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Patients with inflammatory bowel disease (IBD) have increased plasma n3 polyunsaturated fatty acids (PUFAs), which in ulcerative colitis (UC) patients persists six months after colectomy, suggesting a primary abnormality in fatty acid (FA) metabolism in IBD. This finding needed to be confirmed in a larger series of UC long-term colectomized patients. We aimed to assess the plasma FA pattern in UC colectomized patients with either Brooke's ileostomy (UC-BI) or ileal pouch anal anastomosis (UC-IPAA) and the mucosal FA pattern in the ileal reservoir of the UC-IPAA patients. Plasma FAs were assessed in 63 UC colectomized patients (31 with BI and 32 with IPAA) and 30 controls. In 26 UC-IPAA (8 with pouchitis and 18 without pouchitis) and in 13 healthy controls gut mucosal FAs were also investigated. FAs were detected by capillary column gas-liquid chromatography. Increased levels of saturated fatty acids (SFAs) and decreased percentages of monounsaturated fatty acids (MUFAs) were observed in both groups of patients. There were no changes in plasma n3 and n6 PUFAs. The mucosal FA pattern of the ileal reservoir consisted of increased long-chain PUFAs, specially n6 PUFA, and a decrease of their essential precursors. High percentages of SFAs and low percentages of MUFAs were also seen. The plasma FA profile previously described in IBD is not observed long-term after colectomy in UC, suggesting that it is related with the presence of inflamed intestine. High concentrations of SFAs and decreased percentages of MUFAs might represent early events in disturbed FA metabolism in IBD. The changes in FAs of the ileal reservoir, which closely resemble those found in human and experimental IBD, probably represent a common pattern of intestinal inflammation. [ABSTRACT FROM AUTHOR]

OBJECTIVES:Infl ammatory bowel disease (IBD), e.g., Crohn's disease (CD) and ulcerative colitis (UC), is a complex genetic disorder. Tumor necrosis factor (ligand) superfamily, member 15 (TNFSF15) has been previously identified as a susceptibility gene for CD in Japanese and UK cohorts. This replication study was designed in order to confirm and further validate the role of TNFSF15 in IBD.METHODS:A total of 666 IBD families (corresponding to 2,982 relatives) with European ancestry were genotyped for the rs6478108 and rs7869487 polymorphisms, which define the main TNFSF15 haplotypes previously associated with CD. An association between the main haplotypes and CD, UC and IBD was tested using the Genehunter TDT and Unphased statistics. Caspase recruitment domain 15 (CARD15)/TNFSF15 interaction and genotype/phenotype correlations were also studied.RESULTS:The previously reported “high-risk” haplotype (A) was associated with IBD (P=0.001) (OR=1.25 (1.05–1.50)) and CD (P=0.02) (OR=1.31 (1.03–1.67)) whereas the “protective” (B) haplotype was significantly less transmitted to IBD and CD patients. No interaction between CARD15 and TNFSF15 was detected. We also failed to define a clinical subgroup of CD patients specifically associated with TNFSF15 haplotype A.CONCLUSIONS:This study confirms that TNFSF15 or a closely linked gene is involved in the genetic predisposition to CD.Am J Gastroenterol 2009; 104:384–391; doi:10.1038/ajg.2008.36; published online 13 January 2009 [ABSTRACT FROM AUTHOR]

