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PubMed1985

Increased colonic motility during exposure to a stressful situation.

Colonic smooth muscle spike potentials and contractility were recorded during the periods of stress by a bipolar electrode-perfused catheter apparatus placed in the rectosigmoid colon. Healthy subjects and patients with the irritable colon syndrome (ICS) were exposed to three standardized stressful conditions: (1) ice-water immersion, (2) Stroop stimulus differentiation test, and (3) ball sorting. In healthy controls, colonic motility increased after the first exposure to ice-water immersion (P less than 0.05), Stroop test (P less than 0.05), or ball sorting. Respiratory frequency also increased after exposure to the stressful stimuli. However, repeat exposures to the stress tests did not stimulate colonic motility. An increase in colonic motility occurred in patients with the irritable colon syndrome pretreated with a placebo after exposure to ice water (P less than 0.05), Stroop Test, or ball sorting (P less than 0.05). However, after exposure to the stressful situations patients pretreated with chlordiazepoxide had a diminished increase in colonic motility or in respiratory frequency. These studies suggest: (1) in healthy controls habituation reduces the stress-related increase in colonic motility, and (2) in patients with the irritable colon syndrome, chlordiazepoxide decreases the stress-related increase in colonic motility.

Action Potentials↗
PubMed2002

On-table cecoscopy : a novel diagnostic method in acute diverticulitis of the right colon.

PURPOSE: Controversies abound regarding the optimal surgical management in noncomplicated diverticulitis of the right colon, ranging from a conservative approach to diverticulectomy to right hemicolectomy. One of the arguments for resection is to exclude carcinoma. However, there is significant morbidity associated with resection. We aim to introduce on-table cecoscopy as a tool to improve the diagnosis of acute diverticulitis of the right colon, exclude carcinoma, and reduce the rate of resection. METHODS: From October 1999 to June 2000, five patients presented to our unit with suspected acute appendicitis. Intraoperatively, we found a colonic inflammatory mass at either the cecum or the ascending colon. The cecum and ascending colon were mobilized, and bowel clamps were applied to the ascending colon and ileum. A bronchoscope (Olympus(R) BF-P200) was introduced through the appendix stump. To achieve a good endoscopic view, a limited volume of air was introduced through the working channel. RESULTS: After on-table cecoscopy, all the patients were diagnosed as having acute nonperforated diverticulitis of the right colon. They received appendicectomy, and the diverticulitis was managed conservatively. They were treated with a course of cephalosporin and metronidazole. We performed colonoscopy four weeks later and confirmed that none of them had carcinoma of the colon. CONCLUSIONS: On-table cecoscopy is a new, safe, and effective means of diagnosing acute diverticulitis of the right colon. We can confidently exclude carcinoma and reduce the amount of colonic resection in patients with noncomplicated diverticulitis of the right colon.

Acute Disease↗
PubMed1994

Escherichia coli heat-stable toxin receptors in human colonic tumors.

BACKGROUND/AIMS: Escherichia coli heat-stable enterotoxins (ST) are small peptides of 18 or 19 amino acids that bind to specific cell surface receptors located on the intestinal brush border and activate guanylate cyclase, resulting in an increase in the intracellular cyclic guanosine 3',5'-monophosphate content of the cell. The present study examined whether receptors for ST are expressed by primary and metastatic human colonic tumors in vivo. METHODS: Plasma membranes prepared from surgical tissue samples from normal colon, liver and lung, primary colonic adenocarcinomas, and colon carcinomas metastatic to lung and liver were analyzed for the structural and functional characteristics of constituent ST receptors. RESULTS: All primary and metastatic colonic tumors examined bound ST, showing receptors of high (pmol/L) and low (nmol/L) affinity with densities that were similar to those in normal colon. Also, affinity cross-linking of labeled ST to membranes showed similar binding proteins in primary and metastatic tumors and normal colon. ST binding and affinity-labeled proteins were not detected in normal extraintestinal tissues. Guanylate cyclase was activated by ST in membranes from all colonic tumors studied, with efficacies and potencies that were similar to those in normal colon. ST did not activate this enzyme in normal extraintestinal tissues. CONCLUSIONS: Receptors for ST are expressed by primary and metastatic human colonic tumors in vivo, with structural and functional characteristics that are similar to those in normal human colon.

