Controllable Expansion of Primary Cardiomyocytes by Reversible Immortalization

Cardiac tissue engineering will remain only a prospect unless large numbers of therapeutic cells can be provided, either from small samples of cardiac cells or from stem cell sources. In contrast to most adult cells, cardiomyocytes are terminally differentiated and cannot be expanded in culture. We explored the feasibility of enabling the in vitro expansion of primary neonatal rat cardiomyocytes by lentivector-mediated cell immortalization, and then reverting the phenotype of the expanded cells back to the cardiomyocyte state. Primary rat cardiomyocytes were transduced with simian virus 40 large T antigen (TAg), or with Bmi-1 followed by the human telomerase reverse transcriptase (hTERT) gene; the cells were expanded; and the transduced genes were removed by adenoviral vector expressing Cre recombinase. The TAg gene was more efficient in cell transduction than the Bmi-1/hTERT gene, based on the rate of cell proliferation. Immortalized cells exhibited the morphological features of dedifferentiation (increased vimentin expression, and reduced expression of troponin I and Nkx2.5) along with the continued expression of cardiac markers (α-actin, connexin-43, and calcium transients). After the immortalization was reversed, cells returned to their differentiated state. This strategy for controlled expansion of primary cardiomyocytes by gene transfer has potential for providing large amounts of a patient's own cardiomyocytes for cell therapy, and the cardiomyocytes derived by this method could be a useful cellular model by which to study cardiogenesis

Icodextrin-induced peritonitis: Study of five cases and comparison with bacterial peritonitis

Icodextrin-induced peritonitis: Study of five cases and comparison with bacterial peritonitis.BackgroundAn epidemic of aseptic peritonitis related to the presence of peptidoglycan contaminant in some batches of icodextrin solution (Extraneal®, Baxter Healthcare Corporation) occurred in Europe in the first six months of 2002.MethodsBy case-control study we examined the clinical and biologic features of 5 patients with icodextrin-induced peritonitis (group AP) and compared them with 7 patients with bacterial peritonitis (group BP) recruited in our clinical center between January and June 2002.ResultsDiagnosis of icodextrin-induced peritonitis was confirmed in all cases by a positive reintroduction test with contaminated batches of icodextrin. No recurrence was observed on re-exposure to icodextrin free of peptidoglycan. Skin tests were positive with contaminated icodextrin in 2 of 5 patients, while they were negative with icodextrin solution free of peptidoglycan (<0.6ng/mL). During peritonitis, serum level of C-reactive protein (CRP) was lower in group AP (42.4 ± 34mg/L) than in group BP (135 ± 59mg/L) (P = 0.01). Leukocyte number in peritoneal dialysis effluent was lower in group AP (284 ± 101/mm3), with a lower neutrophil/monocyte ratio (N/M = 0.67) than in group BP (1410 ± 973/mm3; N/M = 4) (P < 0.05). A low number of peritoneal fluid eosinophilia (11 ± 8%) was detected in group AP.ConclusionIcodextrin-induced peritonitis was associated with a burst of intraperitoneal cytokines. The phenotype of peritoneal neutrophils was different between aseptic and bacterial peritonitis, indicating that inflammatory stimuli that activate neutrophils in both types of peritonitis are clearly distinct. Finally, peritoneal injury measured by weight gain, peritoneal permeability, and CA125 concentration seemed to be less severe during icodextrin-induced peritonitis than during bacterial peritonitis

Efficacy of rituximab in thymoma associated minimal change disease: case report

International audienceBackground: Thymomas have been associated with a broad spectrum of autoimmune diseases. Minimal change disease (MCD) is the most frequent pathological lesion reported. Pathophysiological mechanisms involved in secondary MCD, and linking MCD to thymoma are not yet fully explained, although the hypothesis of T cell dysfunction has been suggested. The fundamental therapeutic principles are steroids and surgical treatment of thymoma, but failures and relapses often require immunosuppressant combinations. Case presentation: A 62-year-old female was admitted in our unit for a nephrotic syndrome associated with a thymoma. The diagnosis of thymoma associated MCD was confirmed by kidney biopsy. After surgical resection of the thymoma and steroid therapy, no remission was observed. Immunosuppressive therapy was then intensified with introduction of rituximab. Here, we report a steroid-resistant nephrotic syndrome secondary to MCD associated thymoma, which achieved complete remission after rituximab therapy. To the best of our knowledge, this is the first report of the use and efficacy of rituximab therapy in this pathology. Conclusions: Our case report suggests that primary and secondary MCD may share similar pathophysiological mechanisms. It does not allow us to draw any conclusions about the mechanism of action of rituximab, but we believe this report argues for the safety and efficacy of rituximab use in thymoma-associated MCD, and therefore constitutes a rationale for future studies

Outcome of polycystic kidney disease patients on peritoneal dialysis: Systematic review of literature and meta-analysis.

