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David Shoseyov

    David Shoseyov

    printing supported by . Visit Chiesi at Stand D.30 SUNDAY, SEPTEMBER 25TH 2011 changes in sputum arginase activity (R=0.65, p<0.05) and ornithine concentrations (R=0.8, p=0.01). Conclusions: Spermine is significantly increased in the... more
    printing supported by . Visit Chiesi at Stand D.30 SUNDAY, SEPTEMBER 25TH 2011 changes in sputum arginase activity (R=0.65, p<0.05) and ornithine concentrations (R=0.8, p=0.01). Conclusions: Spermine is significantly increased in the airways of patients with CF and linked to increase arginase activity. Further studies of the role of the polyamines for CF lung disease are warranted, as they may contribute to airways obstruction and remodeling. 366 Regulation of corticosteroid binding globulin (CBG) in the inflammatory context of cystic fibrosis Jessica Taytard1, Carine Rebeyrol1, Dominique Debray1, Annick Clement1,2, Nicolas Chignard1, Philippe Le Rouzic1. 1UMR_S938, Inserm, UPMC Univ Paris 06, Paris, France; 2Paediatric Pulmonology, Hôptital Armand Trousseau,
    Preconception carrier screening for cystic fibrosis (CF) is usually performed using ethnically targeted panels of selected mutations. This has been recently challenged by the use of expanded, ethnically indifferent, pan-population panels.... more
    Preconception carrier screening for cystic fibrosis (CF) is usually performed using ethnically targeted panels of selected mutations. This has been recently challenged by the use of expanded, ethnically indifferent, pan-population panels. Israel is characterized by genetically heterogeneous populations carrying a wide range of CFTR mutations. To assess the potential of expanding the current Israeli preconception screening program, we sought the subset of molecularly unresolved CF patients listed in the Israeli CF data registry comprising ~650 patients. An Israeli nationwide genotyping of 152 CF cases, representing 176 patients lacking molecular diagnosis, was conducted. Molecular analysis included Sanger sequencing for all exons and splice sites, multiplex ligation probe amplification (MLPA), and next-generation sequencing of the poly-T/TG tracts. We identified 54 different mutations, of which only 16 overlapped the 22 mutations included in the Israeli preconception screening progra...
    Despite the increase in fungal isolates, the significance of chronic Candida albicans airway colonization in CF is unclear. To investigate the impact of C. albicans airway colonization on CF disease severity. Longitudinal analysis of... more
    Despite the increase in fungal isolates, the significance of chronic Candida albicans airway colonization in CF is unclear. To investigate the impact of C. albicans airway colonization on CF disease severity. Longitudinal analysis of clinical data from CF patients followed during 2003-2009 at our CF center. Patients were stratified based on their C. albicans colonization status - chronic, intermittent, and none. A total of 4,244 cultures were obtained from 91 patients (mean age 19.7 years, range 5-68). The three colonization groups were similar in age, gender,and body mass index (BMI). Compared to the non-colonized group (n = 27, 30%), the chronic C. albicans colonization group (n = 34, 37%), had a significantly lower FEV1 percent predicted (74.3 ± 23.1% vs. 93.9% ± 22.2) with a higher annual rate of FEV1 decline (- 1.9 ± 4.2% vs. 0.7 ± 4.5%). The patients who were intermittently colonized with C. albicans had intermediate values. Chronic respiratory colonization of C. albicans is a...
    To investigate the long-term follow-up of distal intestinal obstruction syndrome (DIOS) in Israeli cystic fibrosis (CF) patients. This is a multi-center, comparative, retrospective study in which we reviewed the medical records of all CF... more
    To investigate the long-term follow-up of distal intestinal obstruction syndrome (DIOS) in Israeli cystic fibrosis (CF) patients. This is a multi-center, comparative, retrospective study in which we reviewed the medical records of all CF patients from three major CF centers in Israel who were treated in the period from 1980 to 2012. Patients diagnosed with DIOS were defined as the study group. The patients were diagnosed with DIOS based on their clinical presentation and typical findings on either abdominal X-ray or computerized tomography scan. For the control group, CF patients with no DIOS were matched to the patients in the study group for age, sex, and cystic fibrosis transmembrane conductance regulator (CFTR) mutations. For both groups, the collected data included age, sex, CFTR genotype, weight, height, and body mass index. Clinical data included respiratory function tests in the last five years prior to the study, respiratory function test immediately before and after the DI...
