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Spectrum of gluten-sensitive enteropathy in first-degree relatives of patients with coeliac disease: clinical relevance of lymphocytic enteritis.

Background: Limited data on a short series of patients suggest that lymphocytic enteritis (classically considered as latent coeliac disease) may produce symptoms of malabsorption, although the true prevalence of this situation is unknown. Serological markers of coeliac disease are of little diagnostic value in identifying these patients. Aims: To evaluate the usefulness of human leucocyte antigen-DQ2 genotyping followed by duodenal biopsy for the detection of gluten-sensitive enteropathy in first-degree relatives of patients with coeliac disease and to assess the clinical relevance of lymphocytic enteritis diagnosed with this screening strategy. Patients and methods: 221 first-degree relatives of 82 DQ2+ patients with coeliac disease were consecutively included. Duodenal biopsy (for histological examination and tissue transglutaminase antibody assay in culture supernatant) was carried out on all DQ2+ relatives. Clinical features, biochemical parameters and bone mineral density were recorded. Results: 130 relatives (58.8%) were DQ2+, showing the following histological stages: 64 (49.2%) Marsh 0; 32 (24.6%) Marsh I; 1 (0.8%) Marsh II; 13 (10.0%) Marsh III; 15.4% refused the biopsy. 49 relatives showed gluten sensitive enteropathy, 46 with histological abnormalities and 3 with Marsh 0 but positive tissue transglutaminase antibody in culture supernatant. Only 17 of 221 relatives had positive serological markers. Differences in the diagnostic yield between the proposed strategy and serology were significant (22.2% v 7.2%, p<0.001). Relatives with Marsh I and Marsh II–III were more often symptomatic (56.3% and 53.8%, respectively) than relatives with normal mucosa (21.1%; p = 0.002). Marsh I relatives had more severe abdominal pain (p = 0.006), severe distension (p = 0.047) and anaemia (p = 0.038) than those with Marsh 0. The prevalence of abnormal bone mineral density was similar in relatives with Marsh I (37%) and Marsh III (44.4%). Conclusions: The high number of symptomatic patients with lymphocytic enteritis (Marsh I) supports the need for a strategy based on human leucocyte antigen-DQ2 genotyping followed by duodenal biopsy in relatives of patients with coeliac disease and modifies the current concept that villous atrophy is required to prescribe a gluten-free diet.

Serum selenium and risk of large size colorectal adenomas in a geographical area with a low selenium status

OBJECTIVE:Selenium is a fundamental nutrient to human health that might have anticarcinogenic effects. Previous studies have assessed the possible relationship of selenium status to colorectal adenomas with controversial results. We primarily aimed to assess the relationship of serum selenium status with the presence of large size colorectal adenomas in subjects living in a poor selenium region. The serum selenium status in colorectal cancer was also evaluated.METHODS:Serum selenium levels were measured in 28 patients with large size sporadic adenomatous polyps, 24 patients with colorectal adenocarcinomas, and 35 age-matched healthy individuals. A logistic regression analysis was performed to assess the relationship of serum selenium to colorectal adenomatous polyps after adjusting for confounding variables (age, sex, smoking habit, and alcohol drinking).RESULTS:Among subjects aged ≤60 yr, mean serum selenium levels were significantly lower in both patient groups (adenoma, 57.9 ± 4.3 μg/L; cancer, 43.7 ± 6.6 μg/L) than in healthy controls (88.9 ± 8 μg/L) (p = 0.0001). There were no difference among subjects >60 yr old. A significant inverse association between selenium status and the diagnosis of large size adenomatous polyps after adjusting for confounding variables was found (adjusted p = 0.029). Subjects with higher selenium status (≥75th percentile value of 82.11 μg/L) had a lower probability (OR = 0.17, 95% CI = 0.03–0.84) to be in the adenoma group than subjects with lower selenium status (<82.11 μg/L). This association was more marked in subjects aged ≤60 yr (adjusted p value = 0.04, OR = 0.08, 95% CI = 0.007–0.91), and was not significant in older subjects.CONCLUSIONS:Results suggest that high selenium status may decrease the risk of large size adenomas in a low selenium region, and that this preventive effect seems to be exclusive to subjects ≤60 yr. These results will need to be confirmed in additional epidemiological studies before recommending selenium supplementation in patients with colon adenomas.

