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Biomedical subjects

W Wilmanns

Publications and source records attributed to W Wilmanns.

At least 145 records · Page 8Linked to original sources
PubMed1989

[Hyperthermia in cancer research. Historical development, current status of research, future perspectives and differentiation from alternative medical procedures].

Already at the beginning of the 19th century first clinical trials with systemically induced fever were performed on malignant tumors. An intensified research in thermobiology in the sixties of this century gave the rationale for using this modality for cancer treatment. Clinical use of hyperthermia in combination with radiation or chemotherapy begun in the mid of the seventies when a better technique for selective heating of the tumor was used. In the technical development the problem of heating deep-seated tumors was mainly solved. Temperature measurements of the tumor and surrounding tissues are performed with specialized thermometry systems using thin implanted catheters to measure inside the body. 1986 a pilot study was initiated at the Medical Clinic III of the Klinikum Grosshadern to study the effects of regional hyperthermia combined with systemic chemotherapy. This study is aimed on feasibility, toxicity, and tumor response.

Abdominal Neoplasms↗
PubMed1989

Spontaneous Epstein-Barr virus transformed B-cell line sharing the identical immunoglobulin gene rearrangement with acute myeloid leukemia.

Mononuclear cells from a 44-year-old patient with acute myeloid leukemia (AML) gave rise to a spontaneous permanent cell line cultured in suspension. The cell line was shown to be positive for Epstein-Barr virus nuclear antigen (EBNA). As expected, its composite phenotype was of B-cell type with B-cell antigens (CD 20, CD 21) and with monoclonal surface IgM of kappa type, but without detectable IgM secretion. Surprisingly, identical monoclonal rearrangements of the immunoglobulin heavy chain (JH) sequences could be demonstrated in the uncultured bone marrow AML cells and in the cell line that also had kappa light chain gene rearrangement. This is the first case to our knowledge of an EBNA positive B-cell line with identical monoclonal Ig heavy chain rearrangement as detected in myeloblastic leukemia cells.

Adult↗
PubMed1989

Multiple brown tumors in a patient with nutritional secondary hyperparathyroidism.

For years, brown tumors have been considered to be a characteristic of primary hyperparathyroidism. However, since 1963 several reports indicate the incidence of brown tumors in patients with renal secondary hyperparathyroidism to be 1.5%-1.7%. The appearance of multiple brown tumor lesions is rather uncommon in secondary hyperparathyroidism which is also true for malabsorption as its cause. We report on a 56-year-old man presenting with pain in the bones and multiple osteolyses. A bone biopsy specimen and the laboratory examinations were indicative of secondary hyperparathyroidism caused by malabsorption most likely due to Billroth's II/I gastric resection. Thus, the patient's osteolyses represent brown tumors which have been induced by nutritional secondary hyperparathyroidism.

Bone Neoplasms↗
PubMed1989

Chemotherapy of Hodgkin's lymphoma with alternating cycles of COPP (cyclophosphamide, vincristin, procarbazine, prednisone) and ABVD (doxorubicin, bleomycin, vinblastine and dacarbazine). Results of the HD1 and HD3 trials of the German Hodgkin Study Group.

Untreated patients with Hodgkin's lymphoma in stages I-IIIA with risk factors (large mediastinal mass, massive splenic involvement, extranodal disease) were entered into the HD1 protocol and received a combined chemo-radiotherapy [2 X (COPP + ABVD) + 40 Gy extended field irradiation (EF) vs 2 X (COPP + ABVD) + 20 Gy EF]. Patients in stages IIIB/IV (HD3 protocol) received induction chemotherapy [3 X (COPP + ABVD)] and were randomized into consolidation by radiotherapy [20 Gy involved field irradiation (IF)] vs chemotherapy [1 X (COPP + ABVD)]. Seventy-three of 89 evaluable patients (82%) treated according to the HD1 protocol achieved a complete remission. Freedom from progression and survival of patients in stages I-IIIA with risk factors treated according to HD1 were no worse than those of patients in stages I and II without risk factors who received only radiotherapy. Eighty-six of 137 patients (63%) treated according to the HD3 protocol achieved complete remission after induction chemotherapy with COPP + ABVD. This is significantly better than the 31% complete remission rate observed in a previous pilot study with COPP alone (P less than 0.01). Including salvage therapy (radiotherapy in case of persisting nodal disease; chemotherapy with 4 X CEVD in case of persisting disseminated disease), a total of 76% complete remissions in stages IIIB/IVAB were achieved. A high erythrocyte sedimentation rate (greater than 80 mm h-1) was the most significant risk factor for achieving freedom from progression.

