Enterotoxigenic Escherichia coli in children with acute diarrhoea and controls in Teresina/PI, Brazil: distribution of enterotoxin and colonization factor genes.

AIMS: To investigate the distribution of the genes that encode enterotoxins and the colonization factors (CF) types as well as the antibiotic susceptibility profile of enterotoxigenic Escherichia coli (ETEC) isolated from children from the Brazilian Northeast. METHODS AND RESULTS: We conducted a 3·5-year prospective study that involved 250 children with and 150 without diarrhoea, aged 1-60 months, from low-income families in Teresina/Brazilian Northeast. All samples were assayed for E. coli, enterotoxin and CF genes and antimicrobial susceptibility by microbiological methods and PCR. ETEC strains were isolated from 9·2% children with and 4·0% without diarrhoea. Infection was more common in children aged 6-24 months in rainy months. elt⁺ /CFA/IV⁺ and elt⁺ /CS14⁺ were the most frequent genotypes. Susceptibility to nalidixic acid, ciprofloxacin and gentamicin and resistance to ampicillin, cephalothin and sulfamethoxazole-trimethoprim were common. CONCLUSIONS: elt ⁺isolates and ETEC strains harbouring genes encoding CFA/IV and CS/14 were the most common ETEC found in Brazilian Northeast. SIGNIFICANCE AND IMPACT OF THE STUDY: Our data, the first generated for north-eastern Brazilian children, may be important for the development of an effective vaccine and for facilitation of an empirical choice of antibiotic treatment or prophylaxis for traveller's diarrhoea in the area studied.

Urothelial cell carcinoma of the bladder in pediatric patients: a systematic review and data analysis of the world literature.

BACKGROUND: Urothelial cell carcinoma (UCC) of the bladder is exceedingly rare in pediatric patients. Limited data are available to guide management in this population. METHODS: The authors systematically searched MEDLINE, Cochrane Library, and Google Scholar (through February 2019) for case reports and series to summarize data regarding presentation, evaluation, management, and follow-up for patients ≤ 18 years diagnosed with UCC of the bladder. Patient-level data were abstracted, and adjusted logistic regression was used to identify factors associated with a combined outcome of recurrence or death. RESULTS: One hundred two articles describing 243 patients from 26 countries met criteria. Average age was 12.5 years, 32.6% were female, 15.3% had medical comorbidities, and 13.2% had known risk factors for bladder cancer. Initial management was transurethral resection in 95.5% of patients, whereas 6.2% required secondary intervention. Tumor stage was TaN0M0 in 86.4% and low grade in 93.4%. Recurrence and death occurred in 8.6% and 3.7%, respectively. Mean time to recurrence or death was 8.6 months (standard deviation [SD] 7.6) for 10.7%. Mean disease free follow-up without recurrence or death was 56.9 months (SD 54.2) for 89.3%. Patients with comorbidities, risk factors, or family history (odds ratio [OR]: 2.4, 95% confidence interval [CI]: 1.02-5.6); ≥TaN0M0 disease (OR: 6.2, 95% CI: 2.5-15.6); and larger tumors at diagnosis (OR: 1.7, 95% CI: 1.2-2.4) had significantly greater adjusted odds of recurrence or death after initial treatment. CONCLUSION: Based on pooled results, disease recurrence or death occurred in 10.7% of pediatric patients and within 9 months for most and within 32 months for all patients. This may suggest that low-grade and stage UCC of the bladder in pediatric patients can be systematically monitored for at least 3 years. However, prospective evaluation of this clinical strategy is warranted.

Plasma cell counts on human jejunal biopsy specimens examined by immunofluorescence and immunoperoxidase techniques: a comparative study.

