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Biomedical subjects

H D Waller

Publications and source records attributed to H D Waller.

At least 73 records · Page 4Linked to original sources

Decreased susceptibility of red blood cells to lipid peroxidation in patients with alcoholic liver cirrhosis.

Red blood cells from alcoholics with and without liver cirrhosis and control subjects were examined for the susceptibility to lipid peroxidation. Red blood cells of patients with liver cirrhosis were found to be less sensitive to hydrogen peroxide-induced peroxidation measured by a new, reliable and sensitive method: the release of pentane during red blood cell lipid peroxidation. Changes of sensitivity to lipid peroxidation correlated with the severity of the liver malfunction, but not with abnormalities of the lipid composition of red cell membranes which are apparent in patients with liver disease. In alcoholics without liver cirrhosis, only minor changes in the susceptibility of red cells to peroxidation were observed.

Erythrocytes↗

Melphalan-resistant multiple myeloma: results of treatment according to the M-2 protocol.

A group of 46 patients with melphalan-resistant multiple myeloma was treated according to the M-2 protocol with melphalan, prednisolone, BCNU, cyclophosphamide, and vincristine. According to the Salmon and Durie classification, four patients had stage II A; 36, stage III A; and six, stage III B disease. Treatment resulted in five patients (11%) entering remission, while 21 (46%) had stable and 20 (43%) had progressive disease. The median survival for all patients was 12.5 months, patients in remission surviving longer (median 46 months) than those with stable disease (median 15.4 months) or progressive disease (median 6.9 months). Compared with other treatment regimens used in melphalan-resistant myeloma, the remission rate is low but the median survival exceeds that reported by most other authors.

Adult↗

Therapy for acute myeloid leukemia in 119 adults: a comparison of two treatment protocols.

Of 119 patients with acute myeloid leukemia, 69 were treated with Adriamycin, Vincristine and Cytosine Arabinoside (Therapy 1) and 50 with Daunorubicin, Cytosine Arabinoside and 6-Thioguanine (Therapy 2) as well as a consolidation therapy. The maintenance therapy with Cytosine Arabinoside and 6-Thioguanine was the same for both groups. The complete remission rate was 44% for Therapy 1 and 68% for Therapy 2 (p less than 0.05). - The median values for remission duration were 7 and 13 months respectively (p = 0.10); for survival time the median values were 18 and 19 months. These figures show in retrospect that high remission rates can be attained through intensive induction therapy and that longer remission duration is correlated with more aggressive induction therapy. A mild form of maintenance therapy seems to have little effect on the duration of complete remission.

Adolescent↗

Divergent expression of HLA-DC/MB, -DR, and -SB region products on normal and pathological tissues as detected by monoclonal antibodies.

A group of eight monoclonal antibodies directed against different monomorphic determinants of HLA-class II molecules was used to investigate the distribution of HLA-DC/DS/MB, -DR and -SB-like antigens on normal and pathological lymphoid and nonlymphoid tissues of human adult and fetal donors. HLA-MB/DC/DS-like molecules, as defined by the antibody TU 22, showed the most limited distribution as they were detected on B-lymphocytes, monocyte/macrophage subpopulations and distinct interstitial cells of various organs. HLA-DR and -SB-like antigens characterized by the other anti-HLA-class II reagents (TU34, TU35, TU37, TU39, TU43, TU58) were also present on these cell types. However, selective expression of HLA-DR and/or -SB like molecules was demonstrated with these antibodies on certain vascular endothelia, as well as different B-cell lymphomas and distinct epithelial cells in adults. Exclusive reactivity of the antibody TU39 shown on endothelial cells of fetal liver and kidney suggested specific functions of HLA-SB antigens during ontogeny. Furthermore, HLA-DR and/or -SB like molecules but not TU22+ HLA-DC/MB antigens were found to be inducible on normally Ia-like antigen negative epithelial cells of various diseased organs. Implications of this differential tissue distribution of HLA-DC/MB/DS, -DR and -SB like products in relation to organ transplantation, regulation of immune responses and cell differentiation are discussed.

Adult↗

[Hodgkin's disease--current problems in etiology and clinical picture].

