Schwan A.; Sjolin S.; Trottestam U.; Aronsson B.
Institute of Clinical Bacteriology, S-75122 Uppsala Sweden
Scand. J. Infect. Dis. (Sweden), 1984, 16/2 (211-215

Repeated recurrence of Clostridium difficile-associated enterocolitis is uncommon but troublesome for the afflicted patient. The patient described here received vancomycin treatment several times but always had a relapse of C. difficile enterocolitis 2-3 weeks after discontinuation of treatment. She did not form serum antibodies to C. difficile cytotoxin (toxin B). Rectal infusion of enemas prepared from fresh faeces resulted in final cure.

Reichlin B.; Gyr K.
Abt. Gastroenterol., Dept. Inn. Med., Univ. Basel Switzerland
Ther. Umsch. (Switzerland), 1980, 37/3 (194-197)

There are many interactions between antibiotics and the intestinal microflora. The purpose of this review is to focus above all on four such interactions with some clinical importance: General side-effects of antibiotics on the gastrointestinal tract are described briefly, problems of antibiotic resistance in intestinal bacteria and the new understanding of pseudomembranous colitis are explained in more detail. Finally some aspects of colonisation of the gastrointestinal tract with Lactobacillus acidus are discussed.

Bischoff S.C.; Herrmann A.; Goke M.; Manns M.P.; Von Zur Muhlen A.; Brabant G.
Dr. S.C. Bischoff, Dept. of Gastroenterology/Hepatology, Medical School of Hannover, D-30623 Hannover Germany
American Journal of Gastroenterology (USA), 1997, 92/7 (1157-1163)

A reduced bone mineral density has been reported in inflammatory bowel disease (IBD).

Objective: To assess the mechanisms of bone disease in IBD.

Methods: We studied in 90 patients (61 with Crohn's disease, 22 with ulcerative colitis, 7 with indeterminate colitis) biochemical markers of bone metabolism in serum and bone mineral density by peripheral quantitative computed tomography at the forearm.

Results: Forty-five percent of the patients had a reduced bone density (Z score < -1). Serum calcium was normal in most patients, vitamin D deficiency was documented in 17%. Osteocalcin, a serum marker of bone formation, was decreased in 26% (1.2 plus or minus 0.1 ng/ml), whereas the carboxyterminal cross-linked telopeptide of type I collagen (ICTP), a recently described serum parameter of bone breakdown, was stimulated in 38% (10.4 plus or minus 2.3 microg/L). Of 33 patients with increased ICTP levels, 19 showed a decreased bone density (Z score < -1), and 2 of them never received steroids. An active status of the underlying disease in most patients with increased ICTP levels suggests a direct effect of the underlying IBD. In the whole series of patients with a history of active disease (n = 34), 47% had signs of an increased bone degradation (ICTP > 5 microg/L; mean, 12.9 plus or minus 4.7 microg/L). Data derived from a retrospective survey of 245 patients with IBD suggest that the prevalence of bone fractures in IBD is unexpectedly high, particularly in patients with a long duration of disease, frequent active phases, and high cumulative doses of corticosteroid intake.

Conclusions: Several mechanisms may be involved in IBD-associated bone disease: (1) a high inflammatory activity directly induces bone degradation via yet unknown pathways, (2) treatment with corticosteroids may exert catabolic effects on the bone, or (3) malabsorption and vitamin D deficiency may activate bone turnover.

Wright D.H.
University Department of Pathology, Southampton General Hospital, Tremona Road, Southampton SO16 6YD United Kingdom
Bailliere's Clinical Gastroenterology (United Kingdom), 1995, 9/2 (351-369)

Neoplasms constitute the major complication of coeliac disease, and high-grade T-cell lymphoma of the small intestine (enteropathy-associated T-cell lymphoma) is the most common neoplasm in this category. HLA genotyping indicates that in patients with enteropathy-associated T-cell lymphoma have the coeliac disease associated DQA1*0501, DQB1*0201 phenotype, although additional HLA-DR/DQ alleles may represent risk factors for lymphoma development. Molecular biological and immunohistochemical studies have shown that the intestinal mucosa distant from the tumour contains clonal populations of small T cells, often of tile same clone as the high-grade T-cell lymphoma. These findings suggest that enteropathy-associated T-cell lymphoma arises in the setting of coeliac disease and evolves from reactive intraepithelial lymphocytes through a low-grade lymphocytic neoplasm to a high-grade tumour, which is usually the cause of the presenting symptoms. Most cases of chronic ulcerative enteropathy (ulcerative jejunitis) are probably part of the same disease process. If the ulceration occurs at a time when the neoplastic T-cells are of a low grade, morphological recognition of tumour cells in the ulcers may be impossible. Carcinoma of the pharynx and oesophagus, and adenocarcinoma of the small intestine, are increased in frequency in patients with coeliac disease. The increased risk of carcinoma of the oesophagus may be related to vitamin A deficiency. A number of reports have indicated an increased prevalence of various types of chronic hepatitis in patients with coeliac disease, but no coherent view of the cause of this association has emerged. Similarly, patients with coeliac disease have been reported to have various forms of fibrosing lung disease of uncertain causation. In recent years, there have been several reports, mainly from Italy, of a syndrome of epilepsy and bilateral brain calcification occurring in coeliac patients. The pathogenesis of this condition is not known and its prevalence in other communities is uncertain. Splenic atrophy occurs frequently in patients with coeliac disease and is related to the severity of the disease and degree of dietary control. Splenic atrophy predisposes to infection with capsulated bacteria, although mortality studies indicate that infection with these organisms is not a major cause of death in patients with coeliac disease.

