Comparison of short- (one month) and long- (twelve months) term outcomes of sirolimus- versus paclitaxel-eluting stents in 293 consecutive patients with diabetes mellitus (from the RESEARCH and T-SEARCH registries)

This study evaluated and compared the efficacy of sirolimus-eluting stents (n = 145 patients) with that of paclitaxel-eluting stents (n = 148 patients) in 293 consecutive unselected patients who had diabetes mellitus. Baseline clinical characteristics and presentations were similar: mean age of 64 years, 50% presented with unstable angina or myocardial infarction, and 66% had multivessel disease. Angiographic and procedural characteristics differed, with more complex lesions and more vein grafts managed in the paclitaxel-eluting stent group. Overall mean stented length was 46 +/- 32 mm. There were no differences in unadjusted outcomes by stent type (1-year major adverse cardiac event rates of 20.4% for sirolimus-eluting stents vs 15.6% for paclitaxel-eluting stents, p = 0.12) or when adjusted for multivariate predictors (adjusted hazard ratio 0.68, 95% confidence interval 0.37 to 1.24, p = 0.21). Independent predictors of outcome in patients who had diabetes mellitus were stenting of the left main artery, stenting of the left anterior descending artery, creatinine clearance, and female gender. Patients who required insulin had a significantly higher, crude major adverse cardiac event rate at 1 year compared with those who used oral agents, but this rate became nonsignificant when adjusted for independent predictors of outcome.     

Hemodynamics of venous cuff interposition in prosthetic arteriovenous fistulas for hemodialysis

PURPOSE: The durability of prosthetic arteriovenous fistulas (AVF) for hemodialysis is jeopardized by thrombotic occlusions due to intimal hyperplastic stenoses. In arterial reconstructive surgery, peripheral arterial bypasses with prosthetic material benefit from a venous cuff at the distal anastomosis. Therefore, a study was performed to assess the effect of a venous cuff at the venous anastomosis of PTFE graft AVFs in terms of stenosis development, hemodynamics and patency rates. METHODS: A subset of 40 patients from a multicenter study were enrolled into the study, of which 20 patients were randomized for venous cuff interposition. Duplex measurements to detect stenoses and volume flows were performed at 6, 12, 26 and 52 weeks postoperatively. Relative distension (RD) and wall shear rate (WSR) were calculated by means of vessel wall Doppler tracking (VWDT). RESULTS: The total number of stenoses was significantly less in the cuff group (21 vs. 33; p = 0.045). This feature was found at the site of the venous anastomosis (cuff 5; no cuff 12). Volume flow, graft and efferent vein diameters, RD and WSR in the graft and efferent vein were comparable for both groups. WSR in the venous anastomosis tended to be lower in the cuff group (768 vs. 1,448 s(-1), p = 0.068).Volume flows and WSR were significantly lower in failing grafts. Patency rates were similar in both groups (primary patency 13 vs. 29%; secondary patency 78 vs. 67%). CONCLUSIONS: A venous cuff at the venous anastomosis of PTFE graft AVFs results in less stenoses, but improved patency rates could not be demonstrated.     

Sarcoplasmic reticulum K(+) channels from human and sheep atrial cells display a specific electro-pharmacological profile