Changes of the mucosal n3 and n6 fatty acid status occur early in the colorectal adenoma-carcinoma sequence.

Despite data favouring a role of dietary fat in colonic carcinogenesis, no study has focused on tissue n3 and n6 fatty acid (FA) status in human colon adenoma-carcinoma sequence. Thus, FA profile was measured in plasma phospholipids of patients with colorectal cancer (n = 22), sporadic adenoma (n = 27), and normal colon (n = 12) (control group). Additionally, mucosal FAs were assessed in both diseased and normal mucosa of cancer (n = 15) and adenoma (n = 21) patients, and from normal mucosa of controls (n = 8). There were no differences in FA profile of both plasma phospholipids and normal mucosa, between adenoma and control patients. There were considerable differences, however, in FAs between diseased and paired normal mucosa of adenoma patients, with increases of linoleic (p = 0.02), dihomogammalinolenic (p = 0.014), and eicosapentaenoic (p = 0.012) acids, and decreases of alpha linolenic (p = 0.001) and arachidonic (p = 0.02) acids in diseased mucosa. A stepwise reduction of eicosapentaenoic acid concentrations in diseased mucosa from benign adenoma to the most advanced colon cancer was seen (p = 0.009). Cancer patients showed lower alpha linolenate (p = 0.002) and higher dihomogammalinolenate (p = 0.003) in diseased than in paired normal mucosa. In conclusion changes in tissue n3 and n6 FA status might participate in the early phases of the human colorectal carcinogenesis.

Plasma polyunsaturated fatty acid pattern in active inflammatory bowel disease.

Plasma fatty acid patterns were assessed by gas liquid chromatography in 73 patients with active inflammatory bowel disease and 107 healthy controls. The influence of the disease activity on fatty acid profile was also investigated. Plasma fatty acid patterns in patients with ulcerative colitis and Crohns disease were similar. Plasma C18:3n3 and C22:6n3 were significantly higher in active ulcerative colitis (p = 0.0143 and p < 0.00001 respectively) and in Crohns disease (p < 0.00001 for both) than in controls, whereas C20:3n6 was significantly lower in patients than in controls, both in ulcerative colitis (p = 0.0001) and in Crohns disease (p = 0.0041). In more severe disease, plasma polyunsaturated fatty acid concentrations fell with a significant stepwise decrease in the desaturation index (p = 0.0031 in ulcerative colitis and p = 0.0355 in Crohns disease). Even in patients with severe disease, however, plasma n3 fatty acids (C18:3n3 and C22:6n3) never fell below those of healthy controls. These findings suggest that in active inflammatory bowel disease, an increased biosynthesis might coexist with an increased consumption of polyunsaturated fatty acids. These observations may be of relevance in the pathogenesis of the disease as polyunsaturated fatty acids are involved in tissue eicosanoid synthesis and cellular membrane function, including that of immunocompetent cells. These results also question the rationale of using n3 polyunsaturated fatty acids in the treatment of inflammatory bowel disease.

Abnormal plasma polyunsaturated fatty acid pattern in non-active inflammatory bowel disease.

