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Biomedical subjects

W Hunstein

Publications and source records attributed to W Hunstein.

At least 73 records · Page 4Linked to original sources
PubMed1987

Combination of low-dose cytarabine and 13-cis retinoic acid in the treatment of myelodysplastic syndromes.

Responses have been reported in patients with myelodysplastic syndromes (MDS) after low-dose cytarabine (Ara-C) or 13-cis-retinoic acid (13-CRA) therapy. Recently, combination of these two substances in vitro was shown to produce a synergistic effect on differentiation of leukemic cells. We conducted a phase II trial with low-dose Ara-C (5 mg/m2 per 12 h s.c.) and 13-CRA (60 mg/m2 per day orally) in 14 patients with MDS, six of whom had refractory anemia with excess of blasts (RAEB), seven had RAEB in transformation (RAEBt) and one chronic myelomonocytic leukemia (CMML). The drugs were administered from day 1 to 14 and the treatment courses repeated every 4 to 8 weeks. One partial response and one minor response could be achieved. Major toxicity included dry skin, mucositis and cheilitis in 11 of the 14 patients. The response rate is no better than the results reported in the literature with either drugs alone. As yet there is no satisfactory treatment for MDS.

Adult↗
PubMed1987

Reduced production of interferon alpha and interferon gamma in leukocyte cultures from patients with active rheumatoid arthritis.

Tests for lymphoproliferation and interferon induction in normal blood donors and patients with rheumatoid arthritis (RA) were performed in a whole-blood assay. Patients with high inflammatory RA showed significantly reduced lymphoproliferation and interferon gamma production after stimulation with phytohemagglutinin (PHA) and concanavalin A (Con A) when compared with patients with low inflammatory activity, or with normal control individuals. Similarly, patients with high and low inflammatory RA exhibited a significantly reduced interferon alpha production after stimulation with Newcastle Disease Virus (NDV) when compared with normal blood donors. Our findings may point to an important immunodeficiency of the circulating lymphocytes of RA patients and may explain some of the in vitro immunoregulatory abnormalities reported in this disease.

Arthritis, Rheumatoid↗
PubMed1986

Enzymes of purine metabolism in hairy cell leukemia.

Differences in activities of the purine degradative enzymes, adenosine deaminase (ADA), purine nucleoside phosphorylase (PNP), and 5'-nucleotidase (5'NT), have been observed among different classes of lymphoid malignancies. Recent studies have shown that hairy cell leukemia (HCL) may respond to treatment with the ADA inhibitor, 2-deoxycoformycin. This study demonstrates that the cells of HCL have significantly lower levels of ADA and 5'NT (P always less than 0.01) when compared to levels in normal B- or T-lymphocytes, but have higher levels of PNP (P less than 0.001 for both comparisons). Recent studies have shown that when treated with 12-O-tetradecanoyl-phorbol-13-acetate (TPA), cells of B-cell chronic lymphatic leukemia (B-CLL) acquire phenotypic characters of HCL. The authors have therefore also investigated the changes in enzyme pattern of B-CLL after incubation with TPA B-CLL cells are characterized by low levels of ADA, PNP, and 5'-NT, but TPA caused a marked increase in PNP activity (P less than 0.001, t test for paired samples), a pattern similar to HCL. The results from biochemical studies are thus in accordance with the hypothesis that HCL cells are more mature than B-CLL cells. The special enzyme profile of HCL suggests that a PNP inhibitor might also be effective in the treatment of this disease.

5'-Nucleotidase↗
PubMed1986

[Results with the use of the M-2 protocol in plasmacytoma].

99 patients with multiple myeloma were treated over a period of 6 1/2 years; 62 of these were initially treated with vincristine, carmustine, cyclophosphamide, melphalan and prednisone: M 2-Protocol. Response to this therapy was assessed after three therapy cycles had been completed, which had been given at intervals of 5-6 weeks. In patients responding to the therapy, treatment was continued until a maximum regression of the paraproteins was achieved. By the end of May 1985, the data of 52 patients could be evaluated, in 31 (60%) of whom remission was observed. Median survival time of all patients was 27 months. In 18 patients with "complete" remission the median has not yet been reached after 40 months. In 13 patients with partial remission, the median survival time was 36 months. In patients with complete remission, the median remission period was 26.5 months, in patients with partial remission 13.9 months.

Adult↗
PubMed1986

An immunoenzymatic staining assay (ISA) for the rapid screening of monoclonal antibodies detecting membrane and cytoplasmic antigens.

