The discovery of a series of genetic and serological markers associated with disease susceptibility and phenotype in inflammatory bowel disease has led to the prospect of an integrated classification system involving clinical, serological and genetic parameters. The Working Party has reviewed current clinical classification systems in Crohn's disease, ulcerative colitis and indeterminate colitis, and provided recommendations for clinical classification in practice. Progress with respect to integrating serological and genetic markers has been examined in detail, and the implications are discussed. While an integrated system is not proposed for clinical use at present, the introduction of a widely acceptable clinical subclassification is strongly advocated, which would allow detailed correlations among serotype, genotype and clinical phenotype to be examined and confirmed in independent cohorts of patients and, thereby, provide a vital foundation for future work.

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Toward an Integrated Clinical, Molecular and Serological Classification of Inflammatory Bowel Disease: Report of a Working Party of the 2005 Montreal World Congress of Gastroenterology

Evidence for the occurrence of microbial breakdown of carbohydrate in the human colon has been sought by measuring short chain fatty acid (SCFA) concentrations in the contents of all regions of the large intestine and in portal, hepatic and peripheral venous blood obtained at autopsy of sudden death victims within four hours of death Total SCFA concentration (mmol/kg) was low in the terminal ileum at 13 +/- 6 but high in all regions of the colon ranging from 131 +/- 9 in the caecum to 80 +/- 11 in the descending colon The presence of branched chain fatty acids was also noted A significant trend from high to low concentrations was found on passing distally from caecum to descending colon pH also changed with region from 56 +/- 02 in the caecum to 66 +/- 01 in the descending colon pH and SCFA concentrations were inversely related Total SCFA (mumol/l) in blood was, portal 375 +/- 70, hepatic 148 +/- 42 and peripheral 79 +/- 22 In all samples acetate was the principal anion but molar ratios of the three principal SCFA changed on going from colonic contents to portal blood to hepatic vein indicating greater uptake of butyrate by the colonic epithelium and propionate by the liver These data indicate that substantial carbohydrate, and possibly protein, fermentation is occurring in the human large intestine, principally in the caecum and ascending colon and that the large bowel may have a greater role to play in digestion than has previously been ascribed to it

https://gut.bmj.com/content/gutjnl/28/10/1221.full.pdf

Short chain fatty acids in human large intestine, portal, hepatic and venous blood.

Part two of this three-part series commences with anomalous dominance and special talents. Part one appears in a previous issue of theArchives. 1 ANOMALOUS DOMINANCE AND SPECIAL TALENTS According to our hypothesis, slowed growth within certain zones of the left hemisphere is likely to result in enlargement of other cortical regions, in particular, the homologous contralateral area, but also adjacent unfaffected regions. The influences that favor anomalous dominance may thus favor talents associated with superior development of certain regions either in the right hemisphere or in adjacent parts of the left hemisphere. Even with excessive retardation of growth and the resultant migration abnormalities and learning disorders (LD), high talents may exist as a result of compensatory enlargement of other cortical regions. Several types of data are in concordance with these conclusions. Several studies have claimed that the average level of spatial talents is higher in male subiects. 2 Hier

https://jamanetwork.com/journals/jamaneurology/articlepdf/584161/archneur_42_5_008.pdf

Cerebral lateralization. Biological mechanisms, associations, and pathology: II. A hypothesis and a program for research.

The Brush Foundation studies on human growth and development, begun in 1931 and terminated in 1942, have been intensively reviewed and studied by Dr Greulich and Miss Pyle in the formulation of this Radiographic Atlas of Skeletal Development of the Hand and Wrist Serial radiographs of from 2 to 20 hand-films made at successive examinations of each of 1000 boys and girls made up the radiographic material Standards were selected that were judged to be the most representative of the central tendency or anatomic mode of each chronologic age group from birth through 18 years

