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Biomedical subjects

M A Gassull

Publications and source records attributed to M A Gassull.

At least 55 records · Page 3Linked to original sources

Serological markers and HLA-DQ2 haplotype among first-degree relatives of celiac patients. Catalonian Coeliac Disease Study Group.

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.

Adult↗

Nutritional issues in cirrhosis and liver transplantation.

In the past year, some relevant papers on the mechanisms of malnutrition in cirrhosis have been published. Studies investigating the metabolic destiny of leucine after protein breakdown, which have contributed to a better understanding of the pathogenesis of muscle wasting and fat depletion in these patients, deserve particular mention. Also, the demonstration that chronically reducing hyperinsulinaemia in cirrhosis is able to improve insulin sensitivity opens novel pathogenic and therapeutic perspectives for such a metabolic derangement in these patients. Other papers dealt with unsaturated lipids, lipoperoxidation and antioxidants in chronic liver disease. However, randomized trials on parenteral or enteral nutrition in cirrhosis and liver transplantation are missing.

Deficiency Diseases↗

Cytomegalovirus infection in patients with inflammatory bowel disease.

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 (1 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.

Adult↗

Randomized clinical trial of Plantago ovata seeds (dietary fiber) as compared with mesalamine in maintaining remission in ulcerative colitis. Spanish Group for the Study of Crohn's Disease and Ulcerative Colitis (GETECCU).

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, multicenter, 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 mg 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.

Adult↗

Translocated intestinal bacteria cause spontaneous bacterial peritonitis in cirrhotic rats: molecular epidemiologic evidence.

BACKGROUND/AIMS: Intestinal bacterial translocation is common in cirrhotic rats with spontaneous bacterial peritonitis, and it is thought to play a major pathogenic role. There has so far been no evidence for clonality between bacteria isolated from intestine and ascites. This study aimed to use molecular epidemiology techniques to show that spontaneous bacterial peritonitis is due to translocated intestinal bacteria. METHODS: Samples of ascitic fluid, portal blood, mesenteric lymph nodes and ileal contents from healthy (n=10) and ascitic cirrhotic rats with (n=12) or without (n=15) spontaneous bacterial peritonitis were cultured. In six infected rats, DNA macrorestriction fragments of 30 bacterial isolates [Escherichia coli (n=13), Enterococcus faecalis (n=12) and Proteus mirabilis (n=5)] from ascites (n=8), mesenteric lymph nodes (n=7), portal blood (n=6), and ileal flora (n=9) were compared. RESULTS: Bacterial translocation was more frequent in animals with (58%) than in those without spontaneous bacterial peritonitis (20%, p=0.049) or controls (10%, p=0.026). The same bacterial strain was simultaneously isolated in ascites and in mesenteric lymph nodes and/or ileum in 7/8 (87%) instances. The identity rate for bacteria present in both ascites and mesenteric lymph nodes was 80% (4/5). Likewise, identity was demonstrated in 3/4 instances of bacteria found in both ascites and portal blood. CONCLUSIONS: These results indicate that spontaneous bacterial peritonitis in cirrhotic rats is mainly due to intestinal bacteria translocated to mesenteric lymph nodes. Portal blood could be a less frequent route.

Animals↗

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) 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.

Adult↗

Nutrition in chronic liver disease and liver transplantation.

Significant contributions to the field of nutrition and liver disease have been published in the last year. The most relevant includes work on the pathogenic role of energy metabolism disturbances in the development of malnutrition in cirrhosis, as well as data on the relationship between preoperative nutritional deficiencies and the outcome of liver transplantation. However, despite these contributions, large-scale multicentric trials on the therapeutic value of nutritional support and metabolic care in cirrhosis and liver transplantation are still lacking.

Chronic Disease↗

Factors related to the presence of IgA class antineutrophil cytoplasmic antibodies in ulcerative colitis.

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.

Adult↗

Spontaneous bacterial peritonitis in patients with cirrhosis undergoing selective intestinal decontamination. A retrospective study of 229 spontaneous bacterial peritonitis episodes.

BACKGROUND/AIMS: Selective intestinal decontamination with norfloxacin is widely used to prevent spontaneous bacterial infections in cirrhosis. The study was performed to compare the spontaneous bacterial peritonitis occurring in patients with and without prophylactic norfloxacin. METHODS: Two hundred and twenty-nine consecutive episodes of spontaneous bacterial peritonitis, (193 in patients without (Group A) and 36 in patients with norfloxacin prophylaxis (Group B)), were retrospectively analyzed. In 100 episodes (86 and 14, respectively), the responsible organism was isolated in ascitic fluid. RESULTS: Clinical and laboratory data at diagnosis were comparable in both groups. There were marked differences (p < 0.001) between group A and B in the frequency of peritonitis caused by gram-negative (67.4% vs. 14.3%) and gram-positive (30.2% vs. 78.6%) bacteria. There were three polymicrobial episodes. Bacteria resistant to cefotaxime and gram-negative bacilli resistant to quinolones were isolated in ascitic fluid in nine (seven in Group A and two in Group B) and three episodes (all in Group A), respectively. No differences in the course of infection and patient survival were observed between groups. CONCLUSIONS: Spontaneous bacterial peritonitis in patients with and without prophylaxis with norfloxacin are not different in clinical features, response to treatment and prognosis. Spontaneous bacterial peritonitis caused by gram-negative organisms resistant to quinolones is extremely uncommon in patients with cirrhosis receiving prophylactic norfloxacin.

