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Biomedical subjects

S A Müller-Lissner

Publications and source records attributed to S A Müller-Lissner.

At least 19 recordsLinked to original sources

Technologies in the evaluation of irritable bowel syndrome.

During a meeting in The Hague, The Netherlands, the IBiS Club evaluated the most important techniques that can be used in the investigation of irritable bowel syndrome, either in the context of scientific research or as a clinical diagnostic tool. In each of these, the relevance of findings made in irritable bowel syndrome was balanced against the applicability of the technique. The discussion of the group is summarized in this paper.

Anal Canal↗

The rectum: a window to irritable bowel syndrome?

This report summarizes current concepts and information gathered to date about the rectum in the irritable bowel syndrome (IBS) that were presented at the 10th meeting of IBiS Club held in Leuven, Belgium. A working group of experts in the field of IBS discussed whether the rectum or the whole colon is the better site to test in IBS patients and provided suggestions for a number of areas where further advances are required.

Biopsy↗

Tegaserod, a 5-HT(4) receptor partial agonist, relieves symptoms in irritable bowel syndrome patients with abdominal pain, bloating and constipation.

AIM: To investigate the efficacy and safety of tegaserod, a novel 5-HT(4) receptor partial agonist, in a randomized, double-blind, placebo-controlled, 12-week treatment, multicentre study. METHODS: Eight hundred and eighty-one patients with irritable bowel syndrome, characterized by abdominal pain, bloating and constipation, received tegaserod, 2 mg b.d. or 6 mg b.d., or placebo for 12 weeks. RESULTS: Tegaserod, 2 mg b.d. and 6 mg b.d., showed a statistically significant relief of overall irritable bowel syndrome symptoms, measured by a weekly, self-administered questionnaire. At end-point, treatment differences from placebo were 12.7% and 11.8% for 2 mg b.d. and 6 mg b.d., respectively. The effect of tegaserod was noted as early as week 1, and was sustained over the 12-week treatment period. Individual irritable bowel syndrome symptoms assessed daily also showed a statistically significant improvement of abdominal discomfort/pain, number of bowel movements and stool consistency, and a favourable trend for reducing days with significant bloating. Adverse events were similar in all groups, with transient diarrhoea being the only adverse event seen more frequently with tegaserod than placebo. CONCLUSIONS: Based upon the results of this study, tegaserod offers rapid and sustained relief of the abdominal pain and constipation associated with irritable bowel syndrome. Tegaserod is also well tolerated.

Abdominal Pain↗

Epidemiological aspects of irritable bowel syndrome in Europe and North America.

The epidemiology of irritable bowel syndrome (IBS) in Europe and North America was analyzed from published material. The percentage of the population of Western civilisation with IBS symptoms is between 10 and 15% in most studies. The proportion of a Western population visiting a doctor for IBS symptoms is around 5%. The prevalence of IBS and the proportion of consulters do not seem to depend on age in an adult population. The female-to-male ratio of IBS in the population is close to 2. It is higher in IBS consulters in primary care and may be as high as 3 or 4 in tertiary referral centers. At least in patients from these centers, the number of physician visits and colonoscopies is considerable. Most of the consulters get a drug prescription.

Colonic Diseases, Functional↗

Dysplasia of the submucous nerve plexus in slow-transit constipation of adults.

AIM: A clinicopathological entity, intestinal neuronal dysplasia type B (IND) has been described in children with severe constipation. The present study was designed to evaluate whether IND could be identified in adult patients with idiopathic slow-transit constipation. METHODS: Rectal biopsies were taken from 27 constipated patients with documented slow colonic transit and 23 controls and stained for S100 protein, acetylcholine esterase and lactate dehydrogenase. The mean and maximal number of ganglion cells per ganglion, mean number of ganglia and mean number of ganglion cells per mm2 of submucosal tissue, mean and maximal diameter of ganglion cells, maximal thickness of submucosal nerve fibres, and number of S100-positive cells per mm2 mucosal tissue were quantified. The density of submucosal ganglia, presence of heterotopic ganglion cells, intensity of staining of the adventitial layer of submucosal arteries, and density of nerve fibres in submucosa and lamina propria were evaluated qualitatively. In addition, subjective evaluation by an experienced pathologist was performed. RESULTS: There were no major differences between patients and controls, except that patients had slightly thicker submucosal nerves than controls (30.8 +/- 1.6 versus 25.5 +/- 2.0 microm, P < 0.05) and more frequent heterotopic ganglion cells (32 versus 6%, P < 0.05). Neither discriminant analysis of the morphometric data nor subjective evaluation was able to correctly classify the slides as originating from patients or controls. CONCLUSIONS: The existence of the clinicopathological entity IND in adults with slow-transit constipation is unlikely. For further classification of slow-transit constipation, rectal biopsies do not appear to be useful at present.