    Triphala (TRP), a herbal extract from Tibetan medicine, has been shown to affect lymphocytes and natural killer T (NKT) cell function. We hypothesize that TRP could ameliorate bronchial hyperreactivity through immune-cell modulations.... more
    Triphala (TRP), a herbal extract from Tibetan medicine, has been shown to affect lymphocytes and natural killer T (NKT) cell function. We hypothesize that TRP could ameliorate bronchial hyperreactivity through immune-cell modulations. Asthma mouse models were generated through intraperitoneal (IP) injections of ovalbumin (OVA)/2 weeks followed by repeated intranasal OVA challenges. Mice were then treated with normal saline (OVA/NS) or Triphala (OVA/TRP). Data were compared with mice treated with inhaled budesonide. All groups were assessed for allergen-induced hyperreactivity; lymphocytes from lungs, livers and spleens were analyzed for OVA-induced proliferation and their alterations were determined by flow cytometry. Oxidative reactivity using chemiluminescence, serum anti-OVA antibodies level and lung histology were assessed. Both TRP and budesonide significantly ameliorated functional and histological OVA-induced bronchial hyperreactivity. TRP had no effect on serum anti-OVA anti...
    Wheezing is one of the most common reasons for the presentation of children to primary care or the emergency ward, before 7 years of age. Current guidelines recommend a short course of oral corticosteroids (OCS) for those children with a... more
    Wheezing is one of the most common reasons for the presentation of children to primary care or the emergency ward, before 7 years of age. Current guidelines recommend a short course of oral corticosteroids (OCS) for those children with a wheezing attack severe enough to require hospitalization. However, the optimal choice of therapy is controversial. We aimed to compare the efficacy of betamethasone to that of dexamethasone in achieving clinical response in preschool children requiring hospitalization for an acute wheezing attack.
    Background: Like the nasal potential difference (NPD) test, ICM may be useful for the diagnosis of atypical CF. However, ICM is easily applicable at all ages. Aim: To assess the diagnostic reliability of ICM in a large cohort of CF,... more
    Background: Like the nasal potential difference (NPD) test, ICM may be useful for the diagnosis of atypical CF. However, ICM is easily applicable at all ages. Aim: To assess the diagnostic reliability of ICM in a large cohort of CF, healthy control and patients with questionable CF. Methods: Rectal biopsies were taken from 3 groups: known CF patients, healthy controls and patients with questionable CF. The last group had a variety of symptoms suggestive of CF: recurrent pneumonia, unexplained bronchiectasis, chronic diarrhea and/or failure to thrive. ICMs were performed using standard protocols by mounting the rectal biopsy in an Ussing chamber and sequentially adding secretagogues while recording current changes. Results: 17 known CF patients and 16 control patients were examined and have remarkably different results (all results are presented as μA/cm 2 ): carbachol 16±7, histamine 13±9 and forskolin 4.8±4 for healthy control group and carbachol -3.7±6.8 (p Conclusion: In this study we have shown that ICM tests may be useful to differentiate between CF and non-CF patients and may be included in diagnostic algorithms. Larger studies are needed to confirm these results.
    Clinical trials are all based on the assumption that patients are adherent to the study protocol. Many reports indicate that general adherence of patients with CF to their daily routine therapies is poor. However, no data exists on... more
    Clinical trials are all based on the assumption that patients are adherent to the study protocol. Many reports indicate that general adherence of patients with CF to their daily routine therapies is poor. However, no data exists on adherence to study drug regimens. All clinical trials carried out at the Hadassah CF Center from 2008 to 2013 were reviewed. Actual adherence as determined by counted drugs was analyzed according to drug administration mode, study lengths and number of study visits. A subset of patients answered a two-part questionnaire covering study specific and general treatment specific issues. Eight studies including 118 patients, with patient numbers varying between 4 and 32 per trial were analyzed. For 7/8 studies mean adherence was between 78% to 100%. Comparison with administration mode showed that adherence decreased substantially if the drugs were not provided as "ready to be used" (63%). Study length influenced adherence, the longer the study the poorer the adherence (82% trial beginning, 44% post 36 months [two combined studies with identical drug]). A substantial decrease was noted over Holiday periods and during the summer vacation months. No correlation was found between number of study visits and adherence to study drug. Adherence to study drug is generally higher than that for regular treatment. Study length, mode of administration, and timing according to Holidays and vacations adversely affect adherence. Pediatr Pulmonol. 2015;9999:XX-XX. © 2015 Wiley Periodicals, Inc.
