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Cystic Fibrosis Patients (cystic + fibrosis_patient)
Selected AbstractsSurvival After Lung Transplantation of Cystic Fibrosis Patients Infected with Burkholderia cepacia ComplexAMERICAN JOURNAL OF TRANSPLANTATION, Issue 5 2008B. D. Alexander Within the Burkholderia cepacia complex (Bcc), B. cenocepacia portends increased mortality compared with other species. We investigated the impact of Bcc infection on mortality and re-infection following lung transplant (LT). Species designation for isolates from Bcc-infected patients was determined using 16S rDNA and recA gene analyses. Of 75 cystic fibrosis patients undergoing LT from September 1992 to August 2002, 59 had no Bcc and 16 had Bcc (including 7 B. cenocepacia) isolated in the year before LT. Of the latter, 87.5% had Bcc recovered after transplantation, and all retained their pretransplant strains. Survival was 97%, 92%, 76% and 63% for noninfected patients; 89%, 89%, 67% and 56% for patients infected with Bcc species other than B. cenocepacia; and 71%, 29%, 29% and 29% for patients with B. cenocepacia (p = 0.014) at 1 month, 1 year, 3 years and 5 years, respectively. Patients infected with B. cenocepacia before transplant were six times more likely to die within 1 year of transplant than those infected with other Bcc species (p = 0.04) and eight times than noninfected patients (p < 0.00005). Following LT, infection with Bcc species other than B. cenocepacia does not significantly impact 5-year survival whereas infection with B. cenocepacia pretransplant is associated with decreased survival. [source] CFTR Rearrangements in Spanish Cystic Fibrosis Patients: First New Duplication (35kb) Characterised in the Mediterranean CountriesANNALS OF HUMAN GENETICS, Issue 5 2010María D. Ramos Summary Developments in quantitative PCR technologies have greatly improved our ability to detect large genome rearrangements. In particular oligonucleotide-based array comparative genomic hybridisation has become a useful tool for appropriate and rapid detection of breakpoints. In this work, we have analysed 80 samples (42 unknown CF alleles) applying three quantitative technologies (MLPA, qPCR and array-CGH) to detect recurrent as well as novel large rearrangements in the Spanish CF population. Three deletions and one duplication have been identified in five alleles (12%). Interestingly, we provide the comprehensive characterisation of the first duplication in our CF cohort. The new CFTRdupProm-3 mutation spans 35.7 kb involving the 5,-end of the CFTR gene. Additionally, the RNA analysis has revealed a cryptic sequence with a premature termination codon leading to a disrupted protein. This duplication has been identified in five unrelated families from Spain, France and Italy with all patients showing the same associated haplotype, which is further evidence for its likely common Mediterranean origin. Overall, considering this and other previous studies, CFTR rearrangements account for 1.3% of the Spanish CF alleles. [source] Uncovering Symptom Progression History from Disease Registry Data with Application to Young Cystic Fibrosis PatientsBIOMETRICS, Issue 2 2010Jun Yan Summary The growing availability of various disease registry data has brought precious opportunities to epidemiologists to understand the natural history of the registered diseases. It also presents challenges to the traditional data analysis techniques because of complicated censoring/truncation schemes and temporal dynamics of covariate influences. In a case study of the Cystic Fibrosis Foundation Patient Registry data, we propose analyses of progressive symptoms using temporal process regressions, as an alternative to the commonly employed proportional hazards models. Two endpoints are considered, the prevalence of ever positive and currently positive for Pseudomonas aeruginosa (PA) infection in the lungs, which capture different aspect of the disease process. The analysis of ever PA positive via a time-varying coefficient model demonstrates the lack of fit, as well as the potential loss of information, in the standard proportional hazards analysis. The analysis of currently PA positive yields results that are clinically meaningful and have not previously been reported in the cystic fibrosis literature. Our analyses demonstrate that prenatal/neonatal screening results in lower prevalence of PA infection compared to traditional diagnosis via signs and symptoms, but this benefit attenuates with age. Calendar years of diagnosis also affect the risk of PA infection; patients diagnosed in more recent cohort show higher prevalence of ever PA positive but lower prevalence of currently PA positive. [source] Plastic bronchitis as an unusual cause of mucus plugging in cystic fibrosisPEDIATRIC PULMONOLOGY, Issue 9 2009Dimas Mateos-Corral MD Abstract Cystic fibrosis patients are known to produce abundant, purulent sputum consisting mainly of DNA and cellular debris. We present a case of a CF patient with recurrent airway obstruction caused by a rare condition known as plastic bronchitis (PB). PB is characterized by the formation of casts of the airways that cause obstruction. Multiple etiologies have been proposed, but to our knowledge, no CF patient has been reported in any PB classification. Histological analysis and in-vitro testing of the cast were important factors in choosing the adequate therapy in this patient. Pediatr Pulmonol. 