Polycystic kidney disease (PKD) is the most frequent hereditary cause of chronic kidney disease. Peritoneal dialysis (PD) is often avoided for patients with PKD because of the suspected risk of mechanical and infectious complications. Only a few studies have analyzed the outcome of PKD patients on PD with sometimes conflicting results. The purpose of this meta-analysis was to investigate outcomes of patients with PKD treated by PD.A systematic review and meta-analysis were performed examining all studies which included "Polycystic kidney disease" and "Peritoneal dialysis" in their titles, excluding commentaries, letters to the authors and abstracts. PubMed, Embase, Google scholar and Scopus were searched to December 31st 2017. The primary outcome was overall patient survival. Additional outcomes were PD technique survival, incidence of peritonitis and incidence of abdominal wall hernia.9 studies published between 1998 and 2016 were included for analysis with a total of 7,197 patients including 882 PKD patients. Overall survival of PKD patients was found to be better compared to non-PKD patients (HR = 0.70 [95% CI, 0.54-0.92]). There were no statistical differences between PKD and non-PKD patients in terms of peritonitis (OR = 0.86 [95% CI, 0.66-1.12]) and technical survival (HR = 0.98 [95% CI, 0.83-1.16]). There was an increased risk of hernia in PKD patients (OR = 2.28 [95% CI, 1.26-4.12]).PKD is associated with a better global survival, an increased risk of abdominal hernia, but no differences in peritonitis rate or technical survival were found. PD is a safe dialysis modality for PKD patients. Properly designed controlled studies are needed to determine whether all PKD patients are eligible for PD or whether some specific criteria should be determined

Adoption of harmonisation policy for the midwives’ training programme in Mali: A policy analysis

West Africa is engaged in a process of harmonising health workers’ training programmes as a means to regulate regional training standards and thus improve their quality. There is currently a lack of documented information regarding the adoption of these revised training programmes. In 2012 a harmonised programme, the WAHO competency-based curriculum, was introduced in Mali for training midwives. The present study explores the barriers and facilitators of the adoption of this programme and how the content, context, process, and actor-related factors influenced this. We used a qualitative research design consisting of document analysis (n = 25) and semi-structured interviews (n = 21) with policymakers, students, and those in charge of implementing the training programme. Information was collected on education and training policies, the context and process of the harmonised curriculum development, its adoption, and the actors involved in the adoption strategy, along with their role. The study shows that the adoption of the harmonised curriculum in Mali offered midwives an opportunity to attain a higher standard of training and level of qualification than before. It also displayed both the government’s and the public school’s willingness and commitment to improve maternal and child health through enhancing midwives’ training standards. The most salient factors that influenced adoption were the lack of available resources, and the lack of involvement of, and coordination with, relevant actors for successful policy adoption. Mali’s experience of adopting the harmonisation policy of training curricula demonstrates the need for the authorities to collaborate with relevant actors for information dissemination and in the adoption process. It also demonstrates the need for finding innovative ways to secure and diversify funding opportunities, as well as establish a supervisory body for health worker training

Master’s degree in sexual and reproductive health: enhancing career development opportunities for midwives in Mali

Abstract Background Midwives’ contribution to improving outcomes for women and newborns depends on factors such as quality of pre-service training, access to continuing professional development, and the presence of an enabling work environment. The absence of opportunities for career development increases the likelihood that health professionals, including midwives, will consider leaving the profession due to a lack of incentives to sustain and increase motivation to remain in the field. It also limits the opportunities to better contribute to policy, training, and research. This study aimed to assess the influence of a Master in Sexual and Reproductive Health (SRH) at the INFSS on midwives’ career progression in Mali. Methods This mixed methods study was conducted using an online questionnaire, semi-structured interviews, and a document review. The study participants included graduates from two cohorts (N = 22) as well as employers, managers, and teachers of the graduates (N = 20). Data were analysed according to research questions, comparing, and contrasting answers between different groups of respondents. Results The study revealed that graduates enrolled in the programme primarily to improve their knowledge and skills in management and public health. The graduates’ expected roles are those of programme and health project manager and participation in planning and monitoring activities at national or sub-national level. The managers expected the programme to reflect the needs of the health system and equip midwives with skills in management and planning. The Master enhanced opportunities for graduates to advance their career in fields they are not usually working in such as management, research, and supervision. However, the recognition of the master’s degree and of the graduates’ profile is not yet fully effective. Conclusion The master’s degree in SRH is a capacity building programme. Graduates developed skills and acquired advanced knowledge in research and management, as well as a postgraduate degree. However, the master programme needs to be better aligned with health system needs to increase the recognition of graduates’ skills and have a more positive impact on graduates’ careers

The Role of Community Pharmacists in the Detection of Clinically Relevant Drug-Related Problems in Chronic Kidney Disease Patients

Community pharmacists (CPs) have traditionally had limited access to patients’ estimated glomerular filtration rate (eGFR) during the medication-dispensing process. The increasing access to shared electronic health records is making eGFR available, but the skills needed to detect and manage clinically relevant drug-related problems (DRPs) are poorly documented. The primary objective of this study was to investigate the role of CPs in the medication-dispensation process for elderly patients with renal impairment. A total of 70 CPs participated in this 6 month study. Community pharmacists asked all patients ≥65 years to bring their laboratory test values for the next medication-dispensing process. Drug-related problem detection rates were compared between CPs (prospective period) and expert pharmacists (retrospectively). The clinical relevance of each DRP was assessed by nephrologists and general practitioners using an appropriate tool. Community pharmacists recruited n = 442 patients with eGFR &lt; 60 mL/min/1.73 m2 and detected n = 99 DRPs, whereas expert pharmacists detected n = 184 DRPs. The most frequently detected DRPs were dosage problems and contraindications. According to assessment by clinicians, CPs and expert pharmacists identified 54.0% and 84.7% of clinically relevant DRPs, respectively. This study suggests a positive impact of the systematic availability of eGFR to CPs on the detection of several DRPs with clinical relevance