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[Screening for celiac disease in high risk groups]. / Cribado de la enfermedad celíaca en grupos de riesgo.

Several epidemiological studies show that celiac disease with extraintestinal manifestations is 15 times more frequent than celiac disease with intestinal symptoms. Fifteen years ago the iceberg model was proposed to explain the epidemiology of this disease. On the one hand, there are a quantifiable number of patients who are correctly diagnosed since they have symptoms suggestive of this disease and who form the visible part of the iceberg. However, several studies using screening serology demonstrate that for each patient diagnosed, there is a mean of 5-10 patients without a diagnosis. These patients form the submerged part of the iceberg (monosymptomatic or silent celiac disease). The most widely accepted strategy to investigate the submerged part of the "celiac iceberg" is screening of known risk groups through a systematic search for celiac disease in these groups.

Cribado de la enfermedad celíaca en grupos de riesgo / Screening for celiac disease in high risk groups

Diversos estudios epidemiológicos muestran que la enfermedad celíaca con manifestaciones extraintestinales es 15 veces más frecuente que la que se presenta con síntomas intestinales. Hace ya años que se propuso el «modelo del iceberg» para explicar la epidemiología de la enfermedad celíaca. Por un lado, hay un número cuantificable de pacientes que son correctamente diagnosticados porque presentan síntomas sugestivos y forman la parte visible del iceberg. Sin embargo, diversos estudios, que emplean técnicas de cribado mediante serología, demuestran que por cada paciente diagnosticado, hay una media de 5-10 casos que no lo estaban. Estos casos forman la parte sumergida del iceberg (enfermedad celíaca monosintomática o silenciosa). La estrategia más aceptada para investigar la porción sumergida del «iceberg celíaco» es el cribado de grupos de riesgo reconocidos, mediante un proceso de búsqueda sistemática de enfermedad celíaca

Several epidemiological studies show that celiac disease with extraintestinal manifestations is 15 times more frequent than celiac disease with intestinal symptoms. Fifteen years ago the iceberg model was proposed to explain the epidemiology of this disease. On the one hand, there are a quantifiable number of patients who are correctly diagnosed since they have symptoms suggestive of this disease and who form the visible part of the iceberg. However, several studies using screening serology demonstrate that for each patient diagnosed, there is a mean of 5-10 patients without a diagnosis. These patients form the submerged part of the iceberg (monosymptomatic or silent celiac disease). The most widely accepted strategy to investigate the submerged part of the "celiac iceberg" is screening of known risk groups through a systematic search for celiac disease in these groups

Granulocyteaphaeresis in steroid-dependent inflammatory bowel disease: a prospective, open, pilot study.

BACKGROUND: Uncontrolled studies suggest that granulocyteaphaeresis might be useful in the management of active ulcerative colitis. AIM: To assess the efficacy of granulocyteaphaeresis treatment in active steroid-dependent inflammatory bowel disease. METHODS: We conducted a multicentre, prospective, open, pilot study in patients with steroid-dependent inflammatory bowel disease. All patients were started on 60 mg/day of prednisone; after 1 week, a five-session programme of granulocyteaphaeresis (once per week) was started. The steroid dose was tapered weekly if there was clinical improvement. Remission was defined as an inactive clinical activity index together with complete withdrawal of steroids at week 6. The patients were followed up for at least 6 months or until disease relapse. RESULTS: Twenty-six patients (14 ulcerative colitis, 12 Crohn's disease) were included. More than a half had been previously treated with immunomodulators. Remission was achieved in 62 and 70% of ulcerative colitis and Crohn's disease, respectively. During a median follow-up of 12.6 months, six of eight ulcerative colitis patients maintained their clinical remission; however, only one Crohn's disease patient remained in remission after the first 6 months of follow-up. CONCLUSIONS: Granulocyteaphaeresis is a safe treatment option in inflammatory bowel disease. A five-session programme of granulocyteaphaeresis seems to be efficient in the treatment of steroid-dependent ulcerative colitis, but not in Crohn's disease.

[Azathioprine and mesalazine in the prevention of postsurgical recurrence of Crohn's disease: a retrospective study]. / Azatioprina y mesalazina en la prevención de la recurrencia posquirúrgica en la enfermedad de Crohn: estudio retrospectivo.

