Alcoholic Cirrhosis Increases Risk for Autoimmune Diseases: A Nationwide Registry-Based Cohort Study

BACKGROUND & AIMS Alcoholic cirrhosis is associated with hyperactivation and dysregulation of the immune system. In addition to its ability to increase risk for infections, it also may increase the risk for autoimmune diseases. We studied the incidence of autoimmune diseases among patients with alcoholic cirrhosis vs controls in Denmark. METHODS We collected data from nationwide health care registries to identify and follow up all citizens of Denmark diagnosed with alcoholic cirrhosis from 1977 through 2010. Each patient was matched with 5 random individuals from the population (controls) of the same sex and age. The incidence rates of various autoimmune diseases were compared between patients with cirrhosis and controls and adjusted for the number of hospitalizations in the previous year (a marker for the frequency of clinical examination). RESULTS Of the 24,679 patients diagnosed with alcoholic cirrhosis, 532 developed an autoimmune disease, yielding an overall increased adjusted incidence rate ratio (aIRR) of 1.36 (95% confidence interval [CI], 1.24-1.50). The strongest associations were with Addison's disease (aIRR, 2.47; 95% CI, 1.04-5.85), inflammatory bowel disease (aIRR, 1.56; 95% CI, 1.26-1.92), celiac disease (aIRR, 5.12; 95% CI, 2.58-10.16), pernicious anemia (aIRR, 2.35; 95% CI, 1.50-3.68), and psoriasis (aIRR, 4.06; 95% CI, 3.32-4.97). There was no increase in the incidence rate for rheumatoid arthritis (aIRR, 0.89; 95% CI, 0.69-1.15); the incidence rate for polymyalgia rheumatica decreased in patients with alcoholic cirrhosis compared with controls (aIRR, 0.47; 95% CI, 0.33-0.67). CONCLUSIONS Based on a nationwide cohort study of patients in Denmark, alcoholic cirrhosis is a risk factor for several autoimmune diseases.

Nonalcoholic fatty liver disease: is all the fat bad?

Nonalcoholic fatty liver disease is now a major cause of liver disease in developed countries, largely as a result of an epidemic of obesity, diabetes and sedentary lifestyles. This has resulted in raised clinical awareness and diagnostic refinement. The entity encompasses several histologic patterns from benign steatosis to nonalcoholic steatohepatitis, the latter having a significant risk of progressive fibrosis and the development of cirrhosis. Labor-atory tests and imaging are not able to distinguish steatosis from steatohepatitis, which requires liver biopsy. However following an assessment of several risk factors, patients can be stratified for the potential risk of fibrosis, allowing the rational use of liver biopsy. This review will describe the various patterns of nonalcoholic fatty liver disease and relate this to disease pathogenesis and progression. Strategies for management, including experimental interventions, will be discussed.

Gastroenterology training in Latin America

Latin America is characterized by ethnic, geographical, cultural, and economic diversity; therefore, training in gastroenterology in the region must be considered in this context. The continent's medical education is characterized by a lack of standards and the volume of research continues to be relatively small. There is a multiplicity of events in general gastroenterology and in sub-disciplines, both at regional and local levels, which ensure that many colleagues have access to information. Medical education programs must be based on a clinical vision and be considered in close contact with the patients. The programs should be properly supervised, appropriately defined, and evaluated on a regular basis. The disparity between the patients' needs, the scarce resources available, and the pressures exerted by the health systems on doctors are frequent cited by those complaining of poor professionalism. Teaching development can play a critical role in ensuring the quality of teaching and learning in universities. Continuing professional development programs activities must be planned on the basis of the doctors' needs, with clearly defined objectives and using proper learning methodologies designed for adults. They must be evaluated and accredited by a competent body, so that they may become the basis of a professional regulatory system. The specialty has made progress in the last decades, offering doctors various possibilities for professional development. The world gastroenterology organization has contributed to the speciality through three distinctive, but closely inter-related, programs: Training Centers, Train-the-Trainers, and Global Guidelines, in which Latin America is deeply involved. (C) 2011 Baishideng. All rights reserved.

Helicobacter pylori and Iron-deficiency Anemia in Adolescents in Brazil

Aim: The aim of the study was to evaluate the association between Helicobacter pylori infection and iron deficiency (ID) in adolescents attending a public school. Patients and Methods: From March to June 2001, a cross-sectional study was conducted among adolescents (10-16 years) enrolled in a single public school in Sao Paulo, Brazil. Of 400 eligible students, 195 agreed to participate, but 1 was excluded due to sickle cell disease. A blood sample was collected from each subject to measure hemoglobin and ferritin. H pylori status was investigated with the 13 C-urea breath test. All of the subjects with either anemia or ID were given iron therapy. Results: H pylori prevalence was 40.7% (79/194), being higher in male subjects (45/90 vs 34/104, P = 0.014). There was no relation between infection and nutritional status. Abnormally low serum ferritin was observed in 12 subjects, half of whom were positive for H pylori (odds ratio [OR] 1.49, 95% confidence interval [CI] 0.38-5.81). The median serum ferritin was 33.6 ng/mL (interquartile range 23.9-50.9) in infected subjects and 35.1 ng/mL (interquartile range 23.7-53.9) in uninfected subjects. Anemia was detected in 2% (4/194) of the students, half of whom were infected (OR 1.47, 95% CI 0.1-20.6). The mean hemoglobin value in infected subjects was 13.83 g/dL +/- 1.02 versus 14 g/dL +/- 1.06 in uninfected subjects. Conclusions: The study was not able to find a relation between H pylori infection and ID or anemia.

