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1
Trimingham, Jack Christine. "Kerever Park : a history of the experience of teachers and children in a Catholic girls' preparatory boarding school 1944-1965." Phd thesis, School of Social and Policy Studies in Education, 1997. http://hdl.handle.net/2123/6641.
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Rees, Gail. "Diet, bowel function and irritable bowel syndrome." Thesis, London South Bank University, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.336373.
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Noor, Nadim. "Small bowel motor responses in irritable bowel syndrome." Thesis, University of Newcastle Upon Tyne, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.311138.
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Berrill, James. "Symptoms of irritable bowel syndrome in patients with inflammatory bowel disease." Thesis, Cardiff University, 2014. http://orca.cf.ac.uk/61734/.
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Irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD) are both chronic relapsing intestinal disorders. Their symptom profiles overlap in terms of abdominal discomfort and altered bowel habit. Meta-‐analysis of patients with IBD demonstrates that 25-‐46% of those in clinical remission have symptoms compatible with IBS. These patients report lower quality of life scores compared to their asymptomatic counterparts. There is uncertainty as to the cause of these symptoms, and concern for the influence they may exert on clinical management. The work described in this thesis investigated the nature of IBS-‐type symptoms occurring in patients with IBD, examined potential diagnostic tools to distinguish between the respective conditions, and conducted a therapeutic trial for the management of functional symptoms in this setting. IBS-‐type symptoms were observed to occur more commonly in female IBD patients, were associated with high anxiety levels, and occurred in patients with no active inflammation as confirmed by a normal faecal calprotectin level. These findings are characteristic of irritable bowel syndrome, and suggest that this disorder may cause persistent symptoms during IBD remission. Two potential biomarkers of IBS were investigated. The first explored a hypothesis that IBS may be a systemic condition caused by the absorption of toxic metabolites produced by the bacterial fermentation of dietary carbohydrates. This mechanism would potentially explain both the gastrointestinal and the systemic symptoms that are observed in patients with IBS. It was proposed that toxic metabolites may covalently modify albumin in patients with IBS, however on investigation of this theory there was no significant difference observed between the plasma samples of IBS patients, IBD patients and healthy controls. The presence of systemic symptoms in patients with IBS and IBD was associated with higher anxiety levels. Cognitive function was also assessed as a potential biomarker of IBS following anecdotal reports that IBS patients experience impaired concentration. However no significant difference between IBS patients, IBD patients, and healthy controls was identified. Concurrent mood disorders, in particular depression, were associated with impaired performance of specific tasks in patients with IBD. A randomised-‐controlled trial of a mindfulness-‐based psychological intervention was performed in IBD patients with IBS-‐type symptoms or high perceived stress levels. Sub-‐group analysis demonstrated a significant improvement in quality of life in the intervention group in those patients who were experiencing IBS-‐type symptoms. Overall, these findings support the theory that IBS can cause persistent symptoms in IBD patients who are in remission. However, until the molecular mechanisms underlying IBS are identified and reliable biomarkers are developed, a systematic diagnostic approach is required to evaluate these patients. IBS-‐type symptoms in IBD patients represent a therapeutic target to improve quality of life and further trials of psychological intervention, medication and dietary modification are required.
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Cotterill, Lynn. "Inflammatory bowel disease genetics." Thesis, University of Manchester, 2011. https://www.research.manchester.ac.uk/portal/en/theses/inflammatory-bowel-disease-genetics(daae1a60-2790-4280-b7d5-ac5ec7533c7c).html.
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Inflammatory bowel disease (IBD), which includes the subtypes Crohn's disease (CD) and ulcerative colitis (UC), is a common disease particularly in the Western world. IBD is characterised by inflammation of the small intestine and/or colon. The two subtypes affect different gut locations but both show an increased intestinal permeability or the 'leaky gut syndrome'. This led to the hypothesis that tight junction (TJ) proteins expressed in the epithelium may affect the intestinal permeability as a cause or effect of IBD.Initially, variants in the CARD15, IL23R and ATG16L1 genes, previously associated with an increased risk of IBD, were genotyped in a cohort of 500 IBD (295 CD and 205 UC) patients and 877 matched controls. These variants were significantly associated in our cohort. A random effects meta-analysis was undertaken on all previously reported CD associations with the variant rs2241880 from ATG16L1 (n=25, p=0.0017, OR: 1.36 95% CI 1.12-1.66) and with rs11209026 from IL23R (n=26, p=0.0006, OR: 0.37 95% CI 0.21-0.67), showing pooled odds ratios consistent with those reported in our cohort. Individuals carrying >1 CARD15 mutant variant were found to have a 2.5 fold increased risk of CD (p=0.0001). Candidate TJ proteins were chosen on the basis of previous reported associations and through the investigation of the claudin proteins which are abundant at TJs. Twenty one candidate genes were selected and 79 variants successfully genotyped in up to 1063 IBD (502 CD and 478 UC) and 870 control patients. Significant associations were detected with variants in the CLDN1, CLDN5 and CDH1 genes with CD; CLDN5, CLDN8 and CDH1 variants were associated to IBD; and the rs7791132 variant (between CLDN4 and ELN) and a CDH1 variant were associated to UC. The CLDN1 rs6809685 variant trended towards association in a Toronto ascertained IBD replication cohort (genotypic p=0.04, allelic p=0.06) suggesting this may be a novel IBD susceptibility variant. Small intestinal biopsies from CD patients with known rs6809685 genotypes showed a dose dependent reduced immunohistochemical staining of claudin 1 with carriage of the mutant G allele. Claudin 1 helps seal TJs and reduced levels may increase risk of CD.Peroxisome proliferator activator receptors (PPARs) can directly affect TJ proteins and could therefore affect intestinal permeability. Twelve PPARγ variants were genotyped in up to 1050 IBD (502 CD and 467 UC) and 725 control patients. Significant genotypic associations were found with the rs2067819 variant in CD (p=0.05) and IBD (p=0.02), and also the rs13099634 variant in UC (P=0.02). There was a strong gender difference particularly for rs2067819 and rs4135247, where allelic associations were highly significant and increased risk of IBD in men (p=0.01 and p=0.007 respectively). However no significant associations were found in the female cohort. Troglitazone a PPARα agonist increased Caco2 cell transepithelial electrical resistance (TEER), a marker of TJ integrity, and increased expression of claudins -3 and -4. In contrast, the PPARα antagonist GW6471 reduced the TEER without causing cell death and PPARγ ligands did not affect TEER measurements. In summary, using a robust cohort of cases and controls the data indicates that variants in genes encoding TJ proteins may affect susceptibility to IBD and that PPARs can regulate these proteins altering intestinal permeability.
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Gwee, Kok Ann. "Bowel disturbances following acute gastroenteritis : a psychobiophysiological model for the irritable bowel syndrome." Thesis, University of Sheffield, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.266724.
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Cederholm, Myella. "INFLAMMATORY BOWEL DISEASE AND IRRITABLE BOWEL SYNDROME IN ADULT LIFE AFTER EXPERIENCING CHILDHOOD ABUSE." Thesis, Örebro universitet, Institutionen för medicinska vetenskaper, 2021. http://urn.kb.se/resolve?urn=urn:nbn:se:oru:diva-91412.
