Effect of carbenoxolone sodium on aspirin-induced injury of the rat gastric mucosa

Investigations were performed in the rat to examine the effect of carbenoxolone sodium on aspirin-induced gastric mucosal injury. Mucosal damage was quantitated histologically in the body of the stomach (corpus) after a single dose of aspirin and after 2 weeks of daily aspirin. Over dosage ranges of 2–30 mg/kg/day of carbenoxolone and 10–120 mg/kg of aspirin, carbenoxolone treatment conferred no protection, despite evidence of a significant carbenoxolone effect on gastric mucus. This contrasts with the known protective action of carbenoxolone against injury by restraint stress and by corticosteroids. Much current evidence suggests that the mechanisms of erosion production by aspirin differ from those by restraint stress and corticosteroids, and it is likely that the present findings reflect such differences in pathogenesis.     

A novel retroviral mutagenesis screen identifies prognostic genes in RUNX1 mediated myeloid leukemogenesis

Using a novel retroviral shuttle vector approach we identified genes that collaborate with a patient derived RUNX1 (AML1) mutant. RUNX1 mutations occurs in 40% of myelodysplastic syndromes (MDS). MDS are a group of hematopoietic stem cell disorders that are characterized by dysplasia that often progress to acute myeloid leukemia (AML). Our goal was to identify genes dysregulated by vector-mediated genotoxicity that may collaborate with the RUNX1 mutant (D171N). D171N expressing cells have a survival and engraftment disadvantage and require additional genetic lesions to survive and persist. By dysregulating genes near the integrated vector provirus, the shuttle vector can promote transformation of D171N cells and tag the nearby genes that collaborate with D171N. In our approach, a gammaretroviral shuttle vector that expresses D171N is used to transduce CD105⁺, Sca-1⁺ mouse bone marrow. Mutagenized cells are expanded in liquid culture and vector integration sites from surviving cells are then identified using a retroviral shuttle vector approach. We repeatedly recovered integrated vector proviruses near genes (Itpkb, Ccdc12, and Nbeal2). To assess the prognostic significance of the genes identified we examined differential expression, overall survival, and relapse free survival of AML patients with alteration in the genes identified using The Cancer Genome Atlas (TCGA) AML data set. We found that ITPKB functions as an independent factor for poor prognoses and RUNX1 mutations in conjunction with ITPKB, CCDC12, and NBEAL2 have prognostic potential in AML.     

Education needs for integrated care: a literature review

Aim. This paper reports a systematic review to identify the education needs of the workforce within primary care to promote the effective delivery of integrated health and social care services. Background. The need for different professionals to work more closely dominates global health policy. The drive to develop a workforce prepared for the future is crucial to the success of integrated services. However, some have argued that nurses are ill‐equipped to meet the challenges of integrated service provision. The ability to work interprofessionally is an important skill which needs to be developed to support integrated working. Methods. Structured searches were undertaken on organizational websites and the Caredata, CINAHL, Cochrane Library, MEDLINE, Sociofile databases between December 2002 and April 2004 to identify policy documents and primary research studies. The robustness of identified research studies were appraised using recognized appraisal tools. Findings. Six themes were identified which indicate essential elements needed for integrated care. The need for effective communication between professional groups within teams and an emphasis on role awareness are central to the success of integrated services. In addition, education about the importance of partnership working and the need for professionals to develop skills in relation to practice development and leadership through professional and personal development is needed to support integrated working. Conclusion. Education which embeds essential attributes to integrated working is needed to advance nursing practice for interprofessional working. Further research exploring this and its impact on integrated provision is essential to ensure that evidence‐based services are provided. The reinforcement of partnerships between higher education institutions and health and social care organizations should ensure that the workforce is educated to manage continuous change in service delivery. Innovative ways of teaching and learning which promote inter‐professional working need to be explored.     

Haemostatic responses and vasopressin release during colonoscopy in man.

1. During major abdominal surgery there are increases in Factor VIII and plasminogen activator activity, associated with elevated plasma concentrations of vasopressin, of a magnitude shown to affect haemostasis. 2. To investigate the mechanisms involved in the haemostatic response to surgery, 12 patients undergoing fibre-optic colonoscopy were studied, of which six had a complete and six had an incomplete examination. 3. Venous blood samples were taken before, during and after the procedure for assay of plasma vasopressin, adrenaline and noradrenaline concentrations, Factor VIII coagulant activity, von Willebrand factor antigen level, euglobulin clot lysis time, tissue-type plasminogen activator activity and tissue-type plasminogen activator inhibition. 4. In the six patients who underwent a complete procedure the median plasma vasopressin concentration rose from 0.6 pg/ml to 153 pg/ml during colonoscopy. Factor VII coagulant activity rose from 0.9 to 2.4 i.u./ml and von Willebrand factor antigen level rose from 139 to 224%. Plasminogen activator activity increased from 20 to 144 units and tissue-type plasminogen activator activity rose from 107 to 1338 m-i.u./ml, whereas tissue-type plasminogen activator inhibition fell from 4.8 to 1.0 i.u./ml. 5. In the six patients in whom a limited procedure was performed, there were no changes in haemostatic function or in plasma vasopressin concentration. Plasma concentrations of adrenaline and noradrenaline did not change in either group. 6. The results indicate that vasopressin regulates the intrinsic coagulation pathway and fibrinolytic system in the absence of adrenaline release.     

