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S Zielen

Publications and source records attributed to S Zielen.

At least 19 recordsLinked to original sources
PubMed2006

Impaired interferon-gamma production in response to live bacteria and Toll-like receptor agonists in patients with ataxia telangiectasia.

Ataxia telangiectasia (AT) is a pleiotropic autosomal recessive neurodegenerative disorder with associated immunodeficiency and cancer predisposition, caused by mutational inactivation of the ATM gene. Early death usually results from lymphoreticular malignancy or recurrent, chronic respiratory infections. Immune deficiency of AT patients is heterogeneous and involves both humoral and cellular responses. Reports on the number and integrity of immunocompetent cells in AT are conflicting. In the early phase of infection, the interleukin (IL)-12/interferon (IFN)-gamma axis plays a crucial role in first-line defence against pathogens. In a whole blood assay we studied the IL-12/IFN-gamma axis in the immune response of AT cells to the Toll-like receptor agonists lipopolysaccharide and heat-killed Staphylococcus aureus, as well as whole live M. bovis bacille Calmette-Guérin (BCG). The function of AT antigen-presenting cells was normal in terms of IL-12 production, while IFN-gamma production by T and natural killer (NK) cells was severely impaired, even in the presence of adequate co-stimulation by exogenous IL-12.

Adolescent↗
PubMed2006

Immunoglobulins and immunogenicity of pneumococcal vaccination in preschool asthma.

Pneumococcal vaccination is advocated for asthmatics. Although routinely performed, data supplying evidence for this recommendation are limited. We examined the immunological background of 215 asthmatic children (2-5 year old) at a university children's hospital and compared the immunogenicity of the recommended pneumococcal vaccines. Testing encompassed serum immunoglobulins, immunoglobulin G (IgG)-subclasses, and pneumococcal antibodies against serotypes 4, 6B, 9V, 14, 18C, 19F and 23F. An infection-prone subgroup received one dose of 23-valent pneumococcal polysaccharide vaccine (PPV-23; n = 38, median age 45 months) or of 7-valent conjugate vaccine (PCV-7; n = 23; median age 35 months). Pneumococcal antibodies were determined again after 4 weeks. Low immunoglobulin- and/or IgG-subclass levels were found in 27 subjects (14 infection-prone). Prevaccination pneumococcal antibody levels ranged from 0.36 to 1.06 microg/ml, depending on the serotype. The percentage of subjects with putative protective antibody levels > or =1.0 microg/ml ranged only from 19.9% to 54.1%, over all. Postvaccination, antibody geometric mean concentrations increased significantly higher in PCV-7 vaccinees for serotype 14 (p < 0.01) and 23F (p < 0.05). Now the percentage of putatively protected subjects ranged from 40.9% (serotype 6B) to 90.9% (serotype 19F) following PCV-7 compared with 31.6% (serotype 6B and 23F) to 81.6% (serotype 19F) in PPV-23 vaccinees. Our data give further evidence for pneumococcal vaccination of asthmatic children. PCV-7 is at least as immunogenic as PPV-23. Moreover, for children suffering from persistent asthma, PCV immunisation should be considered.

Antibodies, Bacterial↗
PubMed2006

Effectiveness of budesonide nebulising suspension compared to disodium cromoglycate in early childhood asthma.

