Aslan A.; Triadafilopoulos G.
Gastroenterology Section, Martinez VA Medical Center, 150 Muir Road, Martinez, CA 94553 USA
Am. J. Gastroenterol. (USA), 1992, 87/4 (432-437)

Arachidonic acid metabolites formed by both the cyclooxygenase and lipoxygenase pathways may contribute to the clinical diarrhea and colitis of inflammatory bowel disease. Patients with active ulcerative colitis have increased levels of leukotriene B4 in their rectal mucosa, and these levels tend to correlate with severity of the disease. In this study, we evaluated the efficacy of ingestion of fish oil n-3-omega-fatty acids, inhibitors of leukotriene synthesis, in the treatment of ulcerative colitis. Eleven patients with ulcerative colitis of mild to moderate severity were studied in a 8-month, double-blind, placebo-controlled, crossover trial of dietary supplementation with fish oil, which provided about 4.2 g of omega-3- fatty acids per day. A disease activity index based on patient symptoms and sigmoidoscopic appearance was used to assess efficacy. Mucosal leukotriene B4 production was measured by radioimmunoassay. Mean disease activity index declined 56% for patients receiving fish oil and 4% for patients on placebo (p < 0.05). There were no statistically significant differences in histopathologic scores or colonic mucosal leukotriene B4 levels. All patients tolerated fish oil ingestion and showed no alteration in routine blood studies. No patient worsened; anti-inflammatory drugs could be reduced or eliminated in eight patients (72%) while receiving fish oil. We conclude that fish oil dietary supplementation results in clinical improvement of active mild to moderate ulcerative colitis but is not associated with significant reduction in mucosal leukotriene B4 production, compared with placebo therapy. Further studies are needed to elucidate the mechanism of action and optimal dose and duration of fish oil supplementation in ulcerative colitis.

Simopoulos A.P.
The Center for Genetics, Nutrition and Health, 2001 S Street, NW, Washington, DC 20009 USA
Am. J. Clin. Nutr. (USA), 1991, 54/3 (438-463)

Several sources of information suggest that man evolved on a diet with a ratio of omega6 to omega3 fatty acids of similar 1 whereas today this ratio is similar 10:1 to 20-25:1, indicating that Western diets are deficient in omega3 fatty acids compared with the diet on which humans evolved and their genetic patterns were established. Omega-3 fatty acids increase bleeding time; decrease platelet aggregation, blood viscosity, and fibrinogen; and increase erythrocyte deformability, thus decreasing the tendency to thrombus formation. In no clinical trial, including coronary artery graft surgery, has there been any evidence of increased blood loss due to ingestion of omega3 fatty acids. Many studies show that the effects of omega3 fatty acids on serum lipids depend on the type of patient and whether the amount of saturated fatty acids in the diet is held constant. In patients with hyperlipidemia, omega3 fatty acids decrease low-density-lipoprotein (LDL) cholesterol if the saturated fatty acid content is decreased, otherwise there is a slight increase, but at high doses (32 g) they lower LDL cholesterol; furthermore, they consistently lower serum triglycerides in normal subjects and in patients with hypertriglyceridemia whereas the effect on high-density lipoprotein (HDL) varies from no effect to slight increases. The discrepancies between animal and human studies most likely are due to differences between animal and human metabolism. In clinical trials eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in the form of fish oils along with antirheumatic drugs improve joint pain in patients with rheumatoid arthritis; have a beneficial effect in patients with ulcerative colitis; and in combination with drugs, improve the skin lesions, lower the hyperlipidemia from etretinates, and decrease the toxicity of cyclosporin in patients with psoriasis. In various animal models omega3 fatty acids decrease the number and size of tumors and increase the time elapsed before appearance of tumors. Studies with nonhuman primates and human newborns indicate that DHA is essential for the normal functional development of the retina and brain, particularly in premature infants. Because omega3 fatty acids are essential in growth and development throughout the life cycle, they should be included in the diets of all humans. Omega-3 and omega6 fatty acids are not interconvertible in the human body and are important components of practically all cell membranes. Whereas cellular proteins are genetically determined, the polyunsaturated fatty acid (PUFA) composition of cell membranes is to a great extent dependent on the dietary intake. Therefore appropriate amounts of dietary omega6 and omega3 fatty acids need to be considered in making dietary recommendations, and these two classes of PUFAs should be distinguished because they are metabolically and functionally distinct and have opposing physiological functions. Their balance is important for homeostasis and normal development. Canada is the first country to provide separate dietary recommendations for omega6 and omega3 fatty acids.

O'Morain C.A.
Department of Gastroenterology, Meath/Adelaide Hospitals, Peter Street, Dublin 8 Ireland
Scand. J. Gastroenterol. Suppl. (Norway), 1990, 25/172 (29-34)

The aetiology of inflammatory bowel disease (IBD) remains unknown, and many methods of treatment have been advocated. Patients with IBD are often nutritionally deficient and in negative nitrogen balance. The cause is multifactorial and includes decreased intake and absorption due to previous resection or mucosal involvement or increased exudation. General recommendations of vitamin and mineral supplements are usually made for these patients. Diet may have a more fundamental role in the aetiology and treatment of Crohn's disease, although this is not certain. Several controlled studies have confirmed that an elemental diet is as effective as steroids in inducing a remission in patients with acute Crohn's disease. Bacteria have also been implicated in the aetiology of Crohn's disease. Dietary measures may alter the intestinal flora and could result in a decrease of toxin production, which has been shown to correlate with clinical improvement. Although elemental diets are not effective in the treatment of ulcerative colitis, dietary measures may still be important. Preliminary studies suggest that eicosapentaenoic acid, which inhibits the production of mediators of inflammation by competing with enzymes in the arachidonic acid pathway, may be effective. Recent findings of increased faecal bile acids in patients with long-standing ulcerative colitis who developed dysplasia or carcinoma suggest that dietary measures may counteract these developments. It does appear that nutritional therapy in patients with IBD has both a primary and adjunctive role.

Jenkins H.R.; Pincott J.R.; Soothill J.F.; et al.
Department of Gastroenterology, The Hospital for Sick Children, London United Kingdom
Arch. Dis. Child. (England), 1984, 59/4 (326-329)

Forty six children presented with colitis between 1977 and 1981, and all 8 of those below the age of 2 years had food allergic colitis which resolved completely after exclusion of certain foods. In most of the 8 the onset was soon after starting foods other than breast milk. The most common offending food was cows' milk protein, but soya (3 cases) and beef (1 case) were also implicated. A history of allergy in the child or family was common as were blood eosinophilia, high concentrations of serum IgE, and positive IgE antibodies. Colonoscopic appearances were distinctive and biopsies showed a noticeable increase in eosinophils and IgE-containing cells in the lamina propria. We suggest that food allergy is the major cause of colitis in infancy and that an exclusion diet is the treatment of choice.

