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No description available.

No description available.

No description available.

No description available.

No description available.

Behçet’s disease (BD) is a vasculitis of unknown aetiology typified by recurrent oral and genital ulcers, skin and ocular lesions. Debilitating manifestations can also affect vascular, gastrointestinal and neurological systems. Previous BD investigations showed increased circulating neutrophils and neutrophil elastase (NE), a serine protease. NE can digest connective tissues compromising their integrity if not regulated. In this study, NE and its two main inhibitors, secretory leukocyte protease inhibitor (SLPI) and alpha1- antitrypsin (α1AT), were investigated to determine if NE dysregulation is triggering oral mucosal damage. Findings were compared to healthy controls (HC) and recurrent aphthous stomatitis (RAS) patients, a disorder of episodic oral ulceration. FlowCytoMixTMmultiplex-assays compared saliva and serum inflammatory cytokines measurements where salivary levels reflected disease activity and correlated with published serum levels. Salivary NE, SLPI, and α1AT were measured by ELISA. Patients with oral ulcers had increased NE. Unexpectedly, BDq (quiescent, without ulceration) had increased NE, but SLPI was significantly lower than RASq and HC. RASq NE levels were similar to HC. Overall, NE correlated with α1AT levels, but showed an inverse relationship with SLPI. Quantitative PCR revealed significantly increased SLPI mRNA expression in both BDq and RASq buccal epithelium. High mRNA/low SLPI protein expression during ulceration could be explained by deficient translation, blocked ELISA antibody binding, or SLPI depletion. Despite high α1AT, all study groups had enzymatically active salivary NE which was successfully inhibited by recombinant SLPI. Confocal microscopy revealed BD patients’ blood neutrophils readily release neutrophil extracellular traps (NETs) in vitro compared to HCs. Antimicrobial NETs have mixed granule contents coating decondensed chromatin fibres and are associated with autoimmunity. During NET production, our novel observation that intracellular SLPI but not α1AT co-localised with NE suggests a regulatory role. This study supports the theory that a protease-antiprotease imbalance may play a role in BD oral and systemic pathology.

The effect of reduced frequency of administration of misoprostol on its ability to prevent aspirin-induced gastric injury was evaluated. Twenty-four random-source dogs were divided into 4 groups which received aspirin and misoprostol as follows: Group I, 25 mg/kg aspirin PO TID and placebo PO TID; Group II, 25 mg/kg aspirin PO TID and misoprostol 3 ug/kg PO TID; Group III, 25 mg/kg aspirin PO TID, misoprostol 3 ug/kg PO BID and placebo PO QD; and Group IV, 25 mg/kg aspirin PO TID, misoprostol 3 ug/kg PO QD and placebo PO BID for 28 days. Groups were stratified to contain an equal number of dogs positive or negative for Helicobacter spp. based on results of ‘CLO test’. Gastroscopy was performed on days –9, 5, 14 and 28. Each region of the stomach was evaluated separately and visible lesions were scored on a scale of 1 (submucosal hemorrhage) to 11 (perforating ulcer). The scores for each region were summed and the median total score for each group at each day and median total score within each group between days was compared using a Kruskal-Wallis test. No difference in total score was identified between Group I and IV on any day. Median total scores for Groups II and III were significantly(p < 0.05) lower compared to Groups I and IV on day 5. Significant difference was observed on Day 14 between the total score of Group III and Group IV. Group III had a significantly lower score (p < 0.05) than Groups I, II and IV on day 28. Gastric erosions were present in all groups in the study. This study suggests that misoprostol 3 ug/kg PO BID dosing is as effective as misoprostol 3 ug/kg PO TID dosing at preventing aspirin-induced gastric injury in this model. However, misoprostol 3 ug/kg PO TID dosing was less effective in preventing aspirin-induced gastric injury on days 14 and 28 than in previous studies. The lack of efficacy of TID dosing on days 14 and 28 may be related to higher salicylate concentrations in Group II dogs or individual variation within the small study population. / Master of Science

