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S Zielen

Publications and source records attributed to S Zielen.

At least 37 records · Page 2Linked to original sources
PubMed2000

Spontaneous and oxidative stress-induced programmed cell death in lymphocytes from patients with ataxia telangiectasia (AT).

T cell lymphopenia in the peripheral blood lymphocytes (PBL) of patients with AT is mainly caused by a decrease of naive CD45RA+/CD4+ cells followed by a predominance of memory CD45RO+ lymphocytes. To relate these findings to the regulation of programmed cell death, we investigated the activation state and apoptotic level of PBL in 12 patients and healthy controls by flow cytometry. In accordance with previous investigations, the number of naive CD4+/CD45RA+ cells was significantly decreased in patients compared with healthy controls. This disturbed balance of CD45RA and CD45RO was also reflected in higher amounts of activated HLA-DR and CD95 expressing cells, with a concomitant decrease of Bcl-2 protected lymphocytes in the T cell population. With regard to its role in preventing oxidative-induced cell death, we analysed Bcl-2 expression and apoptosis in the presence of oxidative stress. In culture, cells of patients are more susceptible to spontaneous programmed cell death. However, in our stress-inducing system (hypoxanthine/xanthine oxidase system) the number of cells undergoing apoptosis was lower in patients' cell populations compared with controls. In addition, preliminary results suggest that Bcl-2 expression and level of spontaneous apoptosis in patients can be modified by IL-2 and interferon-gamma.

Adolescent↗
PubMed2000

Severe adenovirus bronchiolitis in children.

UNLABELLED: Severe adenoviral infections such as the necrotizing adenovirus bronchiolitis occur sporadically in infants. Ascertaining the etiologic role of adenovirus in cases of lung disease can pose a diagnostic problem. We present two cases of severe bronchiolitis in previously healthy children in which adenovirus could be shown to be the causing agent. Both children received immunosuppressive therapy with steroids and Cyclosporin for 3 mo and a course of intravenous Ribavirin for 10 d. The results were conflicting: despite therapy Patient 1 died due to respiratory failure, Patient 2 improved notably. CONCLUSIONS: Adenovirus can cause severe bronchiolitis in previously healthy children. Diagnosis may be difficult to achieve. The role of antiviral therapy in the treatment of adenoviral infections remains to be cleared.

Adenovirus Infections, Human↗
PubMed2000

Immunogenicity and tolerance of a 7-valent pneumococcal conjugate vaccine in nonresponders to the 23-valent pneumococcal vaccine.

There is still a lack of effective vaccination strategies for patients with a deficient antibody response to bacterial polysaccharide antigens. In an open trial, we evaluated the immunogenicity and tolerance of a new 7-valent pneumococcal conjugate vaccine in 22 infection-prone nonresponders to pneumococcal polysaccharide vaccine and 21 controls. In the patient group, nonresponsiveness was confirmed by repeated vaccination with a 23-valent pneumococcal polysaccharide vaccine. The study protocol provided two doses of the pneumococcal conjugate vaccine, given 4 to 6 weeks apart, for both groups. The antibody response was determined before each vaccination and on follow-up by an enzyme-linked immunosorbent assay and compared to the response in a functional opsonophagocytosis assay. Patients showed a significantly lower postvaccination immune response for all serotypes than did controls. The postvaccination response was serotype dependent. A median titer of >1 microgram/ml in patients was recorded only for serotypes 4, 9V, 14, and 19F, which are known to be more immunogenic than serotypes 6B, 18C, and 23F. In the patient group, 70% responded to serotype 19F (Pnc 19F), 65% responded to Pnc 14 and 4, 60% responded to Pnc 9V, 55% responded to Pnc 18C, 50% responded to Pnc 23F, and 25% responded to Pnc 6B. In the control group >95% of individuals showed a titer of >1 microgram/ml to every serotype. The vaccine was tolerated well, and no major side effects have been reported. The new pneumococcal conjugate vaccine is clearly more immunogenic in previous nonresponders than is the 23-valent pneumococcal vaccine. Immunization with a pneumococcal conjugate vaccine should be considered as a strategy to protect high-risk patients.