Deuterium Equilibrium Time in Saliva of Newborn Infants

There is an increasing interest about the use of stable isotopes for body composition analysis in pediatrics. To ensure the success of total body water analysis by the deuterium dilution method, it is fundamental to determine the equilibrium tune (plateau) of deuterium in the body fluid studied. Objectives: We report here the equilibration time of deuterium oxide in the saliva of newborns after oral intake of the isotope. Methods: Twenty healthy term newborn infants, 10 males and 10 females, were analyzed. Saliva was collected from each newborn before the oral administration of a 100 mg/kg dose of deuterium oxide (baseline sample) and then at 1-hour intervals for 5 hours after administration. Deuterium enrichment of saliva was determined by isotope ratio mass spectrometry according to the recommendations of the International Atomic Energy Agency. Results: The plateau time of deuterium in saliva occurred 3 hours after oral administration of the stable isotope. Conclusion: These data are essential for further studies on the body composition of newborn infants. To the best of our knowledge, this is the first study regarding the equilibration time of deuterium in the saliva of term newborns. JPGN 48:471-474, 2009.

Eosinophilic esophagitis: Updated consensus recommendations for children and adults.

Eosinophilic esophagitis (EoE) is a clinicopathologic condition of increasing recognition and prevalence. In 2007, a consensus recommendation provided clinical and histopathologic guidance for the diagnosis and treatment of EoE; however, only a minority of physicians use the 2007 guidelines, which require fulfillment of both histologic and clinical features. Since 2007, the number of EoE publications has doubled, providing new disease insight. Accordingly, a panel of 33 physicians with expertise in pediatric and adult allergy/immunology, gastroenterology, and pathology conducted a systematic review of the EoE literature (since September 2006) using electronic databases. Based on the literature review and expertise of the panel, information and recommendations were provided in each of the following areas of EoE: diagnostics, genetics, allergy testing, therapeutics, and disease complications. Because accumulating animal and human data have provided evidence that EoE appears to be an antigen-driven immunologic process that involves multiple pathogenic pathways, a new conceptual definition is proposed highlighting that EoE represents a chronic, immune/antigen-mediated disease characterized clinically by symptoms related to esophageal dysfunction and histologically by eosinophil-predominant inflammation. The diagnostic guidelines continue to define EoE as an isolated chronic disorder of the esophagus diagnosed by the need of both clinical and pathologic features. Patients commonly have high rates of concurrent allergic diatheses, especially food sensitization, compared with the general population. Proved therapeutic options include chronic dietary elimination, topical corticosteroids, and esophageal dilation. Important additions since 2007 include genetic underpinnings that implicate EoE susceptibility caused by polymorphisms in the thymic stromal lymphopoietin protein gene and the description of a new potential disease phenotype, proton pump inhibitor-responsive esophageal eosinophila. Further advances and controversies regarding diagnostic methods, surrogate disease markers, allergy testing, and treatment approaches are discussed.

Total energy expenditure and patterns of activity in 8-10-year-old obese and nonobese children.

Total energy expenditure (TEE) and patterns of activity were measured by means of a heart rate (HR)-monitoring method in a group of 8-10-year-old children including 13 obese children (weight, 46 +/- 10 kg; fat mass: 32 +/- 9%) and 16 nonobese children (weight, 31 +/- 5 kg; fat mass, 18 +/- 5%). Time for sleeping was not statistically different in the two groups of children (596 +/- 33 vs. 582 +/- 43 min; p = NS). Obese children spent more time doing sedentary activities (400 +/- 129 vs. 295 +/- 127 min; p < 0.05) and less time in nonsedentary activities (449 +/- 126 vs. 563 +/- 135 min; p < 0.05) than nonobese children. Time spent in moderate or vigorous activity-i.e., time spent at a HR between 50% of the maximal O2 uptake (peak VO2) and 70% peak VO2 (moderate) and at a HR > or = 70% peak VO2 (vigorous)-was not statistically different in obese and nonobese children (88 +/- 69 vs. 52 +/- 35 min and 20 +/- 21 vs. 16 +/- 13 min, respectively; p = NS). TEE was significantly higher in the obese group than in the nonobese group (9.46 +/- 1.40 vs. 7.51 +/- 1.67 MJ/day; p < 0.01). The energy expenditure for physical activity (plus thermogenesis) was significantly higher in the obese children (3.98 +/- 1.30 vs. 2.94 +/- 1.39 MJ/day; p < 0.05). The proportion of TEE daily devoted to physical activity (plus thermogenesis) was not significantly different in the two groups, as shown by the ratio between TEE and the postabsorptive metabolic rate (PMR): 1.72 +/- 0.25 obese vs 1.61 +/- 0.28 non-obese. In conclusion, in free-living conditions obese children have a higher TEE than do nonobese children, despite the greater time devoted to sedentary activities. The higher energy cost to perform weight-bearing activities as well as the higher absolute PMR of obese children help explain this apparent paradox.

