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Biomedical subjects

M A Gassull

Publications and source records attributed to M A Gassull.

At least 19 recordsLinked to original sources
PubMed2006

Review article: the intestinal lumen as a therapeutic target in inflammatory bowel disease.

Undigested carbohydrates reaching the colon can act as competitors for epithelial bacterial receptors, making it difficult for noncommensal bacteria to adhere to them. On the contrary, fermentation of these carbohydrates by anaerobic flora produces - among other substrates - butyrate that is involved in numerous important metabolic processes. These include the provision of energy to the colonocytes, the enhancement of sodium and water absorption and the synthesis of mucus and cell membranes. In addition, butyrate inhibits the nuclear translocation of the transcription factor NFkappaB, which exerts a potent anti-inflammatory activity. Clinical experience with probiotics in inflammatory bowel disease (IBD) is controversial. Whereas some probiotic preparations appear to be useful in ulcerative colitis (UC) and pouchitis, most attempts to use probiotics for treating or preventing recurrence in Crohn's disease have failed. It should be pointed out that - unlike in the small bowel - the colon and ileal pouches are well-established microbiological ecosystems with increasing amounts of a wide variety of bacterial strains. These bacterial strains have a high degree of metabolic interaction with luminal nutrients and a greater probability of developing dysbiosis. With this in mind, the rationale for using pre- and probiotics appears to be stronger for colonic IBD (UC or Crohn's colitis) and pouchitis than for IBD mostly involving the small bowel.

Enterobacteriaceae↗
PubMed2006

European evidence based consensus on the diagnosis and management of Crohn's disease: special situations.

This third section of the European Crohn's and Colitis Organisation (ECCO) Consensus on the management of Crohn's disease concerns postoperative recurrence, fistulating disease, paediatrics, pregnancy, psychosomatics, extraintestinal manifestations, and alternative therapy. The first section on definitions and diagnosis reports on the aims and methods of the consensus, as well as sections on diagnosis, pathology, and classification of Crohn's disease. The second section on current management addresses treatment of active disease, maintenance of medically induced remission, and surgery of Crohn's disease.

Anti-Bacterial Agents↗
PubMed2005

Clinical evolution of luminal and perianal Crohn's disease after inducing remission with infliximab: how long should patients be treated?

BACKGROUND: Few data are available regarding the evolution of Crohn's disease after discontinuing a successful course of infliximab. AIM: To evaluate clinical outcome of Crohn's disease after induction of remission with three infliximab infusions (luminal disease) and after maintenance of remission with 1-year course of infliximab every 8 weeks (luminal and perianal). METHODS: Twenty-three patients with active luminal Crohn's disease who responded to three infusions of infliximab (0, 2, and 6 weeks), and 23 patients with sustained response to infliximab every 8 weeks during 1 year, were included. Patients were followed-up until relapse or for at least 6 months after infliximab discontinuation. Clinical outcomes and factors associated to relapse were evaluated. RESULTS: In luminal Crohn's disease, a three-infusion infliximab regimen achieved a sustained response in most patients, especially if a complete response occurred at the time of the third infusion. In patients treated for 1-year, infliximab discontinuation was also successful, with a cumulative probability of being free of relapse of 69% at 12 months. In perianal disease, early relapse was the rule after stopping infliximab treatment, with only 34% of patient maintaining remission at 1 year. CONCLUSIONS: Short regimens of infliximab might be evaluated in patients with luminal Crohn's disease. However, infliximab discontinuation is not recommended in perianal Crohn's disease, because of a high rate of early relapse.

Adolescent↗
PubMed2005

[Autoimmune hemolytic anemia associated with ulcerative colitis].

The incidence of immunological disorders has been reported to be greater in patients with inflammatory bowel disease than among the general population. The association of ulcerative colitis (UC) and autoimmune hemolytic anemia (AIHA) was first described in the early 1950s but no more than 50 cases have been described in the international literature. Detailed description of the pathogenic mechanisms involved in this association is lacking. The clinical course of AIHA and treatment response in these patients seems to be independent of UC, sometimes requiring immunosuppressive treatment and even surgery. We present 2 cases of AIHA associated with UC with distinct response to conventional treatment. We also review the literature on the subject.