The introduction of novel anti-tumor necrosis factor (TNF) agents has not only led to impressive new therapeutic opportunities but also resulted in uncertainty regarding their optimal use and possible side effects. Guidelines are presented here for the use of anti-TNF agents in gastrointestinal disorders. Experts were chosen from different European countries by an algorithm to avoid bias. An expert consensus on guidelines was established using a two-stage procedure of systematic Medline and abstract search for evidence and a qualifying meeting to derive recommendations. Detailed guidelines were developed for the use and the future clinical development of anti-TNF agents in inflammatory bowel disease. Grading of available evidence and grading of recommendations were performed according to AHCPR guidelines. At present infliximab is the only registered agent for Crohn's disease. Infliximab should be always used at a dose of 5 mg/kg. The guidelines define the indications both in refractory and in fistulating disease for the readministration and before surgery. Guidelines for safety and for concomitant treatments are given. Prospects, potential clinical use, and future directions for the clinical development of other anti-TNF agents are detailed. Clinical use of anti-TNF agents will be influenced by a large number of clinical trials being concluded in 2001 and 2002. It is likely that anti-TNF therapies will become an important long-term therapy for a proportion of patients with Crohn's disease. Biological agents will be followed by smaller and more stable, orally available compounds. These guidelines will be succeeded by a formal public consensus in 2002/2003. [ABSTRACT FROM AUTHOR]

OBJECTIVE: It has been suggested that, in inflammatory bowel disease, cytomegalovirus behaves in the intestine as a nonpathogenic bystander, and even its finding in intestinal mucosa has unclear clinical relevance. We report our experience with a small series of patients with refractory inflammatory bowel disease and cytomegalovirus infection and their clinical outcome. METHODS AND RESULTS: Nine patients with moderate-severe attacks of inflammatory bowel disease did not respond to i.v. prednisone (I mg/kg/day) for a mean of 24 days. Four of these patients were further treated with i.v. cyclosporine A (4 mg/kg/day). Cytomegalovirus infection was diagnosed in two patients after resection for treatment failure. In the remaining patients, cytomegalovirus infection was diagnosed in endoscopic mucosal biopsies and i.v. ganciclovir was then administered at a dose of 10 mg/kg/day for 2-3 wk. Five of these patients went into clinical remission, allowing corticosteroid and cyclosporine A discontinuation. Follow-up biopsies were performed and in all cases cytomegalovirus could not be detected in the colonic tissue. Two patients needed to be treated with intravenous cyclosporine A after antiviral therapy because of persistence of clinical symptoms despite the elimination of cytomegalovirus infection. CONCLUSIONS: Cytomegalovirus infection may play a role in the natural history of refractory inflammatory bowel disease and in some of its complications. The clearance of cytomegalovirus in colonic mucosa may lead some of these patients to remission. [ABSTRACT FROM AUTHOR]

Serologic markers, HLA-DQ2 haplotype, and clinical features suggestive of celiac disease were studied to assess their diagnostic value in a multicentric study to detect celiac disease in 675 first-degree relatives of 227 celiac probands. Serum IgA-class anti-endomysium and IgA-class anti-gliadin antibodies were positive in 5.8% and 1.9% of relatives, respectively. HLA-DQ2 haplotype was present in 64% of relatives, and the overall rate of celiac disease diagnosed by intestinal biopsy was 5.5%. The frequency of HLA-DQ2 in the celiac patients and controls was 93% and 18%, respectively. The most frequent clinical features--diarrhea, anemia, food intolerance, and growth retardation--were not present in one third of the celiac disease relatives. We conclude that the assessment of IgA-class anti-endomysium antibodies alone seems a reasonable approach for screening celiac disease in relatives and cannot be replaced by an accurate clinical anamnesis. HLA-DQ2 haplotype may identify the population with a high genetic susceptibility to celiac disease. [ABSTRACT FROM AUTHOR]

The case is reported of a 46-year-old male patient with polycythemia vera (PV) treated with phlebotomy who developed an occlusive thrombosis of the superior mesenteric artery 2 years after the diagnosis. He was successfully managed with percutaneous transluminal angioplasty. The patient did not develop any other thrombotic phenomena. To our knowledge, there are no previous reports on the use of percutaneous transluminal angioplasty in the management of arterial thrombotic complications in PV patients. [ABSTRACT FROM AUTHOR]

