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Biomedical subjects

M A Gassull

Publications and source records attributed to M A Gassull.

At least 37 records · Page 2Linked to original sources
PubMed2002

Azathioprine without oral ciclosporin in the long-term maintenance of remission induced by intravenous ciclosporin in severe, steroid-refractory ulcerative colitis.

BACKGROUND: Intravenous ciclosporin is considered to be the only alternative to avoid surgery in severe, steroid-refractory ulcerative colitis. In responders, some authors recommend a switch to oral ciclosporin to act as a 'bridge' until the therapeutic action of azathioprine is achieved for maintenance treatment. AIM: To report the short- and long-term outcome of intravenous ciclosporin-responsive ulcerative colitis patients treated with oral azathioprine without oral ciclosporin. METHODS: The records of all patients treated with intravenous ciclosporin for severe, steroid-refractory ulcerative colitis were reviewed. Responders following treatment with azathioprine but without oral ciclosporin as maintenance therapy were included. Patients with colonic cytomegalovirus infection and/or follow-up of less than 1 year were excluded. RESULTS: Twenty-seven patients were included. Steroids were discontinued in 24 (89%). The median follow-up was 36 months. Eighteen (75%) patients presented mild or moderate relapses, which were easily managed with salicylates or steroids. Cumulative probabilities of relapse were 42%, 72% and 77% at 1, 3 and 5 years, respectively. Eleven (40.7%) patients underwent elective colectomy. Cumulative probabilities of colectomy were 29%, 35% and 42% at 1, 3 and 5 years, respectively. No opportunistic infections were observed. CONCLUSIONS: Oral azathioprine seems to be enough to maintain long-term remission induced by intravenous ciclosporin in patients with steroid-refractory ulcerative colitis. The 'bridging step' with oral ciclosporin may not be necessary in this subset of patients, although a randomized controlled trial is warranted to confirm this hypothesis.

Administration, Oral↗
PubMed2002

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 < or = 60 yr, mean serum selenium levels were significantly lower in both patient groups (adenoma, 57.9 +/- 4.3 microg/L; cancer, 43.7 +/- 6.6 microg/L) than in healthy controls (88.9 +/- 8 microg/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 (> or = 75th percentile value of 82.11 microg/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 microg/L). This association was more marked in subjects aged < or = 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 < or = 60 yr. These results will need to be confirmed in additional epidemiological studies before recommending selenium supplementation in patients with colon adenomas.

Adenoma↗
PubMed2002

Fat composition may be a clue to explain the primary therapeutic effect of enteral nutrition in Crohn's disease: results of a double blind randomised multicentre European trial.

BACKGROUND: Dietary fat has been suggested to determine the therapeutic effect of enteral diets in Crohn's disease. AIM: To assess the efficacy of two whole protein based diets with different fat compositions (n6 polyunsaturated fatty acids v monounsaturated fatty acids) in inducing clinical remission in active Crohn's disease compared with steroids. METHODS: Sixty two patients with active Crohn's disease were randomised to receive, for not more than 4 weeks: (a) a polymeric enteral diet containing 35 g of lipids per 1000 kcal, high in oleate (79%) and low in linoleate (6.5%) (PEN1), (b) an identical enteral diet except for the type of fat which was high in linoleate (45%) and low in oleate (28%) (PEN2), or (c) oral prednisone (1 mg/kg/day). Diets were double blindly administered. The steroid group received a conventional ward diet. Treatment failure was considered when remission was not achieved at week 4. Clinical activity and biological and nutritional parameters were monitored. Independent predictors of remission were identified by stepwise logistic regression analysis. RESULTS: Overall remission rates (by intention to treat) were 20% (4/20) for PEN1, 52% (12/23) for PEN2, and 79% (15/19) for steroids (overall p=0.001; p<0.0005 steroids v PEN1, and p=0.056 PEN2 v PEN1). After excluding those patients who were non-compliant during the first week (per protocol analysis), remission rates were 27%, 63%, and 79%, respectively (p=0.008, steroids and PEN2 v PEN1). After adjusting for confounding variables, PEN1 remained significantly associated with a poor response. CONCLUSION: The type of dietary fat may be of importance for the primary therapeutic effect of enteral nutrition in active Crohn's disease.