Ten human jejunal biopsy specimens were examined by both immunofluorescence (IF) and immunoperoxidase (IP) methods to compare both plasma cell counts and the distribution of extracellular immunoglobulins. Each specimen was cut into at least two portions, one fixed in 5% formaldehyde in phosphate-buffered saline before being snap-frozen and sectioned on a cryostat for IF, the other being fixed in half-strength Zenker and embedded in paraffin wax by standard methods for IP. Plasma cell counts were comparable in the eight biopsy specimens for which they could be estimated, geometric mean values being IgA 22.9 (IF), 19.3 (IP) and IgM 9.5 (IF), 10.6 (IP). Two specimens showing subtotal villous atrophy had too much extracellular IgA for plasma cell counts to be feasible. For these the IF methods had the advantage that the extracellular immunoglobulin was more readily distinguishable from background staining.

Jejunal mucosal morphometry in children with and without gut symptoms and in normal adults.

Nineteen diagnostic peroral biopsy specimens from 18 children without diarrhoea, vomiting, or abdominal pain ('control' children) were compared with those taken from 23 children with diarrhoea of varying aetiology to establish the morphometric characteristics of jejunal mucosa in childhood. Comparison was also made with normal jejunal mucosa from adults. Statistical analysis of each characteristic individually showed no significant difference between the 'control' children and those with diarrhoea, but there were significant differences between the mucosae of 'control' children and those of adults; the villi tended to be shorter and the crypts longer in children. Thirty-seven per cent of specimens from the 'control' children showed a partial villous atrophy, that is, they were abnormal by adult criteria. Discriminant analysis of the features measured showed effective separation of the following groups: normal histology from partial villous atrophy in children, healthy adults from 'control' children, and normal histology in adults from normal histology in children.

Dose effect of oral Saccharomyces boulardii treatments on morbidity and mortality in immunosuppressed mice.

Survival, weight loss, translocation and histological alterations in the terminal ileum, liver and spleen were studied in mice simultaneously immunosuppressed with cyclophosphamide and treated or not with Saccharomyces boulardii until the death of all animals. The animals were divided into five groups: C1 (not immunosuppressed, not treated); C2 (immunosuppressed, not treated); B1 (immunosuppressed, treated with S. boulardii 10.0 mg); B2 (immunosuppressed, treated with S. boulardii 1.0 mg) and B3 (immunosuppressed, treated with S. boulardii 0.1 mg). Survival was higher in group B3 than in the other immunosuppressed groups. Weight loss was observed for all groups except C1. By day 7, some animals from each group were killed by ether inhalation for the determination of bacterial translocation and histopathological examination. Bacterial translocation to the liver was lower in groups C1 and B3 than in the other groups. The highest translocation to the liver and spleen was observed in group B1. Low S. boulardii translocation was observed in some animals, principally to the mesenteric lymph nodes. Histopathological examination showed a decrease in epithelial cell turnover with villus length reduction and loss of brush borders in group C2. Relative protection against these alterations was obtained when the animals were treated with the yeast, independently of the dose. Higher expression of the lymphoid component was also noted in the ileal lamina propria, liver and spleen of mice treated with the yeast, together with activation of the reticulo-endothelial system, when compared with group C2 where lymphocyte depletion was observed. This study suggests a relative protection of immunosuppressed animals by treatment with S. boulardii, but this phenomenon was inversely proportional to the yeast dose.

Influence of nutritional status, age and sex on infant hair zinc concentration.

1. Zinc concentration was measured in hair samples from 57 infants (27 boys and 30 girls) aged 7 to 24 months. Twenty-eight infants were considered eutrophic and 29 presented chronic and severe malnutrition. 2. Hair segments less than 3-cm long were cut close to the scalp in the occipital area and washed in deionized water and acetone. Zinc levels were measured by neutron-activation. 3. Hair zinc concentration decreased with age in both eutrophic and malnourished infants from 160 micrograms/g at 7 months to 90 micrograms/g at 24 months. 4. No statistically significant difference in hair zinc concentration was detected between eutrophic and malnourished infants (148 +/- 60 vs 128 +/- 57 micrograms/g hair, mean +/- SD) or between sexes.

Dietary fiber intake, stool frequency and colonic transit time in chronic functional constipation in children.

