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Biomedical subjects

S Zielen

Publications and source records attributed to S Zielen.

At least 55 records · Page 3Linked to original sources

[Vaccination of chronically ill children].

Children with chronic diseases (hematologic, metabolic and renal diseases, children with chronic heart and lung disease, children with cerebral defects and immunodeficient patients) have an increased risk to suffer from infectious diseases and should be immunized with priority. In addition to routine immunization, these high-risk children may benefit from influenza, pneumococcal and hepatitis A vaccination. In this paper, general recommendations for vaccination in children with chronic diseases are being discussed, with emphasis on certain disease entities. Furthermore, the importance and indications for influenza and pneumococcal vaccine are being presented.

Adolescent↗

[Bronchial asthma in childhood].

Bronchial asthma in childhood is defined as a disease presenting with wheezing, dyspnea and cough on the basis of an inflammatory bronchial hyperreagibility. It is the most common chronic disease in childhood. There are a variety of causes for asthma. Certainly allergy is the most common cause in childhood but also environmental pollution is of importance. Asthmatic attacks, episodes of asthma and asthmatic cough are the most frequent clinical manifestations where as the malignant, hypoxemic asthma crisis is of special importance since its mortality is as high as 0.5-0.8/100,000. Special notice has to be taken on the evaluation of obstructive bronchitis in infancy and childhood which might be very difficult. During the past years, the use of inhalative steroids in the long term treatment has gained increasing importance also in childhood, since it could be demonstrated that side effects of clinical relevance are hardly to be expected.

Adrenergic beta-Agonists↗

[Pneumococcal vaccination after heart and liver transplantation. Immune responses in immunosuppressed patients and in healthy controls].

BASIC PROBLEM AND OBJECTIVE OF STUDY: Among other effects, therapeutic immunosuppression after organ transplantation impairs antibody formation. But because of the increased risk of infection, the efficacy of prophylactic immunization is of particular importance in patients after transplantation. For this reason the immunogenicity after immunization against pneumococcus was investigated in transplanted patients. PATIENTS AND METHODS: A 23-valent vaccine of capsular polysaccharides (Pneumovax 23) was administered to 31 patients 4-85 months after transplantation (16 hearts transplants, 15 liver transplants; age range 22-63 years). The same immunization was given to 23 healthy control subjects. The immune response was measured serologically in all groups. RESULTS: Immunization was well tolerated by all participants, and there were no infectious or systemic side effects. Mean postvaccinal global pneumococcus-specific antibody titres were comparable in the healthy and transplanted subjects (controls: 5490 U/ml, heart transplanted: 5513 U/ml, liver transplanted: 4148 U/ml; differences not significant). Analysis of individual titres for the nine most important serotypes showed comparable results for six serotypes, reduced titres being found for serotypes 3 and 8 after heart transplantation, and for serotypes 8 and 23 after liver transplantation. CONCLUSION: Safe antipneumococcal immunization is possible during therapeutic immunosuppression after heart or liver transplantation. The achieved immune response is comparable to that in healthy controls. The high efficacy of the pneumococcal vaccine, compared with other vaccines, in immunosuppressed patients may be due to T-cell dependent antibody production against polysaccharides.

Adult↗

Simple determination of polysaccharide specific antibodies by means of chemically modified ELISA plates.

A new ELISA technique using Nunc CovaLink NH microtiter plates has been developed to measure anticapsular polysaccharide specific antibodies. Capsular polysaccharide (PS) of Haemophilus influenzae type b (PRP) and pneumococcal antigens types 3, 6, 8, 14, 19, 23 were immobilized on CovaLink NH. These are modified plates with secondary amino groups bound to their surface which, in the presence of a water-soluble carbodiimide as coupling reagent, facilitate the direct binding of polysaccharides. We compared the binding characteristics of PS antigens to CovaLink NH and a conventional polystyrene ELISA plate. Checkerboard titration of PS antigens between 0.04-30 micrograms/ml clearly demonstrated that with Covalink NH optimal binding of a pooled serum from immunized donors was achieved for all PS antigens tested at a concentration of 1 microgram/ml, while binding of PS to the conventional plate was rather poor even at concentrations of 30 micrograms/ml. The CVs for the ELISA ranged from 1.1 to 2.8% for intra-assay comparisons and from 3.6 to 7.3% for inter-assay comparisons. In addition, when PRP-IgG antibodies were determined with the CovaLink NH ELISA and compared with the Farr assay an acceptable correlation ( r = 0.89, p < 0.0001) was obtained. The technique described provides a simple and sensitive tool for evaluating specific immunity to PS antigens.

Antibodies, Bacterial↗

Pulmonary alveolar microlithiasis in children.

