Respiratory syncytial virus induces phosphorylation of mTOR at ser2448 in CD8 T cells from nasal washes of infected infants.

Respiratory syncytial virus (RSV)-specific CD8(+) T cell responses do not protect against reinfection. Activation of mammalian target of rapamycin (mTOR) impairs memory CD8(+) T cell differentiation. Our hypothesis was that RSV inhibits the formation of CD8(+) T cells memory responses through mTOR activation. To explore this, human and mouse T cells were used. RSV induced mTOR phosphorylation at Ser2448 in CD8 T cells. mTOR activation by RSV was completely inhibited using rapamycin. RSV-infected children presented higher mTOR gene expression on nasal washes comparing to children infected with metapneumovirus and rhinovirus. In addition, RSV-infected infants presented a higher frequency of CD8(+) pmTORser2448(+) T cells in nasal washes compared to RSV-negative infants. Rapamycin treatment increased the frequency of mouse CD8 RSV-M282-90 pentamer-positive T cells and the frequency of RSV-specific memory T cells precursors. These data demonstrate that RSV is activating mTOR directly in CD8 T cells, indicating a role for mTOR during the course of RSV infection.

Effect of neonatal bacille Calmette-Guérin on the tuberculin skin test reaction in the first 2 years of life.

SETTING: Latent tuberculous infection (LTBI) is an important reservoir of disease reactivation that is sufficient to generate new cases for decades. The tuberculin skin test (TST) is an important tool to diagnose LTBI; however, neonatal bacille Calmette-Guérin (BCG) vaccination may impact interpretation of TST data. OBJECTIVES: To analyse the effect of the neonatal BCG vaccine on TST reaction in the first 2 years of life in children with no identified contact with tuberculosis (TB). DESIGN: This was a cross-sectional study in children up to 2 years of age who received neonatal BCG vaccination. In the absence of baseline comorbidities or contact with the bacillus, the children were given the TST. RESULTS: Seventy-nine children participated in the study. A decline in TST reactivity was observed in the first 12-24 months of age in patients who had been vaccinated with neonatal BCG but with no contact with TB. After the age of 10 months, no patient showed a TST reaction of >5 mm. CONCLUSION: BCG had low impact on the TST in children with no TB contact. This finding suggests the need to reassess the cut-off point to 5 mm of induration to improve TST specificity in LTBI identification.

Fecal chymotrypsin: a new diagnostic test for exocrine pancreatic insufficiency in children with cystic fibrosis.

The purpose of this report is to evaluate whether a new, simple, non-invasive method for chymotrypsin measurement in stools is useful for the diagnosis of exocrine pancreatic insufficiency in cystic fibrosis (CF). A hundred children aged from 2 months to 12 years were tested: 50 children had been admitted for chronic diarrhoea, 15 for cystic fibrosis and 40 acted as controls. Chymotrypsin in stools was assayed using a kinetic measurement with Succ-Ala-Ala-Pro-Phe-pNa as substrate in a simple photometric assay. In 13 of 15 children with cystic fibrosis, stool enzyme levels were always remarkably low, while all control subjects and all children not presenting cystic fibrosis had normal stool levels of chymotrypsin. Our data suggest that stool chymotrypsin measurement is a simple and reliable "tubeless" test for the evaluation of exocrine pancreatic insufficiency in children with cystic fibrosis.

Exocrine pancreatic function in children and adolescents with insulin-dependent diabetes mellitus.

Exocrine pancreatic function was evaluated in 21 diabetic children on the basis of a p-aminobenzoic acid (PABA) test and a determination of fasting serum amylase, pancreatic isoamylase, lipase, trypsin and elastase levels. Fecal chymotrypsin was also measured. Compared to the controls, the diabetic children had significantly lower levels of trypsin (P less than 0.001) and elastase (P less than 0.02). Fecal chymotrypsin appeared to be significantly lower (P less than 0.01) in diabetic children than in controls but in all patients fecal chymotrypsin values registered above the limit considered to be normal. No significant correlation was observed between pancreatic enzyme concentrations, serum and urinary PABA values, and chronologic age, HbA1 and insulin requirement. Only for serum PABA a significant negative correlation with duration of disease (P less than 0.01) has been observed. These data show that exocrine pancreatic function may be abnormal in children with IDDM.

Elevated IgA anti-gliadin antibodies in juvenile chronic arthritis.