Adolescent↗
PubMed1999

Lipid-laden alveolar macrophages (LLAM): a useful marker of silent aspiration in children.

At present there is no test available which identifies children suffering from silent aspiration due to gastroesophageal reflux (GER). The purpose of this study was to determine whether lipid-laden alveolar macrophage (LLAM) scoring is a useful method to arrive at the diagnosis. We evaluated bronchoalveolar lavage fluid (BALF) from 68 children aged 6 months to 14 years (median 3.75 years) for the presence of lipid-laden alveolar macrophages. We compared children with chronic chest disease (CCD) and GER to healthy surgical controls without known lung disease, and to children with recurrent pneumonia without GER. By grading the amount of intracellular Sudan Red-positive material, we determined a semiquantitative lipid-laden macrophage (LLAM) score for each patient. Patients with chronic chest disease suspected to be caused by silent aspiration secondary to GER had a significantly higher LLAM score (median, 117; range, 10-956) than children with recurrent pneumonia due to other reasons (median, 29; range, 5-127; P < 0.01) and healthy controls (median, 37; range, 5-188; P < 0.01). We believe that simply observing lipid-laden macrophages is nonspecific, but quantitation of these cells is a useful method for diagnosing silent aspiration in children, especially when the score exceeds 200.

Adolescent↗
PubMed1999

Antireflux surgery in children suffering from reflux-associated respiratory diseases.

The aim of our study was to evaluate the success, complications, and morbidity following a modified Thal fundoplication in children with reflux-associated respiratory disease (RARD). We used a procedure consisting of retroesophageal hiatal plasty, wrapping the gastric fundus around the gastroesophageal junction 180 degrees, and fixation of the lesser curvature at the abdominal wall. Follow-up by questionnaire of 128 (77 male, 51 females) out of 196 antireflux procedures between 1992 and 1995 was achieved. Surgical therapy was considered justified whenever there was gastroesophageal reflux resulting in severe recurrent respiratory symptoms. Eleven percent of the children suffered from bronchiectasis. The diagnosis of RARD was based on a high index of suspicion, barium swallow with fluoroscopy, 24-hr two-level pH-monitoring, bronchoscopy, bronchoalveolar lavage and detection of lipid-laden alveolar macrophages, esophago-gastroscopy, and esophageal biopsy. Patients with bronchopulmonary diseases such as allergy, immunodeficiency, cystic fibrosis, primary ciliary dyskinesia, and malformation of the bronchial tree or vessels had been excluded. "Evident improvement" as a result of surgery was reported in 88%, "no change" in 10%, and a "change for the worse" in 2% of patients. Persistent mild difficulties in swallowing were observed in 11%. Paraesophageal hernia, gas-bloat syndrome, and dumping syndrome were not observed. Two children needed a second operation because of relapse. The use of emergency steroidal medication for acute respiratory distress decreased impressively (219 single doses/year before surgery vs. 30 single doses/year after surgery). The need for more than 4 times/year of antibiotic therapy before surgery was reduced from 52. 3% before to 14% after surgery. Most (90.6%) of the parents stated they would agree to have surgery done again if medically indicated. In conclusion, Thal fundoplication is sufficient, safe, and effective in the management of RARD. Complications of the procedure were minor and of little consequence to the patient.

Adolescent↗
PubMed1999

[Immunoglobulin subclass defects in patients with therapy refractor chronic rhinosinusitis].

In the present study 220 patients suffering from recurrent rhinosinusitis and not responding to antibiotic treatment were evaluated for a defect in IgG-immunoglobulin subclasses. Twenty-one of these patients were found to have an antibody deficiency. These included deficiencies of IgG-2 (n = 10), IgG-1 (n = 6), IgG-3 (n = 1) and IgG-4 (n = 1). A common variable immune disease was diagnosed in three patients that was characterized by an additional defect in the IgG main class. However, an IgG subclass deficiency can only be ascertained by an immunological evaluation. The significance of a deficiency can be identified by a reaction to vaccination using (for example) protein or polysaccharide antigens. Treatment consists of antibiotics, intravenous immunoglobulins and long-term follow-up. Endonasal microsurgery should only be performed in cases that do not respond to conservative treatment. It is particularly necessary to observe these patients because a deficiency of immunoglobulin subclass in certain cases is the first sign of an immunological impairment that can advance to a severe immunodeficiency and predispose to the development of malignancy.

