Robin Spiller, Editor IMPAIRED TONIC RESPONSE TO EATING IN IBS
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Robin Spiller, Editor IMPAIRED TONIC RESPONSE TO EATING IN IBS Patients with irritable bowel syndrome (IBS) often report exacerbation of symptoms after eating. Previous studies that have suggested an increased reactivity in IBS used very substantial (1000 kcal) meals and studied the response within the rectum. This study differs because it used a much smaller meal (200 kcal) and a barostat balloon was positioned at least 12 cm from the anal margin. While healthy volunteers all showed a rapid increase in tone as shown by an average 38% reduction in the barostat balloon volume, IBS patients with constipation showed little response and those patients with IBS with diarrhoea actually showed a reduction in tone, with the balloon volume rising an average of 35%. A cut off of ,28% increase in tone accurately distinguished patients with IBS from those with organic disease in a separate group of patients. However, when larger meals were used (400/1000 kcal) this difference between IBS and healthy volunteers was lost, all then showing an increase in tone. This striking finding should encourage others to explore the mechanisms underlying these differences. See p 1409 ANTI-INFLAMMATORY ROLE OF MELANOCORTIN RECEPTOR 1 (MC1R) IN INTESTINAL MUCOSA In addition to influencing pigmentation, alpha melanocyte stimulating hormone (aMSH) has anti-microbial and anti-inflammatory actions. There are five receptors, MC1R–MC5R. MC1R has the highest affinity for aMSH and is expressed in a range of cells, including immunocytes and enterocytes. Mice with a frameshift mutation in the MC1R gene (MC1Re/e) lack functional MC1R but appear normal apart from having a yellow coat. However, when these animals were given dextran sodium sulphate (DSS) they developed a much more severe colitis and lost weight more rapidly (see figure). Reconstituting the mutant mice with bone marrow from wild type mice failed to ameliorate DSS colitis, indicating that worsening inflammation is due to loss of MC1R on local mucosal cells rather than bone marrow derived immunocytes. This study raises the possibility of MSH agonists as a treatment for gut inflammation. Furthermore, there are several allelic variants in MCR genes associated with differences in pigmentation. The authors suggest that the distribution of these variants in patients with inflammatory bowel disease should also be examined. See p 1415 NARROW BAND IMAGING FOR ASSESSMENT OF DYSPLASIA IN ULCERATIVE COLITIS SURVEILLANCE Narrow band imaging (NBI) illuminates the mucosa with narrowed bands of the optical spectrum, a technique that enhances the mucosal surface and the network of superficial capillaries, causing adenomas and carcinomas to appear a darker brown than normal mucosa. The current case report is of a 62-year-old man with long standing extensive ulcerative colitis who had multiple lesions noted with high-grade dysplasia but was unable to undergo surgery because of comorbity from Parkinson’s disease. The figure shows the enhanced contrast to be seen using NBI in a lesion which proved to harbour a mucinous adenocarcinoma. The authors simultaneously assessed the pit patterns but found the NBI to be more sensitive. As they point out, the most important features of the NBI system are its ease of use with the ability to switch between white light and NBI at the push of a button. Compared with chromoendoscopy, which relies on pit pattern alone, this new technique has the potential to be more specific in detecting dysplasia in these difficult lesions. See p 1432 Mean rectal volume during fasting and after administration of a 200 kcal meal in constipation predominant IBS and diarrhoea predominant IBS patients, and healthy volunteers. The meal was administered after 30 min of fasting measurement. Data are expressed as mean (SEM). 1.10 1.05 1.00 0.95 0.90 0.85 0.80 0.75 Relative body weight * * * * 7 C57BL/6WT MC1Re/e 0 1 2 3 4 5 6 Days after start of DSS application Weight loss in the DSS colitis model. MC1Re/e mice were more severely affected than controls. C D C shows sessile DALM viewed with white light, D same lesion viewed with NBI. The dysplastic tissue appears darker in contrast with the normal surrounding mucosa. on October 7, 2021 by guest. Protected by copyright. http://gut.bmj.com/ Gut: first published as on 11 September 2006. Downloaded from
