The usefulness of factor XIII levels in Crohn's disease.

BACKGROUND AND AIMS: The assessment of inflammatory activity in Crohn's disease (CD) is challenging, and no specific laboratory marker is currently available. Several studies have reported decreased serum factor XIII levels in CD patients as a function of disease activity. We aimed to determine whether the factor XIII level could be a marker for the evolution of CD. METHODS: In this prospective, single-centre trial, 129 patients were included and categorised into two groups: functional bowel disorders (FBDs, n=42) and CD (n=86). The CD group was divided into two subgroups depending on disease activity, as defined by the Crohn's Disease Activity Index score: active disease (CDa, n=41) and disease remission (CDb, n=45). The factor XIII levels were evaluated for each patient. Serial factor XIII levels were evaluated in the patients within the CDa subgroup. RESULTS: The factor XIII levels were significantly different between the FBD (117.69%) and CD (101.89%) groups (p=0.009) but there was no significant difference between the CDa and CDb subgroups (99.04% vs 104.65%, p>0.05), and the levels did not vary during follow-up for the patients in the CDa subgroup. By multivariate analysis, factor XIII levels did not correlate with the time course of disease evolution, CRP, serum fibrin levels, platelet count, disease distribution within the bowel, or the presence of a fistulising form of CD. CONCLUSIONS: Our results confirm that factor XIII levels are decreased in CD patients but cannot be recommended as a marker for the disease activity.

Effect of a corticotropin releasing hormone receptor antagonist on colonic sensory and motor function in patients with irritable bowel syndrome.

BACKGROUND AND AIMS: Corticotropin releasing hormone (CRH) is a major mediator of the stress response in the brain-gut axis. Irritable bowel syndrome (IBS) is presumed to be a disorder of the brain-gut link associated with an exaggerated response to stress. We hypothesised that peripheral administration of alpha-helical CRH (alphahCRH), a non-selective CRH receptor antagonist, would improve gastrointestinal motility, visceral perception, and negative mood in response to gut stimulation in IBS patients. METHODS: Ten normal healthy subjects and 10 IBS patients, diagnosed according to the Rome II criteria, were studied. The tone of the descending colon and intraluminal pressure of the sigmoid colon were measured at baseline, during rectal electrical stimulation (ES), and at recovery after administration of saline. Visceral perception after colonic distension or rectal ES was evaluated as threshold values on an ordinate scale. The same measurements were repeated after administration of alphahCRH (10 micro g/kg). RESULTS: ES induced significantly higher motility indices of the colon in IBS patients compared with controls. This response was significantly suppressed in IBS patients but not in controls after administration of alphahCRH. Administration of alphahCRH induced a significant increase in the barostat bag volume of controls but not in that of IBS patients. alphahCRH significantly reduced the ordinate scale of abdominal pain and anxiety evoked by ES in IBS patients. Plasma adrenocorticotropic hormone and serum cortisol levels were generally not suppressed by alphahCRH. CONCLUSION: Peripheral administration of alphahCRH improves gastrointestinal motility, visceral perception, and negative mood in response to gut stimulation, without affecting the hypothalamo-pituitary-adrenal axis in IBS patients.

Hypothalamic digoxin and irritable bowel syndrome.