Cosnes J.; Tello H.; Le Quintrec M.; et al.
Service d'Hepato Gastroenterologie, Hopital Rothschild, F-75571 Paris Cedex 12 France
Gastroenterol. Clin. Biol. (France), 1983, 7/12 (1003-1009)

In order to assess the effectiveness and potential limitations of continuous enteral nutrition (CEN) to correct denutrition related to underlying digestive diseases, 10 nutritional criteria were measured weekly in 92 undernourished patients fed with CEN for a 3-7 week period. All the patients received a standard non-elemental diet providing a mean daily energy intake of 52.8 kcal/kg BW (36.5 kcal/kg BW by tube feeding and 16.3 kcal/kg BW orally). The influence of preexisting intestinal malabsorption, hypercatabolic status, and post-radiation or inflammatory bowel disease was studied by an a posteriori classification of patients in one of the six following groups: I (no limiting factor), II (malabsorption), III (catabolic disease), IV (catabolic disease and malabsorption), V (colitis), VI (enteritis). During CEN, 8 patients had transient and one had persistent vomiting while 3 developed bronchopneumonia. Gains in body weight, triceps skinfold, midarm muscle circumference, creatinine-height index, urinary sodium and serum transferrin were significant as early as the 2nd week of CEN. Serum albumin and cholesterol, hemoglobin, and total count of lymphocytes were not significantly affected. Sixty-five patients (71 per cent) had an objective nutritional improvement and mean spontaneous oral intake increased from 17.8 to 28.7 kcal/kg BW per day. Significant increase of oral intake and objective nutritional improvement were observed in each group, but a longer period of CEN was necessary to achieve this result in groups II, IV and VI. These results a) confirm that CEN is an effective and well tolerated nutritional treatment in gastrointestinal patients, b) describe the kinetics of nutritional improvement during CEN, and c) show that, in the alimentary conditions of this study, malabsorption, hypercatabolic disease or inflammatory enteropathy are not a contra-indication to the use of CEN. In chronic denutrition CEN must be administered during at least 3 weeks and prolonged until nutritional autonomy is obtained.

Wensinck F.; Custers-Van Lieshout L.M.C.; Poppelaars-Kustermans P.A.J.; Schroder A.M.
Dept. Med. Microbiol., Erasmus Univ., Rotterdam Netherlands
J. Hyg. (England), 1981, 87/1 (1-12)

The faecal flora of patients with Crohn's disease was compared with that of healthy subjects. In patients with terminal ileitis, numbers of anaerobic gram-negative and coccoid rods (species of Eubacterium and Peptostreptococcus) were higher than in the controls whereas anaerobic gram-positive rods and cocci and aerobes occurred in normal numbers. The composition of the flora was neither influenced by duration of the disease nor by ileocaecal resection. In healthy subjects and patients, a chemically defined diet induced only slight changes in the flora. Thus, the flora in terminal ileitis although stable was permanently abnormal. In patients with Crohn's colitis, abnormally low numbers of anaerobes were found in patients with severe, bloody diarrhoea while aerobic counts were normal. The flora in patients with mild colitis was similar to that in terminal ileitis. It is suggested that the abnormal flora composition might be an expression of the genetic predisposition to Crohn's disease.

Axelsson C.; Jarnum S.
Div. Gastroenterol., Med. Dept. P, Rigshosp., Univ. Copenhagen Denmark
Infusionsther. Klin. Ernahr. (Switzerland), 1977, 4/6 (313-318)

During a 4-year period 59 patients were treated with an elemental diet (Vivasorb(Reg.trademark)) for 1-6 weeks. The great majority (41 patients) were suffering from chronic inflammatory bowel disease. The indication for treatment was insufficient remission on prednisone 10-60 mg daily for 1-4 weeks or no remission after a high dose of prednisone (6O-120 mg) for 1-4 weeks. Remission was obtained in 14 patients on elemental diet and a constant or decreasing dose of prednisone and in another 6 on elemental diet and a high dose of prednisone. Thus, a total of 2O patients (50%) remitted. This includes 12 out of 24 with ulcerative colitis, and 8 out of 17 with Crohn's disease. It was not possible to demonstrate significant differences between the groups having moderate and severe disease activity, or between those with topographically restricted and with extensive lesions. The remission was long. During this treatment of patients with chronic inflammatory bowel disease there occurred a significant reduction in faecal bulk, frequency of bowel movements, and the ESR (erythrocyte sedimentation rate). A number of parameters, including serum protein and albumin, remained greatly reduced. Moreover, there was a significant decrease in serum urea and in the renal excretion of urea, due to the low nitrogen content of Vivasorb(Reg.trademark). Treatment of patients with intestinal fistulae (13 patients), the short bowel syndrome (6 patients), intractable diarrhoea (4 patients), recurrent pancreatitis (2 patients) and hyperlipaemia (2 patients) gave good results in several, but far from all cases. In particular, no effect was obtained in patients having the short bowel syndrome.

Goschke H.; Buess H.; Gyr K.; et al.
Dept. Inn. Med., Univ., Basel Switzerland
Schweiz.Med.Wschr. (Switzerland), 1977, 107/2 (43-49)

21 patients with gastroenterological disease and indication for the use of intravenous nutrition received an elemental diet (ED) for 5-44 days. In 6 out of 8 patients with exacerbation of Crohn's disease remissions were achieved, apart from 3 persistent fistulas. In 5 out of 9 cases with various primary diseases and postoperative intestinal fistulas, spontaneous healing was observed. Furthermore, 2 patients with ulcerative colitis, 1 with radiation enteritis and 1 with pancreatitis were treated with ED. On ED, hemoglobin increased from 11.3 + or - 0.4 (m + or - SEM) to 12.0 + or - 0.5 g% (p <0.01) and serum albumin from 2.7 + or - 0.1 to 3.4 + or - 0.1 g% (p <0.001). Nitrogen requirements were studied in 11 patients receiving various quantities of ED. Nitrogen balance was found to be in equilibrium or positive in 7 patients, and negative in 4. In one patient with severe ulcerative colitis, fecal nitrogen losses were higher than urinary nitrogen losses. The unpleasant taste of ED resulting from free amino acids limited the ED supply in 3 patients and led to premature ending of ED administration in 3 other patients. In such cases ED may be given by nasogastric tube feeding. From the results presented it appears that ED is indicated in Crohn's disease and intestinal fistulas. However, the results obtained require confirmation by further observations and comparison with an intravenously fed control group.

