[Palliative care: the demand and the realization].
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Biomedical subjects
Publications and source records attributed to F Momm.
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PURPOSE: To investigate whether amifostine can reduce radiation hematotoxicity. PATIENTS AND METHODS: Seventy-three patients undergoing radiotherapy for squamous cell carcinoma of the head and neck at the university clinics of Freiburg, Heidelberg, and Erlangen were evaluated. All received 60 Gy (50-70 Gy) at 5 x 2 Gy fractions per week employing standard techniques. Thirty-five were randomized to receive 200 mg/m(2) amifostine i.v. 30 min before radiation; 38 served as control patients. Blood counts (total n = 501) were determined before, during, and while completing radiotherapy. Changes of leukocyte, platelet, and hemoglobin levels were determined and compared using the t test. RESULTS: The blood hemoglobin level and the platelet count were not affected by irradiation, for either the amifostine-treated or control patients. Similarly, the leukocyte counts of amifostine-treated patients did not change during irradiation. However, control patients experienced a decrease in leukocyte count from 8.1 x 10(3)/mm(3) to 5.8 x 10(3)/mm(3) (difference: 2.3 x 10(3)/mm(3)). This seems to be line specific: Whereas amifostine does not affect lymphocyte count, a radiation-induced decrease of neutrophil granulocytes seems to be prevented. CONCLUSION: Amifostine protects from radiation hematotoxicity, particularly affecting the granulocytopoiesis. These data confirm results from our former study.
INTRODUCTION: After radiotherapy (XRT) for head and neck tumors, xerostomia is observed as a chronic side effect. We investigated whether the topical use of a mucin-containing spray can help patients to cope with this problem. PATIENTS AND METHODS: A total of 73 patients with xerostomia post XRT received a bottle of the mucin spray (Saliva medac) and a questionnaire, 59 of which were completed and returned. RESULTS: All patients had received some form of prior treatment, which had been applied 16 times/day on average (median: 15 times/day). The mucin spray had to be used less frequently, i.e., 11 times/day (median: 5 times/day), (p < 0.001, Wilcoxon's rank test). Additionally, they reported being able to sleep significantly better when using the mucin spray (2.9 vs 3.9 in the German school grading system: 1 = very good, 6 = poor; p < 0.001, Wilcoxon's rank test). The spray was well accepted by the patients. CONCLUSIONS: The spray was useful against xerostomia in irradiated patients.
PURPOSE: The cytoprotective agent amifostine has been shown to reduce the radiation-induced acute and chronic xerostomia in head and neck cancer patients. The purpose of this study was to evaluate whether or not amifostine also reduces the incidence of dental caries associated with the radiation-induced xerostomia. METHODS AND MATERIALS: The dental status before and 1 year after radiotherapy was retrospectively compared in 35 unselected patients treated as part of the prospective randomized and multicenter open-label Phase III study (WR-38) at the University Hospitals of Heidelberg, Freiburg, and Erlangen. The WR-38 study compared radiotherapy in head and neck cancer with and without concomitant administration of amifostine. RESULTS: Patient and treatment characteristics (particularly the radiation dose and percentage of parotids included in the treatment volume) were equally distributed between the patients who received (n = 17) or did not receive (n = 18) amifostine. Fifteen patients of the amifostine group showed no deterioration of the dental status 1 year after radiotherapy as compared to 7 patients who did not receive the cytoprotector (p = 0. 015, two-tailed Fisher exact test). CONCLUSION: Our data suggest a protective effect of amifostine on the dental health after radiotherapy of the head and neck. The dental status should be used as a primary endpoint in future studies on amifostine.