Adolescent↗
PubMed1999

Immunoglobulin deficiency and determination of pneumococcal antibody titers in patients with therapy-refractory recurrent rhinosinusitis.

We examined 245 patients with chronic rhinosinusitis not responding to prolonged antibiotic treatment and tested each patient for humoral antibody deficiencies. Low immunoglobulin levels were found in 22 patients. Five of them had defects of two or more immunoglobulin isotypes that were diagnosed as common variable immunodeficiency (CVI). Seventeen had an IgG-subclass deficiency. Before and after immunization with pneumococcal vaccine, serotype-specific pneumococcal antibody levels were determined to further evaluate the relevance of the underlying deficiency. Significantly reduced antibody titers of pneumococcal serotypes were found in CVI patients (n = 5), while immunization of 17 patients with IgG-subclass deficiency gave different results. Three of the 17 patients responded poorly to pneumococcal immunization and were prone to a polysaccharide specific immunodeficiency. Patients with CVI or IgG-subclass deficiency failing to produce protective antibody levels in more than five serotypes were chosen for antibiotic and/or immunoglobulin substitution therapy. Since recurrent sinusitis in these patients did not resolve with adequate conservative therapy, endonasal microsurgery was then performed and was seen to be a valuable therapeutic option. Our study suggests that an IgG-subclass deficiency may be the first sign of a basic immunological change, resulting in persisting sinus infections.

Adolescent↗
PubMed1999

Anti-oxidative capacity in patients with ataxia telangiectasia.

Highly reactive oxygen species (ROS) are involved in T-cell activation and in the defense against environmental pathogens. An imbalance of ROS generation and detoxifying scavenger enzymes could contribute to the increased susceptibility to cancer and infections in ataxia telangiectasia. We studied oxidative status, i.e. plasma total antioxidant capacity (TEAC), retinol, alpha-tocopherol, ubiquinol, and the number of activated T cells in 10 patients with ataxia telangiectasia (AT) compared to age-matched healthy controls. As expected, patients showed significantly increased levels of activated human leukocyte antigen-DR and CD45RO expressing T cells. TEAC levels as well as the exogenous antioxidants retinol and alpha-tocopherol were significantly reduced in patients. In addition, patients showed slightly reduced plasma levels of the endogenous ROS scavenger enzyme ubiquinol (Q10). Although no correlation between 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 of patients with AT.

Adolescent↗
PubMed1999

Safety and immunogenicity of an acellular pertussis vaccine in premature infants.

OBJECTIVES: To evaluate the safety and immunogenicity of a two-component acellular pertussis vaccine in preterm infants. STUDY DESIGN: Fifty preterm infants (25-35 weeks of gestation; mean, 30.8 weeks) and 50 term infants as a control group received a two-component acellular pertussis vaccine irrespective of their biological age and actual weight. Adverse reactions were registered by parents on a diary card and reviewed on each visit. Antibodies against pertussis toxoid (PT) and filamentous hemagglutinin (FHA) were determined with an enzyme-linked immunosorbent assay before the first and after the third vaccination. RESULTS: The infants of both groups showed an increase in geometric mean titers (GMT) against PT and FHA after vaccination (3 doses). There was a significant difference of antibody concentration between the preterm and the control group. The GMT for PT antibody of the preterm infants was 64. 16 U/L, and for the term infants it was 98.96 U/L. The GMT for FHA was 50.92 U/L in preterm versus 86.02 U/L in the control group. Efficacy of the immunization (more than a fourfold increase of antibody concentration in each infant) was 93.5% in the preterm group with respect to PT and 82.6% with respect to FHA. The incidence of adverse reactions was low and comparable in both study groups. CONCLUSION: Immunization with an acellular pertussis vaccine is safe for preterm infants. The immune response is significantly lower compared with a control group of term infants, but efficacy is high.