Falchuk K.R.; Falchuk Z.M.
Dept. Med., Massachusetts Gen. Hosp., Peter Bent Brigham Hosp., Boston, Mass. USA
Gastroenterology (USA), 1975, 69/2 (503-506)

A patient with selective immunoglobulin A deficiency, severe ulcerative colitis, and malabsorption had a flat jejunal mucosa demonstrated by peroral biopsy. Treatment at different times with a gluten free diet for the jejunal lesion and corticosteroids for the ulcerative colitis, led to improvement of the malabsorption. A great jejunal biopsy demonstrated histological improvement of the jejunal mucosa, even though the colitis remained active. The occurrence of immunoglobulin A deficiency in a patient with ulcerative colitis and gluten sensitive enteropathy is uncommon.

Ito T.
I Dept. Int. Med., Hirosaki Univ. Sch. Med., Hirosaki Japan
Hirosaki Med.J. (Japan), 1974, 26/2 (167-186)

A comparative study of the absorption of various kinds of fatty acids and corresponding triglycerides and a study of MCT metabolism in experimental animals is presented. Time lapse absorption of MCT and LCT was studied in fasted albino rats by giving orally sup 1sup 4C labeled fatty acid preparations. Octanoic acids were mostly absorbed within an hr but only 32% of palmitate. The absorption of sup 1sup 4C labeled glycerol trioctanoate was studied. Small intestines of the dog were ligated and segmented into 3 parts (upper, middle and lower). Of the 3 segments, the middle showed the fastest absorption of glycerol trioctanoate 1 sup 1sup 4C. Experiments in dogs with indwelling cannulas in the thoracic ducts showed that only 5.21 x 10sup -sup 2 muCi of administered glycerol trioctanoate 1 sup 1sup 4C was transported to the lymphatics in 120 min. The radioactivity in the lipids of albino rat liver was studied 60 and 120 min after an oral administration of glycerol trioctanoate 1 sup 1sup 4C. The radioactivity of the lipid fraction was 1.3% of all activity that was absorbed. Nearly 54.1% of the radioactivity of lipids from liver slices was detected in phospholipids and 36.8% in triglycerides but in free fatty acids and cholesterol esters the activity was extremely low. The radioactivity of administered glycerol was detected in the form of sup 1sup 4COsub 2 as early as 15 min after ingestion and this activity increased abruptly after 30 min and in 75 min it reached 21.3% of the administered dose and 28% of the total absorbed glycerol. Clinical study was performed to evaluate MCT therapy in 10 patients, 7 of them with postoperative malabsorption syndrome, one with liver cirrhosis, one with pancreatic cyst and one with postoperative ulcerative colitis. After a control period, 150 g of MCT was added daily to the diet of the patients. Because of the untoward effects, the MCT regimen was discontinued in 3 cases. The other 7 patients treated for more than a mth showed an increase in body weight of over one kilogram on average. Abnormally low serum cholesterol and albumin in a patient attained a normal range after one month of MCT administration. sup 1sup 3sup 1I triolein test improved and the frequency of bowel movements decreased in all patients. To achieve clinical effectiveness, MCT was continuously administered for at least a mth. In patients with malabsorption syndrome, there was an increase in body weight, serum cholesterol and serum albumin, a decrease in frequency of bowel movements and an improvement in the nature of the stool.

Jarnum S.
Med. Afd. P, Gastroenterol. Afsnit, Rigshosp., Kobenhavn Denmark
Ugeskr.Laeg. (Denmark), 1974, 136/17 (912-920)

Crohn's disease attracts increasing interest on account of its many clinical and pathophysiological aspects and because it seems to be becoming more frequent. Based on case material of 179 patients with Crohn's disease treated in hospital over a 10 yr period, certain epidemiological, clinical and pathophysiological features are discussed. Diagnostic accuracy is considered high. Thus the small intestine was involved in approximately 90%. However, the case material is selected and, therefore, less suited for an epidemiological study. One third was transferred from other hospitals, one fourth lived in Copenhagen, one third in Jutland. Copenhagen citizens in the case material represented a 'minimal' prevalence of 7.8 per 100,000 inhabitants in Copenhagen City, and the total case material a prevalence of 3.6 per 100,000 in the whole country. Owing to selection the true prevalence must be considerably higher. There were 50% more women than men. The pathophysiological characteristics of Crohn's disease are largely due to its liability to involve the ileum. Enterogenous vitamin Bsub 1sub 2 malabsorption occurred in 67% of 118 patients studied. It was also present in 11% of 70 patients with ulcerative colitis. Extensive intestinal resection is another, less frequent consequence of Crohn's disease. Studies in 24 patients subjected to extenseive but intestinal resection (75-270 cm) showed Bsub 1sub 2 malabsorption to occur only after ileal resection, whereas decreased serum folic acid developed mainly following jejunal resection. The serum protein pattern shows a characteristic bun nonspecific change. Albumin and often transferrin are decreased, orosomucoid increased. Immunoglobulin levels are within normal range, but higher in patients who respond favourably to medical treatment than in patients who do not. Intestinal plasma protein loss is almost consistently present. Treatment of Crohn's disease should be a combined and harmonized surgical medical undertaking. Resection is now preferred to 'by pass' interventions. Medical treatment comprises specific and individualized treatment. Specific treatment aiming at suppression of the inflammatory process is possible with salicylazosulfapyridine which is effective in mild and moderate cases, glucocorticoids which may have a dramatic effect in severe cases without obstruction, and, possibly, immunosuppressive agents, the value of which is still disputable. Individualized medical treatment covers a wide range of therapeutic measures: vitamin substitution (especially vitamin Bsub 1sub 2), electrolytes, bile acid binding resin to counteract cholegenic diarrhoea, dietary fat restriction (40 g fat per day) in the short bowel syndrome, symptomatic therapy with analgetic, spasm relieving and constipating drugs. Complete parenteral nutrition or treatment with 'elementary diet' may be beneficial in selected, severe cases, in particular when intestinal fistulas are present.

Tasev T.; Nedkova Bratanova N.; Nikolov N.; et al.
Kat. Gastroenterol. Dietet., ISUL, Sofia Bulgaria
Vatr.Bolesti (Sofia) (Bulgaria), 1973, 12/2 (24-31)

The results are reported from simultaneous clinical, morphological and enzymological examinations of 105 patients with different gastrointestinal diseases. The quantitative determination of lactase, maltase and invertase in homogenate of jejunal mucous membrane was carried out by the Dahlquist method. A decrease of lactase was found in 65.45% of the patients with non specific chronic enteritis, of maltase on 56% and invertase in 43.9%. In patients with gastric resection the figures for these 3 examinations were 45.4%, 25% and 33.3%; and in patients with ulcerative colitis in 55.5%, 57.14% and 25% resp. Comparison of the data after disaccharide loading and the quantitative enzyme determination showed a certain parallelism in 2/3 of the cases. No correlation was established between the morphological investigations and enzyme values. The excluding of non tolerated disaccharides from the diet for a relatively longer time led to clinical improvement and restoration of jejunal mucous membrane with the exception of lactase, the disaccharide content was elevated.

