Abdominal pain is associated with anxiety and depression scores in a sample of the general adult population with no signs of organic gastrointestinal disease.

BACKGROUND: Abdominal pain is common in the community, but only a subset meet diagnostic criteria for irritable bowel syndrome (IBS). Although anxiety and depression have been linked to IBS, the role of mood disturbances in the remainder with symptoms remains unclear. We aimed to study the associations between abdominal pain, anxiety, depression, and quality of life in the general population who were free of organic colonic disease by colonoscopy. METHODS: Two hundred and seventy-two randomly selected subjects from the general population, mean age 54 years (27-71), were clinically evaluated, had a colonoscopy and laboratory investigations to exclude organic gastrointestinal (GI) disease. All subjects completed GI symptom diaries for 1 week, the Rome II modular questionnaire, the Hospital Anxiety and Depression Scale, and Short Form 36. KEY RESULTS: Twenty-two subjects were excluded due to organic disease; 1532 daily symptom records were available for analysis in the remainder. Thirty-four percent (n = 83) recorded at least one episode of abdominal pain on the diary. Twelve percent fulfilled Rome II criteria for IBS. Both anxiety and depression scores were higher in subjects who reported abdominal pain vs those who did not (P < 0.0005 and P < 0.0005). Anxiety and depression scores independently from IBS diagnosis (Rome II) predicted pain reporting and also correlated positively with pain burden. Quality of life scores were generally lower in subjects with abdominal pain. CONCLUSIONS & INFERENCES: Anxiety and depression are linked to functional abdominal pain, not only in subjects with IBS but also in otherwise healthy people with milder, subtle GI symptoms.

Nutritional aspects in patients with functional gastrointestinal disorders and motor dysfunction in the gut. Working team report of the Swedish Motility Group (SMoG).

In reviews regarding the management of patients with functional gastrointestinal disorders and motility disturbances within the gut nutritional aspects and dietary advice is often put forward as being of great importance. However, there are relatively few high-quality, interventional studies in the literature supporting an important role for general dietary advice to improve symptoms in these patients. Nutritional supplementation to patients with malnutrition due to severe dysfunction of the gastrointestinal tract is of course less controversial, even though different views on how this should be performed exist. The content of this article is based on presentations given by the authors during the second meeting of the Swedish Motility Group held in Gothenburg in March 2005, and aims to give an overview on the role of dietary advice and nutritional supplementation to patients with gastrointestinal dysfunction of different severity.

A double-blind, placebo-controlled, randomized study to evaluate the efficacy, safety and tolerability of tegaserod in patients with irritable bowel syndrome.

BACKGROUND: Tegaserod has been shown to be an effective therapy for the multiple symptoms of irritable bowel syndrome (IBS) in Western and Asia-Pacific populations. This study evaluated the efficacy, safety and tolerability of tegaserod versus placebo in patients with IBS. METHODS: Patients with IBS (excluding those whose primary bowel symptom was diarrhoea) were randomized to receive either tegaserod 6 mg b.i.d. (n = 327) or placebo (n = 320) for a 12-week double-blind treatment period. The primary efficacy variable (over weeks 1 to 4) was the response to the question: 'Over the past week do you consider that you have had satisfactory relief from your IBS symptoms?' Secondary efficacy variables assessed overall satisfactory relief over 12 weeks and the individual IBS symptoms. RESULTS: Overall satisfactory relief was greater in the tegaserod group than in the placebo group. Over weeks I to 4, the odds ratio was 1.54, that is, the odds of satisfactory relief were 54% higher in the tegaserod group than in the placebo group (95% confidence interval for odds ratio (CI) (1.14, 2.08), P = 0.0049). Over weeks 1 to 12, the odds ratio was 1.78, that is, the odds of satisfactory relief were 78% higher in the tegaserod group than in the placebo group (95% CI (1.35, 2.34), P < 0.0001). A statistically significant therapeutic gain over placebo was observed for the majority of weeks from week 1 to week 12 (except weeks I and 4), with a mean therapeutic gain of 7.3 and 10.6 percentage points over weeks 1-4 and weeks 1-12, respectively. Headache was the most commonly reported adverse event (8.0% tegaserod versus 4.7% placebo). Diarrhoea was reported by 9.2% of patients on tegaserod (1.3% on placebo) and led to discontinuation in 2.8% of tegaserod patients. CONCLUSION: Tegaserod 6 mg b.i.d. is an effective, safe and well-tolerated treatment in patients suffering from IBS without diarrhoea as primary bowel symptom.

