[Show abstract][Hide abstract] ABSTRACT: Diarrhea is best defined as passage of loose stools, often with more frequent bowel movements. For clinical purposes the Bristol Stool Form Scale works well to distinguish stool form and to identify loose stools. Laboratory testing of stool consistency has lagged behind. Acute diarrhea is likely to be due to infection and to be self-limited. As diarrhea becomes chronic it is less likely to be due to infection; duration of one month seems to work well as a cut off for chronic diarrhea, but detailed scientific knowledge is missing about the utility of this definition. In addition to duration of diarrhea, classifications by presenting scenario, by pathophysiology, and by stool characteristics (e.g., watery, fatty, or inflammatory) may help the canny clinician refine the differential diagnosis of chronic diarrhea. In this regard, a careful history remains the essential part of the evaluation of a patient with diarrhea. Imaging the intestine with endoscopy and radiographic techniques is useful, and biopsy of the small intestine and colon for histologic assessment provides key diagnostic information. Endomicroscopy and molecular pathology are only now being explored for the diagnosis of chronic diarrhea. Interest in the microbiome of the gut is increasing; aside from a handful of well-described infections due to pathogens, little is known about alterations in the microbiome in chronic diarrhea. Serologic tests have well-defined roles in the diagnosis of celiac disease, but have less clearly defined application in autoimmune enteropathies and inflammatory bowel disease. Measurement of peptide hormones is of value in the diagnosis and management of endocrine tumors causing diarrhea, but these are so rare that these tests are of little value in screening since there will be many more false positives than true positive results. Chemical analysis of stools is of use in classifying chronic diarrhea and may limit the differential diagnosis that must be considered, but interpretation of the results is still evolving. Breath tests for assessment of carbohydrate malabsorption, small bowel bacterial overgrowth and intestinal transit are fraught with technical limitations that decrease sensitivity and specificity. Likewise, tests of bile acid malabsorption have had limited utility beyond empiric trials of bile acid sequestrants.
Journal of Gastroenterology and Hepatology 10/2013; 29(1). DOI:10.1111/jgh.12392 · 3.50 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Diarrhea is the result of changes in the regulation of intestinal absorption and secretion, favoring net fluid and electrolyte movement into the intestinal lumen. Factors influencing this process include those that induce active secretion, those that inhibit active absorption, osmotic agents, and factors that stimulate intestinal motility. The most common causes of acute diarrhea include infections and drugs. Chronic diarrhea is often a diagnostic challenge and has a broad etiology. The diagnosis can often be made by a thorough history and examination with the addition of basic blood tests and stool analysis; however, exhaustive investigations are infrequently required. This chapter describes the pathophysiology in relation to the causes and symptom complexes of diarrhea, with simple diagnostic algorithms.
Textbook of Clinical Gastroenterology and Hepatology, 04/2012: pages 32-42; , ISBN: 9781405191821
[Show abstract][Hide abstract] ABSTRACT: 1. We have compared the activities of the endothelin precursors (human big ET-1(1-38), porcine big ET-1(1-39), big ET-2(1-38) and big ET-3(1-41 amide) and their respective mature 21 amino acid peptides as contractors of isolated gallbladder strips of the guinea-pig. We have also used different protease inhibitors and/or epithelial cell removal to investigate the nature and the location of the endothelin-converting enzyme (ECE) activity responsible for the conversion of porcine big ET-1(1-39) in this isolated preparation. In addition, we have conducted binding studies to investigate whether porcine big ET-1(1-39) interacts directly with ET receptors. 2. ET-1, ET-2 and ET-3 were equipotent at causing 50% of the contractions of the isolated strips (22.9 +/- 6.8, 39.5 +/- 9.9 and 35.9 +/- 3.7 (x 10(-9) M), respectively), as estimated with contractions to 3 x 10(-7) M taken as 100%. Big ET-1(1-38) was equipotent to ET-1 while big ET-1(1-39) was one fifth as potent as ET-1, and big ET-2(1-38) was one fifth as potent as ET-2. Precursors of ET-1 and ET-2 induced similar contractions at 3 x 10(-7) M. Conversely, the contraction induced by big ET-3(1-41 amide) (3 x 10(-7) M) was only 14% of that induced by the same concentration of ET-3 (287 +/- 37% of 5 microM histamine). 3. The kinetics of the responses induced by single additions of 3 x 10(-7) M of the endothelin isopeptides were compared.(ABSTRACT TRUNCATED AT 250 WORDS)
British Journal of Pharmacology 01/2012; 114(7):1383-90. DOI:10.1111/j.1476-5381.1995.tb13359.x · 4.84 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The most frequent illness among persons traveling from developed to developing countries is travelers' diarrhea. Travelers to high-risk regions traditionally have been educated to exercise care in food and beverage selection. Innovative research is needed to identify ways to motivate people to exercise this care and to determine its value. Chemoprophylaxis can be recommended for certain groups while monitoring for safety, drug resistance, and efficacy against all forms of bacterial diarrhea. Research to evaluate the value of immunoprophylaxis is recommended. In the following document, the authors used an evidence base when available to determine strength and quality of evidence and when data were lacking, the panel experts provided consensus opinion.