The conception of etiology and pathophysiology of lymphogranulomatosis has essentially changed since the first description made by Hodgkin in 1832. In former communications, this disease was initially regarded as a tuberculosis of the lymphatic system with a pseudoleukemic course, then as an inflammatory disease, then as an intermediate state between cancer and tuberculosis, and finally as a chronic autoimmune process accompanied by interactions between neoplastic and normal lymphoid cells. Today the symptomatology is defined as a malignant disease of the lymphoreticular system beginning in a single lymph node, then expanding to other lymph nodes and spreading out by hematogenic propagation into the parenchymatous organs. The histologic examination of granulomatous tissue shows Hodgkin cells with one nucleus and Sternberg-Reed giant cells with several nuclei. The origin of Hodgkin cells is not yet clear, however, there are some hints resulting from investigations with monoclonal antibodies that the precursor cells possess some characteristics of granulopoietic cells, but also of antigens which are recognized by specific monoclonal antibodies. The immune system shows some modifications, above all with regard to the cellular immunity. The evolution of the disease is probably determined by some correlations with troubles of the cellular immune system. The treatment modalities depend on the stage which is classified according to the Ann Arbor Conference. The diagnosis should be established under rational aspects and with the aid of the most recent image-producing methods.

Hodgkin Disease↗

Immunohistological skin alterations in allogeneic bone marrow transplantation.

Skin biopsies of 26 patients with leukemia and seven patients with aplastic anemia were investigated before and at different stages after allogeneic bone marrow transplantation (BMT) to establish the immunological criteria which distinguish skin alterations during normal reconstitution from dermal lesions mediated by graft-versus-host disease (GvHD). Of the 33 patients studied 27 presented with clinically diagnosed acute and/or chronic GvHD, one patient died of bone marrow rejection. Immunohistological analysis of the respective skin biopsies with selected monoclonal antibodies against human leukocyte antigens (HLA) and differentiation antigens of the lympho-hematopoietic cells revealed low dermal mononuclear cell counts with phenotypically normal constituents in five cases with uncomplicated reconstitution post-grafting. In contrast, increased dermal cellular infiltrates predominantly consisting of Lyt 3+, OKT 8+ T-lymphocytes, as well as of a large number of Ia-like (immune response associated = HLA-D) determinant + monocytes/macrophages were observed in all patients with active acute/chronic GvH reactivity. As sign of activation simultaneous expression of HLA-D region products was also found on a subset of the invading OKT8+ T-lymphocytes. Progression of GvHD was associated with additional surface staining of keratinocytes for Ia-like determinants. Loss of Ia-like determinant+, OKT6+ dentritic epithelial cells in all leukemic patients, as well as in patients with aplastic anemia with or without GvHD suggested damage of Langerhans cells due to the previous radiotherapy and/or specific immunological destruction. In patients with fatal outcome of GvHD prolonged reduction of these dentritic epithelial cells seemed to be indicative of impaired immune reconstitution or bone marrow dysfunction. Thus immunopathological features of skin GvHR may enable early recognition and prognostic evaluation of this disease possibly allowing more effective therapy.

Adolescent↗

[Therapy of multiple myeloma. Results of sequential treatment with melphalan-prednisolone and the M2 protocol].

Melphalan and prednisolone were intermittently used for treatment of 101 patients with multiple myeloma. In case of progression, either initially or after remission or after a phase of stabilisation, treatment was changed to the M-2 protocol. By primary treatment, remission was obtained in 24 patients, a stable phase in 47 patients. The treatment of second choice which became necessary in a total of 46 patients led to remission in 5 patients (11%), 21 (46%) became stabilised and in 20 (43%) the disease progressed. The median survival time for all 101 patients was 40.5 months after commencement of treatment. In patients with remission it was clearly longer (67 months) than in those with stable disease (38.1 months) or in those with progression (16.8 months). The mean time of survival after commencement of treatment of second choice was 12.5 months. Compared to other studies the remission rates are slight, the time of survival, however, is very remarkable. The overall survival rates are equivalent to the results thus far obtained by more aggressive treatment schemes.

Adult↗

Phenylhydrazine-induced lipid peroxidation of red blood cells in vitro and in vivo: monitoring by the production of volatile hydrocarbons.

Human red blood cells and male Sprague-Dawley rats were treated in vitro and in vivo, respectively, with phenylhydrazine in order to determine whether the release of volatile hydrocarbons can serve as a suitable index for phenylhydrazine-induced red blood cell peroxidation. Lipid peroxidation following phenylhydrazine administration (in vitro experiments: dosage calculated at 0.5-50 mM; in vivo experiments: intraperitoneal injection of 2.8 mg/100 g body wt) was monitored by the release of ethane and pentane measured by gas chromatography. Further hydrocarbons such as ethylene, propane, n-butane, iso-butane and iso-butene were monitored to form a basis of comparison. In vitro haemolysis was also determined during the course of incubation. Red blood cell suspensions yielded more than 15-fold concentrations of propane and more than 2-fold concentrations of iso-butane compared to pentane and ethane yields. Haemoglobin solutions also produced propane and iso-butane in the presence of phenylhydrazine, whereas pentane and ethane were not detectable. Time-course studies revealed that ethane and pentane reached maximum in vitro levels after red blood cell suspensions had been incubated for 2 hr whereas the maximum degree of haemolysis (approximately 60%) was attained between 60 and 90 min following the beginning of phenylhydrazine treatment. The dosage did not affect the final degree of haemolysis. Rats treated with phenylhydrazine exhaled greater concentrations of ethane (6-fold increase) and pentane (2-fold increase) compared to control animals. Exhaled propane showed a 30-fold increase in concentration following drug treatment. Our results suggest that the release of pentane and ethane may be useful in assessing red blood cell lipid peroxidation in the presence of phenylhydrazine in vitro and in vivo.