[Functional gastrointestinal diseases. More reliable diagnosis using new criteria. Modification required in primary care, however]. / Funktionella mag-tarmsjukdomar. Säkrare diagnostik med nya kriterier. Behöver dock kompletteras för användning i primärvården.

The diagnosis of functional gastrointestinal disorders is symptom based. New viewpoints go beyond the old concept of a disease-based reductionistic model, according to which effort is directed toward identifying a single underlying biological etiology, to a more integrated biopsychosocial model of illness. "Rome II: A Multinational Consensus Document on Functional Gastrointestinal Disorders" is an attempt to condense present knowledge into a practical systematic manual. Whereas the ordinary clinician may benefit from it in the understanding of the often confusing accumulation of alternating bowel complaints, its main area of application will be international studies. It will also serve as a basis for taking the concept of functional gastrointestinal disorders further.

Spectral analysis of heart rate variability in patients with irritable bowel syndrome.

BACKGROUND: Autonomic dysfunction, both adrenergic and cholinergic, has been associated with the irritable bowel syndrome (IBS). The accuracy of the methods in use, however, has been limited by the need for active co-operation by the patients, with consequent difficulties in standardization. The aim of this study was to investigate the function of the autonomic nervous system in patients with IBS by using spectral analysis of the heart rate variability, an accurate method depending very little on patient cooperation. METHODS: Eighteen patients with IBS were compared with 36 sex- and age-matched controls. Spectral analysis of heart rate variability was performed to quantify sympathetic and parasympathetic nerve activity. RESULTS: The patients with IBS had significantly higher sympathetic activity than controls (P = 0.005). There was no significant (P = 0.308) increase in parasympathetic activity. There were no significant differences in heart rate or blood pressure between the patients and controls. CONCLUSION: Spectral analysis of heart rate variability has been used to assess the function of the autonomic nervous system in patients with IBS. IBS patients have significantly increased symphathetic activity, whereas parasympathetic activity does not differ from that of controls.

Serum 7 alpha-hydroxy-4-cholesten-3-one and selenohomocholyltaurine (SeHCAT) whole body retention in the assessment of bile acid induced diarrhoea.

OBJECTIVE: To assess the reliability of serum 7 alpha-hydroxy-4-cholesten-3-one (7 alpha-3ox-C) in the differential diagnosis of bile acid induced diarrhoea by comparison with 75selenohomocholyltaurine whole body retention (SeHCAT WBR). DESIGN: One hundred and sixty-four patients with chronic diarrhoea were investigated prospectively in two centres (Edinburgh and Sweden) by two different tests which measure bile acid loss or synthesis: the SeHCAT test which measures the 7-day SeHCAT WBR and serum 7 alpha-3ox-C which reflects the rate of bile acid synthesis. RESULTS: Forty-six patients had SeHCAT WBR of less than 10% (19 with ileal disease or resection, nine with idiopathic bile acid induced diarrhoea and 18 with miscellaneous causes for bile acid induced diarrhoea). All patients with ileal or idiopathic disease showed a favorable response to treatment as did 13 of the miscellaneous group. Serum 7 alpha-3ox-C was raised in all subjects with ileal disease/resection, seven patients with idiopathic disease and all subjects in the miscellaneous group who responded to treatment. Sixteen out of 118 patients with SeHCAT WBR greater than or equal to 10% had raised serum 7 alpha-3ox-C. CONCLUSION: The positive predictive value of serum 7 alpha-3ox-C was 74%. The high negative predictive value (98%) of serum 7 alpha-3ox-C indicates the possible use of this test for excluding bile acid malabsorption in this population. All but two subjects who responded to treatment had raised serum 7 alpha-3ox-C concentrations. The possibility that the sensitivity of the test can be improved by repeat testing needs to be further investigated. There was a significant correlation between fractional catabolic rate (FCR) SeHCAT and serum 7 alpha-3ox-C (r = 0.63, P < 0.0001). Further data are required to validate the reference range in women over 70 years of age.

Beeturia and colonic oxalic acid.

