A Clinical Update of the Hb Siirt [β27(B9)Ala→Gly; HBB: c.83C>G] Hemoglobin Variant

We report a clinical update of the hemoglobin (Hb) variant [β27(B9)Ala→Gly; HBB: c.83C>G], named Hb Siirt, that was previously described as a silent variant in a 23-year-old Kurdish female. The patient was also a carrier of the codon 5 (–CT) (HBB: c.17_18delCT) frameshift mutation and of the ααα ^{anti 3.7} triplication. Her initial moderate β-thalassemia intermedia (β-TI) phenotype worsened with time, causing the patient to become a transfusion-dependent subject at the age of ～40 years. Subsequent molecular characterization of both parents revealed that the Hb Siirt variant was inherited by the mother, while the other two globin alterations (HBB: c.17_18delCT and ααα^{anti 3.7} triplication) were genetically transmitted by the father. The latter remained a carrier of a mild β-TI phenotype throughout his life, at least until the age of 65 years. We hypothesize that the worsened clinical conditions in the daughter were due to the additional, maternally inherited Hb Siirt variant. However, protein 3D conformational analysis did not seem to reveal substantial overall structural changes. Among the other three described variants [Hb Volga (HBB: c.83C>A), Hb Knossos (HBB: c.82?G>T), Hb Grange-Blanche (HBB: c.83C>T] that are due to nucleotide substitutions at codon 27 of the β-globin gene; only Hb Knossos causes a β⁺-thalassemia (β⁺-thal) phenotype.     

Westernization of the Filipino population resident in Rome: obesity, diabetes and hypertension

BACKGROUND: Aims of the present study were to examine the anthropometrical and metabolic characteristics of the Filipino population migrant to the Southern European city of Rome, Italy. METHODS: A cross-sectional study was carried out in the city of Rome. Three hundred thirty-five Filipinos (95 M/240 F, mean age: 44.0+/-9.8 years, mean residence in Italy: 12.9+/-6.3 years) were studied. Data were collected by standardized questionnaires; anthropometrical parameters, arterial pressure, and fasting capillary blood glucose (FCG) were measured. RESULTS: Abdominal obesity was found in 52.5%, and BMI >or= 25 kg/m(2) in 44.5% of subjects. History of type 2 diabetes mellitus (T2DM) and hypertension were reported by 6.0 and 9.0% of subjects, respectively. Impaired fasting glucose was found in 13.1%, and FCG >or= 110 mg/dl in 18.5% of subjects. Altered systolic and/or diastolic blood pressure was found in 34.3% of subjects. About three-fourths of subjects were unaware of being diabetic and/or hypertensive. Years of Italy residence showed a direct significant correlation with the degree of changes in alimentary behaviours (rho=0.18, p=0.001), and with weight gain (rho=0.27, p<0.001). Multivariate analysis showed only age and waist circumference to be associated with both diabetes and hypertension. CONCLUSIONS: In the present study, the first to examine the metabolic disorders in a migrant Filipino population resident in Rome, a high prevalence of obesity, diabetes, and hypertension was found. The alarming results emerging from this study should be seriously considered by public health practitioners and decision makers, and made known to the Filipinos resident in Europe.     

Prognostic Implications of Declining Hemoglobin Content in Patients Hospitalized With Acute Coronary Syndromes

BackgroundContemporary definitions of bleeding endpoints are restricted mostly to clinically overt events. Whether hemoglobin drop per se, with or without overt bleeding, adversely affects the prognosis of patients with acute coronary syndrome (ACS) remains unclear.ObjectivesThe aim of this study was to examine in the MATRIX (Minimizing Adverse Haemorrhagic Events by Transradial Access Site and Systemic Implementation of Angiox) trial the incidence, predictors, and prognostic implications of in-hospital hemoglobin drop in patients with ACS managed invasively stratified by the presence of in-hospital bleeding.MethodsPatients were categorized by the presence and amount of in-hospital hemoglobin drop on the basis of baseline and nadir hemoglobin values and further stratified by the occurrence of adjudicated in-hospital bleeding. Hemoglobin drop was defined as minimal (<3 g/dl), minor (≥3 and <5 g/dl), or major (≥5 g/dl). Using multivariate Cox regression, we modeled the association between hemoglobin drop and mortality in patients with and without overt bleeding.ResultsAmong 7,781 patients alive 24 h after randomization with available hemoglobin data, 6,504 patients (83.6%) had hemoglobin drop, of whom 5,756 (88.5%) did not have overt bleeding and 748 (11.5%) had overt bleeding. Among patients without overt bleeding, minor (hazard ratio [HR]: 2.37; 95% confidence interval [CI]: 1.32 to 4.24; p = 0.004) and major (HR: 2.58; 95% CI: 0.98 to 6.78; p = 0.054) hemoglobin drop were independently associated with higher 1-year mortality. Among patients with overt bleeding, the association of minor and major hemoglobin drop with 1-year mortality was directionally similar but had wider CIs (minor: HR: 3.53 [95% CI: 1.06 to 11.79]; major: HR: 13.32 [95% CI: 3.01 to 58.98]).ConclusionsAmong patients with ACS managed invasively, in-hospital hemoglobin drop ≥3 g/dl, even in the absence of overt bleeding, is common and is independently associated with increased risk for 1-year mortality. (Minimizing Adverse Haemorrhagic Events by Transradial Access Site and Systemic Implementation of Angiox; NCT01433627)     