Effects of bovine alpha-lactalbumin and casein glycomacropeptide-enriched infant formulae on faecal microbiota in healthy term infants

Objective: Certain milk factors may promote the growth of a host-friendly gastrointestinal microbiota, for example, one that is predominated by bifidobacteria, a perceived healthpromoting genus. This may explain why breast-fed infants experience fewer intestinal infections than their formula-fed counterparts who are believed to have a more diverse microbiota, which is similar to that of adults. The effects of formulas supplemented with 2 such ingredients from bovine milk, a-lactalbumin (alpha-lac) and casein glycomacropeptide (GMP), on gut flora were investigated in this study. Patients and Methods: Six-week-old (4-8 wk), healthy term infants were randomised to a standard infant formula or 1 of 2 test formulae enriched in alpha-Jac with higher or lower GMP until 6 months. Faecal bacteriology was determined by the culture-independent procedure fluorescence in situ hybridisation. Results: There was a large fluctuation of bacterial counts within groups with no statistically significant differences between groups. Although all groups showed a. predominance of bifidobacteria, breast-fed infants had a small temporary increase in counts. Other bacterial levels varied in formula-fed groups, which overall showed an adult-like faecal microflora. Conclusions: It can be speculated that a prebiotic effect for alpha-lac and GMP is achieved only with low starting populations of beneficial microbiota (eg, infants not initially breast-fed.

rRNA probes used to quantify the effects of glycomacropeptide and alpha-lactalbumin supplementation on the predominant groups of intestinal bacteria of infant rhesus monkeys challenged with enteropathogenic Escherichia coli

Objectives: Certain milk factors may help to promote the growth of a host-friendly colonic microflora (e.g. bifidobacteria, lactobacilli) and explain why breast-fed infants experience fewer and milder intestinal infections than those who are formula-fed. The effects of supplementation of formula with two such milk factors was investigated in this study. Materials and Methods: Infant rhesus macaques were breastfed, fed control formula, or formula supplemented with glycomacropeptide (GMP) or alpha-lactalburnin (alpha-LA) from birth to 5 months of age. Blood was drawn monthly and rectal swabs were collected weekly. At 4.5 months of age, 10(8) colonyforming units of enteropathogenic E.coli O127, strain 2349/68 (EPEC) was given orally and the response to infection assessed. The bacteriology of rectal swabs pre- and post-infection was determined by culture independent fluorescence in situ hybridization. Results: Post-challenge, breast-fed infants and infants fed alpha-LA-supplemented formula had no diarrhea, whilst those infants fed GMP-supplemented formula had intermittent diarrhea. In infants fed control formula the diarrhea was acute. Conclusions: Supplementation of infant formula with appropriate milk proteins may be useful for improving the infant's ability to resist acute infection caused by E.coli.

Physiological and bifidogenic effects of prebiotic supplements in infant formulae

This randomized controlled trial involving 110 healthy neonates studied physiological and bifidogenic effects of galactooligosaccharides (GOS), oligofructose and long-chain inulin (FOS) in formula. Subjects were randomized to Orafti Synergy1 (50 oligofructose: 50 FOS) 0.4g/dl or 0.8g/dl, GOS:FOS (90:10) 0.8g/dl or a standard formula according to Good Clinical Practise (GCP) guidelines. A breast-fed group was included for comparison. Outcome parameters were weight, length, intake, stool characteristics, crying, regurgitation, vomiting, adverse events and fecal bacterial population counts. Statistical analyses used non-parametric tests. During the first month of life weight, length, intake and crying increased significantly in all groups. Regurgitation and vomiting scores were low and similar. Stool frequency decreased significantly and similarly in all formula groups but was lower than in the breast-fed. All prebiotic groups maintained soft stools, only slightly harder than those of breast-fed infants. The standard group had significantly harder stools at wks 2 and 4 compared to 1 (P<0.001 & P=0.0279). The total number of fecal bacteria increased in all prebiotic groups (9.82, 9.73 and 9.91 to 10.34, 10.38 and 10.37, respectively, log10 cells/g feces, P=0.2298) and resembled more the breast-fed pattern. Numbers of lactic acid bacteria, bacteroides and clostridia were comparable. In the SYN1 0.8 g/dl and GOS:FOS groups Bifidobacterium counts were significantly higher at D14 & 28 compared to D3 and comparable to the breast-fed group. Tolerance and growth were normal. In conclusion, stool consistency and bacterial composition of infants taking SYN1 0.8 g/dl or GOS:FOS supplemented formula was closer to the breast-fed pattern. There was no risk for dehydration.