The effect of interferon-beta1a on relapses and progression of disability in patients with clinically isolated syndromes (CIS) suggestive of multiple sclerosis

Objectives: In 85 of young adults with multiple sclerosis (MS), onset is a subacute clinically isolated syndrome (CIS) of the optic nerves, brain stem or spinal cord. The advent of disease-modifying treatments for MS has increased attention on early stages of the disease. Therefore, the aim of this study was to evaluate the effect of interferon on relapses and progression of disability in patients with a CIS. Patients and methods: This randomized, clinical trial was conducted in 25 patients who presented with a CIS indicative of MS. They were evaluated in two groups: 11 patients who were receiving interferon-beta1a (Rebif, Serono) subcutaneous injections three times a week (group A), and 14 patients who were not receiving disease-modifying treatment (group B). The progression of disability was determined using the Kurtzke Expanded Disability Status Scale (EDSS) and the numbers of new relapses were recorded during 21 months of follow-up. Results: The mean numbers of new relapses and changes in EDSS at the end of study period were 0.68 (standard deviation S.D. = 0.80) and -1.09 (S.D. = 0.49), and 1.79 (S.D. = 1.05) and -0.64 (S.D. = 0.49) in groups A and B, respectively. Statistical analysis showed that disease-modifying treatment with interferon-beta1a may reduce relapses (P = 0.007) and prevent progressive disability (P = 0.034). Conclusion: Interferon-beta1a significantly delayed progression to disability and incidence of new relapses. © 2007 Elsevier B.V. All rights reserved

Phase I/II Trial of Liver-derived Mesenchymal Stem Cells in Pediatric Liver-based Metabolic Disorders: A Prospective, Open Label, Multicenter, Partially Randomized, Safety Study of One Cycle of Heterologous Human Adult Liver-derived Progenitor Cells (HepaStem) in Urea Cycle Disorders and Crigler-Najjar Syndrome Patients

Background. Regenerative medicine using stem cell technology is an emerging field that is currently tested for inborn and acquired liver diseases. Objective. This phase I/II prospective, open label, multicenter, randomized trial aimed primarily at evaluating the safety of Heterologous Human Adult Liver–derived Progenitor Cells (HepaStem) in pediatric patients with urea cycle disorders (UCDs) or Crigler-Najjar (CN) syndrome 6 months posttransplantation. The secondary objective included the assessment of safety up to 12 months postinfusion and of preliminary efficacy. Methods. Fourteen patients with UCDs and 6 with CN syndrome were divided into 3 cohorts by body weight and intraportally infused with 3 doses of HepaStem. Clinical status, portal vein hemodynamics, morphology of the liver, de novo detection of circulating anti–human leukocyte antigen antibodies, and clinically significant adverse events (AEs) and serious adverse events to infusion were evaluated by using an intent-to-treat analysis. Results. The overall safety of HepaStem was confirmed. For the entire study period, patient-month incidence rate was 1.76 for the AEs and 0.21 for the serious adverse events, of which 38% occurred within 1 month postinfusion. There was a trend of higher events in UCD as compared with CN patients. Segmental left portal vein thrombosis occurred in 1 patient and intraluminal local transient thrombus in a second patient. The other AEs were in line with expectations for catheter placement, cell infusion, concomitant medications, age, and underlying diseases. Conclusions. This study led to European clinical trial authorization for a phase II study in a homogeneous patient cohort, with repeated infusions and intermediate doses

Liver cell therapy: is this the end of the beginning?

The prevalence of liver diseases is increasing globally. Orthotopic liver transplantation is widely used to treat liver disease upon organ failure. The complexity of this procedure and finite numbers of healthy organ donors have prompted research into alternative therapeutic options to treat liver disease. This includes the transplantation of liver cells to promote regeneration. While successful, the routine supply of good quality human liver cells is limited. Therefore, renewable and scalable sources of these cells are sought. Liver progenitor and pluripotent stem cells offer potential cell sources that could be used clinically. This review discusses recent approaches in liver cell transplantation and requirements to improve the process, with the ultimate goal being efficient organ regeneration. We also discuss the potential off-target effects of cell-based therapies, and the advantages and drawbacks of current pre-clinical animal models used to study organ senescence, repopulation and regeneration

Objective measurement of nasal airway dimensions and resistance using acoustic rhinometry and rhinomanometry in habitual snorers compared with non-snorers