The usefulness of scintigraphy with In-oxinelabelled autologous leucocytes was investigated in 27 patients with inflamatory bowel disease (IBD): 16 with ulcerative colitis and 11 with Crohn's disease. Scans were performed 2-4 h (early scan) and at 24 h (late scan) after leucocyte reinjection. No false-negative results occurred in the early scan; however, in the late scan, 2 patients with Crohn's disease had a normal scintigram. A new index of activity ( I) based on the number and relative activity of abnormal In-leucocyte zones was used for scan quantitation. All patients with clinically active IBD had I≧2. The scintigraphic index showed a significant correlation with the Harvey clinical index, especially in patients with ulcerative colitis. Our results suggest that an early scan (2-4 h) provides useful information in cases of IBD, and that I≧2 is indicative of the degree of disease activity in such patients. [ABSTRACT FROM AUTHOR]

Objective: Butyrate enemas may be effective in the treatment of active distal ulcerative colitis. Because colonic fermentation of Plantago ovata seeds (dietary fiber) yields butyrate. the aim of this study was to assess the efficacy and safety of Plantago ovata seeds as compared with mesalamine in maintaining remission in ulcerative colitis. Methods: An open label, parallel-group, multi-center, randomized clinical trial was conducted. A total of 105 patients with ulcerative colitis who were in remission were randomized into groups to receive oral treatment with Plantago ovata seeds (10 g b.i.d.), mesalamine (500 m t.i.d.), and Plantago ovata seeds plus mesalamine at the same doses. The primary efficacy outcome was maintenance of remission for 12 months. Results: Of the 105 patients, 102 were included in the final analysis. After 12 months, treatment failure rate was 40% (14 of 35 patients) in the Plantago ovata seed group, 35% (13 of 37) in the mesalamine group, and 30% (nine of 30) in the Plantago ovata plus mesalamine group. Probability of continued remission was similar (Mantel-Cox test, p = 0.67; intent-to-treat analysis). Therapy effects remained unchanged after adjusting for potential confounding variables with a Cox's proportional hazards survival analysis. Three patients were withdrawn because of the development of adverse events consisting of constipation and/or flatulence (Plantago ovata seed group = 1 and Plantago ovata seed plus mesalamine group = 2). A significant increase in fecal butyrate levels (p = 0.018) was observed after Plantago ovata seed administration. Conclusions: Plantago ovata seeds (dietary fiber) might be as effective as mesalamine to maintain remission in ulcerative colitis. [ABSTRACT FROM AUTHOR]

Objectives: Few studies have assessed the IgA antineutrophil cytoplasmic antibody (ANCA) positivity in ulcerative colitis patients and there is no information about factors related to its synthesis and its status after colectomy. The aims of the study were to assess the serum IgA ANCA prevalence in ulcerative colitis patients, both nonoperated and operated, and to determine the clinical factors related to this positivity. Methods: Fifty-four ulcerative colitis patients, 63 ulcerative colitis colectomized patients (32 with Brooke's ileostomy and 31 with ileal pouch anal anastomosis), and 24 controls were studied. Antineutrophil cytoplasmic antibodies were detected by specific indirect immunofluorescent assays. Results: The percentage of IgA ANCA was significantly higher in patients with ileal pouch anal anastomosis (45%) than in patients with Brooke's ileostomy (22%). There were no differences related to the presence of pouchitis in ileal pouch anal anastomosis patients. Patients with nonoperated extensive colitis (47%) had a significantly higher percentage of IgA ANCA than patients with proctitis (19%). Total percentage of ANCA (IgA and/or IgG) tended to be higher in ulcerative colitis and in patients with ileal pouch anal anastomosis than in patients with Brooke's ileostomy. However, in ileal pouch anal anastomosis patients, ANCA positivity was mainly due to exclusive IgA production. Conclusions: A substantial percentage of ulcerative colitis patients, and especially colectomized patients with ileal pouch anal anastomosis, had IgA ANCA, suggesting that ANCA production in ulcerative colitis might be stimulated by an immune reaction in the intestinal mucosa. [ABSTRACT FROM AUTHOR]