2009; 44:939,940. © 2009 Wiley-Liss, Inc. [source] The chemotaxis defect of Shwachman-Diamond Syndrome leukocytesCYTOSKELETON, Issue 3 2004Vesna Stepanovic Abstract Shwachman-Diamond Syndrome (SDS) is a rare autosomal recessive, multisystem disorder presenting in childhood with intermittent neutropenia and pancreatic insufficiency. It is characterized by recurrent infections independent of neutropenia, suggesting a functional neutrophil defect. While mutations at a single gene locus (SBDS) appear to be responsible for SDS in a majority of patients, the function of that gene and a specific defect in SDS neutrophil behavior have not been elucidated. Therefore, employing 2D and 3D computer-assisted motion analysis systems, we have analyzed the basic motile behavior and chemotactic responsiveness of individual polymorphonuclear leukocytes (PMNs) of 14 clinically diagnosed SDS patients. It is demonstrated that the basic motile behavior of SDS PMNs is normal in the absence of chemoattractant, that SDS PMNs respond normally to increasing and decreasing temporal gradients of the chemoattractant fMLP, and that SDS PMNs exhibit a normal chemokinetic response to a spatial gradient of fMLP. fMLP receptors were also distributed uniformly through the plasma membrane of SDS PMNs as in control PMNs. SDS PMNs, however, were incapable of orienting in and chemotaxing up a spatial gradient of fMLP. This unique defect in orientation was manifested by the PMNs of every SDS patient tested. The PMNs of an SDS patient who had received an allogenic hematopoietic stem cell transplant, as well as PMNs from a cystic fibrosis patient, oriented normally. These results suggest that the defect in SDS PMNs is in a specific pathway emanating from the fMLP receptor that is involved exclusively in regulating orientation in response to a spatial gradient of fMLP. This pathway must function in parallel with additional pathways, intact in SDS patients, that emanate from the fMLP receptor and regulate responses to temporal rather than spatial changes in receptor occupancy. Cell Motil. Cytoskeleton 57:158,174, 2004. © 2004 Wiley-Liss, Inc. [source] Unorthodox long-term aerosolized ampicillin use for methicillin-susceptible Staphylococcus aureus lung infection in a cystic fibrosis patientPEDIATRIC PULMONOLOGY, Issue 5 2009Luis Máiz MD Abstract Staphylococcus aureus is a significant cause of pulmonary colonization in cystic fibrosis (CF) patients. The optimal strategy of therapy in chronically infected patients with this pathogen is not yet established. We report a successful long-term aerosolized ampicillin treatment of a 14-year-old girl with chronic symptomatic S. aureus lung infection. Pediatr Pulmonol. 2009; 44:512,515. © 2009 Wiley-Liss, Inc. [source] Lung transplantation from a deceased donor into an Asian cystic fibrosis patientRESPIROLOGY, Issue 3 2009Hsao-Hsun HSU No abstract is available for this article. [source] Cushing's syndrome due to pharmacological interaction in a cystic fibrosis patientACTA PAEDIATRICA, Issue 9 2002KM Main Treatment of allergic bronchopulmonary aspergillosis with itraconazole is becoming more widespread in chronic lung diseases. A considerable number of patients is concomitantly treated with topical or systemic glucocorticoids for anti-inflammatory effect. As azole compounds inhibit cytochrome P450 enzymes such as CYP3A isoforms, they may compromise the metabolic clearance of glucocorticoids, thereby causing serious adverse effects. A patient with cystic fibrosis is reported who developed iatrogenic Cushing's syndrome after long-term treatment with daily doses of 800 mg itraconazole and 1600 ,g budesonide. The patient experienced symptoms of striae, moon-face, increased facial hair growth, mood swings, headaches, weight gain, irregular menstruation despite oral contraceptives and increasing insulin requirement for diabetes mellitus. Endocrine investigations revealed total suppression of spontaneous and stimulated plasma cortisol and adrenocorticotropin. Discontinuation of both drugs led to an improvement in clinical symptoms and recovery of the pituitary-adrenal axis after 3 mo. Conclusion: This observation suggests that the metabolic clearance of budesonide was compromised by itraconazole's inhibition of cytochrome P450 enzymes, especially the CYP3A isoforms, causing an elevation in systemic budesonide concentration. This provoked a complete suppression of the