The objective of the present study was to evaluate associations between fiber intake, colonic transit time and stool frequency. Thirty-eight patients aged 4 to 14 years were submitted to alimentary evaluation and to measurement of colonic transit time. The median fiber intake of the total sample was age + 10.3 g/day. Only 18.4% of the subjects presented a daily dietary fiber intake below the levels recommended by the American Health Foundation. In this group, the median left colonic transit time was shorter than in the group with higher dietary fiber intake (11 vs 17 h, P = 0.067). The correlation between stool frequency and colonic transit time was negative and weak for left colon (r = -0.3, P = 0.04), and negative and moderate for rectosigmoid and total colon (r = -0.5, P<0.001 and r = -0.5, P<0.001, respectively). The stool frequency was lower in the group with slow transit time (0.8 vs 2.3 per week, P = 0.014). In conclusion, most patients with chronic functional constipation had adequate dietary fiber intake. The negative correlation between stool frequency and colonic transit time increased progressively from proximal segments to distal segments of the colon. Patients with normal and prolonged colonic transit time differ in terms of stool frequency.

Serum antigliadin antibody levels as a screening criterion before jejunal biopsy indication for celiac disease in a developing country.

The objective of the present study was to determine the efficacy of detection of antigliadin immunoglobulins G and A (IgG and IgA) for the diagnosis of celiac disease in a developing country, since other enteropathies might alter the levels of these antibodies. Three groups were studied: 22 patients with celiac disease (mean age: 30.6 months), 61 patients with other enteropathies (mean age: 43.3 months), and 46 patients without enteropathies (mean age: 96.9 months). Antigliadin IgG and IgA ELISA showed sensitivity of 90.9 and 95.5%, respectively. With the hypothetical values of prevalence ranging from 1:500 to 1:2000 liveborns, the positive predictive value varied from 8.5 to 2.3% for IgG and from 4.8 to 1.1% for IgA. Considering the patients without enteropathies, specificity was 97.8 and 95.7% for IgG and IgA, respectively. In patients with other enteropathies, specificity was 82.0 and 84.1%, respectively. When patients with and without other enteropathies were considered as a whole, specificity was 88.8 and 91.6%, respectively. The specificity of positive IgG or IgA was 93.5% in children without enteropathies and 78.7% in the presence of other enteropathies. The negative predictive value for hypothetical prevalences varying from 1:500 to 1:2000 liveborns was 99.9%. Thus, even in developing countries where the prevalence of non-celiac enteropathies is high, the determination of serum antigliadin antibody levels is a useful screening test prior to the jejunal biopsy in the investigation of intestinal malabsorption.

Morphological changes of the jejunal mucosa in protracted diarrhea and their correlation with disease duration, weight loss and serum albumin levels.

The pathogenesis of protracted diarrhea is multifactorial. In developing countries, intestinal infectious processes seem to play an important role in triggering the syndrome. Thirty-four children aged 1 to 14 months, mean 6.5 months, with protracted diarrhea were studied clinically and in terms of small intestinal mucosal morphology. Mild, moderate or severe hypotrophy of the jejunal mucosa was detected in 82% of cases, and mucosal atrophy was observed in 12%. The intensity of the morphological changes of the jejunal mucosa correlated negatively with serum albumin levels. No correlation was detected between mucosal grading and duration of diarrhea or between mucosal grading and weight reported as percentile. After nutritional support was instituted, serial jejunal biopsies were obtained from 12 patients: five patients submitted to parenteral nutrition for 7 to 38 days, mean 17 days, and 7 patients receiving a hypoallergenic oral diet (semi-elemental formula, 3; chicken formula, 3; human milk, 1). In seven cases (58%) a progressive increase in villus height and a decrease in the number of inflammatory cells were noted. Recovery of the morphologic pattern was accompanied by clinical improvement in all patients.

Fecal loss and clearance of alpha-1-antitrypsin in children with persistent diarrhea.