Absence of inferior vena cava as a rare cause of deep venous thrombosis complicated by liver and lung embolism

Congenital anomalies of the inferior vena cava such as absence or atresia are uncommon vascular defects and result from aberrant development during embryogenesis. We report a case of a young female patient affected by proximal deep venous thrombosis (DVT) complicated by liver and pulmonary embolism; subsequent extensive evaluation revealed the congenital absence of infrarenal inferior vena cava, with emboli probably occurring through collateral veins. Accordingly, in young patients with idiopathic DVT of the lower extremities and pelvic veins, the presence of inferior vena cava abnormalities should always be considered and investigated, together with classic coagulation factors, as a factor predisposing to thromboembolic complications.     

Vascular endothelial growth factor gene polymorphisms in Behçet's disease

OBJECTIVE: To evaluate potential associations of vascular endothelial growth factor (VEGF) gene polymorphisms with Beh?et's disease (BD) and disease expression. METHODS: Case patients were 122 consecutive Italian patients with BD followed at the Rheumatology, Ophthalmology, and Neurology Units in Bologna, Ferrara, Milano, Palermo, Potenza, Prato, Reggio Emilia, and Trento over a 3-year period (1997-99) and who satisfied the International Study Group criteria for BD. Also selected as a control group were 200 healthy age and sex matched blood donors. All patients with BD and controls were genotyped by polymerase chain reaction and allele-specific oligonucleotide techniques for +936 C/T (rs3025039) and -634 C/G (rs2010963) mutations and for an 18 base pair (bp) insertion/deletion (I/D) polymorphism at -2549 of the the VEGF promoter region. In vitro release of VEGF by peripheral blood mononuclear cells (PBMC) was investigated by ELISA in healthy controls homozygous for the polymorphisms studied. RESULTS: The carriage rates of the alleles I and -634C were significantly more frequent in patients with BD than in healthy controls [p corr = 0.036, OR 1.8 (95% CI 1.1-2.9) and p corr = 0.05, OR 1.8 (95% CI 1.1-3.0), respectively]. While the distribution of allele +936T was similar in patients with BD and healthy controls, its frequency was significantly higher in BD patients with posterior uveitis/retinal vasculitis than in those without (p = 0.022, OR 2.4, 95% CI 1.1-5.0). Lipopolysaccharide-stimulated VEGF production from PBMC of healthy subjects was higher in II homozygous than in DD homozygous. CONCLUSION: Our data indicate that carriers of -634C and I alleles are associated with susceptibility to developing BD.     

Radiofrequency ablation of hepatic tissue: a new experimental animal model

BACKGROUND/AIMS: Experimental radiofrequency ablation has already been performed in healthy livers of porcine models, but not in less expensive and easy-to-manage rats, with devices capable of delivering radiofrequency ablation in the 20-30 g liver of such small animals being so far unavailable. METHODOLOGY: We experimented with a modified system of radiofrequency ablation of liver tissue in rat models developing a custom-made needle-microelectrode of very small dimensions (0.3x2 mm) and an electrode-tip cooling technique, based on saline solution infusion. We adjusted duration (seconds) and power (watts) of radiofrequency ablation letting them range between 5-50 seconds and 5-25 W, respectively, to obtain the greatest lesions with the least side effects. After sacrificing the animals, an accurate histological examination of the liver was made. RESULTS: It is possible to establish beforehand the diameter of thermal liver lesion on the basis of joules of applied energy. The greatest increase of liver thermal lesion diameter (8 mm) is obtained with a 250-joule (10 W for 25 seconds) thermal energy cooling the electrode-tissue interface. CONCLUSIONS: Experimental radiofrequency ablation in rat liver is an effective and cheap way to study its effects on healthy hepatic tissues. It might be the first step to treat experimentally caused liver tumors.