Adolescent↗

Functional bowel disorders and functional abdominal pain.

The Rome diagnostic criteria for the functional bowel disorders and functional abdominal pain are used widely in research and practice. A committee consensus approach, including criticism from multinational expert reviewers, was used to revise the diagnostic criteria and update diagnosis and treatment recommendations, based on research results. The terminology was clarified and the diagnostic criteria and management recommendations were revised. A functional bowel disorder (FBD) is diagnosed by characteristic symptoms for at least 12 weeks during the preceding 12 months in the absence of a structural or biochemical explanation. The irritable bowel syndrome, functional abdominal bloating, functional constipation, and functional diarrhea are distinguished by symptom-based diagnostic criteria. Unspecified FBD lacks criteria for the other FBDs. Diagnostic testing is individualized, depending on patient age, primary symptom characteristics, and other clinical and laboratory features. Functional abdominal pain (FAP) is defined as either the FAP syndrome, which requires at least six months of pain with poor relation to gut function and loss of daily activities, or unspecified FAP, which lacks criteria for the FAP syndrome. An organic cause for the pain must be excluded, but aspects of the patient's pain behavior are of primary importance. Treatment of the FBDs relies upon confident diagnosis, explanation, and reassurance. Diet alteration, drug treatment, and psychotherapy may be beneficial, depending on the symptoms and psychological features.

Abdominal Pain↗

Interobserver agreement in defecography--an international study.

BACKGROUND: Defecography is considered to be an essential investigation in the evaluation of functional anorectal disorders, but the agreement between observers from different clinical centers has never been evaluated. METHODS: 14 defecographic studies were selected aimed to cover the most relevant defecographic findings responsible for disordered defecation. Eight studies were considered unequivocal, but six were thought to be controversial. All were sent to the ten participants in Europe and the US (five proctosurgeons, three radiologists, two gastroenterologists). They evaluated the studies using a previously agreed upon questionnaire. Interobserver agreement was quantified by kappa statistics and by the proportions of positive and negative agreement as compared to chance agreement, respectively. RESULTS: Overall, only the completeness of rectal emptying and the presence of a rectocele achieved acceptable kappa values above 0.4. When restricting the evaluation to the studies considered to be unequivocal, agreement improved considerably and was moderate to good for all items describing the images (kappa 0.43-0.63). However, whether proctosurgery should be performed and whether defecography contributed to the management of the particular patient remained controversial with very low kappa. CONCLUSIONS: It is doubtful whether defecography contributes substantially to the management of patients with disordered defecation.

Anus Diseases↗

Paradoxical sphincter contraction is rarely indicative of anismus.

BACKGROUND: Anismus is thought to be a cause of chronic constipation by producing outlet obstruction. The underlying mechanism is paradoxical contraction of the anal sphincter or puborectalis muscle. However, paradoxical sphincter contraction (PSC) also occurs in healthy controls, so anismus may be diagnosed too often because it may be based on a non-specific finding related to untoward conditions during the anorectal examination. AIMS: To investigate the pathophysiological importance of PSC found at anorectal manometry in constipated patients and in patients with stool incontinence. METHODS: Digital rectal examination and anorectal manometry were performed in 102 chronically constipated patients, 102 patients with stool incontinence, and in 18 controls without anorectal disease. In 120 of the 222 subjects defaecography was also performed. Paradoxical sphincter contraction was defined as a sustained increase in sphincter pressure during straining. Anismus was assumed when PSC was present on anorectal manometry and digital rectal examination and the anorectal angle did not widen on defaecography. RESULTS: Manometric PSC occurred about twice as often in constipated patients as in incontinent patients (41.2% versus 25.5%, p < 0.017) and its prevalence was similar in incontinent patients and controls (25.5% versus 22.2%). Oroanal or rectosigmoid transit times in constipated patients with and without PSC did not differ significantly (total 64.6 (8.9) hours versus 54.2 (8.1) hours; rectosigmoid 14.9 (2.4) hours versus 13.8 (2.5) hours). CONCLUSIONS: Paradoxical sphincter contraction is a common finding in healthy controls as well as in patients with chronic constipation and stool incontinence. Hence, PSC is primarily a laboratory artefact and true anismus is rare.