1. Daily fecal loss and daily clearance of alpha-1-antitrypsin were determined in 30 infants without intestinal disorders and in 21 with persistent diarrhea. 2. Stools were collected during a 48-h period and a randomly obtained single sample was also collected. Blood samples were also collected from the infants, and alpha-1-antitrypsin was measured by radial immunodiffusion in both stool and serum. 3. No difference in daily fecal loss (mg/d) of alpha-1-antitrypsin was detected between the control group and the group with persistent diarrhea (11 +/- 9.3 vs 18.5 +/- 20 mg/d). No difference in daily alpha-1-antitrypsin clearance (ml/d) was detected between the control group and the group with persistent diarrhea (4.3 +/- 3.6 vs 5.2 +/- 4.8 ml/d). 4. There was a strong correlation between daily fecal loss and daily clearance of alpha-1-antitrypsin (N = 50). There was a weak correlation between the concentrations of alpha-1-antitrypsin in randomly obtained single samples and daily fecal loss of the antiprotease (N = 25; r = -0.183; P < 0.01). 5. We conclude that: a) there is no increased fecal loss of alpha-1-antitrypsin persistent in diarrhea; b) fecal alpha-1-antitrypsin clearance is not necessary to estimate the enteric loss of the antiprotease; c) the determination of alpha-1-antitrypsin in random samples of feces is not a reliable method.

Diagnosis and distribution of Helicobacter pylori in the gastric mucosa of symptomatic children.

1. The demonstration of the association of H. pylori with gastritis and peptic ulcer has been of increasing interest to gastroenterologists, microbiologists, and histopathologists. 2. In this study, the presence of H. pylori in the gastric mucosa of children was investigated by culture, preformed urease test, and carbolfuchsin staining of biopsy smears. 3. The organism was detected in 44.9% of the children studied, and found to be distributed equally on the antral and fundic mucosa. 4. Compared to culture, the urease test and carbolfuchsin staining proved to be of higher sensitivity and specificity in detecting H. pylori.

Effect of meconium ileus on the clinical prognosis of patients with cystic fibrosis.

The objective of the present study was to determine the possible prognostic factors which may explain the difference in the survival of patients with cystic fibrosis (CF) with and without meconium ileus. Over a period of 20 years, 127 patients with CF, whose diagnosis was confirmed by typical clinical characteristics and altered sweat chloride levels, were studied retrospectively. The patients were divided into two groups: group 1 consisted of patients who presented CF and meconium ileus (N = 9), and group 2 consisted of patients with CF without meconium ileus (N = 118). The characteristics studied were based on data obtained upon admission of the patients using a specific protocol. Demographic, clinical, nutritional and laboratory data were obtained. The genotype was determined in 106 patients by PCR. Survival was analyzed using the Kaplan-Meier method. The median follow-up period was 44 months. A statistically significant difference was observed between the groups studied regarding the following variables: age at diagnosis and weight and height z scores. The presence of meconium ileus was associated with an earlier diagnosis; these patients had greater deficits in height and weight at the time of diagnosis and at the end of the study. The estimated probability of survival for patients with CF without meconium ileus was 62 +/- 14% and for those with meconium ileus 32 +/- 18%. Patients with CF and meconium ileus presented a poor nutritional status at diagnosis and a lower survival rate compared to the general CF population.

Prevalence of anemia among school-children from Rio Acima (State of Minas Gerais, Brazil): use of the standardized prevalence method and evaluation of iron deficiency.

The prevalence of anemia and iron deficiency was investigated in 332 children aged 7 to 15 years, 156 (47%) boys and 176 (53%) girls enrolled in the schools of the municipality of Rio Acima, MG. Seventy-four children were white (22.3%), 218 were mulatto (65.7%), and 40 were black (12%). Mean hemoglobin level was 12.75 +/- 0.75 g/dl. Lower values were determined for black children (12.32 +/- 0.87g/dl) compared to white (12.76 +/- 0.99 g/dl) and mulatto (12.81 +/- 0.94 g/dl) children. The prevalence of anemia was 16.6% when determined on the basis of the percentage of children with hemoglobin values lower than the 3rd percentile for age and sex (standard method), and 36.2% when determined by the standardized prevalence method for the evaluation of the prevalence of malnutrition in populations. Depletion of iron reserves was 8.13% for the population in general and 20% for the anemic children. This low prevalence of iron deficiency may have been the result of the value adopted as the lower normal limit (10 ng/ml) for serum ferritin values. The small percentage of anemic children with iron depletion may also be justified by the standard of normality adopted for hemoglobin values which was originally elaborated for the white population of North America and Finland and therefore may be inadequate for the population studied here, of diverse racial composition.

