Sympathetic (electrodermal) activity during repeated maximal rectal distensions in patients with irritable bowel syndrome and constipation.

Irritable bowel syndrome (IBS) is associated with visceral hypersensitivity, stress and autonomic dysfunction. Sympathetic activity during repeated events indicates excitatory or inhibitory mechanisms such as sensitization or habituation. We investigated skin conductance (SC) during repetitive rectal distensions at maximal tolerable pressure in patients with IBS and chronic constipation. Twenty-seven IBS patients, 13 constipation patients and 18 controls underwent two sets of isobaric rectal distensions. First, maximal tolerable distension was determined and then it was repeated five times. Skin conductance was measured continuously. Subjective symptom assessment remained steady in all groups. The baseline values of SC were higher in IBS patients than in patients with constipation and significantly lower in constipation patients than in controls. The maximal SC response to repetitive maximal distensions was higher in IBS patients compared with constipation patients. The amplitude of the initial SC response decreased successively with increased number of distensions in patients with IBS and constipation but not in controls. Irritable bowel syndrome and constipation patients habituated to maximal repetitive rectal distensions with decreasing sympathetic activity. Irritable bowel syndrome patients had higher sympathetic reactivity and baseline activity than constipation patients. A lower basal SC in constipation patients compared with controls suggests an inhibition of the sympathetic drive in constipation patients.

Pre-experimental stress in patients with irritable bowel syndrome: high cortisol values already before symptom provocation with rectal distensions.

Stress is known to affect symptoms of irritable bowel syndrome (IBS) probably by an alteration of visceral sensitivity. We studied the impact of maximal tolerable rectal distensions on cortisol levels in patients with IBS, chronic constipation and controls, and evaluated the effect of the experimental situation per se. In twenty-four IBS patients, eight patients with chronic constipation and 15 controls salivary cortisol was measured before and after repetitive maximal tolerable rectal balloon distensions and at similar times in their usual environment. Rectal sensitivity thresholds were determined. IBS patients but not controls and constipation patients had higher cortisol levels both before and after the experiment compared with similar times on an ordinary day in their usual environment (P = 0.0034 and 0.0002). There was no difference in salivary cortisol level before compared with after rectal distensions. The IBS patients had significantly lower thresholds for first sensation, urge and maximal tolerable distension than controls (P = 0.0247, 0.0001 and <0.0001) and for urge and maximal tolerable distension than patients with constipation (P = 0.006 and 0.013). IBS patients may be more sensitive to expectancy stress than controls and patients with constipation according to salivary cortisol. Rectal distensions were not associated with a further significant increase in cortisol levels.

Treatment of anaemia in inflammatory bowel disease with iron sucrose.

BACKGROUND: Inflammatory bowel disease (IBD)-associated anaemia usually responds to intravenous iron. If not, additive treatment with erythropoietin has been proposed. The objective of the present retrospective study was to evaluate the effectiveness of treatment with iron sucrose alone. METHODS: Sixty-one patients with IBD and anaemia (average haemoglobin 97 g/L) were treated with iron sucrose (iron dose 1.4 +/- 0.5 g). The indications for iron sucrose were poor response and/or intolerance to oral iron. Treatment response was defined as an increase in haemoglobin of > or = 20 g/L or to normal haemoglobin levels (> or = 120 g/L). Two independent investigators retrospectively assessed laboratory variables, clinical findings, and concomitant medication. RESULTS: Two patients were transferred to other hospitals after treatment and therefore could not be evaluated. Fifty-four of the remaining 59 patients (91%) responded within 12 weeks. Sixty percent of the patients had responded within 8 weeks. Five patients had no or only a partial response to iron sucrose of which three had prolonged gastrointestinal blood losses. Eight patients with normal or elevated levels of ferritin could be considered to have anaemia of chronic disease, and all of them responded to iron sucrose. During a follow-up period of 117 +/- 85 (4-291) (mean +/- s (standard deviation) (range)) weeks 19 patients (32%) needed at least one second course of iron sucrose because of recurrent disease. CONCLUSIONS: Anaemia associated with IBD can be successfully treated with intravenously administered iron sucrose, provided that bowel inflammation is treated adequately and enough iron is given. Treatment with iron sucrose is safe. Follow-up of haemoglobin and iron parameters to avoid further iron deficiency anaemia is recommended.

