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In June 2007, the European Medicines Agency announced the recall by Roche of nelfinavir from European Union markets because of contamination of tablets with ethyl mesylate. Based on this event, we investigated the effect of switching therapy because of nelfinavir recall or for other reasons on the perception of therapy benefits and adherence to treatment in HIV-infected children and their caregivers. Thirty-eight children (mean age 12.1+/-6.7 years) were enrolled. A 35-item questionnaire was administered to the caregivers of enrolled children. Adherence was evaluated through a 4-day recall adherence instrument. Enrolled children were divided into 3 groups: patients who were shifted because of nelfinavir recall (group A, 8 patients); patients who were shifted for other reasons (group B, 12 patients); patients who were not shifted in the last 6 months (group C, 18 patients). All caregivers considered antiretroviral therapy necessary and effective for their children. However, drug shifting generated anxiety in most of them, irrespective of the reason for shifting. At baseline, 74% patients adhered to therapy. Adherence rate was related to the type of caregivers being higher in children cared for by foster parents than in children cared for by biological parents or second-degree relatives. Adherence rates did not change significantly in groups A and B after switching. Drug-switching raises concern in caregivers of HIV-infected children and induces a negative feeling irrespective of the reason for switching. However, switching, including the shift due to nelfinavir recall, did not affect adherence rates.

ORS has led to improved outcome of acute gastroenteritis in both industrialised and developing countries. In both settings there is an increasing demand for active therapy to reduce the duration of diarrhoea and its complications. Persistent diarrhoea is a major consequence of intestinal infections and is responsible for a high number of deaths in poor countries. Bismuth subsalicylate has been used for treatment of acute diarrhoea, with preliminary promising results. In this issue of Acta Paediatrica, a trial with BSS is essential. However the results were marginal and did not justify a mass scale use of BSS, also because of poor cost efficacy rate.

Summary Aims : To assess the incidence of intestinal inflammation in children with cystic fibrosis and to investigate whether probiotics decrease it. Study design : In this two-phase, controlled, prospective study, faecal calprotectin was measured by enzyme-linked immunosorbent assay in 30 children with cystic fibrosis, 30 healthy controls and 15 children with active inflammatory bowel disease. Ten children with cystic fibrosis received Lactobacillus GG, and faecal calprotectin was re-measured 4 weeks later. Rectal nitric oxide production was measured with the rectal dialysis bag technique in 20 children with cystic fibrosis, 20 healthy controls and 15 children with inflammatory bowel disease. Five children with cystic fibrosis received Lactobacillus GG and nitric oxide was re-measured 4 weeks later. Results : Mean faecal calprotectin was significantly higher in the two groups of patients than in controls. Abnormal values were detected in 27 of 30 cystic fibrosis and in 15 of 15 inflammatory bowel disease children. Also mean nitric oxide production was increased in both group of patients, and abnormal values were detected in 19 of 20 cystic fibrosis and in 15 of 15 inflammatory bowel disease children. Calprotectin and nitric oxide concentrations were reduced after probiotics administration. Conclusions : Intestinal inflammation is a major feature of cystic fibrosis and is reduced by probiotics. The latter finding suggests that intestinal microflora play a major role in intestinal inflammation in cystic fibrosis children.

Background: A complex interplay of malnutrition, intestinal dysfunction, and immune impairment increases the progression of human immunodeficiency virus (HIV) disease in children. The authors tested the hypothesis that nutritional support improves intestinal and immune functions in children infected with human immunodeficiency virus (HIV). Methods: A questionnaire was circulated through reference centers for pediatric HIV infection to evaluate the effects of nutritional rehabilitation, total parenteral nutrition (TPN) and enteral nutrition (EN), in children. Information included changes in body weight, CD4 cell numbers, and intestinal absorption - as judged by the xylose load - before and after clinical nutritional support and the outcome of children. Results: Sixty-two children underwent nutritional support: 46 received TPN and 16 received EN. All but three had full-blown acquired immunodeficiency syndrome, and all were severely malnourished. Baseline clinical conditions were worse in children receiving TPN than in those receiving EN. Intestinal dysfunction was detected in all children who received xylose oral load. A significant increase in CD4 cell count, xylose levels, and body weight followed EN. A similar pattern was observed after TPN, but none of the parameters significantly changed. Twenty-seven children who received TPN and three who received EN eventually died. Fourteen who received TPN and eight who received EN were shifted to oral feeding, and five who received TPN and five who received EN continued with clinical nutritional support at the end of the observation period. Conclusions: Nutritional intervention may restore intestinal absorption and increase CD4 cell numbers. The efficacy of nutritional intervention is enhanced if provided before a terminal stage of HIV infection. These data provide evidence of a close association among nutritional condition, intestinal absorption, and immune impairment. © 2002 Lippincott Williams and Wilkins, Inc.

