Increase in the prevalence of the MTHFR 677 TT polymorphism in women born since 1959: potential implications for folate requirements.

BACKGROUND/OBJECTIVES: Folate has been recognized to ensure reproductive health and there is a growing body of epidemiological evidence suggesting that the methylenetetrahydrofolate reductase (MTHFR) 677T allele and reduced dietary folate may increase the risk of cervical cancer. The main focus of our survey was to investigate the distribution of the MTHFR C677T polymorphism in relation to women's year of birth and to assess their folate intake and folic acid supplementation. SUBJECTS/METHODS: During a 6-months period, 307 healthy women of childbearing age in Catania, Italy, were enrolled in the cross-sectional study. Folate intake was estimated by a semiquantitative food frequency questionnaire and DNA extracted from blood samples for MTHFR C677T genotyping. RESULTS: A TT genotype frequency of 20.5% with an increase in the prevalence of the TT genotype in the cohort of women born since 1959 was shown. The prevalence of inadequate folate intake was 51.5%, significantly higher in non-pregnant women (83.4%) than in pregnant ones (12.3%) with a decrease during the three trimesters of pregnancy (from 25.7 to 5.0%; P=0.013). The use of folic acid supplements improved during the three trimester of pregnancy (from 71.4 to 95.0%; P=0.001). CONCLUSIONS: Healthy young women may have higher folate needs due to increasing prevalence of the T allele and reduced folate intake compared with older groups. However, clinicians should be cautious when recommending supplements to women in late pregnancy due to the possible implications in the pregnancy outcome.

Thalassaemic men affected by erectile dysfunction treated with transurethral alprostadil: case report.

The aim of this controlled clinical study, performed in a specialized institutional unit for thalassaemic men, was to consider the possibility of restoring erection in beta-thalassaemic patients with erectile dysfunction by administering E(1) prostaglandins (alprostadil) transurethrally. Four patients affected by beta-thalassaemia, aged between 32 and 52 years, and having an erectile dysfunction were included in the study. Each patient was given 500 microg alprostadil in the distal urethra. Response was evaluated by the erection assessment scale. The main outcome measures were: (i) the clinical study; (ii) FSH, LH, total and free testosterone plasma concentrations; and (iii) basal and dynamic Doppler sonography of cavernous arteries. The treatment produced a response of 3-4 on the erection assessment scale. Average minimum response time was 20 min, while average maximum response time was about 60 min. There was no evidence of significant side effects. Our hypothesis is that the delayed reaction was due to organ damage induced by iron load, causing a reduction or absence of elasticity in the interstitial tissue of the corpora cavernosa. Thus, we believe that treatment with alprostadil can be considered an effective, non-invasive therapy for thalassaemic patients with erectile dysfunction.

Factibilidad de la implementación de un registro de infarto de miocardio en el contexto de un programa de prevención / Feasibility of myocardial infarction record on a prevention program

Se realizó un registro de infarto piloto en la ciudad de La Plata con el fin de analizar su factibilidad de implementación en el marco de un progama de prevención de factores de riesgo. El estudio se llevó a cabo en diez centros de recolección de datos (Unidades Coronarias) de dicha ciudad. La propuesta de realizar un Registro de Infarto en el área de demostración de un proyecto de prevención primaria y a través de un modelo estandarizado, basado en el MONICA, y en el marco de un proyecto de prevención primaria permitiría la obtenció de data genuina tanto de infarto de miocardio como de los factores de riesgo implicados

Factibilidad de la implementación de un registro de infarto de miocardio en el contexto de un programa de prevención / Feasibility of myocardial infarction record on a prevention program

Se realizó un registro de infarto piloto en la ciudad de La Plata con el fin de analizar su factibilidad de implementación en el marco de un progama de prevención de factores de riesgo. El estudio se llevó a cabo en diez centros de recolección de datos (Unidades Coronarias) de dicha ciudad. La propuesta de realizar un Registro de Infarto en el área de demostración de un proyecto de prevención primaria y a través de un modelo estandarizado, basado en el MONICA, y en el marco de un proyecto de prevención primaria permitiría la obtenció de data genuina tanto de infarto de miocardio como de los factores de riesgo implicados (AU)

Laboratory evaluation of a new delivery system to improve patient compliance with chelation therapy.