Increased intestinal permeability secondary to treatment with non-steroidal anti-inflammatory drugs (NSAIDs) and raised levels of anti-gliadin antibodies (AGA) have been reported in adults with rheumatoid arthritis. We have therefore retrospectively investigated the presence of serum AGA of the IgA and IgG classes in 70 patients with juvenile chronic arthritis (JCA). Serum IgA (but not IgG) AGA were found to be higher in JCA patients than in controls (6.2 +/- 8.7 vs 2.1 +/- 1.5 AU/ml; p less than 0.0001). This finding was observed independently of the JCA onset subtype or disease activity; however, lower levels of IgA AGA were found in patients with pauciarticular JCA and in those in remission. No significant differences in IgA AGA serum levels were observed between untreated patients and patients treated with NSAIDs. Five patients who presented the highest levels of IgA AGA were further studied a second time; serum IgA AGA were found to be markedly reduced or normalized and no clinical or laboratory evidence of coexistent coeliac disease was observed. In conclusion, our results suggest that the elevation of IgA AGA seen in our patients is secondary to non-specific immune stimulation rather than to an NSAID-induced increase in intestinal permeability.

Celiac disease and type I (insulin-dependent) diabetes mellitus in childhood: follow-up study.

To ascertain the specificity of IgA and IgG antigliadin (IgA-AGA, IgG-AGA), IgA-antireticulin (R1-ARA), and antiendomysial (AEA) antibodies for the diagnosis of celiac disease, we evaluated 133 type I diabetic children aged 1.4-28.4 years (mean 14.1 +/- 6.6), with diabetes from onset to 20.5 years. Fifty-three patients were considered at onset and 49 of these also during follow-up. IgA-AGA and IgG-AGA were determined by enzyme-linked immunosorbent assay (ELISA), R1-ARA and AEA by indirect immunofluorescence. IgA-AGA were positive in 20 of 133 (15%), IgG-AGA were positive in seven of 133 (5.26%), while R1-ARA and AEA were positive in three patients. At the onset of disease we found elevated IgA-AGA in 17 of 53 (32%) patients, IgG-AGA in four (7.55%) patients, three of them with IgA-AGA as well; R1-ARA and AEA were present in three (5.66%) patients, all with high IgA-AGA levels. During 1-10 year follow-up IgA-AGA decreased to within the normal range in 13 patients, with elevated IgA-AGA at onset but without R1-ARA and AEA; in four patients with high IgA-AGA at onset, IgA-AGA remained constantly elevated as did R1-ARA and AEA in three of them; and two patients, without IgA-AGA, R1-ARA, and AEA at onset, became positive for all three antibodies. Intestinal biopsy confirmed a diagnosis of celiac disease in five of these with IgA-AGA, R1-ARA, and AEA, but not in one patient with persistent IgA-AGA but no AEA and R1-ARA, suggesting that R1-ARA and AEA are more reliable markers for the screening of celiac disease in type I diabetic patients.

[A case of hypophosphatasia in an infant]. / Su di un caso di ipofosfatasia nel lattante.

Hypophosphatasia is a rare familial disease characterized by abnormalities of the skeleton, low serum alkaline phosphatase level and presence of abnormal quantities of phosphorylethanolamine in plasma and urine. The biochemical bases of inadequate calcification of the bone matrix are unknown. We report the case of a 4 month-old infant who presented symptoms of rickets. Laboratory analysis showed normal serum Ca and P levels, low serum alkaline phosphatase activity, PEA level increased in plasma and urine. X-ray examination of the bones disclosed poor mineralization and the presence of focal defects of the skull. The therapeutic problems are discussed.

[Pro-allergy role of infection. A component of the mode of reacting]. / Il ruolo proallergico delle infezioni. Una componente del modo di reagire.

No organism from the cradle lives germ-free or allergen-free. The modalities by which infections facilitate conditions of abnormal reactivity, in particular respiratory asthma and allergy to cow milk proteins, are examined. 216 asthmatic children and 50 infants with rotavirus enteritis have been considered. Infections, besides representing stimuli directly projected on the immune system, also constitute factors which more generally influence the way of reacting.

Saccular aneurysm of infancy and early childhood: report of a case.

A case of intracranial saccular aneurysm with intracerebral haematoma occurring in early childhood and presenting with sudden loss of consciousness and right hemiparesis is reported. The aneurysm was located in the opercular portion of the left middle cerebral artery. Surgery, besides removing the intracerebral haematoma, involved clipping and complete removal of the aneurysmal sac. The child made an uneventful recovery, and he is completely safe after 40 months. Microscopic examination of the lesion shows disruption of the normal sequence of the original layers, with widespread inflammatory cells.

Paroxetine efficacy in the treatment of generalized anxiety disorder.

