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Biomedical subjects

M Zach

Publications and source records attributed to M Zach.

At least 19 recordsLinked to original sources

Detection of an allergen in dog dander that cross-reacts with the major cat allergen, Fel d 1.

BACKGROUND: A considerable proportion of animal-allergic patients are sensitized to both cat and dog allergens but knowledge about cross-reactive allergens in cat and dog dander is limited. OBJECTIVE: To investigate whether dog dander contains an allergen that cross-reacts with the major cat allergen, Fel d 1. METHODS: Recombinant Fel d 1 with the same immunological properties as natural Fel d 1 was used for quantitative (CAP) IgE competition experiments performed with sera obtained from cat-allergic patients (n=36). A Fel d 1 cross-reactive dog allergen was characterized by one- and two-dimensional immunoblotting using rFel d 1 for IgE inhibition experiments and with monospecific, polyclonal rabbit anti-recombinant Fel d 1 antibodies. RESULTS: In 25% of Fel d 1-reactive cat-allergic patients, more than 50% inhibition of IgE reactivity to dog allergens was achieved with recombinant Fel d 1. An Fel d 1 cross-reactive 20 kDa allergen with a pI of approximately 3.4 was detected in dander extracts of several different dog breeds. CONCLUSION: This is the first report demonstrating the presence of an Fel d 1-like allergen in dog dander extracts, which may be responsible for double positivity to cat and dog in serology. However, the clinical relevance of this cross-sensitization needs to be confirmed. These results are important for the diagnostic and therapeutic use of dog dander allergen extracts.

Adult↗

Interstitial lung disease in children: a multicentre survey on diagnostic approach.

Chronic interstitial lung disease (ILD) is a rare disorder in the paediatric age group, with a poor prognosis. The diagnostic approach to ILD is based on more or less invasive methods. This study was implemented to verify which methods are the most often used in children. Questionnaires (333) were sent to members of the European Respiratory Society Paediatric Assembly belonging to 187 European and non-European centres. Questions concerned the use of noninvasive diagnostic methods, e.g. history taking, physical examination, routine laboratory tests, respiratory function tests and radiology (chest radiography, high-resolution computed tomography (HRCT)), and the use of invasive techniques such as bronchoalveolar lavage (BAL), transbronchial biopsy (TBB), open lung biopsy (OLB), video-assisted thoracoscopic biopsy (VAT) and HRCT with fine-needle aspiration biopsy (FNAB). Thirty eight centres returned the questionnaires and 131 children with ILD were studied. A diagnosis of ILD was achieved in five (3.8%) patients using noninvasive techniques alone. Using the various biopsy methods, histological assessment was performed on a total of 98 (74.8%) children. The most frequently used invasive technique both alone and in combination was BAL (83, 63.3%), followed by OLB (64, 48.8%), TBB (26, 19.8%) and VAT (11, 8.4%); FNAB was used in one patient. In conclusion a diagnosis of interstitial lung disease was reached on the basis of aetiological and/or histological findings in 117 (89%) of the 131 patients studied.

Adolescent↗

Cytomegalovirus associated neonatal pneumonia and Wilson-Mikity syndrome: a causal relationship?

Lung injury caused by intrauterine inflammation has recently been strongly implicated in the pathogenesis of Wilson-Mikity syndrome (WMS). This article supports this theory by suggesting a causative role of intrauterine cytomegalovirus (CMV) infection for the development of WMS. A male premature infant, born at 33 weeks of gestational age, developed chronic lung disease compatible with WMS and diagnostic evaluation was positive for CMV infection. High-resolution computed tomography scan and lung histology revealed typical features of WMS in association with signs of interstitial pneumonia. CMV was found in urine, breastmilk, bronchoalveolar lavage material and lung tissue from open lung biopsy. Follow-up after treatment with ganciclovir and steroids showed resolving lung disease at the age of 6, 10 and 16 months, with lung function signs of mild obstruction. Assuming that a chance coexistence of cytomegalovirus pneumonia and Wilson-Mikity syndrome is rather unlikely, it is possible that intrauterine cytomegalovirus infection caused a pattern of lung injury consistent with Wilson-Mikity syndrome. Further cases of Wilson-Mikity syndrome should be investigated as to a possible role of congenital infection.

Cytomegalovirus Infections↗

HRCT features in a 5-year-old child with follicular bronchiolitis.