OBJECTIVE: The optimal treatment for early childhood asthma remains controversial. Budesonide (BUD) has shown superiority over placebo in infants, and over disodium cromoglycate (DSCG) in children aged > 2 years. The aim of this double-blind, randomised, parallel-group study was to compare the effectiveness of nebulised BUD and DSCG in asthmatic children aged < 36 months. RESEARCH DESIGN AND METHODS: 82 infants (mean age 18.0 months [range, 11.6-31.2 months]) with suspected asthma (three exacerbations of dyspnoea and wheezing during the past 12 months, with one or more exacerbations in the past 3 months) were treated for 3 months with nebulised BUD (Pulmicort Respules) 0.5 mg/2 mL bid or DSCG 20 mg/2 mL tid. Follow-up was at 6 months. MAIN OUTCOME MEASURES AND RESULTS: Patients treated with BUD had a lower exacerbation rate than DSCG-treated patients after 3 months of treatment (5.4% vs. 31.7%; p = 0.003) and towards the end of follow-up (30% vs. 49%; p = 0.062). During treatment, days without cough were 80% and 65% for BUD and DSCG, respectively (p = 0.014), and nights without cough were 89% and 78%, respectively (p = 0.016). Side-effects were mild and of similar frequency in both groups. CONCLUSIONS: Inhaled nebulised BUD was well tolerated and more effective than nebulised DSCG in reducing the incidence of asthma exacerbations and days with symptoms. These beneficial effects of BUD were maintained throughout the 6-month follow-up.

Anti-Asthmatic Agents↗
PubMed2005

[Pneumococcal vaccination in obstructive lung diseases -- what can we expect?].

Many countries' guidelines recommend pneumococcal vaccination for patients suffering from obstructive airway disease. This paper reviews the literature as to immunogenicity and safety of this immunization. There is no evidence for a negative effect of pneumococcal vaccination on these patients. Only a few data exist on the preventive impact of pneumococcal vaccination as to exacerbations of obstructive airway diseases. Existing studies mostly took up this question as a side aspect. The effect in children and adults appears limited. On the other hand, the pneumococcal conjugate vaccine prevents life-threatening invasive infections in children younger than 5 years, and pneumococcal polysaccharide vaccine protects healthy adults against bacteriaemic pneumonia. Thus, pneumococcal vaccination of patients suffering from obstructive airway disease is recommendable.

Adolescent↗
PubMed2005

Growth factor deficiency in patients with ataxia telangiectasia.

One prominent feature of patients with the autosomal recessive disease ataxia telangiectasia (AT) is somatic growth retardation. Due to their essential roles in development we examined levels of insulin-like growth factor-I (IGF-I) as well as its main binding protein (IGFBP-3) in a group of AT patients. Growth status of 19 patients was assessed by body mass index (BMI) and nutritional protocols. As suspected, BMI was low in AT patients despite adequate nutrition. Serum levels of IGF-I were found to be below the 3rd percentile in 9 (56%) out of 16 patients and of IGFBP-3 in 13 (81%) out of 16 patients. Our observations demonstrate that IGF-I and IGFBP-3 levels reflect the impaired growth status in patients with AT.

Adolescent↗
PubMed2004

Immunogenity of the pneumococcal polysaccharide vaccine in COPD patients. The effect of systemic steroids.

RATIONALE: To investigate if systemic steroids influence the antibody response to the 23-valent pneumococcal polysaccaride vaccine (23-PPV) in COPD patients. PATIENTS AND METHODS: COPD patients on: (a) > or =10mg of prednisolone/day (SS, n = 30); (b) inhalative steroids (IS, n= 30); (c) controls without COPD (CG, n= 29) were vaccinated with 23-PPV. The concentration (microg/ml) of capsular specific anti-pneumococcal IgG antibodies (AB) for the serotypes (PNC) 4,6B,9V,14,18C,19F,23F were measured by Elisa technique before, 3 and 12 months (m) after vaccination. Non-responders were defined when AB-concentrations did neither doubled nor reach > or = 1 microg/ml. RESULTS: N=24 (CG), n=29 (IS), n= 18 (SS) patients completed the study (mean age 64yrs.). Serious adverse events were not observed. Geometric mean (GM) AB-concentration of all serotypes increased significantly (CG, IS, SS) 3 and 12m after vaccination (P<0.05). The percentage of non-responders ranged between 16% (PNC 19F, IS) and 65% (PNC 4, SS) after 3 m and 21% (PNC 19F, IS) and 82% (PNC 4, CG) after 12m. Neither post-vaccine AB-concentrations (3 and 12m) nor the rate of non-responders differed significantly between patients on systemic steroids and the other groups (IS, CG). CONCLUSIONS: Systemic steroids did not influence the AB-response. In all groups mean AB-concentration increased significantly after vaccination but an important percentage of subjects of all three groups were non-responders.