Acute Disease↗
PubMed2001

Dietary fat intake and inflammatory bowel disease.

The biologic role of fatty acids as immunomodulators has been extensively studied in the in vitro and experimental setting because of its potential therapeutic applications in chronic immune-based diseases. Unlike the conventional treatments for such conditions, this approach seldom produces severe side effects. The possibility of manipulating dietary fat as a treatment of inflammatory bowel disease (IBD) has been explored for a number of years. However, to date, few epidemiologic and experimental studies support the potential use of dietary fatty-acid modification. Most of the attempts to demonstrate the usefulness of this therapeutic approach in clinical studies for both active and maintenance treatment in IBD have not succeeded. This lack of success is due in the majority of cases to defects in study design and the use of inappropriate "placebo" substances. This review analyzes the potential role of manipulating dietary fatty acids in IBD with respect to disease treatment and as a possible public health tool. Also discussed is the fact that fat sources may be at least as important as the individual fatty acids because of their non-fatty acid components.

Dietary Fats↗
PubMed2001

Effect of L-arginine on the course of experimental colitis.

BACKGROUND AND AIMS: L-Arg is the substrate for nitric oxide, and also for L-ornithine which, in turn, is the precursor for the synthesis of collagen and polyamines. By these different metabolic pathways, L-Arg is involved in the mechanisms of inflammation, tissue repair and fibrosis. Thus, the aim of this study was to assess the effect of both different amounts of L-Arg supplementation and L-Arg-free diets upon colonic inflammatory damage and fibrosis in experimental colitis. METHODS: Sprague-Dawley rats with trinitrobenzene sulphonic acid (TNBS)-induced colitis received increasing doses of L-Arg (30, 100, 500 mg/day), or D-Arg (500 mg/day). In a second experiment, two L-Arg-free diets (one supplemented with L-Gly) were compared to a L-Arg diet. Nitrite/nitrate release in the lumen of the colon and colonic damage were evaluated. In the first experiment, tissue collagen levels and colonic mucosal proliferation were also assessed. RESULTS: In the acute phase of colitis, intracolonic nitrite/nitrate levels were significantly higher in the 100 and 500 mg supplemented L-Arg groups than in D-Arg group. However, only rats treated with 500 mg of L-Arg showed moderately higher inflammatory and fibrosis colonic scores than the D-Arg treated rats. There was no significant influence of L-Arg-free diets on the course of TNBS-induced colitis. However, L-Arg diet accelerated weight gain both pre- and post-TNBS. CONCLUSIONS: These results suggest that normal amounts of L-Arg in the diet are not harmful, whereas both absence of L-Arg or supplementation with high doses of this amino acid may be deleterious. In the former this might be due to a decrease of nitrogen retention in injured rats, whereas in the latter it may result from both nitric oxide-mediated tissue damage and collagen deposition.

Acute Disease↗
PubMed2001

Nutrition in inflammatory bowel disease: impact on disease and therapy.

Nutritional derangements are frequent in inflammatory bowel disease. In the last year, significant work was published examining the mechanisms of impaired food intake in animal models of inflammatory bowel disease, which allow a better understanding of these processes. These data have shed new light on the relative role of underfeeding and inflammation on the growth retardation associated with intestinal inflammation. Other studies have provided further information on the risk factors and predictive biomarkers of bone loss in patients with inflammatory bowel disease. The potential role of enteral nutrition as primary therapy for Crohn disease is particularly addressed in the present review. Recent contributions emphasized the special importance of this therapeutic modality in pediatric patients, but the possible mechanisms for such therapeutic effect are still not well understood. Other nutrients may have a therapeutic potential in inflammatory bowel disease. In particular, recent data on the in vivo antiinflammatory action of butyrate merit special mention. Finally, novel nutritional therapeutic strategies for inflammatory bowel disease, such as transforming growth factor-beta2-enriched enteral feeding or hydrothermally processed cereals, have recently been explored.