Adult↗

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.

Journal Article↗

Selective intestinal decontamination with norfloxacin reduces bacterial translocation in ascitic cirrhotic rats exposed to hemorrhagic shock.

Bacterial translocation (BT) can be involved in the pathogenesis of severe infections due to bacteria of enteric origin that complicates bleeding cirrhotic patients. To assess the effect of hemorrhagic shock (HS) on the incidence of BT and if selective intestinal decontamination (SID) reduces this incidence, we studied six groups of Sprague-Dawley rats: ascitic rats, ascitic rats exposed to HS with and without previous norfloxacin prophylaxis, healthy rats, and healthy shocked rats with and without previous norfloxacin prophylaxis. BT tended to be higher in ascitic rats with shock than without shock (69% vs. 41%, P = .15) and was significantly higher in healthy rats with than without shock (50 percent vs. 0 percent, P = .01). Norfloxacin significantly reduced translocation in ascitic shocked rats in comparison with nondecontaminated ascitic shocked rats (31 percent vs. 69 percent, P = .038). This effect was due mainly to a reduction of gram-negative BT (O percent vs. 37 percent, P = .008). In addition, norfloxacin prevented translocation in healthy shocked rats. Accordingly, aerobic gram-negative bacteria disappeared from fecal flora in all rats administered norfloxacin, except for Klebsiella species in one control rat. Cecal severe submucosal edema, chronic inflammatory infiltrate, and intestinal lymphangiectasia were significantly more frequent in ascitic rats than in control rats. Intestinal mucosal injury related with HS, particularly subepithelial cecal edema, was observed only in ascitic shocked rats. In conclusion, HS increases the incidence of BT both in ascitic cirrhotic and healthy rats. Norfloxacin reduces significantly the incidence of translocation after shock, especially in those cases caused by aerobic gram-negative bacilli.

Animals↗

Occlusion of the superior mesenteric artery in a patient with polycythemia vera: resolution with percutaneous transluminal angioplasty.

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.

Angioplasty, Balloon↗

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.

Adenoma↗

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 Brooke's 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.

Adult↗

Intracolonic administration of zileuton, a selective 5-lipoxygenase inhibitor, accelerates healing in a rat model of chronic colitis.

BACKGROUND: 5-Lipoxygenase products play a part in inflammatory response. AIMS: The effect of intracolonic administration of zileuton (a 5-lipoxygenase inhibitor) on colonic damage and eicosanoid local release was assessed in a rat model of colitis. METHODS: Ninety rats with trinitrobenzenesulphonic acid induced colitis were randomised to receive placebo, 5-aminosalicylic acid (50 mg/kg), or zileuton (50 mg/kg) intracolonically for four weeks. Local eicosanoid release was monitored by intracolonic dialysis throughout the study. The colon was removed for macroscopic and histological assessment at weeks 1, 2, and 4 after colitis induction in 10 rats of each group. RESULTS: Zileuton significantly reduced macroscopic damage score after four weeks of treatment in comparison with the other two groups (p = 0.034). In addition, zileuton administration significantly increased the intracolonic release of both thromboxane B2 at week 1 (p = 0.05) and prostaglandin E2 at weeks 2 and 4 (p < 0.05). Zileuton and 5-aminosalicylic acid decreased leukotriene B4 release by 90% at day 3. CONCLUSIONS: Intracolonic zileuton, compared with 5-aminosalicylic acid and placebo, seems to improve the course of the disease in a model of chronic colitis. This effect may be related to an increased and maintained production of prostaglandin E2 together with inhibition of leukotriene B4 synthesis.

Aminosalicylic Acids↗

[Prevalence of hepatocellular carcinoma in cirrhotic patients with with portosystemic shunt. Cohort analysis].

The development of hepatocellular carcinoma is frequent in patients with hepatic cirrhosis of any etiology. Despite the suggestion that portosystemic shunt may increase the risk of developing this neoplasm there are scarce clinical evidence to confirm this suggestion. The present cohort study was aimed at analyzing the follow up data of 232 patients included in 3 prospective randomized controlled studies in which the efficacy of shunt procedures (group I: portocaval or splenorenal anastomosis) versus techniques other than shunt (group II: esophageal transection or variceal sclerosis) in the treatment of upper-6I bleeding secondary to rupture of esophageal-gastric varices were compared. After a mean follow up of 50 months, no differences were observed between the two groups in relation with the prevalence of hepatocellular carcinoma (group I: 17%; group II: 12%; relative risk: 1.41 [CI 95%: 0.72 - 2.75]; p = 0.41) or the actuarial probability of developing this neoplasm (group I: 2% at 2 years, 21% at 5 years; group II: 7% at 2 years, 14% at 5 years; p = 0.42). The results of this analysis suggest that the performance of portosystemic shunt does not increase the risk of developing hepatocellular carcinoma in patients with hepatic cirrhosis.

Adult↗

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.

Adult↗