Adult↗
PubMed2005

[Gasometric alterations in hospitalized cirrhotic patients].

BACKGROUND AND OBJECTIVES: Gas exchange alterations have been described in cirrhotic patients; but by the moment, a few prospective studies have focused in them. The aim of this study was to describe the frequency and severity of gasometric alterations in hospitalized cirrhotic patients, a their correlation with hepatocellular disfunction. PATIENTS AND METHODS: 50 consecutive cirrhotic patients (41 males) admitted for liver decompensation (ascites, liver encephalopathy, alcoholic hepatitis and upper gastrointestinal bleeding) without acute or chronic cardiopulmonary disfunction were included in the study. Patients were classified according with Child-Pugh score (A, n = 13; B, n = 21; C, n = 16). Severe alcoholic hepatitis (SAH) was confirmed in 7 patients. Arterial gasometry was performed in all patients before discharge. Contrast echocardiography was performed in any case of suspicion of hepatopulmonary syndrome (HPS). RESULTS: Light hypoxemia was observed (80.9 mmHg), without differences with Child-Pugh. Hypocapnia was significantly more evident in Child C than in A and B (31.2 +/- 3.1 vs. 38.1 +/- 4.3 y 36.3 +/- 5 mmHg; p < 0,05), respectively. Cirrhotic patients with SAH showed a significantly higher hypocapnia by comparison with others (31.2 +/- 3.1 vs. a 36.3+/-5 mmHg; p < 0.05). In multivariate analysis, independent prognostic variables for hypocapnica were plasmatic levels of protrombin time, albumin and sodium. HPS was confirmed in 8 patients (16%). CONCLUSIONS: The most prevalent gas exchange abnormality in cirrhosis was the alteration of alveolar-arterial oxygen tension gradient, directly correlated with hepatocellur disfunction. Hypocapnia could be a compensatory mechanism or the result of the activation of central respiratory centres by non-depurated substances by the liver.

Adaptation, Physiological↗
PubMed2004

[Azathioprine and mesalazine in the prevention of postsurgical recurrence of Crohn's disease: a retrospective study].

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.

Adult↗
PubMed2004

Expression of HLA-G in inflammatory bowel disease provides a potential way to distinguish between ulcerative colitis and Crohn's disease.

In addition to being involved in nutrient uptake, the epithelial mucosa constitute the first line of defense against microbial pathogens. A direct consequence of this physiological function is a very complex network of immunological interactions that lead to a strong control of the mucosal immune balance. The dysfunction of immunological tolerance is likely to be a cause of inflammatory bowel disease (IBD), ulcerative colitis (UC) and Crohn's disease (CD). HLA-G is a non-classical major histocompatibility complex (HLA) class I molecule, which is highly expressed by human cytotrophoblast cells. These cells play a role in immune tolerance by protecting trophoblasts from being killed by uterine NK cells. Because of the deregulation of immune system activity in IBD, as well as the immunoregulatory role of HLA-G, we have analyzed the expression of HLA-G in intestinal biopsies of patients with UC and CD. Our study shows that the differential expression of HLA-G provides a potential way to distinguish between UC and CD. Although the reason for this differential expression is unclear, it might involve a different mechanism of immune regulation. In addition, we demonstrate that in the lamina propria of the colon of patients with UC, IL-10 is strongly expressed. In conclusion, the presence of HLA-G on the surface of intestinal epithelial cell in patients with UC lends support to the notion that this molecule may serve as a regulator of mucosal immune responses to antigens of undefined origin. Thus, this different pattern of HLA-G expression may help to differentiate between the immunopathogenesis of CD and UC.

Biopsy↗
PubMed2004

Review article: the role of nutrition in the treatment of inflammatory bowel disease.