Background: Several guidelines for the management of respiratory tract infections in children are available in Italy, as well as in other European countries and the United States of America. However, poor adherence to guidelines and the sustained inappropriate use of antibiotics have been reported. In the outpatient setting, almost half of antibiotics are prescribed for the treatment of common respiratory tract infections. In Italy the antibiotic prescription rate is significantly higher than in other European countries, such as Denmark or the Netherlands, and also the levels of antibiotic resistance for a large variety of bacteria are higher. Therefore, the Italian Society of Preventive and Social Paediatrics organised a consensus conference for the treatment of respiratory tract infections in children to produce a brief, easily readable, evidence-based document. Methods: The conference method was used, according to the National Institute of Health and the National Plan Guidelines. A literature search was performed focusing on the current guidelines for the treatment of airway infections in children aged 1 month-18 years in the ambulatory setting. Results: Recommendations for the treatment of acute pharyngitis, acute otitis media, sinusitis, and pneumonia have been summarized. Conditions for which antibiotic treatment should not be routinely prescribed have been highlighted. Conclusion: This evidence-based document is intended to accessible to primary care pediatricians and general practice physicians in order to make clinical practice uniform, in accordance with the recommendations of the current guidelines. © 2013 Elsevier Ltd.

Background & Aims Intestinal inflammation is a hallmark of cystic fibrosis (CF). Administration of probiotics can reduce intestinal inflammation and the incidence of pulmonary exacerbations. We investigated the composition of intestinal microbiota in children with CF and analyzed its relationship with intestinal inflammation. We also investigated the microflora structure before and after Lactobacillus GG (LGG) administration in children with CF with and without antibiotic treatment. Methods The intestinal microbiota were analyzed by denaturing gradient gel electrophoresis (DGGE), real-time polymerase chain reaction (RT-PCR), and fluorescence in situ hybridization (FISH). Intestinal inflammation was assessed by measuring fecal calprotectin (CLP) and rectal nitric oxide (rNO) production in children with CF as compared with healthy controls. We then carried out a small double-blind randomized clinical trial with LGG. Results Twenty-two children with CF children were enrolled in the study (median age, 7 years; range, 2–9 years). Fecal CLP and rNO levels were higher in children with CF than in healthy controls (184±146 µg/g vs. 52±46 µg/g; 18±15 vs. 2.6±1.2 µmol/L NO2−, respectively; P

Background: Nutrient malabsorption is a negative prognostic factor in acquired immunodeficiency syndrome and recent studies have shown that pancreatic insufficiency is a codetermining factor of malabsorption. Aims: To evaluate the effectiveness of open-label oral pancreatic enzyme supplementation therapy in acquired immunodeficiency syndrome patients with fat malabsorption. Patients and methods: Twenty-four consecutive patients with human immunodeficiency virus infection and fat malabsorption were recruited (11 males, 13 females; median age, 9.1 years). Faecal fat loss was evaluated by steatocrit assay at entry to the study (T-0), after 2 weeks (T-1) without pancreatic enzyme treatment and after a further 2 weeks (T-2) of treatment with pancreatic extracts (Creon 10 000 at a dose of 1000 units of lipase per gram of ingested dietary fat). Faecal elastase-1 and chymotrypsin were assayed at entry. Results: Six patients (25%) had abnormally low elastase-1 and/or chymotrypsin faecal concentration. In all patients, steatocrit values were elevated at both T-0 and T-1. Five patients proved intolerant to pancreatic enzyme treatment because of the onset of abdominal pain, and therapy was discontinued. In the 19 patients who concluded the study, steatocrit values during pancreatic enzyme treatment (T-2) were significantly lower than at entry (P

BACKGROUND: Childhood gastroenteritis is associated with considerable health costs. The natural clay dioctahedral smectite increases intestinal barrier function and is effective against infectious diarrhea in children in developing countries. The purpose of this work was to investigate the efficacy of smectite in Italian children with acute diarrhea of mild to moderate severity. METHODS: A national, prospective, randomized, case-controlled study was performed in collaboration with primary care pediatricians. Children seen by pediatricians for acute gastroenteritis were treated with oral rehydration solution (ORS) alone or ORS with smectite. Parents returned a form in which total duration of diarrhea, incidence of vomiting and fever, persistence of diarrhea for more than 7 days and hospital admissions were recorded. RESULTS: Eight hundred four children with acute diarrhea were randomly assigned to treated or control groups. Administration of smectite was associated with significant reduction of the duration of diarrhea, as judged by stool frequency and consistency. The incidence and duration of vomiting and fever were not different. Diarrhea lasted more than 7 days in 10% of treated and in 18% of control children (P < 0.01). Hospital admission was necessary in seven treated and six control children. No side effects were observed. CONCLUSIONS: Smectite reduces the duration of diarrhea and prevents a prolonged course. It may therefore consistently reduce the costs of gastroenteritis.

Preliminary clinical evidence suggests that Helicobacter pylori may be associated with diarrhea through its vacuolating toxin (VacA). To establish whether VacA induces intestinal secretion, epithelial damage, or both, purified pH-activated VacA was added to Caco-2 cell monolayers mounted in Ussing chambers, and electrical parameters were monitored. Mucosal addition of VacA induced an increase in short circuit current, consistent with enterotoxic effect. The effect was time- and dose-dependent and saturable. It was not found if the toxin was not pH-activated, added to the serosal side, or preheated. In cells preloaded with the Ca2+ buffering compound BAPTA/AM or with the Cl- channel inhibitor 5-nitro-2-3-(3-phenylpropylamino)benzoic acid, short circuit current did not change, indicating that VacA induces activation of Ca2+-dependent Cl- channels. VacA did not show cytopathic effects, as judged by tissue resistance. These results support the hypothesis that H. pylori may be associated with diarrhea through production of VacA.