Aged↗
PubMed2004

Lymphadenitis cervicalis due to Mycobacterium interjectum in immunocompetent children.

UNLABELLED: This report presents two cases of cervical lymphadenitis due to Mycobacterium interjectum in healthy young children, identified by sequencing of the 16S rRNA gene. Surgical resection combined with chemotherapy resulted in cure. CONCLUSION: The attention of clinicians needs to be drawn to an emerging mycobacterial pathogen which might be overlooked or misidentified in routine laboratory testing.

Cheek↗
PubMed2004

Effect of anti-immunoglobulin E on nasal inflammation in patients with seasonal allergic rhinoconjunctivitis.

BACKGROUND: Binding of allergens to IgE on mast cells and basophils causes release of inflammatory mediators in nasal secretions. OBJECTIVE: The combined effect of specific immunotherapy (SIT) and omalizumab, a humanized monoclonal anti-IgE antibody, on release of eosinophilic cationic protein (ECP), tryptase, IL-6, and IL-8 in nasal secretion was evaluated. METHODS: Two hundred and twenty five children (aged 6-17 years) with a history of seasonal allergic rhinoconjunctivitis induced by birch and grass pollen were randomized into four groups: either birch- or grass-pollen SIT in combination with either anti-IgE or placebo. Complete sets of nasal secretion samples before treatment Visit 1 (V1), during birch- (V2) and grass (V3)-pollen season and after the pollen season (V4) were collected from 53 patients. RESULTS: A significant reduction in tryptase only was seen in the anti-IgE-treated group at V2 (P<0.05) and V4 (P<0.05) compared with the placebo group. During the pollen season, patients with placebo showed an increase of ECP compared with baseline (V2: +30.3 microg/L; V3: +134.2 microg/L, P< 0.005; V4: +79.0 microg/L, P< 0.05), and stable levels of tryptase, IL-6 and IL-8. Treatment with anti-IgE resulted in stable ECP values and a significant decrease of tryptase compared with V1 (baseline): V2: -80.0 microg/L (P< 0.05); V3: -56.3 microg/L, which persisted after the pollen season with V4: -71.6 microg/L (P< 0.05). After the pollen season, a decrease of IL-6 was observed in both groups (V4 placebo group: -37.5 ng/L; V4 anti-IgE group: -42.9 ng/L, P< 0.01). CONCLUSION: The combination of SIT and anti-IgE is associated with prevention of nasal ECP increase and decreased tryptase levels in nasal secretions.

Adolescent↗
PubMed2004

The co-seasonal application of anti-IgE after preseasonal specific immunotherapy decreases ocular and nasal symptom scores and rescue medication use in grass pollen allergic children.

BACKGROUND: Specific immunotherapy (SIT) and treatment with anti-immunoglobulin (Ig)E antibody are complementary approaches to treat allergic rhinoconjunctivitis, which may be used for single or combined treatment. OBJECTIVE: A randomized, double-blind, placebo-controlled trial was conducted to compare the efficacy of single and combined treatment with SIT and anti-IgE (Omalizumab) in reducing symptom severity and rescue medication use. METHODS: A total of 221 subjects with birch and grass pollen allergic rhinoconjunctivitis aged 6-17 years were analysed during the grass pollen season. Group A (SITbirch + placebo) served as a reference group obtaining no effective treatment for grass pollen allergy. Group B received anti-IgE monotherapy during grass pollen season, group C SIT grass pollen monotherapy, and group D the combined treatment of SIT and Omalizumab. RESULTS: Preseasonal treatment with grass pollen SIT alone compared with SIT with the nonrelated allergen did not reduce symptoms or rescue medication use. Anti-IgE monotherapy significantly diminished rescue medication use and number of symptomatic days. The combined treatment with SIT and anti-IgE showed superior efficacy on symptom severity compared with anti-IgE alone. CONCLUSIONS: Co-seasonal Omalizumab therapy showed considerable effects in children with seasonal allergic rhinitis. The combination of SIT plus Omalizumab was clinically superior to each treatment alone during the first year of observation.

