Selective immunoglobulin A deficiency and celiac disease: let's give serology a chance.

Patients with selective immunoglobulin (Ig) A deficiency have a 10- to 20-fold increased risk of celiac disease. In these patients, serological diagnosis of celiac disease can be difficult, since specific IgA-based assays are usually negative and IgG-specific antibody tests are insufficiently reliable. We describe a girl with selective IgA deficiency who had a troublesome diagnosis of celiac disease that was established only after an unexpected positive test result for antitransglutaminase IgA and antiendomysium IgA. Our observation indicates that IgA-based serology should not be forgotten in patients with selective IgA deficiency, since positive results for antitransglutaminase IgA, antiendomysium IgA, or both can be observed at any time during diagnostic investigations.

Early diagnosis and treatment of celiac disease in type 1 diabetes. A longitudinal, case-control study.

OBJECTIVES: Subjects with type 1 diabetes mellitus (DM) are at increased risk to develop celiac disease (CD). However, most of the published investigations on the association between type 1 DM and CD are cross-sectional ones. In this paper, longitudinal data are presented on the effects of gluten-free diet (GFD) on growth and metabolic control in children and adolescents with type 1 DM screened for CD. METHODS: Clinical records of 27 patients with type 1 DM+CD (7% of a population of 385 subjects with type 1 DM) were reviewed. The following variables were considered at the diagnosis of CD (T0) and after 24 (T24) and 48 (T48) months of GFD according to the length of available follow-up: weight, height, body mass index (BMI), Hb and HbA1c levels and per kg/day dose of insulin. Forty-three patients with type 1 DM alone, matched for sex, age and duration of diabetes were chosen as controls. RESULTS: In patients with type 1 DM+CD, mean (SD) age at type 1 DM diagnosis was 8 (3.3) years. Median time interval between diagnosis of type 1 DM and of CD was 1.8 years (range 0.1-23.9 years). At T0 (n = 23), height and BMI z-score, HbA1c levels and daily insulin dose were comparable in type 1 DM+CD and in control subjects. Mean Hb concentration was significantly lower in subjects with type 1 DM+CD (12.6 (1.3) vs. 13.3 (0.7) g/dl, p < 0.05). At T24 (n = 22) and T48 (n = 16), no difference was detectable in height, BMI, HbAlc and insulin dose and also Hb concentration was comparable in both groups. CONCLUSIONS: This study shows that, at diagnosis of CD, screened subjects with type 1 DM had only minor signs of malnutrition and metabolic disturbances were uncommon. Dietary treatment of CD can allow a growth and diabetes control comparable with subjects with diabetes alone.

Measurement of NADPH oxidase activity in detergent lysates of human and mouse macrophage monolayers.

An assay to measure NADPH oxidase activity in detergent lysates of macrophage monolayers is described. The addition of a reaction mixture containing appropriate concentrations of disrupting detergents, NADPH as oxidase substrate and cytochrome c as electron acceptor, to macrophages monolayers permits the reliable detection of a superoxide dismutase-sensitive NADPH-dependent cytochrome c reductive activity. This activity is strictly substrate dependent and NADH could not substitute for NADPH. The NADPH-dependent superoxide anion-forming activity (NADPH oxidase) was investigated in different populations of human and mouse macrophages. NADPH oxidase was activated by stimulation of macrophages with phorbol-myristate acetate and activity levels correlated with ability of intact cells to produce superoxide anion. The optimal conditions for assay of NADPH oxidase were investigated and the assay was used to measure the kinetic properties of the NADPH oxidase. The assay permits investigations of the enzymatic basis of oxidative metabolism in macrophages cultivated as adherent cells without any requirements for recovery of the cells in suspension and subcellular fractionation.

Evaluation of the effect of food on the absorption of sustained-release theophylline and comparison of two methods for serum theophylline analysis.

Fifteen healthy volunteers took part in a study to investigate the effect of food on the bioavailability of a slow-release formulation of theophylline. Serum theophylline levels were measured every two hours for ten hours after a single oral dose of 500 mg of theophylline. Serum levels were significantly higher after the dose was taken on an empty stomach; however, serum levels were significantly higher 10 hours later when the dose was taken after a standard meal. Despite these differences, eating had no overall effect on theophylline bioavailability. Two analytic methods for measuring serum levels of theophylline were compared, and it was found that fluorometry could measure lower levels and was therefore more precise than an enzyme immunoassay method, which is probably due to the complete automation and reduced interference of bilirubin and hemoglobin.

Bronchial artery embolization in the management of hemoptysis in cystic fibrosis.