Antibodies, Viral↗
PubMed1999

[Hospital admission for bronchial asthma: comparison between inpatient children and patients attending ambulatory asthma education].

BACKGROUND: Asthma bronchiale is a chronic disease with increasing prevalence, increasing numbers of hospital admissions, and a growing mortality rate. Training courses for patients could reduce the number of in-patients, but it is still not clear what leads to an increase in admissions and whether all children have equal access to the special training courses offered. METHODS: In order to settle these questions, 40 in-patients with asthma (clinical group) were compared with a training group of 80 children of the same age, who participated in an out-patients' training course for asthmatics held at Asthma-Zentrum Rhein-Main. During a retrospective examination clinical characteristics (therapy prior to admission, number of times of seeing a doctor before admission, number of days of absence from school) and socio-economic conditions (size of flat, level of education of parents, proportion of children from families of non-German origin), as well as environmental factors (parents' tobacco smoking) were determined. FINDINGS: As expected, significant disadvantages regarding clinical characteristics and socioeconomic data were recorded for the clinical group. Children in the clinical group less often got a regular prophylactic treatment before admission to hospital (43% vs. 80%). They were absent from school three times more often than children from the training group (6 days vs. 2 days); proportionally, their parents smoked twice as often (53% vs. 23%); frequently, the number of persons living in the flat exceeded the total number of rooms (43% vs. 23%), and only 61% had their own bedroom (vs. 81% in the training group). 40% of the children in the clinical group are from families of nationalities other than German vs. only 14% in the training group. Moreover, most parents of the children in the clinical group were undereducated or had no professional training at all, and rarely held university degrees. INTERPRETATION: The results show that the patients' profiles regarding therapy and socio-economic conditions differ substantially between in-patients and children from the training group at the Asthma-Zentrum. A major part of these patients in question had no access to or could not be reached by an ambulant training course for asthmatics. Especially socially and economically disadvantaged families, and families with little compliance must be informed more carefully and should be persuaded of the benefits of ambulant training courses for asthmatics.

Adolescent↗
PubMed1998

Differential immune response to influenza and pneumococcal vaccination in immunosuppressed patients after heart transplantation.

INTRODUCTION: Patients after solid organ transplantation are at an increased risk for microbial infections. Due to therapeutic immunosuppression, the response to active immunizations may be reduced. The serological efficacy of pneumococcal and influenza vaccination was studied in heart transplant recipients. PATIENTS AND METHODS: Sixteen patients over 1 year after heart transplantation and control patients were immunized with a 23-valent pneumococcal vaccine and a triple-split influenza vaccine. Pre- and postvaccinal antibody titers were serologically determined, including quantitation of specific antibodies against nine pneumococcal serotypes. RESULTS: Both vaccines were well tolerated without systemic reactions or infectious complications. Median postvaccinal pneumococcal antibody titers in the transplant patients were comparable to controls (5513 U/ml, range: 694-41007, vs. 5490 U/ml, range: 1088-38042; P=NS); vaccination was successful in 23/23 (100%) of controls and in 15/16 (94% plus 1 borderline positive case) of the transplant recipients. Specific antibody titers were similar for eight of nine serotypes; only the immune response against serotype 3 was reduced after transplantation. The efficacy of influenza vaccination was significantly impaired in transplant patients against all three virus strains (62% vs. 97%, P<0.01/50% vs. 94%, P<0.001/37% vs. 80%, P<0.01), but 9/16 (56%) of patients still showed a sufficient immune response to two out of three virus strains. No clinical or demographic predictors of successful vaccination could be established. CONCLUSIONS: Pneumococcal vaccination under cyclosporine-based immunosuppression after heart transplantation is safe and equally effective as in healthy controls. In contrast, the immune response to influenza vaccination is significantly reduced, although not completely abolished. This differential response might be accounted for by T cell-independent antibody production against polysaccharide antigens contained in the pneumococcal vaccine.