endogenous adrenal function, as well as iatrogenic Cushing's syndrome. Patients on combination therapy of itraconazole and budesonide inhalation should be monitored regularly for adrenal insufficiency. This may be the first indicator of increased systemic exogenous steroid concentration, before clinical signs of Cushing's syndrome emerge. [source] Novel conjugate vaccine for the prevention of Pseudomonas aeruginosa infection in cystic fibrosis patientsDRUG DEVELOPMENT RESEARCH, Issue 8 2007Kelly L. Matson Abstract The published literature evaluating the safety and immunogenicity of the polyvalent O-polysaccharide-toxin A conjugate vaccine is reviewed. Primary immunization followed by annual booster significantly reduced the incidence of chronic Pseudomonas aeruginosa lung infections (particularly mucoid phenotype strains) and extended time to infection. The findings reflected lower frequency of P. aeruginosa in sputum/throat cultures and preservation of lung function. Additionally, studies indicated higher binding affinity of vaccine-induced anti-lipopolysaccharide (LPS) compared with infection-induced anti-LPS serum immunoglobulin G antibodies, suggesting protective capacity. P. aeruginosa prophylaxis with the conjugate vaccine in cystic fibrosis patients has proved safe and useful in preventing and delaying chronic lung infection. Drug Dev Res 68:512,521, 2007. © 2008 Wiley-Liss, Inc. [source] Worldwide distribution of Pseudomonas aeruginosa clone C strains in the aquatic environment and cystic fibrosis patientsENVIRONMENTAL MICROBIOLOGY, Issue 7 2005Ute Römling Summary Highly successful bacterial clones have the ability to effectively colonize environmental niches and patients. However, the factors which determine the complex interplay between the colonization of environmental niches and patients are mainly unknown. In this study we show that Pseudomonas aeruginosa clone C strains are distributed worldwide and highly prone to infect cystic fibrosis (CF) patients in Canada, England, France and Germany. In Hanover, Germany and Vancouver, Canada, clone C strains are highly prevalent in the CF patient community, although the mechanisms of acquisition may have been different. All clone C strains showed highly related macrorestriction fragment pattern of the whole genome as visualized by pulsed-field gel electrophoresis and harboured the 102 kbp plasmid pKLC102. Comparison of three prevalent P. aeruginosa clones with different distribution between the environment and patients revealed that neither enhanced biofilm formation nor antibiotic resistance was responsible for the spread of clone C. Clone M, which was highly prevalent in the clinical environment such as sanitary facilities, lacked motility, which could explain its relatively low prevalence in CF patients. Elucidation of the mechanisms which lead to the prevalence of clone C strain in patients and the environment requires the investigation of additional phenotypes. [source] Analysis of DEFB1 regulatory SNPs in cystic fibrosis patients from North-Eastern ItalyINTERNATIONAL JOURNAL OF IMMUNOGENETICS, Issue 3 2010L. Segat Summary Cystic fibrosis (CF) transmembrane regulator protein (CFTR) gene is undoubtedly the main genetic factor involved in the modulation of CF phenotype. However, other factors such as human defensins and the genes encoding for these antimicrobial peptides have been hypothesized as possible modifiers influencing airways infection in CF patients, but their role in the pathogenesis of lung disease is still debated. Since DEFB1 gene encoding for human beta-defensin 1 displays features such as antimicrobial or chemotactic activity playing a role in inflammation, it has been considered as a possible candidate CF modifier gene. We analysed three single nucleotide polymorphisms (SNPs) in the 5,-untranslated region of the DEFB1 gene (namely g-52G>A, g-44C>G and g-20G>A) in a group of 62 CF patients from North Eastern Italy, and in 130 healthy controls, with the aim of verifying the possible association of these functional SNPs with the pulmonary phenotype of CF patients. DEFB1 SNPs have been genotyped by using Taqman allele-specific fluorescent probes and a real-time PCR platform. No significant differences were found for allele, genotype and haplotype frequencies of DEFB1 g-52G>A, g-44C>G and g-20G>A SNPs in CF patients stratified for Pseudomonas aeruginosa infection, as well as in patients with a severe and mild clinical phenotype or in patients stratified for CFTR genotypes. DEFB1 allele, genotype and haplotype frequencies of CF patients globally considered were similar to those of healthy controls. Our findings are discordant with respect to another recent study performed on CF patients coming from Southern Italy, probably due to different ethnicity of the patients. [source] Five-year prospective analysis of dietary intake and clinical status in malnourished cystic fibrosis patientsJOURNAL OF HUMAN