Snorers represent a heterogeneous group that requires adequate assessment before recommending surgical treatment. Most studies of the pathophysiology of snoring and obstructive sleep apnea have emphasized anatomical abnormalities in the oropharyngeal and hypopharyngeal airways. It is still unclear if nasal airway restriction plays an important role in sleep-disordered breathing and there is no general consensus if treatment of nasal pathology should be included in the management of patients with snoring or sleep apnea. The aim of this study was to compare nasal dimensions and airflow resistance of habitual snorers with non-snoring individuals by means of acoustic rhinometry and rhinomanometry. Sixty individuals were enrolled in this analytical cross-sectional study. They were divided in two groups: group A (case) consisted of 30 patients with a main complaint of chronic snoring referred to ear, nose, and throat (ENT) clinic of Hazrat-e-Rasoul University Hospital, Tehran, Iran. Group B (control) consisted of 30 individuals without any complaint of snoring. The subjects were assessed objectively with acoustic rhinometry and rhinomanometry. Nasal dimensions and airflow resistance were recorded for all individuals. The most common site of minimum cross-sectional area (MCA) was at the left concha-notch in both snoring and non-snoring individuals. Significant reduction of cross-sectional area of both isthmus and concha notches was seen in habitual snorers (P 0.05). The results of our study illustrate that acoustic rhinometry, rhinomanometry may be helpful methods for quantitative assessments of nasal airway respiratory function, and configuration in snorers; especially to evaluate site of MCA, decreased nasal cross-sectional area and increased nasal airflow resistance in habitual snorers which may lead to OSA. © 2008 Springer-Verlag

Burnout among the employees of health and therapy entities: Investigating the role of early maladaptive schemas and mental disorder symptoms(Article) [Sağlık ve terapi alanlarında çalışanlarda tükenme: Erken uyumsuz şemalar ve ruhsal bozukluk belirtilerinin rolünün araştırılması]

Objective: The present study has been done with the main purpose of investigating the relationship between early maladaptive schemas and mental disorder symptoms with burnout among the employees of administration-therapy and health-therapy departments in health entities. Methods: In this cross-sectional study, 300 employees have been selected by simple random sampling method. In this study, collecting data tools consisted of Maslach Burnout Questionnaire, Short Form of Young Early Maladaptive Schema and Symptom Checklist-Revised. The multiple regression analysis method has been used in order to determine each forecast variables (mental disorder symptoms) to determine the criterion variables (burnout dimensions). Results: Among the mental disorder symptoms, aggression, emotional exhaustion, depersonalization and aggression and paranoid ideations the method has been able to predict in positive and significant manner the decline in performance. Among the early maladaptive schemas, only impaired autonomy and performance was able to predict the emotional exhaustion. While, based on the results, 33 percent of the scores' variance of the decline in performance belongs to the scores' variance of impaired autonomy and performance and 44 percent are related to scores' variance of impaired autonomy/ performance and area of vigilance/inhibition. Conclusion: The results of this research reveal that schemas of impaired autonomy/performance, vigilance/inhibition, aggression and paranoid thoughts was able to predict the aspects of burnout. © 2017, Cukurova University, Faculty of Medicine. All rights reserved

Hygienic Quality of Raw Cow Milk Produced by Smallholder Dairy Farmers in BeniMellelarea in Morocco

This study was conducted to evaluate the hygienic quality of raw cow milk produced by smallholder dairy farmers and cooperatives (collecting centers) in BeniMellal area in Morocco. Hygienic quality of milk was determined by assessing the analysis of Total mesophilic aerobic flora or Total Bacterial Count,nbsp Total Coliforms Count, Fecal coliforms count and fungi (Yeast and Molds).nbsp The objective of this study was to evaluate the global milk quality in Moroccan dairy herds (hygienic and pathogenic parameters) and the perspectives on dairy development.For this, we evaluated the variations in the overall quality of raw milk: bacteriological and hygienic characterizations. Thus, samples of raw cow#39s milk produced in 50 farms and cooperatives were selected from different geographical areas in BeniMellal region. The investigation has concerned different cattle farms with different breeding procedures. Taken altogether, the samples analyzed show a moderate to high level of contamination of raw milk during the four seasons investigated exceeding generally the accepted limits. The most contaminated samples were found during the warm seasons: spring and autumn. However small but encouraging load levels percentage is evidenced reflecting an effort in hygienic procedures for the collection of raw milk and its storage in conditions respecting hygiene and temperature. Concerning the high level contamination, for classical causes classical results. Indeed, transportation, milking and pre-storage conditions as well as climate constitute the main factors for heavy bacterial and fungal contamination Taken together these variations reflect essentially differences in practical breeding and milk collecting procedures.nbs