An abnormal plasma polyunsaturated fatty acid pattern (PUFA) (increased n3 and decreased n6 PUFA) has been reported in active inflammatory bowel disease (IBD). The possibility of a primary defect in the PUFA metabolism in IBD was hypothesised. The aim of this study was to assess plasma PUFA pattern in inactive inflammatory bowel disease and to ascertain whether patients who had had a colectomy and who were suffering from ulcerative colitis have a similar PUFA pattern than those patients with non-active ulcerative colitis and who had not had a colectomy. Plasma fatty acids were analysed by semi-capillary column gas-liquid chromatography in three groups of patients with inactive IBD (24 patients with inactive ulcerative colitis who had not had a colectomy, 15 patients with ulcerative colitis who had had a colectomy, and 27 patients with Crohns disease). Plasma concentration and percentage of C22:6n3 and unsaturation index were significantly higher in patients with inactive ulcerative colitis without a colectomy and the Crohns disease group (p < 0.0001) than in controls. Plasma concentration and percentage of C22:6n3 and the unsaturation index remained significantly higher, in both the operated and non-operated ulcerative colitis patients when compared with controls (p < 0.0001). These results suggest that in inactive IBD, an increased PUFA biosynthesis might be the cause of the high values of n3 compounds. These findings although seen in active disease, are more noticeable in remission because of the lack of artefactual factors (malnutrition, steroids, inflammation). In addition, persistence of high values in both groups of ulcerative colitis patients--that is, those who had had a colectomy and those who had not suggests the existence of a primary abnormality in the PUFA metabolism in IBD.

Antineutrophil cytoplasmic antibodies in sera from colectomised ulcerative colitis patients and its relation to the presence of pouchitis.

BACKGROUND: Few studies have evaluated the influence of colectomy on antineutrophil cytoplasmic antibody (ANCA) positivity in ulcerative colitis (UC). In small series of patients it has been suggested that ANCA positivity in UC might be predictive for development of pouchitis after colectomy. AIMS: To assess the prevalence of ANCA in UC patients treated by colectomy and a Brookes ileostomy (UC-BI) or ileal pouch anal anastomosis (UC-IPAA), and the relation between the presence of ANCA, the type of surgery, and the presence of pouchitis. SUBJECTS: 63 UC patients treated by colectomy (32 with UC-BI and 31 with UC-IPAA), 54 UC, and 24 controls. METHODS: Samples were obtained at least two years after colectomy. ANCA were detected by indirect immunofluorescent assay. RESULTS: There were no differences between patients with (36.3%) or without pouchitis (35.0%) and between patients with UC (55%), UC-BI (40.6%), and UC-IPAA (35.4%). However, ANCA prevalence significantly decreases in the whole group of operated patients (38.0%) compared with non-operated UC (p = 0.044). CONCLUSIONS: The prevalence of ANCA in operated patients was significantly lower than in non-operated UC, suggesting that it might be related either to the presence of inflamed or diseased tissue. ANCA persistence is not related to the surgical procedure and it should not be used as a marker for predicting the development of pouchitis.

Malnutrition-related polyunsaturated fatty acid changes in plasma lipid fractions of cirrhotic patients

Cirrhotic patients have both impaired liver function and nutritional derangement. In fact, the prevalence of protein-energy malnutrition (PEM) is very high in these patients. The aim of the present study was to elucidate whether the nutritional status in cirrhosis could be an additional factor that would affect levels of plasma lipids. Plasma lipid phosphorus, cholesterol, and triglycerides (TG), and fatty acid profiles in plasma and plasma fractions were determined in 50 healthy subjects and 92 patients with liver cirrhosis. The cirrhotic patients were prospectively included in three groups according to the result of nutritional assessment: group 1 (n = 38), acceptable nutritional status (including well-nourished and mildly malnourished patients); group 2 (n = 29), moderate PEM; and group 3 (n = 25), severe PEM. The main findings of this study were that the decrease in plasma cholesterol and linoleic, dihomo-gamma-linolenic, and arachidonic acid levels of cirrhotic patients was related to the degree of PEM. Cholesteryl esters (CE) appeared to be the most sensitive indicator of lipid changes in cirrhosis. We consider that the role of malnutrition in the changes observed for polyunsaturated fatty acid (PUFA) profiles in plasma lipids of cirrhotic patients may be of major importance, since severe malnourished subjects exhibited the lowest levels of those compounds. Dietary supplementation of both essential fatty acids (EFA) and long-chain PUFA in adequate amounts to the cirrhotic patient might be of importance in the management of the disease.

