Role of collagen-adherent platelets in mediating fibrin formation in flowing whole blood

Activated platelets provide assembly sites for coagulation enzyme complexes and in this way can mediate coagulation during hemostasis and thrombosis. In this study, we examined the procoagulant activity of platelets adhering directly to fibrillar collagen, a main thrombogenic constituent of subendothelium. For this purpose, we used a human ex- vivo thrombosis model in which collagen-coated coverslips were exposed to flowing nonanticoagulated blood (shear rate, 65/s) for 5.5 minutes, which led to the deposition of adherent platelets, platelet thrombi, and fibrin. To examine the procoagulant activity of adherent platelets only, a selective antagonist of the platelet GPIIb-IIIa complex, Ro 44- 9883, was infused via a mixing device, resulting in a complete abrogation of platelet thrombus formation but leaving the collagen- adherent platelet layer intact. This platelet layer generated increased postchamber fibrinopeptide A (FPA) levels (203 +/- 33 ng/mL) as compared with control experiments without infusion of inhibitor (95 +/- 13 ng/mL). Concomitantly, fibrin deposition measured by morphometric analysis of cross-sections was also increased, as was the platelet adhesion to collagen. An immunochemical staining of fibrin fibers further showed that the adherent platelets formed the nuclei for fibrin fiber formation. This increase in fibrin deposition was mediated by the intrinsic factor X (F.X) activation complex on adherent single platelets, because almost complete inhibition of FPA generation (9 ng/mL) and fibrin deposition (0.4% +/- 0.2% coverage) was achieved upon coinfusion of the GP IIb-IIIa antagonist and active site-inhibited F.IXa. The large platelet thrombi that were deposited in control experiments contained no significant amounts of immunodetectable fibrin except at the thrombus base, where adherent platelets anchored the thrombi to the collagen surface. These results suggest that the collagen-adherent platelets are important promoters of coagulation during the initial phase of thrombogenesis by providing assembly sites for the F.X activation complex.     

Philippine guidelines on the screening for tuberculosis prior to the use of biologic agents

Aim: To develop practice guidelines in tuberculosis screening of patients and their households and close contacts, prior to the use of biologic agents. Method: A technical research committee formulated an evidence‐based draft, based on existing literature regarding the tests used in tuberculosis screening among immunocompromised patients. The evidence‐based draft was then circulated to an expert panel. An en banc meeting of the panelists was held and a consensus was declared if more than 50% agreed on a recommendation. Issues not resolved by consensus were discussed by correspondence and voted upon. The guidelines were presented in a public forum and feedback by stakeholders were reviewed and integrated into the final draft. Recommendations: 1. Patients for biologic therapy should be screened for latent and active tuberculosis prior to initiating treatment. 2. All patients who are candidates for biologic agents should be screened by tuberculin skin test for latent TB, and a chest radiograph for active tuberculosis. 3. Household and close contacts of candidate patients should be screened for active tuberculosis. 4. All household and close contacts of candidate patients should be screened for active TB using chest radiograph. 5. Treat latent and active tuberculosis according to local guidelines. 6. Delay treatment with biologic agents in patients with latent or active tuberculosis. 7. Administer tuberculosis prophylaxis to the patient for biologic therapy exposed to household contacts with active tuberculosis. Conclusion: These recommendations emphasize the importance of screening patients, household and close contacts for latent and active tuberculosis prior to initiating biologic therapy.     

安徽省结核病结核杆菌耐药状况的调查

目的为了解安徽省新发涂阳肺结核病人的耐药状况。方法随机选择安徽皖南、皖中和皖北的6个县结核病项目门诊,收集项目门诊的初治涂阳病人的结核杆菌;采用WHO／IUATLD推荐的比例法,对异烟肼（H）、链霉素（S）、利福平（R）、乙胺丁醇（E）等4种抗结核药敏试验。结果449株结核分枝杆菌中对4种抗结核药物全部敏感者248例,占55．23％;201例耐药,总原发耐药率为44．77％,以耐S为最高,占31．4％。结论安徽省结核病耐药水平是较严重省份,对结核病控制工作将是一个大的挑战,耐药结核杆菌的控制将是下一步结核病控制重点之一。     

A survey on clinical presentation and nutritional status of infants with suspected cow' milk allergy

Background  

Cow's milk is the most common food allergen in infants and the diagnosis of cow's milk allergy is difficult, even with the use of several diagnostic tests. Therefore, elimination diets and challenge tests are essential for the diagnosis and treatment of this disorder. The aim of this study is to report the clinical presentation and nutritional status of children evaluated by pediatric gastroenterologists for the assessment of symptoms suggestive of cow's milk allergy.     

Three-dimensional Transesophageal images of a pulmonary autograft in the mitral position (Ross II Procedure) in an adult

Few images are available in the literature of the Ross II procedure wherein the pulmonary valve is autotransplanted into the mitral position. These images are from a 33-year-old woman who underwent the procedure 18 years ago.     

Contribution of genetic and nutritional factors to DNA damage in heavy smokers

Prior epidemiological evidence suggests that genes controlling the metabolism of carcinogens and antioxidant/nutritional status are associated with lung cancer risk, possibly through their ability to modulate DNA damage by carcinogens. We performed a cross-sectional analysis of 159 heavy smokers from a cohort of subjects enrolled in a smoking cessation program. A total of 159 blood samples were analyzed to determine the relative contributions of genetic polymorphisms [CYP1A1 MspI and exon 7 and glutathione S-transferase M1 (GSTM1)] and plasma micronutrients to polycyclic aromatic hydrocarbon-DNA (PAH-DNA) adduct levels. DNA damage in smokers was affected by genetic polymorphisms and nutritional status. Smokers with the CYP1A1 exon 7 valine polymorphism had significantly higher (2-fold, P < or = 0.03) levels of DNA damage than those without. In parallel models, PAH-DNA adducts were inversely associated with plasma levels of retinol (beta = -0.93, P = 0.01), beta-carotene (beta = -0.18, P = 0.09), and alpha- tocopherol (beta = -0.28, P = 0.21) in 159 subjects. The association between smoking-adjusted plasma beta-carotene levels and DNA damage was only significant in those subjects lacking the GSTM1 detoxification gene (beta = -0.30, P = 0.05, n = 75). There was a statistical interaction between beta-carotene and alpha-tocopherol; when beta- carotene was low, alpha-tocopherol had a significant protective effect (beta = -0.78, P = 0.04) on adducts, but not when beta-carotene was high (beta = -0.16, P = 0.57). Plasma alpha-tocopherol was significantly correlated with beta-carotene (r = 0.36, P = 0.0005) and less strongly with retinol (r = 0.20, P = 0.0005). These results suggest that several micronutrients may act in concert to protect against DNA damage and highlight the importance of assessing overall antioxidant status. In conclusion, a subset of smokers may be at increased risk of DNA damage and possibly lung cancer due to the combined effect of low plasma micronutrients and genetic susceptibility factors. The use of biological markers to assess efficacy of interventions and to study mechanisms of micronutrients is timely given the current debate regarding the use of chemopreventive agents in high risk populations.