Anal Canal↗

Clinical response to dietary fiber treatment of chronic constipation.

OBJECTIVES: To determine the clinical outcome of dietary fiber therapy in patients with chronic constipation. METHODS: One hundred, forty-nine patients with chronic constipation (age 53 yr, range 18-81 yr, 84% women) at two gastroenterology departments in Munich, Germany, were treated with Plantago ovata seeds, 15-30 g/day, for a period of at least 6 wk. Repeated symptom evaluation, oroanal transit time measurement (radiopaque markers), and functional rectoanal evaluation (proctoscopy, manometry, defecography) were performed. Patients were classified on the basis of the result of dietary fiber treatment: no effect, n = 84; improved, n = 33; and symptom free, n = 32. RESULTS: Eighty percent of patients with slow transit and 63% of patients with a disorder of defecation did not respond to dietary fiber treatment, whereas 85% of patients without a pathological finding improved or became symptom free. CONCLUSION: Slow GI transit and/or a disorder of defecation may explain a poor outcome of dietary fiber therapy in patients with chronic constipation. A dietary fiber trial should be conducted before technical investigations, which are indicated only if the dietary fiber trial fails.

Adolescent↗

Decreased substance P levels in rectal biopsies from patients with slow transit constipation.

OBJECTIVE: Previous studies in patients with chronic constipation found abnormalities in the nervous tissue of the large intestine, predominantly in the muscularis externa. Since there is evidence that the nervous system of mucosa and submucosa is also involved in the control of colonic motility we investigated the contents of vasoactive intestinal polypeptide (VIP), somatostatin and substance P in rectal biopsies of patients with slow colonic transit constipation. DESIGN AND METHODS: Twenty-two patients (17 females, 5 males) with chronic slow transit constipation (oro-anal transit with radio-opaque markers on high fibre diet > 70 h) and long-term use of laxatives, and 20 controls (12 females, 8 males) with no history of constipation, were included in this study. Large rectal biopsy specimens including the submucosa were obtained from 5 cm above the dentate line and frozen in liquid nitrogen. After microdissection of the biopsies into mucosa and submucosa the neuropeptides were extracted by boiling and homogenizing the tissue in acetic acid and determined using validated radioimmunoassays. RESULTS: Patients with slow transit constipation showed, compared to healthy controls, significantly lower levels of the excitatory neurotransmitter substance P in the mucosa and submucosa of rectal biopsies. There was no difference between the two groups concerning the levels of the inhibitory neurotransmitters, VIP and somatostatin. CONCLUSION: Slow transit constipation is associated with abnormalities of the substance P content of the enteric nervous system of mucosa and submucosa. This seems not to be related to chronic laxative use, since anthranoids cause a reduction in the levels of inhibitory neurotransmitters (VIP, somatostatin), but not of substance P, in the rat colon.

Biopsy↗

Diagnostic value of histology in non-erosive gastro-oesophageal reflux disease.

