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Stefano Guandalini

Publications and source records attributed to Stefano Guandalini.

16 recordsLinked to original sources
PubMed2006

Reprogramming of CTLs into natural killer-like cells in celiac disease.

Celiac disease is an intestinal inflammatory disorder induced by dietary gluten in genetically susceptible individuals. The mechanisms underlying the massive expansion of interferon gamma-producing intraepithelial cytotoxic T lymphocytes (CTLs) and the destruction of the epithelial cells lining the small intestine of celiac patients have remained elusive. We report massive oligoclonal expansions of intraepithelial CTLs that exhibit a profound genetic reprogramming of natural killer (NK) functions. These CTLs aberrantly expressed cytolytic NK lineage receptors, such as NKG2C, NKp44, and NKp46, which associate with adaptor molecules bearing immunoreceptor tyrosine-based activation motifs and induce ZAP-70 phosphorylation, cytokine secretion, and proliferation independently of T cell receptor signaling. This NK transformation of CTLs may underlie both the self-perpetuating, gluten-independent tissue damage and the uncontrolled CTL expansion leading to malignant lymphomas in severe forms of celiac disease. Because similar changes were detected in a subset of CTLs from cytomegalovirus-seropositive patients, we suggest that a stepwise transformation of CTLs into NK-like cells may underlie immunopathology in various chronic infectious and inflammatory diseases.

Base Sequence↗
PubMed2006

Probiotics for children: use in diarrhea.

The use of probiotics in diarrheal diseases of children is increasing. Probiotics, mostly lactic acid bacteria such as Lactobacilli and Bifidobacteria, but also the yeast Saccharomyces boulardii, have been tried in many double-blinded, randomized, placebo-controlled studies, and several well-conducted meta-analyses are now available. There is some evidence of efficacy in the prevention of community-acquired and nosocomial diarrhea. More solid evidence of efficacy is found in the treatment of sporadic, infectious diarrhea, where several probiotics, and especially Lactobacillus GG, have been found capable of reducing by approximately 1 day the duration of diarrhea, shorten the initial phase of watery stools, and reducing hospital stay in developed countries. The effect is best documented in viral diarrheas. Although there are valid conceptual premises for probiotics to be helpful in inflammatory bowel diseases, only 1 trial has been published in children, showing Lactobacillus GG not to be superior to placebo in maintaining remission of Crohn disease. All considered, more research is needed for a better understanding of the role of probiotics in gastrointestinal diseases of children, addressing issues such as pharmacokinetics, mechanism of action, and role of specific probiotics, alone or in combination, in different disorders.

Acute Disease↗
PubMed2006

Recommendations for probiotic use.

Probiotics are live microbial organisms that are administrated as supplements or in foods to benefit the host. It is the recommendation that they may be helpful in the prevention and treatment of acute diarrhea in adults and children, the prevention of antibiotic-associated diarrhea in adults and children, and the maintenance of remission and prevention of pouchitis. Although early results indicate that probiotics may also be useful in immunologic modulation to prevent atopy, treatment of radiation intestinal disease, vaginosis, ulcerative colitis, and the irritable bowel syndrome, the studies available are not sufficient to say they are definitely helpful. Even fewer data are available to recommend probiotics for the treatment of H pylori and Crohn disease and for the prevention of cardiovascular risk factors or other degenerative diseases. Clearly, larger and better-designed studies of probiotics are necessary, including comparative and dose-ranging trials.

Cardiovascular Diseases↗
PubMed2006

Probiotics in gastrointestinal diseases in children: hard and not-so-hard evidence of efficacy.

The use of probiotics, once discussed primarily in the context of alternative medicine, is now entering mainstream medicine. However, only a few of the potential health benefits attributed to probiotics have been confirmed in well-designed, well-conducted, randomized, controlled trials. This is especially true in the pediatric population. We review here the available evidence on efficacy of probiotics in children in the prevention and treatment of gastrointestinal diseases. Although we restrict our analysis to the pediatric age, whenever potentially relevant information is available only from adult studies, they are examined as well. Probiotics have been most extensively studied in the treatment of diarrheal diseases, where their efficacy can be considered well established. Studies documenting effects in other childhood gastrointestinal illnesses are few, although some preliminary results are promising. Furthermore, only a limited number of probiotic strains have been tested, and, as the effects of different probiotic microorganisms are not equivalent, results cannot be generalized. Thus, at present, we have some positive certainties, lots of exciting promises and many unanswered questions.