Nutrients may be involved in the modulation of the immune response through at least three different mechanisms. First, the intestinal ecosystem plays a pivotal role in the pathogenesis of inflammatory bowel disease, triggering the uncontrolled inflammatory response in genetically predisposed individuals. Nutrients, together with bacteria, are major components of, and can therefore influence, the intestinal environment. Second, as components of cell membranes, nutrients can mediate the expression of proteins involved in the immune response, such as cytokines, adhesion molecules and nitric oxide synthase. The composition of lipids in the cell membrane is modified by dietary changes and can influence cellular responses. Indeed, various epidemiological, experimental and clinical data suggest that the immune response may be sensitive to changes in dietary composition. Finally, suboptimal levels of micronutrients are often found in both children and adults with inflammatory bowel disease, although, with the exception of iron and folate, it is unusual to discover symptoms attributable to these deficits. However, subclinical deficits may have a pathophysiological significance, as they may favour the self-perpetuation of the disease (due to defects in the mechanisms of tissue repair), cause defective defence against damage produced by oxygen free radicals and facilitate lipid peroxidation. These events can occur even in clinically inactive or mildly active disease, as well as in the development of dysplasia in the intestinal mucosa. Some dietary manipulations have been attempted as primary treatment for rheumatoid arthritis, and specially formulated diets for enteral nutrition have proved to be an effective treatment for Crohn's disease. Most trials, although lacking sufficient patient numbers, have demonstrated a role for dietary manipulation as primary therapy for inflammatory disease. Dietary lipids are one of the most active nutritional substrates modulating the immune response. Recently, it has been demonstrated that lipids may be a key factor explaining the therapeutic effect of clinical nutrition in Crohn's disease.

Cell Cycle↗
PubMed2004

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.

Adult↗
PubMed2003

[Opportunistic infections in patients with inflammatory bowel disease undergoing immunosuppressive therapy].

Immunosuppressive agents (azathioprine, methotrexate) are increasingly being used in the treatment of inflammatory bowel disease. The use of immunosuppressive agents is associated with a greater risk of opportunistic infections, the most frequent of which are those caused by cytomegalovirus and varicella zoster virus. We present four cases of opportunistic infections due to Herpesviruses in patients undergoing immunosuppressive treatment with azathioprine for Crohn's disease. We also review the literature published on this topic. Two patients presented cutaneous varicella complicated by pneumonia and esophagitis respectively, one patient had cutaneous herpes zoster and the other had fatal pneumonia possibly caused by the Herpesvirus. In the first three the clinical course of the infection was favorable after withdrawing immunosuppressant treatment and initiating treatment with aziclovir. In patients Crohn's disease azathioprine treatment increases the risk of opportunistic infection by Herpesvirus. However, in the absence of other factors that increase immunosuppression, these infections usually have a benign course with specific antiviral therapy.

Acyclovir↗
PubMed2003

The effects of fish oil, olive oil, oleic acid and linoleic acid on colorectal neoplastic processes.

BACKGROUND AND AIMS: Several nutrients play a significant role in colorectal cancer development, and fats could be among the most determinant. While several studies have shown that the n-3 fatty acids eicosapentaenoic and docosahexaenoic and its main dietary source, fish oil could exert important antineoplastic effects, much less is known about the effects of olive oil and its main fatty acid, oleic acid, and linoleic acid. The aim of these studies is to assess the role of these nutrients in crucial processes involved in colorectal carcinogenesis. METHODS: Caco-2 and HT-29 colorectal cancer cells were supplemented with different fats and their role in apoptosis induction, cell proliferation, and differentiation was studied. COX-2 and Bcl-2 expressions were also assessed. RESULTS: Supplementation with fish oil or olive oil results in an induction of apoptosis and cell differentiation. The latest effect was also induced by oleic and linoleic acid. Fish oil diminishes significantly cell proliferation. Supplementation with fish oil and olive oil results in an early downregulation of COX-2 followed by a decrease in Bcl-2 expression. CONCLUSIONS: Fish oil and olive oil are capable of influencing crucial processes responsible for colorectal cancer development. COX-2 and Bcl-2 may be important mediators of some of these effects.

Apoptosis↗