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Introduction In a national survey from 2016, 5% of Swedish teenagers reported experience of repeated physical abuse and 6% reported repeated psychological abuse. Childhood abuse has been shown to enhance the risk of both psychiatric and somatic diseases, e.g. Irritable bowel syndrome (IBS) and also general inflammation. One type of inflammatory disease is inflammatory bowel disease (IBD), which is composed of Ulcerative colitis (UC) and Chron’s disease (CD), but there is limited scientific evidence regarding the correlation of IBD and child abuse. Objective The aim of this systematic review is to study the correlation between childhood abuse and IBD in adulthood and compare this to the correlation of child abuse and IBS. Method PubMed and Web of Science databases were searched for articles studying childhood maltreatment and adult IBS or IBD. Articles that were not peer reviewed and presented original data or did not study IBD patients were excluded. Results 342 articles were identified, of which nine met the pre-defined criteria and were included in this review. Eight articles studied the frequency of childhood abuse among IBS and IBD patients and one article studied disease activity in IBD patients that experienced childhood abuse. Childhood abuse was found to be more frequent in both IBS and IBD patients than healthy controls (HC). CD patients that were abused in childhood had elevated disease activity. Conclusions Childhood physical abuse was associated with both IBD and IBS. Childhood sexual abuse was associated with IBD, but a stronger association was found with IBS. No conclusions could be drawn regarding childhood psychological abuse.
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Harfmann-Ludwig, Susanne. "Bowel habits after bariatric surgery /." [S.l.] : [s.n.], 2009. http://www.ub.unibe.ch/content/bibliotheken_sammlungen/sondersammlungen/dissen_bestellformular/index_ger.html.
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Pozuelo, del Río Marta. "Metagenomics in inflammatory bowel disease." Doctoral thesis, Universitat Autònoma de Barcelona, 2019. http://hdl.handle.net/10803/669437.
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La microbiota intestinal desempeña un papel crucial en el manteniendo la homeostasis intesitnal. Alteraciones en la composición microbiana, también conocidas como disbisosis, pueden poner en peligro el estado de salud e incrementar el riesgo a padecer una enfermedad. Aunque muchas enfermedades se han asociado a cambios en la microbiota intestinal, todavía se desconoce si dichas alteraciones son la causa o la consecuencia de las patologías.
La enfermedad inflamatoria intestinal (EII) es una enfermedad inflamatoria crónica que se caracteriza por periodos de inflamación y constituye un problema de salud dado. La EII presenta dos subtipos: enfermedad de Crohn y colitis ulcerosa, con síntomas similares pero diferentes manifestaciones clínicas. La EII se ha relacionado ampliamente con cambios en la microbiota intestinal. A pesar de los múltiples estudios que existen, no hay un claro consenso en el perfil microbiano asociado a la enfermedad. Las principales discordancias se dan entre las diferencias asociadas a enfermedad de Crohn y la colitis ulcerosa. Algunos investigadores han demostrado que la composición microbiana en colitis ulcerosa es muy similar a la de individuos sanos y ambas difieren de la composición de enfermos de Crohn. En cambio, otros investigadores han visto que las diferencias de colitis ulcerosa y Crohn respecto a sanos son muy similares por lo que consideran ambos subtipos como una única enfermedad (EII).
El principal objetivo de esta tesis es determinar la disbiosis en una cohorte de EII española para evaluar hasta qué punto las funciones y composición microbiana difieren entre Crohn y colitis y si los datos de microbioma podrían emplearse como herramientas de diagnóstico. Para ello, analizamos muestras fecales de sanos, enfermos de Crohn y enfermos de colitis usando dos metodologías: secuenciación del gen 16SARNr (o 16S ADNr) y secuenciación por fragmentación del genoma.
Como se preveía, observamos la presencia de disbiosis en EII. Además, vimos que las alteraciones en composición microbiana y funciones eran diferentes para Crohn que para colitis, mostrando una mayor disbiosis en Crohn que en enfermos de colitis ulcerosa y con colitis mostrando un patrón muy similar a la microbiota de individuos sanos. Los resultados funcionales encontrados en esta tesis confirman la mayor disbiosis descrita en pacientes de Crohn en comparación con pacientes de colitis ulcerosa en composición microbiana. Estos individuos presentan una mayor cantidad de genes principalmente asociados a metabolismo y enfermedades inmunes que los enfermos de colitis ulcerosa y sanos.
A pesar de que los datos de 16S ADNr y secuenciación por fragmentación no detectaron las mismas diferencias entre Crohn y colitis, ambas metodologías permitieron la clasificación de los distintos subtipos de EII con una proporción similar. Más estudios son necesarios para validar los resultados de esta tesis en otras cohortes de pacientes que incluyan Crohn localizado en colon o pacientes recién diagnosticados que no hayan sido sometidos a tratamiento antes de la aplicación de estas metodologías como herramientas diagnósticas en clínica.The gut commensal microbiota is known to play a crucial role in maintaining intestinal homeostasis. Alterations in the microbial community composition, also known as dysbiosis, may put health status in risk and increase susceptibility to diseases. Although several diseases have been related to shifts in the gut microbiome composition, it is still uncertain whether those alterations are the cause or consequence of the disease. Inflammatory bowel disease (IBD) is a chronic inflammatory disease with periods of active and inactive inflammation that constitutes to an important health problem. It is divided in two subtypes: Crohn’s disease (CD) and ulcerative colitis (UC) that present similar symptoms but different clinical manifestations. IBD has been widely associated with an alteration of the gut microbiome composition. Nevertheless, there is no clear consensus on the microbial pattern characteristic of the disorders. Main discordances between studies are related to differences between UC and CD. Some previous publications indicate that UC microbial composition is very similar to healthy and differs from CD whereas others consider both subtypes as a unique entity and find high alterations in UC and CD microbial composition in comparison with the microbiome of healthy individuals. The aim of this thesis was to characterize the dysbiosis in a Spanish IBD cohort to evaluate to which extend the gut microbiome composition and function could be differentiated between CD and UC and whether microbiome data could be used as diagnostic and prognostic tools. For this purpose, we analyzed fecal samples of healthy individuals, CD (affected in the ileum) and UC patients using two different methodologies: 16S rRNA gene (or 16S rDNA) and shotgun (short genomic fragments) sequencing. As expected, we observed the presence of dysbiosis in IBD. Furthermore, we showed that microbial composition and function alterations were different for CD and UC, with greater dysbiosis in CD than in UC and with UC resembling more to a healthy state. Functional findings also confirmed this higher dysbiosis in CD than in UC and revealed genes implicated in metabolism pathways and in immune diseases in higher abundance in CD compared with healthy individuals and UC. Although 16S rDNA and shotgun data did not detect differences in the dysbiosis in CD and UC in a consistent manner, both methodologies allowed the classification of IBD subtypes in a similar proportion. Future studies should validate these results using other patient cohorts such as colonic CD or recently diagnosed patients before the application of these techniques as diagnostic tools in clinical practice.
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Vandvik, Per Olav. "Irritable bowel syndrome in Norway." Doctoral thesis, Norwegian University of Science and Technology, Department of Cancer Research and Molecular Medicine, 2006. http://urn.kb.se/resolve?urn=urn:nbn:no:ntnu:diva-1698.
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Geerling, B. J. "Inflammatory bowel disease and nutrition." Maastricht : Maastricht : Universiteit Maastricht ; University Library, Maastricht University [Host], 1999. http://arno.unimaas.nl/show.cgi?fid=7216.
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Arya, Shobhit. "Tissue fusion for bowel anastomosis." Thesis, Imperial College London, 2016. http://hdl.handle.net/10044/1/59071.
