Findings from a feasibility study to improve GP elicitation of patient concerns in UK general practice consultations

Objectives

To establish: a) feasibility of training GPs in a communication intervention to solicit additional patient concerns early in the consultation, using specific lexical formulations (“do you have ‘any’ vs. ‘some’ other concerns?”) noting the impact on consultation length, and b) whether patients attend with multiple concerns and whether they voiced them in the consultation.

The Fixomull skin support method for wound closure in patients with fragile skin

We report the Fixomull (BSN Medical, Hamburg, Germany) skin support technique for wound closure, a novel method for closing elliptical incisions in patients with fragile skin. After the lesion of concern is excised, a strip of Fixomull is applied to the skin adjacent to the wound edge with an approximately 2 mm gap between the Fixomull and the incision edge. The wound is then closed with interrupted sutures through the Fixomull, with care to ensure wound edge eversion. Fixomull provides extra tensile strength. The sutures are removed at approximately 14 days, and the patient given a prophylactic course of oral antibiotics only if at high risk of infection. This is a simple, time efficient, inexpensive and effective measure to avoid skin grafts and reduce skin tears and trauma in patients with thin, fragile skin. In our practice there have been no significant skin infections using this technique.     

Cerebrospinal fluid flow dynamics in Huntington's disease evaluated by phase contrast MRI

Multiple targeted therapeutics for Huntington's disease are now in clinical trials, including intrathecally delivered compounds. Previous research suggests that CSF dynamics may be altered in Huntington's disease, which could be of paramount relevance to intrathecal drug delivery to the brain. To test this hypothesis, we conducted a prospective cross‐sectional study comparing people with early stage Huntington's disease with age‐ and gender‐matched healthy controls. CSF peak velocity, mean velocity and mean flow at the level of the cerebral aqueduct, and sub‐arachnoid space in the upper and lower spine, were quantified using phase contrast MRI. We calculated Spearman's rank correlations, and tested inter‐group differences with Wilcoxon rank‐sum test. Ten people with early Huntington's disease, and 10 controls were included. None of the quantified measures was associated with potential modifiers of CSF dynamics (demographics, osmolality, and brain volumes), or by known modifiers of Huntington's disease (age and HTTCAG repeat length); and no significant differences were found between the two studied groups. While external validation is required, the attained results are sufficient to conclude tentatively that a clinically relevant alteration of CSF dynamics – that is, one that would justify dose‐adjustments of intrathecal drugs – is unlikely to exist in Huntington's disease.     

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.     

Differential gene expression in ovarian carcinoma: identification of potential biomarkers

Ovarian cancer remains the fifth leading cause of cancer death for women in the United States. In this study, the gene expression of 20 ovarian carcinomas, 17 ovarian carcinomas metastatic to the omentum, and 50 normal ovaries was determined by Gene Logic Inc. using Affymetrix GeneChip HU_95 arrays containing approximately 12,000 known genes. Differences in gene expression were quantified as fold changes in gene expression in ovarian carcinomas compared to normal ovaries and ovarian carcinoma metastases. Genes up-regulated in ovarian carcinoma tissue samples compared to more than 300 other normal and diseased tissue samples were identified. Seven genes were selected for further screening by immunohistochemistry to determine the presence and localization of the proteins. These seven genes were: the beta8 integrin subunit, bone morphogenetic protein-7, claudin-4, collagen type IX alpha2, cellular retinoic acid binding protein-1, forkhead box J1, and S100 calcium-binding protein A1. Statistical analyses showed that the beta8 integrin subunit, claudin-4, and S100A1 provided the best distinction between ovarian carcinoma and normal ovary tissues, and may serve as the best candidate tumor markers among the seven genes studied. These results suggest that further exploration into other up-regulated genes may identify novel diagnostic, therapeutic, and/or prognostic biomarkers in ovarian carcinoma.     

Expression of C5a in the brain does not exacerbate experimental autoimmune encephalomyelitis

Complement is implicated in the pathology of neurodegenerative and inflammatory disease in the central nervous system (CNS). Although studies demonstrate that inhibition of complement activation attenuates disease development in the CNS, the specific complement components that contribute to the pathogenesis of CNS diseases remain unclear. To dissect the role of C5a in CNS disease, we developed a transgenic mouse that produces C5a exclusively in the brain using the astrocyte-specific, murine glial fibrillary acidic protein (GFAP) promoter. C5a/GFAP mice develop normally and do not demonstrate any signs of spontaneous inflammation or neurodegeneration with age. Using C5a/GFAP mice, we examined the outcome of the animal model of multiple sclerosis, experimental autoimmune encephalomyelitis (EAE). To our surprise the onset and severity of myelin oligodendrocyte glycoprotein-induced EAE was essentially identical between C5a/GFAP and control mice. These results demonstrate that C5a, despite it is pro-inflammatory functions, is not critical to the development and progression of EAE.     

Evidence that exposure to progesterone alone is a sufficient stimulus to cause a precipitous rise in the immunomodulatory protein the progesterone induced blocking factor (PIBF)

Purpose

To determine if exposure to progesterone alone is sufficient to increase the production of the immunomodulatory protein known as the progesterone induced blocking factor (PIBF). Also to determine what method of progesterone delivery or form of P best stimulates PIBF secretion.

Methods

Serum samples from patients with infertility and paid volunteers were evaluated for both PIBF and progesterone at various times during the follicular phase and the luteal phase in both natural cycles and cycles involving embryo transfer after endogenous and exogenous progesterone exposure and after various synthetic progestins. PIBF was measured by a non-commercial research ELISA assay. Comparisons were made of serum PIBF before and after exposure to progesterone, 17-hydroxyprogesterone, and oral contraceptives. PIBF was also measured before and after transfer of embryos.

Results

Progesterone alone without exposure to the fetal allogeneic stimulus was able to produce a marked increase in serum PIBF. Neither a synthetic progestin (19-nortestosterone derivative) nor 17-hydroxyprogesterone caused an increase in PIBF. Some PIBF is generally detected even in the follicular phase.

Conclusions

A previous concept considered that an allogeneic stimulus, e.g., from the fetal semi-allograft, was necessary to induce de novo progesterone receptors in gamma delta T cells, which, in turn, when exposed to a high concentration of progesterone, would secrete high levels of PIBF. These data show that exposure to an allogeneic stimulus is not needed to cause a marked rise in PIBF, merely progesterone alone is sufficient.

     

The paradoxical effects of SKF83959, a novel dopamine D1-like receptor agonist, in the rat acoustic startle reflex paradigm

While the benzazepine SKF83959 elicits classical behavioral responses associated with dopamine D1 receptors, it also acts as a D1 receptor antagonist biochemically. The paradoxical properties of this agent remain an enigma. In the present study, we sought to determine the behavioral effects of SKF83959 in the rat acoustic startle reflex test. Systemic administration of SKF83959 produced a dose-related increase in the startle amplitude with a stimulus of 105 dB, and a significant group difference was observed between animals treated with 1 mg/kg SKF83959 and vehicle controls. SKF83959 also significantly reduced the latency to startle response to stimuli of 95 dB and 105 dB in a dose-dependent manner. However, unlike classical dopamine D1-like receptor agonists, SKF83959 failed to disrupt prepulse inhibition (PPI) of either the startle amplitude or the latency to startle response; rather, the agent dose-dependently increased the PPI latency to startle response of 105 dB stimulus. These results suggest that the behavioral effects of SKF83959 in the rat acoustic startle reflex paradigm are paradoxical, and these paradoxical effects may be associated with its distinct pharmacological properties.