It has recently been proposed that the Ca(2+) uptake by the SR is inhibited by blocking Cl(-) and/or K(+) movements across this intracellular membrane. We have characterised the functional and pharmacological profile of the SR K(+) channel derived from human and sheep atrial cells. Mammalian atrial SR preparations were subjected to [(3)H]-ryanodine binding assays, SDS-PAGE analysis and channel protein reconstitution into planar lipid bilayers. Assessment of [(3)H]-ryanodine binding on the SR Ca(2+) release channel revealed that it was inhibited by both Ruthenium Red and Mg(2+) with IC(50) values of 4.11 microM and 9.12 m M, respectively. In crude populations as well as in all SR-enriched fractions, activity of K(+) selective channels was recorded. This channel displayed a high conductance value of 193 and 185 pS for human and sheep preparations respectively. Gating and conducting behaviours of this channel were unaffected by the addition of up to 5m M 4-Aminopyridine (4-AP), 100 n M Iberiotoxin (IbTX), 10 microM E-4031 and 30 microM amiodarone. However, 100n M Dendrotoxin (gamma-DTX) largely increase the occurrence of the SR K(+) channel subconducting states without an effect on the main unitary conductance. These results demonstrate that the SR K(+) channel, present in all mammalian atrial SR membranes tested (as assessed by [(3)H]-ryanodine binding and its typical inhibition by ruthenium red and the magnesium), displays different properties than those classically described for cardiac sarcolemmal K(+) channels. Despite the fact that the biophysical properties of the SR K(+) channel are well known, its molecular identity remains to be ascertained.     

Biochemical diagnosis of pheochromocytoma: how to distinguish true- from false-positive test results

Measurements of plasma normetanephrine and metanephrine provide a highly sensitive test for diagnosis of pheochromocytoma, but false-positive results remain a problem. We therefore assessed medication-associated false-positive results and use of supplementary tests, including plasma normetanephrine responses to clonidine, to distinguish true- from false-positive results. The study included 208 patients with pheochromocytoma and 648 patients in whom pheochromocytoma was excluded. Clonidine-suppression tests were carried out in 48 patients with and 49 patients without the tumor. Tricyclic antidepressants and phenoxybenzamine accounted for 41% of false-positive elevations of plasma normetanephrine and 44-45% those of plasma and urinary norepinephrine. High plasma normetanephrine to norepinephrine or metanephrine to epinephrine ratios were strongly predictive of pheochromocytoma. Lack of decrease and elevated plasma levels of norepinephrine or normetanephrine after clonidine also confirmed pheochromocytoma with high specificity. However, 16 of 48 patients with pheochromocytoma had normal levels or decreases of norepinephrine after clonidine. In contrast, plasma normetanephrine remained elevated in all but 2 patients, indicating more reliable diagnosis using normetanephrine than norepinephrine responses to clonidine. Thus, in patients with suspected pheochromocytoma and positive biochemical results, false-positive elevations due to medications should first be eliminated. Patterns of biochemical test results and responses of plasma normetanephrine to clonidine can then help distinguish true- from false-positive results.     

Plasma N-terminal pro-B-type natriuretic peptide for prediction of death or nonfatal myocardial infarction following percutaneous coronary intervention

B-type natriuretic peptide (BNP) and the N-terminus of pro-BNP (NT-pro-BNP) have prognostic value in patients with heart failure and patients with acute coronary syndromes. Little is known about the prognostic value of baseline NT-pro-BNP alone or in combination with C-reactive protein (CRP) for clinical outcome after percutaneous coronary intervention (PCI). Within a single center registry of contemporaneous PCI, we investigated the prognostic value of baseline plasma NT-pro-BNP and CRP concentrations for the prediction of death or nonfatal myocardial infarction (MI) during 12 to 14 months of follow-up. Among 1,172 consecutive patients, the occurrence of death or MI increased significantly with baseline NT-pro-BNP before PCI (first quartile 0 of 294, second quartile 6 of 291 [2.1%], third quartile 4 of 294 [1.4%], fourth quartile 22 of 293 [7.5%)]; p <0.0001). NT-pro-BNP in the top quartile significantly predicted death (odds ratio [OR] 13.37, 95% confidence interval [CI] 4.50 to 40.38, p <0.0001) and was associated with nonfatal MI (OR 2.53, 95% CI 0.77 to 8.34, p = 0.22) An abnormal CRP was significantly associated with death (OR 3.47, 95% CI 1.26 to 9.54, p = 0.019). Stepwise multivariate logistic regression analysis identified age >65 years and NT-pro-BNP as independent significant predictors of death/MI (age OR 3.18, 95% CI 1.32 to 7.67, p = 0.01; NT-pro-BNP OR 4.57, 95% CI 2.07 to 10.10, p = 0.0001). Baseline NT-pro-BNP before PCI provides important, independent prognostic information for the occurrence of death or nonfatal MI during long-term follow-up.     