Chronic calcifying pancreatitis in children: a report of six cases.

1. A study of six patients with Chronic Calcifying Pancreatitis (CCP) occurring over a 10 year period, representing an incidence rate of approximately 1:1,000 of the inpatients in the children's ward of a general hospital in central Brazil, is reported. 2. Major clinical manifestations as well as therapeutic management are described. 3. The possible relationship between CCP and primary protein-calorie malnutrition is discussed and the importance of a CCP diagnosis when dealing with malnourished children who do not respond satisfactorily to common therapy is emphasized.

Lack of correlation between jejunal mucosal morphology and intestinal absorption in the hepatosplenic form of schistosomiasis mansoni.

Eleven patients with the hepatosplenic form of schistosomiasis mansoni were studied. Intestinal absorption of fat and xylose was normal in all patients. Despite these normal absorption parameters, the mucosa showed variable degrees of villus atrophy and an increase of the number of inflammatory cells in the lamina propria. Through morphometric analysis it was seen that the villi were shorter and the ratio villus height/crypt depth was increased in schistosomiasis patients as compared to normal control children. Five of the 11 biopsies contained granulomata with ova in the mucosa or submucosa.

Duodenal intubation in the differential diagnosis of obstructive jaundice in infants.

The aim of this work was to analyse the value of duodenal intubation in the differential diagnosis of obstructive jaundice in infants. Thirty-six patients were studied, ages varying between one and five months (average 2.4), 21 males and 15 females, all presenting cholestasis characterized by jaundice, choluria and fecal acholia. Of the 36 patients, 15 with negative intubations had during surgery a confirmation of a diagnosis of biliary atresia. The other 21 infants with positive duodenal intubation received at that moment the diagnosis of "neonatal hepatitis syndrome". Because it is efficient, harmless and inexpensive, duodenal intubation is an useful method in deciding whether cholestasis in infants requires medical or surgical treatment.

Pancreatic steatorrhea: action of a total lyophilized pancreas preparation: an "in vitro" and "in vivo" study.

A total lyophilized pig pancreas (TLP) preparation was assayed "in vitro" and "in vivo". Lipase activity of the four lots studied was 6.180 +/- 1.122 IU by gram of the commercial product. There was no free trypsin detectable in the preparation. Fifteen pancreatic exocrine insufficiency patients were studied in a period of four weeks. Adult patients received from 35.500 to 35.776 IU of lipase contained in TLP preparation by meal. All patients had their steatorrhea reduced, or normalized, stool weight reduced and body weight increased. There is not an obligatory relation between stool fat loss and stool weight. Steatorrhea decreased at least during the 14 first days of treatment before reaching a stable level. This long delay before reaching a maximum effect deserves to be known: to test the efficiency of a pancreatic extract, the treatment must be given at least two weeks before estimating its results on fecal fat excretion.

[Research on enteropathogenic bacteria from children with acute diarrhea, in Belo Horizonte, MG]. / Pesquisa de bactérias enteropatogênicas em crianças com diarréia aguda, em Belo Horizonte, MG.

Enteropathogenic bacteria were searched in feces of 80 children with acute diarrhea from the lower social economical level, all of them younger than twenty seven months old, and without any antimicrobial therapy, in Belo Horizonte, MG, Brazil, from June 1981 to August 1982. The following enteropathogenic bacteria were isolated from 46 children: Shigella in 12 children (15.00%), enterotoxigenic Escherichia coli in 12 children (15.00%), classic enteropathogenic Escherichia coli in 9 children (11.25%), Salmonella in 6 children (7.50%). Association of enteropathogenic bacteria were found in 7 children (8.75%). Yersinia enterocolitica and invasive Escherichia coli were not isolated from any patient.