Adult↗
PubMed2005

Guideline for the diagnosis and treatment of celiac disease in children: recommendations of the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition.

Celiac disease is an immune-mediated enteropathy caused by a permanent sensitivity to gluten in genetically susceptible individuals. It occurs in children and adolescents with gastrointestinal symptoms, dermatitis herpetiformis, dental enamel defects, osteoporosis, short stature, delayed puberty and persistent iron deficiency anemia and in asymptomatic individuals with type 1 diabetes, Down syndrome, Turner syndrome, Williams syndrome, selective immunoglobulin (Ig)A deficiency and first degree relatives of individuals with celiac disease. The Celiac Disease Guideline Committee of the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition has formulated a clinical practice guideline for the diagnosis and treatment of pediatric celiac disease based on an integration of a systematic review of the medical literature combined with expert opinion. The Committee examined the indications for testing, the value of serological tests, human leukocyte antigen (HLA) typing and histopathology and the treatment and monitoring of children with celiac disease. It is recommended that children and adolescents with symptoms of celiac disease or an increased risk for celiac disease have a blood test for antibody to tissue transglutaminase (TTG), that those with an elevated TTG be referred to a pediatric gastroenterologist for an intestinal biopsy and that those with the characteristics of celiac disease on intestinal histopathology be treated with a strict gluten-free diet. This document represents the official recommendations of the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition on the diagnosis and treatment of celiac disease in children and adolescents.

Adolescent↗
PubMed2005

A randomized, double-blind trial of Lactobacillus GG versus placebo in addition to standard maintenance therapy for children with Crohn's disease.

Probiotics are widely used by patients with Crohn's disease (CD) in an attempt to improve their health, but few controlled studies have been done to evaluate the efficacy of these therapies. We conducted a randomized, placebo-controlled trial of the probiotic Lactobacillus rhamnosus strain GG (LGG) to see if the addition of LGG to standard therapy prolonged remission in children with CD. Concomitant medications allowed in the study included aminosalicylates, 6-mercaptopurine, azathioprine, and low-dose alternate day corticosteroids. Seventy-five children (age range, 5-21 yr) with CD in remission were randomized to either LGG (n=39) or placebo (n=36) and followed for up to 2 years. The median time to relapse was 9.8 months in the LGG group and 11.0 months in the placebo group (P=0.24); 31% (12/39) of patients in the LGG group developed a relapse compared with 6/36 (17%) of the placebo group (P=0.18). The LGG was well tolerated, with a side effect profile comparable with placebo. This study suggests that LGG does not prolong time to relapse in children with CD when given as an adjunct to standard therapy.

Adolescent↗
PubMed2003

Prevalence of celiac disease in at-risk and not-at-risk groups in the United States: a large multicenter study.

BACKGROUND: Celiac disease (CD) is an immune-mediated enteropathic condition triggered in genetically susceptible individuals by the ingestion of gluten. Although common in Europe, CD is thought to be rare in the United States, where there are no large epidemiologic studies of its prevalence. The aim of this study was to determine the prevalence of CD in at-risk and not-at-risk groups in the United States. METHODS: Serum antigliadin antibodies and anti-endomysial antibodies (EMA) were measured. In EMA-positive subjects, human tissue transglutaminase IgA antibodies and CD-associated human leukocyte antigen DQ2/DQ8 haplotypes were determined. Intestinal biopsy was recommended and performed whenever possible for all EMA-positive subjects. A total of 13 145 subjects were screened: 4508 first-degree and 1275 second-degree relatives of patients with biopsy-proven CD, 3236 symptomatic patients (with either gastrointestinal symptoms or a disorder associated with CD), and 4126 not-at-risk individuals. RESULTS: In at-risk groups, the prevalence of CD was 1:22 in first-degree relatives, 1:39 in second-degree relatives, and 1:56 in symptomatic patients. The overall prevalence of CD in not-at-risk groups was 1:133. All the EMA-positive subjects who underwent intestinal biopsy had lesions consistent with CD. CONCLUSIONS: Our results suggest that CD occurs frequently not only in patients with gastrointestinal symptoms, but also in first- and second-degree relatives and patients with numerous common disorders even in the absence of gastrointestinal symptoms. The prevalence of CD in symptomatic patients and not-at-risk subjects was similar to that reported in Europe. Celiac disease appears to be a more common but neglected disorder than has generally been recognized in the United States.

