Quantitative evaluation of oxidative stress status on peripheral blood in beta-thalassaemic patients by means of electron paramagnetic resonance spectroscopy.

High oxidative stress status (OSS) is known to be one of the most important factors determining cell injury and consequent organ damage in thalassaemic patients with secondary iron overload. Using an innovative hydroxylamine 'radical probe' capable of efficiently trapping majority of oxygen-radicals including superoxide we measured, by electron paramagnetic resonance (EPR) spectroscopy, OSS in peripheral blood of 38 thalassaemic patients compared with sex-/age-matched healthy controls. Thalassaemic patients showed sixfold higher EPR values of OSS than controls. Significantly higher EPR values of OSS were observed in those with a severe phenotype (thalassaemia major, transfusion-dependent) with respect to mild phenotype (sickle-cell/beta-thalassaemia, not transfusion-dependent) or thalassaemia intermedia. In patients with thalassaemia major, EPR values of OSS were positively correlated with serum ferritin and with alanine aminotransferase levels. In patients with sickle cell/beta-thalassaemia, there was no correlation between EPR value of OSS and all parameters considered. The type of chelating therapy (desferrioxamine or deferiprone) did not have an effect on EPR value of OSS. In conclusion, EPR 'radical probe' seems to be a valid innovative method to determine total OSS in patients affected by thalassaemia and might be used for evaluating new strategies of chelation, new chelators, or the efficacy of antioxidant formula.

Hypogonadism and hormone replacement therapy on bone mass of adult women with thalassemia major.

We studied bone mass and metabolism in 30 adult women (age 28.5 +/- 1.3) with thalassemia major (TM) and evaluated whether prolonged hormone replacement therapy (HRT) was able to optimize bone accrual. TM patients had reduced bone mass, increased bone turnover and lower serum gonadotropin and estradiol levels compared with 10 normal women of similar age. A significant correlation was found between bone mass and sex hormone levels. Six TM patients with normal ovarian function had normal bone turnover markers and modestly low bone mass (lumbar spine -1.29 +/- 0.31; femoral neck -0.60+/-0.21; Z-score). The other 24 TM women were hypogonadic and had significantly lower bone mass for age (lumbar spine -2.35 +/- 0.2, femoral neck -1.83 +/- 0.2) and increased bone turnover relative to eugonadal women. Of the hypogonadal patients, 13 had taken HRT since age 15 +/- 1 years, but their bone mass and turnover markers were not different than untreated hypogonadal patients. In conclusion, while hypogonadism negatively affects bone mass acquisition in adult TM women, HRT at the standard replacement doses is not sufficient to secure optimal bone accrual.

Treatment of isolated articular cartilage lesions of the medial femoral condyle. A clinical nad MR comparison of autologous chondrocyte implantation vs. microfracture.

Microfracture (MFX) and Autologous Chondrocyte Implantation (ACI) have been utilized in an effort to promote the regeneration of articular cartilage in the knee. The purpose of this study is first, to determine which of these two treatments yields the best clinical results and, second, to determine whether the MR appearance of treated cartilage lesions correlates with clinical outcome. Thirty-five patients with isolated articular cartilage lesions of the medial femoral condyle (MFC) were treated either with ACI (17 patients) or with MFX (18 patients, 19 knees). Patients were evaluated clinically using the modified Cincinnati Knee Questionnaire and with a physical exam. MRs were graded using eight different criteria: an MR score of 100% represents normal cartilage. The average follow-up was 2,6 years for the ACI group and 2,8 years for the MFX group. The average size of the lesion was 472 mm2 for the ACI group and 326mm2 for the MFX group. The Cincinnati scores improves an average of 22% for the ACI patients and 42% for the MFX patients from preoperatively to postoperatively. The average MR score was 66% for the ACI group and 44% for the MFX group. Fifty-nine percent of the ACI patients required at least one additional procedure. This is the first clinical and MR comparison of ACI and MFX to treat full thickness cartilage lesions of the MFC. Clinical improvement was 2 times greater for the MFX patients compared to the ACI patients. The MR scores did not correlate with clinical outcome using our grading system.

MR imaging of pancreatic changes in patients with transfusion-dependent beta-thalassemia major.