Adenocarcinoma↗
PubMed1991

Identification and quantification of aberrant crypt foci and microadenomas in the human colon.

The objective of the present study was to determine whether aberrant crypt foci (ACF) similar to those observed in the colons of experimental animals exposed to colon carcinogens could be identified and quantified in the human colon. Twenty-seven colon resections from patients affected by familial adenomatous polyposis (FAP, five cases), colorectal cancer (CRC, 12 cases), and benign diseases of the large bowel (BD, 10 cases) were collected from a pathology repository or immediately after operation. Ten or more 1-cm2 formalin-fixed, methylene-blue--stained samples of colonic mucosa from each colon were scored under light microscopy for ACF. The number of ACF per cm2 and the number of crypts per ACF for each colon were calculated. The average number of ACF per cm2 in the FAP group (20 +/- 19, mean +/- SD) was significantly higher (P less than 0.01) than those of the CRC (0.37 +/- 0.41) and BD (0.18 +/- 0.35) groups. At least one ACF was found in every colon resection from CRC patients and in six out of 10 colon resections from the BD group. The average number of crypts per ACF ranged from five to 35 with absolute values from 1 to over 100. Fifty-five histologic specimens, 43 with ACF of various size and 12 without, were prepared by sectioning the colon parallel to the mucosal surface. There was a close correlation between the number of crypts per ACF in each specimen as scored by methylene-blue and histologic examination. Twenty-six aberrant crypt foci displayed dysplasia as evident by histologic analysis. In these instances we feel the term microadenoma is appropriate and, using this unique approach of examining the human colon, they can be easily identified and quantified. These lesions may well be precursors for adenomatous polyps and colorectal cancer.

Adenoma↗
PubMed1991

Colonic motility in humans--a growing understanding.

As yet, there is limited information about the relationship of colonic motility to colonic flow or transit. The overall flow in the colon is slow and highly variable. The measurement of total and segmental transit time is essential for the differentiation of motor disorders associated with delayed transit. Rapid movements of colonic contents (mass movements) occur only a few times during the day. Their motor equivalent is the giant contraction which migrates in the aborad direction at relatively high velocity. Motor activity in the colon is highly variable, with periods of contraction and motor quiescence. Contractions occur at different frequencies ranging from 2 to 13 cycles per minute. High frequency contractions are stationary. Their myoelectrical equivalent is short spike bursts. Long spike bursts result in sustained, low frequency contractions, which may migrate in both directions. Technological advances now make it possible to obtain ambulant manometric recordings from the colon for 24 h. Such studies show a circadian variation in colonic motility with increases of activity after meals and after awakening. Motor disorders of the colon are not associated with specific abnormal motor patterns. Rather, they are due to changes in the occurrence of motor patterns seen in health. In constipated patients with slow colonic transit the suppression of strong peristaltic activity is the most plausible common pathogenetic mechanism. In diarrhoeal states, propulsive activity such as the giant migrating contractions may be a major mechanism which promotes the passage of stools. There is no agreement that there is disordered basal colonic motor activity in IBS. There is, however, increasing evidence that in IBS the colon responds abnormally to eating, certain forms of stress and distension, and that this may relate to symptoms. The psychopathology of IBS patients is apparently the most important factor in the health care-seeking behaviour of the patients. No specific therapy has yet been shown to be convincingly effective.

Colon↗
PubMed1986

Obstructing malignant lesions of the colon.