Increased liver echogenicity at ultrasound examination reflects degree of steatosis but not of fibrosis in asymptomatic patients with mild/moderate abnormalities of liver transaminases.

AIMS: To investigate whether hyperechogenicity of liver can reliably be interpreted as liver steatosis and if any concomitant or isolated fibrosis can be disclosed. PATIENTS AND METHODS: A series of 165 patients with no signs or symptoms of liver disease referred because of slightly to moderately raised aminotransferases (alanine aminotransferase and/or aspartate aminotransferase 0.7-5.0 microkat/l) for more than 6 months were prospectively investigated with a comprehensive laboratory profile, ultrasound examination of liver and percutaneous liver biopsy Fibrosis was assessed quantitatively and according to Metavir. Steatosis was graded as none, mild, moderate or severe. RESULTS: Of 98 (59.4%) patients with raised echogenicity, 85 (86.7%) had liver steatosis of at least moderate degree, 9 patients with same degree of steatosis had normal echogenicity and 13 patients with no or only mild steatosis had a hyperechogenic liver (sensitivity 0.90, specificity 0.82, positive predictive value 0.87, negative predictive value 0.87). About the same relations were found regardless of body mass index and degree of fibrosis. With increased echogenicity together with high attenuation (n = 591 and reduced portal vessel wall distinction (n = 79), positive predictive value increased to 0.93 and 0.94, respectively. Quantitatively assessed fibrosis (mean +/- SD) was 3.2 +/- 4.6% of biopsy area with normal and 2.3 +/- 1.8% with raised echogenicity (ns). Echogenicity was normal in 5 out of 9 patients with septal fibrosis and in 4 out of 6 patients with cirrhosis. Any structural, non-homogenous findings at ultrasound were not associated with architectural fibrotic changes and none had nodular contours of liver surface. CONCLUSIONS: Assessment of liver echogenicity is of value for detection or exclusion of moderate to pronounced fatty infiltration (correct classification 86.6%) but cannot be relied upon in diagnosing fibrosis, not even cirrhosis in asymptomatic patients with mild to moderately elevated liver transaminases.

Surgery for Crohn colitis over a twenty-eight-year period: fewer stomas and the replacement of total colectomy by segmental resection.

BACKGROUND: This study describes how surgery for Crohn colitis developed between 1970 and 1997, towards the end of which period limited resection and medical maintenance treatment was introduced. METHODS: A cohort of 211 patients with Crohn colitis (115 population-based), of which 84 had a primary colonic resection (42 population-based), was investigated regarding indication for surgery, the time from diagnosis to operation, type of primary colonic resection, risk for permanent stoma and medication over four 7-year periods. RESULTS: Comparison of the periods 1970-90 and 1991-97 revealed that active disease as an indication for surgery decreased from 64% to 25% (P<0.01) while stricture as an indication increased from 9% to 50% (P < 0.001). Median time from diagnosis to operation increased from 3.5 to 11.5 years (P < 0.01). Proctocolectomy or colectomy fell from 68.8% to 10% of the primary resections, whereas segmental resection increased from 31.2% to 90%. At the end of the first 7-year period, 26% had medical maintenance treatment, steroids or azathioprine taken by 7%. Corresponding figures for the last period were 70% and 49%. Patients diagnosed during the last two time-periods had less risk for surgery (P = 0.017), permanent stoma (P < 0.01) and total colectomy (P < 0.01). Findings were similar in the population-based cohort. CONCLUSIONS: Current management of Crohn colitis implies a longer period between diagnosis and surgery, a reduced risk for surgery and permanent stoma, and the replacement of total colectomy by segmental resection.

Abdominal symptoms and anorectal function in health and irritable bowel syndrome.