Recently, there has been a renewed interest in alternatives to the benzodiazepines for the treatment of generalized anxiety disorder (GAD). The aim of the present study was to compare the efficacy of paroxetine vs. imipramine and 2'-chlordesmethyldiazepam in 81 patients with a DSM-IV diagnosis of GAD. Approximately two-thirds of the patients who completed the study improved greatly or moderately on all three active drugs. During the first 2 weeks of treatment, 2'-chlordesmethyldiazepam treatment resulted in the greatest improvement in anxiety ratings. Both paroxetine and imipramine treatment resulted in more improvement than 2'-chlordesmethyldiazepam by the fourth week of treatment. Paroxetine and imipramine affect predominantly psychic symptoms, whereas 2'-chlordesmethyldiazepam affects predominantly somatic symptoms. Our results suggest that paroxetine is effective for the treatment of GAD.

Celiac disease presenting as chronic hepatitis in a girl.

A case of celiac disease presenting as an asymptomatic chronic persistent hepatitis in an 11-year-old girl is reported. Liver biopsy performed because of long-standing elevation of serum transaminase levels showed a mild portal fibrosis with mononuclear infiltrate. Immunofluorescence staining did not reveal deposits of immunoglobulins or complement in the liver specimen. Although the girl was totally asymptomatic, she had steatorrhea, a delayed bone age, and an abnormal D-xylose test. A jejunal biopsy showed villous atrophy and increased intraepithelial lymphocytes. On a gluten-free diet the level of transaminases fell to normal within 1 month and remained normal. According to biological remission, a second intestinal biopsy performed after 1 year of gluten-free diet revealed a normal intestinal mucosa. Our report suggests that an underlying chronic intestinal disorder, and particularly celiac disease, must be ruled out when evaluating a child with elevated levels of serum transaminase.

Defective neutrophil motility in children with chronic liver disease.

Neutrophil motility was assessed in 31 children with chronic liver disease to estimate the eventual increased susceptibility of these patients to bacterial infections. Twelve children had chronic hepatitis (seven with chronic persistent hepatitis and five with chronic active hepatitis), which was mostly related to hepatitis B virus (HBV) infection. Nineteen children had chronic intrahepatic or extrahepatic cholestasis. A total of six serious bacterial infections occurred in four of the 31 patients during the study. Twenty of the 31 children had a persistent defect of neutrophil chemotaxis. This defect was found in four types of childhood chronic liver disease: HBV-related chronic hepatitis and idiopathic intrahepatic cholestasis of infancy, in which the defect did not seem to predispose significantly to bacterial infection, and in Byler's disease and biliary atresia, in which this neutrophil defect was associated with an increased frequency of severe infections.

[Role of children with chronic hepatitis in the intrafamilial spread of hepatitis B virus infection]. / Rôle de l'enfant avec hépatite chronique dans la diffusion intrafamiliale de l'infection par le virus de l'hépatite B (VHB).

In order to evaluate the intrafamilial spread of hepatitis B virus (HBV) infection we studied the serological markers of HBV in 101 relatives of 35 children with chronic hepatitis B. Sixty per cent of relatives had markers of infection and 25% showed persistent HBs antigenemia. The high prevalence of HBeAg versus anti-HBe in chronically infected relatives suggests a close temporal relationship of the infection between adults and children. These results support the hypothesis that the child is the main carrier of HBV infection in his family.

Goodpasture's syndrome in a child: natural history and effect of treatment.

An 8-year-old girl with microhematuria of recent onset developed a picture of pulmonary hemosiderosis in the space of 2 months. Some months later while pulmonary involvement was improving severe extracapillary glomerulonephritis developed. Circulating anti-glomerular basement membrane antibody was detected and linear deposition of IgG along glomerular basement membrane was observed. A diagnosis of Goodpasture's syndrome was made and treatment was started with prednisone, cyclophosphamide and periodic plasmapheresis with complete progressive disappearance of circulating anti-glomerular basement membrane antibody. After suspension of plasmapheresis despite immunosuppressive therapy and lack of evidence for circulating anti-glomerular basement membrane antibody, the child went into terminal renal failure. The natural history of the disease in this case and the results of treatment are discussed. To our knowledge this is the first case of Goodpasture's syndrome reported in childhood with demonstration of the presence of anti-glomerular basement membrane antibody.

Cell-mediated immunity in children with chronic cholestasis.

Cell-mediated immune response was evaluated in 14 children with long-lasting intra- or extrahepatic cholestasis. Cell-mediated immunity was clearly depressed in children with intrahepatic cholestasis while children with extrahepatic biliary obstruction had a more modest and variable degree of impairment. This finding may be related to the longer duration of cholestasis and the higher total bile acid level in the intrahepatic compared to the extrahepatic group. In particular, in children with Byler disease, long-lasting, severe intrahepatic cholestasis was associated with depressed cell-mediated immunity and recurrent severe infections.