Journal Article↗
PubMed2001

Nutrition in inflammatory bowel disease.

Nutritional derangements are frequent in inflammatory bowel disease. In the past year significant work has been published examining the mechanisms of impaired food intake in animal models of inflammatory bowel disease, which allow a better understanding of these processes. Data from the same laboratory have shed further light on the relative role of underfeeding and inflammation on the growth retardation associated with intestinal inflammation. Other studies have provided further data on the risk factors and predictive biomarkers of bone loss in patients with inflammatory bowel disease. The potential role of enteral nutrition as primary therapy for Crohn's disease is particularly addressed in this review. Recent contributions to the field emphasized the special importance of this modality of therapy in paediatric patients. The possible mechanisms for such a therapeutic action are not well understood. Other nutrients may have a therapeutic potential in inflammatory bowel disease. In particular, recent data on the in-vivo anti-inflammatory actions of butyrate merit special mention. Finally, novel nutritional therapeutic strategies for inflammatory bowel disease, such as transforming growth factor-beta2-enriched enteral feeding, or hydrothermally processed cereals have recently been explored.

Adult↗
PubMed2001

Nutritional aspects of liver disease and transplantation.

In the past year, some relevant papers related to the diagnosis of malnutrition and its pathogenesis in cirrhosis have been published. The value of anthropometrics in the nutritional assessment of end-stage cirrhotic patients has been reinforced. Also, the role of bioelectrical impedance analysis in these patients has been redefined. Several papers have investigated the relationship between leptin and malnutrition in chronic liver disease, particularly the role of alcoholism in hyperleptinaemia, and the importance of protein-bound leptin in these patients. In other papers, the impact of both undernutrition and obesity on the outcome of liver transplantation has been investigated. Two randomized, controlled trials on enteral nutrition in liver disease have been published in this period. One of them deals with a clinical situation (i.e. severe alcoholic hepatitis) associated with a high mortality rate, whereas the second is the first controlled trial in the field of preoperative nutrition in liver transplantation. Finally, some papers provide further arguments in the dilemma of which route of nutrition (enteral or parenteral) is better in cirrhosis.

Deficiency Diseases↗
PubMed2000

Comparison of heparin and steroids in the treatment of moderate and severe ulcerative colitis.

BACKGROUND & AIMS: Unfractionated heparin has been found to reduce symptoms and improve healing as adjuvant therapy in patients with ulcerative colitis. The current study evaluated the efficacy and safety of unfractionated heparin in the treatment of ulcerative colitis in comparison with methylprednisolone. METHODS: A multicenter randomized trial with blinded endpoint evaluation was conducted in patients hospitalized for moderate or severe ulcerative colitis. Patients were randomized to receive heparin as a continuous infusion or methylprednisolone (0.75-1 mg x kg(-1) x day(-1)). RESULTS: Twenty-five patients entered the study: 13 received methylprednisolone and 12 received heparin. By day 10, 69% of patients in the methylprednisolone group, but none in the heparin group, achieved significant improvement or remission. C-reactive protein levels significantly decreased in the methylprednisolone group but not in the heparin group. Three patients in the heparin group were withdrawn before day 10 because of an adverse event: rectal bleeding needing transfusion (2 cases) or surgery (1 case). The proportion of patients with persistent rectal bleeding at day 10 was 31% in the methylprednisolone group and 90% in the heparin group (P<0.05). CONCLUSIONS: Unfractionated heparin as monotherapy is not effective in the treatment of moderate or severe ulcerative colitis and is associated with significant bleeding complications.

Adult↗
PubMed2000

Effect of cisapride on intestinal bacterial overgrowth and bacterial translocation in cirrhosis.