Adolescent↗
PubMed2003

Celiac disease.

Celiac disease is a genetically determined, permanent intolerance to gluten, a protein complex found in wheat, rye and barley. As many as 1:163 people are affected by it, but only a small percentage are aware of the condition, which begins either in infancy, with gastrointestinal symptoms, or in childhood and later years with non-Gl signs and symptoms, such as fatigue, depression, anxiety, anemia, stunted growth, and delayed puberty. A strong association with Type 1 diabetes and Down syndrome is also found, thus making screening mandatory for these subjects. Celiac disease is often entirely clinically silent, yet it must be detected in order to prevent long-term complications.

Adolescent↗
PubMed2002

Update on immunologic basis of celiac disease.

During the past few years several seminal studies have greatly expanded our knowledge on celiac disease pathogenesis. This review focuses on aspects that have been most properly addressed and where substantial new information has been gathered include. Topics covered include (a) the identification of T-cell epitopes in gluten and the mechanisms of specific T-cell response in celiac disease small intestine; (b) the mechanisms of induction of mucosal lesion; and (c) the putative role of non-T-cell factors in driving mucosal response to gliadin. After discussing a brief history of the "quest for the cause of celiac disease," we examine the development of the typical celiac lesion (the crypt hyperplastic mucosal atrophy) as it generally unfolds: the increased entry of dietary antigens; the early changes, linked to specific components of the innate immunity rather than to its adaptive branch; the most thoroughly investigated subsequent response, involving a strong T-cell response and cytokines; and the factors responsible for enterocytes' death. The emerging pattern is that of a complex interaction of factors, although far from being completely understood, but fascinating as it opens an incredible window of knowledge on an autoimmune disorder whose environmental factor is known, whose autoantigen is known, whose autoantibodies are known: a truly unique situation in medicine.

Journal Article↗
PubMedDate not supplied

The treatment of acute diarrhea in the third millennium: a pediatrician's perspective.

Diarrheal diseases continue to be a major cause of morbidity and mortality worldwide. Although new, potentially useful drugs such as acetorphan are appearing at the horizon, the cornerstone of treatment remains a proper oral rehydration (ORT). Yet, the rates at which ORT is used are still disappointingly low. Despite dramatic progresses in the understanding of the pathophysiology of diarrhea, the list of available drugs is indeed short. Recently however, several new options have appeared that may bear a great potential in the near future. The first is a potential improvement of ORS. It was recently shown that the addition of a resistant starch to oral rehydration solution reduces fecal fluid loss and shortens the duration of diarrhea in patients with cholera. Starches that are resistant to hydrolysis by amylase in fact generate in the colon short-chain fatty acids, which are known to enhance sodium absorption. The second development in treating diarrheal disease is acetorphan (racecadotril). This enkephalinase inhibitor has in fact been shown to be effective in reducing by almost half the stool output of 135 young children with acute diarrhea. Finally, probiotics. In the last few years, they have attracted a great deal of renewed interest, particularly focusing on their effects in treating and preventing diarrheal diseases. Lactobacillus GG proved effective in several clinical trials, mostly randomized and placebo-controlled, in the prevention and/or treatment of acute diarrheal disease in children. We have recently shown (6) the safety and efficacy in its administration in the ORS, especially in Rotavirus-induced diarrheas, in a large multicenter, randomized, double blind and placebo-controlled study conducted on behalf of the ESPGHAN Working Group on Acute Diarrhea.

Acute Disease↗