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Biomedical subjects

H Honegger

Publications and source records attributed to H Honegger.

At least 19 recordsLinked to original sources

Prognostic factors affecting long-term outcomes in patients with resected stage IIIA pN2 non-small-cell lung cancer: 5-year follow-up of a phase II study.

The aim was to investigate the efficacy of neoadjuvant docetaxel-cisplatin and identify prognostic factors for outcome in locally advanced stage IIIA (pN2 by mediastinoscopy) non-small-cell lung cancer (NSCLC) patients. In all, 75 patients (from 90 enrolled) underwent tumour resection after three 3-week cycles of docetaxel 85 mg m-2 (day 1) plus cisplatin 40 or 50 mg m-2 (days 1 and 2). Therapy was well tolerated (overall grade 3 toxicity occurred in 48% patients; no grade 4 nonhaematological toxicity was reported), with no observed late toxicities. Median overall survival (OS) and event-free survival (EFS) times were 35 and 15 months, respectively, in the 75 patients who underwent surgery; corresponding figures for all 90 patients enrolled were 28 and 12 months. At 3 years after initiating trial therapy, 27 out of 75 patients (36%) were alive and tumour free. At 5-year follow-up, 60 and 65% of patients had local relapse and distant metastases, respectively. The most common sites of distant metastases were the lung (24%) and brain (17%). Factors associated with OS, EFS and risk of local relapse and distant metastases were complete tumour resection and chemotherapy activity (clinical response, pathologic response, mediastinal downstaging). Neoadjuvant docetaxel-cisplatin was effective and tolerable in stage IIIA pN2 NSCLC, with chemotherapy contributing significantly to outcomes.

Adult↗

A randomized phase II trial of capecitabine and two different schedules of irinotecan in first-line treatment of metastatic colorectal cancer: efficacy, quality-of-life and toxicity.

BACKGROUND: To determine the efficacy, impact on quality-of-life (QoL) and tolerability of two different irinotecan administration schedules in combination with capecitabine as first-line treatment of metastatic colorectal cancer. PATIENTS AND METHODS: We carried out a randomized phase II trial to select one of the following treatment regimens for further investigation: weekly irinotecan at a dose of 70 mg/m(2) days 1, 8, 15, 22, 29 (arm A) or 3-weekly irinotecan at a dose of 300/240 mg/m(2) day 1 and days 22 (arm B) in combination with capecitabine 1000 mg/m(2) twice daily days 1-14 and days 22-35 every 6 weeks. RESULTS: Seventy-five patients with good performance status entered the trial. The two arms were well balanced for relevant patient and disease characteristics. The most frequent toxic effects were grade 3/4 diarrhea (arm A: 34%, B: 19%), grade 3/4 neutropenia (A: 5%, B: 19%) and grade 2/3 alopecia (A: 26%, B: 65%). Other grade 3/4 toxic effects were rare (<5%). Response rates were 34% [95% confidence interval (CI) 20% to 51%] in arm A and 35% (95% CI: 20% to 53%) in arm B. Median time to progression was 6.9 (4.6-10.1) and 9.2 (7.9-11.5) months and median overall survival was 17.4 (12.6-23.0+) and 24.7 (16.3-26.4+) months. Patients with an objective tumor response reported better physical well-being (P < 0.01), mood (P < 0.05), functional performance (P < 0.05) and less effort to cope (P < 0.05) compared with the non-responders and stable disease patients. CONCLUSIONS: The primary end point of this study was the objective response rate and based on the statistical design of the trial, the 3-weekly irinotecan schedule was selected over weekly irinotecan administration. The 3-weekly irinotecan schedule also seemed advantageous in terms of grade 3/4 diarrhea, time to progression, overall survival and patient convenience, but the study was not designed to detect differences in these parameters. In addition, tumor response was shown to have a beneficial effect on QoL indicators.

Adult↗

Osseous lesions of the distal ulna: atypical location--unusual diagnosis. Report of three cases with similar imaging and different pathologic diagnoses.

Three cases with destructive bone lesions of the distal end of the ulna caused by different pathologic entities (Ewing's sarcoma, osteosarcoma, rheumatoid pseudotumoral synovitis) are presented, all with similar clinical and comparable x-ray and magnetic resonance imaging features. Although the distal end of the ulna may be resected without significant functional impairment, careful evaluation of treatment strategies compatible with oncologic standards is warranted.

Adult↗

Docetaxel (Taxotere)-cisplatin (TC): an effective drug combination in gastric carcinoma. Swiss Group for Clinical Cancer Research (SAKK), and the European Institute of Oncology (EIO).

