMNC were gained by lymphapheresis and reinjected intravenously after radioactive labeling, 150 microCi (5.55 MBq). The labeling of enlarged palpable lymph nodes was achieved in three out of three patients with Hodgkin's disease and in five out of five with high-malignant lymphoma, whereas three out of seven patients with low malignant lymphoma and no patient with chronic lymphatic leukemia had positive lymph node imaging. We thus conclude that PMNC retain their ability to migrate after [111In]oxine labeling and that these cells traffic to involved lymph nodes of some, but not all hematologic malignancies.

Adult↗

[Defects in the prostaglandin system. VIII. A pathologic thrombocyte population in myeloproliferative syndrome, which forms no thromboxane from exogenous arachidonic acid].

In 2 out of 29 patients suffering from the myeloproliferative syndrome a lack of thromboxane conversion by platelets from exogenous arachidonic acid was discovered. In one patient PGE2 (30.9%) and 12-HETE (12-Hydroxyeicosatetraenoic acid) (42.8%) were formed instead, whilst in the other patient 12-HETE (72.9%) was the main metabolic product. In both the patients, serum and plasma TXB2, as well as malondialdehyde, were quite low. It is claimed that this phenomenon is due to the expression of a pathological population of platelets related to the disease.

Aged↗

Shift in phenotype of acute T-lymphocytic leukemia to eosinophilic leukemia: a case report.

Acute T-lymphocytic leukemia diagnosed in a 14-year old boy on the basis of typical cell morphology, as well as by membrane antigen analysis with monoclonal antibodies, shifted to the phenotype of an acute eosinophilic leukemia 5 months after the initiation of chemotherapy. The transformation was evident by a change in morphology of cells derived from bone marrow aspirates, by cytochemistry and by a shift in the membrane antigen pattern.

Adolescent↗