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.

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.

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.

Adherence to gluten-free diet and serum antigliadin antibodies in celiac disease.

In 134 patients with celiac disease the compliance with a gluten-free diet (GFD) and the presence of antigliadin antibodies (AGA) were evaluated. Compliance with the GFD was good in 71%, moderate in 11% and poor in 18%. High levels of AGA (IgA and IgG) were found in 24.2% of patients with good GFD, in 40% of those with moderate GFD and in 75% of those with poor GFD compliance. Our data suggest that the presence of AGA is correlated with the degree of adherence to the GFD, and that AGA measurement may be of some value in the monitoring of GFD in patients with celiac disease.

Cromoglycate and nedocromil: influence on airway reactivity.

Although basic mechanisms of bronchial hyper-responsiveness (BHR) are still incompletely understood, inflammation of airways is likely to play a fundamental role in modulating BHR in patients with asthma. The involvement of several inflammatory cells (eosinophils, mast cells, lymphocytes, neutrophils, macrophages and platelets) and of bioactive mediators secreted by these cells in the pathogenesis of asthma is well documented. Sodium cromoglycate and nedocromil sodium are two pharmacological agents which have anti-allergic and anti-inflammatory properties. Their clinical effectiveness in mild to moderate asthma, and the capacity to reduce BHR under different natural and experimental conditions, make them valuable drugs for maintenance therapy in patients with asthma.

Desensitization of macrophage oxygen metabolism on immobilized ligands: different effect of immunoglobulin G and complement.

During adhesion and spreading to immobilized immune complexes, casein-elicited mouse peritoneal macrophages produced superoxide anion. This production was time-dependent, ceased after a couple of hours, and was due to interaction with immunoglobulins G (IgG) because neither immobilized antigen alone nor immunoglobulins M with or without complement-derived fragments were efficient stimuli. Cultivation of macrophages on immobilized IgG for 24 hr caused desensitization of the response to an unrelated stimulus like zymosan. Desensitization was due neither to inhibition of binding and uptake of zymosan nor to alterations of NADPH oxidase. In fact, macrophages cultivated on immobilized IgG bound and internalized zymosan and responded to PMA with production of superoxide anion normally. Desensitization was not specific for casein-elicited macrophages because both resident peritoneal and Corynebacterium parvum-activated macrophages underwent desensitization if cultivated for 24 hr on immobilized immune complexes. Desensitization on immobilized IgG was maximal after 24 hr, lasted up to 3 days in culture, and was reversed by detaching macrophages from the IgG surface and further cultivating them in normal tissue culture plastic. Scavengers of products of the oxygen metabolism such as superoxide dismutase and catalase and inhibitors of arachidonic acid metabolism such as indomethacin and nordihydroguaiaretic acid did not prevent desensitization. In addition, the zymosan-stimulated release of arachidonic acid was suppressed after cultivation on immobilized IgG for 24 hr; also in this case, the response to PMA was conserved. Contrary to cultivation on immobilized IgG, cultivation of macrophages on fragments derived from C3 was not accompanied by desensitization of the response to zymosan. These results indicate that although the interaction of Fc receptors with their ligands does not impair binding and uptake of zymosan, alterations in the sequence of signals which leads to the activation of the oxygen metabolism can occur, causing a complete dissociation between phagocytosis and stimulation of the oxygen metabolism.

Improvement of atopic dermatitis following natural measles virus infection. Four case reports.

Five children with atopic dermatitis were studied during natural measles virus infection. Four of the five patients showed temporary clearing of their skin lesions for 3 weeks following the infection. The reduction of cell-mediated immune responses caused by the measles virus may have played a role in the transient improvement of skin conditions in these children. Evidence for T cell involvement in the clinical entity of atopic dermatitis is discussed.

IgA anti-gliadin antibodies in the monitoring of gluten challenge in celiac disease.

The aim of this study was to evaluate the reliability of serum IgA anti-gliadin antibodies (IgA-AGA) in the monitoring of gluten challenge and in the prediction of mucosal relapse in children with celiac disease (CD) in order to reduce the challenging procedure to a minimum. Serial evaluations of serum IgA-AGA titers and 1-h blood xylose levels were performed in 17 children with celiac disease during gluten challenge. Jejunal biopsy was generally done after two consecutive measurements of positive IgA-AGA. The morphological appearance of the mucosa and intraepithelial lymphocyte infiltration were also evaluated. A serum positive for IgA-AGA was observed in 16 of 17 patients between the 15th and 35th day of challenge. The challenge was concluded in all children after 20-45 days from the introduction of a gluten-containing diet after histological confirmation of CD. Plasma xylose test was less reliable in this respect. We conclude that IgA-AGA measurement by gluten challenge is likely to simplify and allow earlier diagnostic confirmation of celiac disease in children, without intestinal biopsy.

Pulmonary hemosiderosis in a child with cystic fibrosis.

Two episodes of acute iron deficiency anemia with blood-stained sputum and symptoms of severe acute pulmonary exacerbation were observed in a child with cystic fibrosis (CF). Hemosiderin laden macrophages (siderophages) were repeatedly found in sputum and gastric juice, suggesting the coexistence of pulmonary hemosiderosis (PH). The possibility that pulmonary immune-mediated mechanisms characteristic of CF may have played a role in the development of PH is considered.