Journal of Travel Medicine 05/2009; 16(3):149-60. DOI:10.1111/j.1708-8305.2008.00299.x · 1.58 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The HIV epidemic in sub-Saharan Africa has had a major impact on infectious disease, and there is currently great interest in the impact of HIV on intestinal barrier function. A three year longitudinal cohort study in a shanty compound in Lusaka, Zambia, carried out before anti-retroviral therapy was widely available, was used to assess the impact of HIV on susceptibility to intestinal infectious disease. We measured the incidence and seasonality of intestinal infection and diarrhoea, aggregation of disease in susceptible individuals, clustering by co-habitation and genetic relatedness, and the disease-to-infection ratio.
Adults living in a small section of Misisi, Lusaka, were interviewed every two weeks to ascertain the incidence of diarrhoea. Monthly stool samples were analysed for selected pathogens. HIV status and CD4 count were determined annually.
HIV seroprevalence was 31% and the prevalence of immunosuppression (CD4 count 200 cells/microL or less) was 10%. Diarrhoea incidence was 1.1 episodes per year and the Incidence Rate Ratio for HIV infection was 2.4 (95%CI 1.7-3.3; p < 0.001). The disease-to-infection ratio was increased at all stages of HIV infection. Aggregation of diarrhoea in susceptible individuals was observed irrespective of immunosuppression, but there was little evidence of clustering by co-habitation or genetic relatedness. There was no evidence of aggregation of asymptomatic infections.
HIV has an impact on intestinal infection at all stages, with an increased disease-to-infection ratio. The aggregation of disease in susceptible individuals irrespective of CD4 count suggests that this phenomenon is not a function of cell mediated immunity.
[Show abstract][Hide abstract] ABSTRACT: Infectious diarrhoea remains a major cause of morbidity and mortality world wide. Viruses, bacteria and protozoa are responsible for the majority of infections which are transmitted most commonly by the faecal-oral route through water, food and person-to-person transmission. Clinical presentation of infectious diarrhoea conforms to three patterns, namely acute watery diarrhoes, dysentery and persistent diarrhoea sometimes with the features of steatorrhoea. Diagnosis still rests heavily on stool microscopy and culture although faecal antigen tests and DNA based assays are under evaluation. Oral rehydration therapy continues to be the most important supportive intervention, particularly in acute watery diarrhoea when death from dehydration and acidosis can be prevented in the vast majority of sufferers. There have been some important advances in the development of new approaches to antibiotic therapy. The non-absorbable antibiotic rifaximin is highly effective in the treatment of traveller’s diarrhoea and is free from the majority of side effects that are associated with systemically absorbed antibiotics. The broad-spectrum antimicrobial nitazoxanide has made a major impact on the treatment of cryptosporidiosis but is also effective in giardiasis, amoebiasis and C. difficile infection. Recent evidence suggests that probiotics and prebiotics are effective in the treatment and prevention of a variety of intestinal infections.
Medicine 05/2007; 35(5):251–256. DOI:10.1016/j.mpmed.2007.02.009 · 4.35 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Assessing the extent of ulcerative colitis determines therapeutic strategies and provides prognostic information. Colonoscopy with mucosal biopsy is considered unsafe in patients with severe disease.
