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Microbiota are present in large numbers and as a diverse population within the gastrointestinal tract. There are approximately 400 different species of microbiota which may be beneficial, harmful or both, but each play an important role in the regulation and modulation of the hosts’ bowel processes (McOrist et al. 2008; Dethlefsen et al. 2008). Many of these colon microbiota allow for saccharolytic fermentation of non-digestible dietary fibres and carbohydrates into by-products and intermediates, followed by a subsequent conversion into short chain fatty acids (SCFAs) (mainly n-butyric acid, propionic acid and acetic acid) each of which play an important role in maintaining colon homeostasis (Topping & Clifton 2001). A balance of ‘good’ microbiota (e.g., Bacteroides spp./ Bifidobacteria spp.) and ‘bad’ microbiota (e.g., Veilonellae) and the optimal production of various SCFAs within the gut could possibly allow for proper functioning of the large intestine and assist in decreasing the onset of various colonic disorders such as Irritable Bowel Syndrome (IBS). The sample group for the study consists of male and female patients, with an average age of 40 to 50 years old, whom of which have been diagnosed with either constipation IBS (C-IBS) or diarrhoea IBS (D-IBS) via the Rome III criteria system for IBS diagnosis. DNA and SCFA extractions were optimised for human stool, colonic fluid and tissue biopsy sample obtained from the aforementioned patients. Optimization steps allowed for starting material with high analysis integrity. Different methods of microbiota analysis, such as ARISA, were investigated; however, real-time qPCR was selected as the best method to identify and quantify specific microbiota. Extracted SCFAs were separated via gas chromatography and identified and quantified via Mass Spectrometry. Significant changes in microbial content and SCFA profiles were found to be associated with healthy and IBS patients. Results obtained would however be influenced by external factors typical of clinical studies of this nature. This study allows for opportunities for future research into understanding IBS.

Lower gastrointestinal bleeding (LGIB) can result in serious adverse events. Appropriate risk stratification of LGIB patients can improve their care. Previous risk scores to identify severe LGIB patients have limitations, therefore we developed clinical decision tool to accurately identify LGIB patients presenting to the emergency department (ED) who are at risk for 30-day adverse outcomes that would overcome these limitations. We conducted a health records review and compared two methods of regression analysis on our data in order to develop a clinical decision tool. We identified five risk factors that have a high sensitivity and good predictive value for identifying low risk LGIB patients: age ≥ 75 years, INR ≥2.0, hemoglobin ≤ 100 g/l, ongoing bleeding in the ED and a medical history of colorectal polyps. Future, large, prospective studies should be done to validate the results, after which implementation studies should be conducted.

Background: Pelvic radiotherapy is a well-established treatment for pelvic malignancies, with 30,000 patients per year in the UK receiving radical pelvic radiotherapy either alone or in combination with other oncological treatments. 80% develop acute gastrointestinal (GI) symptoms and 50% develop chronic GI symptoms and in parallel to improvements in survival, increasing numbers of patients are living to develop the long term consequences of treatment. Despite this, less than 20% of patients who develop chronic GI symptoms are ever referred to a gastroenterologist. Aims: 1. To determine the current practice of clinical oncologists and gastroenterologists with respect to management of chronic GI symptoms following pelvic radiotherapy in 2 parallel national surveys. 2. To determine whether specialist gastroenterological management of chronic GI symptoms following pelvic radiotherapy based on a structured algorithmic approach identifies GI diagnoses and improves outcomes. 3. To determine whether a GI care bundle comprising nutritional assessment and intervention and investigation of GI symptoms and subsequent treatment of diagnoses found is feasible and acceptable to patients. Findings: There is no formal robust screening for GI symptoms, low referral rates, patchy services, use of ineffective treatments and inadequate expertise. Oncologists underestimate the problem and under refer. Gastroenterologists are seeing low numbers of patients and lack expertise. Both groups state that a regional multidisciplinary service for patients with GI symptoms following pelvic radiotherapy would be desirable. Patients who develop GI symptoms following pelvic radiotherapy present with multiple symptoms (median 8) and thorough structured evaluation identified multiple potentially treatable diagnoses, with 28 patients (55%) having ≥2 causes for their GI symptoms. Half of diagnoses were unrelated to previous cancer treatment. Common diagnoses included radiation proctopathy, bile acid malabsorption, diverticulosis and colonic polyps. A clinically and statistically significant improvement in GI symptoms was found in parallel to GI intervention using inflammatory bowel disease questionnaire (IBDQ) (p=0.014), Vaizey incontinence questionnaire (VIQ) (p<0.0005) and the Common Terminology Criteria for Adverse Events (CTCAE) pelvic symptom questionnaire rectum-bowel subset (p=0.001). Initial data show that GI and nutritional intervention during pelvic chemoradiotherapy is both feasible and acceptable to patients. Conclusions: There is inadequate care and services for this patient group in the UK. GI intervention using a structured algorithmic approach is of benefit in terms of identifying potentially treatable diagnoses and improving symptoms. GI intervention during pelvic radiotherapy is feasible and acceptable to patients and ongoing work will determine the benefit of this intervention in terms of symptom control in the short and long term and cost benefit. A programme of mechanistic and clinical research is required to improve the understanding of this scenario.