Objective: To investigate the relationship of sugar malabsorption to the development of clinical symptoms in functional bowel disease. Methods: Twenty-five consecutive outpatients [five men, 20 women; mean age 38.7 ± 2.6 (SEM) yr] with functional bowel disease and symptoms suggestive of carbohydrate malabsorption were studied. Twelve healthy subjects [six men, six women; mean age 35.7 ± 3.7 (SEM) yr] acted as the control group. Sugar malabsorption was assessed by breath-hydrogen test after an oral load of various solutions containing lactose (50 g), fructose (25 g), sorbitol (5 g), fructose plus sorbitol (25+5 g), and sucrose (S0 g). The severity of symptoms developing after sugar challenge was studied. In addition, the effect on clinical symptoms of a diet free of the offending sugars, compared to a low-fat diet, was assessed. Results: Frequency of sugar malabsorption was high in both patients and controls, with malabsorption of at least one sugar in more than 90% of the subjects. Median symptom scores after both lactose [median 6; interquartile (IQ) range 3-7] and fructose plus sorbitol (median 2; IQ range 04) malabsorption were significantly higher than after sucrose load (median 1; IQ range 0-1.5) in functional bowel disease patients (p = 0.001 and p = 0.007, respectively). However, there were no differences in healthy controls. In addition, symptoms score after both lactose and fructose plus sorbitol malabsorption was significantly higher in patients than in control subjects (p = 0.02 and p = 0.008, respectively). On the other hand, H2 production capacity, as measured following lactulose load, was significantly higher in patients than in controls. The clinical symptoms improved in 40% of the evaluated patients after restriction of the offending sugars. Conclusions: These results suggest that sugar malabsorption may be implicated in the development of abdominal distress in at least a subset of patients with functional... [ABSTRACT FROM AUTHOR]

Total plasma fatty acids were measured in 101 cirrhotic inpatients (64 men, 37 women, aged 64.3 ±1 .2 (SEM) yr; range, 34-80) who were subsequently followed for survival for a mean of 14.8 ±1 .0 months. Data on plasma fatty acids have been published elsewhere. Individual values of these variables were categorized in a binary fashion using the 5th or the 95th percentiles of a group of 44 well-nourished healthy controls (24 men, 20 women, aged 51.3 ± 2.1 yr; range, 32-76) as the cutoff limit. Forty-nine patients died during follow-up (2-yr cumulative probability of survival, 52%). Deficiency of palmitate, dihomo-τ-linolenate, and arachidonate (values below the 5th percentile) were univariately associated with death (long-rank test). However, after a multivariate analysis (Cox's proportional hazards regression), only the existence of plasma arachidonate deficiency was included in the final model (β, 0.62; relative risk, 1.86; 95% CI, 1.06-3.25; p < 0.05). We conclude that arachidonic acid deficiency significantly increases the mortality risk in patients with advanced liver cirrhosis. [ABSTRACT FROM AUTHOR]

In order to identify the predictive factors of hospital mortality in cirrhotics with spontaneous bacterial peritonitis (SBP), we studied 64 patients who fulfilled the accepted diagnostic criteria. All cases were treated with cefotaxime up to 2 days after the infection was considered cured (7.7 ± 2.9 days). Eleven patients (17%) died while in hospital, six of them before SBP was cured. After uni- and multivariate analyses, only seven routine clinical, biological, and bacteriological variables studied were independently associated with hospital mortality. These were: the presence of upper gastrointestinal bleeding at admission (13 = 2.01), the absence of abdominal pain as presenting symptom (P = --1.29), the polymorphonuclear count (%) in the ascites (β = 0.48), prothrombin rate (β = --0.22), and serum Na (β = -0.64), creatinine (β = 0.50), and cholesterol (β = -0.68). When the equation obtained was computed in a randomly selected sample of the patients studied, it correctly predicted the outcome in 92.3% of the cases. We conclude that short-term outcome of SBP patients depends on the existence of recent gastrointestinal bleeding, the severity of SBP, and the degree of liver and renal failure. The prognostic value of this model needs prospective validation in a new series of patients. [ABSTRACT FROM AUTHOR]

