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Biomedical subjects

T Zwingers

Publications and source records attributed to T Zwingers.

36 records · Page 2Linked to original sources
PubMed1990

Role of thoracic radiotherapy combined with chemotherapy in limited stage small cell lung cancer (SCLC). A randomized multicenter phase III trial.

We initiated a prospective randomized multicenter trial to clarify the role of radiotherapy in the treatment of the primary tumor in small cell lung cancer stage limited disease. Patients were randomized to receive only chemotherapy (n = 27), or chemotherapy and radiotherapy of 30 Gy (n = 34) or chemotherapy and radiotherapy of 50 Gy (n = 30). Radiotherapy was administered after the third chemotherapy cycle. All patients received prophylactic total-brain irradiation of 30 Gy. The chemotherapy consisted of 6 cycles of adriamycin, cyclophosphamide and vincristin (ACO). 415 patients entered the trial. According to eligibility criteria 97 patients were randomized and 91 patients were evaluable for response. The total response rate (CR and PR) was 69% not being statistically different between all groups. No differences in survival time were observed between patients receiving 30 Gy (median = 13.5 months) and those receiving 50 Gy (median = 12.4 months). However patients treated with radiotherapy and chemotherapy showed a statistically significant improvement of survival time compared to patients receiving chemotherapy alone (median = 9.7 months).

Aged↗
PubMed1989

Plasma levels of soluble CD8 antigen and interleukin-2 receptor antigen in patients with hairy cell leukemia, relationship with splenectomy and with clinical response to therapy.

A soluble form of CD8 antigen (sCD8) has been shown to be released by activated CD8 + lymphocytes. Measurements of sCD8 may serve as an index of suppressor/cytotoxic cell activity. To assess the clinical significance of this observation in response to malignancy, we have investigated the sCD8 concentrations in 38 patients with hairy cell leukemia (HCL) not yet treated with any systemic therapy. The median plasma sCD8 level of the 20 nonsplenectomized patients was 1,025 U/ml and was significantly higher than that in the 18 patients who had previous splenectomy (median = 200 U/ml, p less than 0.0001), or in 14 normal controls (median = 350 U/ml, p less than 0.0001). Compared to controls, splenectomized patients had also significantly lower levels of sCD8 (p less than 0.01). The median concentration of soluble interleukin-2 receptor (sIL2R) in nonsplenectomized patients was 14,500 U/ml and was in the same range as in splenectomized patients (15,000 U/ml). There was no overlap in sIL2-R levels between controls (median = 300 U/ml) and patients. Investigation of serial plasma samples in 7 patients who received deoxycoformycin (DCF) and 11 patients treated with interferon alpha (IFN-alpha) showed a normalization of sCD8 levels and a decrease of sIL2R concentrations in those patients who showed hematological improvement. Normalization of sIL2R was, however, only observed in patients with complete remission. Our observation indicates that splenectomy might cause a reduction of the activation of suppressor/cytotoxic cells in patients with HCL. Treatment with either DCF or IFN-alpha also modulates the sCD8 levels to normal range. Measurements of sCD8 and sIL2-R might give more insight into the pathogenesis of HCL and serve as parameters for monitoring different phases of the disease and response to therapy.

Antigens↗
PubMed1988

Correlation of content of B cells and Leu7-positive cells with subtype and stage in lymphocyte predominance type Hodgkin's disease.

Cases of lymphocyte predominance type Hodgkin's disease were investigated using immunohistochemical methods and compared for morphological subtype and clinical stage. Cases of nodular paragranuloma showed a high, diffuse paragranuloma a moderate, and the mixed type a low, content of B cells. There was no significant correlation between B cell content and clinical stage. The number of Leu7+ cells was significantly increased in stage I of nodular paragranuloma. Hodgkin cells did not react with the CD15 antibody in most cases of paragranuloma but showed reactivity in the mixed type.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1988

[The development of radiation caries after high doses of irradiation].