Beeturia is the excretion of red beetroot pigment (betalaine) in urine and faeces. It occurs in about 14% of humans. Betalaine is a redox indicator whose colour is protected by reducing agents. We investigated pigment-decolourizing systems in the intestinal tracts of beeturic and non-beeturic subjects. Betalaine was decolourized by hydrochloric acid, ferric ions and colonic bacteria preparations, but not by pancreatic or mucosal enzymes. In animals, oral betalaine did not produce beeturia, but injection of betalaine into the peritoneum did. Oral betalaine and 1 g oxalic acid produced beeturia in non-beeturic normal humans, but passed into ileostomies without beeturia. Thus, beeturia results from colonic absorption of betalaine. Oxalic acid preserves the red colour to the colon, otherwise it is decolourized in non-beeturic individuals by non-enzymic processes in the stomach and colon.

Bile acid malabsorption in Crohn's disease and indications for its assessment using SeHCAT.

Patients with Crohn's disease who suffer from longstanding diarrhoea that does not respond to conventional treatment pose a common clinical problem. Bile acid malabsorption is a possible cause, although its prevalence and clinical importance is unclear. This paper explores the clinical indications for referring patients with Crohn's disease for bile acid assessment and the extent of bile acid malabsorption in this selected group of patients. The selenium labelled bile acid SeHCAT was used to assess the effect of disease on the integrity of the enterohepatic circulation. Altogether 76% of the patients referred for bile acid assessment had longstanding diarrhoea that had not responded to conventional anti-diarrhoeal treatment or an increase in steroid therapy as their sole or predominant symptom. Ninety per cent of patients with bowel resections, almost exclusively ileocaecal, had abnormal SeHCAT retention (< 5% at seven days). Twenty eight per cent of patients with Crohn's disease who had not undergone resection 28% had a SeHCAT retention < 5%, signifying bile acid malabsorption. Nineteen of 22 patients given cholestyramine treatment subsequent to the SeHCAT test had a good symptomatic response. In conclusion, the prevalence of bile acid malabsorption in this selected group with Crohn's disease is sufficiently high to justify performing the SeHCAT test in order to separate the various differential diagnoses.

In vivo measurements of lead in bone in long-term exposed lead smelter workers.

In-vivo measurements of lead concentrations in calcaneus (mainly trabecular bone) and tibia (mainly cortical bone) were performed by x-ray fluorescence (XRF) in 70 active and 30 retired lead smelter workers who had long-term exposure to lead. Comparison was made with 31 active and 10 retired truck assembly workers who had no known occupational exposure to lead. After physical examination, all participants provided blood and urine samples and answered a computerized questionnaire. Since 1950, blood lead has been determined repeatedly in lead workers at the smelter, which made it possible to calculate a time-integrated blood lead index for each worker. Lead concentrations in blood, urine, calcaneus, and tibia in active and retired lead workers were significantly higher than in the corresponding control groups (p < .001). The highest bone lead concentrations were found among retired lead workers (p < .001), which was the result of considerably higher lead exposure during 1940 to 1960. Lead concentrations in calcaneus in active lead workers were significantly higher than in tibia when expressed in ug of lead per gram of bone mineral, which suggests a quicker absorption over time in this mainly trabecular bone. The estimated biological half-times were 16 y in calcaneus (95% confidence interval [95% CI] = 11-29 y) and 27 y in tibia (95% CI = 16-98 y). A strong positive correlation was found between lead concentrations in calcaneus and tibia for all lead workers (r = 0.54; p < .001). A strong positive correlation was also found between the bone lead concentrations and the cumulative blood lead index. Blood lead, at the time of study, correlated well with bone lead concentrations in retired--but not in active--workers, reflecting the importance of the endogenous (skeletal) lead exposure. The findings in this study indicate that bone lead measurements by XRF can give a good index of long-term lead exposure. Tibia measurements offer a higher precision than calcaneus measurements. The method is of particular interest in epidemiologic studies of adverse health effects caused by long-term lead exposure.

Non-alimentary aspects of the irritable bowel syndrome.

The irritable bowel syndrome (IBS) is characterized by alimentary and non-alimentary symptoms; the aim of this study was to assess the clinical value and discriminant function of non-alimentary symptoms in the irritable bowel syndrome. Alimentary and non-alimentary symptoms, estimated daily dietary fibre intakes, ability to express personal feelings, anxiety and depression ratings, and life events and difficulties inventories were compared in 128 hospital out-patients with IBS and 113 age and sex matched control subjects not seeking health care, randomly recruited from the community. Alimentary symptoms correlated closely with those non-alimentary symptoms often associated with the hyperventilation syndromes, difficulties in expressing personal feelings and anxiety, and depression ratings. Life events and difficulties, and estimated daily dietary fibre intakes did not differ significantly between patients and controls. With the exception of abdominal bloating, no significant gender differences were observed in IBS symptoms in either the IBS or control groups. The irritable bowel syndrome is one facet of a more general condition of illness behaviour which includes the hyperventilation syndrome and an inassertiveness in expressing personal feelings. Though non-alimentary symptoms did not improve diagnostic accuracy beyond that achieved by a combination of alimentary symptoms, their recognition provides alternative approaches to the management of refractory IBS.