Adolescent↗
PubMed1989

[Risk-adapted therapy of highly malignant non-Hodgkin's lymphomas with COP-BLAM/IMVP-16: a prospective multicenter study].

In a prospective multicenter therapy trial the remission-inducing potential of the COP-BLAM (5 courses) and the possibly not cross-resistant IMVP-16 (2 courses) regimen for advanced diffuse large cell lymphomas were investigated. Inadequately responding patients were switched early after 2-3 courses to the IMVP-16 protocol. Between January 1986 and August 1988 349 previously untreated patients were recruited who fulfilled the entry criteria: age 15-75 (mean 56 years), stage II-IV. A first restaging after 3 courses of chemotherapy was documented for 280 cases, a second restaging following 7 courses of chemotherapy or a final report was available for 221 patients, 130 of which where in CR (59%). These figures include 29 cases who died already during induction-chemotherapy of progressive disease (n = 17) as well as of therapy-related complications in CR (n = 12). Thirty-three patients were switched early to IMVP-16 due to incomplete response at the first restaging; 13 of those achieved CR by the new regimen (39%), 9 achieved a partial remission which was turned into CR by additional radiotherapy in 5 cases. Dose reductions and interval prolongations were necessary at increasing rates with subsequent chemotherapy courses (20-50% of the cycles). Relapses have occurred in 32 patients so far (14 early, 18 after stop of treatment). The median survival was 24 months (n = 309 patients). These data show that this treatment strategy is effective in a large unselected group of patients of relatively high age. However, patients showing only delayed response with this protocol probably need more aggressive regimens to obtain durable remissions.

Adolescent↗
PubMed1989

Combination chemotherapy with vinblastine, ifosfamide and cisplatin in bulky seminoma.

Since 1982, 24 patients with bulky seminoma were treated with the VIP-regimen consisting of vinblastine 6 mg/m2 days 1+2, ifosfamide 1.5 g/m2 days 1-5, cisplatin 20 mg/m2 days 1-5. One patient showed primary progression, another patient partial remission, and one patient died during the first cycle. All the other patients had complete remission (21/24 = 87%), which was documented histologically in 9 patients. One patient relapsed but obtained complete remission after repeated treatment. Thus 21 patients are currently living without disease after a median observation time of 30+ months. Bone marrow toxicity was severe, leading to dose reduction in more than 50% of the patients. No other severe side effects were observed. We conclude that the regimen is highly effective in bulky seminoma. Reduction of the vinblastine dose is recommended because of bone marrow toxicity.

Adult↗
PubMed1989

Bone marrow transplantation for the treatment of leukaemia-results of the Munich Cooperative Group.

This report summarizes the results of marrow transplantation from HLA-identical siblings and syngeneic twins for treatment of acute myelogenous leukaemia, chronic myelogenous leukaemia, acute lymphoblastic and undifferentiated leukaemia from 1975 until December 1986. Three conditioning regimens and treatment of the marrow graft in vitro with absorbed antithymocyte globulin or the monoclonal antibody "Campath 1" for prophylaxis of graft-versus-host disease (GVHD) have been studied and analyzed retrospectively. The regimen of total body irradiation in large fractions of 4 Gy and of cyclosphosphamide (200 mg/kg) has achieved the most favorable results. Inactivation of T-cells by treatment of the marrow "in vitro" has decreased the severity of GVHD without improving survival. The antileukaemic effect of the graft may be important for control of the disease and may be improved by better immunosuppression of the recipient.

Adolescent↗
PubMed1989

Relation between cell cycle stage and the activity of DNA-synthesizing enzymes in cultured human lymphoblasts: investigations on cells separated according to DNA content by way of a cell sorter.

