Diltiazem co-treatment in renal transplant patients receiving microemulsion cyclosporin

BACKGROUND: Usage of cyclosporin (the Hong Kong Hospital Authority's single largest item of drug expenditure) continues to increase, mainly due to increasing numbers of renal allograft patients taking it as long-term antirejection therapy. Diltiazem, an antihypertensive agent, interferes with the first pass extraction of oral cyclosporin, thus serving to conserve its dosage. AIMS: In renal transplant patients, to assess whether diltiazem co-treatment could achieve worthwhile dosage conservation of Neoral (a relatively new microemulsified cyclosporin formulation), safely. METHODS: A randomized, placebo-controlled, double-blind clinical trial was undertaken at three local hospitals. Renal transplant recipients receiving Neoral as prophylactic immunosuppression were randomized to two treatment arms. Active treatment consisted of diltiazem tablets 30 or 60 mg twice daily for patients weighing < 60 or >or= 60 kg, respectively. One hundred and ten eligible patients gave their informed consent, and were followed up for at least six months. The mean difference in the dollar cost in the sixth month was the primary outcome. Secondary/ancillary outcomes included changes in cyclosporin dosage and blood level, and untoward clinical events including rejection. Outcomes were evaluated by intention to treat analyses. RESULTS: During weeks 23-26 (sixth month) post randomization, diltiazem co-treatment yielded an estimated average cost saving per patient on drugs of 15%[the 95% confidence interval (CI) of the difference being HK dollars 609 +/- 517 or pound 50 +/- 42], with no apparent excess of untoward or adverse events, complications, hospitalization, outpatient visits, or inferior quality of life. CONCLUSIONS: This diltiazem co-treatment regime applied to the nearly 1800 surviving renal allograft patients followed up in Hospital Authority hospitals could have saved approximately HK dollars 14.3 million ( pound 1.17 million) annually, without adverse sequelae.     

Further testing of the Mental Health Problems Perception Questionnaire

AIM OF THE STUDY: This paper reports a two-part study relating to the further psychometric development of the Mental Health Problems Perceptions Questionnaire. BACKGROUND: The instrument was developed and used originally in a study to investigate the role of district nurses in caring for people with mental health problems, who live in rural settings. It is underpinned by an explicit theoretical framework in which therapeutic commitment, role support and role competency are core concepts. DESIGN: A two-part study is described. Part One used a test-retest method to examine the stability of the instrument on repeated administration. Part Two examined the instrument's internal reliability and construct validity by calculation of Cronbach's alpha coefficients and exploratory factor analysis. RESULTS: Satisfactory internal reliability for a new instrument was demonstrated. Exploratory factor analysis supported the previously proposed theoretical framework. Significant correlations were demonstrated between the scales which constitute the instrument, thereby providing further evidence of construct validity. CONCLUSIONS: The Mental Health Problems Perceptions Questionnaire provides a potentially useful instrument in relation to future educational, clinical and managerial research.     

An invertebrate model of the developmental neurotoxicity of insecticides: effects of chlorpyrifos and dieldrin in sea urchin embryos and larvae

Chlorpyrifos targets mammalian brain development through a combination of effects directed at cholinergic receptors and intracellular signaling cascades that are involved in cell differentiation. We used sea urchin embryos as an invertebrate model system to explore the cellular mechanisms underlying the actions of chlorpyrifos and to delineate the critical period of developmental vulnerability. Sea urchin embryos and larvae were exposed to chlorpyrifos at different stages of development ranging from early cell cleavages through the prism stage. Although early cleavages were unaffected even at high chlorpyrifos concentrations, micromolar concentrations added at the mid-blastula stage evoked a prominent change in cell phenotype and overall larval structure, with appearance of pigmented cells followed by their accumulation in an extralarval cap that was extruded from the animal pole. At higher concentrations (20-40 microM), these abnormal cells constituted over 90% of the total cell number. Studies with cholinergic receptor blocking agents and protein kinase C inhibitors indicated two distinct types of effects, one mediated through stimulation of nicotinic cholinergic receptors and the other targeting intracellular signaling. The effects of chlorpyrifos were not mimicked by chlorpyrifos oxon, the active metabolite that inhibits cholinesterase, nor by nonorganophosphate cholinesterase inhibitors. Dieldrin, an organochlorine that targets GABA(A )receptors, was similarly ineffective. The effects of chlorpyrifos and its underlying cholinergic and signaling-related mechanisms parallel prior findings in mammalian embryonic central nervous system. Invertebrate test systems may thus provide both a screening procedure for potential neuroteratogenesis by organophosphate-related compounds, as well as a system with which to uncover novel mechanisms underlying developmental vulnerability.     

Transfer of knowledge and skills: some implications for nursing and nurse education

The construct of transfer has enormous importance to nursing as it begins to highlight potential problems in the transfer of knowledge and skills from the campus to the clinical area, from one part of the clinical area to another (e.g. surgical to medical), and from community to the clinical area. Thus, any adequate conceptualization of transfer must account for problems of practice-practice transfer as well as theory-practice transfer. These potential problems are the concern of educators, students and managers who have a responsibility for agency nurses and bank nurses who may find themselves in different specialities on a regular basis. Transfer has relevance to a whole raft of other issues ranging from the application of theories to nursing practice, through to the validity of claims that courses which develop intellectual skills prepare nurses for lifelong learning.     