We report a rapid and very sensitive immunoenzymatic staining assay (ISA) for the determination of the fine specificity of monoclonal antibodies directed against cellular antigens. Reactivity is analysed at the single cell level by light microscopy using alkaline phosphatase-conjugated second and third antibodies on cells bound to Terasaki plates. Reactive cells can be defined by their morphology even in preliminary screening procedures. Only small numbers of cells are necessary for this assay which is comparable to radioimmunoassays in its sensitivity. Plates with fixed cells can be stored at 4 degrees C so that a permanent 'library' of various cell types is always immediately available for use. The test is also suitable for human blood cell phenotyping. Moreover, a simple modification of the procedure by short pretreatment of the cells with the detergent Brij allows the detection of antigens within the cytoplasm. The importance of evaluating the cytoplasmic compartment in order to define antibody specificity and study the distribution of different cytoplasmic and membrane antigens is emphasized.

Antibodies, Monoclonal↗
PubMed1986

Purine degradative enzymes and immunological phenotypes in chronic B-lymphocytic leukaemia: indications that leukaemic immunocytoma is a separate entity.

Investigations of the purine degradative enzymes adenosine deaminase (ADA), purine nucleoside phosphorylase (PNP), and ecto-5'-nucleotidase (5'NT) have been shown to be of value in defining subsets of lymphoid malignancies. We have studied the activities of these enzymes in the circulating malignant cells of 35 patients with chronic B lymphocytic leukaemia and have correlated the biochemical data with immunological phenotypes. Classification of the cases into those without evidence of secretory activity ('true' CLL, 14 patients) and those with cytoplasmic immunoglobulin (CIg) ('immunocytoma'; 21 patients) revealed that immunocytomas are phenotypically and biochemically associated with more mature features. Malignant cells without CIg were characterized by low activities of ADA, PNP and 5'NT. In malignant cells with evidence of secretory activity (immunocytoma), low activity of ADA was also observed, but the activities of PNP and 5'NT were relatively high and approached the range of normal B lymphocytes. The differences in PNP (P less than 0.05) and in 5'NT (P less than 0.01) between these two groups were significant. Phenotypically the cells without CIg were predominantly associated with IgM (+k light chains) as surface membrane immunoglobulin (SmIg) whereas expression of IgG was more often observed in the leukaemic cells with CIg. No correlation between enzyme patterns and the stage of the disease was apparent. Thus both biochemical and immunological criteria show that cases of CLL vary within a range of maturity and that those with CIg might be more mature in the B cell axis. The present study emphasizes the value of purine enzyme studies in defining subsets of B cell neoplasia.

5'-Nucleotidase↗
PubMed1986

Autologous transplantation of blood-derived hemopoietic stem cells after myeloablative therapy in a patient with Burkitt's lymphoma.

A patient with Burkitt's lymphoma in complete remission received myeloablative consolidation treatment with superfractionated total body irradation (1,320 rad) and cyclophosphamide (200 mg/kg) followed by autologous transplantation of previously harvested and cryopreserved blood-derived hemopoietic stem cells. Seven successive leukaphereses were performed to yield a total of 55.2 X 10(9) mononuclear cells (MNC) comprising 15.1 X 10(6) CFU-GM or 4.34 X 10(6) CFU-GEMM. Following autologous blood stem cell transplantation (ABSCT), reconstitution of all cell lines occurred very rapidly, ie, 1,000 leucocytes per microL were reached after nine days, 500 granulocytes and 50,000 platelets per microL after ten days. B cells reached normal values around day 35 post-transplantation. CFU-GM first appeared in the circulating blood exhibiting an enormous overshoot. Some days later CFU-GM also appeared in the marrow. The kinetics and pattern of hemopoietic reconstitution after myeloablative treatment and ABSCT provide clear evidence that blood-derived hemopoietic stem cells are capable of completely restoring hemopoietic function in man. A possible reconstitutive advantage of blood over marrow-derived stem cells is discussed.

Adult↗
PubMed1986

Intracellular sodium concentration and transport in red cells in essential hypertension, hyperthyroidism, pregnancy and hypokalemia.