Massive hemoptysis and/or recurrent expectoration of measurable amounts of blood are common complications of chronic bronchopulmonary infections in cystic fibrosis (CF). When conservative treatment fails to control bleeding, surgery or bronchial artery embolization (BAE) is frequently considered. We present our experience and long-term follow up of BAE in 14 CF patients (age range 15-39 years) with massive (6 subjects) and/or recurrent (8 subjects) hemoptysis not responsive to medical treatment. Seven had chronic hypercapnic respiratory failure. After angiographic evaluation, polyvinyl alcohol particles (Ivalon) were injected to embolize obviously enlarged bronchial arteries. Seventeen procedures were performed in 14 patients and 36 bronchial arteries were embolized. All the patients stopped bleeding immediately upon BAE. Most of the patients had postembolization fever, dysphagia, and transient chest pain which were managed symptomatically. After a median follow-up period of 10.5 months (range 0.5-38 months), no recurrence of hemoptysis was observed in 8 patients who are still alive. In 3 patients hemoptysis recurred and they underwent reembolization after 3, 22, and 25 months, respectively. Three subjects died of respiratory failure within 5 months from BAE. Presently, 50% of patients studied had a > or = 1 year interval free of major hemoptysis after the first BAE. Our experience indicates that massive and/or recurrent hemoptysis in CF patients can be safety and effectively managed by BAE if the procedure is performed by a skilled practitioner. The procedure was well tolerated and resulted in prolonged and satisfactory bleeding control in most patients.

Ultrastructural ciliary defects in children with recurrent infections of the lower respiratory tract.

One hundred fifty-four children with recurrent or chronic infections of the lower respiratory tract compatible with the diagnosis of primary ciliary dyskinesia (PCD) were evaluated for the presence of ultrastructural ciliary abnormalities. Studies were performed on multiple samples of respiratory mucosa obtained by nasal and bronchial brushing. Twenty-eight children showed ultrastructural ciliary defects compatible with the diagnosis of PCD: Twenty-four presented dynein arm deficiency (either as isolated defect or in association with microtubular abnormalities), two had ciliary aplasia, and two showed microtubular abnormalities. Eleven patients with PCD had situs viscerum inversus, bronchiectasis, and chronic sinusitis (Kartagener's syndrome); one child with Kartagener's syndrome had normal ciliary structure. The appearance of respiratory symptoms within the first month of life, the colonization by Haemophilus influenzae, and a history of recurrent rhinitis and otitis were characteristically present in children with PCD. The clinical status of those patients who reached adolescence was, in our experience, remarkably good. An early diagnosis with adequate prevention and therapy of respiratory infections may have an important role in minimizing irreversible lung damage.

Early bronchopulmonary involvement in Crohn disease: a case report.

BACKGROUND: Bronchopulmonary manifestations of Crohn disease have been rarely described in children, including both subclinical pulmonary involvement and severe lung disease. CASE PRESENTATION: A 6.5-year-old girl is described with early recurrent bronchopulmonary symptoms both at presentation and in the quiescent phase of Crohn disease. Pulmonary function tests (lung volumes and flows, bronchial reactivity and carbon monoxide diffusing capacity) were normal. Bronchoalveolar cytology showed increased (30%) lymphocyte counts and bronchial biopsy revealed thickening of basal membrane and active chronic inflammation. CONCLUSIONS: Clinical and histological findings in our young patient suggest involvement of both distal and central airways in an early phase of lung disease. The pathogenesis of Crohn disease-associated lung disorders is discussed with reference to the available literature. A low threshold for pulmonary evaluation seems to be advisable in all children with CD.

Gluten sensitivity and 'normal' histology: is the intestinal mucosa really normal?

BACKGROUND: Early pathogenetic events of gluten intolerance may be overlooked in patients with serologic markers of celiac disease and normal intestinal mucosa by both conventional histology and immunohistochemistry. AIMS: To investigate if a submicroscopical damage of the absorptive cell surface was associated with developing gluten sensitivity. PATIENTS AND METHODS: Duodenal biopsies of seven subjects with positive anti-endomysial antibodies and normal histology underwent ultrastructural evaluation of the epithelial surface by means of both scanning and transmission electron microscopy. Specimens of intestinal mucosa of 14 children with non-celiac conditions were used as controls. RESULTS: In four patients, electron microscopy revealed alterations of the enterocyte brush border with a significant reduction of the height of microvilli. After several months, three of them had a second biopsy that eventually showed histological modifications suggestive of celiac disease. In the other three patients, no significant alteration of enterocyte ultrastructure was observed. One of them, rebiopsied after 12 months, still showed a normal duodenal histology. CONCLUSIONS: Gluten sensitivity can be associated with 'minimal' mucosal changes not detectable with conventional light microscopy. Such lesions, which primarily involve microvillous structure, may imply a reduction of intestinal absorptive surface already in the latent stage of the disease.

Tannic acid supplemented fixation improves ultrastructural evaluation of respiratory epithelium in children with recurrent respiratory tract infections.