Influence of caloric restriction on the development of atherosclerosis in nonhuman primates: progress to date

Caloric restriction (CR) has been observed to retard aging processes and extend the maximum life span in rodents. In an effort to evaluate the effect of this nutritional intervention on physiologic variables in higher species, several nonhuman primate trials are ongoing. In particular, a study evaluating the independent effect of CR on the extent of atherosclerosis was initiated in 1993 in 32 adult cynomolgus monkeys. Therefore, the trial was designed to achieve identical cholesterol intake after animals were randomized to a control group or a calorie-restricted group (30% reduction from baseline caloric intake). The animals were routinely evaluated for glycated proteins, plasma insulin and glucose levels, insulin sensitivity, and specific measures for abdominal fat distribution by CT scans over a 4-year interval. The results from 4 years of intervention demonstrate that CR improves cardiovascular risk factors (such as visceral fat accumulation) and improves insulin sensitivity. In contrast to other primate studies with normolipidemic animals, CR had no independent effects on plasma lipid levels and composition in the presence of equivalent amounts of dietary cholesterol intake. Preliminary analysis of atherosclerotic lesion extent in the abdominal aorta has failed to demonstrate differences between control animals and CR animals. Follow- up studies are being conducted to determine the effect of CR on atherosclerosis extent in coronary and carotid arteries.      

A Prospective Audit of Postoperative Pain Control in Pediatric Patients

Pain is a subjective experience that is affected by physical, emotional, and psychological factors, and reliable assessment of pain can be a challenge in the pediatric population.A quality improvement project was conducted at one Canadian health care facility to examine the effectiveness of the postoperative pain management strategy for children admitted to the postanesthesia care unit (PACU).Effective control of postoperative pain involves several preventive strategies that include preoperative analgesia, appropriate use of intraoperative analgesic techniques, and identification of children at risk for significant postoperative pain. Successful implementation of these techniques requires a multidisciplinary team approach involving the patient, the PACU nurses, the anesthesia care provider, and other surgical team members. AORN J 90 (October 2009) 531-542. © AORN, Inc, 2009.     

Practitioner assessments of ‘good enough’ parenting: factorial survey

Aim. The aim of this study was to measure health visitors’ professional judgements on ‘good enough’ parenting and identify what factors and combinations of these are important when making such judgements. Background. The relationship between parenting and child health is unclear. Whilst agreement exists that ‘good enough’ parenting requires boundary setting, consistency and putting the child’s needs first, attempting to define ‘good enough’ parenting in precise terms is complex. When faced with a complex situation, practitioners rely on relatively few factors to form judgements. Design. Factorial survey methods were employed using vignette techniques. Methods. Vignettes were constructed using previous research on those variables, which may influence nurses’ judgements, for example, accommodation and child dentition. The level of factors was randomly varied. Two thousand vignettes were administered to a sample of 200 health visitors in two Health Boards who then made a judgement about this scenario. Analysis. Data were analysed through multiple regression with dummy variables and one‐way analysis of variance. Regression equations for both good enough mothering and good enough parenting are reported. Results. The models used are significant predictors of parenting and mothering. Significant predictors on health visitor judgements’ were boundary setting in sleep behaviours, type of housing inhabited and health behaviours. Although parenting and mothering are often conflated, health visitors appear to separate these aspects when making judgements based on type of housing. Conclusions. Most professionals can articulate what makes a ‘good’ parent, equally they may have strong views regarding what constitutes ‘poor’ parenting. The difficulty is in determining when parenting is ‘good enough’ to provide a child with a nurturing environment. Relevance to clinical practice. This study suggests that practitioners move their thresholds of what is ‘good enough’ depending on a narrow range of factors. Awareness of the factors, which influence individuals’ judgements is important in safeguarding children.     

Evolution of motor patterns: aquatic feeding in salamanders and ray-finned fishes

Patterns of muscle activity (motor patterns) have generally been found to be strongly conserved during the evolution of aquatic feeding behavior within closely related groups of fishes and salamanders. We conducted a test of the generality of motor pattern conservation with a much broader phylogenetic scope than has been done previously. Activity patterns of three cranial muscles were quantified from electromyographic (EMG) recordings made during suction feeding in a salamander (Ambystoma mexicanum) and 4 widely divergent species of ray-finned fishes (Amia calva, Notopterus chitala, Micropterus salmoides and Lepomis macrochirus). General features of the motor pattern were the same in all species, but multivariate and univariate analyses of variance revealed highly significant differences among the 5 species in the average muscle activity pattern, indicating that the motor pattern has not been precisely conserved among these 5 taxa. Five of eight EMG variables that describe the intensity and timing of muscle activity differed among species. Only the intensity of activity of the adductor mandibulae appears to be a strongly conserved feature of the suction feeding motor pattern in anamniotes. A discriminant function analysis of the 8 EMG variables successfully classified about two thirds of the feeding incidents as belonging to the correct species. In contrast to the results of previous studies of closely related taxa, we found that numerous quantitative differences exist among species, indicating that functionally significant details of suction feeding motor patterns have changed during evolution, whereas several general features of the pattern have been conserved.     

Glutathione S-transferase expression in fetal kidney and Wilms' tumour

The glutathione S-transferases (GSTs) have been implicated in carcinogenesis and tumour drug-therapy resistance. In this study GST pi was the predominant isoenzyme in the fetal human kidney. It was present in differentiated epithelial structures but never in the primitive mesenchyme. By contrast most cases of Wilms' tumours showed GST pi in both epithelial structures and undifferentiated blastema. The level of expression, as assessed by immunostaining, was no more than moderate, and was generally higher in differentiated elements. In only one case was GST alpha found in Wilms' tumour. This study had demonstrated a difference between fetal kidney and Wilms' tumour blastema in terms of GST expression.