Deranged intestinal motility, which occurs in cirrhosis, may facilitate the development of intestinal bacterial overgrowth (IBO), which can lead to bacterial translocation (BT). To assess the effect of cisapride on IBO and BT in cirrhosis, cirrhotic rats received cisapride or a placebo for 7 days, and measurements of jejunal bacterial content and BT studies were performed. In addition, jejunal fluid from 46 cirrhotic patients was obtained for quantitative bacterial culture. Those patients in whom gram-negative IBO was detected were randomized to receive or not to receive cisapride (20 mg twice per day) for 1 week. Cisapride significantly reduced IBO in cirrhotic rats. In addition, no BT was documented in treated animals, whereas it occurred in 40% in nontreated cirrhotic rats. Total IBO was documented in 23 of 46 cirrhotic patients, which was caused by gram-negative organisms in 10 cases. Orocecal transit time (OCT) significantly decreased after cisapride therapy, and was associated with the abolishment of bacterial overgrowth caused by gram-negative organisms in 4 out of 5 treated patients, whereas it persisted in nontreated cases. Cisapride administration to cirrhotic rats resulted in a reduction of the IBO, which is associated with a marked decrease in BT. On the other hand, cisapride facilitates the abolition of IBO caused by gram-negative organisms in cirrhotic patients.

Adolescent↗
PubMed2000

Short- and long-term outcome of severe alcohol-induced hepatitis treated with steroids or enteral nutrition: a multicenter randomized trial.

Steroids are recommended in severe alcohol-induced hepatitis, but some data suggest that artificial nutrition could also be effective. We conducted a randomized trial comparing the short- and long-term effects of total enteral nutrition or steroids in these patients. A total of 71 patients (80% cirrhotic) were randomized to receive 40 mg/d prednisolone (n = 36) or enteral tube feeding (2,000 kcal/d) for 28 days (n = 35), and were followed for 1 year or until death. Side effects of treatment occurred in 5 patients on steroids and 10 on enteral nutrition (not significant). Eight enterally fed patients were prematurely withdrawn from the trial. Mortality during treatment was similar in both groups (9 of 36 vs. 11 of 35, intention-to-treat) but occurred earlier with enteral feeding (median 7 vs. 23 days; P =.025). Mortality during follow-up was higher with steroids (10 of 27 vs. 2 of 24 intention-to-treat; P =. 04). Seven steroid patients died within the first 1.5 months of follow-up. In contrast to total enteral nutrition (TEN), infections accounted for 9 of 10 follow-up deaths in the steroid group. In conclusion, enteral feeding does not seem to be worse than steroids in the short-term treatment of severe alcohol-induced hepatitis, although death occurs earlier with enteral nutrition. However, steroid therapy is associated with a higher mortality rate in the immediate weeks after treatment, mainly because of infections. A possible synergistic effect of both treatments should be investigated.

Adrenal Cortex Hormones↗
PubMed2000

IOIBD questionnaire on the clinical use of azathioprine, 6-mercaptopurine, cyclosporin A and methotrexate in the treatment of inflammatory bowel diseases.

