Limitations of unidimensional indexes of right ventricular contractile function in conscious dogs

OBJECTIVE: Our goal was to examine the validity of unidimensional indexes of right ventricular contractile performance in vivo. METHODS: Unidimensional indexes and global measurements of right ventricular volume and contractile performance were compared in 6 conscious dogs. Vena caval occlusions were performed before (control) and during pulmonary arterial or aortic constriction. RESULTS: Moderately strong relationships were demonstrated between right ventricular septal-free wall indexes and global measurements of right ventricular end-diastolic and end-systolic volumes, stroke volume, stroke work, and the slope of the preload recruitable stroke work relationship, respectively, under control conditions (mean r (2) range 0.69-0.94). These relationships were shifted significantly, however, by increased right ventricular afterload. Increased left ventricular afterload significantly shifted the relationships between right ventricular septal-free wall dimensions and end-diastolic and end-systolic volumes. Relationships between the corresponding regional right ventricular free wall segmental indexes and global measurements under control conditions were weaker (mean r (2) range 0.12-0.65) and were significantly more sensitive to distortion by both increased right and left ventricular afterload, the effects of which were generally in opposite directions. These observations are consistent with significant ventricular interactive effects on the relationship between single right ventricular dimensions and right ventricular volume. CONCLUSION: Unidimensional right ventricular measurements are not reliable surrogates for right ventricular volume when assessing right ventricular contractile performance in the intact heart.     

Body mass index and response to tocilizumab in rheumatoid arthritis: a real life study

Several studies have suggested that obesity could have a negative effect on response to anti-tumor necrosis factor α (anti-TNFα) in rheumatoid arthritis (RA). Little is known about the impact of body mass index (BMI) on other biologic agents. We aimed to evaluate the effect of BMI on response to tocilizumab (TCZ) in RA. RA patients treated with TCZ were included in this multicenter retrospective study. BMI was calculated at the initiation of treatment. After 6 months of treatment, change from baseline in DAS28, pain on a visual analog scale, erythrocyte sedimentation rate and C-reactive protein level, and tender and swollen joints were analyzed. The primary endpoint was decrease in DAS28 ≥ 1.2. Secondary outcomes were good response and remission by EULAR criteria. At baseline, among 115 RA patients included, the median (interquartile range) BMI was 25.4 (22.0–28.8)?kg/m². The number of patients with normal weight, overweight, and obesity was 53 (46 %), 37 (32 %), and 25 (22 %), respectively. Baseline characteristics did not differ between the three subgroups of BMI. The median BMI did not differ between responders and non-responders for DAS28 decrease ≥1.2 (25.7 [22.1–29.9] vs 24.9 [22.0–27.1], P?=?0.38), EULAR good response (25.9 [22.8–30.0] vs 25.4 [22.0–28.4], P?=?0.61), and remission (25.1 [22.5–28.6] vs 25.4 [22.0–28.9], P?=?0.76). BMI did not affect the response to TCZ in RA. If confirmed, these results could be helpful for the selection of a biologic agent in obese RA patients.     

Lenalidomide before and after autologous stem cell transplantation for transplant-eligible patients of all ages in the randomized,phase III,Myeloma XI trial