BACKGROUND: The hypothalamus produces an endogenous membrane Na+-K+ ATPase inhibitor digoxin that can modulate neurotransmitter transport and may play a role in hemispheric dominance. It can also modulate glycoconjugate synthesis and thus affect synaptic connectivity in the bowel wall. Digoxin could play a role in the genesis of irritable bowel syndrome (IBS). AIM: To study digoxin status in IBS and to correlate it with hemispheric dominance. METHODS: The isoprenoid pathway, tryptophan/tyrosine catabolic patterns and glycoconjugate metabolism were assessed in patients with IBS and in right hemispheric dominant/left hemispheric dominant/bihemispheric dominant individuals. RESULTS: The isoprenoid pathway was upregulated in IBS, with increased HMG CoA reductase activity (0.8 [0.07] vs 0.4 [0.06] in controls; p<0.01), serum digoxin (14.8 [1.0] vs 29.0 [1.2] ng/dL; p<0.01) and dolichol levels (63.8 [3.0] vs 120.3 [3.6] mg/dL; p<0.01). RBC membrane Na+-K+ ATPase activity (3.0 [0.2] vs 1.0 [0.1] microg/p/mg protein; p<0.01), serum magnesium (1.7 [0.1] vs 1.0 [0.1] mg/dL; p<0.01) and ubiquinone (86.4 [5.9] vs 39.8 [1.2] microg/dL; p<0.01) were reduced. There was increase in tryptophan catabolites and reduction in tyrosine catabolites. Serum total glycosaminoglycan and carbohydrate component of glycoproteins were increased in IBS. The activity of glycosaminoglycan degrading enzymes and glycohydrolases were increased. This pattern correlated with those obtained in right hemispheric chemical dominance. CONCLUSION: Hypothalamic digoxin and right hemispheric dominance could play a role in the genesis of irritable bowel syndrome.

Psychological and physiological responses to postprandial mental stress in women with the irritable bowel syndrome.

OBJECTIVE: To investigate the psychological (affective and symptomatic) and physiological (autonomic and cortisol) responses to postprandial mental stress in women with irritable bowel syndrome (IBS). It was hypothesized that patients with IBS would show exaggerated autonomic and cortisol responses to the psychological stressor and that the stressor would enhance gastrointestinal symptoms. METHOD: Twenty-four women with IBS and 20 healthy women participated in the two-day study protocol. Both days were identical, with the exception that on one day, a stressful mental task was completed after ingestion of a standard meal. Heart rate variability, cortisol, affective, and symptomatic responses were measured before and after application of the stressor. RESULTS: Patients with IBS demonstrated increased negative affect at baseline and in response to the stressor. Gastrointestinal symptoms were not affected by the stressor. Appraisal of the stressor by patients with IBS was not different from that of controls. There were no group differences in the autonomic response to the stressor. There was no overall cortisol response to the stressor in either group. CONCLUSIONS: Patients with IBS respond with greater negative affect to postprandial psychological stress as well as to food intake alone, and they can be distinguished from controls on the basis of self-report data. Patients with IBS cannot be differentiated from controls on the basis of the pattern of changes in sympathetic activation after the mental stressor. The stressor used in this study did not elicit a cortisol response in either group.

An exaggerated sensory component of the gastrocolonic response in patients with irritable bowel syndrome.

BACKGROUND/AIMS: Visceral hypersensitivity is a feature of the irritable bowel syndrome (IBS). Postprandial symptoms are common in these patients. The effects of nutrients on colonic perception in IBS are incompletely understood. SUBJECTS: We studied 13 healthy subjects and 16 patients with IBS-eight had diarrhoea predominant (IBS-D) and eight constipation predominant (IBS-C) IBS. METHODS: Colonic perception thresholds to balloon distension and viscerosomatic referral pattern were assessed before and after duodenal infusion of lipid or saline, respectively. At the end of the infusions, plasma levels of gastrointestinal peptides were determined. RESULTS: Lipids lowered the thresholds for first sensation, gas, discomfort, and pain in the IBS group but only for gas in the control group. The percent reduction in thresholds for gas and pain after lipids was greater in the IBS and IBS-D groups but not in the IBS-C group compared with controls. IBS patients had an increased area of referred discomfort and pain after lipids compared with before infusion whereas the referral area remained unchanged in controls. No group differences in colonic tone or compliance were observed. In both groups higher levels of cholecystokinin, pancreatic polypeptide, peptide YY, vasoactive intestinal polypeptide, and neuropeptide Y were seen after lipids. Motilin levels were higher in patients and differences in the subgroups were observed. Levels of corticotrophin releasing factor were lower in the constipated group than in the diarrhoea group. CONCLUSIONS: Postprandial symptoms in IBS patients may be explained in part by a nutrient dependent exaggerated sensory component of the gastrocolonic response.