Acute gastroenteritis (AGE) is a major cause of ED visits, hospitalizations, and prescription of investigations, drugs, and changes in diet. Several guidelines on management have been produced. RECENT FINDINGS: There is new information on different rehydration protocols, use of antiemetics, and antidiarrheal drugs that could reduce the burden of AGE. The need of intravenous (i.v.) rehydration is the main cause of hospital admission yet a standardized rehydration scheme is not available. Rehydration therapy through nasogastric tube is better than i.v. rehydration, in children with moderate-severe dehydration. Ultrarapid rehydration has been proposed by enteric or i.v. route to reduce the time in hospital and costs. However, reduced rehydration times are associated with high readmission rates and side effects. Antiemetics may reduce the need of i.v. rehydration because of vomiting and the number of hospital admissions. However, the main antiemetic, ondansetron, has been loaded with a warning for potentially severe side effects. Selected antidiarrheal drugs could reduce the length of stay, but data on their use in inpatients are still not conclusive. SUMMARY: Inappropriate medical interventions are still common in the hospital setting and have a high impact on costs. A validated management is still needed in inpatients.

Background/Aims: This study is aimed at assessing definitions and outcomes used to measure the effects of nutrition in the prevention and treatment of respiratory tract infections in childhood. Methods: We reviewed clinical trials studying the impact of nutritional interventions on upper and lower respiratory tract infections (URTI and LRTI), focusing on definitions and key outcomes. Results: Fifty trials were included (46 on prevention and 4 on treatment). The definitions of respiratory infections were highly heterogeneous. In 15 of the trials, URTI or LRTI were diagnosed by a pediatrician. In 30 trials, definitions were based on symptoms reported by family members or field-workers only. Five trials did not provide any specific definition. Incidence was the most common outcome measure reported in the trials on prevention, and duration and illness severity were the most common in the treatment trials. Conclusions: The results showed a major heterogeneity with the use of a wide array of different definitions and clinical end points. To overcome these limitations, outcome measures might be differentiated into two categories: ‘direct outcomes' in which respiratory infections are diagnosed and monitored by physicians according to rigorous definitions and ‘indirect outcomes' (e.g. chest X-ray, antibiotic prescription and hospitalizations) to assess the burden of respiratory illnesses. Agreement on standard definitions and end points is needed to drive future trials.

Probiotics are an established therapeutic or preventive intervention for gastrointestinal diseases and their efficacy is supported by several mechanisms, including the modulation of the immune response. However, there is evidence that the administration of probiotics may also be effective in the prevention or treatment of respiratory infections. Trials have been performed in general populations of infants and children and in populations at increased risk of respiratory infections, such as those in day care centers, schools, or hospitals, and evidence of a reduced rate of infections has been obtained in all those settings. In addition, the efficacy of probiotics to prevent respiratory infections has also been investigated in children with clinical conditions at increased risk of respiratory infections, such as those with atopy or with chronic diseases, and preliminary evidence of efficacy has been found. In adults, similar data have been obtained, although the body of evidence and the quality of data does not reach that available in childhood. Finally, the efficacy of probiotics in populations at risk of very severe respiratory infections, such as children with cystic fibrosis and preterm infants, has been investigated with promising results. However, differences in definitions, conditions, strains, and study protocols do not allow conclusions and further data are needed. In conclusion, probiotics provide a novel exciting opportunity for prevention and treatment of respiratory infections that is highly appealing in conditions of increased risk, particularly in children.

Oral administration of human serum immunoglobulin reduces the duration of diarrhea and of rotaviral excretion in children. To investigate the in vitro effects of immunoglobulin on virusenterocyte interaction, Caco-2 cells were infected with Rotavirus strain SA11. Immunoglobulin was added prior to and at various times postinfection. Indirect immunofluorescence was performed with an antibody against VP-6 rotaviral antigen. Cell viability and monolayer transepithelial electrical resistance (TEER) were monitored. Immunofluorescence showed a perinuclear distribution in 90% of cells.Rotavirus infection induced a progressive decrease in TEER and a parallel reduction in cell viability, depending on viral load. Preincubation of the virus with immunoglobulin prevented cell infection as judged by immunofluorescence. Immunoglobulin addition to infected cells partially prevented the decrease in TEER and induced a later shift of TEER toward increasing values, suggesting restoration of monolayer's integrity. The efficacy of immunoglobulin depended on its concentration and on the time of its addition. These results indicate that immunoglobulin is effective in preventing infection and in reducing cell damage, through a direct anti-Rotavirus action and may indicate that immunoglobulin should be administered in the early phase of diarrhea, to reduce the severity ofRotavirus infection.