Plasma and Mucosal Fatty Acid Pattern in Colectomized Ulcerative Colitis Patients

Patients with inflammatory bowel disease (IBD)have increased plasma n3 polyunsaturated fatty acids(PUFAs), which in ulcerative colitis (UC) patientspersists six months after colectomy, suggesting aprimary abnormality in fatty acid (FA) metabolism inIBD. This finding needed to be confirmed in a largerseries of UC long-term colectomized patients. We aimedto assess the plasma FA pattern in UC colectomized patients with either Brookes ileostomy (UC-BI)or ileal pouch anal anastomosis (UC-IPAA) and themucosal FA pattern in the ileal reservoir of the UC-IPAApatients. Plasma FAs were assessed in 63 UC colectomized patients (31 with BI and 32 with IPAA) and 30controls. In 26 UC-IPAA (8 with pouchitis and 18 withoutpouchitis) and in 13 healthy controls gut mucosal FAswere also investigated. FAs were detected by capillary column gas-liquid chromatography.Increased levels of saturated fatty acids (SFAs) anddecreased percentages of monounsaturated fatty acids(MUFAs) were observed in both groups of patients. There were no changes in plasma n3 and n6 PUFAs. Themucosal FA pattern of the ileal reservoir consisted ofincreased long-chain PUFAs, specially n6 PUFA, and adecrease of their essential precursors. High percentages of SFAs and low percentages of MUFAs were alsoseen. The plasma FA profile previously described in IBDis not observed long-term after colectomy in UC,suggesting that it is related with the presence of inflamed intestine. High concentrations of SFAsand decreased percentages of MUFAs might represent earlyevents in disturbed FA metabolism in IBD. The changes inFAs of the ileal reservoir, which closely resemble those found in human and experimentalIBD, probably represent a common pattern of intestinalinflammation.

Plasma Polyunsaturated Fatty Acids in Liver Cirrhosis With or Without Chronic Hepatic Encephalopathy: A Preliminary Study

Fatty acid levels (from C14:0 to C22:6n3) in plasma lipid fractions were prospectively studied in 11 cirrhotic patients with chronic hepatic encephalopathy and compared with those in 23 cirrhotic patients without chronic hepatic encephalopathy with similar age, sex distribution, and liver and nutritional status, and in 11 age- and sex-matched, healthy subjects. Plasma lipid fractions were separated by thin-layer chromatography and fatty acids were identified by capillary column gas-liquid chromatography. Total n6 polyunsaturated fatty acid plasma levels were lower in cirrhotic patients--with and without chronic hepatic encephalopathy--than in control subjects. In addition, arachidonic acid levels, both in total lipids and fractions, were lower in patients with than in those without chronic encephalopathy. On the other hand, a selective decrease of plasma docosahexaenoic acid (a major component of neuronal membranes) was observed in those patients with chronic encephalopathy as compared with both control and cirrhotic subjects without chronic encephalopathy. These findings may be due to various mechanisms. Differences in long-chain polyunsaturated fatty acid content in fish- and meat-restricted diets partly may account for these findings. However, it could be speculated that polyunsaturated fatty acid biosynthesis may be reduced further in patients with chronic hepatic encephalopathy because of either a decrease in portal essential fatty acid extraction in the postabsorptive phase due to portal-systemic shunting or to the effect of protein-restricted diets. Furthermore, the finding of low plasma docosahexaenoic acid in these patients raises the possibility that this deficiency might be an additional pathogenic factor in chronic hepatic encephalopathy.

Factors Related to the Presence of IgA Class Antineutrophil Cytoplasmic Antibodies in Ulcerative Colitis

Objective: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 Brookes 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 Brookes 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 Brookes 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.