Effect of a calcium channel blocker and antispasmodic in diarrhoea-predominant irritable bowel syndrome.

BACKGROUND: Irritable bowel syndrome (IBS) is a colonic function disorder. Both pinaverlum bromide (a selective calcium channel blocker) and mebeverine (an antispasmodic) are reported to be effective in the long-term (12-16 weeks) treatment of IBS patients. Their efficacy in the short-term treatment of IBS patients and colonic transit time is unclear. Furthermore, substance P and neuropeptide Y have either excitatory or inhibitory effects on colonic motility. Whether the efficacy of both drugs is mediated through these neuropeptides remains unknown. METHODS AND RESULTS: A clinical trial was conducted with 91 patients with diarrhoea-predominant IBS. After basal measurement of the total colonic transit time, IBS patients were randomized to receive either pinaverlum bromide (50 mg, t.i.d.) or mebeverine (100 mg, t.i.d.) for 2 weeks. The symptomatic scores regarding defaecation, total colonic transit time and serum levels of substance P and neuropeptide Y were measured before and after treatments. The daily defaecation frequency was markedly decreased after treatment (pinaverlum bromide, 2.9+/-1.2 vs 2.0+/-1.0, P< 0.05; mebeverine, 2.7+/-1.1 vs 2.1+/-1.0, P< 0.05). The stool consistency became well formed after both treatments (P< 0.05). Both drugs similarly improved the global well-being in these IBS patients (pinaverlum bromide vs mebeverine 73.4 vs 71.8%, P> 0.05). The total colonic transit time was significantly prolonged only after pinaverlum bromide treatment (21.4+/-15.5 vs 30.8+/-14.8 h, P< 0.01). Neither substance P nor neuropeptide Y serum level was significantly changed after either treatments. CONCLUSION: Pinaverlum bromide and mebeverine have similar therapeutic efficacies on diarrhoea-predominant IBS patients. Prolonged colonic transit time may be one of the factors responsible for the efficacy of pinaverlum bromide on the IBS patients. Substance P and neuropeptideY appear less important in the pathogenesis of diarrhoea-predominant IBS.

G protein levels and function as an objective measure of depression in patients with functional bowel disorders.

Heterotrimeric G proteins play a pivotal role in postreceptor information transduction. These proteins have been implicated in the pathophysiology, diagnosis, and treatment of mood disorders and proposed as a state-dependent biochemical mood marker in mononuclear leukocytes. Irritable bowel syndrome (IBS) is associated with changes in mood, affecting patients' illness perceptions and behavior. We examined whether mononuclear leukocytes of patients with IBS have altered G protein measures. We undertook G protein functional measurements through agonist-enhanced [3H]Gpp(NH)p binding capacity and quantitative measures by immunoblot analysis using anti-Galpha antibodies in mononuclear leukocytes obtained from 19 IBS patients (Rome criteria) and 19 healthy matched subjects. The study groups were similar in age, gender, and years of education. Mononuclear leukocyte functions of G(s) (21.3+/-8.3%) and G(i) (22.2+/-6.7%) proteins in IBS patients were similar to healthy subjects (24.8+/-4.7 and 25.2+/-4.0%, respectively). The relative immunoreactivities of the G(sa) (98.9+/-10.2%) and the G(ia) (104.2+/-11.5%) subunit proteins in mononuclear leukocytes of IBS patients were also similar to those in healthy subjects. Two patients clinically diagnosed as depressed were detected by the G protein assay. The results lend objective support to the contention that major depression is not a causative factor in IBS, nor associated with its severity. The G protein assay may provide an objective biochemical tool for detecting depression in IBS, differentiating it from psychological distress that is commonly diagnosed by subjective tests.