The optimal way to use immunomodulatory drugs as components of induction and maintenance therapy for multiple myeloma is unresolved. We addressed this question in a large phase III randomized trial, Myeloma XI. Patients with newly diagnosed multiple myeloma (n=2,042) were randomized to induction therapy with cyclophosphamide, thalidomide, and dexamethasone (CTD) or cyclophosphamide, lenalidomide, and dexamethasone (CRD). Additional intensification therapy with cyclophosphamide, bortezomib, and dexamethasone (CVD) was administered before autologous stem-cell transplantation to patients with a suboptimal response to induction therapy using a response-adapted approach. After receiving high-dose melphalan with autologous stem cell transplantation, eligible patients were further randomized to receive either lenalidomide alone or observation alone. Co-primary endpoints were progression-free survival (PFS) and overall survival (OS). The CRD regimen was associated with significantly longer PFS (median: 36 vs. 33 months; hazard ratio [HR], 0.85; 95% confidence interval [CI]: 0.75-0.96; P=0.0116) and OS (3-year OS: 82.9% vs. 77.0%; HR, 0.77; 95% CI: 0.63-0.93; P=0.0072) compared with CTD. The PFS and OS results favored CRD over CTD across all subgroups, including patients with International Staging System stage III disease (HR for PFS, 0.73; 95% CI: 0.58-0.93; HR for OS, 0.78; 95% CI: 0.56-1.09), high-risk cytogenetics (HR for PFS, 0.60; 95% CI: 0.43-0.84; HR for OS, 0.70; 95% CI: 0.42-1.15) and ultra-high-risk cytogenetics (HR for PFS, 0.67; 95% CI: 0.41-1.11; HR for OS, 0.65; 95% CI: 0.34-1.25). Among patients randomized to lenalidomide maintenance (n=451) or observation (n=377), maintenance therapy improved PFS (median: 50 vs. 28 months; HR, 0.47; 95% CI: 0.37-0.60; P<0.0001). Optimal results for PFS and OS were achieved in the patients who received CRD induction and lenalidomide maintenance. The trial was registered with the EU Clinical Trials Register (EudraCT 2009-010956-93) and ISRCTN49407852.     

Fos and Jun potentiate individual release sites and mobilize the reserve synaptic-vesicle pool at the Drosophila larval motor synapse

In all nervous systems, short-term enhancement of transmitter release is achieved by increasing the weights of unitary synapses; in contrast, long-term enhancement, which requires nuclear gene expression, is generally thought to be mediated by the addition of new synaptic vesicle release sites. In Drosophila motor neurons, induction of AP-1, a heterodimer of Fos and Jun, induces cAMP- and CREB-dependent forms of presynaptic enhancement. Light and electron microscopic studies indicate that this synaptic enhancement is caused by increasing the weight of unitary synapses and not through the insertion of additional release sites. Electrophysiological and optical measurements of vesicle dynamics demonstrate that enhanced neurotransmitter release is accompanied by an increase in the actively cycling synaptic vesicle pool at the expense of the reserve pool. Finally, the observation that AP-1 mediated enhancement eliminates tetanus-induced forms of presynaptic potentiation suggests: (i) that reserve-pool mobilization is required for tetanus-induced short-term synaptic plasticity; and (ii) that long-term synaptic plasticity may, in some instances, be accomplished by stable recruitment of mechanisms that normally underlie short-term synaptic change.     

Laparoscopic treatment of perforated duodenal ulcer

OBJECTIVE: The aim of this study was to determine if laparoscopic simple closure for perforated duodenal ulcer is possible, efficient and safe. METHODS: Thirty-five consecutive patients with perforated duodenal ulcer and peritonitis were treated by simple closure, peritoneal lavage and omentoplasty. This treatment was performed laparoscopically. RESULTS: Diagnosis was confirmed in all cases. Conversion to laparotomy was necessary in two patients due to a technical problem and poor tolerance to pneumoperitoneum, respectively. Mean operative time was 120 min. Morbidity and mortality rates were 2.8%. Mean hospital stay was 7.8 days. No recurrence was found after eradication of Helicobacter pylori with a long-term follow-up of 38 months. CONCLUSION: Laparoscopic suture of perforated duodenal ulcer is possible and safe. It can avoid laparotomy with septic complications in peritonitis. In emergency there is no place for radical treatment of ulcer disease because of efficiency of medical treatment.     

Experimental characterization and Monte Carlo simulation of Si(Li) detector efficiency by radioactive sources and PIXE

This work relates to the study and characterization of the response function of an X-ray spectrometry system. The intrinsic efficiency of a Si(Li) detector has been simulated with the Monte Carlo codes MCNP and GEANT4 in the photon energy range of 2.6–59.5 keV. After finding it necessary to take a radiograph of the detector inside its cryostat to learn the correct dimensions, agreement within 10% between the simulations and experimental measurements with several point-like sources and PIXE results was obtained.