A high-performance liquid chromatography-tandem mass spectrometric method for the determination of pharmacokinetics of ganaxolone in rat, monkey, dog and human plasma

A method for determining concentration levels of ganaxolone in rat, monkey, dog and human plasma was validated in the range of 5-1500 ng/ml using a 200-microl plasma sample volume. This validation report describes the linearity, specificity. sensitivity, reproducibility, accuracy, recovery and stability of the analytical method. The inter-day C.V. ranged from 0.5 to 9.2%, intra-day C.V. from 0.7 to 8.8% and intra-day accuracy (mean absolute percentage difference) ranged from 0.0 to 14.0% for rat, monkey, dog and human plasma. The method was used for the routine analysis of ganaxolone in rat, monkey, dog and human plasma and summary of the pharmacokinetic data are presented.     

Apoptosis in breast carcinoma

Apoptosis may play a major role in determining tumor growth and aggressiveness. The aim of this study was to examine the relationship between apoptosis, expression of bcl-2 and p53 proteins, proliferation index, and other clinicopathological features of breast carcinoma. Sixty-five formalin-fixed paraffin-embedded tissue sections from invasive ductal breast carcinomas were studied for the presence of apoptosis by the terminaldeoxynucleotidyl-transferase-mediated dUTP-FITC nick end-labeling (TUNEL) method. Immunohistochemical methods were also used to determine the expression of estrogen receptor, Ki67, bcl-2 and p53 proteins. The number of apoptotic cells ranged from 2.0 to 236.0/10HPF (mean 36.26, median 28.0). The observation of 30 apoptotic cells/10HPF was more common in tumors > 3 cm, of histological grade III, with a high mitotic index, Ki67 index > or = 300, and p53 positivity; however, statistical significance was found only for the histological grade. Grade I and III tumors displayed an inverse association between the apoptotic index and bcl-2 and p53 protein expressions; grade I tumors frequently expressed bcl-2 (19/28), lacked p53 (20/28), and presented a low number of apoptotic cells (18/28), whereas grade III tumors tended to express p53 (12/17), lacked bcl-2 (13/17), and displayed a high number of apoptotic cells/10HPF (12/17). Multivariate analysis for survival revealed that estrogen receptors and apoptosis were independent variables. These data suggest that apoptosis, rather than proliferation index or expression of bcl-2 or p53 proteins, is an independent factor for the prognosis of survival.     

Histological discrimination of idiopathic inflammatory bowel disease from other types of colitis.

AIMS--To assess the value of histology in diagnosing inflammatory bowel disease (IBD) in colorectal biopsy specimens. METHODS--Retrospective, double blind evaluation of colorectal biopsy specimens from 41 patients with colitis (28 with ischaemic colitis and 13 with acute self-limited colitis) and 84 patients with IBD (42 with Crohn''s disease and 42 with ulcerative colitis). RESULTS--The features distinguishing IBD from other forms of colitis included distorted architecture, lymphocyte and plasma cell infiltrate, excess of polymorphonuclear leucocytes, polymorphonuclear cryptitis, crypt abscesses, and basal lymphoid aggregates. The features discriminating between Crohn''s disease and ulcerative colitis included an irregular or villous surface, distorted architecture, decrease in mucus content, and polymorphonuclear cryptitis. Using multivariate analysis, 90% of patients with Crohn''s disease and 71% of those with ulcerative colitis were correctly classified, the former being strongly defined by epithelioid granulomas, microgranulomas and isolated giant cells, and the latter best defined by an irregular or villous surface, decrease in mucus content and crypt atrophy. CONCLUSIONS--Examination of colorectal biopsy specimens is a reliable method for diagnosing IBD. In the absence of epithelioid granulomas, microgranulomas and isolated giant cells a diagnosis of Crohn''s disease is based on the absence of histological criteria favouring ulcerative colitis. The histological spectrum of indeterminate colitis remains to be clarified.     