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Anastomosis is the critical step in restoring gastrointestinal continuity following bowel resection and has traditionally been accomplished using suture and stapling techniques. However, both technologies can be associated with complications and are particularly difficult to perform in the laparoscopic environment. As a result there has been an increasing interest in developing novel tools and techniques which would permit safe and reliable intestinal anastomoses to be performed whilst minimising potential complications. In recent years, advanced bipolar radiofrequency (RF) energy powered devices, developed to enable more consistent vascular haemostasis, have been proposed as an alternative method for anastomotic construction and is the basis for the research presented. This thesis investigates: (i) the parameters required to form bowel seals with sufficient mechanical strength to withstand physiological pressures; (ii) methods for monitoring the viability of seals and (iii) the ability to construct functional radiofrequency induced small bowel anastomoses. The role of varying electrical parameters and compressive pressures has been investigated and characterised both in vitro and in vivo. Mucosa-to-mucosa and serosa-to-serosa small bowel seals were formed using both commercial and prototype applicator devices powered by a research based electrical generator and bespoke programmable algorithms. The mechanical strength of bowel seals was assessed through ex vivo burst pressure measurements. This demonstrated seals to be capable of withstanding physiological luminal pressures (>25mmHg) before rupturing. Tissue effects of fusion have been examined microscopically through histological assessment. The viability of fused tissue in vivo was determined utilising a multispectral imaging (MSI) system, which measured tissue oxygenation in the peri-fusion areas and allowed for the calculation of relative concentrations of oxy- and deoxyhaemoglobin and hence, overall bowel oxygen saturation (SaO2). The results of these monitoring tools have suggested that the tissue remains viable in the short term using a specific combination of electrical and mechanical parameters. These ex vivo and acute in vivo findings were applied to construct a series of chronic porcine anastomoses, where animals were recovered for a median of seven days, to compare the macro- and microscopic effects of the novel and gold standard techniques. Fifteen small bowel anastomoses were formed using a commercial and prototype radiofrequency sealer in individual animals. In addition five hand-sewn end-to-end and five stapled side-to-side anastomoses were also constructed in individual animals. Three animals in the radiofrequency anastomosis group were terminated early due to clinical evidence of anastomotic leak. Microscopically, the fused bowel showed evidence of healing at the mucosal and sub-mucosal collagen levels, which was comparable to findings using the gold standard methods. The studies performed demonstrate a method for the formation and assessment of radiofrequency induced bowel fusion and confirm its potential to be ultimately used for both bowel resection and anastomosis.
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Smith, Graeme Drummond. "Counselling in inflammatory bowel disease." Thesis, University of Edinburgh, 1997. http://hdl.handle.net/1842/12244.
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Introduction; The inflammatory bowel diseases (IBD), Crohn's disease (CD) and ulcerative colitis (UC), affect well over 100,000 people in the United Kingdom Health related quality of life (HRQOL) is influenced by many factors in IBD including; the nature and severity of the disease, socio-economic factors, age, psychological well-being as well as· the efficacy and complications of treatment. Pilot Studies; Quality of life was assessed in 140 IBD patients (70 CD/70 UC). Diarrhoea was, not surprisingly, the most commonly reported physical symptom in both CD and UC and impaired faecal continence caused great social disability, with 72% CD patients and 68% UC patients reporting urgency or incontinence. Over a third of all patients reported occupational problems associated with their disease. Anxiety, but not depression, was common in the CD group and a major source of anxiety in many cases was lack of information. Three-quarters of patients felt additional information would have enabled them to cope with their chronic illness. It is a common perception that the provision of psychological support, such as the use of counselling skills, may alleviate many of the psychosocial problems associated with IBD, but this has not yet been proven. Hypothesis: That a nurse led counselling service improves HRQOL in IB D patients. Study Group/Design: Fifty patients with CD (aged 16-64, 33 females), 50 UC patients (aged 17-60, 26 females), 50 healthy volunteers (HV, aged 17- 61, 27 females) and a disease control group comprising 28 psoriatic arthritis (PS) patients (aged 22-66, 16 females) undeiwent structured interviews and completed a range of questionnaires measuring several facets of quality of life and psychological well-being (Hospital Anxiety and Depression Score (HAD), Attitudes and Preferences (AP), Styles and Strategies (SS) and Short-form 36 (SF36)). Patients with IBD were then randomised to receive either a counselling package or routine clinical follow-up. The counselling package consisted of disease specific information and teaching of stress management techniques, based on the "Challenge to change" programme devised by Dr. Derek Roger at the University of York. HRQOL scores were compared on entry at 6 and 12 months. Results; At baseline the scores for all questionnaires were within the nonnal range in the UC, PS, and HV groups. However CD patients recorded significantly higher anxiety scores (p
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Gustavsson, Anders. "Therapy in inflammatory bowel disease." Doctoral thesis, Örebro universitet, Institutionen för hälsovetenskap och medicin, 2012. http://urn.kb.se/resolve?urn=urn:nbn:se:oru:diva-25599.
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The aim of this thesis is to study treatment of inflammatory bowel disease with respect to an acute severe attack of ulcerative colitis and endoscopic balloon dilation in stricturing Crohn’s disease. A retrospective follow-up was made in 158 patients who were given intensive intravenous corticosteroid treatment due a severe, moderate, or mild attack of ulcerative colitis between 1975 and 1982. After 10 years, the colectomy frequency in the severe disease group was 64%, and 49% and28% in the moderate and mild groups, respectively. Severity of the original attack did not influence the subsequent clinical course with respect to colectomy. In 2005, a controlled Swedish–Danish trial of infliximab as rescue therapy in an acute severe attack of steroid refractory ulcerative colitis showed that colectomy frequencies after 3 months were lower in infliximab-treated patients (29%) compared to placebo-treated patients (67%). After 3 years, a statistically significantly lower colectomy frequency remained in patients treated with infliximab (50%) compared to placebo (76%). Between 1989 and 2009, 178 patients underwent endoscopic balloon dilation due to intestinal strictures in Crohn’s disease. Seventy-five patients,with a follow-up of 5 years or longer, underwent dilations due to symptomatic strictures only. After 5 years of follow-up, 39/75 (52%) of the patients had undergone no further intervention or one additional dilation only, and 36% had had surgery. The complication frequency was 5.3%, of which 10 patients (1.3%) required surgery. In 83 patients, we studied whether smoking at diagnosis affected the outcome after index dilation. In the group of active smokers, 31/32 (97%) underwent another intervention compared to 18/33 (55%) in never smokers (HR 2.18, 95% CI: 1.22-3.93,p = 0.01). Clinical parameters such as sex, age at diagnosis, age at first dilation, balloon size, localisation of stricture, treatment with azathioprine and treatment period did not influence outcome.
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Matini, Lawrence. "Adaptation to Inflammatory Bowel Disease." Thesis, University of Surrey, 2017. http://epubs.surrey.ac.uk/841456/.
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Inflammatory bowel disease (IBD) is a term used to describe two chronic diseases of the gastrointestinal tract: Ulcerative Colitis (UC) and Crohn's Disease (CD). Although the efficacy of treatment is continuously improving, Quality of Life (QoL) in this illness population remains low with many patients suffering from psychological and psychiatric comorbidities. Psychological interventions aimed at improving outcomes in these patients have largely demonstrated little improvement. This thesis argues that this may be the result of poor understanding of the experience of living with this condition with too little focus on the adaptation of the patient to their illness. This thesis aimed to address this gap in the literature through four empirical studies. Firstly, Study 1 used a qualitative design to (n = 22) to explore the lived experiences of patients with IBD and to conceptualise adaptation to IBD. The results highlighted the importance of making sense of the illness and the impact and feelings associated with the illness. This was transcended by a notion of uncertainty which was resolved by employing coping mechanisms to restore equilibrium between their identity before and after diagnosis, resulting in a 'new normal'. Study 2 then employed a cross-sectional design (n = 307) to develop a new measure of adaptation to IBD (the A-IBD) which after psychometric analysis revealed four subscales including person identity, patient identity, acceptance and expectations. This study also explored the degree of association of the A-IBD with existing measures of sense making (BIPQ) and QoL (IBDQ), to assess the ability of the A-IBD in predicting QoL and ascertain whether it could predict QoL over and above sense making. The results suggested the A-IBD was not synonymous with these constructs and had utility as a predictor of QoL even when accounting for the predictive ability of the BIPQ. Finally, Study 3 used a combination of qualitative and quantitative design (n = 16). Patients scoring in the top and bottom 25% of the A-IBD from Study 2 completed the measure again to assess the dynamic nature of adaptation and were interviewed about the factors that either encouraged or inhibited their degree of adaptation. This analysis revealed that adaptation is indeed dynamic, and that antecedents of adaptation include 'engagement', 'resilience' and certain 'contingencies' including disease and social factors. Overall, the findings from this thesis indicate that the treatment of IBD must be approached in a biopsychosocial manner, that adaptation can be measured effectively with the new tool and that adaptation, with an emphasis on the notion of person, not patient, predicts quality of life.