Background There are few and debated data regarding possible differences in the clinical presentations of influenza A/H1N1, A/H3N2 and B viruses in children. This study evaluates the clinical presentation and socio-economic impact of laboratory-confirmed influenza A/H1N1, A/H3N2 or B infection in children attending an Emergency Room because of influenza-like illness. Methods Among the 4,726 children involved, 662 had influenza A (143 A/H1N1 and 519 A/H3N2) and 239 influenza B infection detected by means of real-time polymerase chain reaction. Upon enrolment, systematic recordings were made of the patients' demographic characteristics and medical history using standardised written questionnaires. The medical history of the children was re-evaluated 5-7 days after enrolment and until the resolution of their illness by means of interviews and a clinical examination by trained investigators using standardised questionnaires. During this evaluation, information was also obtained regarding illnesses and related morbidity among households. Results Children infected with influenza A/H1N1 were significantly younger (mean age, 2.3 yrs) than children infected with influenza A/H3N2 (mean age, 4.7 yrs; p < 0.05)) or with influenza B (mean age, 5.2 yrs; p < 0.05). Adjusted for age and sex, children with influenza A/H3N2 in comparison with those infected by either A/H1N1 or with B influenza virus were more frequently affected by fever (p < 0.05) and lower respiratory tract involvement (p < 0.05), showed a worse clinical outcome (p < 0.05), required greater drug use (p < 0.05), and suffered a worse socio-economic impact (p < 0.05). Adjusted for age and sex, children with influenza B in comparison with those infected by A/H1N1 influenza virus had significantly higher hospitalization rates (p < 0.05), the households with a disease similar to that of the infected child (p < 0.05) and the need for additional household medical visits (p < 0.05). Conclusions Disease due to influenza A/H3N2 viral subtype is significantly more severe than that due to influenza A/H1N1 subtype and influenza B virus, which indicates that the characteristics of the different viral types and subtypes should be adequately considered by health authorities when planning preventive and therapeutic measures.

A resistance of A/H1N1 influenza viruses to oseltamivir has recently emerged in a number of countries. However, the clinical and socioeconomic importance of this resistance has not been precisely defined. As children have the highest incidence of influenza infection and are at high risk of severe disease, the aim of this study was to evaluate the clinical importance and the impact on the households of oseltamivir-resistant seasonal A/H1N1 influenza virus in an otherwise healthy pediatric population. A total of 4,726 healthy children younger than 15 years with influenza-like illness were tested for influenza viruses by real-time polymerase chain reaction in the winters of 2007-2008 and 2008-2009 in Italy. The influenza A virus-positive samples underwent neuraminidase gene analysis using pyrosequencing to identify mutations H275Y and N294 S in A/H1N1, and E119V, R292K, and N294 S in A/H3N2. Among the A/H1N1 subtypes, the H275Y mutation was found in 2/126 samples taken in 2007-2008 (1.6%) and in all 17 samples (100%; p < 0.0001) taken in 2008-2009. No other mutation was identified in any of the A/H1N1 or A/H3N2 influenza viruses. No significant differences were found in terms of clinical importance or impact on the households between the children with oseltamivir-resistant seasonal A/H1N1 influenza virus and those with the wild-type. The spread of H275Y-mutated A/H1N1 seasonal influenza virus is a common phenomenon and the clinical importance and impact on the households of the mutated virus is similar to that of the wild-type in an otherwise healthy pediatric population.

The mechanisms of diarrhea due to rotavirus infection in humans are not fully understood; no specific therapy is available, but orally administered human serum immunoglobulins are effective in blocking stool output. We aimed to investigate the effect of rotavirus on ion transport and the role of NSP4 in human-derived enterocytes, and to test the efficacy of human serum immunoglobulin in a model of rotavirus infection. Soon after infection, rotavirus induces active chloride secretion in enterocytes. This effect is evident before viral replication leads to cell damage and correlates with NSP4 production. Inhibition of NSP4 prevents the early secretory phase but not cell damage. Incubation with human serum immunoglobulin blocks both ion secretion and cell damage. Rotavirus exerts an early NSP4-dependent ion secretion and subsequent tissue damage. The combined enterotoxic and cytotoxic effects may be responsible for the increased severity of diarrhea due to rotavirus infection, and both are counteracted by human serum immunoglobulin.

AIMS: Iodine supplementation of parenterally fed infants recommended by ESPGHAN is 1 microg/kg/day. To assess nutritional and thyroid status of children on parenteral nutrition (PN) through urinary iodine concentration (UIC). PATIENTS AND METHODS: Children (1-17 yrs), undergoing PN and receiving an iodine supply of 1 microg/kg/day, were enrolled from 2000 to 2007. RESULTS: We observed 15 children (10 males, mean age 76.53+/-60.4 months) on PN from 14 to 84 weeks (mean 38.5+/-21.4). Ten were on TPN and five on PPN; nine had short bowel syndrome (SBS) and six had other intestinal diseases requiring PN. Iodine supply in TPN ranged between 1 and 1.6 microg/kg/day (mean 1.1+/-0.3 microg/kg/day), while in PPN it ranged from 2.3 to 2.8 microg/kg/day (mean 2.6+/-0.7 microg/kg/day). We found an inverse correlation between duration of PN in months and UIC (P=0.05). Four weeks after PN onset, UIC

OBJECTIVES: To assess the features of fat redistribution, detected by clinical and ultrasound (US) methods, and the presence of metabolic disorders in HIV-infected children undergoing antiretroviral therapy. To evaluate if serum levels of resistin, a hormone produced only by visceral adipose tissue, are a marker of fat redistribution in these patients. DESIGN AND METHODS: Forty-five consecutive symptomatic HIV-infected children were considered for inclusion in the study. Patients were enrolled if treated for at least 6 months with antiretroviral therapy with or without protease inhibitor (PI) and if compliant to the study protocol. Patients were evaluated for: anthropometric measures, fat redistribution by clinical and US methods, serum lipids, parameters of insulin resistance by homeostasis model assessment for insulin resistance, serum resistin levels by an enzyme-linked immunosorbent assay. RESULTS: Eighteen children fulfilled the inclusion criteria and were enrolled in the study. Twelve (66%) children had clinical and/or US evidence of fat redistribution; 9 (75%) of them were on PI therapy; only 3 of 6 children without fat redistribution were on PI therapy (p