    Treatment using inhaled bronchodilators for asthma with a metered dose inhaler attached to a spacer device (MDI+S) was shown to be as efficient as nebulizers. Nevertheless, nebulizers remain the treatment of choice in most hospitals. To... more
    Treatment using inhaled bronchodilators for asthma with a metered dose inhaler attached to a spacer device (MDI+S) was shown to be as efficient as nebulizers. Nevertheless, nebulizers remain the treatment of choice in most hospitals. To implement a policy change to improve asthma treatment in pediatric wards and the pediatric emergency department. The study was performed in the emergency department and pediatric wards of a university medical center. The study group comprised all children admitted with a diagnosis of asthma necessitating treatment. The medical and nursing staff of both the pediatric emergency department and the pediatric wards was trained how to use metered dose inhalers attached to spacers on a regular basis in asthmatic pediatric patients. At a preset date nebulizers were replaced by spacers and their use was monitored by the supervising physician. Salbutamol was administered by a metered dose inhaler (100 μg/puff) attached to a spacer device. The number of puffs w...
    Objectives Cystic Fibrosis (CF) is highly associated with vitamin D deficiency. In April 2012, a guidelines-committee of The CF Foundation published new guidelines for screening, diagnosis, management and treatment of vitamin D deficiency... more
    Objectives Cystic Fibrosis (CF) is highly associated with vitamin D deficiency. In April 2012, a guidelines-committee of The CF Foundation published new guidelines for screening, diagnosis, management and treatment of vitamin D deficiency in individuals with CF. The objective of the study was to assess the efficacy of the new guidelines, as well as to test the correlations between vitamin D levels and pulmonary function and exacerbations. Methods Growth parameters, pulmonary function tests, liver functions tests and serum concentrations of 25-hydroxyvitamin D [25(OH)D] were measured in 90 patients from The CF Clinic at Hadassah Mount-Scopus Hospital, Jerusalem. The measurements were held both before changing vitamin D dosage and after at least one year of follow-up. In addition, Days Of Hospitalization (DOH) and Respiratory Exacerbations (RE) were counted and an average per year (DOHA and REA, respectively) was calculated. Results The mean serum concentration of vitamin D at baseline was 20.97 ng/ml compared to 25.41 ng/ml at the end of follow-up (p Conclusion The new guidelines for management of vitamin D deficiency appear to improve vitamin D levels in patients with CF. Improvement in vitamin D levels in individuals with CF appears to decrease both respiratory exacerbations and number of days of hospitalization per year.
    Asthma is a disease manifested by recurrent episodes of shortness of breath, wheezing or cough that often require treatment at the emergency department or even hospitalization. These exacerbations are caused by an increased inflammatory... more
    Asthma is a disease manifested by recurrent episodes of shortness of breath, wheezing or cough that often require treatment at the emergency department or even hospitalization. These exacerbations are caused by an increased inflammatory process in the airways. This review focuses on the various daily long term control medications used to prevent exacerbations. The pharmacotherapy used to manage asthma is based mainly on inhaled corticosteroids (ICS and leukotriene receptor antagonists. In more severe cases, other drugs can be added, such as long-acting beta 2 agonists lare used only in conjunction with ICS] as well as additional drugs such as slow release theophylline, anti-lgE monoclonal antibodies, and more. The step-up step-down approach is used to decide on the controller medication needed. If the preventive therapy fails, it is essential to assess the adherence to therapy, the technique used, the existence of aggravating factors and the possibility that the cause of the symptom...
    One of the measures adopted in Israel since 1959 as part of the tuberculosis control program was screening children aged 12-13 years old. The screening comprised single-step tuberculin skin testing using the Mantoux method. To assess the... more
    One of the measures adopted in Israel since 1959 as part of the tuberculosis control program was screening children aged 12-13 years old. The screening comprised single-step tuberculin skin testing using the Mantoux method. To assess the efficacy of tuberculin skin screening for TB in schoolchildren in southwestern Israel as well as the compliance to treatment for latent tuberculosis infection. We retrospectively reviewed the records of children in the Ashkelon region who underwent a tuberculin skin test during the period 1995-99. Of the 28,016 eligible children, 27,232 were tested. In 923 children, mostly from the former USSR and Ethiopia, an induration of 10 mm or more was found. Only 52 Israeli-born children tested positive. Tuberculosis was found in seven children with a positive test, five of whom were from Ethiopia. All children who tested positive were referred to the local TB clinic; only 266 children (28.8%) presented. Only 151 completed the recommended treatment of isoniaz...