NUTRITION & DIETETICS, Issue 4 2003J. Walkowiak Abstract Background, Poor growth and malnutrition still pose a problem in cystic fibrosis (CF). The aim of the present study was to assess nutrition, as well as clinical status, of malnourished CF patients during a nutritional care programme. Material and methods, The study comprised 38 CF patients, aged 1,18 years old. The prospective annual assessment of dietary intake and clinical status was carried out during 1994,98. Results, The energy intake increased, in comparison with recommended daily allowances, from 83.6 ± 4.8% in 1994 to 107.9 ± 4.9% in 1998. A similar tendency was observed for the percentage of energy derived from fat (30.3 ± 0.8% versus 35.1 ± 0.8%) and protein (11.4 ± 0.4% versus 13.8 ± 0.4%). In subsequent years of the study, an improvement in the fat profile of the diet (with a higher consumption of polyunsaturated fatty acids) was observed. The observed increase of vitamin A and E consumption was related chiefly to changes in the doses of supplementation. During these 5 years, an improvement in nutritional status (Z-score: height ,1.34 ± 0.13 versus ,1.08 ± 0.14 and weight ,1.40 ± 0.09 versus ,1.12 ± 0.08) and lung function (forced expiratory volume in 1 s: 75.5 ± 2.0% versus 77.8 ± 2.2%) was observed. Conclusion, The nutritional care programme resulted in stable quantitative and qualitative changes in dietary intake. Although the diet does not reach the recommended level of high-energy intake, the positive impact of increasing nutrient intake on the nutritional and clinical status of malnourished CF patients was documented. [source] Use of perfluorocarbon (fluorinert) to enhance reporter gene expression following intratracheal instillation into the lungs of Balb/c mice: Implications for nebulized delivery of plasmidsJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 9 2001Aditya Das Abstract Perfluorocarbons combine high respiratory gas dissolving capabilities with extreme chemical and biological inertness and therefore offer an attractive option as an excipient in the area of pulmonary therapeutics. Perfluorocarbons have also been shown to ,float' mucus, because of their high densities (1.9,2.5 g/mL), which may hold potential in gene delivery for cystic fibrosis patients, in terms of enhancing penetration through highly viscous mucus and thereby providing access to target epithelial cells to correct the gene defect. Additionally, their low surface tension allows for better dispersion. A commonly available perflurocarbon, heptacosafluorotributylamine (Fluorinert), was used to deliver either plasmid DNA (pDNA) alone or cationic-lipid-complexed plasmid DNA to the lungs of Balb/c mice by direct intratracheal instillation. The complexes consisted of supercoiled (SC) plasmid DNA (4.7 Kb, 0.625 mg/mL) and lipid (ethyldimyristoyl phosphatidylcholine [EDMPC]/cholesterol [1:1 mole ratio], with pDNA (3:1 mg pDNA/mM EDMPC in 20 mM Tris-HCl pH 8.0) expressing chloramphenicol acetyl transferase (CAT) or ,-galactosidase (,-Gal). pDNA alone was supplemented with 14% w/v Fluorinert. Cationic lipid/pDNA complexes were supplemented with 3, 8, and 14% w/v Fluorinert. Results showed that the CAT expression from pDNA alone was enhanced 24,× using 14% w/v Fluorinert, whereas that from the cationic-lipid-formulated pDNA was enhanced 7,× using 14% w/v Fluorinert. Immunohistochemistry showed that ,-Gal expression was primarily from epithelial cells and not from F4/80 or MAC3 antigen-stained cells (predominantly macrophages), indicating efficient delivery. © 2001 Wiley-Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 90:1336,1344, 2001 [source] Staphylococcus aureus SigB activity promotes a strong fibronectin,bacterium interaction which may sustain host tissue colonization by small-colony variants isolated from cystic fibrosis patientsMOLECULAR MICROBIOLOGY, Issue 6 2008Gabriel Mitchell Summary Genes encoding cell-surface proteins regulated by SigB are stably expressed in Staphylococcus aureus small-colony variants (SCVs) isolated from cystic fibrosis (CF) patients. Our hypothesis is that CF-isolated SCVs are locked into a colonization state by sustaining the expression of adhesins such as fibronectin-binding proteins (FnBPs) throughout growth. Force spectroscopy was used to study the fibronectin,FnBPs interaction among strains varying for their SigB activity. The fibronectin,FnBPs interaction was described by a strength of 1000 ± 400 pN (pulling rate of 2 ,m s,1), an energetic barrier width of 0.6 ± 0.1 Å and an off-rate below 2 × 10,4 s,1. A CF-isolated SCV highly expressed fnbA throughout growth and showed a sustained capacity to bind fibronectin, whereas a prototypic strain showed a reduced frequency of fibronectin-binding during the stationary growth phase when its fnbA gene was down-regulated. Reduced expression of fnbA was observed in sigB mutants, which was associated with an overall decrease adhesion to