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991.
992.
993.
Platè M Asselta R Spena S Spreafico M Fagoonee S Peyvandi F Tenchini ML Duga S 《Blood cells, molecules & diseases》2008,41(3):292-297
Congenital hypofibrinogenemia is a rare bleeding disorder characterized by abnormally low levels of fibrinogen in plasma, generally due to heterozygous mutations in one of the three fibrinogen genes (FGA, FGB, and FGG, coding for Aα, Bβ, and γ chain, respectively). Hypofibrinogenemic patients are usually asymptomatic, whereas individuals bearing similar mutations in the homozygous or compound heterozygous state develop a severe bleeding disorder: afibrinogenemia. The mutational spectrum of these quantitative fibrinogen disorders includes large deletions, point mutations causing premature termination codons, and missense mutations affecting fibrinogen assembly or secretion, distributed throughout the 50-kb fibrinogen gene cluster. In this study, we report the mutational screening of two unrelated hypofibrinogenemic patients leading to the identification of two missense mutations, one hitherto unknown (αCys45Phe), and one previously described (γAsn345Ser). The involvement of αCys45Phe and γAsn345Ser in the pathogenesis of hypofibrinogenemia was investigated by in-vitro expression experiments. Both mutations were demonstrated to cause a severe impairment of intracellular fibrinogen processing, either by affecting half-molecule dimerization (αCys45Phe) or by hampering hexamer secretion (γAsn345Ser). 相似文献
994.
Angelone T Quintieri AM Brar BK Limchaiyawat PT Tota B Mahata SK Cerra MC 《Endocrinology》2008,149(10):4780-4793
Circulating levels of catestatin (Cts; human chromogranin A352-372) decrease in the plasma of patients with essential hypertension. Genetic ablation of the chromogranin A (Chga) gene in mice increases blood pressure and pretreatment of Chga-null mice with Cts prevents blood pressure elevation, indicating a direct role of Cts in preventing hypertension. This notable vasoreactivity prompted us to test the direct cardiovascular effects and mechanisms of action of wild-type (WT) Cts and naturally occurring human variants (G364S-Cts and P370L-Cts) on myocardial and coronary functions. The direct cardiovascular actions of WT-Cts and human variants were determined using the Langendorff-perfused rat heart. WT-Cts dose-dependently increased heart rate and coronary pressure and decreased left ventricular pressure, rate pressure product and both positive and negative LVdP/dt. WT-Cts not only inhibited phospholamban phosphorylation, but also the inotropic and lusitropic effects of WT-Cts were abolished by chemical inhibition of beta2-adrenergic receptors, Gi/o protein, nitric oxide or cGMP, indicating involvement of beta2-adrenergic receptors-Gi/o protein-nitric oxide-cGMP signaling mechanisms. In contrast, G364S-Cts did not affect basal cardiac performance but abolished isoproterenol-induced positive inotropism and lusitropism. P370L-Cts decreased rate pressure product and inhibited only isoproterenol-induced positive inotropism and lusitropism by 70%. Cts also inhibited endothelin-1-induced positive inotropism and coronary constriction. Taken together, the cardioinhibitory influence exerted on basal mechanical performance and the counterregulatory action against beta-adrenergic and endothelin-1 stimulations point to Cts as a novel cardiac modulator, able to protect the heart against excessive sympathochromaffin overactivation, e.g. hypertensive cardiomyopathy. 相似文献
995.
Angelucci E Barosi G Camaschella C Cappellini MD Cazzola M Galanello R Marchetti M Piga A Tura S 《Haematologica》2008,93(5):741-752
New measures of iron accumulation in liver and heart (superconducting quantum inference device and magnetic resonance imaging), and oral iron chelators (deferiprone and deferasirox) are available for managing iron overload in thalassemia major. To assure appropriate use of these new health technologies, the Italian Society of Hematology appointed a panel of experts to produce clinical practice-guidelines for the management of iron overload in thalassemia major and related disorders. The analytical hierarchy process, a technique for multicriteria decision analysis, was applied to relevant key questions in order to identify the alternative strategies, generate explicit criteria for their evaluation, and check how well the alternatives fulfilled the criteria. The result of a comprehensive systematic review of articles released from 1990 to 2007 was used as a source of scientific evidence to compare the decisional options pairwise, and select the final recommendation. Every step in the model was developed from questionnaires and group discussion. The resulting recommendations advise about which examination to carry out in order to plan iron chelation therapy, when to start iron chelation, which iron chelator to choose in regularly transfused patients, how to monitor iron chelation therapy, and when and how to switch standard therapy. 相似文献
996.