To ascertain the role of total enteral nutrition, compared with total parenteral nutrition, as adjunct therapy to steroids in patients with severe acute ulcerative colitis, a prospective randomized trial was conducted in 42 of such patients. Inclusion criteria were the persistence of a moderate or severe attack of the disease (Truelove's index) after 48 h on full steroid treatment (prednisone 1 mg/kg/day). Patients were randomized to receive polymeric total enteral nutrition or isocaloric, isonitrogenous total parenteral nutrition as the sole nutritional support. Remission rate and need for colectomy were similar in both groups. No significant changes in anthropometric parameters were observed in either nutritional group at the end of the study. Median increase in serum albumin was 16.7% (-0.5% to +30.4%) in the enteral feeding group, and only 4.6% (-12.0% to +13.7%) in the parenteral nutrition patients (p = 0.019). Adverse effects related to artificial nutritional support were less frequent (9% vs. 35%, p = 0.046) and milder in enterally fed patients. Postoperative infections occurred more often with parenteral nutrition (p = 0.028). These results suggest that total enteral nutrition is safe and nutritionally effective in severe attacks of ulcerative colitis. It is also cheaper and associated with fewer complications than parenteral nutrition. Total enteral nutrition should be regarded as the most suitable type of nutritional support in these patients. [ABSTRACT FROM AUTHOR]

Portacaval anastomosis has proved to be effective in avoiding active and recurrent hemorrhage from gastroesophageal varices in liver cirrhosis. However, hepatic encephalopathy is the most common and serious complication of this procedure. The aim of this study was to investigate by multivariate analysis the predictive factors of development of hepatic encephalopathy in 50 Child's A and B cirrhotic patients whose variceal bleeding was treated with emergency (n = 17) or elective (n = 33) portacaval anastomosis. The etiology of the cirrhosis was alcoholic in 74% of cases. The mean follow-up was 22.7 ± 16.6 months (range 1-60 months). The 2-yr probability of suffering from at least one episode of hepatic encephalopathy in the overall group was 43%. The multivariate analyses (Cox's regression method) of 37 variables based upon clinical history, physical examination, and laboratory data disclosed that only five of these variables had independent predictive value: need for diuretic treatment in the days prior to surgery, absence of hepatomegaly, and serum levels of total bilirubin, γ-globulin, and hemoglobin. According to the contribution of each one of these factors to the final model, a prognostic index was obtained which allowed the division of patients in two different groups of risk for developing hepatic encephalopathy (20% and 74%, respectively, after 2 yr of surgery; p = 0.0002). This index may help to better choose those candidates for portacaval anastomosis. [ABSTRACT FROM AUTHOR]

Serum levels of zinc, copper, and selenium, and alkaline phosphatase activity were prospectively studied in 29 patients with inflammatory bowel disease. Fifteen patients had extensive active colitis (active colitis group). Seven patients had active, and seven cases inactive small bowel or ileocecal Crohn's disease (small bowel disease group). Ninety-three healthy subjects acted as controls. Serum trace element levels were considered in relation to vitamin A and E levels, nutritional parameters, the activity of the disease, and the recent intake of steroids. The effect of total enteral nutrition on serum trace elements was studied in seven cases. Serum zinc levels were lower and serum copper levels higher in the active colitis group than in controls (p = 0.0007, and p = 0.02, respectively). More than 50% of patients with active colonic or small bowel disease showed zinc levels below the 15th percentile of the control group. Serum zinc levels correlated with plasma vitamin A in acute colitis (r = 0.67; p = 0.006), and with both serum albumin concentration (r = 0.76; p = 0.002) and disease activity score (r = -0.67, p = 0.009) in patients with small bowel disease. The copper:zinc ratio was higher in the active colitis group than in controls (p = 0.002). In spite of the increase in serum albumin levels and the decrease in disease activity, serum zinc levels remained low after total enteral nutrition. The implications of the abnormal trace element status in patients with inflammatory bowel disease are discussed. [ABSTRACT FROM AUTHOR]