PURPOSE: A multi-centric trial was performed to explore the clinical activity, in terms of response and toxicity (primary objectives), duration of response and survival (secondary objectives), of docetaxel with cisplatin in advanced gastric cancer (AGC). PATIENTS AND METHODS: Patients with measurable unresectable and/or metastatic gastric carcinoma, performance status < or = 1, normal hematological, hepatic and renal functions and not pretreated for advanced disease by chemotherapy received up to eight cycles of TC (docetaxel 85 mg/m2 dl, cisplatin 75 mg/m2 dl) q3w. Dose escalation to 100 mg/m2 was performed in five patients and was discontinued for excessive toxicity. RESULTS: Forty-eight patients were accrued. A median of 5 cycles/patient was given. We observed 2 complete and 25 partial responses for an overall intent to treat response rate of 56% (95% CI: 41%-71%). Twelve patients had stable disease for > or = 9 weeks (3 cycles). The median time to progression and overall survival were 6.6 and 9 months, respectively. Grade > or = 3 toxicities were neutropenia 81%, anemia 32%, thrombocytopenia 4%, alopecia 36%, fatigue 9%, mucositis 9%, diarrhea 6%, nausea/vomiting 4%, neurologic 2%, and one anaphylaxis precluding treatment administration. We recorded nine episodes of non-fatal febrile neutropenia in eight patients, two of them with docetaxel at 100 mg/m2. There were no direct treatment-related deaths. CONCLUSIONS: TC is active in AGC with a high response rate in a multicentric trial. Despite its hematotoxicity, this regimen is well tolerated and can be recycled as originally planned in 78% of the cases. These results may serve as basis for further developments of docetaxel containing regimens in this disease.

Adenocarcinoma↗

A prospective study of risk-adapted therapy for large cell non-Hodgkin's lymphoma with VACOP-B followed by high-dose CBV and autologous progenitor cell transplantation for high-risk patients in remission.

Several centres reported a favourable outcome after high-dose chemotherapy with autologous progenitor cell transplantation in selected patients with high-risk large cell non-Hodgkin's lymphoma in first remission. Based on these observations, we wanted to prospectively determine the outcome of a risk-adapted therapy for patients with large cell lymphoma. Patients aged 60 years or less received 12 weeks of VACOP-B chemotherapy. For high-risk patients in remission this was immediately followed by high-dose chemotherapy with cyclophosphamide, carmustine and etoposide and autologous progenitor cell transplantation. High-risk criteria were defined before the establishment of the International Index and included large cell lymphoma stage III or IV or mediastinal large lymphoma with sclerosis stage II or higher, and the presence of bulky tumours and/or an elevated LDH. 89 patients fulfilled the clinical selection criteria and were entered onto this multicentre study. 82 patients were evaluable after confirmation of large cell histology by pathology review. Of these, 51 were considered to be in the low-risk group and 31 in the high-risk group. The 3-year event-free survival for all patients was 68%. The 3-year event-free survival was 76% for the low-risk and 55% for the high-risk group (P = 0.061). Only 22/31 high-risk patients were able to receive the high-dose chemotherapy in first remission as intended. In conclusion, although our study demonstrated that a risk-adapted therapy for large cell lymphoma could be safely administered, the potential impact on outcome of the strategy chosen here is likely to be small.

Adult↗

Randomized trial showing equivalent efficacy of filgrastim 5 micrograms/kg/d and 10 micrograms/kg/d following high-dose chemotherapy and autologous bone marrow transplantation in high-risk lymphomas.

PURPOSE: To evaluate the effect of two filgrastim dosages after autologous bone marrow transplantation (ABMT) in patients with Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS: Eighty-six patients were enrolled onto a multicenter, randomized, open-label study. The study compared the efficacy and safety of two different doses of filgrastim, 5-microgram/kg/d subcutaneous (SC) bolus injection and 10-microgram/kg/d SC continuous infusion, starting on day 1 following ABMT. RESULTS: Both patient groups were well matched in terms of demography and disease. The results showed no statistical difference in the median time to reach an absolute neutrophil count (ANC) of 0.5 x 10(9)/L (11 days; P = .685) and no difference in the median duration of neutropenia (10 v 11 days, respectively; P = .567) between either dose of filgrastim. The incidence and duration of fever and neutropenic fever were the same in both groups. The number and mean duration of clinically and documented infections, duration of intravenous (IV) antibiotics, time to discharge from hospital, and tumor response also were similar in both groups. CONCLUSION: This study demonstrates that a dose of filgrastim 5 micrograms/kg/d administered as a daily SC bolus injection has a similar efficacy and safety profile compared with the 10-microgram/kg/d dose administered as a SC continuous infusion. The lower dose of filgrastim has potential cost-saving implications in terms of both the dose of drug administered and the ease of administration. Based on these findings, the recommended dose of filgrastim after ABMT should be 5 micrograms/kg/d.

