Influence of ionizing radiation on proliferation, c-myc expression and the induction of apoptotic cell death in two breast tumour cell lines differing in p53 status

PURPOSE: To determine the capacity of ionizing radiation to inhibit proliferation, to suppress c-myc expression and to induce apoptotic cell death in the p53 wild-type MCF-7 cell line and the p53 mutated MDA-MB231 cell line. MATERIALS AND METHODS: Growth inhibition and cell killing were determined by cell number and trypan blue exclusion. Apoptosis was assessed through cell morphology and fluorescent end-labelling. c-myc expression was monitored by Northern blotting. RESULTS: Inhibition of cell proliferation by ionizing radiation was similar in both cell lines. MDA-MB231 cells accumulated in G2 while MCF-7 cells accumulated in both the G1 and G2 phases of the cell cycle after irradiation. There was no evidence of apoptosis in either cell line. In MCF-7 cells, growth inhibition correlated closely with an early dose-dependent suppression of c-myc expression; in MDA-MB231 cells, there was no correspondence between growth inhibition and a transient, dose-independent reduction in c-myc message. CONCLUSIONS: These findings suggest that in the absence of classical apoptotic cell death, radiosensitivity is not predictably related to the p53 status of the cell. While both p53 and c-myc may be linked to the DNA damage response pathway, neither p53 nor c-myc are essential for growth arrest in response to ionizing radiation.     

Effectiveness of an organized follow-up system for elder patients released from the emergency department

OBJECTIVES: To determine whether an effective telephone callback system can be successfully implemented in a busy ED and to quantify the benefits that can be obtained related to the follow-up care of elder patients. METHODS: This was a prospective, cohort study conducted at a community teaching hospital during a 6-month period. Consecutive patients > or = 60 years old and released from the ED were selected for telephone follow-up. Calls were made by a research nurse within 72 hours after the patient's ED visit. Follow-up information included current medical status, problems encountered during the ED visit, compliance, and impact of the illness on self-care capabilities. RESULTS: Seventy-nine percent (831/1,048) of the patients selected for telephone follow-up were successfully contacted. The calls lasted an average of 4 +/- 2.5 minutes. Although 94% (778/831) of these patients had a regular physician, 14% failed to make their recommended follow-up arrangements. Compliance was significantly improved when a follow-up physician was contacted during the patient's ED visit. Approximately 96% of the patients were either satisfied or very satisfied with their ED care. However, 13% (109/831) had moderate deterioration in their ability to care for themselves. Of the patients contacted, 333 (40%) required further clarification of their home care instructions, 31 were advised to return to the ED for reevaluation, and 26 were referred to a medical social worker for psychosocial concerns. CONCLUSION: A telephone callback system is a feasible and effective method to improve follow-up care of elder patients released from the ED.     

Flavonoids, dietary-derived inhibitors of cell proliferation and in vitro angiogenesis

Consumption of a plant-based diet can prevent the development and progression of chronic diseases associated with extensive neovascularization, including solid malignant tumors. In previous studies, we have shown that the plant-derived isoflavonoid genistein is a potent inhibitor of cell proliferation and in vitro angiogenesis. In the present study, we report that certain structurally related flavonoids are more potent inhibitors than genistein. Indeed, 3-hydroxyflavone, 3',4'-dihydroxyflavone, 2',3'-dihydroxyflavone, fisetin, apigenin, and luteolin inhibited the proliferation of normal and tumor cells, as well as in vitro angiogenesis, at half-maximal concentrations in the low micromolar range. We have previously demonstrated that genistein concentrations in the urine of subjects consuming a plant-based diet is 30-fold higher than in subjects consuming a traditional Western diet. The wider distribution and the more abundant presence of flavonoids in the plant kingdom, together with the present results, suggest that flavonoids may contribute to the preventive effect of a plant-based diet on chronic diseases, including solid tumors.     

Single lung transplantation in patients with systemic disease

OBJECTIVE: To report functional results and survival in patients undergoing single lung transplantation (SLT) for pulmonary involvement associated with systemic disease or prior malignancy, criteria traditionally considered contraindications to SLT. DESIGN: Case series. SETTING: The University of Texas Health Science Center at San Antonio. PATIENTS: Nine patients who have undergone SLT for end-stage lung disease: four patients with sarcoidosis; two patients with limited scleroderma; and three patients with prior malignancies (two with prior lymphoma and bleomycin-induced pulmonary fibrosis and one who received two bone marrow transplants for acute lymphocytic leukemia and subsequently developed chemotherapy-induced pulmonary fibrosis). MEASUREMENTS: Pulmonary function testing, exercise oximetry, quantitative ventilation-perfusion lung scanning. Actuarial survival. RESULTS: All patients had marked improvement in pulmonary function, exercise oximetry, and quantitative ventilation perfusion to the SLT. One patient with scleroderma died 90 days postoperatively from Pseudomonas pneumonia with a sepsis syndrome. One patient with sarcoidosis died 150 days postoperatively from disseminated aspergillosis. At autopsy, there was no evidence of recurrent fibrosis or sarcoidosis in the transplanted lungs in either of these two patients. The seven surviving patients have returned to work or school and are conducting all activities of daily living without pulmonary disability. The 1- and 2-year actuarial survival rates in these nine patients is 68.6 percent as compared with the 1- and 2-year actuarial survival rates of 66.3 percent and 55.8 percent in the remainder of our SLT group as a whole (n = 49). Despite pharmacologic immunosuppression, there is no evidence of recurrent malignancy in the 3 patients with prior malignancies. CONCLUSIONS: We conclude that carefully selected patients with end-stage lung involvement related to systemic disease or chemotherapy-induced fibrosis may benefit from SLT.     

Bone mineralization and body composition in young patients with celiac disease

OBJECTIVES: The aim of the study was to establish whether body composition in patients with celiac disease is normal and influenced by the age at diagnosis or by the duration of the gluten free diet. METHODS: A group of 66 children with celiac disease and 76 healthy controls were studied by dual energy x-ray absorptiometry. We compared celiac patients with the control group, and within the celiac disease group, we compared patients with different age at diagnosis (28 diagnosed in the first 24 months vs 38 later) and with different duration of the diet (16 in gluten free diet for less than 12 months, 11 for less than 24 months, and 39 for more than 24 months). RESULTS: Overall we did not find any significant difference in body composition between overall celiac patients and controls. However the fat mass, the body mass index, and the spine bone mineral density values in late diagnosed celiac patients were significantly lower than in early diagnosed patients (significance values were p < 0.009; p < 0.002; p < 0.002, respectively). Patients on diet for less than 12 months showed significantly lower bone mineral content and density than those on diet for more than 24 months (significance values were, respectively, p < 0.011 and p < 0.022). Spine mineral density was the only parameter significantly influenced both by age at diagnosis (p < 0.03) and duration of gluten free diet (p < 0.008). CONCLUSIONS: Only an early diagnosis of celiac disease in pediatric age and a strict gluten free diet, lasting more than 12 months, allow celiac patients to reach a normal mineralization.