Do male sex hormones protect from irritable bowel syndrome?

OBJECTIVE: Irritable bowel syndrome (IBS) is more common in women and it is frequently assumed that being female may predispose to the development of this disorder. Alternatively, being male could offer some degree of protection and if so, this might be mediated by testosterone. The aim of this study was to assess whether male patients with IBS have lower levels of testosterone and related gonadotrophins than their unaffected counterparts and if this relates to rectal sensitivity. METHODS: Fifty secondary care, male outpatients with IBS (aged 19-71 yr) were compared with 25 controls (aged 22-67 yr). Each subject had serum testosterone, free testosterone, sex hormone-binding globulin, follicle stimulating hormone, and luteinizing hormone (LH) measured, together with rectal sensitivity to balloon distension. Anxiety and depression were also assessed. RESULTS: The only difference in the hormone levels between patients and controls that reached statistical significance was the lower value for LH in the IBS patients (p = 0.014). Although patients were more anxious and depressed than the controls (p < 0.001), this could not solely account for the reduced level of LH, as adjusting for these (analysis of variance) still tended to show that LH values were lower in men with rather than without IBS [F(1,70) = 2.74; p = 0.10]. Men with IBS were more sensitive to balloon distension of the rectum, with the distension volumes required for "urgency" (p < 0.001) and "discomfort" (p = 0.001) significantly lower than controls. Paradoxically, the patient's sensory thresholds negatively correlated with levels of testosterone (p < 0.05) and free testosterone (p < 0.002), and positively with levels of sex hormone-binding globulin (p < 0.05). Finally, there was a tendency for IBS symptomatology to be inversely related to testosterone levels (p = 0.15). CONCLUSIONS: These results support the need for further exploration of the role of male sex hormones in the pathophysiology of IBS.

Endomysium antibodies are superior to gliadin antibodies in screening for coeliac disease in patients presenting supposed functional gastrointestinal symptoms.

OBJECTIVE: To study the accuracy of IgA- and IgC-gluten antibodies and endomysium antibodies as screening tools for endoscopy with small bowel biopsy for histologic diagnosing of coeliac disease. DESIGN: Comparing serology with histologic examination--the "gold standard" for diagnosing coeliac disease. SETTINGS: 1. The municipality of Osthammar, Sweden. 2. The catchment area of the University Hospital, Uppsala, Sweden. PATIENTS: 1. A random subsample (50 with dyspepsia, 50 with irritable bowel syndrome and 50 symptomless) of a representative sample from an adult Swedish general population (20-80 years; n = 1260). 2. All patients with a diagnosis of coeliac disease admitted to the University Hospital in Uppsala, Sweden during the course of 10 months. MAIN OUTCOME MEASURES: The accuracy of IgA- and IgG-gluten antibodies and endomysium antibodies. RESULTS: There were no significant correlations between IgA-gluten antibodies and IgG-gluten antibodies, on the one hand, and symptoms or symptom severity, on the other. Using duodenal biopsy results as the gold standard, IgA-gluten antibodies had a low specificity and IgG-gluten antibodies a low sensitivity, whereas endomysium antibodies had an excellent accuracy. CONCLUSION: Endomysium antibodies seem to be the screening test of choice. The load of diagnostic upper endoscopies would be considerably decreased compared to using gluten antibodies.

Fenfluramine challenge test predicts outcome in pharmacological treatment of patients with functional gastrointestinal disorder.