[Wilson's disease ("hepatic form") in a region endemic for schistosomiasis mansoni: clinical presentation of 25 patients]. / Doença de Wilson ("forma hepática") em região endêmica para esquistossomose mansoni: apresentação clínica de 25 pacientes.

Brazil has a young population and areas of endemic mansoni schistosomiasis where Wilson's disease might be easily misdiagnosed in patients erroneously classified as having either the hepatosplenic or the hepatointestinal form of the helminthiasis. Twenty five patients with the "hepatic form" of Wilson's disease (14 males and 11 females) were investigated in Belo Horizonte, MG; the mean age was 13.7 years (3 to 22). Nineteen had hepatomegaly (76%) and nine splenomegaly (36%). Twenty two (88%) had cirrhosis. The Kaiser-Fleisher ring was detected in fifteen (60%). Four (16%) had clear neurological abnormalities. Eleven (44%) had ascitis and/or jaundice. Ninety one point three per cent and 92% had low ceruloplasmin and copper serum levels respectively. Eighty four point two per cent showed an increased 24 hours urinary copper excretion; seven patients in whom hepatic copper was determined had increased values. Six out of nine had at least a ten fold increase in 24 hours urinary copper excretion following penicillamine use ("penicillamine test"). Three out of 19 patients (15.8%) had mansoni schistosoma ova in stools examination, a common prevalence in our population. Their biopsies showed inactive cirrhosis without schistosomiasis-associated alterations. At least fourteen patients (56%) could be misdiagnosed as having hepatointestinal or hepatosplenic schistosomisis when in fact they suffered from Wilson's disease with or without asymptomatic intestinal schistosomiasis, losing the chance of an early treatment. The follow-up time of 22 patients was 52 months (1 to 96); eight (36.3%) died, four from bleeding esphageal varices, three from terminal hepatic failure and one from fulminant liver failure. The majority of the patients, including those who died, had abandomned the use of penicillamine or had taken it irregularly, due mainly to its highly expensive cost. A 17 year old patient underwent a successful liver transplant in 1989.

[Clinical and nutritional aspects in patients with cystic fibrosis: 20 years of follow-up in the Clinical Hospital-Federal University of Minas Gerais (HC-UFMG)]. / Quadro clínico e nutricional de pacientes com fibrose cística: 20 anos de seguimento no HC-UFMG.

BACKGROUND: Cystic fibrosis (CF) is the most common severe autosomal recessive disease in caucasian population. The life expectancy of patients with CF has improved dramatically during the past three decades. A better approach to these patients depends on a better knowledge of clinical course and prognosis of CF. The purpose of the present study was to identify aspects clinical and nutritional on admission at Center of CF (HC-UFMG). MATERIAL AND METHODS: Over a period of 20 years 127 patients with CF were admitted, submitted to a systematic protocol and prospectively followed. Data associated with demographic conditions, clinical presentation, nutritional and laboratory findings on admission were studied. The median follow-up was 44 months. The genotype was performed by PCR method. The survival analysis was carried out by Kaplan-Meier method. RESULTS: The median age at diagnosis was 33 months. Sixty-one per cent of patients at diagnosis had chronic pulmonary and gastrointestinal symptoms. Seventeen patients (16%) were homozygous for DF508 mutation and 30 (28%) were heterozygous. There was a standard prevalence of malnutrition of 63% at diagnosis and of 45% at the end of follow up. Twenty patients (15,7%) died during follow up. The estimated probability of survival after one year from diagnosis was 96% and after five years was 80%. CONCLUSIONS: CF diagnosis has been later in our country and the survival is shorter than in developed countries. Management of cystic fibrosis in pediatric specializing centers results in a better nutritional state in spite of clinical progression of the disease.