Physician practices in the prevention of venous thromboembolism

OBJECTIVE: To determine the rate of use of prophylaxis for venous thromboembolism in high-risk hospital patients. DESIGN: A retrospective medical record review. SETTING: A community-wide study in 16 short-stay hospitals in central Massachusetts. PATIENTS: A total of 2017 patients with multiple risk factors for venous thromboembolism. MEASUREMENTS AND MAIN RESULTS: On the basis of age, length of hospitalization, and the presence of at least one additional major risk factor, 17% of 151,349 discharges (25,410 patients) were identified as being at high risk for venous thromboembolism. Eight percent of these discharges were randomly selected for medical record review. Prophylaxis for venous thromboembolism was received by 32% of these high-risk patients. Prophylaxis use among the 16 study hospitals varied widely, ranging from 9% to 56%, and was higher in teaching hospitals than in nonteaching hospitals (44% compared with 19%; P less than 0.001). One or more of the following methods of prophylaxis was used: low-dose heparin (78%), intermittent calf compression (13%), warfarin (12%), and inferior vena caval filter (3%). Use of prophylaxis increased with the number of risk factors identified (P less than 0.001). CONCLUSION: Prophylaxis for venous thromboemobolism is underused, particularly in nonteaching hospitals.     

Recurrent cerebral ischemia and mitral valve vegetation in a patient with antiphospholipid antibodies

A 37-year-old woman presented with a history of acute loss of vision in her left eye and a history of recurrent transient ischemic attacks. Subsequent investigations revealed a prolonged PTT. The lupus anticoagulant and anticardiolipin antibodies (aCL) were identified in her serum. A cardiac murmur was heard and echocardiography demonstrated a mass on the mitral valve. Extensive studies for infection were negative. Cardioembolic phenomena were considered a possible cause of her cerebral ischemic events. The occurrence of nonbacterial endocardial verrucae is well described in systemic lupus erythematosus. The pathogenesis of this lesion remains speculative, however, its occurrence in our patient, with a lupus anticoagulant and aCL suggests a possible association. The clinical manifestations of thrombosis in patients with antiphospholipid antibodies are varied, and may include the development of thrombotic endocardial lesions.     

Vasoconstrictor response to prostacyclin in rabbit pulmonary circulation

We have determined the effect of prostacyclin (PGI2) on segmental vascular resistance in rabbit lungs. Lungs of 26 rabbits were isolated and perfused with blood; 16 adult, greater than 6 months old, five juvenile, 6-8 week old and five neonatal, 2-3-week old. Six of the adult lungs were pretreated with indomethacin to block cyclooxygenase, prior to infusion of PGI2. In all lungs, flow was adjusted initially to keep pulmonary artery pressure approximately 20 cmH2O, left atrial and airway pressures being 8 and 6 cmH2O, respectively (zone 3), and then kept constant. We measured pulmonary artery pressure continuously and in the 10 untreated adult lungs, in which a vasoconstrictor response to PGI2 was obtained, we also measured pressures in 20-50 microns diameter subpleural arterioles and venules by the micropipette-servonulling method. We found that in juvenile and neonatal rabbit lungs, PGI2 did not change total vascular resistance significantly but in untreated adult lungs, it caused a significant increase in total vascular resistance only after a dose of 10 micrograms/kg. This age-related difference in vasoconstrictor response to PGI2 was not related to baseline total vascular resistance in the three groups of lungs. In adult lungs, vasoconstriction occurred mainly in arteries with a small effect in veins. Circulating levels of thromboxane B2, leukotriene C4, and 6-keto-PGF1 alpha increased following PGI2 infusion in adult lungs, whereas in neonatal lungs, only 6-keto-PGF1 alpha increased significantly. Indomethacin pretreatment completely abolished the vasoconstrictor response to PGI2. We conclude that PGI2-induced vasoconstriction is age and dose dependent in isolated rabbit lungs and that a cyclooxygenase product, such as thromboxane A2, may play a role in mediating the vasoconstriction.     