Evidence has been presented to suggest that the patient with an obstructed carcinoma of the colon may have a more malignant form of the disease independent of lymph node status or tumor encirclement of the bowel. Rate of tumor growth is never consistent in patients with this disease. Patients who develop colon obstruction early in the course of the disease seem to have more aggressive tumors with rapid growth and a much poorer long-term prognosis. Perforations frequently accompany obstructions of the colon. Patients in this group have a dismal prognosis. Individuals with obstructed carcinoma of the colon have a higher operative mortality and morbidity and a shorter long-term survival. The higher operative mortality and morbidity may depend entirely on the choice of operative procedures. Tumor location affects prognosis. Obstructing tumors in the left colon have a more favorable prognosis than those in the right colon. Obstructing right colon tumors have a much poorer survival (three times worse) than nonobstructing carcinomas of the right colon. Obstructing tumors in the rectum have a very poor prognosis. Evidence exists that resection of the tumor without preliminary proximal decompression may reduce hospital mortality and morbidity and increase long-term survival. In selected cases, primary resection can be done as safely as staged operative procedures. Primary anastomosis with resection of the left colon carries a higher operative mortality because of anastomotic leaks. Resection without anastomosis is much safer. Primary resection with anastomosis is the procedure of choice in obstructing lesions of the right colon. This has a lower operative mortality and morbidity than a staged procedure. This primary resection with anastomosis is certainly as safe as an ileotransverse colostomy. It is important not to abandon the time-honored surgical principle of never suturing obstructed bowel. Primary resection without anastomosis confirms this surgical principle. Meticulous preoperative and postoperative care employing physiological monitoring, multiple antibiotics, total parenteral hyperalimentation, and respiratory and circulatory support will further reduce the hospital mortality and morbidity. Patients who initially appear to be obstructed on barium enema, but who in truth are only partially obstructed, can be properly managed so that an elective primary resection with anastomosis can be done with the same operative mortality and morbidity as in other elective colon cancer patients.

Aged↗
PubMedDate not supplied

Automatic segmentation of the colon for virtual colonoscopy.

Virtual colonoscopy is a minimally invasive technique that enables early detection of colorectal polyps and cancer. Normally, a patient's bowel is prepared with colonic lavage and gas insufflation prior to computed tomography scanning. An important step for 3D analysis of the image volume is segmentation of the colon. The high-contrast gas/tissue interface that exists in the colon lumen makes segmentation of the majority of the colon relatively easy; however, two factors inhibit automatic segmentation of the entire colon. First, the colon is not the only gas-filled organ in the data volume: lungs, small bowel, and stomach also meet this criterion. User-defined seed points placed in the colon lumen have previously been required to spatially isolate the colon. Second, portions of the colon lumen may be obstructed by peristalsis, large masses, and/or residual feces. These complicating factors require increased user interaction during the segmentation process to isolate additional colonic segments. To automate the segmentation of the colon, we have developed a method to locate seed points and segment the gas-filled lumen sections without user supervision. We have also developed an automated approach to improve lumen segmentation by digitally removing residual contrast-enhanced fluid. Experimental results with 20 patient volumes show that our method is accurate and reliable.

Algorithms↗
PubMed1984

Conjugation of 1-naphthol by human colon and tumour tissue using different experimental systems.

The metabolism of 1-naphthol, a model phenolic substrate, to its glucuronic acid and sulphate ester conjugates has been studied in short-term organ cultures of normal human colon and tumour tissue, subcellular fractions of these tissues, human colonic tumour cell lines and human colonic tumour xenografts. Normal colonic tissue, in short-term organ culture, formed more 1-naphthyl sulphate than glucuronic acid conjugates. In contrast the colonic tumours, under the same conditions, produced more 1-naphthyl beta-D-glucuronide than 1-naphthyl sulphate. A marked interindividual variation in sulphate ester and glucuronic acid conjugation was noted in both normal and tumorous colon. The conjugation of 1-naphthol was also investigated, using subcellular fractions, where the metabolism found with normal colon reflected that observed utilizing short-term organ culture, but that from colonic tumour samples did not. Cell lines derived from human colonic adenocarcinomas metabolised 1-naphthol almost exclusively to its glucuronic acid conjugate. Xenografts derived from human colonic tumours formed similar conjugates to surgical samples in culture. Thus somewhat different results were obtained dependent on the experimental model chosen. However, in all colonic tumour systems studied, when the cells remained intact and where tissue architecture was maintained, 1-naphthol was metabolised predominantly to its glucuronic acid conjugate.

Animals↗
PubMed2002

The use of minimal preparation computed tomography for the primary investigation of colon cancer in frail or elderly patients.

