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1、Methods To evaluate the efficacy of strontium ranelate in preventing vertebral fractures in a phase 3 trial, we randomly assigned 1649 postmenopausal women with osteoporosis （low bone mineral density） and at least one vertebral fracture to receive 2 g of oral strontium ranelate per day or placebo fo

2、r three years. We gave calcium and vitamin D supplements to both groups before and during the study. Vertebral radiographs were obtained annually, and measurements of bone mineral density were performed every six months. Results New vertebral fractures occurred in fewer patients in the strontium ran

3、elate group than in the placebo group, with a risk reduction of 49 percent in the first year of treatment and 41 percent during the three-year study period （relative risk, 0.59; 95 percent confidence interval, 0.48 to 0.73）. Strontium ranelate increased bone mineral density at month 36 by 14.4 perce

4、nt at the lumbar spine and 8.3 percent at the femoral neck （P0.001 for both comparisons）. There were no significant differences between the groups in the incidence of serious adverse events. Conclusions Treatment of postmenopausal osteoporosis with strontium ranelate leads to early and sustained red

5、uctions in the risk of vertebral fractures. 2. EffusiveConstrictive PericarditisBackground Effusiveconstrictive pericarditis is an uncommon pericardial syndrome characterized by concomitant tamponade, caused by tense pericardial effusion, and constriction, caused by the visceral pericardium. We cond

6、ucted a prospective study of its clinical evolution and management. Methods From 1986 through 2001, all patients with effusiveconstrictive pericarditis were prospectively evaluated. Combined pericardiocentesis and cardiac catheterization were performed in all patients, and pericardiectomy was perfor

7、med in those with persistent constriction. Follow-up ranged from 1 month to 15 years （median, 7 years）. Results A total of 1184 patients with pericarditis were evaluated, 218 of whom had tamponade. Of these 218, 190 underwent combined pericardiocentesis and catheterization. Fifteen of these patients

8、 had effusiveconstrictive pericarditis and were included in the study. All patients presented with clinical tamponade; however, concomitant constriction was recognized in only seven patients. At catheterization, all patients had elevated intrapericardial pressure （median, 12 mm Hg; interquartile ran

9、ge, 7 to 18） and elevated right atrial and end-diastolic right and left ventricular pressures. After pericardiocentesis, the intrapericardial pressure decreased （median value, 5 mm Hg; interquartile range, 5 to 0）, whereas right atrial and end-diastolic right and left ventricular pressures, although

10、 slightly reduced, remained elevated, with a dipplateau morphology. The causes were diverse, and death was mainly related to the underlying disease. Pericardiectomy was required in seven patients, all of whom had involvement of the visceral pericardium. Three patients had spontaneous resolution. Con

11、clusions Effusiveconstrictive pericarditis is an uncommon pericardial syndrome that may be missed in some patients who present with tamponade. Although evolution to persistent constriction is frequent, idiopathic cases may resolve spontaneously. In our opinion, extensive epicardiectomy is the proced

12、ure of choice in patients requiring surgery. 3. Effect of Eculizumab on Hemolysis and Transfusion Requirements in Patients with Paroxysmal Nocturnal HemoglobinuriaBackground Paroxysmal nocturnal hemoglobinuria （PNH） arises from a somatic mutation of the PIG-A gene in a hematopoietic stem cell and th

13、e subsequent production of blood cells with a deficiency of surface proteins that protect the cells against attack by the complement system. We tested the clinical efficacy of eculizumab, a humanized antibody that inhibits the activation of terminal complement components, in patients with PNH. Metho

14、ds Eleven transfusion-dependent patients with PNH received infusions of eculizumab （600 mg） every week for four weeks, followed one week later by a 900-mg dose and then by 900 mg every other week through week 12. Clinical and biochemical indicators of hemolysis were measured throughout the trial. Re

15、sults Mean lactate dehydrogenase levels decreased from 3111 IU per liter before treatment to 594 IU per liter during treatment （P=0.002）. The mean percentage of PNH type III erythrocytes increased from 36.7 percent of the total erythrocyte population to 59.2 percent （P=0.005）. The mean and median tr

16、ansfusion rates decreased from 2.1 and 1.8 units per patient per month to 0.6 and 0.0 units per patient per month, respectively （P=0.003 for the comparison of the median rates）. Episodes of hemoglobinuria were reduced by 96 percent （P0.001）, and measurements of the quality of life improved significa