Compston J.E.
Department of Medicine, Addenbrooke's Hospital, Cambridge CB2 2QQ United Kingdom
Alimentary Pharmacology and Therapeutics (United Kingdom), 1995, 9/3 (237-250)

Osteoporosis is a serious complication of inflammatory bowel disease which has not received adequate recognition despite its high prevalence and potentially devastating clinical effects. Its pathogenesis remains poorly defined although corticosteroid therapy and sex hormone deficiency are likely to play a major role. Recent advances in the diagnosis and management of osteoporosis have facilitated early detection of bone loss and identified means by which this may be prevented. Bone density measurements to predict fracture risk and define thresholds for prevention and treatment should be performed routinely in patients with inflammatory disease. Hormone replacement therapy is effective in prevention of bone loss in peri- and post-menopausal patients, but the treatment of younger women and men of all ages requires further study.

Scharla S.H.; Minne H.W.; Lempert U.G.; Leidig G.; Hauber M.; Raedsch R.; Ziegler R.
Innere Medizin I, Universitatsklinik Heidelberg, Bergheimer Strasse 58, D-69115 Heidelberg Germany
Exp. Clin. Endocrinol. (Germany), 1994, 102/1 (44-49)

Inflammatory bowel disease (Crohn's disease and ulcerative colitis) is associated with decreased bone mineral density and increased risk of osteoporosis. However, the pathogenesis of this bone loss is not yet fully understood. In the present study we measured lumbar bone mineral density (by dual photon absorptiometry), serum levels of parathyroid hormone (PTH) and vitamin D metabolites, and serum markers of bone turnover (alkaline phosphatase and osteocalcin) in 15 patients with Crohn's disease and in 4 patients with ulcerative colitis. The median duration of the disease was 4 years and the median lifetime steroid dose was 10g of prednisone. We compared our results to a control group of 19 normal persons, who were matched for age and sex to the patients. We found that lumbar bone density was reduced by 11% in patients compared with control persons (Z-score -0.6 plus or minus 0.6 versus -0.1 plus or minus 0.8: p < 0.05). In patients, the serum levels of PTH, 25-hydroxyvitamin D3, and calcitriol (1.25(OH)2D3) were significantly reduced compared with control persons. Serum alkaline phosphatase activity (AP) was significantly higher in the patients and was inversely related to lumbar bone density. Osteocalcin values were not different between patients and control persons. There was also no difference in serum levels of calcium between the two groups, whereas phosphorus levels were higher in patients. We conclude that malabsorption of calcium was not a primary cause of bone loss in our patients, because we did not find secondary hyperparathyroidism. Accordingly, we did not find a severe vitamin D deficiency, since 25-hydroxyvitamin D3 levels were within the normal range. Therefore, our results favor the hypothesis that glucocorticoid therapy and/or the inflammatory process itself caused changes in bone metabolism leading to a negative bone balance with secondary reduction of PTH and calcitriol levels.

Gracey M.
Aboriginal Health Unit, Health Dept of Western Australia, 189 Royal Street, East Perth, WA 6004 Australia
Curr. Opin. Gastroenterol. (United Kingdom), 1994, 10/1 (88-97)

Gastrointestinal infections are common and important in infants and young children, particularly where poor hygiene and living conditions allow the spread of infectious agents. With increasing information about microorganisms that cause these infections and improved methods to detect them, many episodes that were once undiagnosed can now be attributed to previously unrecognized viruses, bacteria, and other pathogens. These advances facilitate better management and will permit more effective control and preventive strategies. This review highlights some recent reports about enterovirulent classes of Escherichia coli, including E. coli O157:H7, which causes the hemolytic-uremic syndrome and hemorrhagic colitis; Campylobacter species and a new Campylobacter-like organism (Arcobacterbutzlerlli Helicobacter pylori; Aeromonas species; and rotavirus. Important new information about intestinal parasites, including Giardia and Cryptosporidium, has emerged that should prove of practical use in diagnosis and management in places where these parasites are prevalent in children, particularly in parts of the world where HIV infection has become established. A newly described organism, so far called coccidian-like or cyanobacterium-like body, has been found in patients with prolonged diarrhea (including travelers and expatriate residents) in several countries; the name Cyclospora cayetanensis has been proposed for this organism. This year's review concludes with a short commentary on some recent reports about risk factors that predispose children to gastrointestinal infections, eg, nutritional status, domestic hygiene, maternal hygiene behavior, and young children gathered in communal facilities like day care centers. Immune function status is also important, and deficiencies of single nutrients such as vitamin A, pyridoxine, folic acid, iron, and zinc may also play a role.

Silk D.B.A.
United Kingdom
Bailliere's Clin. Gastroenterol. (United Kingdom), 1992, 6/1 (27-41)

