Developing a culture of nursing research through clinical-academic partnership

Evidence based practice is essential to advanced practice nursing, enabling the delivery of quality care and improved patient outcomes. As the name suggests, it requires healthcare decisions to be based on the best available and current evidence. Advanced practice nurses need astute critical analysis skills to appraise the evolving literature, and require research skills to lead on scientific inquiry and develop the profession. Yet, advanced practice nurses may not recognize themselves as research leaders. Participation in a journal club can promote evidence-based practice, improve clinician's critical thinking skills, and expose members to different research methodologies, however, nurses continue to face barriers to participation in these clubs. Establishing a clinical-academic partnership appears to be both mutually beneficial for clinicians and academics and is a significant enabler in the sustainability and functioning of the club through sharing expertise and experience. A supportive workplace culture is favourable to research utilization and knowledge translation. This paper outlines the role, practicalities, challenges, and benefits of setting up a hybrid urology journal and research club for advanced practice nurses in a clinical-academic partnership.     

The effect of stable macromolecular complexes of ionic polyphosphazene on HIV Gag antigen and on activation of human dendritic cells and presentation to T-cells

Neonates and infants are susceptible to infection due to distinct immune responses in early life. Therefore, development of vaccine formulation and delivery systems capable of activating human newborn leukocytes is of global health importance. Poly[di(carboxylatophenoxy)phosphazene] (PCPP) belongs to a family of ionic synthetic polyphosphazene polyelectrolyte compounds that can form non-covalent interactions with protein antigens and demonstrate adjuvant activity in animals and in human clinical trials. However, little is known about their ability to activate human immune cells. In this study, we characterized the effects of PCPP alone or in combination with a model antigen (recombinant HIV-Gag (Gag)), on the maturation, activation and antigen presentation by human adult and newborn dendritic cells (DCs) in vitro. PCPP treatment induced DC activation as assessed by upregulation of co-stimulatory molecules and cytokine production. Studies benchmarking PCPP to Alum, the most commonly used vaccine adjuvant, demonstrated that both triggered cell death and release of danger signals in adult and newborn DCs. When complexed with Gag antigen, PCPP maintained its immunostimulatory characteristics while permitting internalization and presentation of Gag by DCs to HIV-Gag-specific CD4⁺ T cell clones. The PCPP vaccine formulation outlined here has intrinsic adjuvant activity, can facilitate effective delivery of antigen to DCs, and may be advantageous for induction of beneficial T cell-mediated immunity. Moreover, polyphosphazenes can further reduce cost of vaccine production and distribution through their dose-sparing and antigen-stabilizing properties, thus potentially eliminating the need for cold chain distribution.     

One-year prospective study of cases of suspected acute myocardial infarction managed by urban and rural general practitioners.

BACKGROUND: The role of the general practitioner in the management of patients with suspected acute myocardial infarction is important and specific. It has been recommended that eligible patients should receive thrombolysis within 90 minutes of alerting medical or ambulance services. The administration of prehospital thrombolysis by general practitioners is controversial. Most research into the management of acute myocardial infarction has been hospital based and has not explored differences between urban and rural general practice. AIM: In 1993-94 a one-year prospective survey was undertaken of samples of urban and rural general practitioners to examine their management of cases of suspected acute myocardial infarction and to determine whether differences in management existed between the two settings. METHOD: General practitioners were recruited through the continuing medical education faculty network of the Irish College of General Practitioners. Participating general practitioners completed a report form for cases of suspected acute myocardial infarction. Six-week follow-up forms were also completed. RESULTS: A total of 113 general practitioners (54 urban and 59 rural) participated in the study. A total of 57 general practitioners contributed 195 cases, 49 from urban and 146 from rural areas. The mean number of cases of suspected acute myocardial infarction per participant for urban and rural doctors was 0.9 and 2.5, respectively. Median delay time from onset of symptoms to contacting the general practitioner was 90 minutes for both urban and rural patients. Median general practitioner response times for urban and rural doctors were 10 and 15 minutes, respectively. Median estimated journey times from location of the patient to hospital for urban and rural patients were 10 and 40 minutes, respectively (P<0.001). Rural doctors were more likely, in comparison with their urban counterparts, to administer aspirin (given to 40% of patients versus 16%, P<0.01) but less likely to administer intravenous morphine (26% versus 41%, P<0.05). Twenty one patients (11%) died at the scene; follow-up forms were received for 94% of the remaining patients. Of these 163 patients, 99% were admitted to hospital; 49% were discharged with a diagnosis of acute myocardial infarction and a further 25% had final diagnoses consistent with acute coronary heart disease. CONCLUSION: This study suggests that the management of patients with suspected acute myocardial infarction differs in urban and rural settings. Delay times suggest that in order to meet current guidelines, prehospital thrombolysis must become a reality in rural areas.     