OBJECTIVES: Surgical resection is still a mainstay of the treatment of Crohn's disease (CD). However, recurrence is the rule. The aim of the present study was to evaluate CD recurrence in a series of patients who underwent surgical resection with subsequent treatment with azathioprine (AZA) or mesalazine (5-ASA) and to identify the factors associated with recurrence. METHODS: The medical records of patients with CD who underwent bowel resection during a 4-year period were reviewed. Only patients who received AZA or 5-ASA as prophylaxis for recurrence were included. RESULTS: Thirty-three patients treated with AZA and 16 treated with 5-ASA were included. Endoscopic recurrence was found in 8.6% of the AZA group and in 87.5% of the 5-ASA group (p <0.001). Clinical recurrence occurred in 31.2% of patients in the 5-ASA group and in none in the AZA group (p=0.004). The accumulated probability of both clinical and endoscopic recurrence was significantly lower in the AZA group (p=0.0025 and p=0.005, respectively). Factors associated with a greater risk of endoscopic recurrence were termino-terminal anastomosis and 5-ASA treatment. The only factor associated with clinical recurrence was 5-ASA treatment. CONCLUSION: AZA seems to be more effective than 5-ASA in the prevention of postsurgical endoscopic recurrence of CD. Prospective studies with long-term follow-up are required to establish the true utility of AZA in the prophylaxis of CD recurrence.

Changes in mucosal fatty acid profile in inflammatorybowel disease and in experimental colitis: a common response to bowel inflammation.

BACKGROUND AND AIMS: Plasma polyunsaturated fatty acid profile in patients with inflammatory bowel disease is abnormal. We aimed to assess the mucosal fatty acid pattern in patients with ulcerative colitis and Crohn's disease, and in rats with trinitrobenzene-sulfonic acid (TNB) induced colitis. METHODS: Fatty acids were measured in colonic mucosa of patients with ulcerative colitis (n = 30), Crohn's disease (n = 21), and healthy controls (n = 13). Likewise, they were assessed in the colonic mucosa of rats with TNB- and sham-colitis. RESULTS: There was an increase of the end-products (C22:5n3, C22:6n3, C20:4n6, C22:5n6) and a decrease of the precursors (C18:3n3, C18:2n6) of both n3 and n6 polyunsaturated fatty acids in the mucosa of active ulcerative colitis and TNB-colitis. Also, high values of saturated (C16:0, C18:0) and low values of monounsaturated fatty acids (C18:1n9) were observed. Furthermore, the mucosa of active Crohn's disease showed substantial changes in saturated, monounsaturated and essential fatty acids, but not in polyunsaturated fatty acids. Mucosa of patients with inactive disease showed intermediate fatty acid values between the mucosa of active patients and healthy controls. CONCLUSIONS: Colonic inflammation causes a characteristic modification of the mucosal fatty acid profile which appears to be common to different aetiologies and seems to be related to the degree of inflammation.

Azathioprine is useful in maintaining long-term remission induced by intravenous cyclosporine in steroid-refractory severe ulcerative colitis.

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 randomized controlled trials.

How effective is enteral nutrition in inducing clinical remission in active Crohn's disease? A meta-analysis of the randomized clinical trials.

BACKGROUND: The purpose of the study was to evaluate, using meta-analysis techniques, whether enteral nutrition is effective in inducing clinical remission in active Crohn's disease. METHODS: Randomized trials either comparing enteral nutrition with steroids or comparing elemental (amino acid-based) with nonelemental diets were selected using MEDLINE (1984 to 1994), reference lists from published articles, reviews, and abstracts from major gastrointestinal meetings. Sixteen studies fulfilled the inclusion criteria (four published as abstracts). Crude rates for induction of remission were collected on an intention-to-treat basis by three independent observers. Each study was given a quality score, based on predetermined criteria. RESULTS: The pooled odds ratio (OR) for all type of enteral diets compared with steroid therapy was 0.35 (95% CI, 0.23 to 0.53). This result was similar for the best studies (by quality score) combined, for trials using tube feeding combined, and when noncompliant patients were withdrawn. Further subgroup analyses were conducted on the basis of the type of diet administered. Peptide-based diets were significantly inferior to steroids (pooled OR, 0.32; CI, 0.20 to 0.52). There was a trend to lower remission rate after elemental diets than after steroids (pooled OR, 0.44; CI 0.17 to 1.12). On the other hand, pooled OR for whole protein-based diets compared with elemental diets was 1.28 (CI, 0.40 to 4.02). CONCLUSIONS: Data available to date show that steroids are better than enteral nutrition to induce remission in active Crohn's disease. These results are more evident when peptide-based diets are administered, but they are not conclusive when either elemental or whole protein-based diets are used.

Determinants of plasma Fatty Acid abnormalities in patients with active inflammatory bowel disease: a multivariate analysis.