High-resolution CT (HRCT) is the most sensitive radiographic method to image small airways disease. We discuss the HRCT features of follicular bronchiolitis in a 5-year-old boy and correlate them with the histopathological findings. The changes described include centrilobular nodules, bronchiectasis and bronchiolectasis, branching opacities and areas of reduced lung attenuation.

Biopsy↗

Pulmonary infection due to Mycobacterium gordonae in an adolescent immunocompetent patient.

We report the case of 17-year-old male adolescent immunocompetent patient with an operated transposition of the great arteries after the Mustard technique admitted to our hospital because of a cough and hemoptysis. Two nodules and an area of ground glass appearance located in the lower lobe of the left lung were diagnosed by ultrafast computed tomography (UF-CT) after ruling out cardiovascular complications. The gastric aspirate revealed acid-fast bacilli despite a repeatedly negative tuberculin skin test identified as Mycobacterium gordonae by the Gen-Probe Rapid Diagnostic Test. After an initial standard antimycobacterial therapy with isoniazid, rifampin and pyrazinamide the therapy was changed to clarithromycin and after a treatment course of 14 days, the UF-CT revealed a normal scan of both lungs. The case described suggests that one has to consider M. gordonae as a rare cause of infection even in immunocompetent patients.

Adolescent↗

Use of the paediatric bronchoscope, flexible and rigid, in 51 European centres.

We have undertaken a survey to establish current practices and differences in the use of bronchoscopes in children in European centres. A questionnaire was sent to all 220 members of the Paediatric Assembly of the European Respiratory Society (ERS). The questions concerned the following points: indications for bronchoscopy; site of bronchoscopy; type of sedation; any oxygen supplementation during the procedure; number of procedures performed in the previous 12 months; number of procedures performed in the neonatal intensive care unit; number of bronchoalveolar lavages (BALs); side-effects during and after the procedures; and diagnostic yield. Fifty one European centres (40.8% of the European centres contacted) took part in the study. A total of 7,446 bronchoscopies had been performed in the last 12 months: 4,587 using the flexible bronchoscope and 2,859 using the rigid bronchoscope. At centres using only the fibreoptic bronchoscope, the most frequent indication was "recurrent/persistent pneumonia" (17%); at centres using only the rigid bronchoscope, it was "foreign body inhalation" (36.7%); at centres using both methods, the most frequent indication was "other indications" (23.9%). In 12 months, 2,231 BALs were performed: 1,419 in immunocompetent children and 812 in immunocompromised patients. In centres using only the fibreoptic bronchoscope, the highest yield was for "stridor" (81%); in centres using only the rigid bronchoscope, the highest yield was for "persistent atelectasis" (68%); and in centres using both instruments, it was for "foreign body inhalation" (93%). The results of the study suggest that bronchoscopy in children is now a well-established procedure at several European centres, while others are just beginning to use this technique.

Bronchoalveolar Lavage Fluid↗

Effective radiochemotherapy with cisplatin and etoposide for the management of patients with locally inoperable and metastatic esophageal carcinoma.