BACKGROUND: It is unclear how the quality and quantity of abdominal symptoms and anorectal function differ between irritable bowel syndrome (IBS) patients and healthy controls, and whether different anorectal function in patients is associated with abdominal symptoms in IBS. METHODS: Fifty-two outpatients with IBS and 12 healthy controls kept daily symptom records over 1 week. At the end of the week, anorectal function was assessed by manovolumetry before and after a standard fatty meal. Patients were divided into symptom and manovolumetric subgroups using a cluster analysis and also into those below (hypersensitive) and those within (normosensitive) the 95% confidence interval of the controls' mean for maximal tolerable distension (MTD). RESULTS: Regardless of subgroup, the patients were distinguished from the controls by pain, bloating, straining and incomplete evacuation. Compared with controls, MTD was lower in the pain/bloating subgroup characterized by considerable pain and the bowel habit subgroup characterized by hard stools, variable stool consistency and heavily disturbed stool passage. Preprandial rectal hypersensitivity was highly prevalent in this bowel habit subgroup. No similar association with the pain/bloating subgroup was found. Patients and controls showed a significant and similar postprandial decrease in MTD. CONCLUSIONS: IBS is distinguished from health by pain, bloating, straining and a feeling of incomplete evacuation. Baseline rectal hypersensitivity is associated with constipation-like bowel habit. Increased rectal sensitivity after a meal and/or preceding distension is a normal reaction unimportant in the genesis of symptoms in IBS.

[Irritable bowel syndrome. Survey of definitions, differential diagnosis and pathogenesis]. / Irriterade tarmens syndrom. Oversikt över definitioner, differentialdiagnostik och patogenes.

Abdominal pain/discomfort, bloating, need to rush to the toilet, straining, feeling of incomplete bowel emptying and alternating periods of diarrhea and constipation is the clinical definition of the irritable bowel syndrome. The internationally used syndrome definition is based on expert opinions and answers to patient questionnaires. When symptoms are registered prospectively, abdominal pain starts or worsens after meals and is not relieved by defecation. As in the general population patients with the syndrome define diarrhea as loose stools and constipation as hard stools regardless of stool frequencies. Variation in defecatory symptoms and discrepancies between these symptoms and stool consistency are the hallmarks of the syndrome, and the degree of variation per fortnight is relatively stable in the individual patient. Fermentation of carbohydrates by colonic bacteria, increased sensitivity to bowel distention by gas, gas-producing food, increased secretion of cholecystokinin after fatty meals and/or increased sympathetic nerve tone at stress can give rise to symptoms. Symptoms can start after a single period of bacterial gastroenteritis. Although patients seeking medical care for the syndrome are more often anxious, the syndrome itself is not psychosomatic. Symptoms are possibly mediated through partial degranulation of mast cells in bowel mucosa, but this does not make it an allergic disease. If bowel dysmotility can be measured, early stage or a mild case of intestinal pseudoobstruction should be considered. Hyperreactivity in the enteric nervous system and/or in the brain is the likely main cause of the symptoms. More widespread activity in the brain after exposure to stimuli originating from bowel nerves or less inhibition of this stimulation in the brain are possible mechanisms.

A double-blind, randomized, placebo-controlled dose-ranging study to evaluate the efficacy of alosetron in the treatment of irritable bowel syndrome.