To assess the correlation between proximal extent of ulcerative colitis as determined by Technitium-99-m hexamethylpropylene amine oxime labelled leucocyte scan (white cell scan) with that determined by histological assessment.
One hundred and thirty-five patients, with histologically-confirmed ulcerative colitis, who had a white cell scan and histological assessment of colonic inflammation within 6 months of each other, during the years 1991-2004, were included. Overall agreement, quadratic-weighted kappa (kappa) and polychoric correlations (rho) were calculated to estimate the inter-rater reliability.
The correlation between white cell scan and histological extent was excellent (kappa = 0.7 rho = 0.8). Macroscopic appearance on colonoscopy did not correlate as well with histological extent (kappa = 0.62 and rho = 0.67). White cell scans correlated significantly better in patients with extensive disease (P = 0.02). Colonoscopy predicted disease extent more accurately in patients with limited colitis (P = 0.002).
Proximal extent of ulcerative colitis determined by white cell scans correlates well with histological assessment especially in patients with more extensive disease. White cell scans offer a reasonable alternative to colonoscopy with mucosal biopsies in determining the proximal extent of colitis.
[Show abstract][Hide abstract] ABSTRACT: Persistent diarrhoea continues to present a management challenge to clinicians around the world. The investigation of persistent diarrhoea requires a logical hierarchical approach to ensure that resources are used appropriately and patients are not put at unnecessary risks during the investigative process. A 5-step process is described in which functional diarrhoea is excluded early in the workup, which might include a measurement of 24h faecal weight. Once infection, drugs and laxatives have been excluded more invasive tests such as endoscopy are sequentially introduced to exclude inflammatory disease and small bowel and pancreatic malabsorption. When the common causes have been excluded there remains a group of patients with high volume watery diarrhoea due to a variety of causes include the neuroendocrine diarrhoeas. A case of fictitious diarrhoea is described which illustrates the value of complete fluid balance studies, faecal osmolality and other biochemical faecal analyses. The management of some selected causes of refractory diarrhoea is discussed including functional diarrhoea, diabetic diarrhoea, diarrhoea dues to protozoal infections, microscopic colitis and antibiotic associated diarrhoea.
Baillière' s Best Practice and Research in Clinical Gastroenterology 02/2007; 21(3):485-501. DOI:10.1016/j.bpg.2007.01.006 · 3.48 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Accumulating evidence suggests that intestinal epithelial cells (IECs) constitutively express the immunoregulatory cytokine interleukin (IL)-18. IECs also serve as the host cell for the intracellular parasitic protozoan Cryptosporidium parvum. In the present study, C. parvum infection of a human enterocyte cell-line HCT-8 resulted in increased expression of IL-18 mRNA as measured by quantitative reverse transcription-polymerase chain reaction (RT-PCR). IL-18 protein was detected in control uninfected cells and following infection there was increased expression as measured by enzyme-linked immunosorbent assay (ELISA). Gene expression revealed the presence of the IL-18 receptor subunits not only in cell-lines but also in freshly isolated IECs, suggesting that IL-18-mediated signalling events may contribute to epithelial host defence during infection. Recombinant IL-18 inhibited intracellular development of the parasite in HCT-8 and HT-29 cells. Increased expression of bactericidal antibiotic peptides LL-37 and alpha-defensin 2 by IL-18 in HCT-8 and HT-29 cells may represent one mode of action by which this pluripotent cytokine aids in limiting the development of intracellular pathogens such as C. parvum in the gastrointestinal tract.
[Show abstract][Hide abstract] ABSTRACT: Pathogenic intestinal protozoa are responsible for clinically important infections in both the developed and the developing world. These organisms are responsible for both acute and chronic diarrhea, and Entamoeba histolytica, which affects the colon, can spread to involve the liver. Many of these pathogens, particularly the intracellular protozoa that predominantly affect the small intestine, produce their most devastating effects in patients with HIV/AIDS and other forms of immune deficiency. There are also various intestinal protozoa that do not seem to have any adverse effects on humans and can, therefore, be regarded as harmless commensal organisms. Although treatment has been available for several decades for giardiasis, isosporiasis and amoebiasis, until recently there have been no effective remedies for infection with intestinal coccidia--Cryptosporidium, Microsporidium and Cyclospora species. Cyclospora respond well to co-trimoxazole, microsporidia respond variably to albendazole, and cryptosporidia can often be eradicated by nitazoxanide. In chronically infected HIV-positive patients, treatment with multidrug regimens usually results in rapid resolution of the diarrhea and, in many instances, eradication of the parasite.