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Campbell, Simon Scott. "Azathioprine use in inflammatory bowel disease." Thesis, University of Edinburgh, 2003. http://hdl.handle.net/1842/24109.
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Jarrett, Michael Eugene Dominic. "Sacral nerve stimulation for bowel dysfunction." Thesis, University of Oxford, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.491901.
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Sacral nerve stimulation (SNS) was introduced for urge urinary incontinence in 1981. It resulted in a significant improvement in 80% of patients. In the 1990s it was recognised that the treatment had a beneficial effect on bowel function, particularly faecal incontinence. This led to prospective trials to assess its role in this condition's treatment and more recently in the treatment of constipation. SNS has, so far, been assessed in specialist centres for the treatment of faecal incontinence in patients with an intact external. anal sphincter. The aetiology of incontinence has varied in the reported series. This thesis demonstrates that SNS for faecal incontinence may be undertaken on a national scale, in units with a specialist interest, without compromise of the outcome. Specific aetiologies of faecal incontinence including partial spinal injury and full thickness rectal prolapse or following anterior resection for rectal cancer are assessed separately. The results indicate that SNS has a role to playin each of these groups. Supplied by The British Library - 'The world's knowledge' The work leading to this thesis includes new indications. These include patients with obstetric-related external anal sphincter defects, which would otherwise have been treated by overlapping sphincter repair. All patients tested in this group proceeded to pennanent SNS with improvement in faecal incontinent episodes from a median (range) of 5.5 (4.5-21.5) to 2 (0-5.5) episodes per week (p=0.017) at a median (range) follow up of 4.5 (1-12) months. In this group of females of childbearing age sexual activity is investigated by a retrospective sex life questionnaire analysis. Quality of sexual activity is improved in nearly 80% of patients with a statistically greater improvement in younger patients. It had been noted in patients treated with SNS for UrInary incontinence that constipation was improved. Subsequent pilot studies in the UK and Italy have led to a pan-European trial of the use of SNS in patients with slow and normal transit constipation. The thesis presents work undertaken at S1. Mark's Hospital that will be included in the European trial. Results suggest that SNS may be beneficial in both types of constipation. The proportion of patients with constipation proceeding to pennanent implant was 57% as opposed to approximately 85% for incontinence. In those proceeding to permanent implant, bowel opening over a three week period improved from a median (range) of 7 (1-23) at baseline to 21 (4-102) (p=0.003). Significant improvements in abdominal symptoms were associated with an improvement in quality of life. The results suggest that SNS could become an exciting new treatment option for patients in this difficult clinical group. Supplied by The British Library - 'The world's knowledge' Solitary rectal ulcer syndrome (SRUS) is a discrete clinical condition associated with an evacuation disorder and specific histopathological features. The condition is difficult to treat. Biofeedback is often the first line therapy. This research shows that rectal mucosal blood flow in these patients is reduced compared to controls (mean (sd) 163(27) versus 186 (14) flux units (FU) (p<0.01)). The findings are similar to those found in patients with normal transit constipation. It also demonstrates that successful biofeedback results in a significant improvement in rectal mucosal blood flow in patients who feel subjectively better after biofeedback from 165 (30) FU to 190 (40) FU (p=0.001). Knowing SNS increases rectal mucosal blood flow and leads to improvement in patients with constipation, three patients with SRUS were trialed with SNS. No patient proceeded to permanent implantation, although all felt some benefit. The results of physiology testing carried out during the studies into SNS have allowed theorisation concerning the mechanism of action of SNS. This is likely to be multifactorial with effects on the sphincter complex, bowel motility, rectal sensitivity and cerebral cortex all having a role.
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Poullis, Andrew Patroclos. "Bowel inflammation in health and disease." Thesis, University of London, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.407795.
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Cole, Simon John. "Physiological studies in irritable bowel syndrome." Thesis, Imperial College London, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.408422.
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Ljung, Tryggve. "Nitric oxide in inflammatory bowel disease /." Stockholm, 2003. http://diss.kib.ki.se/2003/91-7349-602-2/.
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Törnblom, Hans. "Pathogenetic mechanisms in irritable bowel syndrome /." Stockholm : Karolinska institutet, 2007. http://diss.kib.ki.se/2007/978-91-7357-287-3/.
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Weersma, Rinse Karel. "Genetic susceptibility for inflammatory bowel diseases." [S.l. : Groningen : s.n. ; University Library Groningen] [Host], 2007. http://irs.ub.rug.nl/ppn/304870935.
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Parkes, Miles. "The genetics of inflammatory bowel disease." Thesis, University of Oxford, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.326030.
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Dalton, Harry Richard. "Suppressive phenomena in inflammatory bowel disease." Thesis, University of Oxford, 1992. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.305970.
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Satsangi, Jack. "The genetics of inflammatory bowel disease." Thesis, University of Oxford, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.337627.
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Eadala, Praveen. "Lactose sensitivity and inflammatory bowel disease." Thesis, Cardiff University, 2013. http://orca.cf.ac.uk/53992/.
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Controversy still exists as to the incidence, role and impact of lactose sensitivity in inflammatory bowel disease. The thesis shows that there is a higher than previously reported incidence of lactose sensitivity determined by a combination of genotype, breath test and symptoms after a lactose challenge. Lactose sensitivity in patients with inflammatory bowel disease who are in remission is 70%. There was no difference compared to healthy volunteers in terms of lactase genotyping; however there was a significantly greater prevalence of positive breath test and symptoms after lactose challenge. This suggests that lactose sensitivity in inflammatory bowel disease is related to the disease itself or a consequence of it and not due to a genetic predisposition. A significant proportion of inflammatory bowel disease patients [16%] are methane producers which warrants further investigation. A pilot study of reduced lactose intake in patients with Crohn’s disease and lactose sensitivity, who were in remission, showed a promising improvement in symptoms reported and quality of life scores. The Real-Time Polymerase Chain Reaction is simple and quick compared to Restrictive Fragment Length Polymorphism for assessing the lactase genotype. The Quintron MicroLyzer to assess breath samples after lactose challenge is preferred to the hand held Micro H2 meter. This detects methane in addition to hydrogen and without this a number of cases of lactose sensitivity would be II missed. It may be possible to predict a negative breath test with the absence of any GI symptoms after a breath test and vice-versa a positive breath test is very likely if multiple GI symptoms are reported. The ‘hidden’ lactose in drugs used to treat inflammatory bowel disease and co-existing conditions should be considered as it is present in many drugs and can make a significant contribution to the amount of lactose ingested; lactose free alternatives are widely available.
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Arsenescu, Razvan I. "NOVEL MECHANISMS IN INFLAMMATORY BOWEL DISEASE." UKnowledge, 2011. http://uknowledge.uky.edu/gradschool_diss/211.