BACKGROUND: The limited therapeutic value of available chemotherapeutic drug combinations in patients with advanced esophageal carcinoma, the documented synergistic activity of etoposide and cisplatin, which might be further enhanced by simultaneous radiotherapy, and promising though only preliminary therapeutic results with this combination regimen have stimulated the present Phase II trial. The specific aim of the study was to determine the efficacy and tolerance of this combined treatment approach in previously untreated patients with either local regional unresectable or metastatic esophageal carcinoma. METHODS: Thirty patients with Stage IIIB or IV squamous cell or adenocarcinoma of the esophagus were entered in this study between October 1992 and November 1994. Chemotherapy was comprised of cisplatin, 30 mg/m2, combined with etoposide, 120 mg/m2, both given intravenously on 4 consecutive days. Treatment courses were repeated every 4 weeks. Radiation therapy (total dose, 5000 centigray) was administered concurrently during the 2nd and 3rd chemotherapy course, during which both drugs were given with a 25% dose reduction. RESULTS: After a median of 4 chemotherapeutic treatment courses (range, 1 to 6 courses), 3 patients had a complete response for 5, 8, and 11.5 months, and 9 patients had a partial response lasting for a median duration of 5.3 months (range, 2.5 to 7.5 months), yielding an overall response rate of 40% (95% confidence interval, 23-59%). The response rates tended to be higher for squamous cell carcinomas (11 of 23; 48%) than for adenocarcinomas (1 of 7), as well as for locoregional disease (7 of 13; 54%) than for patients with disseminated disease (5 of 17; 29%). For the entire study population, median time to progression was 5.4 months (range, 1.5 to 13.5 months), and median survival was 9.2 months (range, 1.5 to 28 months), with 4 patients still alive at the time of this report. Clinically, the most important toxic effect was myelosuppression. Grade 3-4 granulocytopenia occurred in 16 patients (53%), severe thrombocytopenia in 11 (37%), and Grade 3 anemia in 5 (17%). There were four hospitalizations among three patients for the management of fever during neutropenia. Other nonhematologic side effects were generally mild or modest, and most commonly included nausea/emesis (40%), mucositis and/or esophagitis during simultaneous radiotherapy (40%), and alopecia (43%). CONCLUSIONS: Combined radiochemotherapy with cisplatin and etoposide is active against advanced esophageal carcinoma, but can be associated with significant hematotoxicity. Although the therapeutic potential of this regimen appears to be comparable to other, conventional fluorouracil/cisplatin-based chemotherapy, less toxic and more effective regimens need to be identified.

Adenocarcinoma↗

Spirometric reference values for white European children and adolescents: Polgar revisited.

We analyzed six spirometric data sets collected in the Netherlands, Austria, the United Kingdom, Spain, and Italy. The objectives were to establish whether (1) it was possible to describe spirometric indices from childhood to adulthood, taking into account the adolescent growth spurt, and (2) there are systematic differences in ventilatory function between children and adolescents in different parts of Western Europe. The study comprised 2,269 girls and 3,592 boys, aged 6-21 years. The range in standing height was 110-185 in girls, 110-205 in boys. The model applicable to all data sets was ln FVC or ln FEV1 = a + (b + c x A) x H, where H = standing height and A = age; this model prevents the phase shift between the adolescent growth spurt in length and lung volume from leading to an age-dependent bias in predicted values. There was surprising agreement between most of the data sets; systematic differences are probably due to technical factors arising from ATPS-BTPS corrections and from defining the end of breath with pneumotachometer systems. Taking those into account, prediction equations for FVC, FEV1, and FEV1%FVC were developed with "lower limits of normal" which should be applicable to children and adolescents of European descent. It is proposed that the approach of analyzing available data sets should also be applied to other ventilatory indices, data collected in adults and elderly subjects, or in other ethnic groups, and that an international data base be set up to that end.

Adolescent↗

Molecular and clinical findings in Austrian cystic fibrosis patients with mutations in exon 11 of the CFTR gene.

In order to determine the heterogeneity of mutations in exon 11 of the cystic fibrosis transmembrane conductance regular (CFTR) gene in Austrian cystic fibrosis (CF) patients, we analysed 207 non-delta F508 chromosomes by direct sequencing of PCR-amplified genomic DNA. A total of four previously described point mutations present on 14/207 (6.8%) non-delta F508 chromosomes were detected: G542X, G551D, R553X, and R553Q. The second CF mutation was delta F508 in most patients, W1282X (a nonsense mutation in exon 20) in one and a currently unknown non-delta F508 mutation in another case. One patient was documented to be homozygous for G542X. The proportion of non-delta F508 chromosomes among total CF chromosomes is 45% in Austria and 32% in the world population. In our population the mutations G542X, G551D, and R553X were found on 3.9% (1.7%), 1.9% (0.9%) and 0.5% (0.2%) of non-delta F508 chromosomes (of total CF chromosomes), respectively. The average worldwide frequencies of these mutations are higher: 7.1% (2.4%), 4.8% (1.6%), 2.1% (0.7%) of non-delta F508 chromosomes (of total CF chromosomes screened), respectively. A comparison of the allele frequencies in Austria with those detected in neighbouring countries reveals some notable differences. In a subsequent retrospective analysis we found that all nucleotide changes, identified by direct sequencing, can be detected by denaturing gradient gel electrophoresis (DGGE). The lack of any false positive or false negative result suggests that DGGE is a convenient and reliable screening method for point mutations.

Adolescent↗

[Flexible fiberoptic bronchoscopy in pediatrics--an analysis of 420 examinations].