Adolescent↗
PubMed2003

Safety and tolerability of methacholine challenge in infants with recurrent wheeze.

Bronchial hyperreactivity (BHR) is a key feature of asthma, but measurement can usually not be achieved in infants with standard lung function tests. We investigated the safety and tolerability of methacholine challenge in infants with recurrent wheezing episodes. 78 methacholine challenges in 51 sedated infants aged 12-36 months with recurrent wheezing episodes were performed. Methacholine challenge was stopped when clinical signs (coughing, wheezing, or cyanosis) or a drop of oxygen saturation (SPO2) of at least 5% or a drop of transcutaneous oxygen tension (PtcO2) of at least 0.8 kPa or an increase of resistance (RrsSO), of 50% by single occlusion technique were observed. Prior to methacholine challenge, all children were symptom-free with a mean SPO2 of 97.4% (SD 1.80%). In 48 cases (61.5%), no clinical sign was observed, 17 (21.8%) coughed, and 13 (16.7%) wheezed. A mean reduction of SPO2 of 5.0% (SD 3.89%) for the entire population was observed. In 15 of 78 cases, a decrease of SPO2 <90% occurred. This SPO2 drop was short-lasting and resolved spontaneously or after bronchodilator inhalation. Infants whose SPO2 dropped <90% showed a greater increase of RrsSO compared to infants who did not drop <90% (133% vs. 65% RrsSO increase, p<0.001). Methacholine challenge, using a combination of clinical observation, monitoring of SPO2 and PtcO2, and airway resistance using the single-occlusion technique, is a safe and tolerable tool to measure the BHR in infants with recurrent wheezing episodes.

Airway Resistance↗
PubMed2002

Deficiencies in CD4+ and CD8+ T cell subsets in ataxia telangiectasia.

Chronic sinopulmonary infections that are associated with immunodeficiency are one of the leading causes of death in the multi-systemic disease ataxia telangiectasia (AT). Immunological investigations of AT patients revealed a broad spectrum of defects in the humoral and the cellular immune system. Based on their important role in host defence the aim of our study was an extensive analysis of cell distribution and function of CD4+ and CD8+ T lymphocytes and NK cells. We found that naive (CD45RA+) CD4+ lymphocytes, as well as CD8+/CD45RA+ lymphocytes, are decreased, whereas NK cells (CD3-/CD16+CD56+) are significantly elevated in AT patients. In our culture system proliferation and cytokine production was normal in purified memory (CD45RO+) lymphocytes after stimulation with phorbol-12,13-dibutyrate (PBu2) and after PHA activation, indicating that differences in proliferation and cytokine production are due solely to reduced numbers of CD45RA+ lymphocytes. However, activation, and especially intracellular interferon production of AT lymphocytes, seem to follow different kinetics compared to controls. In contrast to polyclonal activation, stimulation via the T cell receptor results consistently in a reduced immune response. Taken together, our results suggest that deficiency of immunocompetent cells and an intrinsic immune activation defect are responsible for the immunodeficiency in AT.

Adolescent↗
PubMed2001

Persistent adenoviral infection and chronic obstructive bronchitis in children: is there a link?

Chronic obstructive bronchitis with inadequate response to inhaled steroid and bronchodilator therapy is a rather rare disorder in children. Persistence of an adenoviral infection has been described as a possible cause of unremitting airway obstruction. We studied a group of 11 children with the clinical feature of chronic bronchial obstruction. A high-resolution computed tomography (HR-CT) scan was performed and typically showed hyperinflation and ground-glass-like opacities. All children underwent either bronchoscopic transbronchial or open lung biopsy. Biopsy specimens were stained with monoclonal antibodies detecting adenoviral antigen and analyzed by light-microscopy. Bronchoalveolar lavage (BAL) fluid was cultured for adenovirus, and antigen detection tests were performed. While some children had a history of proven adenoviral infection at the onset of their disease, in none of the cases could a persistence of adenovirus be shown. We conclude that adenoviral infection might act as a starter of chronic obstructive bronchitis in children, but that pathogenetic mechanisms other than persistent infection must be responsible for the chronicity of the disease.