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Inflammatory Bowel Diseases, Crohn's Disease and Ulcerative colitis, are idiopathic chronic conditions with multifactorial determinants. In general, terms, intestinal inflammation results from abnormal host-microbe interactions. Alterations in homeostasis involve host genetic factors, environmental cues and unique luminal microbial niches. We have examined the coordinated expressions of several molecular targets relevant to the mucosal immune system and identified signature biomarkers of IBD. Qualitative and quantitative changes in the composition of microbiota can be related to unique immuno-phenotypes. This in turn can have more systemic effects that involve energy metabolism. Adiponectin, an adipose tissue derived adipokine, can restore cellular ATP levels and fulfills innate immune functions. We have concluded that IBD might represent a state of adiponectin resistance relating to chronic inflammation and obesity status.
Lastly we hypothesized that activation of xenobiotic pathway (AHR-aryl hydrocarbon receptor) can further modulate host immune and metabolic responses, and thus contribute to IBD phenotypes. We found that IBD is associated with robust mucosal, aryl hydrocarbon receptor pathway and related to proinflammatory cytokine secretion. We conclude that IBD heterogeneity is reflected through distinct immunophenotypes. Furthermore, environmental cues that involve the AhR receptor and adipose tissue derived adiponectin are important regulators of the inflammatory process in IBD.
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Rankin, B. J. "Colonic mucus in inflammatory bowel disease." Thesis, University of Newcastle Upon Tyne, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.320821.
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Hamlin, Peter John. "Genetic studies in inflammatory bowel disease." Thesis, University of Leeds, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.400166.
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Collins, Carole Elizabeth. "Platelet dysfunction in inflammatory bowel disease." Thesis, King's College London (University of London), 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.362539.
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Cook, Amanda Laurie. "Diet and bowel function in adults." Thesis, London South Bank University, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.313002.
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Kamperidis, Nikolaos. "Nutrient effects in inflammatory bowel disease." Thesis, Queen Mary, University of London, 2016. http://qmro.qmul.ac.uk/xmlui/handle/123456789/23488.
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Background: Not only does IBD lead to nutritional deficiencies, but also nutrients influence its pathophysiology: exclusive enteral nutrition (EEN) is an effective primary treatment in Crohn's disease; and vitamin D (VitD) is involved in its pathogenesis and course. Aims: We hypothesised that nutrients impact on the course of IBD. We therefore studied the effect of EEN i) on long term clinical course in children; ii) on CD58, a costimulatory molecule at the intestinal epithelial cell (IEC) lines, iii) adults with Crohn's disease. We examined the possible effect of serum vitamin D levels on the course of IBD and also the possible role of ethnicity in our paediatric and adult populations that were treated with EEN but also in our general adult population. Results Chapter II: 56 paediatric patients with Crohn's disesase were followed up for 5 years. 57% of patients achieved remission after 6 weeks of EEN. Achievement of clinical remission within 6 weeks of EEN was significantly associated with a longer time to relapse and to treatment escalation. VitD deficiency was common; and those patients who were deficient were significantly more likely to require corticosteroids and also needed thiopurines sooner. Chapter III: CD58 was expressed in the IEC isolated from IBD patients and healthy controls. EN down-regulated the expression of CD58 on IEC lines. Chapter IV: 22 adult patients with Crohn's disease with a mean age of 30.8 years were given EEN and followed up for a mean time of 1.9 years. 22.7% of patients went into clinical remission and 77.3% experienced a clinical response. By the end of follow up 63.6% (14/22) of patients had clinically relapsed and 36.4% required surgery during their follow up. There was no difference between South Asian and Caucasian patients in the disease outcomes after administration of EEN. Chapter V: Bangladeshis were more often vitamin D deficient than white Caucasian patients; however vitamin D status was not associated with the course of IBD. Bangladeshis developed perianal disease and required thiopurines earlier in their disease course. Bangladeshi patients with UC had more extensive disease. Conclusions: EEN, when successful, improves the long term outcome of Crohn's disease in children, possibly in part, by down-regulating CD58 on the IEC. VitD deficiency may influence the clinical course of IBD; however our results were contradictory between children and adults and significantly limited by the assessment of the vitamin D level at a single time point.
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Sood, Ruchit. "Approaches to diagnosing irritable bowel syndrome." Thesis, University of Leeds, 2017. http://etheses.whiterose.ac.uk/18530/.
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Introduction: Differentiating irritable bowel syndrome (IBS) from organic disease is inherently challenging as symptoms can overlap. Symptom-based diagnostic criteria were developed to aid the clinician in making a positive diagnosis of IBS, and therefore avoid unnecessary invasive investigations. However, previous studies have shown these criteria perform only modestly in differentiating IBS from organic disease. Aim: The aim of this thesis is to assess the accuracy of the symptom-based diagnostic criteria, as well as address some of the limitations in their performance. Methods: A systematic review and meta-analysis was conducted in order to summarise the approaches that are currently available to aid in the diagnosis of IBS, including symptoms, biomarkers, psychological markers, and combinations thereof, as well as to understand the strengths and weaknesses of the available diagnostic tests for IBS. Using these findings, two diagnostic test studies were designed and undertaken with the intention of creating accurate, inexpensive, and easily administrable tests for clinicians consulting in routine clinical care. Results: A meta-analysis undertaken showed that symptom-based diagnostic criteria, biomarkers, and psychological markers perform only moderately well in diagnosing IBS. Combining symptoms with markers of organic disease or psychological affect seemed to represent the best way forward in improving the accuracy of diagnosing IBS. The first diagnostic test study undertaken confirmed this finding, and showed that modifications to the symptom-based diagnostic criteria with the addition of symptoms, markers of affect, and simple laboratory tests resulted in improved diagnostic accuracy. The second diagnostic test study used latent class analysis to derive and validate a model that performs with similar accuracy to the symptom-based diagnostic criteria, but importantly this method has the potential for improvement in its accuracy through the addition of clinical markers, such as faecal calprotectin. Conclusions: This thesis has shown that combining symptoms with clinical markers, markers of affect, and/or novel biomarkers leads to greater accuracy in diagnosing IBS. The novel findings of two diagnostic test studies undertaken suggests that this approach may represent the best way forward in developing an accurate and non-invasive diagnostic test for IBS.
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Langhoff, C. H. "Phenomenology of bowel/bladder-control anxiety." Thesis, University College London (University of London), 2013. http://discovery.ucl.ac.uk/1408025/.
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Volume 1 of this thesis is presented in three parts. Part 1 is a systematic review of Internet-based cognitive behavioural therapy for social anxiety disorder, which includes an objective assessment of study quality. Part 2 describes two studies exploring bowel/bladder-control anxiety (BBCA). Study 1 is an Internet-based survey to obtain initial clinical and demographic details about BBCA and study 2 uses postal questionnaires to explore the relationship of BBCA with panic attacks. This is a joint thesis as it forms part of a larger project and was conducted alongside that of another Trainee Clinical Psychologist. Part 3 is a critical appraisal of the research process, which considers implications of the conceptualisation of BBCA for the research project as well as multiple testing and advertising. It further discusses issues of conducting research and delivering psychological therapy via the Internet.
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Khodiyar, Varsha Kumari. "Microarray profiling of inflammatory bowel disease." Thesis, University of Leicester, 2002. http://hdl.handle.net/2381/29415.