Two asymptomatic Turkish sibs are presented, a 4-year-old boy and his 7-year-old sister, with pulmonary alveolar microlithiasis (PAM) confirmed by transbronchial lung biopsy and bronchoalveolar lavage. Chest radiographs and high resolution CT demonstrated widespread intra-alveolar calcifications in both lungs. The lesions were sharply defined and less than 1 mm in diameter. CT documented a high concentration of microliths along the bronchovascular bundles, the intralobular fissure and the (sub)pleural lung parenchyma. The combination of bronchoalveolar lavage and roentgenographic appearance in high resolution CT are characteristic and pathognomonic, and can confirm the diagnosis. The more severe changes in the elder sib and the radiographic controls suggest that the pulmonary disease may be progressive in our patients. The described family of consanguineous, unaffected parents with two affected and one healthy child confirmed the autosomal recessive inheritance of PAM (McKusick 265100). In addition, the affected girl had autosomal recessive Waardenburg-anophthalmia syndrome (McKusick 206920), raising the question of whether this is a chance occurrence or possibly a contiguous gene syndrome.

Biopsy↗

Molecular genetic haplotype segregation studies in three families with X-linked lymphoproliferative disease.

Three families with X-linked lymphoproliferative disease were studied. Affected males clinically presented with severe or fatal infectious mononucleosis, acquired hypogammaglobulinaemia, hypergammaglobulinaemia M, and malignant lymphoma including Hodgkin disease. Haplotype analysis using various DNA markers from Xq25-q27 allowed the prediction of the carrier status in females and identification of the XLP status in asymptomatic males.

Base Sequence↗

Defective CD2 T cell pathway activation in common variable immunodeficiency (CVID).

Clonal T cell expansion requires simultaneous activation of the TCR and secondary signals, e.g. CD2, CD4, CD28. Interference of CD2/CD58 interaction with MoAbs abrogates the primary immune response and antibody production. Given this functional importance of CD2/CD58 interaction for the generation of specific immune responses, we demonstrate for the first time a defective CD2 pathway activation in patients with CVID (seven children and four adults). The costimulatory effect of monocytes upon CD2-triggered proliferation was significantly impaired in CVID patients: 4.080 ct/min versus 20.769 ct/min in controls (P < 0.05). Second, IL-1, which is a strong comitogenic factor for activation via CD2 in normal T cells, showed a defective amplifier function of the CD2 pathway in most patients (median 1.714 ct/min in patients versus 17.521 ct/min in controls; P < 0.05). In addition, by using a mitogenic combination of CD2 plus CD45 MoAb, median proliferation of T cells was severely depressed in patients: 10.577 ct/min versus 34.685 ct/min in controls (P = 0.005). In conclusion, the marked dysfunction seen in responsiveness to phytohaemagglutinin (PHA) (median 24.594 ct/min in patients versus 52.229 ct/min in controls; P < 0.001) and after CD2 triggering, together with the unaffected response to TCR-CD3, suggest that the T cell deficiency in CVID is in part due to deficiencies in the CD2 pathway. Since direct activation of protein kinase C(PKC) by phorbol ester restores defective T cell responses to normal, our results suggest that an early signal-transducing defect might exist at a step proximal to PKC activation in patients with CVID.

Adolescent↗

[Reconstitution of immunoglobulin production in patients with variable immunodeficiency syndrome (CVI) by the CD40 system and IL-10].

Common variable immunodeficiency (CVI) is widely believed to involve a primary B cell defect, however, there is increasing evidence of T cell dysfunction in these patients. To test the hypothesis that B cells of patients with CVI are not defective, we investigated whether immunoglobulin production can be induced by activation through the CD40 system. Our results show that 6 of 7 children with CVI produced IgG when B cells were activated through CD40 plus IL-10. In most patients, IgM and IgA production were also induced. However, we could demonstrate that failure of immunoglobulin production was not due to a defective CD40 ligand expression on T cells. Taken together, our data show that B cells of patients with CVI are functionally normal when activated through CD40 plus IL-10. IL-10 seems to be more effective than IL-2 in restoration of immunoglobulin production in such patients.

Adolescent↗

[Hyper-IgE syndrome--two case reports of unusual complications].

The hyper-IgE syndrome (HIS) is a complex immunologic disease, caused by an unknown basic defect. We report on two cases showing complications, which have not been described so far. Case 1: A 15-year-old boy suffering from HIS developed a liver tumour with severe eosinophilic infiltration and degranulation. The transformation process of the liver histologically resembled focal nodular hyperplasia. Therapy with cyclosporine A did not lead to clinical benefit. Now, a therapeutic attempt with interferon gamma is made. Case 2: In a 17-year-old female HIS patient, multiple papillomas and ulcers of the mucous membrane, caused by infection with human papilloma virus, emerged in the ENT region. Under treatment with interferon alpha, papillomatosis could be restrained. As therapy of the hyper-IgE syndrome only symptomatic treatment has been recommended so far. Future therapies should strive for systemic immunomodulation by application of cytokines or soluble cytokine receptors like interferons or sIL-4R.

Adolescent↗

[Effectiveness of Haemophilus influenzae B-diphtheria conjugate vaccination in German children].