Transcript of Robin Spiller, Editor IMPAIRED TONIC RESPONSE TO EATING IN IBS
Robin Spiller, Editor
IMPAIRED TONIC RESPONSE TO EATING IN IBSPatients with irritable bowel syndrome (IBS) often report exacerbation of symptomsafter eating. Previous studies that have suggested an increased reactivity in IBS usedvery substantial (1000 kcal) meals and studied the response within the rectum. Thisstudy differs because it used a much smaller meal (200 kcal) and a barostat balloonwas positioned at least 12 cm from the anal margin. While healthy volunteers allshowed a rapid increase in tone as shown by an average 38% reduction in thebarostat balloon volume, IBS patients with constipation showed little response andthose patients with IBS with diarrhoea actually showed a reduction in tone, with theballoon volume rising an average of 35%. A cut off of ,28% increase in toneaccurately distinguished patients with IBS from those with organic disease in aseparate group of patients. However, when larger meals were used (400/1000 kcal)this difference between IBS and healthy volunteers was lost, all then showing anincrease in tone. This striking finding should encourage others to explore themechanisms underlying these differences.See p 1409
ANTI-INFLAMMATORY ROLE OF MELANOCORTINRECEPTOR 1 (MC1R) IN INTESTINAL MUCOSAIn addition to influencing pigmentation, alpha melanocyte stimulating hormone(aMSH) has anti-microbial and anti-inflammatory actions. There are five receptors,MC1R–MC5R. MC1R has the highest affinity for aMSH and is expressed in a rangeof cells, including immunocytes and enterocytes. Mice with a frameshift mutation inthe MC1R gene (MC1Re/e) lack functional MC1R but appear normal apart fromhaving a yellow coat. However, when these animals were given dextran sodiumsulphate (DSS) they developed a much more severe colitis and lost weight morerapidly (see figure). Reconstituting the mutant mice with bone marrow from wildtype mice failed to ameliorate DSS colitis, indicating that worsening inflammation isdue to loss of MC1R on local mucosal cells rather than bone marrow derivedimmunocytes. This study raises the possibility of MSH agonists as a treatment forgut inflammation. Furthermore, there are several allelic variants in MCR genesassociated with differences in pigmentation. The authors suggest that thedistribution of these variants in patients with inflammatory bowel disease shouldalso be examined.See p 1415
NARROW BAND IMAGING FOR ASSESSMENT OFDYSPLASIA IN ULCERATIVE COLITIS SURVEILLANCENarrow band imaging (NBI) illuminates the mucosa with narrowed bands of theoptical spectrum, a technique that enhances the mucosal surface and the network ofsuperficial capillaries, causing adenomas and carcinomas to appear a darker brownthan normal mucosa. The current case report is of a 62-year-old man with longstanding extensive ulcerative colitis who had multiple lesions noted with high-gradedysplasia but was unable to undergo surgery because of comorbity from Parkinson’sdisease. The figure shows the enhanced contrast to be seen using NBI in a lesionwhich proved to harbour a mucinous adenocarcinoma. The authors simultaneouslyassessed the pit patterns but found the NBI to be more sensitive. As they point out,the most important features of the NBI system are its ease of use with the ability toswitch between white light and NBI at the push of a button. Compared withchromoendoscopy, which relies on pit pattern alone, this new technique has thepotential to be more specific in detecting dysplasia in these difficult lesions.See p 1432
Mean rectal volume during fasting and afteradministration of a 200 kcal meal inconstipation predominant IBS and diarrhoeapredominant IBS patients, and healthyvolunteers. The meal was administered after30 min of fasting measurement. Data areexpressed as mean (SEM).