We investigated if response to the fenfluramine challenge test could predict outcome in 47 nonpsychiatric patients with chronic functional gastrointestinal disorder (FGD) treated with mianserin, a drug closely related to mirtazepine, or placebo. Sixty milligrams of fenfluramine was given orally in the morning on nonfasting basis. Serum cortisol (COR) and prolactin (PRL) were analyzed at baseline, and after 120, 180, and 240 minutes. Patients were then randomized into a 7-week double-blind treatment trial with mianserin or placebo. Response to treatment with mianserin (76% vs.18% for placebo) was closely linked to a high increase in PRL and COR following a fenfluramine challenge test (positive predictive power=72%). Adding length of illness history increased both positive and negative predictive power to 92%. Our results indicate that the fenfluramine challenge test may be a potentially useful tool to identify nonpsychiatric subjects with FGD, who will most likely respond to treatment with a combined alpha2 and 5HT-2 and -3 antagonist.

Impact of corticotropin-releasing hormone on gastrointestinal motility and adrenocorticotropic hormone in normal controls and patients with irritable bowel syndrome.

BACKGROUND: Corticotropin-releasing hormone (CRH) plays a key role in modulating intestinal motility in stressed animals. AIMS: To evaluate the effect of CRH on intestinal motility in humans and to determine whether patients with irritable bowel syndrome (IBS) have an exaggerated response to CRH. SUBJECTS: Ten IBS patients diagnosed by Rome criteria and 10 healthy controls. METHODS: CRH (2 micrograms/kg) was intravenously administered during duodenal and colonic manometry and plasma adrenocorticotropic hormone (ACTH) was measured by radioimmunoassay. RESULTS: CRH induced motility of the descending colon in both groups (p < 0.001) and induced greater motility indexes in IBS patients than in controls (p < 0.05). CRH produced duodenal phase III motor activity in 80% of the subjects and duodenal dysmotility in 40% of IBS patients. Abdominal symptoms evoked by CRH in IBS patients lasted significantly longer than those in controls (p < 0.05). CRH induced significant increases in plasma ACTH levels in both groups (p < 0.001) and produced significantly higher plasma ACTH levels in IBS patients than in controls (p < 0.001). CONCLUSION: Human intestinal motility is probably modulated by exogenous CRH. The brain-gut in IBS patients may have an exaggerated response to CRH.

Postprandial plasma 5-hydroxytryptamine in diarrhoea predominant irritable bowel syndrome: a pilot study.

BACKGROUND: Increased concentrations of 5-hydroxytryptamine (5-HT) can be detected in the systemic circulation after a meal and may be involved in the physiological control of gastrointestinal motility. Abnormalities of 5-HT release after a meal might explain some of the postprandial symptoms associated with the irritable bowel syndrome (IBS). AIM: To investigate the effect of a standard meal on plasma 5-HT and urinary 5-hydroxyindole acetic acid (5-HIAA) concentrations in patients with diarrhoea predominant IBS and in healthy volunteers. METHODS: After an overnight fast, six volunteers and five patients with IBS were given a carbohydrate-rich meal. Blood and urine samples were taken before and for four hours after the meal. Platelet-poor plasma 5-HT and urinary 5-HIAA were analysed by reversed phase high performance liquid chromatography with fluorometric detection. 5-HIAA was expressed as a ratio with urinary creatinine concentration, which was measured by spectrophotometry. RESULTS: During the four hour postprandial period, 5-HT concentrations were significantly higher in patients with IBS than in healthy volunteers at 0.5 hours (p < 0.05), 2 hours (p < 0.05) and 2.5 hours (p < 0.05). 5-HT was not detected in the plasma in the fasting state in patients or volunteers. Median peak 5-HT in patients with IBS (359 (198-796) nmol/l) was significantly greater than volunteers (83 (7-190)) (p < 0.05). "Area under the curve" for 5-HT detection was greater for patients with IBS (317 (138-771)) than for healthy volunteers (51 (4-129); p < 0.05). The duration of the 5-HT peak was significantly longer in patients with IBS (3 (1-3) hours) than in the healthy volunteers (1 (1-1) hours; p < 0.01). Postprandial urinary median 5-HIAA values in controls (5.6 (5.5-5.8) mumol/mmol creatinine) and patients with IBS (3.0 (2.5-6.8) mumol/mmol creatinine) were not significantly different from preprandial values (controls: 5.9 (5.5-6.6) mumol/mmol creatinine; patients with IBS: (6.2 (2.4-9.3) mumol/mmol creatinine). CONCLUSION: These findings indicate that there may be a difference in the way that 5-HT is released in patients with diarrhoea predominant IBS, and could suggest a possible role for 5-HT in the postprandial symptoms of these patients.