A radioimmunoassay was developed, specific for the gastrointestinal polypeptide, motilin. Antisera were raised in guinea pigs and rabbits. The immunogen was porcine motilin, conjugated to bovine serum albumin by the carbodiimide condensation reaction. The routine antiserum behaved identically towards endogenously- released motilin and the pure standard preparation. A radioactive tracer of high 125 specific activity was obtained after incorporation of - iodine into the motilin molecule by the chloramine-T method. The optimum conditions for all other assay variables were established to produce the most sensitive displacement Cstandard) curve. Motilin antiserum, coupled directly to an agarose matrix, retained full antibody activity and sensitivity. It is a feasible technique for use in both the radioimmunoassay and in the extraction of motilin from both serum and tissue extracts. The fasting serum levels of IR- motilin was 190 - 131 pg/ml in men and 294 -'.44 pg/ml in dogs (mean - SD) . The increase in motor activity in the extrinsically denervated fundic pouch of the dog after duodenal alkalinization was associated with a concomitant elevation in serum IR- motilin levels. This increase in serum IR- motilin was in the same range as that achieved by the exogenous administration of the porcine polypeptide which produced the same motor response. Duodenal acidification produced an apparent increase in serum IR-motilin with no associated increase in gastric motor activity. Only one peak of motilin immunoreactivity was detected when serum containing alkali-stimulated motilin or a partially purified duodenal extract were subjected to gel filtration on Sephadex G-50. The distribution of motilin throughout the hog gastrointestinal tract, determined by radioimmunoassay on partially purified extracts, agreed with the immunocytochemical findings that motilin was predominantly located in the duodeninn and jejunum, with traces.in the upper ileum. Virtually the intact molecule was required for the expression of full biological potency. The individual amino acids were important inasmuch as they contributed to the charge distribution and conformation of the molecule. The physiological release and function of motilin have yet to be determined. Elevated levels of circulating IR- motilin have not been associated with any gastro-intestinal function, although they appear to be depressed by feeding. Motilin has been implicated in the control of the interdigestive phase of gastric motor activity. It may be acting in a local or paracrine manner. Motilin has not been implicated in any .•cU'in±cal.rst"ait"eC&s sjffetfce i The hormonal status of gastric inhibitory polypeptide (GIP) has been studied with the existing radioimmunoassay, modified to improve the label specific activity (by ion exchange chromatography). Direct coupling of GIP antisera to agarose beads was unsatisfactory, antibody activity and sensitivity being greatly reduced by the close proximity of the solid matrix. The postulated role of GIP as the enterogastrone1 of Kosaka and Lim, suggested by studies with exogenously-administered polypeptide, was confirmed by experiments in the dog. Pentagastrin-stimulated gastric acid secretion was inhibited by intra-duodenal infusion with glucose or fat; this inhibition being associated with a significant elevation in the circulating serum IR- GIP levels, within the range produced by ingestion of a mixed meal. GIP does not appear to be involved in the inhibition of gastric acid secretion produced by duodenal acidification. Endogenous;GIP.stimulated by either fat or glucose exhibited at least 3 Immunoreactive components after column chromatography. The IR- GIP eluting in the void volume appeared to represent a non-specific complex between GIP and a serum protein and is possibly biologically inactive. A second IR-GIP component with a molecular weight of 7500-8000 (ProGIP), eluted ahead of the established form of GIP (molecular weight = 5105). ProGIP has been found to be relatively unstable. ProGIP and GIP^QQQ have also been detected in extracts of hog duodenal mucosa. The established insulinotropic effect of GIP correlates best with that percentage of the total IR- GIP composed of ProGIP and GIP500(). The relative proportions of IR- GIP500Q and IR- ProGIP in serum samples taken at different times after ingestion of either fat or glucose, suggest that ProGIP is either a precursor of GIP or that the ProGIP-producing cells occupy a more distal region of the duodenal and jejunal mucosa than the GIP- producing cells. Exogenous administration of synthetic somatostatin in dogs and man will inhibit both.GIP release by either fat or glucose and the insulino-tropic action of GIP at the level of the 8/-cell. Naturally-occurring intestinal or pancreatic somatostatin may contribute to the control of GIP release and serve to modulate the GIP- mediated response of the gastric parietal or pancreatic β-cell. / Medicine, Faculty of / Cellular and Physiological Sciences, Department of / Graduate