Immunohistochemical characterization of fibroblast subpopulations in normal peritoneal tissue and in peritoneal dialysis-induced fibrosis

Peritoneal fibrosis is one of the most common morphological changes observed in continuous ambulatory peritoneal dialysis (CAPD) patients. Both resident fibroblasts and new fibroblast-like cells derived from the mesothelium by epithelial-to-mesenchymal transition are the main cells involved fibrogenesis. In order to establish markers of peritoneal impairment and pathogenic clues to explain the fibrogenic process, we conducted an immunohistochemical study focused on peritoneal fibroblasts. Parietal peritoneal biopsies were collected from four patient groups: normal controls (n=15), non-CAPD uremic patients (n=17), uremic patients on CAPD (n=27) and non-renal patients with inguinal hernia (n=12). To study myofibroblastic conversion of mesothelial cells, -smooth muscle actin (SMA), desmin, cytokeratins and E-cadherin were analyzed. The expression of CD34 by fibroblasts was also analyzed. Fibroblasts from controls and non-CAPD uremic patients showed expression of CD34, but no myofibroblastic or mesothelial markers. The opposite pattern was present during CAPD-related fibrosis. Expression of cytokeratins and E-cadherin by fibroblast-like cells and -SMA by mesothelial and stromal cells supports that mesothelial-to-myofibroblast transition occurs during CAPD. Loss of CD34 expression correlated with the degree of peritoneal fibrosis. The immunophenotype of fibroblasts varies during the progression of fibrosis. Myofibroblasts seem to derive from both activation of resident fibroblasts and local conversion of mesothelial cells.Manuel López-Cabrera and Rafael Selgas contributed equally to the article.     

Impact of Game-Based Interventions on Health-Related Outcomes in Hospitalized Older Patients: A Systematic Review

ObjectivesTo examine the effectiveness of game-based interventions compared with usual care on health-related outcomes for acutely hospitalized older patients.DesignSystematic review of randomized controlled trials (RCT) and nonrandomized trials.Setting and ParticipantsAdults aged 65 years or older admitted to an Acute Care for Elderly unit were selected.MeasuresHealth-related outcomes (eg, functional capacity, quality of life, adherence to treatment).ResultsFour RCTs were included in the review. The interventions were based on the implementation of serious-game programs using Nintendo Wii in acute medical patients. Across the included studies, no significant differences were observed between groups on functional capacity and health-related quality of life. Significant differences were found between groups on the adherence to treatment (in favor of the control group), but no differences were obtained in other outcomes such as enjoyment and motivation.Conclusions and ImplicationsIn general, there is very limited evidence for the efficacy to reach conclusions about the effects of game-based interventions on health-related outcomes in acutely hospitalized older patients. Future studies are needed to improve our knowledge in the field; however, we consider that these strategies should be considered in the future complementary to usual care.     

Adolescent Substance Use Behavior Change Through School Intervention Is Improved by Teacher and School Implementation Support Together,Especially for Girls

Prevention Science - An earlier trial of a school-based, preventative intervention, HealthWise South Africa, demonstrated some efficacy in preventing adolescent drinking and smoking in the Western...     

Top 100. Revisión de los artículos más citados sobre cirugía laparoscópica del páncreas

IntroductionThe number of citations is considered as an indirect indicator of the merit of an article, journal or researcher, although it is not an infallible method to determine scientific quality. Our goal is to determine the characteristics of the articles most cited about pancreas and laparoscopy.MethodsWe performed a search of all articles published in any journal about pancreas and laparoscopy until September 2019 and selected the 100 most cited papers. We recorded number of citations, journal, year of publication, quartil, impact factor, institution, country, authors type of paper, type of surgery, topic and area.ResultsThe top 100 citations account 10,970 citations in total. The journal with the most articles is Surgical Endoscopy and 2007 is the year with the highest number of articles in the top 100 citations. The percentage of publications from America and Europe are similar.Case series is the most frequently paper, outcomes/morbidity is the most frequently discussed topic, and distal pancreatectomy is the most frequently type of surgery.ConclusionsThis bibliometric study on pancreas and laparoscopy is conditioned by the time factor, since laparoscopy has arrived later at pancreatic surgery, probably due to the morbidity and mortality associated with pancreatic surgery and the need for a high specialization in this field. The literature is recent and scarce. More and better-quality studies are needed in this field.     

Rehabilitación multimodal en cirugía de urgencias: ¿utopía o realidad?

Enhanced Recovery After Surgery (ERAS) constitutes the application of a series of perioperative measures based on the evidence, in order to achieve a better recovery of the patient and a decrease of the complications and the mortality. These ERAS programs initially proved their advantages in the field of colorectal surgery being progressively adopted by other surgical areas within the general surgery and other surgical specialties. The main excluding factor for the application of such programs has been the urgent clinical presentation, which has caused that despite the large volume of existing literature on ERAS in elective surgery, there are few studies that have investigated the effectiveness of these programs in surgical patients in emergencies. The aim of this article is to show ERAS measures currently available according to the existing evidence for emergency surgery.