Incidence of Crohn's disease and CARD15 mutation in a small township in Sicily.

BACKGROUND: The incidence of Crohn's disease (CD) has been shown to be lower in Southern than in Northern Europe. Data on the frequency of the NOD2/CARD15 mutations for Mediterranean area are very scant. AIM: To determine the incidence of CD from 1979 to 2002 in a township in Sicily together with the allele frequency of NOD2/CARD15 mutations in patients, family members and controls, and to determine the allele frequency of these mutations in sporadic CD from other areas of Sicily in comparison with a control population. METHODS: Casteltermini is a small town close to Agrigento (Sicily) with a population of 9,130 inhabitants. All the diagnoses of inflammatory bowel disease (IBD) made from 1979 to 2002 were obtained through the local health authority. NOD2/CARD15 mutations were studied in 23 out of the 29 patients with CD in Casteltermini, in 60 family members and in 64 controls. NOD2/CARD15 was also studied in 80 sporadic cases of CD disease among Sicilians outside Casteltermini and 118 healthy controls. RESULTS: From 1979 to 2002, 29 patients with CD and 13 patients with ulcerative colitis (UC) were registered. The 6-year mean incidence of CD ranged from 8.0 to 17 new cases for every 100,000 inhabitants, whereas the mean incidence of UC ranged from five new cases to 7.8 for every 100,000 inhabitants. The allele frequencies of NOD2/CARD15 mutations (L1007finsC, G908R, R702W) were 8.7, 4.3 and 8.7%, respectively, in CD cases; 5.0, 4.2 and 3.1% in family members; 1.6, 2.3 and 3.1% in controls. In sporadic Sicilian CD patients outside Casteltermini the allele frequency was 7.5, 8.1, 6.2% whereas in control population it was 3.3, 1.6, 1.6%. CONCLUSIONS: A high incidence of CD compared with UC was observed in this small town in Southern Italy. The frequency of NOD2/CARD15 mutations in CD is similar to other Caucasian population studied so far.

Clinical and hematological responses to hydroxyurea in Sicilian patients with Hb S/beta-thalassemia.

Although, several reports have detailed that hydroxyurea can ameliorate the clinical course of adult and pediatric patients with sickle cell anemia (Hb S or beta(S)), few clinical studies have been carried out in patients with beta(S)/beta-thalassemia. In a two-year clinical study, we evaluated the efficacy of hydroxyurea in a group of 22 adult Sicilian patients with beta(S)/beta-thalassemia with severe phenotypes. Among the 20 patients evaluated during 2 years of treatment, we observed a very good clinical response with a 93% reduction of the annual number of crises (median 7 versus 0.5 crises per year; P < 0.001) and of days in hospital (mean 22+/- 21.9 versus 1.2 +/- 2.3; P < 0.001), a significant increase in Hb F (7.5 +/- 5.3% versus 25.2 +/- 5.2%; P < 0.001) and in MCV (73.1 +/- 4.8 fL versus 96.4 +/- 7.2 fL; P < 0.001), and no significant modifications in Hb (9.6 +/- 1.3 g/dL versus 10.0 +/- 1.5 g/dL; P > 0.05) and in WBC (11.4 +/- 3.9 x 10(9)/L versus 10.2 +/- 3.9 x 10(9)/L; P > 0.05). Twelve patients had no crises from the first month of treatment; 16 patients showed a 2-3-fold increase over baseline in Hb F. During the study no severe complications and no important side effects of hydroxyurea were observed. Our data suggest that hydroxyurea efficacy in patients with beta(S)/beta-thalassemial may be greater than that described in patients with sickle cell disease. This pattern and durability of response will need to be confirmed in a larger, randomized, clinical trial.

Evidence of alloreactive T lymphocytes in fetal liver: implications for fetal hematopoietic stem cell transplantation.

The use of hematopoietic stem cells for in utero transplantation to create permanent hematochimerism represents a new concept in fetal therapy, although this approach has provided heterogeneous results. In this paper we have undertaken molecular, phenotypic and functional studies aimed at identifying the presence of fully competent T lymphocytes in samples of fetal livers and cord blood. We found mature VDJ TCR beta chain transcripts in fetal liver cells taken from 7 to 16 weeks of gestation and a similar pattern was detected in cord blood cells sampled from 13.5 to 20.5 weeks of gestation. A Vbeta8 gene sequence comparable to that detected in adult PBMC was found in fetal liver samples at 9 or 17 weeks gestation. PreTalpha message was detected in all samples and its expression decreased in fetal blood samples with increasing gestational age while Calpha message appeared at 9.4 weeks and its expression increased during gestational age. T cell clones obtained from fetal liver cells showed a mature TCR alphabeta+, CD8+ phenotype and displayed strong alloreactivity against allo-MHC class I molecules. The presence of alloreactive T lymphocytes may explain the failure to engraft in fetuses older than 13 to 16 weeks and may provide insights into fetal liver transplantation. Bone Marrow Transplantation (2000) 25, 135-141.

Clinical and hematological response to hydroxyurea in a patient with Hb Lepore/beta-thalassemia.

The possibility of increasing Hb F in vivo using drugs like 5-azacytidine, hydroxyurea, and butyrate has been established. However, in many cases this does not entail an increase in total hemoglobin. We report on a patient with Hb Lepore/beta-thalassemia being treated with hydroxyurea (30 mg/Kg/day) because of the presence of erythroid extramedullary masses with severe neurological abnormalities. During therapy the patient showed a remarkable improvement in neurological signs due to the reduction in extra-medullary masses, a significant increase in both total hemoglobin (from 5.8 to 9.7 g/dl) and Hb F (from 4.9 g/dl to 9.1 g/dl). The marked improvement in hemoglobin level in our patient with Hb Lepore/beta-thalassemia suggests gamma-globin gene activation due to the DNA structure determined by the crossover event.