Adhesion molecules expression as a potential marker of prostate cancer aggressivity. A TMA study of radical prostatectomy specimens.

Adhesion molecule disorders may be important in different cell control pathways, and consequently in neoplastic cell disorders. This paper will consider only some of the aspects of intercellular relationship. The main anchoring molecule of these two structures is E-cadherin, which is bound to a molecule complex (catenins and vinculin) that connects it to the actin of the cytoplasmatic cytoskeleton. This adhesion molecule complex maintains cell adhesion but it is also involved in differentiation phenomena and may be pathways of action of different growth factors. When we study the expression of E-cadherin according to the Gleason pattern, we verify progressive loss of the adhesion molecule as the Gleason grade increases (abnormal in 35% of Gleason < 7 score versus 75% in cases of Gleason > 7 score). This correlation reinforces the idea of using the expression of adhesion molecules as a prognostic factor. Considering the great interrelation between the various cell-cycle regulating systems, it is probable that an approach to this interweaving through regulation and de-regulation of the adhesion molecule expression may turn out to be one of the most useful pathways in the future.

The ABO blood group genotype and factor VIII levels as independent risk factors for venous thromboembolism.

Factor VIII (FVIII), von Willebrand factor (vWF) and the ABO blood groups have been associated with thrombosis. The ABO locus has functional effects on vWF and FVIII levels and is genetically correlated with FVIII, vWF and thrombosis. We carried out a case-control study to assess the role of FVIII, vWF and ABO types on thrombotic risk. We analyzed 250 patients with venous thrombosis and 250 unrelated controls. FVIII, vWF and other factors related to thrombophilia were measured, ABO groups were analyzed by genotyping. FVIII and vWF were higher in non-O individuals. Group O was more frequent in the controls (44.3% v 23.3%; difference 21.1%; 95% CI: 13.0-29.3%) and Group A in patients (59.2% v. 41.5%; difference 17.7%, 95% CI: 9.1-26.4%). Individuals carrying the A1 allele had a higher risk of thrombosis (OR 2.6; 95% CI, 1.8-3.8). The risk attributed to vWF disappeared after adjusting for the ABO group. Patients with FVIII above the 90th percentile had a high thrombotic risk (adjusted OR 3.7; 95% CI, 2.1-6.5), and a high risk of recurrence (OR 2.3; 95% CI: 1.3-4.1). In conclusion, high FVIII levels and non-O blood groups, likely those with the A1 allele, are independent risk factors for venous thromboembolism and should be considered in evaluating of thrombophilia.

Comparing self-management of oral anticoagulant therapy with clinic management: a randomized trial.

BACKGROUND: Control of oral anticoagulant treatment has been reported to be suboptimal, but previous studies suggest that patient self-management improves control. OBJECTIVE: To compare the quality of control and the clinical outcomes of oral anticoagulant treatment in self-managed patients versus patients following conventional management. DESIGN: Randomized, controlled trial. SETTING: University-affiliated hospital in Spain. PATIENTS: 737 patients with indications for anticoagulant treatment. INTERVENTION: The self-management group (n = 368) received simple instructions for using a portable coagulometer weekly and self-adjusting treatment dose. The conventional management group (n = 369) received usual care in an anticoagulation clinic (monthly measurement and control of international normalized ratio [INR], managed by hematologists). MEASUREMENTS: Percentage of INR values within the target range and major related complications. RESULTS: The median follow-up period was 11.8 months (range, 0.3 to 16.9 months). The unadjusted percentages of in-range INRs were 58.6% in the self-management group and 55.6% in the conventional management group (difference, 3.0 percentage points [95% CI, 0.4 to 5.4 percentage points]). Twenty-seven patients (7.3%) in the conventional management group and 8 (2.2%) in the self-management group had major complications related to anticoagulant treatment. The unadjusted risk difference for major complications between groups was 5.1 percentage points (exact 95% CI, 1.7 to 8.5 percentage points). Fewer patients had minor hemorrhages in the self-management group (14.9%) than in the conventional management group (36.4%). Fifteen patients (4.1%) in the conventional management group and 6 (1.6%) in the self-management group died (unadjusted risk difference, 2.5 percentage points [exact 95% CI, 0.0 to 5.1 percentage points]). LIMITATIONS: The trial was performed at only 1 center and was not blinded. The dropout rate in the intervention group was 21%. CONCLUSIONS: Compared with conventional management by an anticoagulation clinic, self-management of oral anticoagulant treatment achieved a similar level of control. Of note, major complications and minor hemorrhages were less common in the self-management group.

Homozygosity of the T allele of the 46 C->T polymorphism in the F12 gene is a risk factor for ischemic stroke in the Spanish population.