: Patients with active inflammatory bowel disease (IBD) have increased levels of n3 and decreased levels of n6 plasma long-chain polyunsaturated fatty acids (LC-PUFA). Using multivariate statistical techniques, this study assessed the influence of the potentially important factors of diagnosis (ulcerative colitis versus Crohn's disease), disease activity, malnutrition, location of disease, therapy, age, and sex on these plasma fatty acid abnormalities. Plasma fatty acids were analyzed by semicapillary column gas-liquid chromatography in 73 patients with IBD and 107 healthy controls. The effect of each confounder upon either "low" (below the first quartile of the control group) or "high" (above the third quartile of the control group) levels of each fatty acid (FA) was assessed by means of stepwise logistic regression analyses. After controlling for these factors, disease activity remained the primary factor associated with changes in the plasma FA profile. Moderate/severe activity was significantly associated with low n6 LC-PUFA and was inversely related to high n3 LC-PUFA. Corticosteroid therapy was independently associated with high C16:0 and C18:2n6 plasma values and low C20:3n6 values and unsaturation index. Sulfasalazine therapy was inversely associated with low percentages of both C18:0 and C20:3n6. Hypoalbuminemia was significantly related only to low values of C18:0. No relationship between any confounder and high levels of n3 LC-PUFA was found. The observed relationships may be of importance in the pathogenesis and treatment of IBD.

Factors associated with low values of biochemical vitamin parameters in healthy subjects.

Levels of vitamins A, E, C, B1, B2, B6, B12, folate and beta-carotene were assessed in plasma or whole blood in a group of 114 healthy adults. Biochemical vitamin status was classified into acceptable or suboptimal (moderate or severe). The independent association of various factors with the finding of a suboptimal vitamin status was studied by means of logistic regression analyses. Seventy seven per cent of subjects had suboptimal vitamin status for vitamin B2, 20% for vitamin A, and 84% for beta-carotene. Although few subjects had suboptimal biochemical levels for vitamin E, plasma levels of this vitamin were significantly lower in smokers than in non-smokers (p < 0.01). Likewise, plasma folate levels were significantly related to body mass index and the season of blood sampling (p < 0.05). Old age was protective (OR 0.15; 95% CI 0.03-0.67), whereas current smoking was harmful (OR 3.63; 95% CI 1.09-12.1) for riboflavin status. Age group of 25-59 years was independently associated to a low risk of suboptimal vitamin A status (OR 0.29; 95% CI 0.09-0.88). On the other hand, female sex had a negative effect on plasma vitamin A levels (OR 2.39; 95% CI 0.82-6.92) and smoking had a harmful effect on biochemical beta-carotene status (OR 2.72; 95% CI 0.82-8.99). This cross sectional study provides information about the determinants of vitamin inadequacy, and may be the basis for further pathophysiological studies.

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 Crohn's 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 Crohn's 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.

The relationship of plasma polyunsaturated fatty acid deficiency with survival in advanced liver cirrhosis: multivariate analysis.

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-tau-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 (beta, 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.

Enteral versus parenteral nutrition as adjunct therapy in acute ulcerative colitis.

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.

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 Crohn's 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 Crohn's 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 Crohn's 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 Crohn's 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.

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.

Plasma fatty acid profile in advanced cirrhosis: unsaturation deficit of lipid fractions.

Fatty acid (FA) profile of plasma total lipids, phospholipids (PL), cholesteryl esters (CE), and triglycerides (TG) were measured in 101 patients with advanced liver cirrhosis and in 44 age- and sex-matched healthy controls. Plasma levels of lipidic phosphorus, esterified cholesterol, and TG also were measured, and the unsaturation index (UI) was calculated for each fraction. Total plasma concentrations of saturated FA, linoleate, and polyunsaturated FA (PUFA) were lower in cirrhotics than in controls. This profile was also found in plasma levels of PL- and CE-associated FA. No detectable amounts of C20:3n9 were found in cirrhotic patients. Percent FA distribution of lipid fractions showed a lower percentage of linoleate and PUFA and a higher relative amount of saturated and monoenoic FA in cirrhotics than in controls. As a consequence, the UI of PL and CE was diminished in liver cirrhosis. Linoleate and PUFA deficiency was more marked in CE than in PL, as shown by the number of patients with values below the 5th percentile of the control group, suggesting an attempt to maintain the unsaturation of PL as the most important component of cell membranes. Hepatic failure, poor essential FA intake, and malnutrition are some of the possible etiologic factors for PUFA deficiency in cirrhosis. Their relative contribution to plasma FA abnormalities, as well as the clinical and pathophysiological consequences of PUFA deficit in cirrhotic patients, requires further investigation.