AIM: To assess the place of computed tomography (CT) of the colon in frail or elderly patients with symptoms suggestive of colon cancer. METHOD: A total of 195 patients (median age 76 years) underwent CT of the abdomen and pelvis following the administration of positive oral contrast medium but no bowel preparation. All had symptoms suggestive of colon cancer. CT findings were classified as normal/diverticular disease (DD), possible colon cancer, definite colon cancer or extracolonic pathology. Accuracy of CT was assessed against patient outcome. Association between symptoms and colon cancer was assessed by chi-squared test. RESULTS: There were 47 deaths and median follow up for those alive was 16 months. Overall sensitivity of CT was 100% and specificity 87% for detection of colon cancer. One hundred and ten normal/DD CT examinations had no significant bowel lesion on follow up. Of 12 cases defined as 'definite cancers' on CT, there were nine colon cancers, two extracolonic cancers, and one normal. Of 23 'possible cancers' on CT, there were two colon cancers, three DD masses and 18 normal/DD. Fifty examinations had extracolonic findings including 33 (17%) cases of significant abdominal disease. CT findings led to a halt in investigations in 115 cases (59%), colonoscopy in 18 (9%) cases and surgery in 16 (8%) cases. None of the symptoms present showed a significant association with colon cancer (all P > 0.05). CONCLUSION: Minimal preparation CT is a non-invasive and sensitive method for investigating colon cancer in frail or elderly patients. It has a 100% negative predictive value and also detects a large number of extracolonic lesions.

Aged↗
PubMed2004

Colonic transit time in long-term dialysis patients.

BACKGROUND: Constipation is a frequent health concern for long-term dialysis patients. The increased incidence of constipation in long-term dialysis patients is based mainly on self-reported data. Our aim is to investigate this problem objectively by using colonic transit time in long-term hemodialysis (HD) and continuous ambulatory peritoneal dialysis (CAPD) patients. METHODS: Segmental and total colonic transit time studies measured by means of radiopaque markers were conducted in 56 HD patients, 63 CAPD patients, and 25 healthy control subjects. Segmental colonic transit times were calculated separately for 3 segments of the colon (right, left, and rectosigmoid) and total transit time, which was the sum of all 3 segment times. RESULTS: Colonic transit time was significantly prolonged in HD patients (43.0 +/- 22.2 versus 32.7 +/- 13.7 hours in CAPD patients and 24.3 +/- 11.9 hours in controls; P < 0.001). Increased colonic transit times in the right and rectosigmoid segments, but not the left segment, contributed to the prolongation in total colonic transit time. Age and interdialytic weight gain correlated well with prolongation of total and segmental colonic transit times in HD patients (P < 0.01). Diabetes and female sex in all groups were associated with longer total and segmental colonic transit times, but this trend was not statistically significant. CONCLUSION: Total, right segmental, and rectosigmoid segmental colonic transit times are prolonged in long-term HD patients compared with CAPD patients and healthy controls. We believe colonic transit time measurement is helpful to tailor therapy because it helps define the pathogenesis of constipation.

Adult↗
PubMed2004

Bone morphogenetic protein 2 is expressed by, and acts upon, mature epithelial cells in the colon.

BACKGROUND AND AIMS: The recent findings of bone morphogenetic protein (BMP) receptor Ia mutations in juvenile polyposis and frequent Smad4 mutations in colon cancer suggest a role for BMPs in the colonic epithelium and colon cancer. We investigated the role of BMP2 in the colon. METHODS: We assessed BMP receptor expression in cell lines using the reverse-transcribed polymerase chain reaction and immunoblotting. We investigated the effect of BMP2 on cell lines using the MTT assay and by immunoblotting for markers of differentiation, proliferation, and apoptosis. We assessed the expression of BMP2, its receptors, and signal transduction elements in mouse and human colon tissue using immunohistochemistry. We also investigated the effect of the BMP antagonist noggin in vivo in mice by assessing colon tissue with immunohistochemistry and immunoblotting. Finally, we investigated the expression of BMP2 in microadenomas from familial adenomatous polyposis patients. RESULTS: BMP receptors (BMPR) Ia, BMPR Ib, and BMPR II are all expressed in colonic epithelial cell lines. BMP2 inhibits colonic epithelial cell growth in vitro, promoting apoptosis and differentiation and inhibiting proliferation. BMP2, BMPRIa, BMPRIb, BMPRII, phosphorylated Smad1, and Smad4 are expressed predominantly in mature colonocytes at the epithelial surface in normal adult human and mouse colon. Noggin inhibits apoptosis and proliferation in mouse colonic epithelium in vivo. BMP2 expression is lost in the microadenomas of familial adenomatous polyposis patients. CONCLUSIONS: These data suggest that BMP2 acts as a tumor suppressor promoting apoptosis in mature colonic epithelial cells.