It is clear that the nutritional state of patients with inflammatory bowel disease is often impaired and can be improved by the provision of nutritional support. Improvement in nutritional status can be achieved as effectively with enteral as with parenteral nutrition. Nutritional support appears to have no primary therapeutic effect in patients with ulcerative colitis. With regard to nutritional support in Crohn's disease, parenteral nutrition should be restricted to use as supportive rather than primary therapy. Available information now seems to suggest that most of the benefits of parenteral nutrition in Crohn's disease are related to an improvement in nutritional state rather than as primary therapy, and its use should be restricted to the treatment of specific complications of Crohn's disease, such as intestinal obstruction related to stricture formation or short bowel syndrome following repeated resection. Although some doubt exists over the efficacy of oligopeptide-containing elemental and polymeric enteral diets, the present evidence indicates that chemically defined free amino acid-containing elemental diets have primary therapeutic efficacy in the management of acute exacerbations of Crohn's disease. As such, these diets are worthy of therapeutic trial in patients with severe Crohn's disease involving the distal colon and rectum, particularly in those patients who are malnourished and who prove to be resistant to treatment with a combination of topical corticosteroids and S-aminosalicylic acid-containing compounds. Clinicians should be aware, though, that the beneficial effects are likely to be restricted to the short term, with high relapse rates by 1 year, this being particularly so in patients with distal Crohn's proctocolitis (Teahon et al, 1988). Volatile fatty acid enemas clearly have potential in the management of patients with severe steroid-resistant proctitis. Finally, one of the most important observations made in recent years is the one concerning the large losses of nitrogen that will occur in patients with inflammatory bowel disease treated with corticosteroids in the absence of adequate protein intake (O'Keefe et al, 1989). Hopefully the days of treating patients with severe inflammatory bowel disease with high dose corticosteroids and a peripheral dextrose or dextrose-saline drip have passed into history.

Janczewska I.; Bartnik W.; Butruk E.; Tomecki R.; Kazik E.; Ostrowski J.
Department of Gastroenterology, Goszczynskiego 1, P-02-616 Warsaw Poland
Hepato-Gastroenterology (Germany), 1991, 38/5 (391-395)

The aim of this study was to determine serum retinol levels in patients with inflammatory bowel disease and to attempt to elucidate the mechanism of changes in vitamin A metabolism in these disorders. It was found that in 15 patients with active ulcerative colitis, 14 patients with active Crohn's disease and in 3 operated patients with recurrent Crohn's disease serum retinol levels and retinol-binding protein were significantly lower than in controls. Concentrations of vitamin A did not depend on the localization of inflammatory bowel disease, previous ileal resections, duration of the disease or age and sex of the patients. During successful treatment of active ulcerative colitis normalization of serum retinol levels without substitution of vitamin A was observed. Repeated determinations in patients with Crohn's disease who had low serum retinol levels in an active phase of disease revealed normal vitamin A levels in an inactive phase. The absorption of vitamins A and E in patients with inflammatory bowel disease was normal. The normal serum retinol concentrations in patients with diarrhea due to irritable bowel syndrome, and in those with anorexia nervosa exclude the influence of diarrhea and body weight itself on vitamin A levels. The results of this study indicate that serum retinol levels in patients with active inflammatory bowel disease are secondary to the decreased serum retinol-binding protein concentrations, and probably depend on the increased protein catabolism in these disorders.

Albers J.W.; Nostrant T.T.; Riggs J.E.
Neuromuscular Section, Department of Neurology, University of Michigan Medical Center, Ann Arbor, MI 48109-0032 USA
Neurol. Clin. (USA), 1989, 7/3 (525-548)

The neurologic manifestations of gastrointestinal disease are generally thought to be uncommon, although an increasing number of previously unidentified associations are being established. These neurologic disorders may result from nutritional or non-nutritional causes. In the absence of clear malnutrition, it is likely that many of these disorders are underdiagnosed. As an example, Wernicke's encephalopathy is found at autopsy in as many as 2 per cent of brains, a very high percentage, given the rare recognition during life. The likely underdiagnosis of nutritional neurologic disorders is unfortunate because many are treatable and, more importantly, are preventable if malabsorption is suspected and appropriate supplementation initiated. For the neurologist, familiarity with the occasional association between neurologic abnormalities and specific gastrointestinal disorders is important, as is familiarity with the neurologic characteristics of disorders, such as Whipple's disease, that may present as isolated neurologic syndromes without gastrointestinal symptoms or signs. Renewed interest in selective deficiency states has resulted in identification of causative factors in several neurologic syndromes of previously presumed degenerative etiology. Recognition of the potential neurologic consequences of prolonged deficiency states also is important for the internist, because many of the syndromes are poorly reversible once symptomatic. The benefits of prevention invariably exceed those of treatment.

Fernandez-Banares F.; Abad-Lacruz A.; Xiol X.; Gine J.J.; Dolz C.; Cabre E.; Esteve M.; Gonzalez-Huix F.; Gassull M.A.
Department of Gastroenterology, Hospital de Bellvitge 'Princeps d'Espanya', Barcelona Spain
Am. J. Gastroenterol. (USA), 1989, 84/7 (744-748)

The status of water- and fat-soluble vitamins was prospectively evaluated in 23 patients (13 men, 10 women, mean age 33 plus or minus 3 yr) admitted to the hospital with acute or subacute attacks of inflammatory bowel disease. Protein-energy status was also assessed by means of simultaneous measurement of triceps skin-fold thickness, mid-arm muscle circumference, and serum albumin. Fifteen patients (group A) had extensive acute colitis (ulcerative or Crohn's colitis), and eight cases (group B) had small bowel or ileocecal Crohn's disease. Eighty-nine healthy subjects (36 men, 53 women, mean age 34 plus or minus 2 yr) acted as controls. In both groups of patients, the levels of biotin, folate, beta-carotene, and vitamins A, C, and B1 were significantly lower than in controls (p < 0.05). Plasma levels of vitamin B12 were decreased only in group B (p < 0.01), whereas riboflavin was lower in group A (p < 0.01). The percentage of patients at risk of developing hypovitaminosis was 40% or higher for vitamin A, beta-carotene, folate, biotin, vitamin C, and thiamin in both groups of patients. Although some subjects had extremely low vitamin values, in no case were clinical symptoms of vitamin deficiency observed. Only a weak correlation was found between protein-energy nutritional parameters and vitamin values, probably due to the small size of the sample studied. The pathophysiological and clinical implications of the suboptimal vitamin status observed in acute inflammatory bowel disease are unknown. Further studies on long-term vitamin status and clinical outcome in these patients are necessary.