39 patients, who were irradiated with doses of 50 to 70 Gy for ENT-tumors over a period of 3.5 months to three years prior to the examination, showed a rapidly progressing caries of the teeth inside the target volume. The teeth outside the target volume developed a caries of less extent. Radiation induced xerostomia, effects of the irradiation of the soft tissues, nutrition habits and hygiene are discussed as causes for the damage of the teeth.

Adult↗
PubMed1987

[Scintigraphic findings in fracture of the vertebral body].

The "region-of-interest technique" was applied for taking 85 quantifying skeleton scintigrams in 60 patients suffering from 75 stable impression fractures of the inferior thoracic spine or the lumbar spine. The skeleton scintigrams were made between 3 days and 6 years after the accident, predominantly between the first and twelfth posttraumatic week. The evaluation curves of the scintigraphic quotients following to fractures of the vertebral bodies show a linear increase of the quotient until the fourth week and afterwards an exponential decrease. The quantifying skeleton scintigraphy is not only valuable in diagnostic evaluation but allows also to assess the age of fractures of the vertebral bodies. In the future, quantifying skeleton scintigraphy may thus play an important role in the examination of fractures of the vertebral bodies.

Adolescent↗
PubMed1987

Spectrum and frequency of autoimmune derangements in lymphoproliferative disorders: analysis of 637 cases and comparison with myeloproliferative diseases.

The records of 637 patients with lymphoproliferative disorders and 346 patients with myeloproliferative disorders were retrospectively analysed for the presence of additional autoimmune derangements. The frequency of autoimmune perturbations in lymphoproliferative diseases (51 cases; 8.0%) was significantly higher than in myeloproliferative diseases (six cases; 1.7%; P less than 0.0001). Rheumatic disorders, autoallergic haematological manifestations and other organ-specific autoimmune derangements were responsible for about one third each of the observed disturbances. Autoimmune diseases which preceded the onset of malignancy, occurred in lymphoproliferative and myeloproliferative disorders with a comparable frequency without significant differences between individual subgroups of lymphoproliferative diseases. In contrast, autoimmune complications developing in the course of the neoplastic disease were significantly more frequent in lymphoproliferative (4.9%) than in myeloproliferative disorders (0.3%; P less than 0.0005). Here marked differences were observed between individual lymphoma entities, the rate of concomitant autoimmune derangements ranging from zero to over 15%. With the exception of centroblastic-centrocytic lymphoma which in no case was associated with secondary autoimmune complications, the proportion of patients with autoimmune perturbations increased with improving prognosis of the lymphoproliferative diseases. Possible pathogenetic mechanisms involved in the manifestation of autoimmune complications in malignant lymphomas are discussed.

Autoimmune Diseases↗
PubMed1987

[Primary treatment of hairy cell leukemia with low-dose human recombinant interferon-alpha-2c (Hr-IFn alpha 2c) in comparison with therapy following splenectomy. Interferon (IFn-alpha 2c) in HCL before or after splenectomy].

Within less than 14 months of recruitment 32 centers enrolled 97 patients in a multicenter trial for low-dose treatment of hairy cell leukemia (1.2 X 10(6) IU/m2 X 28 days s.c. with dose reduction according to clinically judged improvement) or ultra-low dose treatment (1.2 X 10(5) IU/m2, s.c. daily increasing to a well-tolerated dose) with Hr IFn-2c (arg). Induction therapy was limited to 84 days. Patients who reached the clinical stage Jansen I or A were then randomized to 2 arms either to receive further IFn (1.2 X 10(6) IU/m2 s.c.) twice a week or to be taken off treatment. For both arms induction therapy was reinstituted whenever a patient lost the criteria of Jansen stage A or I. The study included obligatory central diagnostic procedures and several special investigations. During the first year of the study a special problem evolved in the group of 34 patients with recurrent disease after splenectomy. Ten of them died, 9 of septicemia and 1 of bleeding complications, whereas only 1 death occurred in those patients who received IFn before splenectomy. The risk factors and the response to therapy in the two groups will be analyzed in order to define the criteria that will be needed for the proper choice of primary treatment for HCL. It appears important to us to restrict splenectomy to selected patients.