Plasma nitrate concentration in infective gastroenteritis and inflammatory bowel disease.

BACKGROUND: In subjects on a low nitrate diet, plasma nitrate concentration and urinary nitrate excretion are thought to reflect endogenous nitric oxide (NO) production, and have been reported to increase during infective and inflammatory bowel disease. AIMS: To compare the extent of NO production in patients with infective versus non-infective forms of bowel dysfunction. SUBJECTS: Four groups: 20 healthy, volunteer clerical and laboratory staff, 12 patients with irritable bowel syndrome, 19 patients with inflammatory bowel disease, and 20 patients with infective gastroenteritis. METHODS: The plasma nitrate concentration was determined with a copper coated cadmium column and spectrophotometry. Mean and median plasma nitrate concentrations were calculated and compared within the four groups. Mann-Whitney distribution free rank testing was used to compare the median values. RESULTS: Median plasma nitrate concentrations in the four groups were: controls 32.7 mumol/l; irritable bowel syndrome 35.5 mumol/l; inflammatory bowel disease 35.1 mumol/l; and gastroenteritis 117.9 mumol/l (p < 0.001 gastroenteritis v all other groups). CONCLUSIONS: Plasma nitrate concentration could serve as a discriminant between infective and inflammatory or functional bowel disease in patients presenting with diarrhoea. It is not clear why there is considerable difference in endogenous nitrate synthesis in these two conditions, which are both characterised by severe gut inflammation.

Serum cholesterol, cholesterol precursors and plant sterols in different inflammatory bowel diseases.

The role of cholestasis and ileal dysfunction on sterol metabolism was studied in 79 patients with inflammatory bowel diseases (IBDs) and in 23 irritable bowel syndrome (IBS) controls by determining serum sterol/cholesterol proportions. The sterols included cholesterol precursors (delta 8-cholestenol, desmosterol and lathosterol), markers of cholesterol synthesis, cholestanol and plant sterols (campesterol and sitosterol), markers of cholesterol absorption and biliary secretion. The IBD patients were subgrouped into distal ulcerative colitis (dUC, n = 21), pancolitis (pUC, n = 29), ileal Crohn's disease (iCD, n = 20) and colonic Crohn's disease (cCD, n = 9). The cholestanol proportions were increased in the 3 colonic IBD groups, up to two times in cCD patients and seven times in a case with clinically overt primary sclerosing cholangitis, but were within the control IBS levels in the patients with iCD. The sitosterol, but not campesterol, proportion was significantly increased only in the pUC group. In the iCD group only the serum precursor sterol proportions, especially those for delta 8-cholestenol and lathosterol, were elevated probably due to ileal dysfunction induced bile acid malabsorption and compensatorily increased cholesterol synthesis. In conclusion, the findings suggest that the increased cholestanol proportion in colonic IBD is determined mainly by impaired biliary elimination of this sterol, while in ileal affision the dominating change in sterol balance is activated cholesterol synthesis. Thus increased serum cholestanol is a novel finding in colonic IBD, apparently indicating the presence of subclinical cholestasis in a marked number (20-50%) of IBD patients.

Peptic ulcer disease, irritable bowel syndrome and constipation in two populations in Iran.