UNLABELLED: Intracellular sodium content ([Nai]), ouabain-sensitive ('Na-K ATPase') and ouabain-insensitive ('passive permeability') sodium efflux, Na-K cotransport and Na-Li ('Na-Na') countertransport were estimated in erythrocytes in 39 control subjects, 20 patients with essential hypertension, 14 patients with hypokalemia of renal or unknown etiology, 13 hyperthyroid patients and 19 pregnant women. In normokalemic essential hypertension there was only a moderate, but significant elevation of the activity of the Na-Li countertransport system. In the group of patients with hypokalemia, there was a significant increase of [Nai], ouabain-insensitive sodium efflux and Na-Li countertransport. In hyperthyroidism, a marked decrease of Na-Li countertransport was associated with a marked elevation of [Nai], in pregnancy an elevation of the Na-Li countertransport with a [Nai] 43% lower than the control values. The ouabain-sensitive sodium efflux was elevated in hyperthyroidism and hypokalemia, in which [Nai] was increased. In the control subjects there was a positive linear correlation between ouabain-sensitive sodium efflux and [Nai]. The sodium component of the Na-K cotransport was decreased to about one third of the unchanged furosemide-sensitive potassium component during pregnancy. CONCLUSIONS: The changes of cellular sodium metabolism in essential hypertension are of minor degree as compared to those in the other conditions studied. Cellular sodium metabolism in blood cells is influenced by thyroid hormones and metabolic disorders. Na-Li countertransport, i.e. Na-Na countertransport, seems to be involved in the regulation of [Nai]: an increase of its activity diminishes [Nai] (pregnancy); a decrease elevates [Nai] (hyperthyroidism). Ouabain-sensitive sodium efflux, i.e. 'Na-K ATPase', is mainly regulated by its substrate, [Nai].

Adult↗
PubMed1986

Combination therapy with mitoxantrone and etoposide in refractory acute myelogenous leukemia.

We have investigated the efficacy of mitoxantrone in combination with etoposide in patients with refractory acute myelogenous leukemia. The regimen consisted of 10 mg/m2/day of mitoxantrone given iv on Days 1-5; and 100 mg/m2/day of etoposide as short infusion, initially on Days 1-3 and extended to Days 4 and 5 as appropriate. Of the 26 patients treated with this combination, nine (34.6%) have achieved complete remission and two have achieved partial remission. The median duration of continuous complete remission was 85 days (range, 21-183+). Toxicity was mild and only one case of early death was observed. This combination seems to be an active regimen in refractory acute myelogenous leukemia, and its incorporation in front-line therapy seems warranted.

Adult↗
PubMed1985

[Therapeutic possibilities in hypereosinophilia syndrome with Löffler's fibroplastic endomyocarditis. Efficacy of cytarabine and 6-thioguanine].

In two of four patients with hypereosinophilia and Löffler's myocarditis (confirmed by biopsy) the activity of the disease was contained with prednisone, in one instance combined with hydroxycarbamide. In two patients, in whom the disease was taking a fulminant course and other treatment had failed, cytarabine and 6-thioguanine proved effective, providing a 16-month symptom-free period in one of them. But the second patient died from septicaemia associated with treatment-induced bone-marrow hypoplasia. Prednisone (1 mg/kg daily) and hydroxycarbamide (0.5-1.5 g daily) are the drugs of choice in the hypereosinophilia syndrome. If they fail, cytarabine (100 mg/m2 on days 1-5, repeated on day 28) and 6-thioguanine (100 mg/m2 daily) should be given.

Adult↗
PubMed1985

[Plasmacytomas without paraproteins].

Rare plasmocytomas without paraprotein (frequency less than 1%) can present a diagnostic trap. Three observations give grounds for drawing attention to misinterpretation of symptoms and the problematic nature of the diagnosis. In one patient, a monoclonal immunoglobulin (kappa light-chains) was detectable in the bone-marrow myeloma cells (non-excretory plasmacytoma). In a further patient no paraprotein could be found in the myeloma cells (non-secretory plasmacytoma) despite repeated investigations. An additional unusual feature in a third patient was the simultaneous presence of chronic lymphocytic leukaemia; his plasmocytoma was first detected at autopsy.

Adult↗
PubMed1985

[Bronchial asthma, eosinophilia and lung infiltrates (Churg-Strauss syndrome)].

In a patient suffering from bronchial asthma of several years' standing, recently worsening physical condition, marked eosinophilia and pulmonary infiltrates, the clinical diagnosis of Churg-Strauss syndrome (CSS) was confirmed histologically. The patient improved impressively after the initiation of immunosuppressive therapy, in contrast to the often lethal course of this disease. Therefore, the possibility of CSS should be considered in every case of bronchial asthma with progressive worsening of the physical condition or in presence of leukocytosis with significant eosinophilia.

Adult↗