Increased factor VIII coagulant activity levels in male carriers of the factor V R2 polymorphism.

A common factor V gene haplotype, the FVR2 haplotype (FVHR2), has been associated with a reduced cofactor activity in activated protein C-mediated activated factor VIII inactivation. Our aim was to investigate the role of FVHR2 as a possible determinant of factor VIII levels in a population study. A total of 516 individuals (401 men, 115 women; mean age 58.4 +/- 10.8 years) were enrolled within the frame of a regional cardiovascular survey, characterized for factor VIII coagulant activity (FVIII:c) and factor V coagulant activity (FV:c) levels, and genotyped for factor V polymorphisms. In men without signs of overt inflammation, FVHR2 carriers had higher levels of FVIII:c than noncarriers (154 IU/dl, 95% confidence interval = 143-166 versus 142 IU/dl, 95% confidence interval = 138-147; P = 0.045) and were more represented in individuals with high (> or = 150 IU/dl) FVIII:c levels (21.2 versus 10.8%; odds ratio = 2.27, 95% confidence interval = 1.17-4.39 after adjustment for age, blood group and high-sensitivity C-reactive protein levels). In conclusion, this clinical report suggests the common FVHR2 as a possible independent determinant of FVIII:c levels. The report concomitantly addresses the relationship between factor V and factor VIII levels and supports the hypothesis of a mild prothrombotic role of FVHR2 by means of increased factor VIII levels.     

Transitional progressive multiple sclerosis: MRI and MTI findings

Transitional progressive multiple sclerosis (MS) is quite an unusual form of presentation and course of the disease. A case with this progressive form is presented and brain MRI and MTI findings are discussed in relation to the possible insight they may provide for understanding the mechanisms that determine progressive disability in MS.     

Diffusion-weighted imaging study of patients with essential tremor.

The pathophysiology of essential tremor (ET) is unknown. PET and fMRI studies have revealed bilateral activation and (1)H-MRS studies metabolic abnormalities in the cerebellum and other functionally related brain structures in ET. Diffusion-weighted imaging (DWI) was used to search for evidence of tissue integrity abnormalities in these areas in ET patients and 10 matched controls by calculating water apparent diffusion coefficients (ADCs). Regions of interest included the left and right cerebellum, red nucleus, thalamus, caudate, putamen, pallidum, and frontal white matter. Histograms of ADCs were generated for all pixels in the infratentorial compartment and manually segmented areas corresponding to brainstem, vermis, and cerebellar hemispheres. ADC values were similar in all brain areas in patients and controls. Our study did not detect changes affecting the investigated brain regions in ET patients. These findings argue against major structural damage in the ET brain, although more subtle neurodegenerative changes cannot be ruled out.     

Recombinant interferon alfa-2a with or without vinblastine in metastatic renal cell carcinoma: results of a European multi-center phase III study.

A total of 178 patients with metastatic renal cell cancer were randomized to receive interferon alfa-2a (rIFN alfa-2a) or interferon alfa-2a+vinblastine (VLB). IFN alfa-2a was injected intramuscularly at a dose of 18 MIU 3 times a week and VLB was given intravenously at a dose of 0.1 mg/kg once every 3 weeks. The response rate was 11% for patients on monotherapy and 24% for those on combination treatment. The 5-year survival for 145 eligible patients was 9%, independently from the treatment arm. The performance status was significantly related to long-term prognosis, and 13% of the patients with performance status 0 were alive at 5 years, as compared to 6% and 0% for patients with a WHO grade of 1 and 2, respectively. The most frequent adverse events in both treatment arms were flu-like symptoms (95%), fatigue (70%) and gastrointestinal disturbances (68%). Leukopenia was observed more frequently with combination treatment (53%) than with IFN alfa-2a alone (30%). In conclusion, rIFN alfa-2a monotherapy at this dose and schedule has modest antitumor activity in metastatic renal cell cancer. The combination of rIFN alfa-2a+VLB results in a doubling of the response rate, but this does not translate into prolonged survival. Toxicity (except leukopenia) and tolerance were similar in both treatment arms.     

Occurrence of thyroid autoimmunity in relapsing remitting multiple sclerosis patients undergoing interferon-β treatment

We analyzed the titer of antithyroid autoantibodies Abs) and thyroid function in 17 multiple sclerosis (MS) patients undergoing interferon-β (IFN-β) treatment and in 40 MS control patients. Basal evaluation revealed normal thyroid function in all patients. Abs were detected in 5 IFN-β-treated patients (29%) and in 4 MS control patients (10%). Our results indicate that IFN-β treatment may lead to thyroid autoimmunity. We therefore recommend periodic evaluations of antithyroid Abs and thyroid functionality in IFN-β-treated MS patients.     

Unusual forms of venous thrombosis and thrombophilia

Venous thromboembolism (VTE) results from multiple interactions between inherited and environmental risk factors. The lower limbs are the most common site of VTE, but more rarely other venous sites can be involved. The role of risk factors for VTE can be different in the various thrombotic manifestations, and there are specific risk factors for specific sites. Coagulation abnormalities causing inherited thrombophilia are frequently found in patients with cerebral vein thrombosis, but are more rare in those with "isolated" pulmonary embolism, upper limb or retinal vein thrombosis. Transient situations, such as surgery, trauma, prolonged immobilization, the use of oral contraceptives or hormone replacement therapy, and pregnancy or puerperium, are often recognized in patients with lower limb deep vein thrombosis, "isolated" pulmonary embolism, abdominal and cerebral vein thrombosis, but not in patients with upper limb deep vein thrombosis. Major risk factors for deep vein thrombosis of the upper limbs are strong efforts with the arms, whereas for abdominal vein thrombosis are myeloproliferative disorders and liver cirrhosis. In conclusion, there is increasing evidence that inherited and environmental risk factors may interact differently in determining VTE in different sites.     

Study of folate receptor genes in nonsyndromic familial and sporadic cleft lip with or without cleft palate cases

Folate receptor family members (FOLRs) mediate the delivery of 5-methyltetrahydrofolate to the interior of, out of within, or between cells in a process known as potocytosis. Three FOLRs and a pseudogene map to 11q13.4. The aim of this study was to verify whether FOLRs could be responsible for the onset of nonsyndromic cleft lip with or without cleft palate (CL/P). Linkage and linkage disequilibrium between genetic markers and disorder were analyzed. Patients and their mothers from 71 familial CL/P pedigrees and 75 sporadic cases from Italian population were investigated by PCR-SSCP analysis. Data from mutation scanning allowed us to find only a silent mutation in FOLR1 present in a mother and her child. Our findings do not support FOLR1 and FOLR2 genes in the onset of CL/P.