BACKGROUND: In 1990 the Haemophilus influenzae b-Diphtheria conjugate vaccine (Hib-D) was introduced in Germany. In addition, most children under 18 months of age failed to develop protective levels of Hib antibodies in response to systemic infections. METHODS: To evaluate the protective efficacy of the Hib-D vaccine in Germany a post marketing case-control study was performed during 1.5. 1990-30.4. 1992. Surveillance for invasive Hib-infections was maintained by pediatricians of 8 hospitals in the Rhein-Main area. The antibody responses to Hib were evaluated by ELISA at the onset (days 0-3) and during remission of disease. RESULTS: During the first year of the study 23 cases per 100,000 children of invasive Hib-infections were recorded. Of these children, 15 suffered from meningitis, 6 from epiglottitis and one from cellulitis and pericarditis respectively. None of these patients had been vaccinated except for one, who received two injections of Hib-D. Due to increased acceptance of the Hib-D vaccine we found a significant reduction of invasive Hib-infections (6 cases per 100,000 children) in the second year of the study. Again, of these children only one child was vaccinated. As expected, in all patients investigated the initial Hib antibody level was below 1 microgram/ml. The development of Hib specific immunity to invasive disease was clearly age dependent: 10 of 11 children below 18 months failed to produce any Hib antibodies (> 0.15 microgram/ml) in response to their infection. In contrast 8 of 10 children older than 18 months developed protective antibody levels to Hib. CONCLUSIONS: The incidence of serious Hib-disease has significantly decreased in Germany since the introduction of the Hib-D vaccine. Because no other Hib vaccine was licensed in Germany our data confirm efficacy and safety of Hib-D reported previously. In addition, children, who contracted disease before 18 months of age, remain susceptible to Hib and require active immunization for protection.

Antibodies, Bacterial↗

[Atypical pathogen spectrum in community-acquired infections of the lower respiratory tract in childhood].

Over a period of 14 months, we obtained nasal and throat swabs for virological examinations from patients, admitted to hospital with suspected pneumonia. Fifty-five cases of perihilar bronchitis and 103 cases of pneumonia were diagnosed based on radiological criteria. In 36% (n = 57) of the children, a pathogen could be determined by antigen ELISA. We found the following spectrum: Respiratory syncytial virus: 42%; Influenza A: 8%; Influenza B: 10%; Parainfluenza 1: 3%; Parainfluenza 2: 10%; Parainfluenza 3: 2%; Chlamydia: 17%; and Mycoplasma pneumoniae (serology only): 7%. In a control group of 59 healthy children, only one child showed a pathogen. In the past, viruses and Chlamydia have been underestimated as causes of lower respiratory tract infections. Antigen determination by ELISA has proved to be a reliable and rapid method for their detection.

Adolescent↗

[The modification of ciliary motility by salbutamol: a comparative study on subjects: oral vs inhalation administration].

15 healthy adults received for 3 days twice daily 8 mg salbutamol orally. Ciliary beat frequency was measured before, on the day of drug administration, 1 and 3 days after the beginning of the treatment, by means of nasal brush biopsy. In the same subjects ciliary beat frequency was determined before and 10 minutes following to the inhalation of 2.5 mg salbutamol with 2 ml of 0.9% saline. Findings suggest that by orally administered salbutamol a positive effect on ciliary beat frequency is yielded. The increase of frequency is more distinct in patients suffering from bronchial hyperreactivity. There was no statistically significant effect after inhalative administration of the drug.

Administration, Inhalation↗

[IgG subclass level in healthy children].

In 159 healthy German children aged 3 months to 16 years IgG subclass concentrations were measured by radial immunodiffusion using polyclonal antisera. IgG-4 levels were also determined by a monoclonal ELISA kit (Binding Site). Both methods for IgG-4 determination showed a significant correlation (r = 0.91); the WHO reference serum 67/97 was used for calibration. The mean range and percentiles for age are given. IgG subclass levels were correlated with the age of the children in the order IgG-2 greater than IgG-1 greater than IgG-4, but this was not the case for IgG-3. The normal ranges of IgG subclasses were in good agreement with those of previous studies. No IgG-4 was detected by RID in only 8.8% of all the children, but in all aged 7 years and above.

Adolescent↗

[Clinical relevance of immunoglobulin subclasses in children with chronic pulmonary diseases].

In 52 children (age 4-19.5 years; 17 female, 35 male) with chronic chest symptoms IgG-Subclass levels were measured by radial immunodiffusion techniques. Thirteen children had proven bronchiectasis, 22 chronic bronchitis and 17 steroid dependent asthma bronchiale. Cystic fibrosis, alpha-1-antitrypsin deficiency, tuberculosis and chronic foreign bodies were excluded in each patient; all of them showed normal levels of total IgG. Four children (3 with bronchiectasis, one with steroid dependent asthma bronchiale) had a complete lack if IgG4. In two children with chronic bronchitis one showed fluctuating levels of IgG2 and IgG4 and another deficiency of IgG3. All patients with an isolated IgG4 deficiency were treated with immunoglobulins. Of 3 patients with bronchiectasis one improved, two remained unchanged as shown by positive sputum cultures and of chronic chest symptoms. One patient with steroid dependent asthma bronchiale markedly improved during immunoglobulin therapy. It is concluded, that early screening of IgG subclass deficiency is indicated in all children with chronic chest symptoms.

Adolescent↗