Adherence to antiretroviral (ART) therapy, as reported by children caregivers, was investigated and compared with physicians' estimates of adherence. Two parallel structured questionnaires were administered to caregivers of 129 HIV-infected children and to their physicians in seven different Italian reference centers. Doses omitted in the last four days were recorded. Perfect adherence (95% of prescribed doses taken in the last four days before interview) was reported by caregivers of 103 (79%) children. Five children (5%) omitted one dose of any ART drug in four days and were considered adherent. Low (95 but80% of doses) and poor (80% of doses) adherence were reported by 15 (12%) and six (5%) caregivers, respectively. Forty-eight children (37%) were judged to be non-adherent by their physicians, including 35 children who were receiving all the prescribed doses according to caregivers. The physicians identified eight out of the 21 non-adherent children as adherent. Non-adherence estimates by physicians closely correlated with poor clinical conditions. These data indicate that adherence is a major problem but there is a clear discrepancy between caregiver reports and physician judgement. The results underline the need of close surveillance of adherence in HIV-positive children in order to evaluate the effectiveness of ART therapy.

Summary Background There is conflicting evidence as to whether ursodeoxycholic acid (UDCA) reduces the incidence of parenteral nutrition-associated cholestasis. Aim To investigate the efficacy of UDCA on parenteral nutrition-associated cholestasis in children with intestinal failure due to short bowel syndrome or to other causes. Methods Children with cholestasis received 30 mg/kg/day UDCA. Improvement or normalization of parenteral nutrition-associated cholestasis was evaluated at 6 months of therapy and at the last follow-up. In a subgroup of children, serum UDCA levels were measured while receiving UDCA and after 4 weeks withdrawal. Results Twelve children were treated with UDCA. Full remission or partial improvement of parenteral nutrition-associated cholestasis occurred in 11 of 12 children. In three of four children, withdrawal of UDCA was associated with a rebound rise of cholestasis. Only one of 12 treated children showed no improvement and in this patient, in contrast to four other patients, plasma levels of UDCA did not increase during treatment. Conclusions Ursodeoxycholic acid was effective in controlling parenteral nutrition-associated cholestasis. The efficacy of UDCA also in children with short bowel is related to intestinal absorption.

Summary Background & aims Probiotics reduce intestinal inflammation in children with cystic fibrosis (CF). We want to determine the effects of Lactobacillus GG (LGG) on pulmonary exacerbations in CF. Methods A prospective, randomized, placebo-controlled, cross-over study was performed. Nineteen children received LGG for 6 months and then shifted to oral rehydration solution (ORS) for 6 months. In parallel nineteen received ORS and then shifted to LGG. Main outcome parameters were: incidence of pulmonary exacerbations and of hospital admissions, forced expiratory volume (FEV 1 ), and modifications of body weight. Results Patients treated with LGG showed a reduction of pulmonary exacerbations (Median 1 vs. 2 , range 4 vs. 4, median difference 1, CI 95% 0.5–1.5; p =0.0035) and of hospital admissions (Median 0 vs. 1, range 3 vs. 2, median difference 1, CI95% 1.0–1.5; p =0.001) compared to patients treated with ORS. LGG resulted in a greater increase in FEV 1 (3.6%±5.2 vs. 0.9%±5; p =0.02) and body weight (1.5kg±1.8 vs. 0.7kg±1.8; p =0.02). Conclusions LGG reduces pulmonary exacerbations and hospital admissions in patients with CF. These suggest that probiotics may delay respiratory impairment and that a relationship exists between intestinal and pulmonary inflammation.

Background The severity of childhood gastroenteritis is generally believed to be age-related rather than aetiologyrelated. Rotavirus-induced gastroenteritis is more severe than gastroenteritis caused by other enteric pathogens and is also age-related. We thus addressed the question of whether the increased severity of rotavirus-induced gastroenteritis is related to age or to features intrinsic to the agent. Study design In this multicentre, hospital-based, prospective survey, we evaluated the severity of diarrhoea in rotavirus-positive and rotavirus-negative children up to 4 years of age. Severity was assessed with a score in four groups of age-matched children. Results Rotavirus was detected in 381 of 911 children. Disease severity was evaluated in 589 cases for which clinical data were complete. The rotavirus-positive and rotavirus-negative groups differed with regards to diarrhoea duration, hospital stay, degree of dehydration and the number of episodes of vomiting. Gastroenteritis was more severe in rotavirus-positive than in rotavirus-negative children. In contrast, none of the main severity parameters differed in the four age groups, irrespective of the presence of rotavirus. Conclusions These data provide the evidence that aetiology and not age determines diarrhoeal severity. The demonstration that diarrhoea was more severe in rotavirus-positive children supports the need for a rotavirus vaccine and for studies that address the duration of vaccine protection.