Clinical Trials as Topic↗
PubMed1987

A prospective multicenter trial with human recombinant alpha 2c-interferon in hairy cell leukemia before and after splenectomy.

Our multicenter study on the treatment of hairy cell leukemia (HCL) started in December 1984 and the present data cover the time up to June 30, 1986. Ninety-seven patients were enrolled. For induction of response daily doses (6 micrograms) of low dose human recombinant alpha 2c-interferon (arg) was chosen. Further dose reduction (3 micrograms) was possible for patients who improved within the first 3-4 weeks. Patients with known risk factors started at lower doses (0.6 microgram daily). As infections are known to be the main cause of death in HCL, splenectomy was not mandatory before treatment. Thirty-nine patients received treatment with interferon. Nevertheless, infections remained the major cause of death in the study. The protocol did not prevent fatal infections in nine of the 34 splenectomized patients. The regimen proved safe for all but one of the nonsplenectomized patients. According to this experience, new criteria are needed for the choice of primary treatment in HCL. In our opinion splenectomy should become restricted to selected cases.

Antineoplastic Agents↗
PubMed1984

Clinical features of nodular paragranuloma (Hodgkin's disease, lymphocyte predominance type, nodular).

Clinical aspects of 145 cases of nodular paragranuloma (nodular subtype of lymphocyte predominance type of Hodgkin's disease) were investigated. There was a marked male predominance, and the age curve showed a peak in the 4th decade. In a majority of cases lymphadenopathy developed within 1 year. General (B) symptoms were observed in only 15 patients. The most frequent sites of primary involvement were cervical, axillary, and inguinal lymph nodes. Other organs were rarely involved. At the time of diagnosis 50% of patients were in stage I, 21% in stage II, 22% in stage III, and 7% in stage IV. The prognosis was usually favorable or very favorable and depended on the stage of disease at diagnosis and on the age of the patient. Patients with stage I or III disease without splenic involvement had about the same probability of survival as the normal population. Stage III patients with splenic involvement had a lower probability of survival. The prognosis for stage II was also less favorable. Patients in stage IV had the lowest probability of survival. Closer analysis of the ten stage IV cases revealed two groups with different outcomes. Four cases showed progressive disease that did not respond to treatment and led to death within 12 months. The second, more favorable form (6 patients) responded well to chemotherapy. Nine patients in stage I who were not treated after lymph node biopsy were free of disease even after periods of up to 14 years. A total of 52 patients had one or more relapses. The recurrent tumors developed locally in a majority of cases. There was transformation of nodular paragranuloma into another subtype of Hodgkin's disease in only four cases. Five cases showed transformation into large-cell tumors that resembled immunoblastic lymphoma and require further immunological study.

Adolescent↗
PubMed1984

Tetralogy of Fallot. Development of hypoplastic pulmonary arteries after palliation.

Thirty-one patients with tetralogy of Fallot were studied angiographically before and after palliation with Blalock-Taussig operation (n = 9), Brock operation (n = 12), or enlargement of the right ventricular outflow tract with extracorporeal circulation (ECC) (n = 10). The relative diameter of the pulmonary vascular ring (PVR), pulmonary trunk (PT), and right and left pulmonary arteries (RPA, LPA) were measured before and 24.8 +/- 20.9 months after palliation. Using correlation analysis, the magnitude of growth of the pulmonary artery system was inversely related to its initial size. Mean pressure in the pulmonary artery after palliation as well as the period between date of surgery and recatheterization did not correlate significantly with growth. After Blalock-Taussig operation, the ipsilateral pulmonary artery predominantly increased in size without significant growth of PVR and PT. Brock operation and enlargement of the right ventricular outflow tract with ECC, improving the flow in the pulmonary vascular system centrally, induced a significant, symmetrical growth of the pulmonary vascular system and, therefore, are our methods of choice for palliation in patients with tetralogy of Fallow combined with hypoplastic pulmonary arteries.