Exponentially growing human lymphoblasts (culture LS-2) were separated by cell sorting (FACS II, Becton Dickinson) according to their deoxyribonucleic acid (DNA) content, designating them at particular phases of the cell cycle. Prior to cell sorting the DNA has been fluorochrome-labeled with the Hoechst stain H 33342. Maximum cell enrichments of 94% for G0 + G1 cells, 96% for S cells and 74% for G2 + M cells could be achieved. The enzyme activities of thymidine kinase (TK), thymidylate synthase (TS), DNA polymerase (DNA-P), dihydrofolate reductase (FH2-R), methionine synthase (MS), and hexokinase (HK) were determined in the obtained cell fractions. Although incorporation of 3H-thymidine (3H-dTR) and the 3H-dTR labeling index were significantly inhibited by the dye, no evidence of cell staining's having a significant effect on the enzyme activities was found. The enzyme activities for approximately 100% pure G0 + G1, S, and G2 + M cells were computed. With exception of TK, all the enzymes under study were shown to exhibit activities--although of differing degree--in the G0 + G1, S, and G2 + M cells. No TK activity was shown in G0 and G1 cells; its activity, however, was approximately the same in S and G2 + M cells. This applies likewise for TS which, in contrast to TK, exhibits minor activity in G0 + G1 cells. DNA-P was highly active in G0 + G1 cells, but maximum activity was in S cells. FH2-R exhibited maximum activity in S cells, although the difference in activity between S and G2 + M cells was not significant. None of the observed differences in MS activity was significant, indicating equally high activity in cells of all cell cycle phases. HK activity is approximately twice as high in G2 + M cells as in G0 + G1 cells.

Benzimidazoles↗
PubMed1989

[Echocardiography with angiotensin administration in the diagnosis of adriamycin-induced cardiomyopathy].

Noninvasive assessment of early cardiotoxicity of doxorubicin is still a problem of clinical concern. We studied whether echocardiography during afterload stress induced by angiotensin II (1,000-3,000 ng/min) allows earlier detection of left ventricular impairment than echo at rest. We compared 30 normals (N) to 30 patients with carcinoma, who had received doxorubicin at a cumulative dose of at least 360 mg/sqm. At rest echocardiograms of patients were either normal (P1; n = 24) or abnormal (P2; n = 6; fractional shortening less than 28%, distance of mitral E-point to septum greater than 7 mm). Best parameter for separation of P1 vs N was the slope K of the regression line of the relation between endsystolic diameter and systolic blood pressure (cuff-method). 38% of P1 and 100% of P2 had K-values below the range of N (less than 4.7 mm Hg/mm). Four of five patients with reduced ejection fraction assessed by scintigraphy (less than 55%) after continued therapy with doxorubicin have had, in previous echocardiographic studies, normal resting parameters but abnormal K-values. We conclude that afterload-stress increases the sensitivity of echocardiography in detecting cardiotoxicity due to doxorubicin.

Adolescent↗
PubMed1988

[Value of preoperative thrombocyte marking in patients with idiopathic thrombocytopenic purpura].

51Cr-platelet kinetic studies were performed in 77 patients with idiopathic thrombocytopenic purpura. The sequestration site was splenic for 63, splenic/hepatic for 7 or hepatic for remaining 7 patients. In 20 patients platelet survival was extremely shortened to 0-3 h, whereas only 26 patients had a survival time of more than 24 h. Those patients with low platelet counts also had a very short platelet survival time, whereas patients with higher platelet counts (greater than 50 x 10(9)/l) had longer platelet survival times. 51 patients (66%) were splenectomized following the kinetic studies. 25 patients who had a splenic sequestration site had normalized platelet counts and 6 patients had platelet counts between 80-149 x 10(9)/l 12 months after splenectomy (i.e. in 92% of cases with splenic sequestration site a full or partial remission). Of the 11 patients with a hepatic or splenic/hepatic sequestration site, 2 patients had full remission, 1 partial remission, 3 patients had minimal improvement and 5 other patients were treatment failures in respect to the splenectomy.

Adolescent↗
PubMed1988

[Exchange transfusion and (or) plasmapheresis: effective measures in severe tropical malaria?].