Radiographic Atlas of Skeletal Development of the Hand and Wrist

This paper is the second in a series of three publications relating to the European evidence-based consensus on the diagnosis and management of Crohn's disease and concerns the management of active disease, maintenance of medically induced remission and surgery. The aims and methods of the ECCO Consensus, as well as sections on diagnosis and classification are covered in the first paper [van Assche et al. JCC 2009a]. The final paper covers post-operative recurrence, fistulating disease, the management of paediatric and adolescent IBD, pregnancy, psychosomatics, extraintestinal manifestations and complementary or alternative therapy for Crohn's disease [Van Assche et al JCC 2009b]. #### Principal changes with respect to the 2006 ECCO guidelines

The early use of azathioprine/mercaptopurine or methotrexate in combination with steroids is an appropriate option in moderately active localised ileocaecal CD. Anti-TNF therapy should be considered as an alternative for patients with objective evidence of active disease who have previously been steroid-refractory, steroid-dependent, or steroid-intolerant (based on Statement 5B).

For those patients with severely active localised ileocaecal Crohn's disease and objective evidence of active disease who have relapsed, anti-TNF therapy with or without an immunomodulator is an appropriate option [EL1a, RG B for infliximab]. For some patients who have infrequently relapsing disease, restarting steroids with an immunomodulator may be appropriate (based on Statement 5C).

All currently available anti-TNF therapies appear to have generally similar efficacy and adverse-event profiles for inflammatory (‘luminal’) Crohn's disease, so the choice depends on availability, route of delivery, patient preference, cost and national guidelines \[EL5, RG D\] (Statement 5I).

Patients receiving azathioprine or mercaptopurine who relapse should be evaluated for adherence to therapy and have their dose optimised. Changing their maintenance therapy to methotrexate [EL1b RG B] or anti-TNF therapy [EL1a RGB] should be considered. Surgery should always be considered as an option in localised disease [EL4, …

/pdf/the-second-european-evidence-based-consensus-on-the-2blhqp1c4c.pdf

The second European evidence-based Consensus on the diagnosis and management of Crohn's disease: Current management

Double-blind withdrawal trial of azathioprine as maintenance treatment for crohn's disease

Controlled trial of azathioprine in crohn's disease

Using a pH-sensitive radiotelemetering device the effect of lactulose on luminal pH in the ileum, colon, and rectum has been compared with that of two other laxative agents. Lactulose produced marked acidification of proximal colonic contents but this effect was not consistently maintained into the distal colon. Sodium sulphate acidified distal rather than proximal colonic contents. However, for a similar degree of laxation it was not possible to produce a significantly more uniform reduction of pH along the length of the colon by combining these laxatives compared with lactulose alone. Magnesium sulphate had little effect upon luminal pH except in the rectum where a significant rise occurred. These results are discussed in relation to both normal colonic physiology and to their possible relevance to the treatment of chronic hepatic encephalopathy by colonic acidification.

https://gut.bmj.com/content/gutjnl/15/12/999.full.pdf

Effects of lactulose and other laxatives on ileal and colonic pH as measured by a radiotelemetry device

Site of pain from the irritable bowel

Bacterial growth and the production of ammonia from urea and by deamination of peptone has been examined at various pHs in both conventional static bacterial cultures and in a continuous cultivation system. Growth occurred on primary testing of 93 out of 100 strains of aerobic Gram-negative bacteria at pH 5, and 48 out of 50 strains of Esch. coli at pH 4.6. Hydrolysis of urea by Proteus mirabilis decreased steadily from pH 7.2 to pH 5.3; below pH 5.3 little hydrolysis occurred. Ammonia production from peptones by Esch. coli decreased from pH 7.2 to pH 4.6. Considerable variation was noted in the ability of different strains to produce ammonia. Experiments with cultures containing both Esch. coli and Pr. mirabilis showed that more ammonia was produced at low pH than was produced by cultures of single organisms. At low pH reduction in the count of organisms was not found to be an essential prerequisite for reduction of ammonia formation.

https://gut.bmj.com/content/gutjnl/14/3/171.full.pdf

A. M. Dawson

Papers

Double-blind withdrawal trial of azathioprine as maintenance treatment for crohn's disease

Controlled trial of azathioprine in crohn's disease

Effects of lactulose and other laxatives on ileal and colonic pH as measured by a radiotelemetry device

Site of pain from the irritable bowel

Ammonia production by intestinal bacteria