BACKGROUND: Irritable bowel syndrome is a common gastrointestinal disorder characterized by abdominal pain and discomfort and altered bowel habit. Antagonism at the 5-HT3 receptor may be of benefit in the treatment of irritable bowel syndrome. AIMS: To evaluate the effect of 12 weeks of treatment with alosetron, a 5-HT3 receptor antagonist at doses of 0.1 mg b.d., 0.5 mg b.d. and 2 mg b.d. in irritable bowel syndrome patients. METHODS: A double-blind, placebo-controlled, parallel-group study with a 2-week screening and a 12-week treatment period was conducted. A total of 462 patients (335 female) recorded details of the severity of their abdominal pain, and bowel function daily on a diary card throughout the study. At monthly clinic visits patients recorded the severity of their abdominal pain/discomfort and diarrhoea on a visual analogue scale. RESULTS: In the total population and in the female subpopulation (but not in males) alosetron 2 mg b.d. significantly increased the proportion of pain-free days and decreased the visual analogue scale score for diarrhoea compared with placebo. Alosetron at doses of 0.5 mg b.d. and 2 mg b.d. led to a significant hardening of stool, and a reduction in stool frequency in the total population. CONCLUSION: Alosetron at a dose of 2 mg b.d. is an effective treatment for female patients with irritable bowel syndrome.

Division of the irritable bowel syndrome into subgroups on the basis of daily recorded symptoms in two outpatients samples.

BACKGROUND: If subgroups exist in a sample of patients with irritable bowel syndrome (IBS), they may represent different etiologic and pathophysiologic entities. Our aim was to identify subgroups on the basis of symptoms in IBS. METHODS: Two independent groups of 56 (sample I) and 52 (sample II) outpatients recorded their abdominal symptoms daily for 6 weeks and 1 week, respectively. The daily records were assessed by using cluster analysis. RESULTS: Similar subgroups appeared in both samples. Three bowel habit subgroups were identified. The first was distinguished by hard stools, varying stool consistency, and highly disturbed stool passage, the second by loose stools and urgency, and the third by normal stools and the least disturbed stool passage. Two pain/bloating subgroups were identified, one distinguished by little and the other by considerable pain and bloating. No relation was found between pain/bloating and bowel habit subgroup membership. Most patients had stool frequency within the normal range regardless of subgroup. In sample I the subgroups had stable symptoms during the study, and subgroup placement was not related to the presence of dyspepsia, smoking habits, or use of bulk agent and/or sporadic intake of loperamide. The degree of pain and bloating was inversely related to illness duration. CONCLUSIONS: Subgroups exist in IBS. Division of IBS into bowel habit subgroups should be based on stool consistency, not frequency. Mechanisms mediating pain and bloating may be different from those mediating symptoms at defecation.

Abdominal symptoms are not related to anorectal function in the irritable bowel syndrome.

BACKGROUND: The pathophysiologic significance of altered intestinal motility and perception in irritable bowel syndrome (IBS) is unclear, as a consistent association with abdominal symptoms has not been proved. Our aim was to investigate the association between abdominal symptoms and anorectal function in IBS. METHODS: Fifty-two patients recorded their symptoms daily for I week. At the end of the week anorectal function was investigated by manovolumetry before and after a standardized fatty meal. Cluster analysis of daily recorded symptoms and both pre- and postprandial manovolumetric data was performed to identify symptom and physiologic subgroups. RESULTS: Symptom subgroups did not differ with regard to anorectal function. Physiologic subgroups did not differ with regard to daily recorded symptoms. Postprandially, the thresholds eliciting maximal tolerable distention were decreased in 22 of the patients. This increase in rectal sensitivity was not related to symptoms and may have been caused by the preprandial anorectal measurement, since thresholds for maximal tolerable distention decreased significantly in nine patients retested without an intervening meal. CONCLUSIONS: Abdominal symptoms and anorectal function are not related in IBS.

The clinical significance of slightly to moderately increased liver transaminase values in asymptomatic patients.