Breuer R.I.; Soergel K.H.; Lashner B.A.; Christ M.L.; Hanauer S.B.; Vanagunas A.; Harig J.M.; Keshavarzian A.; Robinson M.; Sellin J.H.; Weinberg D.; Vidican D.E.; Flemal K.L.; Rademaker A.W.
Dr. R.I. Breuer, Evanston Hospital, Special GH Laboratory, 2650 Ridge Avenue, Evanston, IL 60201 USA
Gut (United Kingdom), 1997, 40/4 (485-491)

Background - Short chain fatty acid (SCFA) deficiency is associated with colitis in animals and humans, and the mucosal metabolism of these compounds is decreased in ulcerative colitis. Aims - To assess the efficacy of topical SCFA treatment in ulcerative colitis.

Patients and Methods - 103 patients with distal ulcerative colitis were entered into a six week, double-blind, placebo controlled trial of rectal SCFA twice daily; patients who were unchanged on placebo were offered SCFA in an open-label extension trial.

Results - Of the 91 patients completing the trial, more patients in the SCFA treated than in the placebo treated group improved (33% v 20%, p = 0.14, NS). Those on SCFA also had larger, but statistically non-significant, reductions in every component of their clinical and histological activity scores. In patients with a relatively short current episode of colitis (<6 months, n = 42), more responded to SCFA than to placebo (48% v 18%, p = 0.03). These patients also had larger, but statistically non-significant, decreases in their clinical activity index (p = 0.08 v placebo). Every patient who improved used at least five of six of the prescribed rectal SCFA irrigations, whereas only 37% who did not improve were as compliant. In the open-label extension trial, 65% improved on SCFA; these patients also had significant reductions (p < 0.02) in their clinical and histological activity scores.

Conclusions - Although SCFA enemas were not of therapeutic value in this controlled trial, the results suggest efficacy in subsets of patients with distal ulcerative colitis including those with short active episodes. Prolonged contact with rectal mucosa seems to be necessary for therapeutic benefit.

Williams C.N.
CRC, Dalhousie University, 5849 University Avenue, Halifax, NS B3H 4H7 Canada
Can. J. Gastroenterol. (Canada), 1993, 7/2 (196-199)

There are many issues and controversies concerning nutrition in inflammatory bowel disease (IBD). Most authorities now accept that total parenteral nutrition (TPN) is useful, both as primary and adjunct therapy in the management of patients with Crohn's disease, but only useful as adjunct therapy in patients with acute flare-ups of ulcerative colitis. In both, there is a role for TPN in preparing patients for imminent surgery. In comparison with TPN, defined formula (elemental diet) therapy has less complications, is easier to monitor, is less costly, and gives equivalent results. Several controlled trials have shown that elemental diet therapy is as useful as prednisone in inducing remission in patients with active Crohn's disease. Elemental diets have been compared with polymeric diets in patients with Crohn's disease, and have been shown to be effective; recently a semi-elemental diet has also been shown to be as effective as elemental diet, but with a conferred benefit of maintaining essential fatty acid levels. Elemental diets do not appear to be effective in closing fistulas. If the problems of palatability and, in some patients, nausea, vomiting, abdominal cramps and diarrhea persist, these can be overcome to some extent by flavour changes, chilling, gradual introduction and counselling or nasogastric tube feeding. Recently, fish oils have been used in patients with IBD. There is suggestive evidence that they are of benefit in patients with ulcerative colitis but not in Crohn's disease. There is a suggestion that fish oils have a steroid-sparing effect which, if confirmed, will be of great potential benefit to patients with ulcerative colitis.

Greenfield S.M.; Green A.T.; Teare J.P.; Jenkins A.P.; Punchard N.A.; Ainley C.C.; Thompson R.P.H.
Gastrointestinal Laboratory, The Rayne Institute, St Thomas' Hospital, London SE1 7EH United Kingdom
Aliment. Pharmacol. Ther. (United Kingdom), 1993, 7/2 (159-166)

In a placebo-controlled study, 43 patients with stable ulcerative colitis were randomized to receive either MaxEPA (n = 16), super evening primrose oil (n = 19), or olive oil as placebo (n = 8) for 6 months, in addition to their usual treatment. Treatment with MaxEPA increased red-cell membrane concentrations of eicospentaenoic acid (EPA) at 3 months by three-fold and at 6 months by four-fold (both P < 0.01), and doubled docosahexaenoic acid (DHA) levels at 6 months (P < 0.05). Treatment with super evening primrose oil increased red-cell membrane concentrations of dihomogamma-linolenic acid (DGLA) by 40% at 6 months (P < 0.05), whilst treatment with placebo reduced levels of DGLA and DHA at 6 months (both P < 0.05). Clinical outcome was assessed by patient diary cards, sigmoidoscopy and histology of rectal biopsy specimens. Super evening primrose oil significantly improved stool consistency compared to MaxEPA and placebo at 6 months, and this difference was maintained 3 months after treatment was discontinued (P < 0.05). There was however, no difference in stool frequency, rectal bleeding, disease relapse, sigmoidoscopic appearance or rectal histology in the three treatment groups. Despite manipulation of cell-membrane fatty acids, fish oils do not exert a therapeutic effect in ulcerative colitis, while evening primrose oil may be of some benefit.

Hawthorne A.B.; Daneshmend T.K.; Hawkey C.J.a; Belluzzi A.; Everitt S.J.; Holmes G.K.T.; Malkinson C.; Shaheen M.Z.; Willars J.E.
Department of Therapeutics, University Hospital, Nottingham NG7 2UH United Kingdom
Gut (United Kingdom), 1992, 33/7 (922-928)

The effect of fish oil on the course of ulcerative colitis was investigated in a randomised blinded controlled study. Eighty seven patients received supplements of 20 ml HiEPA fish oil as triglyceride (4.5 g of eicosapentaenoic acid) or olive oil placebo daily for one year. The oils were given in addition to standard drug therapy and trial entry was stratified for disease activity. Fish oil significantly increased the eicosapentanoic acid content of rectal mucosa to 3.2% of total fatty acids at six months, compared with 0.63% for patients on olive oil. This was associated with increased synthesis of leukotriene B5, and 53% suppression of leukotriene B4 synthesis by ionophore-stimulated neutrophils. Leukotriene B4 suppression persisted for at least two months after treatment was stopped. Treatment with fish oil resulted in measurable, but only limited clinical benefit. For patients entering the trial in relapse (n = 53), there was a significant reduction in corticosteroid requirement after one and two months treatment. There was a trend towards achieving remission (off corticosteroids) faster in the patients on fish oil, although differences were not significant. For patients in remission at trial entry or during the trial (n = 69), there was no significant difference in the rate of relapse by log rank analysis. We conclude that fish oil supplementation produces a modest corticosteroid sparing effect in active disease, but there is no benefit in maintenance therapy.