Clinical and molecular basis of classical lissencephaly: Mutations in the LIS1 gene (PAFAH1B1)

Classical lissencephaly (LIS) and subcortical band heterotopia (SBH) are related cortical malformations secondary to abnormal migration of neurons during early brain development. Approximately 60% of patients with classical LIS, and one patient with atypical SBH have been found to have deletions or mutations of the LIS1 gene, located on 17p13.3. This gene encodes the LIS1 or PAFAH1B1 protein with a coiled‐coil domain at the N‐terminus and seven WD40 repeats at the C‐terminus. It is highly conserved between species and has been shown to interact with multiple proteins involved with cytoskeletal dynamics, playing a role in both cellular division and motility, as well as the regulation of brain levels of platelet activating factor. Here we report 65 large deletions of the LIS1 gene detected by FISH and 41 intragenic mutations, including four not previously reported, the majority of which have been found as a consequence of the investigation of 220 children with LIS or SBH by our group. All intragenic mutations are de novo, and there have been no familial recurrences. Eight‐eight percent (36/41) of the mutations result in a truncated or internally deleted protein—with missense mutations found in only 12% (5/41) thus far. Mutations occurred throughout the gene except for exon 7, with clustering of three of the five missense mutations in exon 6. Only five intragenic mutations were recurrent. In general, the most severe LIS phenotype was seen in patients with large deletions of 17p13.3, with milder phenotypes seen with intragenic mutations. Of these, the mildest phenotypes were seen in patients with missense mutations. Hum Mutat 19:4–15, 2002. © 2001 Wiley‐Liss, Inc.     

Computational investigation of in situ chondrocyte deformation and actin cytoskeleton remodelling under physiological loading

Previous experimental studies have determined local strain fields for both healthy and degenerate cartilage tissue during mechanical loading. However, the biomechanical response of chondrocytes in situ, in particular the response of the actin cytoskeleton to physiological loading conditions, is poorly understood. In the current study a three-dimensional (3-D) representative volume element (RVE) for cartilage tissue is created, comprising a chondrocyte surrounded by a pericellular matrix and embedded in an extracellular matrix. A 3-D active modelling framework incorporating actin cytoskeleton remodelling and contractility is implemented to predict the biomechanical behaviour of chondrocytes. Physiological and abnormal strain fields, based on the experimental study of Wong and Sah (J. Orthop. Res. 2010; 28: 1554–1561), are applied to the RVE. Simulations demonstrate that the presence of a focal defect significantly affects cellular deformation, increases the stress experienced by the nucleus, and alters the distribution of the actin cytoskeleton. It is demonstrated that during dynamic loading cyclic tension reduction in the cytoplasm causes continuous dissociation of the actin cytoskeleton. In contrast, during static loading significant changes in cytoplasm tension are not predicted and hence the rate of dissociation of the actin cytoskeleton is reduced. It is demonstrated that chondrocyte behaviour is affected by the stiffness of the pericellular matrix, and also by the anisotropy of the extracellular matrix. The findings of the current study are of particular importance in understanding the biomechanics underlying experimental observations such as actin cytoskeleton dissociation during the dynamic loading of chondrocytes.     