Mattioli S.; Miglioli M.; Montagna P.; Lerro M.F.; Pilotti V.; Gozzetti G.
Istituto di Clinica Chirurgica II, Universita di Bologna, 40138 Bologna Italy
J. Parenter. Enter. Nutr. (USA), 1988, 12/6 (626-627)

A patient operated for toxic megacolon secondary to ulcerative colitis developed a Wernicke syndrome (thiamine deficiency) during the postoperative period despite the administration of the usually recommended doses of vitamin B1 during total parenteral nutrition (TPN) treatment. Vitamin B1 deficiency should be checked in order to evaluate the patients' nutritional condition before starting TPN, especially those suffering from severe chronic malnutrition. Routine administration of vitamin B1 in repletion doses may be reasonably proposed in order to avoid the development of a Wemicke syndrome which is potentially lethal in a short time if not recognized and corrected in time.

Van Noort B.A.A.; Bos P.J.M.; Klopping C.; Wilmink J.M.
Department of Ophthalmology, G2N, A.M.C., University of Amsterdam, 1105 AZ Amsterdam Netherlands
Doc. Ophthalmol. (Netherlands), 1987, 67/1-2 (45-51)

A 35-year-old man with ulcerative colitis who was receiving parenteral feeding with large amounts of glucose, suddenly developed severe optic neuropathy and oculomotor palsy. The visual acuity fell bilaterally to 0. Although it was stated that thiamine has been regularly suppleted in the preceding period, high doses of vitamin B1 were given. Visual acuity promptly returned to 1.0 but large visual field defects persisted. Later on it appeared that erroneously no vitamin B1 has been given before.

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.

Schoelmerich J.; Becher M.S.; Hoppe-Seyler P.; et al.
Department of Internal Medicine, University of Freiburg, Freiburg Germany, West
Hepato-Gastroenterol. (Germany, West), 1985, 32/1 (34-38)

A study of serum zinc and plasma vitamin A concentrations in 54 patients with Crohn's disease was performed. Compared with controls the patients had significantly lowered zinc and vitamin A concentrations. There was a marked correlation between zinc and vitamin A and the activity of the disease, as measured by the Crohn's disease activity index, and a weaker correlation with serum proteins considered to be indicators of disease activity. No correlation was found to vitamin B12 absorption, to the localization of the disease, or to previous ileal resection. The results suggest that zinc and vitamin A deficiency occurs in patients with active Crohn's disease and is not primarily caused by absorption abnormalities. Substitution might be helpful or even necessary in patients with highly active disease.

Krasinski S.D.; Russell R.M.; Furie B.C.; et al.
USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA 02111 USA
Am. J. Clin. Nutr. (USA), 1985, 41/3 (639-643)

Vitamin K deficiency results in the appearance of abnormal prothrombin, deficient in gamma-carboxyglutamic acid, in the blood. The presence of abnormal prothrombin can be eliminated or lowered by the administration of vitamin K. Since the abnormal prothrombin antigen assay is approximately 1000-fold more sensitive than the prothrombin time for the diagnosis of vitamin K deficiency, this assay was used to evaluate patients with intestinal abnormalities. Vitamin K deficiency was found in 18 of 58 patients (31%) with chronic gastrointestinal disease and/or resection. All patients with vitamin K deficiency had either Crohn's disease involving the ileum or ulcerative colitis treated with sulfasalazine or antibiotics. Abnormal prothrombin levels returned toward normal in patients treated with vitamin K but not in patients who were not treated with vitamin K. The mean plasma vitamin E level in patients with vitamin K deficiency was significantly lower than in vitamin-K sufficient patients (p<0.01). We conclude that certain chronic forms of gastrointestinal disorders are associated with vitamin K deficiency.

Dageforde J.; Otte M.; Normann D.; et al.
Klinik fur Innere Medizin der Medizinischen Hochschule Lubeck, D-2400 Lubeck Germany, West
Arztl. Lab. (Germany, West), 1985, 31/3 (100-102)

Decreased serum levels of 25-OH-vitamin Dsub 3 are a not uncommon finding in ulcerative colitis and Crohn's disease. Exogenous factors, in particular a lack exposure, are the main causes. Vitamin Bsub 1sub 2 levels are only decreased in some Crohn patients with involvement of the ileum. This is explainable by malabsorption. Absorption of folic acid is reduced in both diseases through the interaction with salazosulfaphyridine. Organic malabsorption probably plays a minor role. Elimination of the deficiency states be means of solar irradiation and substitution therapy is necessary.

Dept. Int. Med., Univ. California, Davis, CA 95616 USA
N. Engl. J. Med. (USA), 1981, 305/25 (1513-1517)

Folate deficiency, a common occurrence in patients with inflammatory bowel disease, has been ascribed in part to the therapeutic use of sulfasalazine. However, a clear relation between the use of sulfasalazine (salicylazosulfapyridine) and the development of folate malabsorption and deficiency has not been shown. The authors designed studies to evaluate the relation of the use of sulfasalazine to folate malabsorption and deficiency in patients with ulcerative colitis. They compared the incidence of low serum folate levels in patients who were using sulfasalazine and those who were not. In a selected group of patients, the intestinal-perfusion method was used to study the effects of graded concentrations of sulfasalazine at the site of jejunal hydrolysis and luminal disappearance of folates. The data indicate that sulfasalazine inhibits the hydrolysis of polyglutamyl folate and also decreases the absorption of both polyglutamyl and monoglutamyl folates.