Hillier K.; Jewell R.; Dorrell L.; Smith C.L.
Clinical Pharmacology Group, Faculty of Medicine, University of Southampton, Southampton SO9 3TU United Kingdom
Gut (United Kingdom), 1991, 32/10 (1151-1155)

The incorporation of the fatty acids in fish and olive oil into the colonic mucosa of patients with inflammatory bowel disease was examined during 12 weeks' dietary supplementation with the oils, and the influence on colonic mucosal prostaglandin and thromboxane generation was measured. With a dietary supplement of 18 g fish oil daily, concentrations of the major polyunsaturated fatty acids in fish oil, eicosapentaenoic acid and docosahexaenoic acid, were significantly raised in mucosal lipids. The first time these were measured, after three weeks' supplementation, the mean increases in eicosapentaenoic and docosahexaenoic acid were seven fold and 1.5 fold respectively, and these increases were maintained during the 12 week study. Arachidonic acid values fell throughout the study and this reduction was significant at 12 weeks. Mucosal prostaglandin E2 (PGE2), thromboxane B2, and 6-keto prostaglandin F(1alpha) synthesis were suppressed, and this reached significance (p < 0.05) at three and 12 weeks for PGE2 and at 12 weeks for thromboxane B2. The predominant fatty acid in olive oil is oleic acid. Supplementation with 18 g/day resulted in a significant increase in oleic acid in colonic mucosa at 12 weeks (p < 0.05) and a fall in stearic acid and docosahexaenoic acid; there was no significant change in eicosanoid synthesis. It is concluded that colonic lipids and prostaglandin and thromboxane synthesis can be readily altered by dietary supplementation with fish oil. The extent of incorporation of the fatty acids present in oils is dependent upon the individual fatty acid.

Krizek V.; Sadilek L.
Vyzkumny Ustav Balneologicky, Marianske Lazne Czech Republic
Fysiatr. Revmatol. Vestn. (Czech Republic), 1993, 71/4 (195-212)

1. Carlsbad mineral water is a hydrogencarbonate-sulphur containing thermal water with a mineralization of cca 6.4 g.l-1. It is drunk at the springs in the spa and is bottled under the name 'Mlynsky pramen' (Mill spring).

2. 28-day controlled clinical trial comprising two weeks of drinking Carlsbad water was to provide new information on the suitability of this water in nephrourological indication.

3. The trial comprised 16 experimental subjects, mostly suffering from urolithiasis, four suffered from gout. During the first and fourth week the subjects drank 1.5 litres of ordinary drinking water, during the second and third week the same amount of Carlsbad water. The standard diet which was the same every week made it possible to compare the excretion of minerals and other substances during individual periods in the course of the investigation.

4. Drinking of Carlsbad water induced desirable diuresis. The demand of a diuresis of more than 2 l.d-1 was met only by 52 to 55% of the daily amounts.

5. Drinking of Carlsbad water led to slight alkalization of the urine from pH 5.8 to 6.8 with a corresponding decline of titratable acid and ammonia in urine. Acid-base indicators in blood were not affected.

6. Calciuria rose by 4 to 7%, magnesiuria, on the other hand, declined slightly. The Ca/Mg quotient in urine rose insignificantly. The blood levels of calcium and magnesium declined slightly. It was not possible to confirm analogous effects to those described formerly by Stransky.

7. A 20% rise of natriuria was recorded and elevated inorganic sulphaturia by 45 to 57%. The urinary potassium excretion increased slightly. The chloride excretion, on the other hand, declined by 8.5%. Serum electrolytes did not display major changes.

8. The tolerance of the Carlsbad water drinking cure - 3 times 0.5 l - was good. The water had a minor purgative effect. The daily frequency of bowel movements increased by 36 to 60% and there was a higher proportion of loose but not diarrhoeal stools.

9. Uricaemia declined by 17% and uricuria by 13 to 16%. The uric acid clearance declined by 7 to 11%. In the four patients suffering from gout analogous effects were recorded as in subjects without gout. No uricosuric effect was found.

10. During the drinking cure in the investigated non-diabetic subjects the morning blood sugar and insulin level were not affected.

11. The Carlsbad water drinking cure is indicated in particular in urate and cystine urolithiasis. It will be useful to use the drinking cure more frequently to ensure primary and secondary prevention of oxalate lithiasis in gastroenterological patients with malabsorption syndromes, in conditions following intestinal bypasses, jejunostomies, similarly as in the prevention of urate lithiasis in ulcerative colitis, in particular after operations such as ileostomies, colectomies etc.

12. The Carlsbad water drinking cure, in particular larger amounts, must be indicated carefully in conditions where the ingestion of sodium or alkalization of urine are not desirable.

Ferraris L.; Karmeli F.; Eliakim R.; Klein J.; Fiocchi C.; Rachmilewitz D.
Department of Medicine, Hadassah University Hospital, Mount Scopus, PO Box 24035, Jerusalem 91240 Israel
Gut (United Kingdom), 1993, 34/5 (665-668)

Generation of platelet activating factor by intestinal mucosal epithelial cells and lamina propria mononuclear cells was evaluated to elucidate the possible role of this mediator in the pathogenesis of inflammatory bowel disease. Epithelial and lamina propria mononuclear cells were isolated from surgical specimens from control, Crohn's disease, and ulcerative colitis patients. Platelet activating factor was extracted from highly purified cell preparations with 80% ethanol after stimulation with and without 0.2 uM calcium ionophore A23187 and was measured by platelet aggregation assay. Both cell types generated platelet activating factor activity and this was generally comparable for epithelial and lamina propria cells. Basal and stimulated platelet activating factor activity of epithelial and lamina propria cells from ulcerative colitis but not Crohn's disease patients was appreciably higher than that of control. Stimulation with calcium ionophore increased appreciably platelet activating factor activity in lamina propria cells from all groups. In contrast, only epithelial cells from ulcerative colitis showed an appreciable increase after calcium ionophore induction. These results suggest that epithelial cells are important contributors to intestinal platelet activating factor generation under normal and inflammatory conditions and that epithelial cells actively play a part in the pathogenesis of ulcerative colitis.