The status of water- and fat-soluble vitamins was prospectively evaluated in 23 patients (13 men, 10 women, mean age 33 ± 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 eases (group B) had small bowel or ileocecal Crohn's disease. Eighty-nine healthy subjects (36 men, 53 women, mean age 34 ± 2 yr) acted as controls. In both groups of patients, the levels of biotin, folate, β-carotene, and vitamins A, C, and B1 were significantly lower than in controls (p < 0.01). 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, β-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. [ABSTRACT FROM AUTHOR]

Plasma fatty acids (FA) from C14:0 to C22:6ω3 were measured in five healthy subjects and in 27 patients with liver cirrhosis. According to the assessment of triceps skinfold, mid-arm muscle circumference, and serum albumin concentration, patients were prospectively included in three groups: group A (n = 7) with acceptable nutritional status (including good nutrition and mild malnutrition), group B (n = 10) with moderate malnutrition, and group C (n = 10) with severe malnutrition. Plasma levels of total FA, saturated FA, linoleic acid, and ω6 > 18C and ω3 > 18 polyunsaturated fatty acids (PUFA) were lower in cirrhotics than in controls. Linoleic:arachidonic ratio was increased and Δ5-desaturation precursors:products ratio did not change, suggesting a reduction in Δ6-desaturase and/or C18-C20 elongase activities, in addition, a stepwise fall in plasma levels of all but saturated FA was found as the nutritional status worsened, suggesting that, in cirrhosis, impairment in PUFA biosynthesis is related to the severity of associated malnutrition. Since PUFA have important biological functions as components of cell membranes and precursors of eicosanoids, the results reported here may open new perspectives in the understanding of the cirrhosis-malnutrition relationship. [ABSTRACT FROM AUTHOR]

A 64-yr-old woman developed acute hepatitis after 3 wk of treatment with 40 mg/day of piroxicam (Feldene). Jaundice was preceded by a skin rash associated with eosinophilia. Despite withdrawal of the drug, she developed severe hepatocellular failure and died 53 days after the onset. Hepatitis was attributed to piroxicam because of the absence of other etiological factors. [ABSTRACT FROM AUTHOR]

Background/Aim: Therapeutic regimens with intravenous (i.v.) cyclosporine followed by oral cyclosporine maintenance therapy reduce the need for immediate surgery in steroid-refractory severe ulcerative colitis, but the short-term colectomy rate is still as high as 70%. We report our experience with long-term azathioprine maintenance therapy in a small series of ulcerative colitis patients with i.v. cyclosporine-induced remission. Methods and Results: Twelve of thirteen patients with severe ulcerative colitis refractory to i.v. prednisone (1 mg/kg/day for at least 10 days) went into remission after adding i.v. cyclosporine (4 mg/kg/day) and are the subjects of this report. After a discouraging initial experience with oral cyclosporine plus mesalazine as maintenance therapy in the first four patients, we treated the following patients with azathioprine plus mesalazine starting immediately after response to i.v. cyclosporine was obtained. Overall, only 1 of 10 patients treated with azathioprine relapsed after a mean follow-up of 16.3 months (range: 6-48). Moreover, this relapse probably occurred when the drug was still not therapeutically active because, after reinducing remission with oral prednisone, the patient remained symptomless on azathioprine. Steroids could be discontinued in all patients. Conclusions: The relapse rate on maintenance therapy with azathioprine (10%) is a figure considerably lower than that previously reported with oral cyclosporine. This promising experience should be confirmed in ran-domized controlled trials. [ABSTRACT FROM AUTHOR]

Presents a letter to the editor in response to the article "Food Impaction and Strictures After Sclerotherapy of Esophageal Varices," by J. P. Waring and R. A. Sanowski in the 1988 issue.