Romero GA de la Glória Orge Orge M de Farias Guerra MV Paes MG de Oliveira Macêdo V de Carvalho EM 《Acta tropica》2005,93(1):49-56
The antibody response against Leishmania (Leishmania) amazonensis crude antigen was measured through the indirect immunofluorescent assay (IFA) and the immunoenzymatic assay (ELISA) in 114 patients with cutaneous leishmaniasis (CL) in Brazil. Fifty-four patients were infected by Leishmania (Viannia) braziliensis, and 60 patients had L. (V.) guyanensis infection. Patients were comparable by age, sex, disease duration and the Montenegro skin test diameter. L. (V.) braziliensis-infected patients showed significant lower number of ulcerated lesions, greater ulcerated area and higher proportion of lymph node enlargement. Sensitivity of IFA was 79.6% (95% CI 66.1-88.9) and 71.7% (95% CI 58.4-82.2) for L. (V.) braziliensis and L. (V.) guyanensis-infected patients, respectively (P=0.324). Sensitivity of ELISA was 98.2% (95% CI 88.8-99.9) and 85.0% (95% CI 72.9-92.5) for L. (V.) braziliensis and L. (V.) guyanensis-infected patients, respectively (P=0.018). Significant differences were observed in the magnitude of the antibody response before treatment with higher levels detected in L. (V.) braziliensis-infected patients by both serologic techniques. Eighty-four patients had serologic evaluations before and 12 weeks after treatment with meglumine antimoniate, 20 mg/kg/day for 20 days. Significant lower optic density values were observed after treatment with both species independent of cure or failure. Our data showed that L. (V.) braziliensis induces a higher antibody response against L. (L.) amazonensis antigens than L. (V.) guyanensis and that down-modulation of the antibody response occurs shortly during disease evolution after treatment. Moreover the data support the use of ELISA as a better tool for detection of antibodies in CL. 相似文献
997.
Lengyel M Horstkotte D Völler H Mistiaen WP;Working Group Infection Thrombosis Embolism Bleeding of the Society for Heart Valve Disease 《The Journal of heart valve disease》2005,14(5):567-575
Prosthetic valve thrombosis (PVT) is a life-threatening disease, for which treatment strategies have been controversial. Herein, existing data on management options are reviewed, and conclusions drawn as to the choice and use of treatment strategies for PVT. The use of transesophageal echocardiography (TEE) allows distinction to be made between obstructive and non-obstructive PVT by the presence or absence of occluder motion limitation. The differentiation of PVT from pannus and vegetation is, however, still limited by TEE. The incidence of PVT has been underestimated by not taking into account a large percentage of non-obstructive PVT. Although the standard treatment for PVT has been surgery, thrombolysis has lower mortality rates, particularly in patients in NYHA functional classes III-IV. The lowest complication rates with thrombolysis have been achieved in patients with non-obstructive PVT. Pregnancy, left atrial appendage thrombi and large PVT are not contraindications to thrombolysis. The third therapeutic option is anticoagulant therapy. The detrimental effect of anticoagulant treatment in obstructive PVT was shown in a prospective study. Non-obstructive thrombi of > 5 mm length have been treated with higher success rates and lower complication rates by thrombolysis than by anticoagulant treatment. In conclusion, all patients with suspected PVT should undergo multiplane TEE. Thrombolysis is the first-line treatment for obstructive PVT, independent of NYHA class and thrombus size if there are no contraindications. Serial TEE studies must be conducted during thrombolysis. Surgery should be reserved for those patients in whom thrombolysis is contraindicated, or has failed. Initial anticoagulant therapy is recommended only for small, non-obstructive PVT if anticoagulation had been subtherapeutic; otherwise, thrombolysis is the treatment of choice if there are no contraindications. 相似文献
998.
Vergara C Tsai YJ Grant AV Rafaels N Gao L Hand T Stockton M Campbell M Mercado D Faruque M Dunston G Beaty TH Oliveira RR Ponte EV Cruz AA Carvalho E Araujo MI Watson H Schleimer RP Caraballo L Nickel RG Mathias RA Barnes KC 《American journal of respiratory and critical care medicine》2008,178(10):1017-1022
999.
Objective: We examined the role of personal, family and institutional factors on the work status of older adults in urban China. Method: The analysis was based on data from a large population survey (N = 7381) of community‐dwelling urban Chinese aged 60 years and older. Multivariate logistic regression was used to model work status. Results: Demographic variables such as gender, ethnicity, age and self‐perceived health status were identified as important determinants of work status. Having material assets, savings, a public pension and health insurance were all negatively correlated with remaining in the workforce, whereas earning a high income was positively correlated. Conclusions: Our findings have implications regarding the impact of health policy and pension reform on employment retention. While economic growth may create an incentive for some to continue working, the lack of widespread public and private old‐age support may force others to remain in the workforce out of economic necessity. 相似文献
1000.
Luna Gargani Cosimo Bruni Tatiana Barskova Valentina Hartwig Martina Marinelli Maria Giovanna Trivella Marco Matucci-Cerinic Antonio LAbbate 《Seminars in arthritis and rheumatism》2019,48(5):867-873