Kirsner J.B.
Department of Medicine, University of Chicago, Chicago, IL USA
Dis. Mon. (USA), 1991, 37/11 (673-675)

Once regarded as medical curiosities, ulcerative colitis and Crohn's disease have achieved a remarkable change in status recently and today are among the more compelling of all human illnesses. The cause(s) of inflammatory bowel disease (IBD) are not known. Genetic, environmental, microbial, and immunologic factors are involved, but the precise mechanisms are obscure. The incidence of ulcerative colitis is relatively stable, while Crohn's disease continues to increase in frequency. In 10% to 15% of patients, it is hard to differentiate between ulcerative colitis and Crohn's colitis, however, problems with diagnosis usually resolve with time and repeated examinations. In part I of his two-part monograph on IBD, Dr. Kirsner addressed the nature and pathogenesis of the disease. Increased study of ulcerative colitis and Crohn's disease in recent years has generated new knowledge regarding their etiology. Part I focused on microbial, immunologic, and genetic mechanisms of, and the inflammatory process involved in the disease. In this part, Dr. Kirsner deals with the clinical features, course, and management of IBD, based on the author's 55 years of experience with these problems and supplemented by critical examination of the recent (1988-1990) literature. Particular attention is directed to the symptoms and physical findings of ulcerative colitis and Crohn's disease. The laboratory, radiologic, endoscopic, and pathologic features, and the many systemic complications. IBDs are mimicked by several enterocolonic infections and other conditions making differential diagnosis necessary. Inflammatory bowel disease in children and the elderly conforms to conventional clinical patterns modified by the health circumstances of the respective age groups. Because the cause of IBD has not been established, current medical therapy is facilitative and supportive rather than curative. The principles of medical treatment are approximately the same for ulcerative colitis and Crohn's disease. Treatment emphasizes a program rather than a drug and also considers the individuality of the therapeutic response. A clearer understanding of dietary and nutritional needs, including hyperalimentation and electrolyte and fluid balance, aids treatment. Antidiarrheal and antispasmodal preparation and sedatives are prescribed for symptom relief. The bowel inflammation is controlled with sulfasalazine or the newer 5-amino-salicylic acid (5-ASA) compounds, antibacterial drugs for complications of Crohn's disease and IBD, adrenocortical steroids, and the immunosuppressive compounds 6-mercaptopurine (6MP), azathioprine, and cyclosporine, as determined in each patient. The surgical procedures available for treatment of ulcerative colitis include total protocolectomy and ileostomy or ileoanal anastomosis. In Crohn's disease of the small bowel, the usual approach is intestinal resection and reanastomosis. Strictureplasty is possible in some instances of stenotic intestinal disease. For treatment of Crohn's colitis, procedures include total proctocolectomy, total colectomy with ileal anastomosis, and occasionally, segmental resection of the large intestine. Chronic IBD requires prolonged observation, periodic adjustments in therapy, and colonic and radiologic surveillance. The prognosis of ulcerative colitis and Crohn's disease is much improved over the years, but a cure has not yet been found reemphasizing the need for further investigation of these challenging diseases.

Harries A.D.; Brown R.; Heatley R.V.; et al.
Department of Gastroenterology, University Hospital of Wales, Cardiff United Kingdom
Gut (England), 1985, 26/11 (1197-1203)

Forty patients with Crohn's disease were divided into undernourished (18) and well nourished (22) groups depending on whether their midarm circumference was below or above 90% of the ideal standard. Plasma 25-(OH)D3 and the dihydroxylated metabolites, 24,25-(OH)sub 2D3 and 1,25-(OH)sub 2D3 were measured in the summer. Results were related to clinical and biochemical parameters and also compared with results from patients with ulcerative colitis and healthy subjects who served as controls. Plasma 25-(OH)D3 was reduced in the undernourished Crohn's group compared with the well nourished Crohn's group, who did not differ from the controls. Over 50% of the undernourished Crohn's group had evidence of secondary hyperparathyroidism and raised alkaline phosphatase concentrations, although concentrations of 1,25-(OH)sub 2D3 were normal. The low 25-(OH)D3 concentrations related to disease activity. It is suggested that undernourished Crohn's patients who have high levels of disease activity are at risk of vitamin D deficiency, and attempts should be made to improve their vitamin D nutrition.

Bellaiche G.; Le Pennec M.P.; Slama J.L.; Ley G.; Choudat L.; Giacomini T.; Godefroy Y.; Paugam B.
Service de Gastroenterologie, Ctr. Hosp. General Robert Ballanger, Boulevard Robert-Ballanger, 93602 Aulnay-Sous-Bois Cedex France
Annales de Gastroenterologie et d'Hepatologie (France), 1996, 32/1 (11-17)

The goal of this study was to evaluate the contribution of sigmoidoscopy with bioptic microbiology to the etiologic diagnosis of acute diarrhea in adults. Patients and methods. Sixty-five patients with acute diarrhea were included prospectively from February 1993 to November 1994. Ages ranged from 17 to 83 years. In each patient, two stool samples were cultured and three examined for parasites. Clostridium difficile toxin was looked for in the 18 patients who had taken antimicrobials before onset of the diarrhea. Sigmoidoscopy with collection of biopsy specimens for bacteriologic cultures was performed routinely. Results. A pathogenic organism was identified in 35 patients (54%). Eighteen patients (28%) had positive stool cultures. Clostridium difficile toxin was detected in six patients. Colonic biopsy cultures were positive in 26 patients (40%). Endoscopic findings established the diagnosis of pseudomembranous colitis with negative tests for C. difficile toxin in two patients, diverticulitis in one, ischemic colitis in two, and cryptogenic colitis in seven. Conclusions. Sigmoidoscopy ensured the diagnosis in over 72% of cases of acute diarrhea. This investigation complements stool cultures and should be done routinely in adults with severe acute diarrhea.

Patterson M.; Healy G.R.; Shabot J.M.
Gastroenterol. Div., Dept. Med., Univ. Texas Med. Branch, Galveston, Tex. 77550 USA
Gastroenterology (USA), 1980, 78/1 (136-141)

The diagnosis of amoebiasis presents problems, particularly if one relies on finding the organism. Thus, serologic tests are expedient. A gel diffusion precipitin test (GDP), commercially available, simple to perform, and inexpensive, was compared with the indirect hemagglutination test (IHA). 257 Patients' sera were tested; 14 had amoebic colitis, 21 had amoebic liver abscess, 63 had suspected amoebic liver abscess, and 46 had inflammatory bowel disease. GDP tests were positive in 85% of amoebic colitis and 95% of amoebic liver abscess patients; IHA was positive in 91% of amoebic colitis and 94% of abscess patients. Within 6 mo, GDP tests became negative in 66% of patients. IHA tests were observed positive up to 20 yr. The performance characteristics of diagnostic methods for amoebiasis, fecal examination, IHA and GDP, show serologic tests have superior sensitivity and predictive value in recognizing invasive disease.