Adolescent↗

Localization of bursicon in CCAP-immunoreactive cells in the thoracic ganglia of the cricket Gryllus bimaculatus

Bursicon is a neuropeptide that induces tanning of the cuticle in freshly moulted insects. In an earlier investigation, we demonstrated that bursicon activity can be detected throughout the ventral nerve cord of the cricket Gryllus bimaculatus. This study aims at identifying the neurosecretory cells within the thoracic ganglia that produce bursicon. When homogenates of anterior pieces of thoracic ganglia were separated using SDS gel electrophoresis, proteins with bursicon activity could be eluted only from a slice of the gel spanning the 28-33 kDa region. In the anterior lateral cortex of the thoracic ganglia, there are two bilaterally paired neurosecretory cells with large vacuoles that project contralaterally to neurohaemal release sites associated with segmental nerves N5 and N6. These cells and their processes in N5 and N6 were labelled using antisera against crustacean cardioactive peptide (CCAP). The cell projecting into N6 showed a Tyndall effect (i.e. appeared opaque under oblique illumination) in older adults, and single isolated somata contained bursicon activity. Homogenates of nerves N5 and N6 also showed bursicon activity, but neither bursicon activity nor CCAP-immunoreactive processes were found in segmental nerve N4. The thoracic connectives, which contain three major CCAP-immunoreactive processes, also showed bursicon activity. Homogenates of posterior pieces of the thoracic ganglia did not contain bursicon activity. Western blots demonstrated that the anti-CCAP serum does not recognize the 30 kDa bursicon-active protein fraction. These results suggest that a CCAP-like neuropeptide and a protein with bursicon activity are co-localized in the anterior lateral neurosecretory cells of the thoracic ganglia and in their segmental homologues in the other ganglia. Additionally, we have shown using western blots that a monoclonal antibody raised against a 56 kDa protein from the housefly Musca domestica, a protein thought to be bursicon, does not label the 30 kDa bursicon-active protein of crickets. However, this antibody does label an unidentified 56 kDa protein isolated from anterior as well as posterior pieces of thoracic ganglia.

Journal Article↗

Randomized study of recombinant human granulocyte colony-stimulating factor after high-dose chemotherapy and autologous bone marrow transplantation for high-risk lymphoid malignancies.

PURPOSE: The aim of this prospective randomized trial was to examine the efficacy and safety of filgrastim after high-dose chemotherapy and autologous bone marrow transplantation (ABMT). PATIENTS AND METHODS: Patients with poor-risk non-Hodgkin's lymphoma or relapsed Hodgkin's disease were treated in a randomized, open-label trial to study the use of filgrastim as an adjunct to high-dose chemotherapy and ABMT. Of 43 assessable patients, 19 were randomized to receive filgrastim by continuous subcutaneous infusion at a dose of 10 micrograms/kg/d, 10 to filgrastim 20 micrograms/kg/d, and 14 to a parallel control group that received no filgrastim after ABMT. RESULTS: For all filgrastim-treated patients analyzed together, the median time to neutrophil recovery > or = 0.5 x 10(9)/L after the day of ABMT was significantly accelerated to 10 days compared with 18 days in control patients (P = .0001). The median number of platelet transfusions was identical in both groups. Clinical parameters, including the median number of days with fever (1 v 4, P = .0418) and neutropenic fever (5 v 13.5, P = .0001) were significantly shorter in the filgrastim than in the control group. The number of days on intravenous antibiotics and duration of hospitalization were also shorter in the treated groups; however, the differences did not reach statistical significance. For patients treated with the two different dose levels of filgrastim, the neutrophil recovery and clinical results were similar. Filgrastim-associated toxicity appeared to be minimal, with five adverse events considered at least possibly related to filgrastim: two in the higher-dose group and three in the lower-dose group. All of these were rated moderate, except one case of severe bone pain that did not preclude continued filgrastim treatment at a lower dose. Survival and relapse-free survival were similar for control and filgrastim-treated patients. CONCLUSION: Taken together, the results of this first randomized study support the role of filgrastim given as an adjunct to ABMT in accelerating neutrophil recovery, as well as in reducing treatment-related morbidity and overall duration of the treatment procedure.

Adolescent↗

[Pars plana vitrectomy in chronic uveitis].

Sixty-eight patients (74 eyes) with chronic endogenous uveitis underwent pars plana vitrectomy. An increase in visual acuity was observed in 70% postoperatively. Visual results basically depended on the extent of previous damage to the macula. A lensectomy-vitrectomy was done in 23 eyes, while 51 eyes underwent merely a pars plana vitrectomy. The frequency and severity of uveitic relapses were diminished in virtually all cases.

Adolescent↗

[Is pindolol suitable for the therapy of glaucoma? Evaluation of the dose-effect of various concentrations of pindolol eyedrops].