Samples of the respiratory mucosa of children with recurrent respiratory infections suspected of having primary ciliary dyskinesia are routinely fixed with glutaraldehyde before ultrastructural examination. This standard technique, however, may not be optimal for visualizing ciliary components or for preserving several cellular and extracellular structures during dehydration and embedding procedures. In this study, brushes of nasal (28 samples) and/or tracheal (9 samples) mucosa from 32 children with recurrent respiratory tract infections were examined. Twenty-nine samples were fixed with glutaraldehyde supplemented with tannic acid to determine if the ultrastructural analysis of respiratory epithelium and bronchial secretions could be improved. Eight samples were conventionally fixed with glutaraldehyde alone. Lesions of the cellular membrane and damaged cells were easily visualized using tannic acid supplemented fixation. Internal ciliary structures including individual microtubules and dynein arms were also more clearly observed. In addition, the internal structure of microvilli of the respiratory epithelium could be studied and the presence of phospholipid-rich surfactant-like material within nasal and tracheal secretions were visualized after tannic acid supplemented fixation. We suggest that addition of tannic acid during fixation is useful for accurate ultrastructural evaluation of respiratory mucosa in both clinical and experimental situations.

A new sustained-release theophylline suspension for asthmatic children: evaluation of serum theophylline concentrations.

Theophylline level variability obtained with standard slow-release theophylline tablets was compared to that obtained with a new sustained-release theophylline suspension in asthmatic children. The sustained-release preparations were administered every 12 hours and serum samples were collected after ten days of treatment during the steady-state period. In this crossover study, the sequence of the two regimens (slow-release tablets versus slow-release suspension) was selected at random. Both preparations of theophylline were administered at a mean dosage (+/- s.d.) of 19.3 +/- 1 mg/kg/day. The results of our study demonstrated that theophylline serum levels remain within the therapeutic range for both preparations, but there was a greater fluctuation with theophylline suspension compared to the tablets. The tolerability of the two drugs was satisfactory.

Education in asthmatic children.

Several educational programmes have been developed for patients with asthma, in order to promote changes in behaviour and to improve health and quality of life. Such programmes are commonly termed "asthma self-management" programmes. First generation self-management programmes started in the early 1980s and were intended to develop the concept of "partnership" between physician, patient and family, and to teach children the skills necessary to manage asthma at home. As a result of participation in these programmes, children experienced a reduction of emergency room and unscheduled physician visits, and an improvement in their physical and social activities. The need to assess the long-term persistence of self-management skills led to the development of second generation programmes. These programmes will pay more attention to the within-subject assessment of acquisition and application of self-management techniques. Crucial issues, such as decision-making strategies and evaluation of quality of life should also have a prominent role.

[How and why is the diagnostic approach to celiac disease changing]. / Come e perchè sta cambiando l'approccio diagnostico alla malattia celiaca.

The first classic description of celiac disease (CD) was published in 1888. The introduction in the clinical practice of the jejunal biopsy, in 1957, offered a powerful tool for a more objective approach to the disease. The correct diagnostic procedure for CD was finally established by a document of the European Society for Pediatric Gastro-enterology and Nutrition (ESPGAN) in 1970, and the ESPGAN suggestions were rapidly adopted by the scientific community. During these years, alternative and non-invasive diagnostic approaches were developed such as non-immunological (tests of intestinal absorption and permeability) and immunological (anti-reticulin, anti-endomysium and anti-gliadin antibodies, HLA antigens) tests. Due to the increased reliability of some of these laboratory investigations and to the increased knowledge about CD, it has been recently proposed that a simplification of the usual ESPGAN protocol should be eventually adopted in well defined subjects suspected to have CD.

[Bronchial hyperreactivity. III. Clinical manifestations]. / Iperreattività bronchiale. III. Manifestazioni cliniche.

Bronchial hyperreactivity is a common report in several respiratory tract diseases such as bronchial asthma, chronic bronchitis and cystic fibrosis. Atopic patients and children who suffered lung diseases in early life (laryngotracheobronchitis, bronchiolitis, bronchopulmonary dysplasia) may have also persistent abnormalities in pulmonary function that frequently include bronchial hyperreactivity. A review of the actual literature, specially concerning with the clinical aspects of bronchial hyperreactivity in children and with the possible etiopathogenetic mechanism is presented.

[Neutrophil chemotaxis. II. Clinical implications and therapeutic indications in children]. / La chemiotassi del neutrofilo. II. Implicazioni cliniche e cenni di terapia in età pediatrica.