Adenomatous Polyposis Coli↗
PubMedDate not supplied

Use of pelvic flexure biopsies to predict survival after large colon torsion in horses.

OBJECTIVE: To determine if morphologic evaluation of intraoperative biopsies of the large colon could be used to accurately predict outcome in horses with large colon torsion. STUDY DESIGN: Clinical study. ANIMALS: Fifty-four horses with large colon torsion. METHODS: A full-thickness biopsy was collected from the pelvic flexure of the ascending colon after correction of naturally occurring colonic torsion. Morphologic changes were evaluated and graded for interstitial tissue to crypt ratio (I:C ratio), percentage loss of superficial and glandular epithelium, and the degree of hemorrhage and edema. These variables were then used to predict survival. RESULTS: Morphologic variables could be used to correctly predict survival or death in 51 horses (P < .0001). This corresponded to a sensitivity of 95.1% (82.2%-99.2%; 95% CI) and a specificity of 92.3% (62.0%-99.6%; 95% CI). Of 6 horses that had colonic resection, 5 survived; an accurate prediction of outcome based on morphologic criteria was made for each horse. CONCLUSIONS: Interpretation of changes in colonic morphology can be used to accurately predict postoperative survival in horses with large colon torsion. CLINICAL RELEVANCE: Use of frozen colonic tissue sections is a rapid, reliable, and relatively inexpensive method for assessing morphologic damage associated with large colon torsion during surgery. Intraoperative evaluation of pelvic flexure biopsies can aid in the prediction of survival and guide surgical judgment as to the need for colonic resection.

Animals↗
PubMed2006

15-Hydroxyprostaglandin dehydrogenase is an in vivo suppressor of colon tumorigenesis.

15-Hydroxyprostaglandin dehydrogenase (15-PGDH) is a prostaglandin-degrading enzyme that is highly expressed in normal colon mucosa but is ubiquitously lost in human colon cancers. Herein, we demonstrate that 15-PGDH is active in vivo as a highly potent suppressor of colon neoplasia development and acts in the colon as a required physiologic antagonist of the prostaglandin-synthesizing activity of the cyclooxygenase 2 (COX-2) oncogene. We first show that 15-PGDH gene knockout induces a marked 7.6-fold increase in colon tumors arising in the Min (multiple intestinal neoplasia) mouse model. Furthermore, 15-PGDH gene knockout abrogates the normal resistance of C57BL/6J mice to colon tumor induction by the carcinogen azoxymethane (AOM), conferring susceptibility to AOM-induced adenomas and carcinomas in situ. Susceptibility to AOM-induced tumorigenesis is mediated by a marked induction of dysplasia, proliferation, and cyclin D1 expression throughout microscopic aberrant crypt foci arising in 15-PGDH null colons and is concomitant with a doubling of prostaglandin E(2) in 15-PGDH null colonic mucosa. A parallel role for 15-PGDH loss in promoting the earliest steps of colon neoplasia in humans is supported by our finding of a universal loss of 15-PGDH expression in microscopic colon adenomas recovered from patients with familial adenomatous polyposis, including adenomas as small as a single crypt. These models thus delineate the in vivo significance of 15-PGDH-mediated negative regulation of the COX-2 pathway and moreover reveal the particular importance of 15-PGDH in opposing the neoplastic progression of colonic aberrant crypt foci.

Animals↗
PubMed1995

Chemopreventive effects of calcium but not aspirin supplementation in cholic acid-promoted colon carcinogenesis: correlation with intermediate endpoints.