fibronectin. These results suggest that the fibronectin,FnBPs interaction plays a role in the formation of a mechanically resistant adhesion of S. aureus to host tissues and supports the hypothesis that CF-isolated SCVs are locked into a colonization state as a result of a sustained SigB activity. [source] The dual roles of AlgG in C-5-epimerization and secretion of alginate polymers in Pseudomonas aeruginosaMOLECULAR MICROBIOLOGY, Issue 4 2003Sumita Jain Summary Pseudomonas aeruginosa strains causing chronic pulmonary infections in cystic fibrosis patients produce high levels of alginate, an exopolysaccharide that confers a mucoid phenotype. Alginate is a linear polymer of d -mannuronate (M) and variable amounts of its C-5-epimer, l -guluronate (G). AlgG is a periplasmic C-5-epimerase that converts poly d -mannuronate to the mixed M+G sequence of alginate. To understand better the role and mechanism of AlgG activity, a mutant was constructed in the mucoid strain FRD1 with a defined non-polar deletion of algG . Instead of producing poly mannuronate, the algG deletion mutant secreted dialysable uronic acids, as does a mutant lacking the periplasmic protein AlgK. High levels of unsaturated ends and the nuclear magnetic resonance spectroscopy pattern revealed that the small, secreted uronic acids were the products of extensive polymer digestion by AlgL, a periplasmic alginate lyase co-expressed with AlgG and AlgK. Thus, AlgG is bifunctional with (i) epimerase activity and (ii) a role in protecting alginate from degradation by AlgL during transport through the periplasm. AlgK appears to share the second role. AlgG and AlgK may be part of a periplasmic protein complex, or scaffold, that guides alginate polymers to the outer membrane secretin (AlgE). To characterize the epimerase activity of AlgG further, the algG4 allele of poly mannuronate-producing FRD462 was shown to encode a protein lacking only the epimerase function. The sequence of algG4 has a Ser-272 to Asn substitution in a serine,threonine-rich and conserved region of AlgG, which revealed a critical residue for C-5-epimerase activity. [source] Isolation of Exophiala dermatitidis from endotracheal aspirate of a cancer patientMYCOSES, Issue 6 2006S. J. Taj-Aldeen Summary Exophiala (Wangiella) dermatitidis is a melanised (darkly pigmented) yeast-like organism that has been reported from the environment and wild animals. The organism is a frequent coloniser of lungs of patients with cystic fibrosis and causes occasional disseminated phaeohyphomycosis and fungaemia. Exophiala dermatitidis is distributed worldwide, but cerebral cases are restricted to East Asia. We report a case of 54-year-old Qatari female patient with a known history of cancer, suffering from pulmonary disorder. Culture of endotracheal aspirate revealed the growth of E. dermatitidis concomitant with Candida krusei. The final diagnosis of E. dermatitidis and attribution to genotype B was achieved by sequencing the rDNA internal transcribed spacer (ITS) region. The present case concerns a pulmonary colonisation by E. dermatitidis, similar to that commonly seen in cystic fibrosis patients. For the detection of E. dermatitidis in clinical specimens culturing techniques are required. The patient finally expired with persistent cancer and C. krusei fungaemia. Review of literature and listing of E. dermatitidis cases published after 1992 show a sharp increase in clinical cases during the 1990s. [source] Phenotypic and genotypic characterization of reference strains of the genus AspergillusMYCOSES, Issue 3-4 2001P.-M. Rath Aspergillus; Genotypisierung; Biotypisierung; SDS-PAGE; RAPD Summary. Twenty-five culture collection strains from four Aspergillus species (A. fumigatus n = 8, A. flavus n = 8, A. niger n= 4, A. nidulans n = 5) were characterized by four methods: (i) determination of patterns in an assimilation assay; (ii) protein pattern of whole mycelial cell lysates in the sodium dodecyl sulphate (SDS)-polyacrylamide gel electrophoresis (PAGE); (iii) reactivity of a pool serum obtained from cystic fibrosis patients with mycelial lysates in the immunoblot; and (iv) random amplification of polymorphic DNA (RAPD) with eight primers having arbitrary or repetitive sequences. In the assimilation assay the A. fumigatus strains showed identical patterns in contrast to the strains of the species A. flavus, A. niger, and A. nidulans, which each showed four patterns. In the SDS-PAGE no differences in the band patterns in the A. fumigatus strains were found, in contrast to the A. flavus (three patterns), A. nidulans (five patterns) and A. niger strains (two patterns). The immunoblot patterns were characteristic for each species with bands at 62 and 17/18 kDa in the A. fumigatus strains, at 51 and 18 kDa in the A. flavus strains, at 51 kDa in the A. niger strains, and at 51, 40 and 17/18 kDa in the A. nidulans strains allowing, however, no intraspecies typing. In