Adult↗
PubMed1998

Sibs affected with both Ehlers-Danlos syndrome type IV and cystic fibrosis.

We report on the unprecedented combination of two recessively inherited disorders, the kyphoscoliosis type of Ehlers-Danlos syndrome (EDS type VI) and cystic fibrosis (CF), in two sibs born to consanguineous Turkish parents. Because of failure to thrive and bronchitis CF was diagnosed in the index patient early whereas EDS VI was recognized only very late. Both patients had marked muscular hypotonia at birth, delayed gross motor development, progressive kyphoscoliosis, joint dislocations, Marfanoid habitus, hypertrophic and atrophic scars, and osteopenia. EDS VI was proven by collagen studies and the pathognomonic pattern of urinary pyridinolines. Because the genes coding for the two disorders are located on different chromosomes and a chromosomal rearrangement was excluded, we conclude that their combination is a chance association. The cardiopulmonary impairment common to both diseases makes the prognosis dismal.

Amino Acids↗
PubMed1998

Human b cell differentiation: dependence on interactions with monocytes and T lymphocytes via CD40, CD80 (B7.1), and the CD2-Ligands CD48 and CD58 (LFA-3).

B cell differentiation depends on cellular interactions with T lymphocytes and monocytes via adhesion molecules (AM). In order to characterize AM which are required for B cell differentiation immunoglobulin production using unseparated peripheral blood mononuclear cells (PBMC) was studied. Unstimulated human PBMC were cultured for 9 days with mAb directed at CD2/CD48, /CD58, CD59, CD5/CD72, CD11a-CD18/CD54, CD28/CD80, CD86, CD40/CD40L, or rat CD2 (control). B cell differentiation was quantified measuring IgM and in some cases IgA, IgG, and IgE production. IgM levels were significantly reduced by mAb against CD40, CD48, CD58 and CD80. The reduction was not due to isotype switching to IgA, IgG or IgE. The role of CD40, CD48, CD58 and CD80 was further investigated after depletion of different cell types. Depletion of monocytes and NK cells resulted in no detectable IgM production irrespective of added mAbs. In contrast, IgM production was still present after depletion of T cells and NK cells. Only mAb against CD80 and CD48 significantly reduced IgM production, the reduction of IgM production by anti-CD40 mAb was less than in the presence of T cells. Importantly, anti-CD58 mAb had no effect on IgM production after T cell and NK cell depletion. Taken together, the AM CD40, CD48, CD58, and CD80 are involved in Ig production of unseparated PBMCs. In this model of B cell differentiation only the AM CD58 depend on the presence of T cells while CD48 and CD80 help was found to be T cell independent.

Animals↗
PubMed1998

[Safety aspects of bronchoalveolar lavage in risk patients in childhood--continuous end-expiratory pCO2 monitoring].

Although bronchoalveolar lavage (BAL) is a useful tool even in childhood pulmonary diseases, only little is known about the problems attendant to its use. Hence, we investigated from a total of 212 rigid bronchoscopy procedures 22 patients of 1-10 years of age. General inhalation anaesthesia was performed and BAL was carried out using a paediatric standardised protocol. BAL volume was adjusted to body weight. Before BAL and 2, 7 and 20 minutes after BAL capillary blood gas, blood pressure, heart rate and SaO2 were measured. Continuously end-tidal PCO2 (ET (PCO2) measurement was done by using a catheter placed in the main stream bronchus. Mean ET PCO2 increased from 39.6 +/- 9.5 mmHg to 45.7 +/- 6.87 mmHg. Concomitantly mean capillary PCO2 increased from 46.68 +/- 10.7 mmHg to 50.1 +/- 10.47 mmHg. Correlation of ET PCO2 compared to cap PCO2 was good (r = 0.89). One patient showed desaturation up to 72% another patient hypercapnia up to 77 mmHg. We conclude that generally speaking BAL is a safe procedure, even in high-risk patients. Complications are minor and of little consequence to the patient. However, severe unforeseen events may occur. Therefore, bronchoscopy and bronchoalveolar lavage should not be performed without availability of an intensive-care unit.

