Role of Rab27 in synaptic transmission at the squid giant synapse

Small GTPase Rab is a member of a large family of Ras-related proteins, highly conserved in eukaryotic cells, and thought to regulate specific type(s) and/or specific step(s) in intracellular membrane trafficking. Given our interest in synaptic transmission, we addressed the possibility that Rab27 (a close isoform of Rab3) could be involved in cytosolic synaptic vesicle mobilization. Indeed, preterminal injection of a specific antibody against squid Rab27 (anti-sqRab27 antibody) combined with confocal microscopy demonstrated that Rab27 is present on squid synaptic vesicles. Electrophysiological study of injected synapses showed that the anti-sqRab27 antibody inhibited synaptic release in a stimulation-dependent manner without affecting presynaptic action potentials or inward Ca²⁺ current. This result was confirmed in in vitro synaptosomes by using total internal reflection fluorescence microscopy. Thus, synaptosomal Ca²⁺-stimulated release of FM1-43 dye was greatly impaired by intraterminal anti-sqRab27 antibody. Ultrastructural analysis of the injected giant preterminal further showed a reduced number of docked synaptic vesicles and an increase in nondocked vesicular profiles distant from the active zone. These results, taken together, indicate that Rab27 is primarily involved in the maturation of recycled vesicles and/or their transport to the presynaptic active zone in the squid giant synapse.     

A clinical comparison of unrelated cord blood transplantation and unrelated bone marrow transplantation for adult patients with acute leukaemia in complete remission

We performed a clinical comparison of unrelated cord blood transplantation (UCBT) and unrelated bone marrow transplantation in adult acute leukaemia patients in complete remission (CR) who received the same conditioning regimen, graft-versus-host disease (GvHD) prophylaxis and supportive treatment. The incidence of acute GvHD was almost the same between the two groups, but the haematopoietic recovery was delayed and the incidence of chronic GvHD was higher in the UCBT group. The probability of 2 year disease-free survival was similar between the two groups. These results suggest that adult acute leukaemia patients in CR without a suitable donor should be considered as candidates for UCBT.     

Infective endocarditis caused by lactobacillus

Lactobacillus (LB) is a gram-positive rod-shaped bacterium that inhabits the oral cavity, gastrointestinal tract, vagina and nasal cavity. Although LB plays a role in the prevention of infections caused by pathogenic bacteria, it causes some critical infectious diseases such as infective endocarditis (IE). IE due to LB is rare; however, early diagnosis and early treatment are important because of its high mortality rate. We report the onset of IE after otologic treatment in a heavy drinker of alcohol, the second case of IE due to LB in Japan.     

Percutaneous radiofrequency ablation for early hepatocellular carcinoma: Risk factors for survival

AIM: To evaluate outcomes of radiofrequency ablation(RFA) therapy for early hepatocellular carcinoma(HCC) and identify survival- and recurrence-related factors. METHODS: Consecutive patients diagnosed with early HCC by computed tomography(CT) or magnetic resonance imaging(MRI)(single nodule of ≤ 5 cm, or multi-(up to 3) nodules of ≤ 3 cm each) and who underwent RFA treatment with curative intent between January 2010 and August 2011 at the Instituto do Cancer do Estado de S o Paulo, Brazil were enrolled in the study. RFA of the liver tumors(with 1.0 cm ablative margin) was carried out under CT-fluoro scan and ultrasonic image guidance of the percutaneous ablation probes. Procedure-related complications were recorded. At 1-mo post-RFA and 3-mo intervals thereafter, CT and MRI were performed to assess outcomes of complete response(absence of enhancing tissue at the tumor site) or incomplete response(enhancing tissue remaining at the tumor site). Overall survival and diseasefree survival rates were estimated by the Kaplan-Meier method and compared by the log rank test or simple Cox regression. The effect of risk factors on survival was assessed by the Cox proportional hazard model. RESULTS: A total of 38 RFA sessions were performed during the study period on 34 patients(age in years: mean, 63 and range, 49-84). The mean follow-up time was 22 mo(range, 1-33). The study population showed predominance of male sex(76%), less severe liver disease(Child-Pugh A, n = 26; Child-Pugh B, n = 8), and single tumor(65%). The maximum tumor diameters ranged from 10 to 50 mm(median, 26 mm). The initial(immediately post-procedure) rate of RFAinduced complete tumor necrosis was 90%. The probability of achieving complete response was significantly greater in patients with a single nodule(vs patients with multi-nodules, P = 0.04). Two patients experienced major complications, including acute pulmonary edema(resolved with intervention) and intestinal perforation(led to death). The 1- and 2-year overall survival rates were 82% and 71%, respectively. Sex, tumor size, initial response, and recurrence status influenced survival, but did not reach the threshold of statistical significance. Child-Pugh class and the model for end-stage liver disease score were identified as predictors of survival by simple Cox regression, but only Child-Pugh class showed a statistically significant association to survival in multiple Cox regression analysis(HR = 15; 95%CI: 3-76 mo; P = 0.001). The 1-and 2-year cumulative disease-free survival rates were 65% and 36%, respectively. CONCLUSION: RFA is an effective therapy for local tumor control of early HCC, and patients with preserved liver function are the best candidates.     

Medical error and systems of signaling: conceptual and linguistic definition

In recent years the issue of patient safety has been the subject of detailed investigations, particularly as a result of the increasing attention from the patients and the public on the problem of medical error. The purpose of this work is firstly to define the classification of medical errors, which are distinguished between two perspectives: those that are personal, and those that are caused by the system. Furthermore we will briefly review some of the main methods used by healthcare organizations to identify and analyze errors. During this discussion it has been determined that, in order to constitute a practical, coordinated and shared action to counteract the error, it is necessary to promote an analysis that considers all elements (human, technological and organizational) that contribute to the occurrence of a critical event. Therefore, it is essential to create a culture of constructive confrontation that encourages an open and non-punitive debate about the causes that led to error. In conclusion we have thus underlined that in health it is essential to affirm a system discussion that considers the error as a learning source, and as a result of the interaction between the individual and the organization. In this way, one should encourage a non-guilt bearing discussion on evident errors and on those which are not immediately identifiable, in order to create the conditions that recognize and corrects the error even before it produces negative consequences.