BACKGROUND: Our aim was to study liver disorders in asymptomatic patients with slightly to moderately increased liver transaminase values in a population living in an area with a low prevalence of viral and hereditary liver diseases. METHODS: One hundred and fifty consecutive patients with slightly to moderately increased liver transaminases for at least 6 months without symptoms or signs of liver disease were included. Median (range) was 0.75 microkat/l (0.24-2.9) for aspartate aminotransferase (ASAT) and 1.18 microkat/l (0.28-4.5) for alanine aminotransferase (ALAT). A percutaneous liver biopsy was performed, and blood was sampled for a detailed biochemical and serologic profile. RESULTS: Chronic viral hepatitis C was found in 15.3% of the patients, autoimmune hepatitis in 1.3%, primary biliary cirrhosis in 1.3%, and heterozygotic alpha-1-antitrypsin deficiency in 0.7%. Presumed alcoholic liver disease was diagnosed in 8%, and non-alcoholic steatohepatitis in 2%. Chronic hepatitis with no obvious etiology was diagnosed in 24%, of whom 39% had interface hepatitis (piecemeal activity). Seventy-one per cent of these 39% had measurable levels of autoantibodies, but IgG levels within normal limits prevented the 'clinical' diagnosis of autoimmune hepatitis. Liver steatosis was the diagnosis in 40%. Most were overweight and had increased serum triglyceride levels. However, in 13.3% the fatty infiltration was considered 'essential', as both body mass index (BMI) and triglyceride levels were normal. Other diagnoses were liver fibrosis with no obvious inflammatory activity (3.3%), cirrhosis of unknown etiology (0.7%), and for the remaining (3.3%) patients histopathologic findings were considered 'normal'. Cirrhosis was found in five biopsy specimens: hepatitis C (n = 2), autoimmune hepatitis (n = 1), primary biliary cirrhosis (n = 1), and cryptogenic cirrhosis (n = 1). No concomitant disease was of importance for the diagnosis and/or histopathologic findings. No obvious drug-related increased liver test results were found with any single drug. However, patients with chronic hepatitis of unknown etiology, especially with interface hepatitis, significantly more often than the rest of the population were receiving drug treatment. CONCLUSION: Most transaminitis patients had steatosis, and some had defined diseases including chronic hepatitis C. Chronic hepatitis of unknown etiology was found in a substantial proportion (24%) of a population living in an area with a low burden of hepatic viruses and genetic disorders.

Pain is temporally related to eating but not to defaecation in the irritable bowel syndrome (IBS). Patients' description of diarrhea, constipation and symptom variation during a prospective 6-week study.

OBJECTIVES: To study the intensity and variation of pain and its temporal relation to eating and defaecation. Furthermore, what irritable bowel (IBS) patients mean by constipation and diarrhea and how bowel symptoms vary. DESIGN: Prospective daily symptom recording over 6 weeks. SETTING: The primary catchment area of University Hospital of Linköping. PARTICIPANTS: Eighty consecutive patients fulfilling the Rome criteria; 63 finished the study. RESULTS: Fifty-nine of 63 patients recorded an average of 29 pain periods and 24 days with pain during the 6 weeks. Over-all pain burden decreased slightly over the study period. At inclusion 38 (64%) patients claimed that pain was relieved by defaecation. However, on average, only 10% of each patient's recorded pain periods were relieved by defaecation. At inclusion 29 (49%) patients claimed postprandial worsening of pain. On average, 50% of each patient's recorded pain periods worsened postprandially. The patients defined constipation as hard stools and diarrhea as loose stools and urgency. Stool frequency did not differ. Bowel symptoms varied within, but not between, fortnightly periods. CONCLUSIONS: Postprandial worsening of pain should be included as a criterion in the clinical definition of IBS while the criterion 'pain relieved by defaecation' should be re-evaluated. IBS patients can probably be divided into subgroups based on stool consistency, not frequency. Daily records are superior to structured clinical interviews or questionnaires for a detailed study of symptoms in IBS.

Low symptomatic load in Crohn's disease with surgery and medicine as complementary treatments.

BACKGROUND: The treatment of Crohn's disease has changed owing to the recognition of its chronicity. Medical maintenance treatment and limited resections have evolved as major concepts of management, regarded as complementary, and both aim at reducing the symptoms. METHODS: We investigated the symptomatic load in Crohn's disease as reflected in a cross-sectional study of the symptom index, physicians' assessment, and the patients' perception of health. A cohort of 212 patients from the primary catchment area and 125 referred patients were studied. RESULTS: Of catchment area patients, 83% were receiving medication, and the annual rate of abdominal surgery was 5.7%. Corresponding figures for the referred patients were 82% and 10.3%. According to the symptom index, 87% of catchment area patients were in remission or had only mild symptoms; according to the physicians' assessment, 90% were. The patients' median perception of health was 90% of perfect health according to the visual analogue scale. The figures were similar for referred patients, except that referrals were considered more diseased by the physician. CONCLUSION: The great majority of patients with Crohn's disease are able to live in remission or experience only mild symptoms.