The role of androgens in sertoli cell proliferation and functional maturation: studies in mice with total or Sertoli cell-selective ablation of the androgen receptor

The role of androgens in the proliferation and maturation of Sertoli cells (SC) and the development of their capacity to support spermatogenesis remains poorly understood. We evaluated these functions in complete androgen receptor knockout (ARKO) and SC-selective androgen receptor knockout (SCARKO) mice. Compared with controls, ARKO mice exhibited a progressive reduction in SC number/testis, whereas SCARKOs showed minor changes, suggesting that androgen effects on SC number are not mediated via direct action on SCs. Immunoexpression of anti-Mullerian hormone (AMH), p27(kip1), GATA-1, and sulfated glycoprotein-2, which changes according to SC maturational status, occurred normally in ARKOs and SCARKOs. Functional capacity of SCs to support spermatogonia was similar in SCARKOs and controls, whereas ARKOs showed reduced capacity with age. SC capacity to support total germ cells revealed major deficits in ARKO and SCARKO adults, particularly with respect to postmeiotic germ cells. Using quantitative RT-PCR, the expression of SC markers was compared in d 50 testes. In ARKOs, expression of Pem, fatty acid binding protein, platelet-derived growth factor-A, and transferrin were all significantly reduced, whereas FSH receptor and AMH were increased. In SCARKOs, there were modest reductions in expression of cystatin-related gene highly expressed in testis and epididymis (cystatin-TE) and claudin-11, whereas expression of Pem, fatty acid binding protein, and platelet-derived growth factor-A was markedly reduced, highlighting these as potentially androgen-regulated SC genes that merit further study. In conclusion, androgen action is not required for maturation-dependent changes in immunoexpression of the SC markers AMH, p27(kip1), GATA-1, and sulfated glycoprotein-2 but is essential for expression of other SC genes, the attainment of normal SC number, and the support of meiotic and postmeiotic germ cell development.     

Submucosal tumors of the colon: Experience with twenty-five cases

Summary and Conclusions Submucosal tumors of the colon are rare and require alertness on the part of the physician for early diagnosis. These tumors may not cause symptoms before attaining large size. In most cases the clinical histories are atypical. Because of the possibility of malignancy, adequate diagnosis and treatment are necessary. This report deals with 25 cases of submucosal tumors of the colon. The tumor series included seven leiomyomas, one granular-cell myoblastoma, two leiomyosarcomas, seven carcinoid tumors, six lipomas, one lymphangioma, and one neurofibroma. Five of the tumors were asymptomatic. The endoscopic appearances of the tumors, although not diagnostic, may give some indications as to their natures. Endoscopic removal is possible, although it is indicated for high-risk patients only. Because submucosal tumors may be malignant, and because differentiation from secondary tumors (metastases) or tumor-like lesions is difficult without histologic examination, complete removal of the tumor is the treatment of choice.     

Hip Fracture Incidence from 1981 to 2009 in the Czech Republic as a Basis of the Country-Specific FRAX Model

The aim of this study was to calculate rates of hospitalization for hip fracture and the incidence of hip fractures in the Czech Republic over a period of 29 years. A second aim was to use the most recent data to populate a FRAX^? model for the assessment of fracture probability in individual patients. Data on hospitalizations for hip fracture (1981–2009) and number of women and men with hip fractures (2000–2009) were obtained, and incidences were computed for the entire population ≥50 years of age. Incidence of hospitalization for hip fracture in the Czech population aged ≥50 years increased progressively by calendar year. Age-standardized incidence of hip fractures increased to 2004 but leveled off thereafter and decreased after 2005. Data for hip fracture risk in 2008 and 2009 and the death hazard were used to populate a Czech-specific FRAX model for the computation of 10-year fracture probability. The customized FRAX model, using the verified epidemiological data, will be used to identify patients at increased fracture risk.