BACKGROUND AND PURPOSE: Ischemic stroke (IS) is a complex disease that involves genetic and environmental factors. In a family-based study (the Genetic Analysis of Idiopathic Thrombophilia [GAIT] Project) that included a genome-wide scan, we demonstrated that a common polymorphism (46 C-->T) in the exon 1 of the F12 gene jointly influences variability of plasma Factor XII levels and susceptibility to thrombotic disease. We have investigated the risk of IS related to this polymorphism in a case-control study. METHODS: We studied 436 individuals: 205 diagnosed with IS and 231 age-gender-ethnic control subjects. We measured Factor VIIIc, fibrinogen, and Factor XIIc levels, and we genotyped the 46 C-->T polymorphism in the F12 gene. RESULTS: There were 91 women and 114 men in the IS group and 109 women and 122 men in the control group. We confirmed our previous observation that individuals with different genotypes for the 46 C-->T polymorphism showed significant differences in Factor XIIc levels. Most importantly, the mutated T allele in the homozygous state (genotype T/T) was associated with an increased risk of IS with an adjusted odds ratio of 4.1 (95% CI, 1.1 to 15.9). CONCLUSIONS: This study suggests that the 46 C-->T polymorphism is a genetic risk factor for IS in the Spanish population. In addition, our results confirm that the use of genetic linkage studies along with a case-control association study is an extremely valuable approach for identifying DNA variants that affect complex diseases.

Association of functional thrombin-activatable fibrinolysis inhibitor (TAFI) with conventional cardiovascular risk factors and its correlation with other hemostatic factors in a Spanish population.

Our aim was to determine the associations of functional thrombin-activatable fibrinolysis inhibitor (TAFI) levels in plasma with conventional cardiovascular risk factors, sex and age, and possible correlations with other hemostatic factors in a Spanish population. We included 303 individuals from a Spanish population. Hemostatic factors such as von Willebrand Factor, VII ag, VIIIc, XIc, XIIc, APCR, protein S, protein C, antithrombin, fibrinogen, and t-PA antigen were assayed. The functional TAFI assay was based on the activation of plasma TAFI with thrombin-thrombomodulin, and the measure of TAFIa activity on the hippuryl-Arg substrate. There were no statistical differences in mean values of functional TAFI among the various female age groups or among the different male age groups, with or without cardiovascular risk factors. Only women younger than 30 years of age showed lower levels of functional TAFI compared to older women. No differences were found among men of different ages. Adjusted for sex and age, hemostatic factors did not show a correlation with functional TAFI levels in plasma. Women with hypercholesterolemia showed higher levels of TAFI; other conventional cardiovascular risk factors did not modify functional TAFI levels either in men or in women. We also found no correlation of functional TAFI levels related to any other hemostatic factors.

Fondaparinux (ARIXTRA) as an alternative anti-thrombotic prophylaxis when there is hypersensitivity to low molecular weight and unfractionated heparins.

During the last decade, new anticoagulant drugs with anti-factor-Xa properties have been described (1, 2). Among them is fondaparinux that has been licensed recently. It is a pentasaccharide mimicking the site where heparin binds to antithrombin III (1). This new drug has produced very promising clinical results in the prophylaxis of venous thrombosis after orthopedic surgery (3). Here we report two different clinical situations in which fondaparinux has yielded a successful outcome: first, a patient with repeated cutaneus reaction to several different low molecular weight heparins (LMWH), and second, a patient with severe heparin-induced thrombocytopenia (HIT). We decided to use fondaparinux in both cases since it is commercially available in Spain and mostly because the absence of in vitro cross-reaction with heparins, as discussed later.

Cistinuria y litiasis renal de cistina. Estudio y enfoque terapéutico / Cystinuria and cystine renal lithiasis: and therapeutic approach

La litiasis renal de cistina es la única consecuencia clínica de la cistinuria, enfermedad hereditaria de transmisión autosómica recesiva que afecta de promedio a 1 de cada 7.000 nacidos vivos, existiendo una gran variabilidad geográfica. Los avances realizados en estos últimos 8 años sobre la genética y biología molecular de la enfermedad han permitido caracterizar por el momento dos genes responsables, lo cual demuestra el origen poligénico de la enfermedad. Desde un punto de vista fenotípico clasificamos la cistinuria en dos tipos: el tipo I y el tipo no I, ambos presentan diferencias genéticas y bioquímicas pero no clínicas. Desde un punto de vista terapéutico el objetivo primordial será la eliminación de los cálculos existentes y sobre todo la prevención de la recidiva incidiendo en los mecanismos fisiopatológicos de la cistina a nivel renal. La experiencia nos indica que aún a pesar de emplear correctamente el arsenal terapéutico existente y aplicar las normas generales comentadas en este capítulo, algunos pacientes cistinúricos mantienen un índice de actividad litiásica importante. El estudio clínico-genético del paciente y su familia será decisivo para la catalogación fenotípica (AU)