the RAPD assay four out of eight primers gave interpretable patterns with 3,20 bands. None of the primers showed sufficient discriminatory power when used alone. However, when combining the results of two of the primers (5,-GTA TTG CCC T-3, and 5,-GAT AGA TAG ATA GAT A-3,) all strains except two A. fumigatus strains could be clearly separated from each other. It is concluded that the the RAPD assay showed the most discriminatory power in all Aspergillus species investigated. In contrast to the phenotypically similar A. fumigatus strains, the strains of the species A. flavus, A. nidulans and A. niger differed in their phenotypic characteristics. The presented data of strains from international culture collections may serve as basis for interlaboratory standardization of typing methods. Zusammenfassung. Fünfundzwanzig Aspergillus -Stämme aus internationalen Stammsammlungen (A. fumigatus n = 8, A. flavus n = 8, A. niger n = 4, A. nidulans n = 5) wurden mit vier Methoden charakterisiert: (1) Reaktionsmuster in einem Assimilationstest (2) Proteinmuster von Ganzzell-Lysaten in der SDS-PAGE (3) Reaktionsmuster eines Poolserums von Patienten mit Mukoviszidose mit Zellextrakten im Immunoblot und (4) random amplification of polymorphic DNA (RAPD) mit acht Primern zufälliger oder repetitiver Sequenz. Im Assimilationstest zeigten die A. fumigatus -Stämme identische Muster, während die Stämme der Spezies A.flavus, A. niger und A. nidulans je vier Reaktionsmuster aufwiesen. In der SDS-PAGE wiesen die A. fumigatus -Stämme identische Muster auf, während die A. flavus -Stämme drei, die A. niger -Stämme zwei, und die A. nidulans -Stämme fünf verschiedene Muster zeigten. Im Immunoblot waren die Muster für jede Spezies charakteristisch mit Banden bei 62 kDa und 17/18 kDa bei A. fumigatus, bei 51 kDa und 18 kDa bei A. flavus, bei 51 kDa bei A. niger und bei 51, 40 und 17/18 kDa bei A. nidulans. Eine Intraspezies-Typisierung gelang jedoch nicht. In der RAPD ergaben vier der acht Primer interpretierbare Muster mit 3 bis 20 Banden. Keiner der Primer alleine zeigte eine ausreichende Diskriminationskapazität. Wurden die Resultate von zwei Primern (5,-GTA TTG CCC T-3, and 5,-GAT AGA TAG ATA GAT A-3,) kombiniert, konnten mit Ausnahme von zwei A. fumigatus -Stämmen alle Isolate voneinander abgegrenzt werden. Die Ergebnisse zeigen, daß die RAPD die größte Diskriminationskapazität aufweist. Im Gegensatz zu den phänotypisch ähnlichen A. fumigatus -Stämmen unterschieden sich die Stämme der Spezies A. flavus, A. nidulans und A. niger voneinander. Die gezeigten Daten von Stämmen internationaler Stammsammlungen können als Grundlage für die Standardisierung von Typisierungsmethoden dienen. [source] Viral and atypical bacterial infections in the outpatient pediatric cystic fibrosis clinic,PEDIATRIC PULMONOLOGY, Issue 12 2006Hanne Vebert Olesen MD Abstract Background Respiratory viral and atypical bacterial infections are associated with pulmonary exacerbations and hospitalisations in cystic fibrosis patients. We wanted to study the impact of such infections on children attending the outpatient clinic. Methods Seventy-five children were followed for 12 months at regular clinic visits. Routine sputum/laryngeal aspirations were tested with PCR for 7 respiratory viruses. Antibodies against C. pneumoniae, M. pneumoniae and B. pertussis were measured every 3,4 months. FEV-1, FEF25,75 and specific airway resistance, "viral" symptoms and bacterial culture were recorded. Results Ninety-seven viral and 21 atypical bacterial infections were found. FEV-1 was significantly reduced during viral infection (,12.5%, p=0.048), with the exception of rhinovirus infection. A small change in FEV-1 (,3%) was seen during atypical bacterial infection (p=0.039). Viral and atypical bacterial infections caused no change in type and frequency of bacterial culture. Positive predictive value of "viral symptoms" was low (0.64%). Eight patients received "unnecessary" antibiotics because of viral symptoms. Conclusions Some viral infections and atypical bacterial infections affect FEV-1 acutely. Viral infections did not precipitate bacterial infection or change of colonisation. Clinical symptoms failed to diagnose viral infection accurately. Routine surveillance for virus or atypical bacteria seems not to be justified in this patient category. Pediatr Pulmonol. 