Dionigi R.; Guaglio R.; Bonera A.; et al.
Inst. Clin. Surg., Univ. Pavia Italy
Int. J. Clin. Pharmacol. Biopharm. (Germany, West), 1979, 17/3 (107-118)

The term 'total parenteral nutrition' (TPN) refers to the maintenance of an adequate nutritional status, normal body weight and positive nitrogen balance solely by intravenous means. It requires solutions providing calories, amino acids and other nutrients in amounts much greater than those indicated for maintenance of normal body weight. Nutrient solutions have been studied, selected and prepared in our Hospital Pharmacological Service utilizing a sterile closed system, which allows large-volume filtering, sterilizing and bottling devices. For maintenance of weight gain in adults, a basic formula is employed, which provides 1,100 Kcal/l with pure crystalline amino acids mixed with 50% anhydrous dextrose in water in a ratio of 5.8:1 (160 Kcal:1 g nitrogen). Minerals and vitamins are added to the base solution prior to use and may be increased or decreased by simple addition or omission depending on the patient's condition. This paper is based on 192 surgical patients who received TPN and have been followed in strict cooperation between the Hospital Pharmacological Service and the Surgical Department. The patients, ranging from 23 to 79 years of age, with life threatening diseases and unable to maintain adequate nutrition by the oral route, received TPN through a central catheter inserted via subclavian puncture (146 cases) or through a surgically created internal A-V fistula (46 cases). The condition of the patients generally improved within a few days after starting TPN; and weight gain, wound healing general improvement and a shorter period of hospitalization were observed. TPN could be efficiently combined with oncologic treatment, and a significant improvement of the patients' performance status and decrease of toxic side-effects due to chemotherapeutic agents were observed. TPN has been successfully applied also in patients with fistulas of the alimentary tract obtaining spontaneous closure and in patients with ulcerative colitis, showing its beneficial effect in allowing complete bowel rest for healing. No major complications or deaths could be attributed to TPN or to the route of administration.

Thomson A.B.R.; Brust R.; Ali M.A.M.; et al.
Dept. Med., Univ. Alberta, Edmonton Canada
Am. J. Dig. Dis. (USA), 1978, 23/8 (705-709)

The prevalence of iron-deficiency anemia was defined in 105 patients with inflammatory bowel disease and an appraisal made of the diagnostic value of serum ferritin for the assessment of iron stores. Iron deficiency, defined by the absence of bone-marrow hemosiderin was found with anemia in 36% of 41 patients with ulcerative colitis (UC) and 22% of 64 patients with Crohn's disease (CD). Iron deficiency without impaired erythropoiesis was detected in an additional 32% of patients with UC and 2% with CD. Anemia with plentiful bone-marrow iron was present in 33 (51%) of patients with CD, only one of whom had vitamin Bsub 1sub 2 deficiency. Red blood cell morphology, RBC indices, serum iron, and percent transferrin saturation correlated poorly with stainable marrow iron. Serum ferritin, assayed in samples from 45 patients, was <18 ng/ml in 4/12 with iron-deficiency anemia and 0/5 with absent marrow iron and a normal hemoglobin level; values >55 ng/ml were invariably associated with the presence of marrow hemosiderin. Based on a lower normal limit of 18ng/ml, the serum ferritin had an excellent predictive value (100%) but a high predictive error (32%) in the diagnosis of iron deficiency in inflammatory bowel disease. Serum ferritin >55 ng/ml ruled out iron deficiency as the basis for anemia.

Husainov O.H.
Kaf. Infekts. Bol., Tadzhik. Medinst., Dushanbe USSR
Zdravookhr.Tadzh. (USSR), 1973, 20/4 (10-12)

Investigation of 39 patients suffering from acute bacterial dysentery and 25 with an exacerbation of the chronic form revealed disturbances of the vitamin C metabolism in all cases, manifested by a low content of the vitamin in the blood and its low excretion in the urine. The degree of the changes depended on the clinical manifestations of the disease. Administration of vitamin C in therapeutic doses corrected the vitamin deficiency in acute bacterial dysentery. In patients with exacerbations of chronic dysentery the indices of the ascorbic acid metabolism failed to reach the normal values, thereby indicating more prolonged and massive vitamin therapy.

Stedman J.D.; Spyrou N.M.; Millar A.D.; Altaf W.J.; Akanle O.A.; Rampton D.S.
J.D. Stedman, Department of Physics, University of Surrey, Guildford, Surrey GU2-5XH United Kingdom
Journal of Radioanalytical and Nuclear Chemistry (Hungary), 1997, 217/2 (189-191)

Ulcerative colitis (UC) is a type of inflammatory bowel disease (IBD) in which there is recurrent inflammation of the mucous membranes of the colon. Inflammation is accompanied by the production of reactive oxygen species (ROS) including, amongst others, hydrogen peroxide. Selenium in the form of the selenoprotein glutathione peroxidase (GSH-Px) acts as a catalyst in the reaction which reduces hydrogen peroxide to watch. It may therefore beneficial to supplement the diets of patients who suffer from UC with selenium. In this preliminary study nine patients suffering from moderate UC were supplemented with selenium-beta tablets (300 microg Se per tablet) twice daily. Blood samples were taken at the start of the trial and at 1, 2 and 4 week intervals. Freeze-dried serum samples were analysed for their selenium content using the technique of instrumental neutron activation analysis (INAA). Samples were also analysed by particle induced X-ray emission (PIXE) to monitor other trace elements levels. Selenium concentrations were found to increase during supplementation and iron concentrations to decrease. Stool frequency was also found to improve suggesting that ROS may be important in the pathogenesis of UC.