    Bronchial asthma in the pediatric age group has become prevalent recently. Many children who suffer from asthma arrive at the emergency room (ER) with exacerbations which did not respond to medical treatment at home. Between July and... more
    Bronchial asthma in the pediatric age group has become prevalent recently. Many children who suffer from asthma arrive at the emergency room (ER) with exacerbations which did not respond to medical treatment at home. Between July and December 1997, 136 children 8 months to 14 years of age (61% below 3 years), were studied in our pediatric ER. Investigation included physical examination and pulse oximetry, which were used as guidelines for scoring the children on arrival and post-treatment. Spirometry was done in those who could cooperate. For each patient a detailed questionnaire about medical and sociodemographic factors was filled. Primary pediatricians used mainly beta-agonist and corticosteroid inhalators, while pediatric pulmonologists used mainly inhaled steroids. There was no relationship between severity of attack on arrival at the ER, mode of treatment and speed of recovery in the ER. More children treated by a general pediatrician more were admitted to hospital. Low parent...
    To compare the outcome of treatment with narrow spectrum versus broad spectrum antibiotics in children hospitalized with community-acquired pneumonia (CAP) who received oral antibiotic treatment prior to their hospitalization. A review of... more
    To compare the outcome of treatment with narrow spectrum versus broad spectrum antibiotics in children hospitalized with community-acquired pneumonia (CAP) who received oral antibiotic treatment prior to their hospitalization. A review of all previously healthy children from 3 months to 18 years with non-complicated CAP who received an oral antibiotic course in the community and were admitted from 2003 to 2008 to our pediatric departments. Clinical course and outcome parameters were compared for treatment with narrow and broad spectrum antibiotics. Of the 337 children admitted with non-complicated CAP after an oral antibiotic treatment course in the community, 235 were treated with broad spectrum, and 102 with narrow spectrum antibiotics. The two groups were similar regarding age, sex, days of fever prior to admission, type of preadmission oral antibiotic treatment, and laboratory indices at admission (P > 0.1). The broad spectrum-treated group had significantly better outcomes in terms of number of febrile days (1.2 ± 1.1 vs. 1.7 ± 1.6, P < 0.001), number of days treated with intravenous antibiotics (3.1 ± 1.3 vs. 3.9 ± 2.0, P < 0.001), and days of hospitalization (3.5 ± 1.5 vs. 4.2 ± 2.0, P < 0.001). The odds ratio for remaining hospitalized at 72 hr and 7 days was significantly higher for the narrow spectrum group (2.0 and 5.5 respectively, P < 0.05). In previously healthy children hospitalized with CAP after oral antibiotic treatment in the community treatment with broad spectrum antibiotics showed better outcome. Prospective studies are needed for appropriate recommendation. Pediatr Pulmonol. © 2015 Wiley Periodicals, Inc.
    Type 1 congenital plasminogen deficiency (CPD) is a rare autosomal recessive disease which causes formation of fibrin pseudomembranes that affect multiple systems/organs: the eyes, respiratory system, urinary and genital systems,... more
    Type 1 congenital plasminogen deficiency (CPD) is a rare autosomal recessive disease which causes formation of fibrin pseudomembranes that affect multiple systems/organs: the eyes, respiratory system, urinary and genital systems, gastrointestinal system, and the central nervous system. We present a rare manifestation of the disease-severe upper airway obstruction due to a rapidly growing mass in the supraglottic region-6 months after dental treatment under general anesthesia. The management of such a manifestation has not been discussed in the current literature. Due to deterioration in his clinical status, the patient eventually underwent both a tracheotomy in order to bypass the obstruction, and excision of the supraglottic mass. Within a few days the mass recurred with complete obstruction of the upper airway.
    The incidence of complicated pneumonia caused by S. pneumoniae is reported to be increasing. This increase may be related to host susceptibility and/or pathogen virulence. The objective of this study was to evaluate clinical and... more
    The incidence of complicated pneumonia caused by S. pneumoniae is reported to be increasing. This increase may be related to host susceptibility and/or pathogen virulence. The objective of this study was to evaluate clinical and laboratory characteristics associated with complicated pneumococcal pneumonia, and to identify risk factors associated with prolonged fever and hospitalization. The study involved reviewing the records of all children who were hospitalized in four major hospitals in Jerusalem with a confirmed diagnosis of pneumococcal pneumonia during a 12-year period (1986-1997). Demographic, clinical, laboratory, and outcome variables were compared between those with uncomplicated and complicated pneumonia. One hundred and eleven children (median age, 2.2 years) were hospitalized with pneumococcal pneumonia during the study period. Forty-four (39%) of them had complicated pneumonia, characterized by pleural effusion, empyema, pneumothorax, pneumatocele, and/or atelectasis. There was no correlation between the isolation of penicillin-resistant S. pneumonia (16% of cases) and complicated pneumonia. Factors that were significantly associated with complicated pneumonia included weight <or=10% for age, respiratory distress (e.g., tachypnea, dyspnea), anemia, and a white blood cell count (WBC) <15,000/mm(3) at time of admission. Complicated pneumonia and a WBC <15,000/mm(3) on admission increased the risk for prolonged fever and an extended length of hospitalization. Based on these results, it is concluded that host factors such as anemia, low weight, and a low WBC are associated with complicated pneumonia. Both the presence of pulmonary complications and a relatively low WBC in children hospitalized for pneumococcal pneumonia are independent risk factors for protracted fever and extended hospitalization.