2006; 41:1197,1204. © 2006 Wiley-Liss, Inc. [source] Pulmonary exacerbations in cystic fibrosis,PEDIATRIC PULMONOLOGY, Issue 5 2004Harvey R. Rabin MD Abstract The clinical characteristics most relevant to the decision to treat for a pulmonary exacerbation with antibiotics in cystic fibrosis patients were determined. Variables including age, increased cough frequency and sputum production, new crackles and wheezing, asthma, symptomatic sinusitis, hemoptysis, decreased lung function, weight loss, and new acquisition of Pseudomonas aeruginosa were collected in a large prospective multicenter database (Epidemiologic Study of Cystic Fibrosis). During a 12-month baseline period, data from 11,692 patients were compared with data collected during the subsequent 6-month study period. Because pulmonary function assessments were unavailable for patients <6 years of age, separate analyses were done for those <6 and ,6 years of age. The outcome of interest was any antibiotic treatment in the 6-month study period reported as indicated for an exacerbation. Characteristics with the most discriminatory power were determined using stepwise multiple logistic regression. For patients <6 years of age, the strongest independent associations with treatment for a pulmonary exacerbation were new crackles, increased cough frequency, decline in weight, and increased sputum production. For those patients ,6 years of age, the strongest independent associations were a relative decrease in percent predicted forced expired volume in 1 sec, increased cough frequency, new crackles, and hemoptysis. The presence of three or more of these key characteristics was strongly associated with the occurrence of a treated exacerbation. The reproducibility of the model over time was confirmed by application to a subsequent set of data. This model has potential for use as an outcome measure in clinical trials, and to assist in treatment decisions for individual patients. Pediatr Pulmonol. 2004; 37:400,406. © 2004 Wiely-Liss, Inc. [source] Is FEV1 < 30% an indicator for lung transplantation in cystic fibrosis patients?PEDIATRIC TRANSPLANTATION, Issue 5 2001Marlyn S. Woo MD No abstract is available for this article. [source] Analysis of the periplasmic proteome of Pseudomonas aeruginosa, a metabolically versatile opportunistic pathogenPROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 7 2009Francesco Imperi Abstract The Gram-negative bacterium Pseudomonas aeruginosa is a main cause of infection in hospitalized, burned, immunocompromised, and cystic fibrosis patients. Many processes essential for P. aeruginosa pathogenesis, e.g., nutrient uptake, antibiotic resistance, and virulence, take place in the cell envelope and depend on components residing in the periplasmic space. Recent high-throughput studies focused on P. aeruginosa membrane compartments. However, the composition and dynamics of its periplasm remain largely uncharacterized. Here, we report a detailed description of the periplasmic proteome of the wild-type P. aeruginosa strain PAO1 by 2-DE and MALDI-TOF/TOF analysis. Three extraction methods were compared at proteome level in order to achieve the most reliable and comprehensive periplasmic protein map. A total of 495 spots representing 395 different proteins were identified. Most of the high intensity spots corresponded to periplasmic proteins, while cytoplasmic contaminants were mainly detected among faint spots. The majority of the identified periplasmic proteins is involved in transport, cell-envelope integrity, and protein folding control. Notably, more than 30% still has an unpredicted function. This work provides the first overview of the P. aeruginosa periplasm and offers the basis for future studies on periplasmic proteome changes occurring during P. aeruginosa adaptation to different environments and/or antibiotic treatments. [source] Achromobacter xylosoxidans respiratory tract infections in cystic fibrosis patients,APMIS, Issue 9 2008TIZIANA RASO Achromobacter xylosoxidans is a ubiquitous Gram-negative non-fermenting rod, recently characterized as an emerging pathogen in cystic fibrosis (CF) patients. Its pathogenic potential and prevalent transmission routes are still unclear. This study investigated the PFGE genetic pattern and antimicrobial resistance profile of 42 A. xylosoxidans isolates obtained over 4 years from the respiratory tract of 22 CF patients. By genotypic analysis, 31 isolates were attributed to 8 distinct PFGE patterns (A,H), whereas 11 isolates were not typable because their DNA was not restricted by XbaI and DraI restriction enzymes. The majority of the isolates showed multidrug resistance; imipenem and piperacillin were the most active drugs. During the course of A. xylosoxidans chronic infection forced expiratory volume and body mass index values were not significantly lowered. The demonstration of widespread antibiotic resistance underscores the importance of antibiogram-directed therapy. Our data suggest that in some cases the infection may have been acquired from other patients or from a common contaminated source. Further epidemiological studies may be important for the design and implementation of prophylactic measures in CF centers. [source] Mycobacterium abscessus: an emerging rapid-growing potential pathogen,APMIS, Issue 5 2006Review article Mycobacterium abscessus is the most pathogenic and chemotherapy-resistant rapid-growing mycobacterium. It is commonly associated with contaminated traumatic skin wounds and with post-surgical