OBJECTIVE: The aim of this study was to evaluate MR imaging changes of the pancreas in patients with transfusion-dependent beta-thalassemia major. SUBJECTS AND METHODS: Twenty patients with transfusion-dependent beta-thalassemia major were examined using MR imaging at 0.5 T, with spin-echo T1-weighted, fast spin-echo T2-weighted, and gradient-echo T2*-weighted sequences. Image analysis was performed to assess pancreas-to-fat signal intensity ratios for all pulse sequences. Pancreatic exocrine and endocrine function and serum ferritin levels were assessed. Twenty healthy volunteers underwent MR imaging with the same three sequences and served as a control group. RESULTS: The pancreas-to-fat signal intensity ratio was significantly decreased in 17 (85%) of the 20 patients on spin-echo T1-weighted images (p < .05), fast spin-echo T2-weighted images (p < .01), and gradient-echo T2*-weighted images (p < .01) when compared with the 20 volunteers in the control group. The pancreas-to-fat signal intensity ratio was significantly increased in three (15%) of the 20 patients on spin-echo T1-weighted images (p < .01) and fast spin-echo T2-weighted images (p < .05). In addition, in the 20 patients, we found a significant correlation between increased pancreas-to-fat signal intensity ratios and decreased serum trypsin levels (r = -.77, p < .01 for spin-echo T1-weighted sequences; r = -.75, p < .05 for fast spin-echo T2-weighted sequences; and r = -.74, p < .05 for gradient-echo T2*-weighted sequences). Likewise, for the 20 patients, we found a significant correlation between decreased pancreas-to-fat signal intensity ratios and increased serum ferritin levels for gradient-echo T2*-weighted images (r = -.65, p < .01). No correlation was found for the other clinical parameters evaluated. CONCLUSION: MR imaging revealed signal intensity changes in the pancreas of patients with transfusion-dependent beta-thalassemia major. Patients with a major impairment of the exocrine pancreatic function had higher signal intensity of the pancreas because of fatty replacement of the parenchyma.

Short stature and body proportion in thalassaemia.

Short stature and short trunk have been reported in thalassaemic patients. We report a study on stature and body proportions in 476 patients (2-36 years old) with beta-thalassaemia major, followed in 12 Italian centres. Auxological data (standing height, sitting height, subischial leg length, target height), haematological data (age at first transfusion, age at start of desferrioxamine [DFX] chelation, mean dose of DFX, ferritin values) and information regarding the presence of endocrine disorders and of bone lesions, were collected and analysed according to the age of the patients, in order to investigate the natural history of the disproportion and the role of siderosis, DFX toxicity and endocrine disorders. Our data indicate that about 18% of thalassaemic patients exhibit short stature; disproportion between the upper and lower body segments is present in 14%; however, a short trunk despite normal stature is present in another 40% of patients. This is due to a spinal growth impairment which starts in infancy and progressively aggravates. We think that a short trunk is peculiar to the disease itself; however, other factors such as hypogonadism, siderosis, or DFX-induced bone dysplasia are probably involved in aggravating the body disproportion in these patients.

Serum and fecal pancreatic enzymes in beta-thalassemia major.

CONCLUSION: This study, using indirect tests, demonstrated that exocrine pancreatic function is impaired in a proportion of patients with beta-thalassemia major (TM), though this impairment is generally mild or moderate. BACKGROUND: Impaired structure and function of the exocrine pancreas has been reported in patients with Beta-thalassemia major. METHODS: In this study we measured fecal fats and serum and fecal pancreatic enzymes in 30 patients (13 M, 17 F) with TM, mean age 22.1 yr (range 14-39) and compared them with those of a matched group of healthy controls. Results were correlated with age, serum ferritin, blood transfusion, and various nutritional parameters. Enzymes assays included: serum pancreatic amylase (PA), lipase (L), trypsin (T), fecal chymotrypsin (FCT), and fecal elastase (FE). RESULTS: No patient was positive for steatorrhea. Comparison of the mean values showed a significant difference only for FE (p < 0.002). Using only the fecal tests as a reference, we found that 12 patients had FE values below the cutoff limit; of these, five had values between 100 and 185 micrograms/g, three between 50 and 99 micrograms/g and four below 50 micrograms/g. Ten patients had FCT values below the cutoff limit; seven presented impairment in both tests and six of them had FE values below 100 micrograms/g (including four diabetics). No correlations were found between enzyme values and mean serum ferritin values or mean blood consumption over the previous 3 yr. No correlation was found between FE and FCT levels or between enzymes and age.

Long-term efficacy of alpha-interferon in beta-thalassemics with chronic hepatitis C.

Hepatitis C virus (HCV) infection is a common cause of liver disease among polytransfused thalassemics. We treated a cohort of subjects with beta-thalassemia major and chronic hepatitis C with alpha-interferon. The aims of the study were to assess the long-term biochemical and virologic efficacy of alpha-interferon and to evaluate the influence of HCV type and liver siderosis on the outcome of therapy. Seventy subjects (mean age, 14.1 years) with chronic HCV infection and abnormal aminotransferases received recombinant alpha-interferon for 12 months and were observed after therapy for at least 24 months. Sixty-three subjects (90%) were HCV-RNA positive at the start of therapy. HCV type 1b was found in 41 subjects (65.1%), non-1b types in 13 (20.6%), and mixed HCV types in 9 (14.3%). Liver biopsy showed cirrhosis in 11 subjects (15.7%) and siderosis grade 3-4 in 24 patients (34.2%). Three patients stopped therapy due to adverse events. Twenty-eight subjects (40%) had normal aminotransferases and had cleared HCV-RNA when last observed (mean follow-up, 36.5 months; range, 25 to 49 months). Of 41 patients who did not normalize aminotransferases, 9 had become HCV-RNA negative at the end of follow-up. The absence of cirrhosis, low liver iron content, and infection with non-1b HCV type were independently associated to complete sustained response upon multivariable analysis. In conclusion, alpha-interferon may induce a sustained virologic and biochemical remission of hepatitis in beta-thalassemic patients with chronic HCV infection and nonadvanced liver disease.