Epidemiological studies have suggested that increased intake of calcium (Ca) or aspirin (ASA) is associated with a reduced risk for colon cancer. To delineate a possible mechanism of action, the present study used male F344 rats in an azoxymethane (AOM)-induced colon tumor model to study the single and interactive effects of Ca and ASA on cholic acid-promoted experimental colon carcinogenesis. Following initiation with AOM, a promotion diet containing 0.5% cholic acid was fed for 34 weeks until the adenoma development stage. Cholic acid was used as a surrogate for high-fat diets and to promote carcinogenesis. Diets were supplemented with CaCO3 (2% Ca by weight), 250 p.p.m. ASA, or both. After 34 weeks, the diets were switched during the progression stage and rats were killed at week 51. Several intermediate endpoints were examined during the course of AOM carcinogenesis to determine their reliability as predictors of colon cancer risk. Intermediate endpoints included colon crypt height measurement, colon mucosal ornithine decarboxylase (ODC) and colon mucosal protein kinase C (PKC) activities. The biomarkers were examined at the beginning of the study at 2 weeks, and thereafter at 5, 15, 30 and 40 weeks of dietary treatment. Animals were necropsied at week 51 and tumor incidence and numbers were analyzed for correlation with biomarkers. Survival was highest in the group fed CaCO3 during the promotion stage and tumor burden was lowest in groups fed CaCO3 during this stage. Supplementation during the progression stage was ineffective. The cholic acid promotion model resulted in increased ODC which was inhibited by intervention during the promotion stage with Ca, but not ASA. PKC was also activated by cholic acid feeding, and this effect was modulated by intervention in the promotional stage with Ca or ASA. Colon tumor incidence and burden was increased by cholic acid promotion and decreased by Ca, but not affected by ASA. In summary, Ca is a more effective chemopreventive agent in cholic acid-promoted colon carcinogenesis than ASA, impacting both incidence and tumor number. Colonic ODC, but not PKC may be a suitable predictor of risk and response in chemoprevention trials for colon cancer.

Animals↗
PubMed1999

Chemoprevention of colonic aberrant crypt foci by an inducible nitric oxide synthase-selective inhibitor.

Inducible nitric oxide synthase (iNOS) is overexpressed in colonic tumors of humans and also in rats treated with a colon carcinogen. iNOS appear to regulate cyclooxygenase-2 (COX-2) expression and production of proinflammatory prostaglandins, which are known to play a key role in colon tumor development. Experiments were designed to study the inhibitory effects of S,S'-1,4-phenylene-bis(1,2-ethanediyl)bis-isothiourea (PBIT) a selective iNOS-specific inhibitor, measured against formation of azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF). Beginning at 5 weeks of age, male F344 rats were fed experimental diets containing 0 or 50 p.p.m. of PBIT, or 2000 p.p.m. of curcumin (non-specific iNOS inhibitor). One week later, rats were injected s.c. with AOM (15 mg/kg body wt, once weekly for 2 weeks). At 17 weeks of age, all rats were killed, colons were evaluated for ACF formation and colonic mucosa was assayed for isoforms of COX and NOS activities. Both COX and iNOS activities in colonic mucosa of the AOM-treated rats were significantly induced. Importantly, 50 p.p.m. PBIT suppressed AOM-induced colonic ACF formation to 58% (P < 0.0001) and crypt multiplicity containing four or more crypts per focus to 78% (P < 0.0001); it also suppressed AOM-induced iNOS activity. Curcumin inhibited colonic ACF formation by 45% (P < 0.001). These observations suggest that iNOS may play a key regulatory role in colon carcinogenesis. Developing iNOS-specific inhibitors may provide a selective and safe chemopreventive strategy for colon cancer treatment.

Animals↗
PubMed2003

Abnormal levels of neuropeptide Y and peptide YY in the colon in irritable bowel syndrome.