Various concentrations of Pindolol eye drops (0.17%, 0.35%, 0.5%, 0.72%, 1.0%), a beta-blocking agent with an intrinsic sympathomimetic activity, were investigated with regard to their pressure-lowering effect in open-angle glaucoma. It was found that all of these concentrations reduce intraocular pressure, but that only the 1% solution has a significantly stronger effect after 24 hours. It is therefore preferable to use this relatively high concentration, especially as it is not accompanied by a bronchopulmonary risk.

Adult↗

[Demonstration of the effects on the corneal epithelium of a mucomimetic collyrium. Study using scanning microscopy].

Ocular surface drying was studied in rabbits using an experimental model of blinking interruption. This model produces a discontinuity in the pre-corneal tear film after a few minutes of exposure to air. Changes in superficial epithelial cell structure were studied using a scan microscope. A decrease of micro-folds and an increase in epithelial cell desquamation were observed. Prolonged exposure to air produced similar cellular lesions in deeper layers. The instillation of a single mucomimetic eye-drop containing chondroitin sulphate prevented total interruption of epithelial humidification, kept the epithelial surface intact and preserved normal cellular structure.

Animals↗

[Stress on the eyeball caused by mechanical vibration. Studies of patient transport and experimental models].

The acceleration forces which occur in the eye and in the head region in transport of patients were investigated. It was to be established whether the finding often deteriorates appreciably in perforating eye injuries between the accident site and the ophthalmological operating theater. The investigation showed that smaller acceleration forces become active in the eye in the sitting position than in the lying position in patient transport. In transport in the hospital area, e.g., in the patient lift and on a stretcher, the maximum acceleration amplitudes which occur are greater than those occurring in the ambulance.--In the second part of the study, the region of the eyeball most sensitive to oscillation was determined experimentally in cadaver eyes in order to permit an evaluation of the acceleration parameters relevant in patient transport. It was shown that the eye is largely insensitive to the accelerations occurring in patient transport. It was shown that the eye is largely insensitive to the accelerations occurring in patient transport. Furthermore, it was shown that a vitreous prolapse cannot occur for this reason in an experimentally induced sclera injury.--Therefore, deteriorations in the condition of the bulb occurring in patient transport are due to movements of the eyelid and eyeball.

Eye Injuries↗

Delayed alloimmunization using random single donor platelet transfusions: a prospective study in thrombocytopenic patients with acute leukemia.

A randomized study was performed in 54 thrombocytopenic patients with acute leukemia. Alloimmunization of recipients of random multiple-donor platelet concentrates (MD group) was compared to that of patients receiving random single-donor platelets (SD group). In the SD patients, formation of alloantibodies (mostly anti-HLA) occurred less frequently (p less than 0.002), after a longer time period (p less than 0.002), and after a higher number of transfusions (p less than 0.005) as compared to MD patients. SD patients also became refractory to random platelets less frequently (p less than 0.005), after a longer time period, and after a higher number of transfusions (p less than 0.02). In SD patients, the increments after the first and the last transfusion were in the same range, whereas in MD patients, the 1-hr (p less than 0.001) and the 24-hr (p less than 0.025) increments decreased from the first to the last transfusion. Thus, the use of random SD platelet transfusions postponed alloimmunization.

Acute Disease↗

Acute myelogenous leukemia: successful treatment of relapse with cytosine arabinoside, VP 16-213, vincristine and vinblastine (A-triple-V).

Between March 1980 and January 1982, 15 patients with acute myelogenous leukemia (AML) in relapse were treated with one or more cycles of a combination chemotherapy consisting of cytosine arabinoside (Ara-C), VP 16-213, vincristine and vinblastine (A-triple-V). Of a total of 20 treatment cycles given, one partial and 15 complete remissions were achieved, there was no change in the bone marrow in two cases, one patient died due to Pseudomonas septicemia during an apparently normal bone marrow regeneration and one patient died of Candida infection while in aplasia. With 15 out of 20 (75%) successful relapse treatment courses, A-triple-V should be tested in first-line protocols.

Adult↗

Thrombin inhibition by malignant and normal cells: a cell-bound antithrombin effect.

Analysis of fresh surgical specimens of normal tissue and tumor tissue show a cellular antithrombin activity to be present in certain organs. In normal tissues it was noted chiefly in normal colon, testes, breast, and uterus. In malignant tissues it was prominent in adenocarcinomas of the colon, breast, and lung. No epidermoid tumors showed evidence of thrombin binding. The thrombin- binding activity required the presence of intact cells and was distinct from the soluble antithrombins normally present in plasma and serum. There is growing evidence to suggest an interrelationship between clotting and the growth and dissemination of cancer. The implications of cellular antithrombins are reviewed in this context.

Adenocarcinoma↗