Anesthesia, General↗
PubMed1997

Chronic sinusitis refractory to standard management in patients with humoral immunodeficiencies.

Chronic refractory sinusitis is a common feature in patients with primary immunodeficiencies. The efficacy of standard therapeutic strategies is questionable. In an open trial we evaluated the efficacy of azithromycin, N-acetylcysteine and topical intranasal beclomethasone (100 microg twice daily for 6 weeks) in 16 patients with primary immunodeficiencies (median age 13.5 years, range 5-32 years). All patients suffered from chronic sinusitis despite regular immunoglobulin replacement therapy every 3 weeks. Magnetic resonance imaging (MRI) scans were performed before and after 6 weeks of treatment to evaluate morphological changes in the paranasal sinuses. Nasal swabs and washings were taken for microbial analysis and measurement of inflammatory mediators (IL-8, tumour necrosis factor-alpha (TNF-alpha), eosinophilic cationic protein (ECP)) before and post therapy. Inflammatory mediators in nasal secretions were significantly elevated in patients: IL-8 median 2436 pg/ml (range 441-5435 pg/ml), TNF-alpha 37.3 pg/ml (3.75-524 pg/ml) and ECP 33 ng/ml (1.5-250 ng/ml) versus age-matched healthy controls: IL-8 median 212 pg/ml (99-825 pg/ml), TNF-alpha 3.77 pg/ml (2.8-10.2 pg/ml) and ECP 1.5 ng/ml (1.5-14.8 ng/ml) (P < 0.0001). Inflammation of the maxillary sinuses was confirmed by MRI scans in all patients, additionally infection of the ethmoidal and frontal sinuses was recorded in five patients. Bacterial growth appeared in 11 out of 16 cultures. In spite of therapy, no improvement in sinal inflammation visualized by MRI was achieved. Moreover, no significant decrease in pathogens and levels of inflammatory mediators could be detected (IL-8 1141 pg/ml, 426-4556 pg/ml; TNF-alpha 13.9 pg/ml, 4.1-291.6 pg/ml; ECP 32.3 ng/ml, 3.7-58.4 ng/ml). Our results demonstrate that conventional management of sinusitis is of little benefit in patients with chronic refractory sinusitis with an underlying immunodeficiency. More studies are needed to test antibiotic regimens, probably combined with surgical drainage and anti-inflammatory agents.

Acetylcysteine↗
PubMed1997

[Differential cytology of bronchoalveolar lavage fluid in healthy children in comparison with children colonized by lung-specific pathogens].

BAL is increasingly used in the assessment of pulmonary diseases, however, the role in children remains to be defined. Therefore bronchoalveolar lavage (BAL) was performed on 21 healthy children in order to enable quantification and characterization of the alveolar cell populations. Reference values for cellular constituents of BAL fluid using rigid bronchoscopes are lacking-even though in children still 90% of bronchoscopies are done by rigid instruments and BAL is performed using a catheter leading into the lower lobe. The children, 12 months to 14 years of age, were lavaged adjusted to body weight with three 1 ml/kg aliquots of normal saline. Recovery was 31 +/- 12%. Each aliquot was analysed separately. The number of total cell count per milliliter was 29.8 x 10(4) (range 0.6-161 x 10(4). Percentages of different cell types of the third simple were (mean): macrophages 88.5, lymphocytes 6.4, neutrophils 4.8, eosinophils 0.1, basophils 0%. Significantly more neutrophils and less lymphocytes were found in the first as compared to the second and third sample. No age dependency was observed for either cell type. The comparison to cellularity of BAL-fluid with proven evidence of Adenovirus, Streptococcus pneumoniae, Moraxella catarrhalis and Haemophilus influenzae type B showed a marked influence of viral and bacterial germs. The study provides the first reference data on BAL differential cytology in healthy children using rigid bronchoscopy.

Adolescent↗