The normal sonographic appearance of the adult canine gastrointestinal tract has been well described. Interpretation of ultrasonographic findings in puppies presented for gastrointestinal evaluation is difficult due to the lack of information on normal ultrasonographic findings. The gastrointestinal tract, jejunal lymph node size and appearance as well as the presence or absence of peritoneal fluid were prospectively investigated in a group of 23 normal, 7 – 12 week old Beagle puppies. The duodenal wall thickness was significantly greater than other parts of the gastrointestinal tract (mean 3.8 mm). The mean stomach wall thickness was 2.7 mm, mean jejunal wall thickness 2.5 mm and mean colonic wall thickness 1.3 mm. In addition, the mean thickness of the duodenal mucosal layer (2.7 mm) was significantly thicker than that of the jejunal mucosal layer (1.5 mm). The mucosa was isoechoic to the muscularis layer and had a crisp luminal-mucosal interface in all puppies. There were no intestinal corrugations observed and wall layering was distinct in all gastrointestinal segments. The homogenous, hypoechoic jejunal lymph nodes were easily found and their mean thickness measured 7.1 mm (± SD 2.2 mm). A mild amount of anechoic free peritoneal fluid was seen in all puppies. Conclusions drawn from this study were that prominent jejunal lymph nodes and a mild amount of anechoic free peritoneal fluid can be considered normal findings in puppies. Information from the above study was utilised to interpret findings of a prospective clinical study on the ultrasonographic appearance of the gastrointestinal tract of puppies suffering from parvoviral enteritis. Forty puppies between six and 24 weeks of age were examined ultrasonographically within 24 hours of admission for canine parvoviral enteritis confirmed on faecal transmission electron microscopy. A clinical score (assessing habitus, appetite, vomiting, faecal consistency, mucous membranes, abdominal palpation and borborygmi) was attributed to each puppy prior to the ultrasonographic examination. Sonographic findings included fluid filled small intestines in 92.5% of cases, and stomach and colon in 80% and 62.5% of cases respectively. Generalised atony was seen in 30 cases and weak peristaltic contractions indicative of functional ileus observed in the remaining 10 cases. The duodenal and jejunal mucosal layer thicknesses were significantly reduced when compared to values obtained in the normal Beagle puppies with mean duodenal mucosal layer measuring 1.7 mm and jejunal mucosal layer 1.0 mm. Additionally, a mucosal layer with diffuse hyperechoic speckles was seen in the duodenum (15% of cases) and the jejunum (50% of cases). The luminal surface of the duodenal mucosa was irregular in 22.5% of cases and the jejunal mucosa in 42.5% of cases. In all of these puppies, changes were accompanied by generalised indistinct wall layering. Small intestinal corrugations were seen within the duodenum in 35% of cases and within the jejunum in 7.5%. A mild amount of anechoic free peritoneal fluid was observed in 26 cases and was considered within normal limits for puppies and a moderate amount of anechoic free peritoneal fluid was observed in six cases. The jejunal lymph node size was within normal limits for puppies and thus parvoviral enteritis does not appear to be associated with ultrasonographic evidence of regional lymphadenopathy. There was a tendency for animals with the most dramatic ultrasonographic changes to be in poor condition clinically i.e. they had a low clinical score. Each of the above described changes cannot be considered pathognomonic for canine parvoviral enteritis but in combination, are suggestive of the disease. It is hoped that information from this study may alert the clinician as to the possibility of underlying parvoviral enteritis in puppies presented for abdominal ultrasound for investigation of gastrointestinal disease. Further studies are needed to document the ultrasonographic appearance of other paediatric gastrointestinal diseases such as severe verminosis, giardiasis, coccidiosis and distemper etc. before further conclusions can be drawn from this study. Daily ultrasonographic examinations of puppies suffering from canine parvoviral enteritis are needed to further understand the progression of this disease over time as well as the possible ultrasonographic indicators of clinical improvement or deterioration. / Dissertation (MMedVet)--University of Pretoria, 2009. / Companion Animal Clinical Studies / unrestricted