Solomon G.E.
Mount Sinai Sch. Med., City Univ. New York, N.Y. 10029 USA
Mt.Sinai J.Med. (USA), 1976, 43/5 (602-624)

The currently available clinical and laboratory data (119 references) make it still premature to conclude that IBD represents an autoimmune process. None of the 6 definitive criteria for autoimmune disease have been well established for either chronic ulcerative colitis (CUC) or Crohn's disease (CD). Nevertheless, there is a good deal of available data which supports an autoimmune etiology. Virtually all of the ancillary findings which Sell labels as presumptive evidence for autoimmune disease have been demonstrated in IBD. These include: a morphologic picture consistent with known allergic reactions; the demonstration of antibody or a positive delayed skin reaction; a depression of complement during any stage of the disease; a beneficial effect from agents known to inhibit some portions of an allergic reaction (steroids, radiation, anti-metabolites, etc.); an association with other possible autoimmune diseases; identification of a reasonable experimental model in animals that mimics the human disease: an increased familial susceptibility to the same or other autoimmune disease; and an association between the disease state and specific HLA (human histocompatibility antigen) types (Sell, S; Immunol., Immunopathol., and Immunity, New York, 1972). A framework, consistent with the available data, in which these criteria are satisfied consists of a breakdown of colonic mucosal barriers, which might represent a distinct immunizing event in which the underlying enteric lymphatic tissue becomes exposed to coliform antigens. Following immunization, a latent period might ensue during which sensitized cells or antigen or both communicate with the systemic immune system, possibly via Peyer's patches. Clones of cells programmed to respond to the coliform antigen are produced, possibly in the thymus, and migrate to the lamina propria of the enteric tract. Subsequent exposure to coliform antigen or cross-reacting colonic antigens causes release of lymphotoxin from these sensitized lymphocytes resulting in local cytolysis. Damage to mucosal cells leads to the release of mucosal cell antigens and further compromises the mucosal barrier, allowing a self perpetuating reaction in which the inflammatory process leads to the release of those antigens which initiated the inflammation. These antigens, both bacterial and colonic, have been fairly well identified. The evidence for a transmissable agent may well represent a transfer of the sensitive state by cells from an affected individual to a normal individual, and the periods of remission which punctuate IBD may represent the temporary induction of tolerance by optimal concentration of antigen. Although these proposed mechanisms are purely speculative, they are useful in that they clearly point out those areas to which future research must be directed.

Fabia R.; Ar'Rajab A.; Johansson M.-L.; Willen R.; Andersson R.; Molin G. Bengmark S.
Dept. of Surgery, Lund University, S-221 85 Lund Sweden
Scand. J. Gastroenterol. (Norway), 1993, 28/2 (155-162)

The potential beneficial effect of exogenous administration of Lactobacillus on acetic acid-induced colitis was evaluated in the rat. Colitis was induced by instillation of 4% acetic acid for 15 sec in an exteriorized colonic segment. This produced uniform colitis with a threefold increase in myeloperoxidase (MPO) activity of the colonic tissue (an index of neutrophil infiltration) and a sixfold increase in plasma exudation into the lumen of the colon (mucosal permeability) as evaluated 4 days after acetic acid administration. Intracolonic administration of L. reuteri R2LC immediately after acetic acid administration, at a dose of 5 ml of 7 x 107 colony-forming units (CFU)/ml in two forms: either as pure bacterial suspension or as fermented oatmeal soup, prevented the development of colitis. Thus, the morphologic score, MPO activity, and mucosal permeability were almost normalized by Lactobacillus treatment. Initiating the treatment 24 h after acetic acid administration or using lower doses of 1 ml for 3 consecutive days resulted in a smaller protective effect. We conclude that exogenous administration of L. reuteri R2LC prevents the development of acetic acid-induced colitis in the rat.

Besterman H.S.; Mallinson C.N.; Modigliani R.; et al.
Dep. Med., R. Postgrad. Med. Sch., London W12 0HS United Kingdom
Scand. J. Gastroenterol. (Norway), 1983, 18/7 (845-852)

We have studied fasting levels and the response to a standard test breakfast of blood glucose and several gut hormones in 24 patients with ulcerative colitis, in 14 patients with Crohn's disease, and in 14 healthy control subjects. Patients with ulcerative colitis had significantly elevated fasting human pancreatic polypeptide (HPP) concentrations, and both basal and postprandial levels of gastrin, gastric inhibitory polypeptide (GIP), and motilin were greater than normal. In contrast, patients with Crohn's disease had normal gastrin levels but had increased fasting and postprandial levels of GIP and motilin and, in addition, of enteroglucagon, compared with controls. These patients also had greater than normal HPP concentrations 30 min after the breakfast. Normal levels of insulin, pancreatic glucagon, neurotensin, and vasoactive intestinal polypeptide were found in both groups of patients. Much remains to be known about the pathophysiology of these two debilitating diseases, and the abnormal release of gut hormones may be of importance.

Rutgeerts P.; Ghoos Y.; Vantrappen G.
Dept. Med., Univ. Hosp. St Rafael, 3000 Leuven Belgium
Eur. J. Clin. Invest. (England), 1982, 12/2 (135-143

The metabolism of cholic acid and chenodeoxycholic acid was studied in seventeen patients with non-operated Crohn's disease, eleven ileitis and six ileocolitis patients. The turnover of cholic acid was significantly increased in patients with ileitis (k = 2.0 + or - 1.13 dayssup -sup 1; P < 0.001) and ileocolitis (k = 0.91 + or - 0.47 dayssup -sup 1; P < 0.005) as compared to normals (k = 0.35 + or - 0.19 dayssup -sup 1). Although chenodeoxycholic acid was better preserved in the enterohepatic circulation than cholic acid its turnover was also significantly faster in ileitis (k = 0.81 + or - 0.56 dayssup -sup 1; P < 0.005) and ileocolitis patients (k = 0.62 + or - 0.18 dayssup -sup 1; P < 0.01) than in normals (k = 0.20 + or - 0.09 dayssup -sup 1). The fractional turnover of cholic acid was related to the length of ileal involvement (r = 0.761; P < 0.001; n = 17). Patients with Crohn's ileitis tended to preserve normal fasting total bile acid pools by increased synthesis of primary bile acids and efficient absorption of deoxycholic acid and ursodeoxycholic acid by the normal colon. Patients with active ileocolitis had decreased total fasting pool sizes (2.62 + or - 1.83 mmol; P < 0.001) as compared to normals (7.69 + or - 1.61 mmol). In these patients there was no increase in bile acid synthesis as compared to normals and secondary bile acids were absent frome bile. It is concluded that the colon has an important role in maintaining the fasting pool size to a normal level in the presence of an interrupted enterohepatic circulation of bile acids due to ileal disease.