[Show abstract][Hide abstract] ABSTRACT: Campylobacter jejuni infection frequently presents as acute enteritis with diarrhoea, malaise, fever and abdominal pain. Vomiting and bloody diarrhoea are reported less frequently. To investigate potential host, micro-organism or environmental factors that might explain the different clinical presentations, the features of laboratory-confirmed Campylobacter jejuni cases presenting with vomiting and/or bloody diarrhoea were compared with cases who did not report either clinical manifestation. Single variable analysis and logistic regression were employed. Explanatory variables included food, water and environmental risks. Cases who reported vomiting and/or bloody diarrhoea tended to suffer a longer illness and were more likely to require hospital admission. Independent risks identified were being a child, female gender, consumption of poultry other than chicken, pre-packed sandwiches and sausages, and reported engineering work or problems with drinking-water supply. A dose-response relationship with vomiting and/or bloody diarrhoea and increasing daily consumption of unboiled tap water was observed also. Vomiting and/or bloody diarrhoea characterized the more severe end of the disease spectrum and might relate to host susceptibility and/or infective dose. The role of unboiled tap water as a potential source of C. jejuni infection in England and Wales requires further investigation.
Journal of Medical Microbiology 07/2006; 55(Pt 6):741-6. DOI:10.1099/jmm.0.46422-0 · 2.25 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Acute diarrhea is a major cause of morbidity and mortality worldwide. Infants and pre-school children are the most vulnerable in whom there are 2-3 million deaths each year as a result of the associated dehydration and acidosis. Although oral rehydration therapy has reduced mortality during the past 30 years ago, the search for agents that will directly inhibit intestinal secretory mechanisms and thereby reduce faecal losses in patients with high-volume watery diarrhea has continued for more than 20 years. A variety of potential targets for antisecretory agents have been explored which include loci within the enterocyte (the chloride channel, calcium-calmodulin) and other sites such as enteric nerves and endogenous mediators (such as 5-HT, prostaglandins). Although the potential of calcium-calmodulin inhibition has as yet not been realised, preliminary studies suggest that there are chloride channel blockers under development that will find a place in the management of secretory diarrheas. Recent work has highlighted the importance of neurohumoral mechanisms in the pathogenesis of acute diarrhea. Potentiation of the effects of endogenous enkephalin activity by enkephalinase inhibition has already produced a safe, effective anti-secretory drug, racecadotril. Speculative early work indicates that there may be a role for antagonists of 5-HT, substance P, and VIP receptors. There now seems to be a real possibility that antisecretory therapy will become more widely available in the future.
[Show abstract][Hide abstract] ABSTRACT: Although authors are usually considered to be the main perpetrators of research and publication misconduct, any person involved in the process has the potential to offend. Editors may breach ethical standards particularly with respect to conflicts of interest. In the same way that authors are now required to declare competing interests, notably commercial affiliations, financial interests and personal connections, so must editors. Editors can influence the chances of acceptance or rejection of a paper by reviewer selection. Reviewers should also be ready to disclose conflicts of interest. They must ensure that their reviews are evidence based and free from destructive criticism driven by self interest. It seems likely that ultimately we will progressively move towards 'open' peer review in which both the authors and the reviewers are known to each other. There is an urgent need for increased transparency of the relationship between editors and owners. The events of the last few years indicate that unless this interface is fully understood by all parties, conflicts may arise. There is also a need for a radical overhaul in the relationship between journals, journal editors and the biomedical industry. It is now increasingly accepted that all clinical trials should be registered in a centrally held database and that protocols should include the primary and secondary outcome measures and the intended approach to data analysis thereby avoiding opportunistic post hoc analyses. However, the even more radical proposal that journals should cease to publish clinical trials sponsored by industry deserves wider debate.