OBJECTIVE: To determine the prevalence of peptic ulcer disease, irritable bowel syndrome (IBS) and chronic constipation in two Iranian populations (pastoral nomads and industrial labourers) with different life styles, and to evaluate the risk factors associated with these diseases. SUBJECTS: A total of 455 randomly selected pastoral nomads and 492 industrial labourers (all male) aged between 35-55 years. METHODS: Demographic and social data were obtained by interviews. An upper gastrointestinal tract endoscopy was performed and biopsy specimens were taken from subjects complaining of abdominal symptoms and randomly selected asymptomatic subjects. A urease test was performed on antral specimens. Serum pepsinogen I concentrations and Helicobacter pylori antibody titres were measured by radioimmunoassay and immunoglobulin (Ig) G enzyme-linked immunosorbent assay tests, respectively. RESULTS: Serum pepsinogen I concentrations were similar in both nomads and industrial labourers, and the percentage with positive antibody titres for H. pylori was high in both populations (86.3 and 91% in nomads and industrial labourers, respectively). Industrial labourers were twice as likely to have duodenal ulcer (P < 0.05) than nomads. The prevalence of duodenal ulcer disease and gastric ulcer was 4.6 and 0.6% in nomads and 10.3 and 0.4% in industrial labourers, respectively. The prevalence of IBS was similar in nomads (3.1%) and industrial labourers (3.6%). Fewer nomads (1.4%) than industrial labourers (3.3%) had chronic constipation. Logistic regression analysis showed that being an industrial labourer, or smoker and having undergone previous non-gastric surgery were risk factors for duodenal ulcer disease. When the variable 'urease test' was included in the logistic regression analysis, smoking, a positive urease test and the quantity of fruit eaten per week were associated risk factors. The risk factors associated with IBS were the use of analgesics and back pain. The only risk factor associated with chronic constipation was being an industrial labourer. CONCLUSIONS: Industrial labourers were twice as likely to have duodenal ulcer disease as nomads. The prevalence of IBS and chronic constipation in the two male Iranian populations was lower than that found in western countries. Duodenal ulcer disease was associated with H. pylori colonization but not with a positive serum antibody titre for H. pylori. H. pylori colonization of the antral mucosa and smoking are causative factors for duodenal ulcer disease and fruit intake is possibly an associated factor.

Depression and T lymphocytes in patients with irritable bowel syndrome.

In 74 patients (23 male, 51 female) with irritable bowel syndrome (IBS) and in 15 matched control persons, an assessment of depression by means of the Zung Depression Self-Rating Scale (ZDS) and a determination of the number of total lymphocytes and T lymphocytes were carried out. In patients with IBS, the depression score was significantly higher than in controls. Among patients with IBS, the intensity of depressive symptoms did not relate to age, gender or to the type of the illness. IBS patients with a depression score on ZDS of 50 or more (31% of subjects) had a significantly lower number of total lymphocytes and T lymphocytes than the rest of IBS patients. The results may suggest a possible association between depression and indices of cellular immunity in IBS patients.

Concentrations of 5-ASA and Ac-5-ASA in human ileocolonic biopsy homogenates after oral 5-ASA preparations.

Intramucosal 5-aminosalicylic acid (5-ASA) and acetylated 5-ASA (Ac-5-ASA) concentrations were determined in ileocolonic biopsy specimens from 61 patients with irritable bowel syndrome treated for one week with near equimolar doses of different slow release preparations of 5-ASA (Claversal, Asacol, or Pentasa) or azo-bound drugs (Salazopyrin, Dipentum). The transit time in these patients was accelerated by a laxative, metoclopramide, and colonic lavage. The presence of 5-ASA in the mucosa was confirmed by autofluorescence. The highest concentrations of 5-ASA were obtained after Asacol (mean (SEM), 298.5 (37.3) ng/mg wet wt), followed by Claversal 500 mg (108.8 (11.7) ng/mg wet wt) and Pentasa (25.7 (2.2) ng/mg wet wt). Very low concentrations only were observed after Claversal 250 mg (0.3 (0.03) ng/mg wet wt), Salazopyrine (1.2 (0.1) ng/mg wet wt), and Dipentum (11.0 (3.2) ng/mg wet wt). The results for Ac-5-ASA were similar but the concentrations were generally lower. Serum concentration-time curves over eight hours were obtained from 34 healthy volunteers after a single oral dose of 400 to 500 mg of the different drugs. For the slow release forms, an apparently inverse relationship was found between the area under the curve of the serum concentrations and the intramucosal concentrations, supporting the importance of the local availability of the drug. This inverse relationship was absent for the azo-bound drugs. Colonic washout induced mechanical removal of intraluminal 5-ASA with a secondary disturbance in absorption resulting in a rapid decline in the serum concentrations. However, only for Dipentum did this result in significantly lower 5-ASA mucosal concentrations. This is the first reported attempt to evaluate the mucosal availability of 5-ASA after different oral preparations. It shows that where transit time is accelerated higher mucosal concentrations occur after slow release preparations (except for Claversal 250 mg) than after azo-bound drugs. Additional studies are necessary to correlate these concentrations with clinical effects.