It is becoming clear that intestinal microflora plays an important role in the development of local and systemic immune response. Nutritional ingredients have been added to infant formula in an attempt to make its composition similar to that of human milk. The effects of these modifications have been observed in the composition of intestinal microflora. Prebiotics are non-digestible foods able to selectively stimulate the growth/activity of a limited number of colonic bacteria. A mixture of galacto-oligosaccharides and fructo-oligosaccharides (GOS/FOS) induces an increase in Bifidobacteria, similar to that of breast-fed infants. What is less clear is whether the modifications of intestinal microflora obtained by functional foods are associated with clinically measurable effects. Preliminary indirect data suggest that increasing the load of Bifidobacteria and Lactobacilli may protect from infections and allergies and this effect may persists beyond infancy. The emerging concept is that early nutritional intervention may be effective in modifying the intestinal microflora composition in a phase in which microbiological imprinting may drive immunological imprinting thereby producing clinical effects. Further investigations and well designed randomised clinical trials are needed to demonstrate the potential beneficial effects and to exclude the potential side effects.

Antiemetics are not included for treatment of vomiting associated with acute gastroenteritis (AGE) in children by standard guidelines. We performed a survey to determine antiemetic prescribing rates by Italian pediatricians. A structured questionnaire was distributed at a pediatric national conference. The majority of responders reported prescribing antiemetics for pediatric gastroenteritis. Although there is insufficient evidence to justify their use, the use of antiemetics is widely present among pediatricians. © 2006 Lippincott Williams & Wilkins.

Several lines of evidence link inflammatory bowel diseases to modifications of intestinal microflora. Epidemiologic and clinical data suggest a triggering role for select agents in ulcerative colitis and in Crohn disease. Experimental evidence indicates that intestinal microorganisms are needed for developing intestinal inflammation in IL-10 knockout mice, and this is associated with an increased number of adherent clostridia and a decrease of lactobacilli and bifidobacteria. It may be hypothesized that a host-agent-specific relationship leads to an abnormal immune response, which may be genetically driven in select inflammatory bowel diseases. However, different from adults, the pattern of intestinal microflora undergoes profound changes during the early stage of life, contributing to the development of the immune system. A close relationship exists between microbiologic and immunologic imprinting. The microbiologic imprinting in neonates may be modified using bacterial probiotics that colonize the intestine, modify the immune response, and decrease the risk for atopy. Probiotics may decrease the recurrences of inflammatory bowel diseases. Preliminary evidence of intestinal antiinflammatory effects has been detected in children with cystic fibrosis. Overall these data provide the rationale to investigate the interaction between intestinal microflora and the local and general immune response in children with, or at risk for, inflammatory bowel diseases. This approach may be a key for understanding the pathophysiology of intestinal inflammation and may disclose novel strategies to educate better the immune system, particularly during its developmental stage.

Aim: To investigate rates and determinants of adherence to antiretroviral therapy in Italian children infected with the human immunodeficiency virus (HIV). Methods: An observational, cross-sectional multicentre study was performed through a structured interview with the caregivers of HIV-infected children. The interview included quantitative information on adherence in the 4 d before interview. Sociodemographic, clinical and psychosocial characteristics of children were recorded. Results: 129 children (median age 96 mo) were enrolled, of whom 94 were on highly active antiretroviral therapy (HAART). Twenty-one (16%) omitted more than 5% of total doses in 4 d and were considered non-adherent. However, only 11% of caregivers reported that therapy had been administered at the correct times. No significant difference was found between age and the stage of HIV infection. Children aware of their HIV status were less adherent. Individual drugs showed a broad adherence pattern and children who received HAART were more adherent. Children receiving therapy from foster parents were more adherent than those receiving drugs from biological parents or relatives. Conclusions: Adherence is a major problem in children. Psychological rather than clinical or sociodemographic features and types of drug are major determinants of adherence.

A double scenario characterizes the epidemiology of HIV infection in children. In countries where highly active antiretroviral therapy (HAART) is available, the pattern of HIV infection is evolving into that of a chronic disease, for which control strictly depends on patients' adherence to treatment. In developing countries with no or limited access to HAART, AIDS is rapidly expanding and is loaded with a high fatality ratio, due to the combined effects of malnutrition and opportunistic infections. The digestive tract is a target of the disease in both settings. Opportunistic infections play a major role in children with severe immune impairment, with Cryptosporidium parvum being the leading agent of severe diarrhea. Several therapeutic approaches are effective in reducing fecal output, but the eradication of the parasite is rarely obtained. Other opportunistic infections may induce severe and protracted diarrhea, including atypical mycobacteria and cytomegalovirus. Diagnosis of diarrhea should be individually tailored based on presenting symptoms and risk factors. A stepwise approach is effective in limiting patient discomfort and minimizing the costs of investigations, starting with microbiologic investigation and proceeding with endoscopy and histology. Aggressive treatment of infectious diarrhea is required in severely immunocompromised children. However, antiretroviral therapy prevents the development of severe cryptosporidiosis. The liver and pancreas are also target organs in HIV infection, although functional failure is rare. The digestive-absorptive functions are impaired, with steatorrhea, nutrient malabsorption, and increased permeability occurring in 20-70% of children. Intestinal dysfunction contributes to growth failure and further immune derangement, leading to wasting, the terminal stage of AIDS. Nutritional management is crucial in HIV-infected children and is based on aggressive nutritional rehabilitation through enteral or parenteral routes and micronutrient supplementation.HIV may play a direct enteropathogenic role and is implicated in both diarrhea and intestinal dysfunction. This explains the efficacy of antiretroviral therapy in inducing remission of diarrhea and restoring intestinal function. Gastrointestinal side effects of antiretroviral drugs are increasingly observed; they are often mild and transient. Severe reactions are rare but require the withdrawal of drugs. In conclusion, severe enteric infections and intestinal dysfunction characterize the intestinal involvement of HIV infection. This is more common in, but not limited to, children who do not receive effective antiretroviral therapy. Diagnostic approaches include microbiologic and morphologic examinations and assessment of digestive processes, but immunologic and virologic data should be also carefully considered. Treatment is based upon specific anti-infectious drugs, antiretroviral therapy, and nutritional rehabilitation.