Training communication partners of people with traumatic brain injury: A randomised controlled trial

Background: Communication disorders after traumatic brain injury (TBI) are difficult to modify due to the cognitive limitation imposed by frontal lobe damage. As an alternative approach, this paper describes a training programme designed to improve communication partners' responsiveness to people with TBI during routine service inquiries with a community agency. Aims: To evaluate the effectiveness of a training programme aimed at improving the communication of police officers during service encounters with people with TBI. Methods & Procedures: A total of 20 police officers were randomly assigned to two groups (training or control). Prior to the 6‐week training programme, participants with TBI made a routine telephone inquiry to the police officers. Training focused on specific aspects of telephone inquiries previously documented to be aberrant in service encounters of people with TBI. Following the training programme, police subjects received another telephone service inquiry. Service encounters were transcribed and analysed using generic structure potential analysis. Outcome & Results: Comparison of pre‐ and post‐training measures indicated that trained police had learned strategies to successfully establish the nature of the inquiry, provide a clear answer to the inquiry, and ensure appropriate leave taking, resulting in more efficient, focused interactions in the post‐training telephone calls. People with TBI also altered their communication in the post‐training calls, with reduced episodes of unrelated utterances and an increased proportion of the interaction devoted to completing the service encounter. This appeared to be in response to the communicative options they were given. Conclusions: This study demonstrates the efficacy of an approach based on training communication partners rather than people with TBI themselves. Training communication partners led to the provision of appropriate feedback, support, and structure of everyday interactions. Service encounters account for a significant amount of everyday communication exchanges, therefore training service providers has the potential to have a significant impact on the communicative effectiveness of people with TBI.     

Hepatic endothelial CCL25 mediates the recruitment of CCR9+ gut-homing lymphocytes to the liver in primary sclerosing cholangitis

Primary sclerosing cholangitis (PSC), a chronic inflammatory liver disease characterized by progressive bile duct destruction, develops as an extra-intestinal complication of inflammatory bowel disease (IBD) (Chapman, R.W. 1991. Gut. 32:1433-1435). However, the liver and bowel inflammation are rarely concomitant, and PSC can develop in patients whose colons have been removed previously. We hypothesized that PSC is mediated by long-lived memory T cells originally activated in the gut, but able to mediate extra-intestinal inflammation in the absence of active IBD (Grant, A.J., P.F. Lalor, M. Salmi, S. Jalkanen, and D.H. Adams. 2002. Lancet. 359:150-157). In support of this, we show that liver-infiltrating lymphocytes in PSC include mucosal T cells recruited to the liver by aberrant expression of the gut-specific chemokine CCL25 that activates alpha4beta7 binding to mucosal addressin cell adhesion molecule 1 on the hepatic endothelium. This is the first demonstration in humans that T cells activated in the gut can be recruited to an extra-intestinal site of disease and provides a paradigm to explain the pathogenesis of extra-intestinal complications of IBD.     

An individual differences perspective on change in psychotherapy: The case of health care utilization

Abstract

The purpose of this study was to explore systematic interindividual variation in change of a number of health care utilization variables (HCUVs) during psychotherapy and identify patient characteristics associated with this variation. Three-wave panel data from 420 patients were analyzed with nonparametric latent class regression followed by chi-square interaction analyses among patient variables. For the various HCUVs, three to six classes were identified, with widely different patterns of change during treatment. Axis I diagnosis, chronicity, functional impairment, gender, and level of education were among the patient characteristics that differentiated the classes. It was concluded that main effects analyses seriously distort heterogeneity of change and that health care utilization, unless it is a specific therapeutic aim, may be irrelevant as an indication of outcome of psychotherapy.     

The effects of therapy for mild hypertension on circulating level of dopamine beta-hydroxylase.

Circulating dopamine beta-hydroxylase levels and norepinephrine excretion were measured in 76 mild hypertensive patients. Levels of dopamine beta-hydroxylase, norepinephrine excretion and blood pressure were obtained both before and after the initiation of therapy. Data from 20 patients exhibiting a diastolic blood pressure decrease of 10 mmHg or more were compared with data from 10 normotensive individuals. Changes in dopamine beta-hydroxylase levels were similar for the two groups and were not related to blood pressure changes. Intra-individual variation was small in both groups. There were no detectable functional relationships between diastolic pressure and urinary norepinephrine, norepinephrine and dopamine beta-hydroxylase or dopamine beta-hydroxylase and diastolic pressure. It dose not seem likely that dopamine beta-hydroxylase levels can replace urinary catecholamines as a commonly used index of sympathetic activity.