ABSTRACT
AIMS: To assess insulin sensitivity and secretion in the fasting state in regularly transfused patients with beta-thalassaemia major with normal glucose response during an oral glucose tolerance test and to estimate its possible relation to iron overload. METHODS: We measured fasting glucose, insulin and C-peptide levels in 24 patients with beta-thalassaemia major and 18 control subjects matched for age and body mass index. Insulin sensitivity and insulin release index were calculated according to the homeostasis model assessment (HOMA). Correlations with age, body mass index and serum ferritin were also calculated. RESULTS: Fasting glucose levels in patients were increased compared with control subjects (5.5 +/- 0.12 vs. 4.7 +/- 0.13 mmol/l, mean +/- SEM, P < 0.001). Pancreatic B-cell insulin secretion in the fasting state (estimated by SC(HOMA)) was lower in thalassaemic patients (SC(HOMA) 88.5 +/- 11.11 vs. 184.3 +/- 23.72 in control subjects, P < 0.001). Patients were then divided into those with impaired (IFG) and normal (NFG) fasting glucose. SC(HOMA) was higher in the patients with NFG compared with those with IFG patients (110.6 +/- 17.63 vs. 66.3 +/- 10.88, respectively, P < 0.05) but estimated insulin sensitivity (ISI(HOMA)) was similar. Plasma values of C-peptide correlated positively with ferritin (r = 0.42, P = 0.04) and SC(HOMA) (r = 0.45, P = 0.02) and negatively with ISI(HOMA) (r = -0.43, P = 0.03). CONCLUSIONS: These results support the concept that impaired B-cell function, as reflected by a reduction in the insulin secretion index, is present in beta-thalassaemic patients with normoglycaemia before changes in oral glucose tolerance tests are apparent.
Subject(s)
Diabetes Mellitus/etiology , Insulin/metabolism , beta-Thalassemia/complications , Adult , Blood Glucose/metabolism , C-Peptide/metabolism , Case-Control Studies , Diabetes Mellitus/blood , Diabetes Mellitus/metabolism , Female , Glucose Tolerance Test , Homeostasis , Humans , Insulin/deficiency , Insulin Secretion , Male , Models, Biological , beta-Thalassemia/bloodABSTRACT
BACKGROUND: Several factors are currently employed for prognosis assessment and treatment determination in breast cancer. An array of molecular parameters, such as p53, Her2-neu (c-erbB 2) and Cathepsin-D, are also examined to improve clinical patient management. We have conducted a statistically powerful study of the prognostic value of conventional factors and of the investigational factors p53, Her2-neu and Cathepsin-D in patients with invasive breast carcinoma, in order to compare their significance. Our analysis was extended to determine the associations of p53 and Her2-neu with risk of death and relapse among patients with and without lymph node metastases. MATERIALS AND METHODS: In a set of 125 primary breast tumors, p53 and Her2-neu expression were immunohistochemically evaluated. Cathepsin-D, estrogen and progesterone receptor concentrations were determined in cytosols by a standard immunoradiometric assay. RESULTS: Over a mean of 62 months, 49 patients (39%) had a relapse and 29 patients (23%) died. Overexpression of p53, Her2-neu and Cathepsin-D was observed in 31%, 46% and 88% of cases, respectively. Overall survival was associated with histology (hazard ratio 0.04, 95% confidence interval: 0.01, 0.49 for lobular tumors) and stage (hazard ratio 5.94, 95% confidence interval: 1.30, 27.15 for stage III samples). Disease-free survival was also related to histology (hazard ratio 0.23, 95% confidence interval: 0.08, 0.73 for lobular tumors) and stage (hazard ratio 4.27, 95% confidence interval: 1.36, 13.36 for stage III tumors). Patients with both negative nodal status and Her2-neu overexpression tended to display an elevated risk of death. CONCLUSION: Our results support the prognostic power of tumor histology and stage and emphasize the need for further studies on the prognostic impact of p53. Her2-neu and Cathepsin-D in breast cancer. Additionally, our analysis indicates that deregulation of Her2-neu might characterize a subgroup of node-negative patients with poor prognosis who could benefit from an aggressive adjuvant therapy.
Subject(s)
Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Cathepsin D/biosynthesis , Receptor, ErbB-2/biosynthesis , Tumor Suppressor Protein p53/biosynthesis , Adult , Aged , Aged, 80 and over , Breast Neoplasms/surgery , Disease-Free Survival , Female , Humans , Immunohistochemistry , Lymph Nodes/pathology , Middle Aged , Multivariate Analysis , Neoplasm Staging , Proportional Hazards Models , Receptors, Estrogen/biosynthesis , Receptors, Progesterone/biosynthesis , Survival AnalysisABSTRACT
OBJECTIVE: To evaluate the results of computed tomography (CT)-guided fine needle aspiration (FNA) cytology following negative fiberoptic bronchoscopy and sputum cytology. STUDY DESIGN: Retrospective study of 64 patients who underwent CT-guided needle aspiration of lung opacities over one year. Following a review of the CT studies, patients were selected according to image characteristics of a primary neoplasm and pleural effusion in cases with pleural lesions. The lesions were classified into three categories--intrapulmonary and peripheral pulmonary, pleuropulmonary and pleural--and were localized and aspirated under CT using a fine needle (22-23 gauge) for obtaining cellular material. Lesions diagnosed as benign on FNA cytology were followed by serial CT scans for a period of two years at six-month intervals. RESULTS: Thirty-nine of 64 (61%) lesions were diagnosed as malignant on FNA cytology and 25 of 64 (39%) as benign. There was one false negative case. There were no serious complications from the procedure. CONCLUSION: FNA under CT guidance may be applied as the initial procedure in the diagnosis of peripheral malignant pulmonary lesions, rendering a high diagnostic yield.