    Intestinal protein loss has been reported mainly in diseases affecting the gastrointestinal tract. Intestinal protein loss during pneumonia with effusion has not been reported to date. The authors attempted to assess the associations... more
    Intestinal protein loss has been reported mainly in diseases affecting the gastrointestinal tract. Intestinal protein loss during pneumonia with effusion has not been reported to date. The authors attempted to assess the associations between pneumonia with effusion and intestinal protein loss and hypoalbuminemia in children. This was a prospective consecutive case series study of in children hospitalized with pneumonia and effusion during a period of 4(1/2) years. Serum albumin, C-reactive protein (CRP), and fecal alpha-1 antitrypsin (alpha-1-AT) were measured in the first 72 hours of hospitalization. Two control groups were studied: one consisted of 50 febrile children hospitalized because of viral or mild bacterial infections, and the other consisted of 20 afebrile children hospitalized because of convulsive disorders. Sixty-seven children ages 4 months to 14 years hospitalized with pneumonia and effusion were enrolled in the study. Fifty-nine percent (40 children) were found to have elevated fecal alpha-1-AT excretion (range, 2-10 mg/g) compared with none in the two control groups (P < 0.000).Fifty-two percent (35 children) of the children with pneumonia and effusion had mild to moderate hypoalbuminemia (range, 22-34 g/L). Only one child (2%) in the febrile control group had a low albumin of 34 g/L; none were found in the afebrile control group. The level of fecal alpha-1-AT was inversely correlated with serum albumin level. Pneumonia with effusion in children is often associated with an intestinal protein loss that can be monitored by measuring gastrointestinal loss of protein, namely fecal alpha-1-AT. In most cases the development of hypoalbuminemia correlates with the development of intestinal protein loss.
    Activation of naive T and B cells occurs only within the context of organized lymphoid tissue. Thus, the continuous recirculation of mature lymphocytes is crucial for the development of primary immune response to foreign Ags. We have... more
    Activation of naive T and B cells occurs only within the context of organized lymphoid tissue. Thus, the continuous recirculation of mature lymphocytes is crucial for the development of primary immune response to foreign Ags. We have previously shown that low levels of IFN-γ inhibit homing of B cells to the secondary lymphoid organs. In this study, we demonstrate that similarly low doses of IFN-γ down-regulate integrin-mediated adhesion and migration of naive T and Th2 cells, and have a profound effect on the in vivo homing of naive T cells to the lymph nodes. Moreover, we show that these low doses of IFN-γ have anti-inflammatory effects in an in vivo asthma model. Thus, in contrast to the proinflammatory effects of IFN-γ at relatively high concentrations, low dose IFN-γ appears to exert global suppressory effects on T cell trafficking and may have clinical application as an anti-inflammatory agent.
    Grass and mite allergens are of the main causes of allergy and asthma. A carbohydrate-binding module (CBM) represents a common motif to groups I (β-expansin) and II/III (expansin-like) grass allergens and is suggested to mediate... more
    Grass and mite allergens are of the main causes of allergy and asthma. A carbohydrate-binding module (CBM) represents a common motif to groups I (β-expansin) and II/III (expansin-like) grass allergens and is suggested to mediate allergen-IgE binding. House dust mite group II allergen (Der p 2 and Der f 2) structures bear strong similarity to expansin's CBM, suggesting their ability to bind carbohydrates. Thus, this study proposes the design of a carbohydrate-based treatment in which allergen binding to carbohydrate particles will promote allergen airway clearance and prevent allergic reactions. The aim of the study was to identify a polysaccharide with high allergen-binding capacities and to explore its ability to prevent allergy. Oxidized cellulose (OC) demonstrated allergen-binding capacities toward grass and mite allergens that surpassed those of any other polysaccharide examined in this study. Furthermore, inhalant preparations of OC microparticles attenuated allergic lung i...

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