Use of angiotensin-converting enzyme inhibitor therapy and dose-related outcomes in older adults with new heart failure in the community

OBJECTIVE: To evaluate the dose-related benefit of angiotensin-converting enzyme (ACE) inhibitor therapy among older adults with heart failure and to evaluate whether low-dose ACE inhibitor therapy is better than none. DESIGN: Observational cohort study. SETTING: Community-dwelling older adults in Ontario, Canada. PATIENTS/PARTICIPANTS: We identified 16539 adults 66 years or older who survived 45 days following their first heart failure hospitalization discharge. MEASUREMENT AND MAIN RESULTS: Multivariate techniques including propensity scores were used to study the association between the dose of ACE inhibitor therapy dispensed and 3 outcomes: survival, survival or heart failure rehospitalization, and survival or all-cause hospitalization at 1 year of follow-up. Logistic regression models explored the association between initial dose dispensed and subsequent dose reduction or drug cessation. Overall, 10793 (65.3%) of patients were dispensed ACE inhibitor therapy, with more than a third (3935; 36.5%) initiated on low-dose therapy. Relative to dispensing of low-dose ACE inhibitor therapy, nonuse was associated with increased mortality (hazard ratio [HR], 1.12; 95% confidence interval [CI], 1.02 to 1.22). Dispensing medium-dose therapy provided a benefit similar to low-dose (HR, 0.94; CI, 0.86 to 1.03) and dispensing of high-dose therapy was associated with improved survival benefit (HR, 0.76; CI, 0.68 to 0.85). Relative to dispensing of low-dose ACE inhibitor therapy, dispensing high-dose conferred a benefit (HR, 0.87; CI, 0.80 to 0.95) on the composite outcome of 1-year mortality or heart failure hospitalization and the composite outcome of 1-year mortality or all-cause hospitalization (HR, 0.87; CI, 0.81 to 0.93). Relative to those dispensed low-dose ACE inhibitor therapy, those initially dispensed high-dose therapy were twice as likely to have their subsequent dose reduced or the therapy discontinued (odds ratio, 2.36; CI, 2.07 to 2.69). CONCLUSION: Our findings suggest that when possible, older adults should be titrated to the higher doses of ACE inhibitor therapy evaluated in clinical trials. If older adults cannot tolerate higher doses, then low-dose ACE inhibitor therapy is superior to none. High-dose ACE inhibitor therapy is not as well tolerated as lower doses.     

Differentiation-induced replication-timing changes are restricted to AT-rich/long interspersed nuclear element (LINE)-rich isochores

The replication timing of some genes is developmentally regulated, but the significance of replication timing to cellular differentiation has been difficult to substantiate. Studies have largely been restricted to the comparison of a few genes in established cell lines derived from different tissues, and most of these genes do not change replication timing. Hence, it has not been possible to predict how many or what types of genes might be subject to such control. Here, we have evaluated the replication timing of 54 tissue-specific genes in mouse embryonic stem cells before and after differentiation to neural precursors. Strikingly, genes residing within isochores rich in GC and poor in long interspersed nuclear elements (LINEs) did not change their replication timing, whereas half of genes within isochores rich in AT and long interspersed nuclear elements displayed programmed changes in replication timing that accompanied changes in gene expression. Our results provide direct evidence that differentiation-induced autosomal replication-timing changes are a significant part of mammalian development, provide a means to predict genes subject to such regulation, and suggest that replication timing may be more related to the evolution of metazoan genomes than to gene function or expression pattern.     

Persistent truncus arteriosus: A study of 66 autopsy cases with special reference to definition and morphogenesis

Sixty-six hearts were examined in which a single arterial trunk, leaving the base of the heart through a single semilunar valve, supplied the aorta, pulmonary artery and coronary arteries. Careful attention was paid to the infundibular morphologic features in these hearts, and these were compared with findings in 24 hearts with single aortic trunk, pulmonary atresia and ventricular septal defect. It was concluded that the two anomalies represented morphologically discrete conditions. This was particularly true with regard to the disposition of the infundibular septum, the ventriculo-infundibular fold and the relation of the coronary arteries to the semilunar sinuses. Although it is theoretically possible for a heart with true persistent truncus arteriosus to have absence of the pulmonary trunk and right and left pulmonary arteries, it is argued that such hearts (“truncus type IV”) are best classified as pulmonary atresia with ventricular septal defect. It is also argued that hearts with a common arterial trunk supplied through discrete ventricular outflow tracts and two semilunar valves are best considered examples of aorticopulmonary window. It is suggested that persistent truncus arteriosus is best defined as that condition in which a single arterial trunk leaves the heart through a single semilunar valve and supplies the aorta, one or both pulmonary arteries and the coronary arteries.