Kidney effects in long term exposed lead smelter workers.

Occupational exposure to lead may cause kidney damage. This study was carried out on a cohort of 70 active and 30 retired long term exposed lead smelter workers. Their kidney function was compared with 31 active and 10 retired truck assembly workers who had no occupational exposure to lead. The lead workers had been regularly followed up with measurements of lead concentration in blood since 1950. Previous exposure to lead was calculated as a time integrated blood lead index for each worker. Blood and urine samples were obtained from all subjects. The concentration of lead in blood (B-Pb) and urine (U-Pb) was analysed. The urinary concentrations of several sensitive indicators of early tubular (U-beta 2-microglobulin (U-beta 2-m); U-N-acetyl-beta-glucosaminidase (U-NAG)) and glomerular kidney damage (U-albumin) were determined. The B-Pb and U-Pb values were significantly higher among active and retired lead workers compared with their corresponding control groups. The highest concentrations were found among the active lead workers. The concentrations of the parameters of kidney function investigated were of the same magnitude for exposed workers and controls. No clinical signs of renal impairment were found among the workers. No correlations of clinical importance existed between concentrations of U-albumin, U-beta 2-m, and U-NAG activity on the one hand and the concentrations of B-Pb, cumulative blood lead index, U-Pb, and lead concentrations in the calcaneus and tibia on the other, among lead workers and controls. Despite many years of moderate to heavy exposure to lead, particularly for the retired lead workers, no signs of adverse effects on the kidney such as early tubular or glomerular malfunction were found. Reversible changes in kidney function during the 1950s and 1960s could not be excluded, however, due to a greater exposure to lead during that time.

Chronic diarrhoea after radiotherapy for gynaecological cancer: occurrence and aetiology.

The occurrence of chronic diarrhoea was evaluated in 173 consecutive patients previously treated with radiation for gynaecological cancer. A survey of gastrointestinal symptoms showed a high frequency of diarrhoea; 13% of the patients had 21 or more bowel movements a week and 3% had 28 or more. Significantly more patients who had a cholecystectomy were in the group with diarrhoea (chi 2 = 6.26; p less than 0.02). Twenty patients with chronic or intermittent diarrhoea were subject to extended gastrointestinal investigation. Bile acid malabsorption was evaluated by the 75Selenahomocholic acid-taurine test (SeHCAT). Bile acid malabsorption was found in 13 (65%) of the 20 patients further investigated, of whom seven had extremely low whole body retention values, which is consistent with severe malabsorption. The results suggest that bile acid malabsorption is a common cause of diarrhoea after radiation treatment for gynaecological cancer. Bacterial contamination was diagnosed in nine patients (45%) by the [14C]-D-xylose breath test or by the cholyl-[14C]-glycine breath test in combination with a normal test for bile acid malabsorption. All patients with vitamin B-12 deficiency, who were tested for bile acid malabsorption, had low retention times for the SeHCAT (p = 0.05). A significant decline in the frequency of diarrhoea was found after treatment with antibiotics or bile acid sequestrants, or both, in combination with a reduced fat diet.

Bile acid malabsorption after intestinal bypass surgery for obesity. A comparison between jejunoileal shunt and biliointestinal bypass.

Seventeen patients were operated on with intestinal shunts for morbid obesity, in eight a biliointestinal bypass (BI) was constructed and in the rest a conventional jejunoileal (JI)-shunt. The reduction in weight was similar in both groups, and so was malabsorption of fat, but the BI-group had significantly less bowel motions with less watery diarrhoea. Bile acid malabsorption was measured both chemically by estimating the total amount of faecal bile acids excreted, as well as indirectly by using a 75Se-labelled synthetic bile acid (SeHCAT). Both techniques revealed a substantial loss of bile acid after both types of operation, but patients with BI bypass surgery had significantly lower elimination time of the bile acid than those with JI-shunts. There was a significant negative correlation between SeHCAT retention and total faecal bile acids. However, some patients with low SeHCAT retention had normal or even reduced output of faecal bile acids. Estimation of faecal bile acids may display false negative results when the bile acid pool is decreased. The SeHCAT-test seems to be a better technique for measuring bile acid losses. The study suggests that BI bypass surgery for obesity seems to be advantageous over the JI shunt in reducing the postoperative loss of bile acids and choleretic diarrhoea, without influencing the weight loss.

