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S Breitenstein

Publications and source records attributed to S Breitenstein.

6 recordsLinked to original sources

DNA concentrations in BAL fluid of cystic fibrosis patients with early lung disease: influence of treatment with dornase alpha.

Recombinant DNase (dornase alpha) was shown to improve lung function and reduce pulmonary exacerbations in cystic fibrosis (CF) patients, but its effects on DNA concentrations in the lower airways remain unclear at the present time. As part of the Bronchoalveolar Lavage in the Evaluation of Anti-Inflammatory Treatment (BEAT) Study, a multicenter open study to evaluate the evolution of inflammation in CF patients with early lung disease and its modulation by dornase alpha treatment, we studied DNA concentrations in the bronchoalveolar lavage (BAL) fluid of 48 CF patients with mild lung disease. After the initial BAL, 29 patients received daily treatment with 2.5 mg of dornase alpha; 19 patients served as controls. BAL was repeated after 18 months in all patients. Mean BAL fluid DNA concentrations were not different between groups at baseline (mean +/- SD, 14.1 +/- 6.9 microg/ml for controls, and 17.6 +/- 11.2 microg/ml for the dornase alpha group), but higher than previously reported for infants with CF. A weak but positive correlation (P <0.01) was observed between the percentage of neutrophils in BAL fluid and DNA levels. On reassessment after 18 months, the percentage of neutrophils was not different between the two groups, but DNA had increased in controls, whereas decreased levels were observed in treated patients (P <0.03, t-test). DNA concentrations increased by more than 10 microg/ml in 7 of 19 controls compared to 2 of 29 CF patients treated with rhDNase (P=0.01, Fisher's test). Therefore, treatment with dornase alpha over 18 months reduces DNA load in BAL fluid, which may have a positive effect on the clearance of lower airway secretions.

Adolescent↗

Incarcerated vermiform appendix in a left-sided inguinal hernia.

We report here of a patient with an incarcerated vermiform appendix occurring in a left-sided indirect inguinal hernia. Occasionally, appendices are found in a hernial sac; however, the finding of an incarcerated vermiform appendix in an inguinal hernia on the left side is very unusual and has only been previously described once. The patient suffering this rare entity underwent appendectomy and repair of the hernia and experienced an uneventful postoperative recovery. The possibility of the presence of a situs inversus, or malrotation, as an underlying cause for the observed pathology was excluded by x-ray examination.

Aged↗

Direct sputum analysis of Pseudomonas aeruginosa macrorestriction fragment genotypes in patients with cystic fibrosis.

The distribution of bacterial populations in the airways of 13 patients with cystic fibrosis who were colonized for 6-23 years with Pseudomonas aeruginosa was investigated by genotyping of bacterial chromosomes directly isolated from 21 sputa. After removal of host material from sputum by hypotonic cell lysis and repetitive washing and centrifugation steps, agarose-embedded bacterial cells were lysed, residual eukaryotic DNA separated by field inversion gel electrophoresis, and the purified bacterial chromosomes subjected to macrorestriction fragment pattern and Southern analyses. Bacterial populations consisted of a single P. aeruginosa clone in 17 sputa, of which more than one clonal variant was apparent in two SpeI fragment fingerprints. Two clones of P. aeruginosa and another species co-existed in four samples. Genomically homogeneous populations of P. aeruginosa are characteristic for chronically colonized lungs in most cases of cystic fibrosis.

Adolescent↗

Infections with Pseudomonas aeruginosa in patients with cystic fibrosis.

The lung infection with Pseudomonas aeruginosa is regarded as one of the major causes of health decline in patients with cystic fibrosis (CF). The CF host response to the persistent bacterial antigen load in the endobronchiolar lumen is characterized by a pronounced humoral response, local production of cytokines, influx of neutrophils into the lung and a protease-protease inhibitor imbalance predominantly sustained by released neutrophil elastase. CF is an autosomal recessive disease, and we could demonstrate for our local patient population that the age-dependent risk to become chronically colonized with P. aeruginosa can be differentiated by the disease-causing CFTR mutation genotype. The age-specific colonisation rates were significantly lower in pancreas sufficient than in pancreas insufficient patients. P. aeruginosa is occasionally detected in throat swabs already in infancy or early childhood in most patients although there is a lapse of several years amenable to preventive measures such as vaccination until onset of persistent colonization. The epidemiology of the infection with P. aeruginosa was investigated by quantitative macrorestriction fragment pattern analysis. The distribution and frequency of clones found in CF patients match that found in other clinical and environmental aquatic habitats, but the over-representation of specific clones at a CF clinic indicates a significant impact of nosocomial transmission for the prevalence of P. aeruginosa-positive patients at a particular center. Most patients remain colonized with the initially acquired P. aeruginosa clone. According to direct sputum analysis the majority of patients is carrying a single clonal variant at a concentration of 10(7)-10(9) CFU. Co-colonization with other species or other clones is infrequent. Independent of the underlying genotype, the CF lung habitat triggers a uniform, genetically fixed conversion of bacterial phenotype. Most CFP, aeruginosa strains become non-motile, mucoid, LPS-, pyocin- and phage-deficient, secrete less virulence determinants and shift the production of cytokines evoked in neutrophils. On the other hand, other properties such as antimicrobial susceptibility or adherence to bronchial mucins remain highly variable reflecting the capacity of P. aeruginosa to adapt to ongoing changes in the CF lung habitat.

Cystic Fibrosis↗

DNA concentration and length in sputum of patients with cystic fibrosis during inhalation with recombinant human DNase.

BACKGROUND: The clinical benefit of the administration of aerosolised recombinant human DNase (rhDNase) on pulmonary function in patients with cystic fibrosis has already been demonstrated but the biochemical action of rhDNase on DNA in bronchial secretions in vivo has not yet been investigated. METHODS: Sputum was collected from 135 patients with cystic fibrosis before and during treatment with aerosolised rhDNase and examined to ascertain DNA concentration and length by colorimetric assay and densitometry of gel separated DNA. RESULTS: Treatment with rhDNase reduced the concentration and the size of extracellular DNA in the sputum. The median interquartile range of DNA length decreased from 0.5-2.6 kbp before treatment to 0.3-1.0 kbp during treatment. CONCLUSIONS: rhDNase was delivered to the secretions and was enzymatically active in vivo.

Cystic Fibrosis↗