Selective 5-hydroxytryptamine type 3 receptor antagonism with ondansetron as treatment for diarrhea-predominant irritable bowel syndrome: a pilot study.

Serotoninergic innervation may contribute to the control of colonic motility and to visceral sensation from the large bowel. Indeed, ondansetron hydrochloride, a selective 5-hydroxytryptamine type 3 receptor antagonist, has been shown to slow colonic transit in healthy volunteers. Thus, we wished to determine whether 5-hydroxytryptamine type 3 receptor blockade slows colonic and small bowel transit in patients with diarrhea-predominant irritable bowel syndrome (IBS) and whether symptoms would be ameliorated with drug therapy. Of 14 patients with well-established IBS who entered a randomized, double-blind, placebo-controlled crossover pilot trial of 4 weeks of treatment with ondansetron, 16 mg three times daily, 11 completed the study. A minimal "washout period" of 4 weeks (median, 7 weeks) separated the two phases of the trial because patients were required to have similar symptoms before both periods of the study. Colonic transit tended to be longer during drug therapy than during the placebo trial, but this difference was not significant. Small intestinal transit and orocecal transit were unchanged by the drug. The integrated and peak postprandial increases in neurotensin, peptide YY, and human pancreatic polypeptide in serum were not significantly different in the drug and placebo periods. After treatment with ondansetron, stool consistency improved significantly; however, stool frequency, stool weight, abdominal pain, and the symptom criteria for IBS were not significantly altered by the drug. The results of this pilot study suggest that the motor effects expected with 5-hydroxytryptamine type 3 receptor blockade (namely, slowed colonic transit) may be diminished in some patients with IBS. The subjective improvement in stool consistency may reflect changes in the perception of defecation.(ABSTRACT TRUNCATED AT 250 WORDS)

Short report: plasma somatostatin concentrations in the irritable bowel syndrome.

The description of a patient with the irritable bowel syndrome whose symptoms were completely relieved by the administration of somatostatin raised the possibility that a deficiency of somatostatin may be involved in the pathogenesis of the disorder. We have examined this possibility by studying 11 healthy controls (35 +/- 12 years; mean +/- S.D. 8 female) and 10 irritable bowel syndrome patients (39 +/- 14 years; 7 female) complaining of frequency of defaecation of 4 or more times a day. Plasma somatostatin concentrations were determined by specific radioimmunoassay, fasting and at 15, 30, 45, 60, 90, 120 and 180 min after a standard breakfast. Irritable bowel syndrome patients and controls had similar fasting (27.4 +/- 5.1 vs. 35.2 +/- 4.3 pg/ml; mean +/- S.E.M. and integrated increment of post-prandial (5105 +/- 858 vs. 3885 +/- 793 pg.min/L) plasma concentrations of somatostatin, as assessed by student's t-test. These observations do not support the idea that a state of somatostatin deficiency exists in the irritable bowel syndrome.