Adhesion of bacteria to the human small-intestinal mucosa. A scanning electron microscopic study.

During the period 1 January 1980 to 30 June 1986, a total of 543 small-intestinal biopsy specimens from adults with gastrointestinal symptoms were available for routine analysis with correlated scanning electron microscopy and light microscopy. Adhesion of microorganisms was found in 77 biopsy specimens. Microorganisms in 64 specimens were classified as bacteria, in 10 as microfungi and in 4 as protozoa, including 1 specimen with both bacteria and microfungi. The structural types of bacteria found were morphologically cocciform, 8; short rod-shaped, 14; and long rod-shaped, 43. One specimen demonstrated adhesion of two structural types of bacteria. Bacteria were found in specimens from all age groups in roughly equal frequency. There was no difference in villus structure when comparing specimens from the groups with and without adhering bacteria, whereas ultrastructural alteration--that is, thinning of glycocalyx layer--was significantly more frequent in the group with bacteria. Moreover, within the group of specimens with bacteria the presence of long rod-shaped bacteria was associated with both damage of villus structure and deviation of cell surface ultrastructure. An increased amount of neutrophil granulocytes as an indicator of acute inflammation was found in 6 of 51 specimens with bacterial adhesion but in none of a matched reference material. In contrast, the amount of plasma cells and lymphocytes in the lamina propria and the amount of intraepithelial lymphocytes did not differ.

Bile acid malabsorption demonstrated by SeHCAT in chronic diarrhoea, with special reference to the impact of cholecystectomy.

SeHCAT is a gamma-labelled synthetic bile acid, suitable for external measurements and detection of bile acid malabsorption. In this study 138 subjects were investigated with 75SeHCAT. The technique was modified by calculating the biologic half-life of the isotope (WBR-50) within 48 h. All patients with ileocaecal resection had reduced WBR-50 values, as did most (8 of 12) with Crohn's disease affecting the small bowel. Among patients with chronic diarrhoea 24 out of 62 patients had reduced WBR-50 values. Four of the patients with low WBR-50 and one in the group with normal WBR-50 had previously been cholecystectomized. In a consecutive study, 15 patients were investigated before and after cholecystectomy. In 12, WBR-50 decreased after the operation (p less than 0.05). The results demonstrate the impact of cholecystectomy on the interpretation of the SeHCAT retention results. The results may also add to the understanding of diarrhoea secondary to cholecystectomy.

Muscle magnesium and capillary basement membrane thickness in diabetes mellitus.

To evaluate a possible relationship between Mg deficiency and the development of microvascular disease in diabetes mellitus, quadriceps muscle biopsies for estimating Mg content and capillary basement membrane thickness, were studied in 16 patients with type I diabetes. The diabetic individuals had a slightly but significantly reduced muscle Mg content as compared with 13 healthy controls. There was a significant, positive correlation between capillary basement membrane width and age in the diabetic group, but no relationship between membrane thickness and muscle or serum concentration of Mg. However, diabetic patients with retinopathy (n = 6) showed a nonsignificant inverse correlation between basement membrane thickness and Mg parameters. The opposite tendency was found in patients without retinal lesions.

Incidence of Crohn's disease in a defined population in northern Sweden, 1974-1981.

An epidemiologic study of Crohn's disease, comprising the population of the two most northerly counties of Sweden and covering the 8-year period 1974-1981, was carried out. The basic population was about 510,000, and the area is regarded as rural, with a mean density of 3 inhabitants per km2. In all, 199 patients with a hospital discharge diagnosis of Crohn's disease were identified. A mean annual incidence of 4.9 per 10(5) inhabitants and a peak incidence of 6.7 were found. There was no sex difference and no obvious change in incidence during the time period studied. The highest incidence was observed in young adults, and ileal disease predominated. A significantly higher incidence was observed in the town of Umeå than in the rest of northern Sweden. The increase was confined to the ages between 20 and 40 years. The present study concludes that the incidence of Crohn's disease is high in northern Sweden, even though it is a sparsely populated rural area. The incidence figures are similar to those obtained for other parts of Sweden.