Background & Aims: Severe diarrhea and enteropathy of unknown origin are frequent in patients infected with human immunodeficiency type 1 virus (HIV-1). The HIV-1 transactivating factor protein (Tat) is a key factor in the pathogenesis of acquired immunodeficiency syndrome. We investigated whether Tat could directly induce ion secretion and cell damage in enterocytes. Methods: Electrical parameters (ion transport studies) were measured in Caco-2 cell monolayers and in human colonic mucosa specimens mounted in Ussing chambers. The effect of Tat on intestinal mucosa integrity was determined by monitoring the transepithelial electrical resistance of Caco-2 cell monolayers. 3 H-thymidine incorporation and cell count were used to evaluate the effect of Tat on cell growth. Intracellular calcium concentrations were measured at the single-cell level using microfluorometry technique. Results: Tat protein induced ion secretion in Caco-2 cells and in human colonic mucosa similar to that induced by bacterial enterotoxins. It also significantly prevented enterocyte proliferation. In both instances, the effect of Tat was maximum at concentrations within the range detected in the sera of HIV-1–infected patients. Anti-Tat antibodies inhibited both effects. Ion secretion and the antiproliferative effects were mediated by L-type Ca 2+ channels. An increase in intracellular calcium concentration in Caco-2 cells was found after addition of Tat. Conclusions: These results indicate that Tat may be involved in HIV-1–related intestinal disease through direct interaction with enterocytes.

The role of nitric oxide (NO) in the intestinal basal ion transport and under conditions of enterotoxin-induced ion secretion is controversial. Namely it is not clear whether NO enhances or counteracts intestinal ion secretion and whether the effects on transport result from a direct interaction with the enterocyte. The cell origin of NO is also unclear. We have tested the hypothesis that NO produced by the enterocyte directly regulates ion transport processes either in basal condition or in response to cholera toxin-induced secretion. Electrical variables reflecting transepithelial ion transport were measured in Caco-2 cell monolayers mounted in Ussing chambers exposed to the NO synthase inhibitor Nomega-nitro-l-arginine methyl ester, in the presence or absence of cholera toxin. cAMP concentrations were also measured. NO release was determined by nitrite-nitrate concentration. NO synthase activities were assayed by Western blot analysis. Nomega-nitro-l-arginine methyl ester had a secretory effect, as judged by increased basal short-circuit current and cAMP concentration. It also increased cholera toxin-induced electrical response and cAMP production. Either cholera toxin or the cAMP analog 8-bromo-cAMP induced a rapidly progressive and Ca2+-dependent increase in NO concentration, suggesting a homeostatic up-regulation of the constitutive form of NO synthase. Western blot analysis showed an increase in constitutive NO synthase enzyme isoform. These results indicate that the enterocyte regulates its own ion transport processes, either in basal condition or in the presence of active secretion, through the activation of a constitutive NO synthase-NO pathway, functioning as a braking force of cAMP-induced ion secretion.

The incidence of inflammatory bowel disease (IBD) is progressively increasing in children in Western countries (1). At present, IBD diagnosis and staging is based on a combination of clinical, endoscopic, histological, and radiographic criteria, and there is no simple, noninvasive reliable individual marker for evaluating disease activity and topographical involvement, to predict relapses, and to select distinct treatment strategies (2, 3). Increased nitric oxide (NO) levels have been detected in the stools and plasma of children with IBD (4). This is the likely result of an upregulation of inducible NO synthase activity, which has been detected in intestinal mucosal segments of patients with active ulcerative colitis (UC) and, with lower intensity, of those with Crohn's disease (CD), suggesting a role of NO in IBD pathophysiology . The aim of this study was to determine whether rectal NO production, measured by a simple and noninvasive technique, reflects local inflammatory changes and disease activity in children with IBD. Forty children were included in the study: diagnosis, disease activity, and topographical involvement were obtained in all subjects by endoscopy and mucosal biopsy. Mean NO concentration was significantly higher in children with active UC than in control subjects. In nonactive UC patients and in active CD patients with rectal involvement, an overproduction of NO was also detected, but its magnitude was significantly lower than that observed in active UC children. On the contrary, in active CD children with rectal sparing NO production was similar to that of controls