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In this study of inflammatory bowel diseases (IBD, i.e. Crohn's disease and ulcerative colitis), the gene transcription profile of colonic IBD resection specimens were analysed by oligonucleotide microarray analysis. A total of 33,625 genes were profiled across 23 colonic mucosa samples; 5 involved Crohn's disease, 4 uninvolved Crohn's disease, 5 involved ulcerative colitis, 3 uninvolved ulcerative colitis and 6 samples from macroscopically normal areas of colorectal cancer resections (controls). A number of data-mining tools, encompassing clustering (e.g. hierarchical & K-means) and matrix-based methods were evaluated for the analysis of this microarray data. Mining strategies were formulated, tested and then applied to the data set to identify genes showing interesting and novel expression patterns across the samples. The application of these tools to the data set resulted in the generation of gene expression profiles for Crohn's disease and ulcerative colitis. Genes of interest were annotated using publicly accessible sequence and literature databases. Potential links by previous research in the inflammatory bowel disease field were analysed for selected genes. Common pathways emerging from the annotation effort and potentially linking together several of the genes of interest were investigated. Specifically, the energy deficiency hypothesis proposed by Roediger in 1980 and the relevance of potential cancer and apoptosis related genes were reviewed with regard to the findings.
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Kalla, Rahul. "Biomarker discovery in inflammatory bowel diseases." Thesis, University of Edinburgh, 2018. http://hdl.handle.net/1842/31040.
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There is an unmet need for novel biomarker discovery in Inflammatory Bowel Diseases (IBD) to aid clinical management in several clinical settings including diagnosis and prognosis. With an ever-advancing repertoire of biological therapies on the horizon, it is important to personalise treatments at an early stage. The aim of this thesis is to explore the clinical utility of novel blood-based biomarkers in diagnosis, disease classification and prognosis in 2 cohorts: newly diagnosed IBD and acute severe colitis. Investigating the circulating methylome, 290 probes exhibited Holm significant IBD-associated methylation differences, including VMP1/MIR21 (p=7.5×10-14) and RPS6KA2 (1.1×10-19) and were consistent within the European cohort. 11 Differentially methylated positions (DMPs) predicted treatment escalation after Holm adjustment (top probe p=0.003). A panel of 6 probes identified 2 patient subgroups that have significantly different disease courses (Hazard Ratio (HR) 10.5, 95%CI: 4.3-25.6; logrank p=1.5×10-24). The 6 probe marker outperformed conventional biomarkers in predicting treatment escalation (hsCRP > 4mg/L, HR 3.2(1.7-5.8), logrank p=0.0004 and Alb < 36g/L, HR 2.9(1.5-5.6), p=0.0001). Within the same cohort, a novel proximity extension assay (PEA) was then utilised to identify novel diagnostic and prognostic protein markers. 61 proteins were significantly associated with IBD including MMP12 (Holm-adjusted p=4.1×10-26). A total of 9 proteins predicted disease course in this cohort. Using a panel of 7 randomly selected top prognostic probes, 2 patient groups were identified that had significantly different disease courses: logrank p=2.2×10-10, HR 5.6(2.0-15.6), outperforming conventional biomarkers in predicting treatment escalation (hsCRP > 4mg/L, HR 3.2(1.7- 5.8), logrank p=0.0003 and Alb < 36g/L, HR 2.7(1.4-5.2), p=0.0004). In a subcohort, serum calprotectin (SC) and conventional blood markers were investigated for their utility in diagnosis and prognosis in IBD. SC performed at par with CRP at differentiating IBD from controls with an area under the curve (AUC) of 0.87 (CI 0.81-0.92). For prognostication, both albumin and SC remained significant predictors of treatment escalation in IBD (logrank test p=5.1×10-5). MicroRNAs (miRNA) are small non-coding nucleic acids that have the capacity to modulate gene expression. Using small RNA sequencing in acute severe colitis (ASUC) and healthy controls (HC), 10 serum-based miRNA markers were significantly associated with acute severe colitis, including miR-30a-5p. Validating the findings using qPCR, miR-30a-5p was downregulated in ASUC (p=0.003). Furthermore, miR30a-5p remained a significant predictor of eventual colectomy in acute colitis (logrank test p=0.0014). These data highlight the translational potential for methylation, miRNA and proteomic biomarkers in diagnosing and prognosticating in IBD.
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Labuschagne, Annemarie. "Haemorrhagic bowel syndrome in grower pigs." Diss., University of Pretoria, 2010. http://hdl.handle.net/2263/27236.
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In the past five years generally well managed farms reported an increase in acute deaths in their grower herds to their consulting veterinarian. At the same time reports from across the world indicated that this is not a problem seen only in South Africa. The syndrome is generally referred to as haemorrhagic bowel syndrome (HBS), red gut or balloon pig. Veterinarians generally believed that the cause of these acute deaths were due to the acute form of Lawsonia intracellularis, also known as porcine haemorrhagic enteropathy (PHE). Because neither the clinical symptoms present prior to death, nor the post mortem changes were typical for a L. intracellularis case it was decided to investigate this syndrome in more depth. Five commercial farms were purposefully selected where growers that died peracutely were necropsied and intestinal samples collected for histological as well as bacteriological examination. A total of 28 pigs were sampled with the histological sections from all samples indicating a Clostridium species as the cause and from 11 of samples Clostridium perfringens were cultured as the predominant bacterium. Although pigs on the farms were seropositive for Lawsonia intracellularis there was no evidence that this bacterium was the cause of death in the pigs. Rather the aetiology points to C. perfringens being the cause, possibly together with other predisposing factors such as rapid growth, high ambient temperatures and interruption in fedding patterns. Based on these results further studies to determine the toxin type as well as predisposing factors should be done. CopyrightGedurende die afgelope vyf jaar het plase met ’n algemene goeie bestuur ’n verhoging in akute vrektes in hulle groeikuddes opgemerk en hulle het hulle kommer oor die vrektes aan hulle konsulterende veeartse oorgedra. Diè verhoging in groeivrektes is nie uniek aan Suid Afrika nie. Dieselfde tendens is regoor die wêreld opgemerk, maar niemand is seker wat presies die oorsaak van die akute vrektes is nie. In die literatuur word daar na “haemorrhagic bowel syndrome (HBS)” oftewel hemoragiese derm sindroom verwys. Boere verwys na die sindroom as rooiderm of “balloon pig”. Tot nou toe het veeartse aanvaar dat die oorsaak moontlik Lawsonia intracellularis is. Die organisme is verantwoordelik vir ’n groep sindrome waarvan “porcine haemorrhagic enteropathy” die akute form is. Omrede die kliniese simptome en die nadoodse ondersoek nie tipies vir ’n L. Intracellularis geval is nie, is daar besluit om die akute vrektes verder te ondersoek. Vyf plase, waar die sindroom baie voorkom, is geidentifiseer en dermonsters is geneem vir histopatalogiese sowel as mikrobiologiese ondersoeke. In totaal is monsters van 28 varke geneem. Die histologies seksies van al die monsters het gedui op ’n Clostridium spesie as die hoofoorsaak van vrekte en Clostridium perfringens is uit 11 van die monsters geisoleer. Alhoewel al 5 plase serologies positief getoets is vir Lawsonia intracellularis, was daar geen bewyse gewees dat die bakterium verantwoordelik vir die vrektes was nie. Die etiologie dui eerder op C. perfringens as die oorsaak. Daarby saam speel ander faktore soos vinnige groei, hoë omgewingstemperature asook onderbrekings in beskikbaarheid van voer heelwaarskynlkik ’n belangrike rol in die sindroom. Verdere navorsing om die toksien tipe te identifiseer asook die identifikasie van moontlike faktore wat die sindroom aanhelp moet gedoen word.
Dissertation (MMEdVet)--University of Pretoria, 2009.
Production Animal Studies
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Johnston, Colette. "Metabolomic profiling in inflammatory bowel disease." Thesis, University of Manchester, 2014. https://www.research.manchester.ac.uk/portal/en/theses/metabolomic-profiling-in-inflammatory-bowel-disease(1eb7a48f-af12-4bd2-8497-ebad4eae0e4e).html.