OBJECTIVE: To assess the levels of gut peptides involved in gastrointestinal motor, secretory and sensory function in colonic biopsies in irritable bowel syndrome (IBS) patients and healthy controls. METHODS: We studied 34 patients with IBS and 15 subjects without gastrointestinal symptoms. The predominant bowel pattern in the IBS patients was constipation in 17 patients (IBS-C) and diarrhoea in 17 patients (IBS-D). With radioimmunoassay, the levels of vasoactive intestinal peptide (VIP), substance P, neuropeptide Y (NPY) and peptide YY (PYY) were analysed in biopsies from the descending colon and ascending colon obtained during colonoscopy. RESULTS: The IBS patients had lower levels of PYY in the descending colon than the controls, but the levels in the ascending colon did not differ. The NPY levels were lower in IBS-D than in IBS-C, both in the ascending colon and in the descending colon. Low levels of VIP were more common in IBS patients, but mean levels did not differ between groups. No group differences were observed for substance P. The levels of VIP, substance P and NPY were higher in the ascending colon than in the descending colon, whereas the opposite pattern was seen for PYY. CONCLUSION: IBS patients demonstrate lower levels of PYY in the descending colon than controls. Colonic NPY levels differ between IBS subgroups based on the predominant bowel pattern. These findings may reflect the pathophysiology of IBS and the symptom variation within the IBS population.

Adult↗
PubMed2003

Colonic manometry in children with defecatory disorders. role in diagnosis and management.

OBJECTIVE: The aim of this study was to evaluate the role of colonic manometry in clarifying pathophysiology of childhood defecatory disorders and to evaluate its impact on management. METHODS: We conducted a retrospective review of medical records of children referred to undergo colonic manometry to a tertiary care Motility Center from 1996 to 2001. Families were followed up a median of 20 months after evaluation (range 3-60 months). RESULTS: A total of 150 colonic manometries were performed in 146 children (74 male, median age 79 months, range 4-225 months). Colonic manometry had been requested to clarify the pathophysiology of lower GI symptoms in 68%; as part of diagnostic workup for chronic intestinal pseudo-obstruction in 11%; to decide about reanastomosis of a diverted colon in 7%; and to clarify the pathophysiology of persisting symptoms after surgery for Hirschsprung's disease in 14%. Normal motility was found in the entire colon in 38% of children. In 17%, there was normal motility in the proximal colon with abnormality limited to the dilated distal colon. Abnormal motility was found in 45% of children. After colonic manometry, treatment changes were recommended in 93% of patients. We were able to follow up 65% of the families. When recommendations were followed (96% of the contacted patients), the symptoms improved in 78%, were unchanged in 18%, and were worse in 4% of patients. Among the parents, 88% believed that the suggestions given after colonic manometry had been helpful in improving their children's health. CONCLUSIONS: Colonic manometry may provide information useful in guiding therapy in a subgroup of patients with defecatory disorders.

Adolescent↗
PubMed2002

Pregabalin (CI-1008) inhibits the trinitrobenzene sulfonic acid-induced chronic colonic allodynia in the rat.

In human, digestive disorders are often associated with visceral pain. In these pathologies, visceral pain threshold is decreased indicating a visceral hypersensitivity. Pregabalin [CI-1008; S-(+)-3-isobutylgaba] presents antihyperalgesic actions in inflammatory somatic pain models. This study was designed to evaluate 1) the effect of injection of TNBS into the colon on visceral pain threshold, and 2) the antihyperalgesic effect of pregabalin on TNBS-induced chronic colonic allodynia. A significant decrease in the colonic pain threshold was observed in trinitrobenzene sulfonic acid (TNBS)-treated animals (17.8 +/- 1.27 versus 43.4 +/- 1.98 mm Hg). Pregabalin (30-200 mg/kg s.c.) and morphine (0.1-1 mg/kg s.c.) showed a dose-related inhibition of TNBS-induced colonic allodynia. Pregabalin did not inhibit the colonic inflammatory effect of TNBS. In normal conditions (control animals), morphine (0.3 mg/kg s.c.) significantly increased the colonic pain threshold, whereas pregabalin (200 mg/kg s.c.) did not modify the colonic pain threshold. Pregabalin suppressed the TNBS-induced colonic allodynia but did not modify the colonic threshold in normal conditions. The ability of pregabalin to block the chronic colonic allodynia indicates that it is effective in abnormal colonic hypersensitivity, suggesting a possible effect in chronic pain in irritable bowel syndrome.

Analgesics, Opioid↗