This study tested the hypothesis that administration of immunosuppressive doses of prednisone in conjunction with ultralow-dose aspirin (0.5 mg/kg/day) would result in gastroduodenal lesion scores similar to those found in dogs administered only immunosuppressive doses of prednisone, but that the gastroduodenal scores from both of these treatment groups would be significantly higher than placebo when administered to healthy dogs for 27 days. Eighteen healthy adult purpose-bred dogs were divided randomly into three groups. Group I received placebo capsules and placebo suspension, Group II received prednisone capsules (mean 2.3 mg/kg, range 2.0-2.4) and placebo suspension, and Group III received prednisone capsules (mean 2.3 mg/kg, range 2.3-2.5) and aspirin suspension (0.5 mg/kg) by mouth once daily for 27 days. Gastroduodenoscopy was performed on days -7 (baseline), 5, 14, and 27 of treatment. Four regions of the stomach (angularis incisura, body, pylorus, and cardia) and the proximal descending duodenum were systematically scored on a scale of 1 (normal) to 11 (perforating ulcer) by an experienced observer who was blinded to the treatment groups and clinical signs of each subject. Dogs were observed every 8 hours for vomiting, diarrhea, and inappetence. Feces were scored on a scale of 1-5 with diarrhea defined as a fecal score <4. Lesion scores for each group, at each location, and total scores, at each time period were evaluated for the effects of time and treatment using a Kruskal-Wallis test. Total dog days of vomiting and dog days of diarrhea in each group were compared using a Wilcoxon rank sums test. Significance was determined at p<0.05. There were no significant differences in median total gastric lesion scores between any of the groups at any time during the study. There was no location effect on regional gastroduodenal lesion scores and there was no significant change in gastroduodenal lesion scores over time in any of the groups during treatment. Significantly more dog-days of diarrhea occurred within the prednisone and aspirin group during the experimental period (Period 2) in comparison to Period 1. However, no significant differences were found between any of the groups for dog-days of vomiting, diarrhea or inappetence at any time in the study. / Master of Science

There is a paucity of scientific evidence into the lived experience of people who have a history of injecting drug use and are living with leg ulceration. Portraying the true voice of injecting drug users (IDUs) through narrative means is a novelty in contemporary literature. The representation of the life and the person behind the leg ulcer, having experienced addiction, is original from a purist narrative perspective. This study, led from the perspective of a nurse-researcher leading in the field of wound management, offers a unique opportunity to gain a rare glimpse into the daily life of IDUs, as reported in their own words. The aim of this study was to explore the experience of injecting drug users living with leg ulceration using qualitative methodology. A naturalistic paradigm framed the design by allowing participants to control the data in an unrestricted an open manner without direct intrusion form the researcher. Qualitative methodology was central to collecting data on life experience and feelings. The ethics process detailed a rigorous application to explore the professional, ethical virtues from the perspective of an insider-outsider working with sensitive data in a marginalised population. Diaries were kept and recorded by participants over four weeks in their routine daily life; this was followed by semi-structured interviews. The diaries allowed a unique insight into the past, present and future of IDUs and how their ulcer affected their lives. The diaries also facilitated a means of reflection on themselves and their wounded body. The interviews offered an opportunity to explore in detail the diary entries and other stories participants wished to share. The study recruited twelve participants from leg ulcer clinics set in London; three women and nine men older than 18 years of age (median age of 52 years; range 35 - 62 years). Ten completed the data collection process; two of the participants, aged 61 and 62 years, were married. Gatekeepers working with IDUs with leg ulceration were central to the process of engagement and recruitment. Participants welcomed the design as an opportunity to voice and share their journey of living with an open wound. The findings revealed the detailed suffering participants endured living with their ulcer: pain, shame and stigma were clearly voiced in their narratives. The majority of participants had experienced some form of stigma during their life and this was exacerbated as they were drug users. The self-blame and punishment triggered by this felt stigma was a detriment to the health of participants. Those in contact with specialist wound care services saw a significant improvement in wound healing and this had a positive impact on their wellbeing and their overall outlook on life. Participants also voiced enacted-stigma experienced from encounters in health practice. These negative experiences exacerbated the self-stigma. Findings also portrayed the multiple characteristics and talents of participants including humour, art and resilience. This research contributes to science and practice by understanding the lives of IDUs living with leg ulceration. It provides a platform from which to engage both generalists and specialists who care for these patients and has the potential to influence medical and social policy-making and clinical practice in this field. By means of narrative inquiry, this study may challenge the conventional social stereotypes, the taboos and the stigma still experienced by this patient group in health care.