Increased intestinal permeability and NOD2 variants in familial and sporadic Crohn's disease.

BACKGROUND: Abnormal barrier function may be genetically determined in Crohn's disease. AIM: To examine the role of abnormal intestinal permeability in genetic predisposition in multiplex vs. sporadic Crohn's disease families. METHODS: Intestinal permeability was measured in patients, relatives and partners by means of lactulose/mannitol test. Healthy subjects from the hospital staff served as controls. CARD15 mutations were investigated in sporadic and familial Crohn's disease patients and in a group of blood donors. RESULTS: The median lactulose/mannitol ratio was increased significantly in Crohn's disease patients vs. their relatives [0.03 (0.01-0.24) vs. 0.01 (0.003-0.19), P=0.005]. The percentage of abnormal tests was significantly higher in familial vs. sporadic first-degree relatives of Crohn's disease patients (29% vs. 11%, P=0.0281). Abnormal permeability occurred significantly more frequent in patients with familial Crohn's disease carrying the frameshift mutation. The frameshift mutation 3020 insC was associated with increased permeability in 75% in the multiplex and in 61% of the sporadic CD patients. One partner had abnormal lactulose/mannitol ratio. Conclusion Intestinal permeability is raised in Crohn's disease patients and relatives, with higher rates in familial vs. sporadic healthy relatives. CARD15 mutations are associated with abnormal permeability in ileal Crohn's disease.

Effect of heparin and aspirin on platelet and clotting activation during leukapheresis.

Beta-thromboglobulin (beta TG), serotonin (5HT) and fibrinopeptide A (FPA) were assessed in twenty-two normal donors before, during, and at the end of leukapheresis. Seven procedures were carried out adding heparin to the circuit, and seven adding acetyl salicylic acid (ASA). The remaining eight procedures were carried out using only citrate and served as controls. Plasma beta TG increased both during and after the apheresis, together with a significant decrease of the intra-platelet content. Platelet 5HT did not show significant changes whereas FPA increased significantly. Using heparin, we obtained a complete prevention of FPA cleavage during the entire procedure, while beta TG increased at the middle of the procedure. No significant effects were observed using ASA both on beta TG and FPA levels. These features clearly indicate the activation of platelets and the thrombin generation in the apheresis circuit. Nevertheless, the activation of the clotting system seems to be predominant, as supported by the improved effect of heparin on beta TG and FPA amounts.

Incidence, significance, and subtypes of hemophilia BM in a large population of hemophilia B patients.

Eleven patients with hemophilia BM were found out of a population of 66 patients with hemophilia B. Factor IX activity in the hemophilia BM varied between less than 1% and 1.6% of normal but factor IX antigen was normal or only slightly reduced in each instance. Thrombotest clotting time was variably prolonged and was not corrected by the addition of normal plasma. Thrombotest mixing experiments and dilution curve studies confirmed the presence of the inhibitor in every patient. There are at least two forms of hemophilia BM, a severe one and a mild one. In the first form, Thrombotest is severely prolonged (90-120 s). In the other, the prolongation is mild or moderate (60-80 s). A positive correlation exists between the antigen-activity difference (delta antigen-activity) and the prolongation of Thrombotest both in the propositi and in obligatory carriers. The criteria for the diagnosis of hemophilia BM are the following: prolonged PTT, prolonged Thrombotest, lack of correction of Thrombotest by the addition of normal plasma while PTT is fully corrected. The lack of correction of Thrombotest in the presence of a full correction of PTT, is the unique clotting feature.

An immunological study of prothrombin in liver cirrhosis.

Prothrombin was assayed in 24 patients with liver cirrhosis both as activity and as antigen. Prothrombin was found to be decreased by all methods and a good correlation was found among the three methods used. The serum prothrombin assay by means of the electroimmunoassay showed levels comparable to those observed in plasma, as expected. In the bidimensional electrophoresis system, plasma prothrombin appeared decreased but showed a normal mobility. Serum prothrombin in the same system showed the presence of three normal albeit reduced peaks or precipitates.