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Introduction: Inflammatory bowel disease is a common, complex relapsing disorder characterised by immune dysregulation, altered intestinal permeability and microbial insult. Limited knowledge is available regarding the metabolic changes observed during progression of the disease, and limited biomarkers of disease available that have been validated and shown to be of sound clinical value. Aim of Study: A two stage metabolomics approach was adopted to determine if metabolic signature profiles, could distinguish inflammatory bowel disease Crohn’s disease (CD) patients from ulcerative colitis (UC) patients and from healthy controls. Methods: A serum metabolomics approach was undertaken to define metabolic changes associated with UC and CD. Serum samples from a discovery study of 30 UC, 30 CD and 29 ethnically, age and gender matched controls were analysed by ultra-performance liquid chromatography mass spectrometry. A subsequent validation study was preformed using 28UC, 31CD, and 29 gender matched controls were also analysed using UPLC-MS.ResultsClasses of metabolites, identified as biologically interesting and at significantly different levels (p<0.05) in comparisons of control and CD and UC cohorts included: steroids and steroid derivatives, phosphocholine, Vitamin D metabolites, fatty acids and conjugates, glycerolipids, isoprenoids, amino acids, and phosphosphingolipids. There were fewer discriminatory metabolites differentiating the CD and UC cohorts. Conclusion: Serum Metabolomic profiling may represent a novel technology which could be used to distinguish individuals with CD from those with UC and healthy controls.
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Hildebrand, Diane Rosemary. "Metabolomic profiling in inflammatory bowel disease." Thesis, University of Edinburgh, 2017. http://hdl.handle.net/1842/28850.
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Introduction Inflammatory bowel disease (IBD) is a chronic gastrointestinal disorder that encompasses two major subtypes; Crohn’s Disease (CD) and Ulcerative Colitis (UC). Our knowledge regarding disease pathogesis is rapidly increasing. However, these disease entities provide challenges in diagnosis, monitoring of disease activity and assessing individual response to treatment, because there is a lack of validated clinical biomarkers. Metabolomics involves the study of numerous analytes that have very diverse physical and chemical properties and occur in a wide concentration range. Early evidence suggests there is potential for metabolomic profiling to be used in the differentiation of CD and UC. However, knowledge is limited regarding the metabolic changes seen in relation to disease activity or to medical or surgical treatments. Aims A metabolomics approach was taken to determine whether metabolomic profiles could distinguish between patients with CD or UC and healthy controls. We also aimed to define the relationship between metabolomic profile and disease activity, and to determine the effect of medical (anti-TNFa agents) and surgical treatment on the metabolome. Methods A metabolomics approach was undertaken. Serum and urine sample sets were collected from a total of 41 patients with ulcerative colitis, 43 patients with Crohn’s disease, and 62 healthy controls (HC). In order to allow a comparison of metablomic profile and disease activity, 4 sample sets were taken from the same patient at 3 monthly intervals over the period of one year. Those patients undergoing either surgical or biological treatment had sample sets taken pre and post intervention. Metabolomic analysis using gas chromatography time of flight mass spectrometry (GC-ToF-MS) and ultra-high performance liquid chromatography Fourier Transform mass spectrometry (UHPLC-FTMS) was carried out on both serum and urine. Results Serum and urine GC-ToF-MS and UHPLC-FTMS metabolomic analyses show differentiation between UC, CD and healthy controls, most significantly in urine analyses. No significant differentiation was seen in pre- and post-surgical patients, or pre- and post-biological therapy patients. It was possible to differentiate surgical patients from healthy controls, especially in the urine analyses. Metabolite identification revealed consistently more dietary variation in the healthy controls than in the IBD patients. Significant differences (p < 0.05) were seen between healthy controls and IBD patients in classes of metabolites relating to the citric acid cycle and the uronic acid pathway, as well as amino acids, fatty acids and cholesterols. The behaviour or location of disease, or the disease activity score did not appear to influence the metabolome in either serum or urine analyses using GC-ToF-MS and UHPLC-FTMS. Conclusion Metabolomic profiling of urine and serum in IBD may provide a novel methodology aiding both clinical diagnosis through biomarker development, and advancing knowledge of disease pathogenesis.
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Chan, Kwong-leung. "Management of intestinal failure - parenteral nutrition, experimental small bowel transplantation and preservation injury of small bowel allograft." Hong Kong : University of Hong Kong, 1999. http://sunzi.lib.hku.hk/hkuto/record.jsp?B22237586.
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Gracie, David John. "The prevalence and impact of irritable bowel syndrome-type symptoms and psychological co-morbidity on inflammatory bowel disease." Thesis, University of Leeds, 2018. http://etheses.whiterose.ac.uk/22054/.
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Introduction: The brain-gut axis may influence disease outcomes in inflammatory bowel disease (IBD). Evidence supporting brain-gut axis activity would highlight a need for novel management strategies targeting this pathophysiological mechanism in IBD. The aim of this thesis was to examine these issues directly. Methods: In simultaneous cross-sectional studies, the relationship between symptom-reporting, psychological co-morbidity, and disease activity, and the prevalence of irritable bowel syndrome (IBS)-type symptoms, as well as their association with impaired mood and quality of life, was assessed. In longitudinal follow-up, the temporal relationship between disease activity and psychological co-morbidity was examined to assess for the presence of brain-gut axis activity. The relationship between the reporting of IBS-type symptoms and the natural history of IBD was also assessed. A systematic review and meta-analysis of randomised controlled trials was conducted to investigate the efficacy of psychological therapies in IBD. Results: The correlation between symptom-reporting and mucosal inflammation was poor. Symptom-reporting, but not mucosal inflammation, was associated with psychological co-morbidity. Baseline disease activity was associated with new-onset anxiety (odds ratio = 5.17; 95% confidence interval (CI) 1.35-19.8), and baseline anxiety was associated with new-onset disease flare (hazard ratio = 2.08; 95% CI 1.31-3.30), suggesting possible bi-directional brain-gut axis activity in IBD. IBS-type symptom-reporting was associated with psychological co-morbidity and poor quality of life, but reporting these symptoms was not associated with adverse longitudinal disease activity outcomes. Psychological therapies were associated with short-term beneficial effects on depression and quality of life, but had no effect on disease activity. Conclusions: Bi-directional brain-gut axis activity may influence the natural history of disease activity, and psychological wellbeing, in IBD. Patients reporting IBS-type symptoms exhibit psychological co-morbidity and reduced quality of life. Evidence supporting the use of psychological therapies in IBD is poor, but trials of these treatments in patients at risk of mood disorders may still prove beneficial.
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Salim, Sa'ad Yislam. "Mucosal dendritic cells in inflammatory bowel disease." Doctoral thesis, Linköpings universitet, Kirurgi, 2009. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-52234.