Postheparin plasma diamine oxidase in health and intestinal disease

In animals, the distribution of the enzyme diamine oxidase is confined, almost exclusively, to the small bowel mucosa. In humans, plasma diamine oxidase is at or below assay detection limits but can be liberated into the circulation from binding sites in the intestine by i.v. heparin. Therefore, the authors wished to see if diamine oxidase could be released by a low and safe dose of heparin (5000 U) and if the resultant area under the concentration-time curve would provide a noninvasive marker of segmental intestinal disease. In 17 control subjects, the mean area under the curve (following administration of 5000 U i.v. heparin) was 35.9 +/- 5.0 (SEM) mU.L-1.2 h-1; in 6 individuals studied on two separate occasions, postheparin plasma diamine oxidase profiles were reproducible (r = 0.98; p less than 0.001). The longitudinal distribution of diamine oxidase in the gastrointestinal tract, measured in 12 gastric, 16 jejunal, 6 ileal, and 18 colonic biopsies, was similar in humans to that found in animals. In patients with normal peroral biopsies, there was a linear relationship between jejunal mucosal and postheparin plasma diamine oxidase activities (r = 0.84; p less than 0.01). The areas under the curve in controls were then compared with those in patients with segmental intestinal diseases: 21 with ileal disease with or without colonic Crohn's disease (10 unoperated and 11 with ileal resection), 7 with non-Crohn's ileal resection, 8 with ulcerative colitis, 10 with untreated and 7 with treated celiac disease (6 studied before and after a gluten-free diet), and 5 studied during total parenteral nutrition and again after resumption of oral feeding. The results in the 18 ileectomized patients were subdivided into those with major (arbitrarily greater than 75 cm) and minor (less than 75 cm) resections. Areas under the curve were markedly reduced in nonresected Crohn's patients (6.0 +/- 1.79 mU.L-1.2 h-1; p less than 0.001 vs. controls), correlating inversely, in a first-order relationship, with disease activity (r = 0.82; p less than 0.001) and returning toward normal in 4 patients achieving disease remission. Low areas under the curve in total parenteral nutrition patients (4.5 +/- 0.9; p less than 0.001) were also reversible on resumption of oral feeding. However, areas under the curve were not significantly lower in patients with limited ileal resection (less than or equal to 75 cm), with celiac disease (untreated and treated), or ulcerative colitis than in controls.(ABSTRACT TRUNCATED AT 400 WORDS)     

Gastric morphology and serum gastrin levels in pernicious anaemia.

Mucosal biopsies from multiple sites in the stomachs of 21 patients with pernicious anaemia have been examined. The histological changes almost always involved the entire gastric mucosa, including that of the pyloric antrum. Metaplastic changes were almost universal and consisted of intestinal metaplasia in the body and antrum and pyloric metaplasia in the body. The severity of the pyloric metaplasia was such as to make the distinction between body and antrum on biopsy impossible. No relationship was found between serum gastrin activity and the histological appearances of the gastric antrum or body.     

Liver structure and function following small bowel resection

The observation that patients with extensive small bowel resection have impaired hepatocellular function with reduced BSP clearance and fatty change in biopsies from the liver led to a systematic study of liver structure and function following proximal and distal small bowel resection in the rat.While anaesthesia and surgery impaired BSP clearance per se, small bowel resection further reduced BSP clearance with impairment of both uptake and excretion phases of BSP excretion.The increased BSP retention was more marked after distal than after proximal small bowel resection, but in both experimental groups the abnormalities of BSP excretion spontaneously returned to normal three to four weeks after surgery.Circulating liver enzymes were normal but serum alkaline phosphatase was significantly depressed, particularly after distal resection. Isoenzyme studies showed that the depression of serum AP was due to a reduced intestinal isoenzyme. While serum levels remained consistently depressed up to eight weeks after proximal resection, in parallel with mucosal regeneration, serum AP returned to normal two to four weeks after ileectomy.While these minor changes in hepatic structure and function would normally be of little clinical importance, the additional insult of hepatic dysfunction may well be important in malnourished patients after extensive small bowel resection.