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.

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.

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.

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.

Crohn's disease and the enterohepatic circulation.

Crohn's disease is a chronic inflammatory process which may affect any part of the alimentary tract. This cause is unknown. Overall the distribution of the lesions coincides with that of the enterohepatic circulation. A possible causative agent is a metabolic or ingested substance excreted into the bile in the form of a polar and inactive conjugates. The agent would have to have a prolonged half life in the enterohepatic circulation. In the ileocaecal region and elsewhere when bacterial colonisation occurs the inactive conjugates may be hydrolysed to release the active substance. This would act locally on the intestinal tissues either as a result of altering the physicochemistry of mucus or during passage through the gut wall.

Clinical application of a selenium (75Se)-labelled bile acid for the investigation of terminal ileal function.

With the introduction of a selenium bile acid SeHCAT (tauro-23-75Se-Selena-25 homocholic acid) a new and clinically valuable test for the functioning of the terminal ileum has been made available. Previous studies have shown that the test detects patients with bile acid malabsorption due to ileal disease. In this study SeHCAT retention was evaluated in nine patients with Crohn's disease and in seven healthy controls after intravenous administration of 0.15 MBq (4 muCi). A simple way of expressing the results is proposed. By using the calculated time required to eliminate 50% of the SeHCAT (WBR50), information is obtained as to the degree of terminal ileum malfunction regarding bile acid absorption. Accurate values seem to be achieved within 48 hours. As the SeHCAT is a gamma-ray emitter the dose retained could be measured by external counting. We suggest a practical design for the test using a simple scintillation spectro-photometer with a single detector in a low-background room. In patients and healthy controls the SeHCAT retention as calculated by WBR50 was 63 hrs (15-163) and 120 hrs (range 99-141), respectively. There was no overall relation between SeHCAT elimination and the intestinal transit time, although in the patient group a significant correlation was demonstrated, probably secondary to the impairment of the terminal ileum. A significant correlation was shown between the outcome of the test and the faecal excretion of total bile acids.

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.

[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.

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.

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.

The small-intestinal mucosa in patients with Crohn's disease assessed by scanning electron and light microscopy.

Small-intestinal mucosal biopsy specimens obtained by a Watson capsule were assessed by light (LM) and scanning electron (SEM) microscopy in 18 patients with various sites of Crohn's disease and in 6 healthy controls. By means of LM, partial villous atrophy of the upper small-intestinal mucosa was assessed in six patients. With the use of SEM a further seven patients were shown to have mucosal abnormalities of possible clinical significance. These specimens showed a convoluted villous pattern at low-power SEM and some also enterocyte irregularity, bulging, and surface ultrastructural distortion at medium- and high-power SEM. The medium- and high-power mucosal alterations were unevenly distributed. The high prevalence of abnormalities of the upper small-intestinal mucosa in patients with Crohn's disease elsewhere in the gastrointestinal tract adds further weight to the concept of a diffuse involvement along the entire gastrointestinal tract in Crohn's disease.

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.

The relationship between active peptic ulcer, endoscopic duodenitis and symptomatic state after treatment with cimetidine.

Fifty patients with active peptic ulcers on endoscopy were randomly allocated for treatment with placebo or cimetidine (1.0 g daily) over a period of four weeks. All patients had free access to antacids to relieve epigastric pain. In the cimetidine group a significantly higher proportion of the ulcers had healed (82.6% of the patients) compared with the placebo group (48.0%). There was poor correlation between the healing of the ulcer and dyspeptic symptoms in the placebo group. The results suggest that the presence of endoscopic duodenitis is to a great extent responsible for the dyspepsia. Cimetidine treatment, besides healing the ulcers, also improved the endoscopic duodenitis and the symptomatic state more than placebo treatment. No significant clinical side effects were observed. Chemical abnormalities were only noted with respect to serum creatinine. In the cimetidine group there was a statistically significant rise in serum creatinine, which was most apparent after two weeks of treatment. However, the increase was slight and not significant among the males, whereas in the case of the females there was a large and highly significant rise. The reason for this sex difference is at present unknown.

Effect of long term treatment with hydrophilic colloid on serum lipids.

Thirteen patients with essential hyperlipoproteinaemia were treated over periods of 2--29 months with hydrophilic colloid made from Psyllium. Reduction of the increased serum cholesterol levels averaged 16.9 per cent, and the corresponding figure for the increased triglyceride levels was 52.0 per cent. The reduction of cholesterol and triglyceride was statistically significant (p less than 0.0025 and p less than 0.0005 respectively). No significant change in normal blood lipid levels was observed on administration of the Psyllium colloid.

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.

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.

Aggravation of thiamine deficiency by magnesium depletion. A case report.

A patient with Crohn's disease and long-standing diarrhea resulting in a combined thiamine and magnesium deficiency is presented. Despite massive doses of thiamine i.v., the symptoms of thiamine deficiency could not be suppressed until the magnesium deficiency was corrected as well. This case report emphasizes the dependence of thiamine on magnesium for an adequate function in the body.

Plasma and skeletal muscle electrolytes in patients with Crohn's disease.

Plasma and skeletal muscle electrolytes were measured in 13 patients with Crohn's disease, and in an age- and sex-matched reference group. Patients with Crohn's disease demonstrated significantly lower muscle potassium content (p less than 0.01) than did controls. Patients with extensive involvement of the bowel tended to have lower muscle potassium content. The patient population did not differ significantly from the controls with regard to skeletal muscle magnesium content but displayed a far wider range of values. Our results indicate that potassium depletion is present in nonresected patients with Crohn's disease.