Burke A.; Lichtenstein G.R.; Rombeau J.L.
Prof. J.L. Rombeau, Department of Surgery, Hospital University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA 19104 USA
Bailliere's Clinical Gastroenterology (United Kingdom), 1997, 11/1 (153-174)

The role of diet in the aetiology and pathogenesis of ulcerative colitis (UC) remains uncertain. Impaired utilization by colonocytes of butyrate, a product of bacterial fermentation of dietary carbohydrates escaping digestion, may be important. Sulphur-fermenting bacteria may be involved in this impaired utilization. Oxidative stress probably mediates tissue injury but is probably not of causative importance. Patients with UC are prone to malnutrition and its detrimental effects. However, there is no role for total parenteral nutrition and bowel rest as primary therapy for UC. The maintenance of adequate nutrition is very important, particularly in the peri-operative patient. In the absence of massive bleeding, perforation, toxic megacolon or obstruction, enteral rather than parenteral nutrition should be the mode of choice. Nutrients may be beneficial as adjuvant therapy. Butyrate enemas have improved patients with otherwise recalcitrant distal colitis in small studies, Non-cellulose fibre supplements are of benefit in rats with experimental colitis. Eicosapentaenoic acid in fish oil has a steroid-sparing effect which, although modest, is important, particularly in terms of reducing the risk of osteoporosis, but it seems to have no role in the patient with inactive disease. gamma-Linolenic acid and anti-oxidants also are showing promise. Nutrients may also modify the increased risk of colorectal carcinoma. Oxidative stress can damage tissue DNA but there are no data published at present on possible protection from oral anti-oxidants. Butyrate protects against experimental carcinogenesis in rats with experimental colitis. Folate supplementation is weakly associated with decreased incidence of cancer in UC patients when assessed retrospectively. Vigilance should be maintained for increased micronutrient requirements and supplements given as appropriate. Calcium and low-dose vitamin D should be given to patients on long-term steroids and folate to those on sulphasalazine.

Campbell J.M.; Fahey G.C. Jr.; Lichtensteiger C.A.; Demichele S.J.; Garleb K.A.
G.C. Fahey Jr., Division of Nutritional Sciences, Department of Animal Sciences, University of Illinois, Urbana, IL 61801 USA
Journal of Nutrition (USA), 1997, 127/1 (137-145)

Evidence supports a pathogenic role of arachidonic acid-derived inflammatory mediators within the gastrointestinal tract of patients with inflammatory bowel disease. The purpose of this study was to assess the effects of an ulcerative colitis nutritional formula (UCNF) containing oligosaccharides, fish oil, gum arabic and antioxidants on plasma and colonic phospholipid fatty acid and prostaglandin profiles in pigs. Twenty-four growing barrows in two replications were equally randomized among four killing times (d 0, 7, 14 and 21), and one of two diets, a control and the UCNF. Diets contained comparable levels of protein, fat, and nonstructural carbohydrate and met 100% of the energy requirements of the pig. Intake and body weight were recorded daily while blood, urine and tissue samples were collected at time of kill. Within 1 wk of ingestion of the UCNF, the composition of plasma phospholipid fatty acids showed an increase in 20:5(n- 3) and 22:6(n-3) (P < 0.0001) and a decrease in 20:4(n-6) and 18:2(n-6) (P < 0.0001). Similar effects were observed for the phospholipids in the colonic and cecal mucosa. Plasma prostaglandin E was unaffected by treatment, whereas thromboxane B2 and 6-keto-prostaglandin F(1alpha) levels were significantly decreased after 7 d of UCNF ingestion. Ingestion of the UCNF resulted in a suppression in the synthesis of proinflammatory prostaglandins by cecal and colonic mucosal cells. Levels of colonic and cecal prostaglandin E, 6- ketoprostaglandin F(1alpha) and thromboxane B2 were significantly decreased after 7 d of UCNF ingestion. These changes may have been mediated by rapid increases of (n-3) fatty acids into cellular phospholipids. Dietary supplementation with the UCNF may prove beneficial for patients with ulcerative colitis by modulating colonic prostaglandin synthesis.

Lashner B.A.; Provencher K.S.; Seidner D.L.; Knesebeck A.; Brzezinski A.
USA
Gastroenterology (USA), 1997, 112/1 (29-32)

Background and Aims: Two case-control studies have shown that folate may protect against neoplasia in ulcerative colitis. This historical cohort study was performed to better define this association. Methods: The records of 98 patients with ulcerative colitis who had disease proximal to the splenic flexure for at least 8 years were reviewed. Documented folate use of at least 6 months was deemed a positive exposure. Results: Of the patients, 29.6% developed neoplasia and 40.2% took folate supplements. The adjusted relative risk (RR) of neoplasia for patients taking folate was 0.72 (95% confidence interval (CI), 0.28-1.83). The dose of folate varied with the risk of neoplasia (RR, 0.54 for 1.0 mg folate; RR, 0.76 for 0.4 mg folate in a multivitamin compared with patients taking no folate). Folate use also varied with the degree of dysplasia (RR for cancer, 0.45; RR for high-grade dysplasia, 0.52; RR for low-grade dysplasia, 0.75 compared with patients with no dysplasia) (P = 0.08). Conclusions: Although not statistically significant, the RR for folate supplementation on the risk of neoplasia is <1 and shows a dose-response effect, consistent with previous studies. Daily folate supplementation may protect against the development of neoplasia in ulcerative colitis.