Adolescent↗
PubMed1984

The treatment of tetralogy of Fallot: early repair or palliation?

Between 1974 and 1983, 380 consecutive patients with tetralogy of Fallot underwent surgery. In 73 patients, undergoing palliative surgery, the operative mortality and late mortality was 6.8%. Twenty-five of these patients have undergone subsequent complete repair, while 38 are awaiting correction. During the last 4 years we preferred operative procedures with enlargement of the right ventricular outflow tract (80%) to shunt operations (20%). In contrast to shunts, enlargement of the outflow tract induces a symmetrical growth of hypoplastic pulmonary arteries without the risk of acquired pulmonary atresia or peripheral stenosis at the site of anastomosis. Three hundred twenty-nine patients have undergone repair. In 101 patients, who had palliative operations before complete repair, the operative mortality was 12.9% and late mortality 2.9%. Those patients undergoing repair as a first operation had an operative mortality of 8.8%, and a late mortality of 1.3%. In the last 5 years the operative mortality for all patients, whether or not they had had previous palliative surgery, was 4.7%. The incidence of transannular outflow tract patching was not greater in children less than 2 years of age (16.9%) than in older children, 2 to 14 years of age (16.5%). However, in our experience the requirement for subvalvular outflow patches was higher in younger children (52.1%) than in the older children (34.1%). Because of this high incidence, particularly in younger patients, we have now begun to repair tetralogy of Fallot using the transatrial approach, thus reducing our use of subvalvular patches.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1984

Rheumatology trials: selection of adequate response variables and their evaluation.

Response variables in rheumatology trials should describe not only the disease manifestations, but should also measure the changes of impairment, disability and handicap. One should use the following criteria, at least: analogue pain scale, score of patient's overall well-being, functional score (A.R.A., Ritchie or Keitel) and Arthritis Impact Measurement Scale (A.I.M.S.). The statistical evaluation of these time-dependent measurements should be done with nonparametric methods using all information over time.

Arthritis↗
PubMedDate not supplied

Dose intensity phase I/II trial with carboplatin, ifosfamide, etoposide and vincristine combined with filgrastim in patients with small-cell lung cancer.

BACKGROUND: The purpose of the study was to evaluate the feasibility of increasing dose intensity by a stepwise reduction of the time intervals between chemotherapy cycles in separate patient cohorts with small-cell lung cancer. Patients received up to 6 courses of combination chemotherapy with carboplatin, etoposide, ifosfamide and vincristine followed by support with filgrastim. Dose intensity, incidence, duration and severity of neutropenic fever and infections, objective response to chemotherapy, and safety of filgrastim were determined. PATIENTS AND METHODS: 29 patients with small-cell lung cancer (limited disease: 2, extensive disease: 27) were treated with a combination of carboplatin 250 mg/m2 i.v. day 1, ifosfamide 2 g/m2 and etoposide 120 mg/m2 i.v. days 1 and 2, etoposide 120 mg/m2 orally day 3, and vincristine 1.4 mg/m2 day 14. Initially, filgrastim (5 micrograms/kg) was administered subcutaneously from day 7 to 16. With shorter treatment intervals, filgrastim was administered on days 4-16 or 4-14. RESULTS: An overall increase in dose intensity by a factor of 1.44 was achieved after reducing the treatment interval from 27 to 17 days. Further reduction to 14 days was not feasible due to persistent thrombocytopenia. Six patients (21%) developed a total of 9 febrile episodes, and 14 patients (48%) had to be withdrawn from the study before the completion of six cycles of chemotherapy. The median duration of infectious episodes was 6 days. Overall, a total of 22 of 27 evaluable patients had an objective response. Longer treatment intervals resulted in a lower probability for objective response (> or = 23 days: 10/14 patients vs. < or = 17 days: 7/7 patients). CONCLUSION: Filgrastim allows for the reduction of treatment intervals in patients with small-cell lung cancer and increased dose intensity with acceptable hematologic and nonhematologic toxicities.

Adult↗