Alkanes↗

Mitoxantrone and cyclophosphamide in patients with advanced breast cancer.

Twenty-eight patients with advanced breast cancer who had no prior chemotherapy received 14 mg/m2 of mitoxantrone iv on Day 1 and 600 mg/m2 of cyclophosphamide on Day 2, repeated every 4 weeks. Three patients (10%) achieved complete response and ten (36%) achieved partial response. The dose-limiting toxicity was leukopenia, and no septicemia occurred. Slightly greater than 50% of the patients had a wbc count nadir less than 2000/mm3. Based on the remarkably good tolerability, ie, mild nausea, rarely severe alopecia, and observed remission rate, this combination represents a positive addition to chemotherapy for advanced breast cancer.

Adult↗

CNS manifestations in non-Hodgkin lymphomas (NHL).

In a group of 241 patients with non-Hodgkin lymphoma investigated retrospectively, CNS manifestations occurred in 8%, mainly as meningeosis lymphoblastomatosa. Lymphoblastic and immunoblastic NHL showed the highest risk of CNS infiltration (40.7% and 12.5% respectively). Further risk factors were disseminated stage of the disease, prior involvement of the bone marrow and juvenile age. Characteristic symptoms were eye muscle paresis, paresthesias and pareses of peripheral muscles. The most fruitful diagnostic measure was lumbar puncture. More than 80% of the patients observed with CNS manifestations died within one year. The factor limiting life was less the CNS infiltration itself than the systemic progression. CNS prophylaxis should be incorporated in the treatment plan in patients with lymphoblastic and immunoblastic non-Hodgkin lymphoma at an early stage. In contrast CNS prophylaxis is not justified in uncontrollable systemic non-Hodgkin lymphoma spread.

Adult↗

[Treatment of idiopathic thrombocytopenic purpura in adults with high-dosage immunoglobulins].

Four of five patients with idiopathic thrombocytopenic purpura (ITP) responded to high-dose immunoglobulin treatment with transitory rise in platelet count to normal values, while the fifth had only minimal improvement. In the individual case there was good correlation between serum-IgG concentration and platelet count, but an influence on platelet-associated IgG could not be demonstrated with certainty. Treatment with high-dose IgG is apparently particularly suitable for patients with ITP refractory to steroids or splenectomy, in whom bleeding complications or operative procedures make a transitory rise in platelet count desirable.

Adult↗

[Combined chemo- and radiotherapy of small cell bronchial carcinoma with high dosages of radiation].

35 patients with small cell carcinoma of the lung were treated with adriamycin, cyclophosphamide and vincristine according to the ACO-protocol. Between the third and fourth course of chemotherapy the primary tumor region was irradiated with a dose of 50 to 60 Gy. In addition, the cranium and the parts of the mediastinum, which were not yet invaded by the tumor received irradiation with 30 Gy. The complete remission rate was 71% (10 out of 14 patients) in limited disease and 29% (6 out of 21 patients) in extensive disease. The median survival time was 13 months in LD and 7 in ED. The relapses occurred mainly outside the fields of the radiation. Only 3 of the 16 patients who achieved a complete remission relapsed in the irradiated field. In contrast to the results obtained with combined chemo- and radiotherapy with doses of only 30-40 Gy to the primary area, there was better local control of the tumor but without a better remission rate or survival time. The toxicity was not increased by the high dose irradiation.

Adult↗

[Comparison of the therapeutic results in treating chronic myelosis with splenic irradiation or busulfan].

In a retrospective study the survival of 111 patients with chronic myeloid leukemia was analyzed. There was a slight superiority of the patients primarily treated with busulfan over those first getting splenic irradiation and busulfan subsequently. This difference was statistically not significant. If spleen size prior to treatment was less than 10 cm below left costal margin, there was also a tendency in favor of primary busulfan therapy. In patients having bigger spleens, neither form of treatment had any advantage.

Adolescent↗