Background: Growth hormone (GH) stimulates intestinal growth and differentiation and promotes water and ion absorption in the rat intestine. Epidermal growth factor has similar effects, which involve tyrosine kinase activity. The effects of growth hormone on ion transport and cell growth and the role of tyrosine kinase in these effects were examined in a human-derived intestinal cell line (Caco-2). Methods: For transport study, electrical parameters were measured in human intestinal Caco-2 cell monolayers mounted in Ussing chambers. Cell growth was monitored by counting and 3 H-thymidine incorporation in the presence and absence of growth hormone. The role of tyrosine kinase was investigated by using its specific inhibitor genistein. Results: The addition of growth hormone induced a rapid. Cl - -dependent, decrease in short-circuit current without affecting tissue conductance, which is consistent with an anion-absorptive effect. Incubation with growth hormone increased cell count by 85% and 3 H-thymidine incorporation by 64% versus the count in control specimens. The absorptive and trophic effects of growth hormone were dose-dependent, and the maximum effective concentration was identical for each effect. Genistein blocked the growth hormone effect on ion transport and cell growth. Conclusions: Growth hormone stimulates ion absorption and cell growth in human enterocytes. Both effects result from a direct growth hormone-enterocyte interaction, and both require tyrosine kinase activity. Growth hormone may have therapeutic potential in intestinal diseases characterized by epithelial atrophy and loss of water and electrolytes.

history of respiratory distress and ab ingestis bronchial-pneumonia and at 2 years old, he underwent surgical intervention for ultra-short Hirshproung Disease. After the exclusion of neurological and otolaryngological causes, he underwent upper endoscopy, which showed two Mallory-Weiss bleeding tears of about 1.5 cm each. He was immediately admitted and received intravenous treatment with Omeprazole and Ampicillin/Sulbactam. After one week of hospitalization a control upper endoscopy showed superficial erosions till the middle oesophagus, improved over the last. Besides the oesophagus presented a “trachealized” aspect, suspicious for eosinophilic oesophagitis and an hyperaemic gastropathy at the body and at the antrum. However the histological report defined an eosinophilic gastritis. He, also, underwent a ileocolonoscopy that described a linfoid nodular hyperplasia and an severe inflammation of ileo-caecal valve, left-colon and sigmoid-rectum tract to complete the diagnosis. The eosinophilic infiltrate was also significant at the colic level. Finally, chest X-ray, brain RNM and abdominal ultrasound resulted negative while allergic test were positive to many allergens (kiwi, hazelnuts). Faecal research of bacterial and parasites were negative; the peripheral blood smear was negative for blasts. Between biochemical parameters, eosinophils were increased (12.6%) as well as ECP (200 μg/l) and triptase (3 μg/l). According to the allergologist, the child begin a steroid therapy at full dose, a diet restriction and stopped the assumption of Montelukast, because of the possible increasing of eosinophilia. At the moment, his clinical conditions are improved: he no longer vomits, his biochemical parameters are normalizing (eosinophils: 8.2%; ECP: 86 μg/l; triptase: 2.47 μg/l), the last upper endoscopy was showed no lesions and at the histology the eosinophilic infiltrate is decreasing. Discussion: EGIDs are a group of emerging disease, which manifestations can be unspecific and chronic, but also, like in this case, severe and sudden. More studies are needed to evaluate if there were conditions that could trigger the disease (eg. drugs -Montelukast-). Finally, we report this case because of the Mallory-Weiss Syndrome is a rarely complication of EGIDs.

reversed 2 months later. Post-operative follow-up (1-3-6 months) included a clinical, nutritional haematological and biochemical examination. Results: Pre-operatively 1 patient was asymptomatic; 1 patient presented with hematochezia; 1 patient suffered abdominal pain. All patients had hundreds of colonic adenomatous polyps with mild dysplasia; 2 patients had gastric polyps; 1 patient ileal polyps; 1 patient had echo-structural thyroid abnormalities remaining euthyroid. No intra-operative or early post-operative complications occurred. Fifteen days post-operatively, 1 patient had partial small bowel obstruction caused by intestinal infection. After closure of ileostomies, all patients had voluntary bowel movements (mean: 4 movements/day) and no soiling, improving with diet and psyllium. A gradual weight increase was observed in 2 patients. Conclusions: Laparoscopic total colectomy with transanal rectal mucosectomy assures a low rate of complications, good functional outcome and excellent cosmetic results.

MI Spagnuolo, MP Cicalese, E Bruzzese, MA Caiazzo, S Di Caro, V Squeglia, A GuarinoDepartment of Paediatrics, University Federico II, Naples, ItalyBackground: Children with intestinal failure need parenteral nutrition to survive, and the only alternative is intestinal transplantation which still entails high mortality. The aim of this study was to compare the outcomes in candidates and noncandidates for intestinal transplantation, and to compare the outcomes with and without transplant surgery.Patients and methods: The clinical records of children admitted to hospital from 1997 to 2008 because of intestinal failure were reviewed for etiology of intestinal failure, age at start of parenteral nutrition, duration of parenteral nutrition, indications for intestinal transplantation, and outcome.Results: Thirty-four children were enrolled. Median age at start of parenteral nutrition was 13.1 (median 20.7) months. There was no difference in survival rate between candidates and noncandidates for intestinal transplantation. Survival was significantly higher in candidates who did not undergo intestinal transplantation than in children who underwent intestinal transplantation (P < 0.001).Conclusion: Candidates for intestinal transplantation who did not undergo transplant surgery had a better outcome than children who underwent transplant surgery.Keywords: intestinal transplantation, intestinal failure, parenteral nutrition, children