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Rela
tive
body
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ght * * * *
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C57BL/6WTMC1Re/e
0 1 2 3 4 5 6Days after start of DSS application
Weight loss in the DSS colitis model. MC1Re/emice were more severely affected thancontrols.
C
D
C shows sessile DALM viewed with white light,D same lesion viewed with NBI. The dysplastictissue appears darker in contrast with thenormal surrounding mucosa.
on October 7, 2021 by guest. P
rotected by copyright.http://gut.bm
j.com/
Gut: first published as on 11 S
eptember 2006. D
ownloaded from
CASTING A LIGHT ON THE RISK OF COLORECTALCANCERHereditary non-polyposis colorectal cancer (HNPCC or Lynch syndrome), which isthe commonest form of hereditary colorectal cancer, is caused by mutations in themismatch repair genes. Recent studies suggest abnormalities of the blood vessels inthe oral cavity. This study used photographs of the oral mucosa, which were scannedby an imaging spectrophotometer, to perform reflectance analysis which clearlydiffers between HNPCC and controls (see figure). This difference is thought to reflectalterations in blood vessel geometry. This may in turn relate to abnormalities of theextracellular matrix, which may also increase the risk of developing colorectalcancer. Because family histories are often inadequate, this new marker might beclinically valuable to identify susceptibility to colorectal cancer and allow betterfocusing of the more expensive molecular diagnostic techniques.See p 1436
INCREASED DNA METHYLATION IN THE NORMALMUCOSA OF PATIENTS WITH HYPERPLASTIC POLYPOSISThere are two types of hyperplastic polyposis, one characterised by multiple, small,mainly distal and essentially benign lesions and the other by larger, mainly proximallesions with a predisposition to malignant transformation. This study examinedthree patients with the latter type of lesion who had multiple sessile serratedadenomas (see figure) and at least one colorectal cancer. Becuase methylation andinactivation of the promoter region of the DNA mismatch repair gene MLH1 is a keyrate-limiting step in the development of colorectal cancer, they examinedmethylation of a range of genes in both polyps and cancers and the normalmucosal. There was extensive methylation in the tumours and polyps, but also in thenormal mucosa of patients with the severe phenotype, something that was absent inpatients with sporadic serrated polyps of the proximal colon. The authors speculatethat the mutation of a gene that controls the regulation of DNA methylation couldpredispose to methylation of pro-apoptotic genes, the loss of its activity is thought tounderlie the development of serrated adenomatas polyposis.See p 1467
COINFECTION WITH HIV REDUCES T CELL RESPONSE TOHEPATITIS C VIRUSBecause up to 80% of intravenous drug users and 98% of people with haemophiliaare coinfected with both HIV and hepatitis C virus (HCV, the impact of HIV infectionon the response to HCV is of great importance, especially now that highly activeantiretroviral treatment (HAART) treated patients with HIV are surviving manyyears. This study examined the response to HCV antigens in HCV infectedindividuals both with and without HIV infection. As the figure shows, monoinfectedindividuals had a much stronger response with increased numbers of CD4+ T cellsproducing interferon-c in response to either core or NS3-5 antigens. Coinfectedindividuals also had a much higher HCV viral load. The immune suppression did notappear specific to HCV because the CD4 response to HCV was only found in thosewho also had a response to HIV/P24 antigen. All these patients were studied withoutHAART and further studies are now required to identify means of restoring the HCVspecific CD4+ positive T cell response in these individuals in order to control the HCVinfection and its long term sequelae.See p 1484
A sessile serrated adenoma showing dilatedmucin filled crypts with exaggerated serration
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Oral mucosal light reflectance versuswavelength. Differences between HNPCC andcontrols in the 590–700 nm wavelength range,p,0.0004.
Percentage of individuals who had CD4+ T cellinterferon-c response to HCVantigens ( coreand NS3-5) as assessed by ELISpot.
on October 7, 2021 by guest. P
rotected by copyright.http://gut.bm
j.com/
Gut: first published as on 11 S
eptember 2006. D
ownloaded from
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