PURPOSE: To evaluate the influence of blood hemoglobin concentration on the radiosensitivity of acutely reacting normal tissues. METHODS AND MATERIALS: Weekly scores (EORTC/RTOG criteria) for acute reactions of skin and mucosa are available for 60 patients with cancer of the head and neck undergoing a standard conventional radiotherapy. The prognostic significance of blood hemoglobin levels on the development of acute reactions is studied by multivariate analysis (Cox Proportional Hazards Model). Further, the incidence and the time to development of these reactions is looked at in cohorts of patients with different mean blood hemoglobin concentrations during radiotherapy. Patients are therefore classified into a "severely anemic group" (hemoglobin < 11.0 g/100 mL), and into a cohort with a blood hemoglobin value equal or above 11.0 g/100 mL. RESULTS: Normal tissue scoring and monitoring of blood hemoglobin levels allows for a detailed analysis of possible correlations. A decrease in the mean blood hemoglobin value of 1 g/100 mL predicts a reduced risk to develop a skin reaction of Grade 2 or 3 (RR = 0.9; p = 0.08; RR = 0.8; p = 0.26, respectively) or a mucosa reaction of Grade 3 (RR = 0.8; p = 0.16), independent from the radiation dose, the treatment time and from previous surgery within the radiation volume (multivariate analysis). Likewise, patients with severe anemia develop grade 3 mucositis or dermatitis less often (0%; 13%) as compared to those with blood hemoglobin concentrations equal or above 11.0 g/100 mL (21%; 19%). Skin and mucosa reactions further tend to occur later in the course of radiation. The observations are not statistically significant and possible reasons will be discussed. CONCLUSIONS: A decreased blood hemoglobin concentration may-perhaps by an impaired tissue oxygenation-reduce the radiosensitivity of normal tissue such as skin and mucosa. However, the data is preliminary and needs further confirmation.
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BACKGROUND: Radiotherapy--even of small volumes--can decrease leukocyte counts. We examined whether the radio-protector amifostine can reduce this hematotoxicity. PATIENTS AND METHODS: Twenty-six patients (Table 1) undergoing radiotherapy for squamous cell carcinoma of the head and neck were evaluated. All were given 60 (to 70) Gy 5 x 2 Gy per week in standard radiation techniques. Thirteen patients are randomized to receive 200 mg/m2 amifostine i.v., 30 minutes before radiation. Blood counts and differentials were determined before, during and following radiotherapy. Differences of these parameters are calculated and compared by t-test. RESULTS: The blood hemoglobin and the thrombocyte levels did not change during the radiotherapy course, neither for the amifostine treated, nor the control patients. Similarly the leukocyte counts of amifostine treated patients did not change during irradiation. The control patients, however, had a decrease of leukocytes from 8.4 to 6.0 x 10(3)/microliter, p = 0.03 (Table 2), and the reduction of the neutrophilic granulocyte count was more impressive for these patients. CONCLUSION: In this explorative study amifostine diminished radiation induced leukocyte toxicity.
Cadmium toxicity to renal cells was investigated in Madin-Darby canine kidney (MDCK) and LLC-PK1 cells as models of the distal tubule/collecting duct and proximal tubule, respectively. Cells were grown on two-compartment filters and exposed to 0.1-50 microM Cd2+. In MDCK cells, Cd2+ was more toxic from the basolateral than from the apical side and dependent on the extracellular Ca2+ concentration. Toxicity was evident within 24 h, as shown by a decrease in transepithelial resistance (TER), reduced proliferation (bromodeoxyuridine incorporation), reduction in ATP concentration, and morphological changes. On confocal microscopy, E-cadherin and alpha-catenin staining patterns indicated interference with the cadherin-catenin complex. LLC-PK1 cells showed a similar toxicity pattern, which was evident at lower Cd2+ concentrations. An increase of E-cadherin and alpha-catenin molecules in the Triton X-100-insoluble fraction was detectable at high Cd2+ concentrations in LLC-PK1 cells but not in MDCK cells. Lactate dehydrogenase release indicated membrane leakage in LLC-PK1 cells. Rhodamine-phalloidin staining, a probe for F-actin filaments, demonstrated alterations of the actin cytoskeleton in both cell lines. In conclusion, cadmium caused ATP depletion and interfered with the cadherin-catenin complex and probably the tight junctions changing renal cell morphology and function.
BACKGROUND: The levels of mRNA-expression of multidrug resistance (MDR1) and glutathione-S-transferase pi (GST-pi) were measured and correlated with the immunohistochemical expressions of tumour markers. MATERIALS AND METHODS: Analysis of total mRNA was performed by Northern and slot blots. The expression of carcinoembryonic antigen (CEA) and other tumour markers was assessed by immunohistochemistry. The tumour panel comprised tumours of different histologies. RESULTS: CEA-positive tumours showed a significantly higher ex-pression of MDR1 and GST-pi than CEA-negative tumours. Wilcoxon-Test: mean rank of the MDR1 expression (14.3 vs. 7.8; p < 0.05) and GST-pi expression (15.3 vs. 5.9; p < 0.001). No other correlation could be found. CONCLUSIONS: The relationship of MDR1 and GST-pi with the tumour marker CEA implies that evaluation of CEA can help in discriminating between tumours with high or low expression of drug resistance. Furthermore, correlation between MDR1, GST-pi and CEA indicates that there might be a common mechanism, regulating drug resistance and expression of CEA.