Vantrappen G.; Ghoos Y.; Rutgeerts P.; Janssens J.
Lab. Gastrointest. Pathophysiol., Dept. Med. Res., Univ. Leuven Belgium
Gut (England), 1977, 18/9 (730-735)

The pool size and composition of bile acids were studied in 13 unoperated patients with uncomplicated Crohn's disease, 10 patients with ulcerative colitis, and 10 normal subjects. Many patients with Crohn's disease had in their bile a significantly increased amount of ursodeoxycholic acid. The bile acid pool size was significantly decreased and the ratio of glycine to taurine conjugates was significantly increased in the Crohn's disease patients. The reduction in bile acid pool size was related to the activity of the disease. The disorders of bile acid metabolism suggest that the intestinal involvement in Crohn's disease is much more extensive than can be demonstrated by careful radiological examinations.

Lenz K.
Med. Dept. P, Div. Gastroenterol., Rigshosp., Copenhagen Denmark
Scand.J.Gastroent. (Norway), 1976, 11/8 (769-775)

Bile acid and vitamin Bsub 1sub 2 malabsorption were evaluated in 34 cases of ulcerative colitis. Twenty four patients were non operated and 10 patients were colectomized. The postprandial duodenal bile acid concentration was abnormally low in 13 of 24 non operated cases and found to be correlated to the activity of the disease. Two of six patients subjected to colectomy had a reduced bile acid concentraion. Bile acid absorption was assessed by the cholyl glycine 1 sup 1sup 4C breath test combined with faecal analysis. The sup 1sup 4C excretion in breath was abnormally elevated in only one of the patients in the total material. The faecal sup 1sup 4C output was related to the disease activity in the non operated group. Patients colectomized for ulcerative colitis had an extremely high excretion of isotope in the ileal effluent, from 15 to 81 per cent of the dose given. The faecal sup 1sup 4C output was correlated with the duration of the ileostomy and the mass of ileal discharge. Vitamin Bsub 1sub 2 malabsorption was only present in five patients. It is concluded that patients with ulcerative colitis during the active phase of the disease have bile acid malabsorption, and patients colectomized for ulcerative colitis have an abnormal high bile acid deconjugation in the ileal effluent.

Grimes D.S.
Dept. Med., Withington Hosp., Manchester United Kingdom
Lancet (England), 1976, 1/7956 (395-397)

A diet high in refined carbohydrate is implicated in the aetiology ofsome diseases of the colon i.e., diverticular disease, irritable bowel syndrome, ulcerative colitis, non occlusive ischaemic colitis, and pseudomembranous colitis. It is suggested that spasm of the smooth muscle is the common pathogenetic mechanism in these colonic diseases. The strength of the spasm producing increased pressure in the colonic lumen or wall and the length of time for which the colon has been affected are believed to determine the type of disease resulting. A diet high in refined carbohydrate allows the intense muscle spasm to occur because the physical buffering effect of faecal bulk is considerably reduced.

Ellestad Sayed J.J.; Nelson R.A.; Adson M.A.; et al.
Dept. Ped., Univ. Manitoba, Winnipeg USA
Amer.J.Clin.Nutr. (USA), 1976, 29/12 (1333-1338)

To investigate further an apparent relationship between chroniculcerative and granulomatous colitis and pantothenic acid deficiency,colonic tissues obtained at the time of colectomy in 29 patients with these disorders were assayed for pantothenic acid and for coenzyme A (CoA) activity. For comparison, normal colonic tissues free of pathological lesions were obtained from 31 patients having colectomy for carcinoma or diverticulitis. Plasma, red blood cells, and colonic mucosa were assayed microbiologically for free and total pantothenic acid. The activity of CoA in colonic mucosa was determined by assaying the acetylation of sulfanilamide. Concentrations of free, bound and total pantothenic acid in blood and in colonic mucosa did not differ between the two groups of patients. Bound pantothenic acid increased linearly with total pantothenic acid. Colonic mucosa concentrated free pantothenic acid to about 50 times the level of blood, and pantothenic acid in red cells was similar to the concentration in plasma. Compared to normal gut mucosa, CoA activity was markedly low in mucosa from patients with chronic ulcerative or granulomatous disease despite the presence of normal amounts of free and bound pantothenic acid. A block in the conversion of bound pantothenic acid to CoA in diseased mucosa is suggested.

Murch S.H.; MacDonald T.T.; Walker-Smith J.A.; Levin M.; Lionetti P.; Klein N.J.
Dept. Paediatric Gastroenterology, St Bartholomew's Hospital, London EC1A 8BE United Kingdom
Lancet (United Kingdom), 1993, 341/8847 (711-714)

We have studied the distribution and nature of sulphated glycosaminoglycans (GAGs) within normal and inflamed intestine. There is increasing evidence that these negatively charged polysaccharides, which both regulate the ability of albumin to leave the vasculature and inhibit thrombosis, may be affected by inflammatory cells and their products. We obtained samples of freshly resected intestinal tissue from eight controls, eleven patients with Crohn's disease, and six with ulcerative colitis. Sulphated GAGs were detected by means of a gold-conjugated poly-L-lysine probe, and the tissue density of anionic sites was assessed semiquantitatively by means of a Lennox graticule. In normal intestine there was staining in the vascular endothelium and the subepithelial basal lamina and throughout the extracellular matrix of the lamina propria and submucosa. Tissue from the patients with inflammatory bowel disease showed inflammation macroscopically and on histology. There were profound abnormalities of extracellular matrix GAGs, limited to the mucosa in ulcerative colitis and greatest in the submucosa in Crohn's disease. There was also substantial loss of GAGs from the subepithelial basal lamina in both disorders and from the vascular endothelium in submucosa in Crohn's disease. The extent of local GAG disruption was associated with the distribution of macrophages immunoreactive for tumour necrosis factor alpha and the activation marker RM 3/1. We suggest that inflammatory disruption of vascular and connective tissue GAGs may be an important pathogenetic mechanism, contributing to the leakage of protein and fluid, thrombosis, and tissue remodelling seen in inflammatory bowel disease.

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