Candy S.; Borok G.; Wright J.P.; Boniface V.; Goodman R.
Gastro-intestinal Clinic, Department of Medicine, Groote Schuur Hosp., Univ. Cape Town, Cape Town South Africa
South African Medical Journal (South Africa), 1995, 85/11 (1176-1179)

Debate exists about the role of diet in both the aetiology and the management of ulcerative colitis. To examine the latter, a group of patients with documented ulcerative colitis was studied at the Groote Schuur Hospital Gastro-intestinal Clinic. A total of 18 subjects, 9 female and 9 male, were randomised into active or control groups and followed up weekly for 6 weeks. Subjects in the control group were asked to document but not alter their intake of food and drink. Those in the experimental group had their diets systematically manipulated to exclude foods that appeared to provoke symptoms. The symptoms, sigmoidoscopy and biopsy findings of all subjects were compared before and after. 'Remission' was defined as the passage of normal stools with absence of rectal bleeding. 'Improvement' was defined as a decrease in the number of diarrhoeal stools and/or a diminution of rectal bleeding. At the end of the trial the diet group displayed significantly fewer symptoms than did the controls (P = 0.009; Fisher's exact test). Sigmoidoscopic findings improved in 8 subjects in the diet group compared with 2 of the controls. Histological findings improved in 3 of the diet group as well as in 3 of the controls. There were no foods that provoked symptoms in all patients, though spiced and curried foods and fruits, especially grapes, melon and the citruses, commonly caused diarrhoea. In only 2 patients were symptoms reproduced consistently on reintroduction of a particular food, pork in 1 case and yellow cheese in another.

Fujita T.; Sakurai K.
First Department of Surgery, Jikei University School of Medicine, 3-25-8 Nishishinbashi, Minato-ku, Tokyo 105 Japan
British Journal of Surgery (United Kingdom), 1995, 82/6 (749-751)

Intact intestinal epithelium and associated lymphatic tissue act as body defences against luminal toxins. This barrier may become threatened or compromised in inflammatory bowel disease, leading to an increase in mucosal permeability and subsequent translocation of endotoxins. The effect of oral glutamine on gut mucosal ornithine decarboxylase activity and on endotoxin levels in portal vein blood was studied in a guinea-pig model of carrageenan- induced colitis. Despite failure to show induction of ornithine decarboxylase activity by glutamine administration, the mean endotoxin level of portal vein blood in guinea-pigs fed a glutamine-enriched elemental diet was 25.3 pg/ml compared with 71.2 pg/ml in animals given a standard elemental diet (P<0.01). A glutamine-enriched elemental diet may be therapeutically beneficial in patients with inflammatory bowel disease.

Nagel E.; Bartels M.; Pichlmayr R.
Klinik fur Abdominal, Transplantationschirurgie, Konstanty-Gutschow-Stras se 8, D-30625 Hannover Germany
Langenbecks Archiv fur Chirurgie (Germany), 1995, 380/1 (4-11)

Nutritional therapy for ulcerative colitis (UC) is controversial. Studies are usually designed to investigate total parenteral (TPN) or total enteral nutrition (TEN), and before these can be compared it is necessary to differentiate between the different therapeutic aims. The aims of artificial nutritional support in patients with UC are the readjustment of the nutritional status, possible remission of disease activity, and decrease in the incidence of surgical intervention or postoperative complication. Owing to the heterogeneity of the results published so far, it is still difficult to compare studies. Nevertheless, they indicate that the extent and severity of the colitis and the patient selection are of paramount importance in the implementation of nutritional therapy. Positive effects of TPN reported from non-controlled studies were not confirmed by controlled trials. Moreover, TPN was no more effective than an oral diet. Regarding remission rates or operative interventions needed, TPN had more side effects than and no defined advantages over TEN. TEN seems to be useful for certain patients. In some patients with UC, it seems to be accompanied by fewer postoperative complications. However, a definitive conclusion on the effects of TEN or TPN is not yet possible. In this context, certain fatty acids may have an important role in the treatment of UC. In prospective, randomized and controlled studies omega-3 fatty acids were found to be therapeutically useful. A reduction of the steroid doses needed is particularly important. Another therapeutic approach in distal UC is seen in the rectal administration of short chain fatty acids.

Frankel W.L.; Choi D.M.; Zhang W.; Roth J.A.; Don S.H.; Afonso J.J.; Lee F.- H.; Klurfeld D.M.; Rombeau J.L.
Harrison Department of Surgery, University of Pennsylvania Hospital, 34th and Spruce Street, Philadelphia, PA 19104 USA
J. Parenter. Enter. Nutr. (USA), 1994, 18/1 (55-61)

Clostridium difficile colitis is a disabling complication in critically ill patients who commonly receive broad-spectrum antibiotics and liquid diets. To date, there is no experimental model specifically designed to investigate the effects of liquid diets on this type of colitis. The addition of fiber to liquid diets normalizes gut structure and improves absorptive function in selected conditions of intestinal dysfunction. The purposes of this study were the following: (1) to develop a reproducible model to examine the interaction of acute C difficile-induced colitis and liquid diets, (2) to determine whether the addition of soy fiber to a liquid diet improves disease, and (3) to investigate possible mechanisms of fiber-mediated disease improvement. Syrian hamsters were pair-fed with either a polymeric liquid diet or the same diet with 1.4% soy fiber for 10 days. Animals were given either clindamycin and C difficile (to produce ileocecitis), or equivalent volumes of saline. Mean survival time and systematic stool examinations for C difficile toxin positivity, liquidity, and percent water were performed to determine the effect of soy fiber on disease. Survival time was prolonged by 34% (p < .05), and C difficile toxin positivity and stool liquidity were significantly reduced (p < .05) with fiber. Additional animals were studied to determine possible mechanisms for improved survival in fiber-supplemented animals. Cecal histology, colonic water absorption, cecal microflora, and gastric to anus transit time were measured in these animals. Colonic water absorption and gastric to anus transit time were significantly increased (p < .05) and decreased (p < .05) with fiber, respectively. A hamster model of C difficile ileocecitis has been designed to investigate the effects of liquid diets. Fiber supplementation prolongs survival in this model due in part to a delay in onset of C difficile infection and improved colonic water absorption.