Defects of neutrophil chemotaxis are usually accompanied by recurrent or chronic infections of the skin and the respiratory tract. The onset of clinical symptoms may occur early in infancy; infections tend to be severe and they are generally due by organisms which are of relatively low pathogenicity in the healthy subject. Abnormalities of neutrophil chemotaxis were classified and described as humoral, cellular and unclassified defects. The relevance of neutrophil chemotaxis in the single clinical entities was discussed, taking in particular account the most recent views on the argument. Some details on practical and theoretical therapeutic approaches were also reviewed.

[Chronic suppurative bronchopathy and motility defect of neutrophils: evaluation of an immunomodulating treatment]. / Broncopatia suppurativa cronica e difetto di motilità dei neutrofili: valutazione di un trattamento immunomodulante.

Five patients with recurrent infections of the lower respiratory tract, chronic bronchial suppuration and significant defect of polymorphonuclear granulocyte (PMN) motility were studied. Clinical evaluation and in vitro studies of PMN motility were performed before, during and after the treatment with levamisole chlorhydrate (2.5 mg/Kg twice a week). Clinical improvement was obtained in all the patients, together with a significant increase in the chemotactic response of PMN. No side effects were reported. After a follow-up of 7-18 months PMN chemotaxis remained normal in all the patients and a reappearance of respiratory symptoms was observed only in one subject.

[Neutrophil chemotaxis. I. Physiology aspects and study methods]. / La chemiotassi del neutrofilo. I. Aspetti di fisiologia e metodi di studio.

Neutrophil chemotaxis is a complex orchestration of biochemical and morphologic events that requires the integrity and coordination of a complicated series of cellular functions. Different substances (both endogenous and exogenous) with chemotactic activity for human neutrophils were described; their interaction with specific receptors on neutrophil cell membrane is requested to induce a directional motility. The ligand-receptor interaction causes the activation of intracellular metabolic pathways and the modification of cytoskeletal structures involved in the chemotactic response. Neutrophil chemotaxis may be studied, for clinical purpose, by in vitro and in vivo methods. The two approaches of investigation are complementary, and, if properly used, they may give a valuable help in defining the nature of the chemotactic defect.

[Limits in the evaluation of bronchial reactivity in children with asthma]. / Limiti della valutazione della reattività bronchiale nel bambino con asma.

Bronchial hyperresponsiveness (BHR) reflects an exaggerated sensitivity of airways to pharmacologic and/or physical stimuli. Patients with symptomatic asthma often have a higher degree of BHR than nonasthmatics, even though BHR shows a variable relationship with the clinical expression of the disease and with medication requirements. Methods of bronchial challenge, initially developed in adults, are increasingly employed also in children. The Authors discuss the clinical significance of the evaluation of bronchial responsiveness in the diagnostic approach and follow-up of children with asthma. Some methodological aspects and limits of bronchial challenging in childhood are expecially addressed.

[Diagnostic problems in a 7-month-old boy with tubercular lobitis]. / Problemi diagnostici in un bambino di 7 mesi con lobite tubercolare.

A 7-month child with pulmonary tuberculosis infection involving the whole right upper lobe is described. He was referred to us after diagnosis of recurrent asthmatic bronchitis. In spite of the severity of bronchopulmonary involvement, the outcome was good after 5 months of antitubercular chemotherapy.

[Latent celiac disease in subjects with serum anti-endomysial antibodies and normal intestinal biopsy]. / Celiachia latente in soggetti con anticorpi antiendomisio positivi e biopsia intestinale normale.

OBJECTIVES: Data on the follow-up of a group of subjects with serum antiendomysial antibodies (EMA) and normal mucosal architecture at the intestinal biopsy are reported. Clinical problems concerning possible evolution of potential celiac disease (CD) towards gluten-induced histological damage are discussed. METHODS: Eleven patients belonging to high-risk groups for CD (5 with type-1 diabetes, 2 with familiarity for CD and 4 with symptoms suggesting CD) who had a normal intestinal biopsy, despite positive antiendomysial test, were followed-up. Antigliadin and antitransglutaminase antibodies (anti-tTG) and HLA genotyping were also assessed. According to clinical and serological data a second biopsy was performed in six of them. RESULTS: At the time of the first normal biopsy, all patients were positive for EMA and 5/8 for anti-tTG. Five of 6 subjects genotyped were HLA-DQ2+ or DQ8+. Six patients were rebiopsed after 1 to 4 years. Three had mucosal atrophy, 1 had mild increase of intraepithelial lymphocytes and 2 were morphologically normal. CONCLUSIONS: Subjects with antiendomysial antibodies and normal intestinal biopsy deserve clinical and serological follow-up to reduce the time of possible latency of CD. Although good predictors of progression of the disease are not still available, antiendomysial antibodies assessment and HLA genotyping may help to suggest individuals at higher risk to develop gluten-induced enteropathy. This study confirms that subjects with persistent signs of gluten sensitivity and normal biopsy should be re-examined.