As thalassaemia patients live longer, compliance with chelation therapy becomes more and more of a problem. Teenagers rebel against the continual need for treatment, and young adults with jobs, active social lives and families, find it hard to find the time to prepare and deliver their treatments. In an effort to find a solution to this problem, we evaluated a non-electronic, disposable pump (Infusor 5 ml/h, Baxter Healthcare) to determine its suitability for high dose desferrioxamine (DFO) infusions. We wanted an infusion time of 12 h to support overnight delivery in the patient's home. Because of DFOs viscosity, infusion times vary at different concentrations. We found the optimal prescription for total delivery within 12 h to be a dose of 70 mg/kg x patient's body weight diluted in constant volume of 40 ml of water for injection. Our tests were carried out in vitro and the results show that the 5 ml/h Infusor may be used to deliver high dose DFO chelation therapy within 12 h. The variability of the flow rate, dependent on the concentration of the solution, and the absence of a warning system, are more than compensated for by the simplicity of the pump.

High-dose intravenous desferrioxamine (DFO) delivery in four thalassemic patients allergic to subcutaneous DFO administration.

To test the hypothesis that allergy to desferrioxamine is not an immunologic mechanism, but arises from a local effect on the dermal mast cell, we have treated four patients who were not receiving chelation therapy because of hypersensitivity to standard subcutaneous (SC) therapy, with high-dose desferrioxamine (DFO) by the intravenous (IV) route. Three patients had central venous access ports implanted on the anterior chest wall. The fourth patient had the therapy delivered by the peripheral vein route. All patients had the drug delivered via an elastomeric infusor. Intravenous therapy was successful for all patients. During one year of therapy no local or systemic allergic manifestations were noted. In addition, no impairment of hearing or vision or any catheter complications were reported. A very high level of patient compliance to the therapy resulted in dramatically decreased iron stores and ferritin levels (2,759 ng/ml to 717.5 ng/ml) and a significant improvement in the clinical status of all patients. The absence of allergic episodes in this patient group after 1 year of i.v. therapy would strongly support the hypothesis that SC DFO allergy is related to a direct effect on dermal mast cells and is not an immunological reaction. This study suggests that patients with severe allergy to SC DFO can therefore safely receive their chelation therapy via the i.v. route.

Cardiac iron overload in thalassemic patients: an endomyocardial biopsy study.

Secondary heart failure induced by organ siderosis is the main cause of death in patients affected by thalassemia major. At present it cannot be predicted whether heart siderosis is correlated with iron overload and little is known about the real cardiac histological pattern of post transfusional hemochromatosis in patients with thalassemia major and intermedia. The study aim was to evaluate cardiac iron overload by non invasive and invasive techniques. Fifteen thalassemic patients were investigated and endomyocardial biopsy performed in ten revealed different grades of endomyocardial iron overload with histochemical positivity. Non invasive techniques are not able to furnish an exact picture of the cardiac hemochromatosis. There was a significant correlation between serum ferritin and myocardial iron grade. Patients with elevated ferritin levels and poor compliance to chelating therapy are at high risk of severe heart hemochromatosis. It was seen that endomyocardial biopsy is a useful tool in studying myocardial iron.

Presence of an African beta-globin gene cluster haplotype in normal chromosomes in Sicily.

African admixture in Sicily has been long suspected because of the presence of the sickle gene. Nevertheless, the degree of African admixture cannot be derived from the study of HbS frequency, since this gene was most likely expanded by the selective pressure of malaria, for a long time endemic to the region. We have examined 142 individuals from the Sicilian town of Butera (12% sickle trait) to search for other markers of the globin gene cluster less likely to be selected for by malaria. The TaqI polymorphism in the intervening sequences between the two gamma genes is informative. We have found only two instances of this African marker (TaqI(-)) among 267 normal chromosomes, demonstrating that the admixture occurred at a much lower level than previously thought.

HCV and HBV infection among multitransfused thalassemics from eastern Sicily.

Serum specimens from 152 Sicilian multitransfused thalassemic subjects were tested for antibodies to hepatitis C virus (anti- HCV) and for HBV markers by enzyme linked immunoassay and with reference to anti-HCV, confirmed by recombinant immunoblot assay. A high rate (47%) of subjects was anti-HCV positive. HBsAg was found in 8% of patients and 55% had anti-HBs or anti-HBc antibodies or both. Contrary to HBV infection, anti-HCV seropositivity was related to the number of transfused units. The highest anti-HCV prevalence was observed between 16 and 20 years; 100% of persons older than 50 years had at least one marker of HBV infection. In conclusion, HCV and HBV are widespread among multitransfused thalassemic. Probably in our area, particularly during the pre-HBsAg screening era, several multitransfused patients were infected by HBV more readily than by HCV.