Assessing an AI knowledge-base for asymptomatic liver diseases.

Discovering not yet seen knowledge from clinical data is of importance in the field of asymptomatic liver diseases. Avoidance of liver biopsy which is used as the ultimate confirmation of diagnosis by making the decision based on relevant laboratory findings only, would be considered an essential support. The system based on Quinlan's ID3 algorithm was simple and efficient in extracting the sought knowledge. Basic principles of applying the AI systems are therefore described and complemented with medical evaluation. Some of the diagnostic rules were found to be useful as decision algorithms i.e. they could be directly applied in clinical work and made a part of the knowledge-base of the Liver Guide, an automated decision support system.

Use of air enema radiography to assess depth of ulceration during acute attacks of ulcerative colitis.

BACKGROUND Acute colitis is usually assessed by means of plain abdominal radiographs, the diagnostic utility of which can be enhanced by barium enema. Colonoscopy can also be useful. The latter methods may be laborious and carry risk. We describe a radiographic technique using air as the contrast medium to show mucosal or deeper ulceration. METHODS Of 60 patients undergoing colectomy for acute ulcerative colitis, 35 had air enema radiography and 14 had plain films with sufficient amount of spontaneously occurring gas to allow visualisation of the mucosa, during the 10 days before surgery. The degree of inflammation on air enema films and the extent of histopathological ulceration in colectomy specimens were independently graded and compared with each other. Depth of ulceration was compared with clinical data including a preoperative risk stratification, the APACHE II score. FINDINGS The degree of inflammation on air enema radiography correlated significantly with depth of ulceration at histopathological examination (rs 0.61, p<0.001). Presence of mucosal changes had a close association with deep ulceration extending into the muscularis propria layer or beyond (p<0.001). Air enema radiography had a high sensitivity (0.91) for presence of and specificity (0.75) in the exclusion of deep ulceration, with positive and negative predictive values of 0.88 and 0.80. 42 of 49 patients were correctly classified as regards deep ulcers. The correlation between higher preoperative APACHE II scores and severity of histopathological colitis was weak (rs 0.30, p<0.05). INTERPRETATION Air enema radiography reliably assesses the presence of colonic ulceration in patients with an acute attack of ulcerative colitis. It is a first-line investigation to assess the presence of deeper ulceration in acute colitis.

Natural history and prognostic factors in 305 Swedish patients with primary sclerosing cholangitis.

BACKGROUND/AIMS--The course of primary sclerosing cholangitis (PSC) is highly variable and unpredictable. This study describes the natural history and outcome of PSC. These data were used to construct a prognostic model for patients with PSC. METHODS--A total of 305 Swedish patients with PSC were studied. The median follow up time was 63 (1-194) months and all patients could be traced for follow up. Some 79 patients died or had a liver transplant. The prognostic significance of clinical, biochemical, and histological findings at the time of diagnosis were evaluated using multivariate analysis. RESULTS--The estimated median survival from time of diagnosis to death or liver transplantation was 12 years. Cholangiocarcinoma was found in 24 (8%) of the patients and 134 (44%) of the patients were asymptomatic at the time of diagnosis. The estimated survival rate was significantly higher in the asymptomatic group (p < 0.001). However, 29 (22%) of the asymptomatic patients became symptomatic during the study period. It was found that age, serum bilirubin concentration, and histological stage at the time of diagnosis were independent predictors of a bad prognosis. These variables were used to construct a prognostic model. CONCLUSIONS--This prognostic model developed from a large homogeneous population of PSC patients should be of value for the timing of transplantation and patient counselling in PSC.