Over a 4-year period we performed 420 endoscopic investigations in 262 patients (aged 1 day-26 yrs) under sedation and local anesthesia, using several different flexible instruments; repeat procedures were performed in 58 children. The most common indications for diagnostic endoscopy were tracheostomy evaluation (27.1%), non-specific chest x-ray changes (13.8%), stridor (12.4%), atelectasis (7.9%), and the sampling of airway secretions or cells by bronchoalveolar lavage (5.5%); indications for 17 therapeutic endoscopies (4%) included the removal of airway secretions and mucus plugs, and aid in difficult intubations. Bronchomalacia (46X), tracheomalacia (41X), obstructing granulation tissue (36X), and laryngomalacia (35X) were the most common diagnoses; in addition, subglottic stenosis was found in 13, a subglottic hemangioma in 5, vocal cord paralysis in 5 and an endobronchial foreign body in 5 children. Findings were normal in 39 (9.3%) cases. A relevant diagnosis was established on 73.7% of all investigations. The diagnostic yield was highest in patients with stridor, persistent wheezing, atelectasis, non-specific chest x-ray changes, and in patients with a tracheostomy. The success rate of therapeutic procedures was 70.6%. Minor complications occurred in altogether 4.3% of cases; all were completely and rapidly reversible. Flexible fiberoptic bronchoscopy is a safe and valuable diagnostic and therapeutic tool for the management of infants and children with respiratory problems.

Adolescent↗

[Measuring lung volume in the infant--problems with the nitrogen washout method].

The open-circuit nitrogen washout technique, as developed by Gerhardt et al., seems to be ideally suited for assessing functional residual capacity (FRC) in infants. By performing this measurement in over 250 infants throughout the last three years, we gathered considerable practical experience of our own, but also encountered several methodological problems, which, so far, have received only little attention by the relevant literature, or have remained unresolved altogether. Our data illustrate the importance of reproducing the infant's own breathing rate and tidal volume when calibrating the system. The choice of the O2-background-flow should be based on the individual peak tidal inspiratory flow, as derived from the tidal flow-volume loop. The importance of maintaining this O2-background-flow unchanged between calibration and measurement is also demonstrated. The question, at which N2-concentration the measurement should be terminated, has remained unresolved. Diffusion of N2 from blood and tissue into the alveolar space is responsible for considerable noise. Our own measurements resulted in widely differing FRC-values for different N2-target-concentrations; these differences seem to increase with more severe bronchial obstruction. Finally, there remains the question, how long the minimal interval between two subsequent measurements should be. In conclusion, these unresolved questions have to be answered in relevant prospective studies, before recommending this technique for routine clinical application.

Airway Obstruction↗

Late-onset miliary pneumonitis after near drowning.

We report a 7-year-old pediatric patient with an apparently self-limiting, subacute miliary pneumonitis that occurred 6 weeks after a near-drowning accident in shallow, muddy water. After biopsy, histological examination revealed aspirated foreign bodies (algae and pollen grains) in the affected lung areas and a foreign body reaction in the form of a granulomatous inflammation. The lack of any detectable infectious agents suggested a causative role of these aspirated algae and pollen grains in the development of lung disease.

Biopsy↗

High-resolution computed tomography of the lungs in irradiated breast cancer patients.

Fifty-five breast cancer patients underwent high-resolution computed tomography (HRCT) of the lungs before, 8-12 weeks, 6, 9 and 12 months after adjuvant radiotherapy. During the follow-up time, 17 of them (30%) were found to develop minimal parenchymal alterations in the irradiated lung volume by HRCT evidence. The parenchymal alterations were classified by five scores. Scores 1-4 described chronic radiologic changes, score 5 acute radiologic changes. Three patients presented with acute radiologic changes (alveolar filling) within the first 3 months after radiotherapy. Two did not show any abnormalities at later follow-ups. Chronic radiologic fibrosis (15 patients) was not seen before the sixth month post irradiation except in 2 cases. There was no correlation between acute changes and chronic fibrosis. None of these changes were seen at a lung dose of less than 40 Gy. The appearance of interstitial pulmonary lesions secondary to breast irradiation was comparable to that of other interstitial diseases of the lungs. Chest radiographs were normal in all patients. None of the 55 patients presented with clinical symptoms.

Adult↗