A thesis submitted to the Faculty of Medicine, University of the Witwatersrand, Johannesburg, for the degree of Doctor of Medicine. / An attempt was made to document iron losses from the body as a whole, as well as from individual excretory routes using a combination of radioisotopic and chemical techniques. The purpose of this work was to gain a better understanding of external body exchange, and to resolve some of the existing controversies regarding the magnitude of daily iron losses. The basis for this controversy is extensively reviewed in the thesis / IT2018

The gastrointestinal (GI) tract is a diverse habitat for multiple microorganisms. Disturbances in the microbiome of the GI tract have been associated with psychiatric disorders including autism spectrum disorder (ASD). Individuals with ASD, when compared to neurotypical individuals, have demonstrated differing gut species. Also, it has been shown that microbial transplant therapies impact ASD symptoms in patients. Animal models of behaviors associated with ASD might offer insight for the actual role these microbial differences may occupy regarding symptoms. Unfortunately, ASD does not have an accepted animal model where the GI alterations have been thoroughly explored. In this study, we sought to determine if the microbiome and other GI alterations were observed in two potential mouse models of social behavior deficits, the genetic BTBR T+Itpr3tf/J (BTBR) mouse strain and an environmental mouse strain consisting of offspring of valproic acid (VA) treated pregnant controls. Both mouse models have been shown to exhibit social and repetitive behaviors that are found in human ASD. Using the Illumina MiSeq, we were able to identify taxonomy associated with 16S ribosomal DNA sequences extracted from fecal matter. We were able to compare the sequencing results from the two affected strains and a control C5BL/6J mouse strain for both female and male animals using the Qiagen CLC Genomics Workbench software. Overall, microbiome composition was found to be significantly different between the male control animals (N=6) when compared to the VA (N=5; p-value=.00216; F-score 11.20904) or the BTBR (N=7; p-value=.00216; F-score 18.47839) males using a PERMANOVA analysis. This was replicated in female groups where composition significantly differed between the control (N=14) and VA (N=14; p-value=.00001; F-score 3.53307) or BTBR (N=14; p-value=.00001; F-score 11.23443) females. Additionally, short-chain fatty acid analysis using gas capillary-based chromatography was used to examine acetate, butyrate, propionate, and valerate levels in feces. Only valerate levels were significantly lower (p

Immunofluorescence was used to study immunoreactivity (IR) for corticotropin-releasing factor (CRF) in the guinea pig enteric nervous system. CRF-IR was expressed in both the myenteric and the submucosal plexuses of all regions of the large and small intestine and the myenteric plexus of the stomach. CRF-IR nerve fibers were present in the myenteric and submucosal plexuses, in the circular muscle coat, and surrounding submucosal arterioles. Most of the CRF-IR fibers persisted in the myenteric and submucosal plexuses after 7 days in organotypic culture. CRF-IR was not coexpressed with tyrosine hydroxylase-IR or calcitonin gene-related peptide-IR fibers. The proportions of CRF-IR cell bodies in the myenteric plexus increased progressively from the stomach (0.6%) to the distal colon (2.8%). Most of the CRF-IR myenteric neurons (95%) had uniaxonal morphology; the remainder had Dogiel type II multipolar morphology. CRF-IR cell bodies in the myenteric plexus of the ileum expressed IR for choline acetyltransferase (56.9%), substance P (55.0%), and nitric oxide synthase (37.9%). CRF-IR never colocalized with IR for calbindin, calretinin, neuropeptide Y, serotonin, or somatostatin in the myenteric plexus. CRF-IR cell bodies were more abundant in the submucosal plexus (29.9-38.0%) than in the myenteric plexus. All CRF-IR neurons in submucosal ganglia expressed vasoactive intestinal peptide-IR and were likely to be secretomotor/vasodilator neurons. CRF-IR neurons did not express IR for the CRF1 receptor. CRF 1-IR was expressed in neuronal neighbors of those with CRF-IR. Collective evidence suggests that VIPergic secretomotor neurons might provide synaptic input to neighboring cholinergic neurons.

Actinomycotic infections involving the oesophagus are uncommon but have been reported in both immunocompromised and immunocompetent individuals. We report a case of actinomycosis oesophagitis in a patient with lung cancer who received chemo- and radiotherapy. This patient was admitted with severe dysphagia and odynophagia and biopsy from an oesophageal ulcer found on oesophagogastroduodenoscopy (EGD) revealed actinomycosis. The patient was treated with intravenous penicillin G followed by ceftriaxone with clinical improvement and repeat EGD showed reduction in the size of the oesophageal ulcer, but he relapsed due to non-compliance. We review the English literature regarding the clinical features, diagnosis, and management of actinomycotic infections of the oesophagus.