Adenoviridae Infections↗
PubMed2001

[Congenital cystic adenomatoid malformation--clinical spectrum and management].

Congenital cystic adenomatoid malformation (CCAM) is one of the most frequent dysplasias of the lung. Diagnosis is often suspected in utero and urges obstetricians, pediatricians, and pediatric surgeons to make appropriate management decisions as to an optimal management for the affected patients. We report on a preterm baby with a gestational age of 33 weeks, suffering from hydrops fetalis and postnatal respiratory distress syndrome, a two-year old boy with clinical signs of a foreign body aspiration, and a seven-year old boy with a funnel chest. In each case, surgical resection was performed, the histology revealing CCAM. Our case report describes the broad clinical spectrum of CCAM. An algorithm is presented, helping to make diagnostic and therapeutic decisions.

Algorithms↗
PubMed2000

Immunoglobulin levels in bronchoalveolar lavage fluid of children with chronic chest disease.

The concentration and distribution of immunoglobulin isotypes (IgG, IgM, sIgA) and IgG-subclass levels (IgG-1-4) were measured in bronchoalveolar lavage fluid (BALF) in 47 children with chronic chest disease (age range 1.0-9.9 years) and 18 healthy controls (age range 1.0-6.25 years). Of these patients, 19 had nonallergic asthma (Group A), 19 suffered from recurrent pneumonia or chronic bronchitis (Group B), and 9 patients had IgG-2 deficiency (Group C). In all individuals, IgG was the predominant immunoglobulin in the lower respiratory tract, followed by IgA and IgM. In patients of Group A and B, IgG, IgM and IgA levels in BALF were significantly elevated when compared to controls. Assessment of IgG-subclass concentrations in BALF revealed that IgG-1 levels were increased in Group A and B when compared to controls (P < 0.05). Since this difference could not be explained by difference in age, it is possibly due to the inflammatory process at the mucosal level. IgG-2 levels were elevated in all patients except those with IgG-2 deficiency. IgG-2 concentration in the IgG-2 deficent group was lower compared to controls (P < 0.005) and patients in Group A (P < 0.0005) and B (P < 0.005). IgG-3 levels were elevated in asthmatics in group A compared to healthy controls (P < 0.005). IgG-4 concentrations were the same in all study groups. Since IgG-subclasses in percentage of total IgG were similar in BALF and serum, our results do not indicate a local production of any of the IgG-subclasses in the respiratory tract.

Asthma↗
PubMed2000

Antioxidative capacity in patients with common variable immunodeficiency.

Highly reactive oxygen species (ROS) are involved in T-cell activation and in the defense against environmental pathogens. An imbalance of ROS generation, detoxifying scavenger enzymes, and molecules with antioxidant capacity could contribute to the increased susceptibility to cancer and infections in severe humoral immunodeficiency. We studied antioxidant status, i.e., plasma antioxidant capacity (TEAC), retinol, alpha-to-copherol, ubiquinol, and the number of activated T cells in 16 patients with common variable immunodeficiency (CVID) compared to age-matched healthy controls. As expected, patients showed significantly increased levels of activated HLA-DR and CD45RO-expressing T cells. Plasma levels of the endogenous ROS scavenger ubiquinol (Q 10) were significantly lower in patients as compared to controls. However, patients showed only slightly reduced levels of TEAC as well as the exogenous antioxidants retinol and alpha-tocopherol. Although no correlation of the number of activated T cells and antioxidant capacity could be demonstrated, an increase in ROS and a diminished reactive oxygen scavenger capacity may be involved in the disease process in patients with common variable immunodeficiency.

Adolescent↗