BACKGROUND: In the absence of oesophageal erosions longterm pH monitoring is the present gold standard for diagnosing gastro-oesophageal reflux disease (GORD). This method, however, is invasive, time consuming, expensive, and not generally available. AIMS: As histological changes have been described in GORD, this study looked at the possibility of whether the diagnosis of non-erosive reflux disease could be made by histological examination routinely during endoscopy. SUBJECTS: A total of 24 prospectively selected patients with symptoms suggestive of GORD and seven healthy volunteers. METHODS: Oesophageal erosions and other peptic lesions were excluded by oesophago-gastroduodenoscopy. Oesophageal pinch biopsy specimens were taken 2 cm and 5 cm above the oesophagogastric junction and evaluated blindly for the histological parameters cellular infiltration, basal zone hyperplasia, and papillary length. Twenty four hour pH monitoring was used as gold standard for the definition of reflux disease. It was abnormal in 13 patients (reflux patients) and normal in 11 patients (symptomatic controls) and in seven healthy volunteers. RESULTS: Sparse infiltration of the epithelium with lymphocytes in at least one biopsy specimen was found in all patients and volunteers, with neutrophils in three reflux patients, and with eosinophils in two reflux patients and in two healthy volunteers. The basal zone thickness was increased in three reflux patients, in one symptomatic control, and in one healthy volunteer. The papillary length was greater than two thirds of total epithelium in six of 13 reflux patients in contrast with none in 11 symptomatic controls (p < 0.05) and to one healthy volunteer. The sensitivity of the parameter papillary length hence was only 46%. CONCLUSIONS: Although gastro-oesophageal reflux produces slight histological changes apart from oesophageal erosions in a few subjects, none of the established histological parameters can fulfil the for the diagnosis of GORD in patients without visible oesophageal erosions.

Adult↗

Functional diagnostic work-up in patients with irritable bowel syndrome.

The first aim of the study was to find a cause of symptoms in patients suffering from "irritable bowel syndrome" using diagnostic tests aimed at functional disorders of lower gut. A second aim was to test, whether the presence of irritable bowel syndrome (or, synonymously, absence of classic organic disease) can be predicted by specific symptoms. 134 consecutive patients (50 +/- 16 SD years, range 17 to 88, 94 women) presenting in our gastroenterological outpatient department with abdominal pain and altered bowel habits were included. A conventional diagnostic work-up aimed at classic organic diseases and, if negative, a functional diagnostic work-up aimed at gastrointestinal malfunction such as dietary fibre trial, functional proctoscopy, defecography, colonic transit of radiopaque markers, anorectal manometry, and lactose tolerance test were done. A classic organic disease was found in only 15 of 134 patients by conventional diagnostic tests. Functional diagnostic work-up yielded a diagnosis in 70 of the remaining 119 patients that else would have been labeled to suffer from IBS (25 slow transit constipation, 20 disordered defecation, nine low fibre intake, and nine lactose intolerance among them). When symptoms were evaluated with a standardized questionnaire, "constipation" and the "necessity of straining to open bowels" were very specific for functional bowel disorder (92% and 100%), but sensitivity of both symptoms was only about 60%. The so-called "Manning criteria" had a very low prevalence in our sample and so were not discriminatory. Since in more than half of the patients with "irritable bowel syndrome" a specific diagnosis can be reached, functional tests should be considered in such patients. The symptom "constipation" in patients with lower gut complaints predicted a functional disorder rather than a classic organic disease with a high specificity.

Adolescent↗

Empiric therapy for gastroesophageal reflux disease.

BACKGROUND: In the absence of highly specific symptoms and without esophageal erosions, long-term pH monitoring is necessary for diagnosing gastroesophageal reflux disease. This method, however, is not generally available. OBJECTIVE: To determine whether gastroesophageal reflux disease can be diagnosed empirically by acid suppression in patients with normal results of endoscopy. METHODS: We studied 33 consecutive outpatients with pathologic findings on pH monitoring who had symptoms compatible with gastroesophageal reflux disease and normal results of esophagogastroduodenoscopy, particularly a normal appearance of the esophageal mucosa. The severity of symptoms was graded on a visual analog scale from 1 to 10 by the patient. The patients were treated for at least 7 days with either ranitidine, 150 mg twice daily (patients 1 through 10), omeprazole, 40 mg/d (patients 11 through 21), or omeprazole, 40 mg twice daily (patients 22 through 33). A reassessment of symptoms and second pH monitoring were performed during the last day of treatment. RESULTS: Omeprazole, 40 mg/d, significantly reduced the severity of symptoms from 7.1 (range, 4 to 9) to 3.7 (0 to 8) and the reflux measure mean acidity from 0.98 mmol/L (0.21 to 76 mmol/L) to 0.02 mmol/L (0 to 0.47 mmol/L). Omeprazole, 40 mg twice daily, significantly reduced the severity of symptoms from 6.8 (3 to 10) to 0.6 (0 to 2) and the mean acidity from 0.38 mmol/L (0.13 to 8.5 mmol/L) to 0.01 mmol/L (0 to 0.14 mmol/L). Both doses of omeprazole were superior to ranitidine, 150 mg twice daily. When a 75% reduction of symptoms was defined as positive, the "omeprazole test" with 40 mg twice daily had a sensitivity of 83.3%, whereas the sensitivity with 40 mg/d was only 27.2%. CONCLUSION: In practice, the diagnosis of gastroesophageal reflux disease can be ruled out if symptoms do not improve with a limited course of high-dose proton pump inhibitors.