17、ntly. Conclusions Eculizumab is safe and well tolerated in patients with PNH. This antibody against terminal complement protein C5 reduces intravascular hemolysis, hemoglobinuria, and the need for transfusion, with an associated improvement in the quality of life in patients with PNH. 4. Use of B-Ty

18、pe Natriuretic Peptide in the Evaluation and Management of Acute DyspneaBACKGROUND B-type natriuretic peptide levels are higher in patients with congestive heart failure than in patients with dyspnea from other causes.METHODS We conducted a prospective, randomized, controlled study of 452 patients w

19、ho presented to the emergency department with acute dyspnea : 225 patients were randomly assigned to a diagnostic strategy involving the measurement of B-type natriuretic peptide levels with the use of a rapid bedside assay, and 227 were assessed in a standard manner. The time to discharge and the t

20、otal cost of treatment were the primary end points.RESULTS Base-line demographic and clinical characteristics were well matched between the two groups. The use of B-type natriuretic peptide levels reduced the need for hospitalization and intensive care : 75 percent of patients in the B-type natriure

21、tic peptide group were hospitalized, as compared with 85 percent of patients in the control group （P=0.008）,and 15 percent of those in the B-type natriuretic peptide group required intensive care, as compared with 24 percent of those in the control group （P=0.01）. The median time to discharge was 8.

22、0 days in the B-type natriuretic peptide group and 11.0 days in the control group （P=0.001）. The mean total cost of treatment was $5,410 （95 percent confidence interval, $4,516 to $6,304） in the B-type natriuretic peptide group, as compared with $7,264 （95 percent confidence interval, $6,301 to $8,2

23、27） in the control group （P=0.006）. The respective 30-day mortality rates were 10 percent and 12 percent （P=0.45）. CONCLUSIONS Used in conjunction with other clinical information, rapid measurement of B-type natriuretic peptide in the emergency department improved the evaluation and treatment of pat

24、ients with acute dyspnea and thereby reduced the time to discharge and the total cost of treatment.5. Impaired Mitochondrial Activity in the Insulin-Resistant Offspring of Patients with Type 2 DiabetesBackground Insulin resistance appears to be the best predictor of the development of diabetes in th

25、e children of patients with type 2 diabetes, but the mechanism responsible is unknown. Methods We performed hyperinsulinemiceuglycemic clamp studies in combination with infusions of 6,6-2H2glucose in healthy, young, lean, insulin-resistant offspring of patients with type 2 diabetes and insulin-sensi

26、tive control subjects matched for age, height, weight, and physical activity to assess the sensitivity of liver and muscle to insulin. Proton （1H） magnetic resonance spectroscopy studies were performed to measure intramyocellular lipid and intrahepatic triglyceride content. Rates of whole-body and s

27、ubcutaneous fat lipolysis were assessed by measuring the rates of 2H5 glycerol turnover in combination with microdialysis measurements of glycerol release from subcutaneous fat. We performed 31P magnetic resonance spectroscopy studies to assess the rates of mitochondrial oxidative-phosphorylation ac

28、tivity in muscle. Results The insulin-stimulated rate of glucose uptake by muscle was approximately 60 percent lower in the insulin-resistant subjects than in the insulin-sensitive control subjects （P0.001） and was associated with an increase of approximately 80 percent in the intramyocellular lipid

29、 content （P=0.005）. This increase in intramyocellular lipid content was most likely attributable to mitochondrial dysfunction, as reflected by a reduction of approximately 30 percent in mitochondrial phosphorylation （P=0.01 for the comparison with controls）, since there were no significant differenc

30、es in systemic or localized rates of lipolysis or plasma concentrations of tumor necrosis factor , interleukin-6, resistin, or adiponectin. Conclusions These data support the hypothesis that insulin resistance in the skeletal muscle of insulin-resistant offspring of patients with type 2 diabetes is

31、associated with dysregulation of intramyocellular fatty acid metabolism, possibly because of an inherited defect in mitochondrial oxidative phosphorylation. 6. Circulating Angiogenic Factors and the Risk of PreeclampsiaBackground The cause of preeclampsia remains unclear. Limited data suggest that excess circulating soluble fms-like tyrosine kinase 1 （