Grimminger F.; Fuhrer D.; Papavassilis C.; Schlotzer E.; Mayer K.; Heuer K.-U.; Kiss L.; Walmrath D.; Piberhofer S.; Lubbecke F.; Kramer H.-J.; Stevens J.; Schutterle G.; Seeger W.
Department of Internal Medicine, Justus-Liebig-University, Klinikstrasse 36, D-6300 Giessen Germany
Eur. J. Clin. Invest. (United Kingdom), 1993, 23/11 (706-715)

N-3 fatty acids were supplied to a 36-year-old female patient suffering from ulcerative colitis and severe steroid side-effects, in a sequence of parenteral and enteral administration. During a moderately active period of disease, 200 ml d-1 fish oil-derived lipid emulsion (eicosapentaenoic acid (EPA), 4.2 g; docosahexaenoic acid (DHA), 4.2 g) was infused for 9 days, in parallel with rapid tapering of the steroid dose. Disease activity declined rapidly, and the patient was subsequently provided with 16 fish oil capsules per day (EPA, 2.9 g; DHA, 1.9 g) for 2 months. At the end of this period of therapy, severe colitis recurred with intestinal and extraintestinal manifestations. The n-3 lipid emulsion was then used for intravenous alimentation (29 days, maximum dose 300 ml per day); during this time, marked improvement of the inflammatory bowel disease was noted. During both periods of parenteral n-3 lipid administration, total plasma EPA and DHA contents increased several-fold, surpassing that of arachidonic acid; this plasma n-3 fatty acid enrichment was only maintained to a minor extent during the intermediate period of dietary fish oil supplementation. The intravenously administered EPA-containing triglycerides were rapidly hydrolyzed, as evidenced by the appearance of substantial quantities of EPA in the plasma free fatty acid fraction. Platelet and neutrophil total membrane content of EPA and DHA as well as n-3 fatty acid/AA membrane ratios similarly increased during the periods of intravenous n-3 lipid administration and declined during oral fish oil uptake. In contrast, erythrocyte membrane enrichment in EPA and DHA occurred only after the prolonged (2 month) period of dietary n-3 lipid supplementation. Ex vivo stimulation of neutrophils with A23187 showed progressive increase in 5-series leukotriene- and 5-HEPE-generation during both periods of n-3 lipid infusion, in parallel with the rise of plasma EPA contents. Maximum 5-series/4-series leukotriene ratios surpassed 0.25. Similarly, ratios of thromboxane B3/B2 liberated from ex vivo stimulated platelets surpassed 0.4 during ongoing n-3 lipid infusion. The profound changes in fatty acid profiles and lipid mediator generation may be related to the reduction in colitis activity observed during the periods of intravenous n-3 lipid supplementation.

Ross E.
Department of Internal Medicine, Tufts University School of Medicine, Boston, MA 02111 USA
Nutr. Rev. (USA), 1993, 51/2 (47-49)

Recent studies suggest that marine fish-oil supplements, which are rich in n-3 fatty acids, may reduce the inflammation associated with ulcerative colitis. Fish oils may exert their beneficial effects by shifting eicosanoid synthesis to less inflammatory species or by modulating tissue levels of certain cytokines.

Heimburger D.C.; Colby F.; Benitez L.; Raiten D.J.; Butterworth C.E.
Department of Nutrition Sciences, University of Alabama, Birmingham, AL 35294 USA
Ann. New York Acad. Sci. (USA), 1992, 669/- (87-96)

The notion that requirements for folic acid may be higher in some tissues than others, resulting in localized deficiencies in spite of blood levels in the normal range was first suggested by the observation of megaloblastic changes in the cervical epithelium that responded to folate supplementation. Theoretically, such deficiencies may arise from elevated folate turnover in response to rapid tissue proliferation or repair; inactivation or alteration of its function by external agents such as tobacco, alcohol, or drugs; or altered metabolism or tissue uptake caused by an inborn error. Marginal dietary intake could aggravate these effects on cells at risk. Evidence for the possible existence of localized folate deficiencies in the aerodigestive tract includes lower circulating folate levels in smokers as compared with nonsmokers; yet lower circulating levels in smokers with bronchial metaplasia; lower folate levels in scrapings of the buccal mucosa of smokers than non-smokers; apparent improvement in bronchial atypical metaplasia in smokers supplemented with folic acid; lower erythrocyte folate levels and higher prevalence of cellular features compatible with folate deficiency in geographic areas and individuals in South Africa at high risk for esophageal cancer; and a trend toward a lower prevalence of colonic dysplasia in ulcerative colitis patients who use folic acid supplements. These observations, as well as animal and in vitro studies, also suggest that folate deficiency may be co-carcinogenic. Further research in this area will be aided by the development of animal models of localized folate deficiency and of methodologies capable of measuring folate levels in minute quantities of tissues and exfoliated cells.

Continued on the next page...