Adult↗

The effect of hormones and peptides involved in water balance on rat colonic motility in vitro.

We have previously shown that restriction of water intake decreased stool frequency and stool weight in volunteers. The aim of this study was to investigate whether these effects of thirst could be mediated by an action of systematically released hormones on colonic smooth muscle. Using isolated colonic smooth muscle strips the effect of arginine-vasopressin (AVP), angiotensin II (ANG II) and aldosterone on rat colonic motility in vitro was investigated. AVP (10(-12)-10(-10) mol/l) and aldosterone (3 x 10(-10)-3 x 10(-8) mol/l) and physiological hormonal concentrations of ANG II (10(-13)-10(-10) mol/l) had no effect on either basal activity, direct stimulation of colonic smooth muscle or neurally stimulated contractions using carbachol 10(-7)-3 x 10(-5) mol/l or neurally stimulated contractions using electrical field stimulation at various stimulation frequencies (1-10 pps, 1 ms, 40 V). ANG II in higher concentrations (10(-7)-10(-6) mol/l) increased basal activity and neurally mediated contractions. Accordingly, ANG II (10(-6) mol/l) caused a prestimulation but did not increase the maximum contractile effect of carbachol. The response to ANG II was not affected by atropine (10(-6) mol/l). TTX (10(-6) mol/l) and N-nitro-L8-arginine (L-NNA) (3 x 10(-4) mol/l) stimulated basal muscular activity but did not affect the maximum contractile effect of ANG II. Systemic serum concentrations of AVP, aldosterone and ANG II are presumably not involved in thirst-induced colonic motility changes. The ANG II effect in higher concentrations is mediated by a direct stimulatory smooth muscle effect and/or by facilitating neuronal liberation of acetylcholine.(ABSTRACT TRUNCATED AT 250 WORDS)

Aldosterone↗

Effects of long-term treatment with anthranoids and sodium picosulphate on the contents of vasoactive intestinal polypeptide, somatostatin and substance P in the rat colon.

OBJECTIVE: To examine the effects of chronic treatment and a single high-dose application of anthranoids and sodium picosulphate on the neuropeptide content of the rat colon. DESIGN AND METHODS: Over a 6-month period, eight groups of rats were each given one of the following: sennosides or sodium picosulphate in low daily doses (10 and 2.5 mg/kg/day, respectively), in high daily doses (40 and 10 mg/kg/day, respectively), and in high twice-weekly doses (30 and 7.5 mg/kg/day, respectively); high daily doses of danthron (500 mg/kg/day); and vehicle (tragacanth 0.5%) only. Four further groups of rats each received a single dose of vehicle or a high dose of one of the three laxatives. All rats were killed 48 h after the last dose. The ascending and descending colon were removed and separated into mucosa, submucosa, and muscularis externa. Vasoactive intestinal polypeptide (VIP), somatostatin, and substance P were extracted by boiling and homogenizing the tissue in acetic acid, and their levels were determined using validated radioimmunoassays. RESULTS: After long-term treatment with high doses of sennosides and danthron, but not after a single high-dose administration, there was a significant reduction in mucosal levels of VIP and somatostatin and in submucosal levels of somatostatin of both colonic segments, as well as in the level of VIP in the muscularis externa of the descending colon. Substance P levels remained unaffected. Sodium picosulphate had no effect. CONCLUSIONS: Chronic treatment with anthranoids in high doses, but not with sodium picosulphate, reduces VIP and somatostatin levels in the rat colon. This may represent damage to the enteric nervous tissue or a pharmacological effect of the anthranoids, causing decreased synthesis or increased breakdown of these peptides.

Animals↗