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Crohn's disease, a chronic inflammation of the bowel, is a multi-factorial condition where uncontrolled immune responses to luminal bacteria occur in genetically predisposed individuals. The first observable clinical signs are small ulcers that form at a specialised form of epithelium, follicle-associated epithelium (FAB). The FAB covers immune inductive sites, Peyer's patches, which function primarily as sensory areas that sample the externaI gut environment. Dendritic cells are one of the key cells that are involved in sensing luminal contents and orchestrating the gut immune system. The main aim of this thesis was to determine whether the barrier of the FAB is breached in Crohn's disease and if dysfunctional immune regulators, namely dendritic cells, playaroIe in initiating and/or maintaining the chronic intestinal inflammation. Using biopsies and surgical specimens, we were able to show that in Crohn's disease, there was an increased transmucosaI transport of Escherichia coli compared to specimens from ulcerative colitis and non-inflammatory bowel disease (IBD) controIs. Dendritic cells internalised a higher percentage of bacteria that had translocated across the FAB in the Crohn's samples. Furthermore, significantly higher concentrations of TNF-u was released upon bacterial stimulation by tissues from patients with Crohn's disease than in controIs. We went on to characterise the dendritic cells present in the Peyer's patches of patients with Crohn's disease. We found an accumulation of both immature and mature dendritic cells beneath the FAB, in the sub-epithelial dome (SED). Normally, mature dendritic cells migrate towards T cell-rich areas. However, we observed mature dendritic cells accumulating in the SED because they lacked the CCR7 migratory receptor. Furthermore, they were more prone to take-up bacteria, and produced TNF-α. To study the function of mucosal dendritic cells, we performed isolation experiments and mixed Iymphocyte reactions. Dendritic cells from both the ileum and blood of patients with active Crohn's had reduced capacity for inducing T cell proliferation than non-IBD controIs. Blood dendritic cells of patients in remission had normalised function that was similar to dendritic cells from healthy controls. The SAMPl/YitFc mice, considered an appropriate murine model for Crohn's disease, had an inherent permeability defect that increased with the chronicity of intestinaI inflammation. However unlike in human Crohn's disease, dendritic cells did not seem to playaroIe in murine ileitis. This thesis highlights the accumulation of the actively surveying dendritic cells that are prone to bacterial internalisation, and points to their possible different functional roles in active versus in-active disease; thereby confirming dendritic cells as one ofthe key components in the pathogenesis ofCrohn's disease.
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Dolk, Alma, and Ida Lundin. "Livskvalitet hos personer med Irritable Bowel Syndrome." Thesis, Sophiahemmet Högskola, 2012. http://urn.kb.se/resolve?urn=urn:nbn:se:shh:diva-1230.
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Ababio, Frank James Kweku. "The endocannabinoid system in inflammatory bowel system." Thesis, Nelson Mandela Metropolitan University, 2014. http://hdl.handle.net/10948/d1020338.
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Crohn’s disease (CD) and ulcerative colitis (UC) constitute the two major forms of inflammatory bowel disease (IBD), which are disorders of chronic inflammation in the gastrointestinal tract that are associated with significant morbidity and socioeconomic burden. IBD patients with long-standing intestinal inflammation are more prone to developing colorectal cancer (CRC). Until now, none of the existing IBD treatments is able to heal the mucosal ulcerations satisfactorily. The endocannabinoid system (ECS), which comprises of endogenous cannabinoid ligands, their receptors, and metabolic enzymes, has been implicated in gut homeostasis, visceral sensation, inflammation and gastrointestinal motility. Available studies in rodent models of IBD suggest that enhancing the ECS tone may reduce inflammation and improve mucosal integrity. This evidence indicates that the components of the ECS seem well positioned to exert a protective role in IBD and also to offer a great opportunity for therapeutic exploitation. Despite the role of the ECS in the gut, the presence and function of the components of the ECS is not well characterised in human IBD. The primary aim of the study was to investigate the state of the major components of the ECS in human IBD and to establish whether IBD is associated with any changes of the components of the ECS. Cannabinoid CB1 and CB2 receptors, enzymes for endocannabinoid biosynthesis PLC, “LRAT”, NAPE-PLD and DAGL, and endocannabinoid metabolic enzymes FAAH and MAGL were analysed from colonic tissue samples of CD, UC and control patients by reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) to determine the relative mRNA expression of the above genes. The RT-qPCR analysis showed that the mRNA expression of PLC, LRAT, and NAPE-PLD were unchanged in both CD and UC, whiles DAGL mRNA was decreased in UC but was unchanged in CD. The endocannabinoid degradation enzymes, FAAH mRNA expression was also unchanged in CD but decreased in UC, whereas the mRNA expression of MAGL was significantly decreased in both CD and UC. NAPE-PLD/FAAH and DAGL/MAGL ratios, an estimation of the balance of AEA and 2-AG levels, showed that AEA and 2-AG levels could be increased and unchanged, respectively, in IBD. The mRNA expression of CB1 was significantly decreased in CD and UC whilst CB2 mRNA expression was unchanged in both forms of IBD. The study demonstrated that the components of the ECS which were investigated were present in colonic tissues of both IBD patients and healthy individuals, but they appear to be off balance in CD and UC patients. The decreased CB1 receptors in IBD patients could be an important modifier in the disease and could also provide a possible pathoaetiological mechanism linking IBD and CRC. Although these findings look promising, more studies with larger sample size are required to characterise the components of the ECS in human IBD.
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Ingram, John Robert. "Topical nicotine therapy for inflammatory bowel disease." Thesis, University of Oxford, 2007. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.491900.
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This thesis covers several areas which are related to the potential therapeutic effect of topical nicotine in ulcerative colitis (UC) and Crohn's colitis. It also examines a possible mechanism which may be pertinent to its mode of action. Transdermal nicotine is of benefit for active UC but adverse events (AEs) are frequent and limit its use. This prompted development of topical delivery systems which made direct application of nicotine to the colonic mucosa possible. Nicotine liquid enemas and delayed-release oral preparations produce lower systemic blood levels of nicotine and initial work with the enema in active DC gave encouraging results. My work commenced with a dose-ranging pharmacokinetic study of nicotine enemas to establish the maximum tolerated dose, which was subsequently used in a randomised, placebo-controlled trial which involved patients with active DC. Results for the primary endpoint - induction of clinical remission, were negative, although the enemas were welltolerated with only one withdrawal due to an AE. Plasma fibrinogen was measured in a subgroup ofpatients to assess the effects of nicotine and disease activity - there appeared to be no effect of topical nicotine on fibrinogen levels and plasma fibrinogen was not suf1iciently sensitive to be of clinic~l use as a biochemical marker of disease severity. Patients previously treated with nicotine in this depaltment had commented that urge~cy to defaecate settled quickly. To examine this, a comparative study of enema retention and preference was perfOlmed but there was no difference between nicotine and other enemas. 2 Supplied by The British Library - 'The world's knowledge' Smoking has a detrimental effect in Crohn's disease (CD) but this could be due to factors other than nicotine and related to smoking. Given the considerable overlap in the . . treatment ofUC and CD, a small pilot study of nicotine enemas for active Crohn's colitis was conducted; there was no clinical deterioration and some patients improved. A delayed-release oral formulation was given to patients with more extensiv~ colitis. There was a wide vmiation in the dose of nicotine tolerated; assessment of efficacy was limited because of the 'open' nature of the observations - but some patients appeared to benefit. The laboratory work was an extension of evidence that 0.7 nicotinic acetylcholine receptors (nAChRs) on monocytes have an impOltant anti-inflanunatory role. It is conceivable that nicotine exerts an anti-inflammatory effect through these receptors but there was no data relating to the colon. LabeIledo.-bungarotoxin was used to detect 0.7 nAChRs in human colonic mucosa. They were present on a few cells of the lamina proplia which are possibly dendritic cells (DCs) based on their morphological and phenotypic features. Future investigations might include the roles in colitis of delayed-release oral nicotine e and formulations which reproduce the phannacokinetic profile ofplasma nicotine seen in smokers. The possibility that nicotine may help us understand the pathogenesis ofcolitis and lead to therapeutic alternatives is attractive and requires further exploration.
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Irving, Peter Miles. "Platelet-leucocyte aggregates in inflammatory bowel disease." Thesis, Queen Mary, University of London, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.441946.
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Rahman, Arman. "Defensins and cytokines in inflammatory bowel disease." Doctoral thesis, Umeå : Univ, 2007. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-1377.
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Simmonds, Nicola Jane. "Reactive oxygen metabolites and inflammatory bowel disease." Thesis, University of Oxford, 1992. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.317911.
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