Nosocomial outbreak of infant rotavirus diarrhea due to the appearance of a new serotype 4 strain.

An outbreak of acute gastroenteritis, involving 30 infants and young children aged 2 months to 4 years, took place in a pediatric ward of the University Hospital of Pavia, Northern Italy, in the period from November 9 to December 1, 1986. Out of the 14 patients examined, ten were found to shed rotavirus with stools. All strains were characterized for serotype, using a monoclonal antibody-based enzyme-linked immunosorbent assay, and for electropherotype, by polyacrylamide gel electrophoresis of genomic RNA. It was shown that a single serotype 4 (subtype 4A) strain spread within the ward from a primary case to seven other patients. The remaining two patients were found to be infected by a serotype 1 strain that was circulating in the same area prior to the outbreak. The clinical symptoms were unusually severe, since significant dehydration was observed in four of the eight serotype 4 rotavirus-infected children. Previous epidemiological studies had shown that since 1983 serotype 4 strains had not been circulating in Pavia, and the electropherotype of the newly circulating serotype 4 strain was different from those observed in 1981-1983. Thus, the severity of the diarrheal disease appeared to be related to the circulation of both a new serotype and a new electropherotype.

A new faecal chymotrypsin method for evaluating the exocrine pancreatic function in patients with different pancreatic diseases.

Using a new colorimetric method we measured the faecal chymotrypsin in 407 subjects, divided as follows: 252 adult subjects with a normal exocrine pancreatic function as shown by duodenal intubation, 24 adult patients with a mild to moderate pancreatic insufficiency, and 26 adult patients with severe pancreatic insufficiency. In addition, 40 healthy children, 50 children with chronic diarrhoea, and 15 with cystic fibrosis were studied before and after substituting enzyme therapy. Faecal chymotrypsin was found to be useful in evaluating the degree of exocrine functional insufficiency in subjects with diseases of the pancreas that had already been clinically ascertained. The same cannot be said for its ability to provide an early diagnosis of subjects with a slight-moderate insufficiency in exocrine pancreatic function.

Hepatitis B virus infection and Schönlein-Henoch purpura.

Sch onlein -Henoch purpura developed in two children in association with hepatitis B virus (HBV) infection. The first child, an 8-year-old boy, first had a clinical picture of Sch onlein -Henoch purpura and then was found to have HBV-related chronic persistent hepatitis. In the second child, a 6-year-old girl, characteristic skin lesions, arthralgia, and proteinuria developed during acute hepatitis B. Immunofluorescence demonstrated IgA deposition in the renal glomeruli of the first patient. We suggest that evidence of HBV infection should be sought in patients with Sch onlein -Henoch purpura.

Malignant small cell tumor of the thoracopulmonary region in childhood: a case report.

A case of malignant small cell tumor of the thoracopulmonary region in a 3-year-old boy is presented. The rarity of this tumor in children justifies the presentation of a new case. Differential diagnosis with other childhood neoplasms is discussed.

[Chronic HB virus hepatitis in children. A study of 29 cases]. / L'hépatite chronique à virus HB de l'enfant. Une étude de ving-neuf observations.

Clinical, biochemical and histological features of chronic hepatitis type B were studied in 29 children aged 8 months to 13 years. On entry into the study, all were known to have had hepatitis B surface antigen (HBsAg) with elevated serum transaminase levels for at least six months. A possible source of infection was found in 15 children. When they entered the study, all patients were anicteric and all but one asymptomatic. Hepatomegaly was detected in 15 patients and was associated with splenomegaly in two. Hypergammaglobulinemia was present in 4 children. Serological evaluation of hepatitis B virus markers showed evidence of complete viral replication (HBeAg positivity) in 24 cases and incomplete replication (anti-HBeAg positivity) in 5. Liver histology showed chronic persistent hepatitis (CPH) in 18 children, and chronic aggressive hepatitis (CAH) in 10 (3 moderately active and 7 with major signs of aggressivity ) associated with cirrhosis in 5. One patient had only minimal histological changes. Evaluation of clinical, biochemical and virological parameters did not strictly parallel the histological diagnosis in terms of "activity" of the disease. Follow-up for a mean period of 13 months showed good clinical tolerance to the disease in both CPH and CAH patients. Only 2 children with CAH were given corticosteroids and/or azathioprine for a short period. During follow-up no children with active disease developed liver insufficiency or evidence of portal hypertension. No significant difference in the percentage of children who had seroconversion to antiHBe was found between CPH and CAH groups. Only one child with CAH became HBsAg negative.(ABSTRACT TRUNCATED AT 250 WORDS)