OBJECTIVE: To obtain information on the clinical experience with azathioprine (AZA), 6-mercaptopurine (6-MP), cyclosporin A (CyA) and methotrexate (MTX) in the treatment of patients with inflammatory bowel disease (IBD) by gastroenterologists and internists in different countries. DESIGN: A questionnaire designed by the International Organization for the Study of Inflammatory Bowel Disease (IOIBD) was mailed to 300 gastroenterologists, living in North America (n = 76) and Europe (n = 224) (12 countries), to obtain information on clinical experience. PARTICIPANTS: More than half of the respondents (168/298; 56.4%) worked in university hospitals and 58/298 (19.5%) in general (non-university) hospitals. Two-thirds (65%) had more than 10 years' experience in gastroenterology. RESULTS: The respondents had personal experience with AZA (88.4%), 6-MP (33.3%), CyA (48.7%) and MTX (36.3%). AZA was prescribed more frequently in Europe (92.6%) than in North America (74.2%) (P = 0.0002), 6-MP less frequently by the European than the North American respondents (23.8 and 53.3% respectively, P = 0.0001). Two-thirds (69.7%) usually prescribed AZA together with steroids to Crohn's disease patients; 62.4% of the respondents prescribed AZA for periods longer than 24 months. For ulcerative colitis, 77.9% had experience with AZA (Europe > North America, P = 0.0001). AZA had been prescribed by 69 respondents to pregnant patients, without apparent toxicity. Acute pancreatitis had been observed after AZA by 56.7% respondents; 25 malignancies were mentioned (six lymphoma, three leukaemia, three colon cancer, four renal carcinoma, nine others). CyA had been prescribed in acute ulcerative colitis by 140/291 respondents (North America 45.1%, Europe 49.1 %); of all respondents 63.9% treated < 5 patients with CyA, 36.1% 6-20 cases. CyA results were considered good in 29.5%, acceptable but with recurrences in 58.6%, and poor in 14.3%. MTX was prescribed in North America by 47.8% of the respondents, and by 33.9% in Europe (not significant). Several significant differences were observed between the prescription behaviour of respondents working at university hospitals and non-university hospitals, in particular in relation to participation in clinical trials. CONCLUSIONS: Considerable experience exists in the use of immunosuppressive therapy in IBD; however, differential prescription behaviour exists in the choice of immunosuppressives between North America and Europe. These IOIBD study results may contribute to a better insight in the daily use of immunosuppressive agents in IBD by gastroenterologists and other specialists.

Azathioprine↗
PubMed2000

Nutritional and metabolic issues in cirrhosis and liver transplantation.

In the last year some relevant papers on nutrition and metabolism in chronic liver disease and transplantation have been published. Studies investigating the reliability of predicting energy expenditure in cirrhosis, and some relevant contributions to the understanding of metabolic consequences of liver transplantation, deserve particular mention. These include the first direct evidence that liver transplantation corrects the insulin resistance present in cirrhosis, as well as studies on the role of genetic polymorphism of the vitamin D receptor gene in bone loss after transplantation. Other papers have dealt with body composition, polyunsaturated fatty acid and antioxidant status in cirrhosis. However, relevant contributions in the field of nutritional support in cirrhosis are surprisingly lacking.

Adaptation, Biological↗
PubMed2000

Effect of olive oil on early and late events of colon carcinogenesis in rats: modulation of arachidonic acid metabolism and local prostaglandin E(2) synthesis.

BACKGROUND: Animal model studies have shown that the colon tumour promoting effect of dietary fat depends not only on the amount but on its fatty acid composition. With respect to this, the effect of n9 fatty acids, present in olive oil, on colon carcinogenesis has been scarcely investigated. AIMS: To assess the effect of an n9 fat diet on precancer events, carcinoma development, and changes in mucosal fatty acid composition and prostaglandin (PG)E(2) formation in male Sprague-Dawley rats with azoxymethane induced colon cancer. METHODS: Rats were divided into three groups to receive isocaloric diets (5% of the energy as fat) rich in n9, n3, or n6 fat, and were administered azoxymethane subcutaneously once a week for 11 weeks at a dose rate of 7.4 mg/kg body weight. Vehicle treated groups received an equal volume of normal saline. Groups of animals were colectomised at weeks 12 and 19 after the first dose of azoxymethane or saline. Mucosal fatty acids were assessed at 12 and 19 weeks. Aberrant crypt foci and the in vivo intracolonic release of PGE(2) were assessed at week 12, and tumour formation at week 19. RESULTS: Rats on the n6 diet were found to have colonic aberrant crypt foci and adenocarcinomas more often than those consuming either the n9 or n3 diet. There were no differences between the rats on the n9 and n3 diets. On the other hand, administration of both n9 and n3 diets was associated with a decrease in mucosal arachidonate concentrations as compared with the n6 diet. Carcinogen treatment induced an appreciable increase in PGE(2) formation in rats fed the n6 diet, but not in those fed the n3 and n9 diets. CONCLUSIONS: Dietary olive oil prevented the development of aberrant crypt foci and colon carcinomas in rats, suggesting that olive oil may have chemopreventive activity against colon carcinogenesis. These effects may be partly due to modulation of arachidonic acid metabolism and local PGE(2) synthesis.