A 42-year-old man was admitted to hospital with, previously wrongly diagnosed, fulminant falciparum malaria, 14 days after a two-week trip to Kenya. He had a high fever and was jaundiced, with severe anaemia and thrombocytopenia. He was given quinine intravenously and pyrimethamine/sulfadoxine (Fansidar) by mouth. He developed acute renal failure and increasingly severe cerebral symptoms, at times coma. An exchange transfusion and several plasmaphereses were, therefore, performed. The cerebral symptoms quickly abated during the exchange transfusion, but renal function failed to improve. Because of continuing fever, mefloquin (Lariam) and doxy-cycline (Vibramycin) were also administered. After several dialysis periods the patient improved gradually and was discharged after three weeks in generally good condition with normal renal function.

Acute Disease↗
PubMed1988

Limited fibrinogenolysis in stored whole blood and in fresh frozen plasma.

Measurement of the F-CB3 related antigen of the fibrinogen alpha-chain shows a time dependent increase of fibrino(geno)lysis in whole blood during storage from 70.7 +/- 16.4 pmol/ml (day 2) to 356.3 +/- 110 pmol/ml (day 39). Simultaneously PMN-elastase increases from 95 +/- 44 micrograms/l (day 2) to 3492 +/- 954 micrograms/l (day 39). The significant correlation between PMN-elastase and F-CB3 values (n = 180, r = 0.73, p less than 0.001) may reflect a relationship between the liberation of granulocyte enzymes and the extent of fibrino(geno)lysis. The isolation and separation of fibrinogen material on SDS-PAGE indicates a limited degradation of the parent fibrinogen molecule (340 kD). During storage the fraction of slightly degraded fibrinogen (300 kD) and pre-X fragment (280 kD) increases. The separation of the reduced fibrinogen material demonstrates that the limited fibrinogenolysis mainly took place in the A alpha-chain. Additional studies on fresh frozen plasma show that PMN-elastase values (98.6 +/- 41.8 micrograms/l), F-CB3 values (84.8 +/- 31.2 pmol/ml) and the SDS-PAGE pattern of the fibrinogen material are similar to the results in whole blood stored for two days.

Blood Preservation↗
PubMed1988

The role of coagulation, fibrinogenolysis and fibrinolysis in the development of fluid and clotted cadaver plasma.

Parameters for coagulation, fibrinogenolysis and fibrinolysis were measured in order to understand the formation of fluid or clotted cadaver plasma. All values found were distinctly elevated without significant differences between fluid and clotted material. The electrophoretic banding pattern of the fibrinogen and fibrin material also proved extensive coagulation and fibrinolysis in all cases. In vitro experiments in which similar electrophoretic banding patterns were obtained suggested that the development of fluid cadaver plasma depends on the activation of fibrinolysis prior to complete coagulation, and is enhanced by persistence of circulation as well as a physiological pH (7.4). In correspondence to post mortal time only an increase in elastase values was found.

Blood Coagulation↗
PubMed1988

Promotion of cystine uptake and its utilization for glutathione biosynthesis induced by cysteamine and N-acetylcysteine.

Chinese hamster ovary (CHO) cells obtain a high capacity to utilize cystine from the growth medium by exposure to cysteamine (2-mercaptoethylamine, MEA) or N-acetylcysteine (NAC). For uptake studies a modified McCoy's 5A medium supplemented with 0.1 mM [35S]cystine was used. The uptake of cystine was dependent on the time of exposure (0-60 min) and the concentrations of MEA or NAC (0-8 mM). At high concentrations of MEA or NAC, the uptake of cystine became saturated. Half-maximal uptake of cysteine was observed at concentrations of 0.12 mM MEA and 0.66 mM NAC, respectively. Increase in temperature (37-44 degrees) or pH (6.0-8.0) during MEA or NAC exposure further increased the cystine uptake. The increased uptake of cystine was not affected in the presence of glutamate or homocysteate which both inhibited the cystine uptake of control cells. Determination of both reduced (GSH) and oxidized (GSSG) cellular glutathione showed a twofold increase in MEA- or NAC-treated CHO cells. DL-buthionine-S,R-sulfoximine (BSO), an inhibitor of GSH biosynthesis completely blocked the promotion of cystine uptake by MEA and NAC. By further analysis using reversed-phase HPLC of cell extracts, more than 90% of the [35S] radioactive cystine taken up by the cells could be recovered within the pool of GSH. The results demonstrate that exposure of CHO cells with MEA and NAC leads to a promoted uptake of cystine from the culture medium and its rapid utilization for cellular GSH biosynthesis.

Acetylcysteine↗