Hepatic repopulation capacity and advanced metabolic liver functions of adult human liver progenitor cells revealed their potential use for the treatment of liver metabolic diseases

The potential use of stem/progenitor cells as alternative cell sources to mature hepatocytes for liver disease treatment depends on their ability to exhibit advanced metabolic liver functions and hepatic repopulation capacity. In the current study, four major liver functions were investigated in adult derived human liver stem/progenitor cell (ADHLSCs) populations subjected to in vitro hepatogenic differentiation: gluconeogenesis, ammonia detoxification, and activity of phase I and phase II drug-metabolizing enzymes. Engraftment and hepatogenic regeneration capacity were evaluated seven, thirty and sixty days after intrasplenic transplantation of undifferentiated ADHLSCs into six to eight SCID mice without regeneration stimulus. We demonstrated that differentiated ADHLSCs displayed higher de novo synthesis of glucose, correlating to an increased activity of glucose-6 phosphatase and mRNA expression of key related enzymes. In addition, these differentiated cells were able to metabolize ammonium chloride and produce urea. This was correlated to an increase mRNA levels of relevant key enzymes. With respect to drug metabolism, differentiated ADHLSCs expressed mRNAs for all the major cytochromes. Such increased expression is correlated to an enhanced phase I activity as independently demonstrated using fluorescence based assays. The most important cytochrome CYP3A4 was pharmacologically modulated in differentiated ADHLSCs using activators (phenobarbital) and inhibitors (Naringin) in a similar way than mature hepatocytes. Phase II enzyme activity and amino acid levels also show a significant enhancement in differentiated ADHLSCs. The application of such hepatogenic differentiation protocol on cryopreserved/thawed ADHLSCs did not alter these acquired metabolic activities. Analysis of transplanted mice livers revealed that ADHLSCs engrafted as isolated cells or clusters of hepatocyte-like cells expressing both human albumin and human Alu sequences in the parenchyma of SCID mice mostly near vascular structures. Analysis of serial sections revealed that these human albumin immuno-positive cells lost their initial mesenchymal marker vimentin and acquired the expression of ornithine transcarbamylase, suggesting in situ hepatic maturation of ADHLSCs. Displaying hepatic regeneration capacity in vivo as well as advanced liver metabolic functions after hepatogenic differentiation in vitro support the possibility to develop ADHLSCs as potential alternatives to primary hepatocytes for liver disease treatment

Early Detection of Renal Scarring in Children With Suspected Pyelonephritis: Comparison of Diuretic MAG3 Scintigraphy (F0) and DMSAScan

Background:Screening for patients at risk of renal scarring is a challenge in children with acute pyelonephritis(APN).Diuretic Tc-99m mercaptoacetyltriglycine (MAG3) scintigraphy with zero time injection of furosemide (MAG3-F0) was observed to display focal parenchymal disorders.The advantages of MAG3 include: lower radiation dose and short duration of the test.The aim of this study was to compare the role of Tc-MAG3(F0)dynamic study and Tc-99m dimercaptosuccinic acid (DMSA) scan in early detection of renal scarring of children with suspected pyelonephritis in comparison to after-6-month Tc-DMSAscan as gold standard. Methods:28 patients (56 renal units) with their first urinary tract infection (UTI) episode were evaluated prospectively for renal scarring with radioisotope scan. The patients were divided into 2 groups: Group Aconsisted of patients who underwent MAG3 scintigraphy in acute phase of pyelonephritis and Group B consisted of patients who underwent DMSA scan in this phase for renal cortical assessment.Follow up DMSA scan was performed for all patients in both groups 4-6 months after UTI episode.Results: The accuracy of MAG3-F0 scintigraphy and DMSA scan in detecting parenchymal changes in acute pyelonephritic phase were 89.3% and 96.4%,respectively.Positive predictive value(PPV)of both MAG3-F0 and DMSA was 100%.Whereas,negative predictive values (NPV) of MAG3-F0 and DMSA scan were 62.5% and 75%,respectively.Conclusion:Conclusively, if the MAG3 parenchymal image is abnormal, then there is renal damage but if this image is normal, a focal defect has not been excluded. Thus an abnormal MAG3-F0 precludes the need for a Tc-DMSAscan for detection of persistent renal damage in acute phase of pyelonephritis