Adenocarcinoma↗
PubMed2000

Antineutrophil antibodies associated with ulcerative colitis interact with the antigen(s) during the process of apoptosis.

BACKGROUND: Cell death by apoptosis seems to be an important mechanism for translocation to the cell surface of a variety of intracellular components capable of inducing autoantibody production. AIMS: To identify the cellular location of antigen (Ag)-antineutrophil cytoplasmic antibodies (ANCA) in non-apoptotic human neutrophils, and to assess if ANCA associated with ulcerative colitis reacts with neutrophil antigen(s) during neutrophil apoptosis. The cellular distribution of Ag-ANCA in apoptotic neutrophils was also investigated. METHODS: Sera from 18 ulcerative colitis patients known to be positive for perinuclear IgG-ANCA (titre > or =1/320), as assessed by indirect immunofluorescence (IIF), were analysed by immunofluorescent confocal laser scanning microscopy. ANCA were identified with fluorescein isothiocyanate (FITC) and tetramethylrhodamine isothiocyanate (TRITC) in non-apoptotic and apoptotic neutrophils, respectively. Apoptotic and non-apoptotic DNA was labelled with FITC and propidium iodide, respectively. Cycloheximide was added to polymorphonuclear leucocyte culture to induce apoptosis. RESULTS: Three patterns of scanning laser immunofluorescence microscopy in non-apoptotic neutrophils were observed with respect to cellular ulcerative colitis associated ANCA distribution: (1) diffuse nuclear localisation (16.7%); (2) nuclear localisation in the nuclear periphery (50%); and (3) mixed nuclear and cytoplasmic localisation (33.4%). In all sera ANCA fluorescence colocalised almost completely with apoptotic DNA, with persistence of a diffuse and intense fluorescence. No significant changes in ANCA titres were found in non-apoptotic neutrophils. CONCLUSIONS: The antigen(s) of ANCA associated with ulcerative colitis seems to be localised in most cases in the neutrophil nucleus. The almost identical colocalisation of ANCA and apoptotic cleaved DNA suggests that intracellular DNA redistribution during neutrophil apoptosis may play a role in antigen exposure to the immune system and ANCA production in ulcerative colitis.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed2000

Abnormal fatty acid pattern in rheumatoid arthritis. A rationale for treatment with marine and botanical lipids.

OBJECTIVE: To assess the fatty acid pattern in plasma and synovial fluid (SF) in rheumatoid arthritis (RA) and to determine clinical factors related to possible abnormalities. METHODS: Thirty-nine patients with RA were included. SF samples were obtained from 9 patients. Disease activity was assessed using the Ritchie Articular Index and erythrocyte sedimentation rate. Fatty acids were assayed with gas liquid chromatography. RESULT: Decreased levels of eicosapentaenoic acid (p < 0.0001) and total n3 polyunsaturated fatty acids (p < 0.05) were observed in plasma and in joint fluid, respectively. An increase of the substrates of delta-5-desaturase (C20:3n6 and C20:2n6) and decrease of their products (C20:4n6 and C22:4n6) was observed in plasma total lipids and phospholipids. The long chain mono-unsaturated fatty acids (C20: 1n9, C22: 1n9, C24: ln9) were increased in the joint fluid and in plasma phospholipids. Patients with active disease showed a mild decrease of several saturated fatty acids, n3, and n6 polyunsaturated fatty acids. Minor abnormalities or no changes in fatty acid profile were found related to use of steroids, nonsteroidal antiinflammatory drugs, and gold salts, or malnutrition. CONCLUSION: The fatty acid pattern found in RA (decreased levels of n3 polyunsaturated fatty acids) may explain the beneficial effect of fish oil. Changes in n6 polyunsaturated fatty acids suggest that delta-5 desaturation is decreased and this might facilitate the antiinflammatory effect of botanical lipids in RA.

Aged↗