soft tissue infections. It is also one of the mycobacteria that are most often isolated from cystic fibrosis patients. It is essential to differentiate this species from the formerly indistinct "M. chelonae -complex", as chemotherapy is especially difficult in M. abscessussenso strictu. Clarithromycin or azithromycin are the only regular oral antimycobacterial agents with an effect on M. abscessus, and should preferably be supplemented with other drugs since long-term monotherapy may cause resistance. Amikacin is a major parenteral drug against M. abscessus that should also be given in combination with another drug. The recently introduced drug tigecycline may prove to be an important addition to chemotherapy, but has yet to be fully clinically evaluated as an antimycobacterial agent. Surgery can be curative, or at least helpful, in the healing of M. abscessus infection, and if conducted, it should include the removal of all foreign or necrotic material. There is increasing awareness of M. abscessus as an emerging pathogen. [source] Serum concentrations of GM-CSF and G-CSF correlate with the Th1/Th2 cytokine response in cystic fibrosis patients with chronic Pseudomonas aeruginosa lung infection,APMIS, Issue 6 2005CLAUS MOSER The inflammation in cystic fibrosis (CF) patients with chronic Pseudomonas aeruginosa lung infection is dominated by polymorphonuclear neutrophils (PMNs). There seems to be a relationship between the PMN-dominated inflammation, pronounced antibody production and a Th2-dominated response. Apart from mobilizing monocytes and PMNs from the bone marrow, GM-CSF, G-CSF and IL-3 select subsets of dendritic cells, which subsequently induce distinct Th responses. Therefore, the present study examines the correlation between the mobilizing cytokines in serum and the Th responses. The IFN-, and IL-4 production by peripheral blood mononuclear cells, and the concentrations of GM-CSF and G-CSF in serum as well as lung function, were determined in 37 CF patients with and 6 CF patients without chronic P. aeruginosa lung infection. The GM-CSF/G-CSF ratio correlated both with the IFN-, production and good lung function. In addition, an inverse correlation between IL-3 and IFN-, was observed. The results indicate involvement of endogenous GM-CSF, G-CSF and IL-3 in the skewed Th response in CF, and change to a Th1-dominated response might be achieved with GM-CSF treatment. [source] The immune response to chronic Pseudomonas aeruginosa lung infection in cystic fibrosis patients is predominantly of the Th2 typeAPMIS, Issue 5 2000Claus Moser Most cystic fibrosis (CF) patients with chronic Pseudomonas aeruginosa lung infection have a persistent acute type lung inflammation dominated by polymorphonuclear neutrophils (PMN) and a pronounced antibody response against P. aeruginosa. We speculated whether this immune response in CF is of the Th2 type and whether a change to a Th1 type immune response could improve the prognosis. Therefore, we studied 14 CF patients with (CF +P) and 14 CF patients without (CF ,P) chronic P. aeruginosa lung infection. The specific production of interferon-gamma (IFN-,) and interleukin-4 (IL-4) by peripheral blood mononuclear cells was determined. Cells from CF +P patients had lower IFN-, (p<0.05) and higher IL-4 (p<0.005) production as compared to cells from CF -P patients. Furthermore, a positive correlation between IFN-, production and lung function was found (FVC: Rho=0.637; p<0.03; FEV1: Rho=0.524; p<0.07). We conclude that a Th2 type immune response is most frequent in CF patients with chronic P. aeruginosa lung infection, and the patients with a Th1-dominated immune response had the best lung function. The clinical implication is that a change to a Th1 type immune response might improve the prognosis in these patients. [source] Cloning, expression, purification, crystallization and preliminary crystallographic studies of BceC, a UDP-glucose dehydrogenase from Burkholderia cepacia IST408ACTA CRYSTALLOGRAPHICA SECTION F (ELECTRONIC), Issue 3 2010Joana Rocha Bacteria of the Burkholderia cepacia complex (Bcc) have emerged as important opportunistic pathogens, establishing lung infections in immunocompromised or cystic fibrosis patients. Bcc uses polysaccharide-biofilm production in order to evade the host immune response. The biofilm precursor UDP-glucuronic acid is produced by a twofold NAD+ -dependent oxidation of UDP-glucose. In B. cepacia IST408 this enzymatic reaction is performed by the UDP-glucose dehydrogenase BceC, a 470-residue enzyme, the production and crystallization of which are described here. The crystals belonged to the orthorhombic space group P212121 and contained four molecules in the asymmetric unit. Their crystallographic analysis at 2.09,Å resolution and a molecular-replacement study are reported. [source] Partly Functional Temporal Process Regression with Semiparametric Profile Estimating FunctionsBIOMETRICS, Issue 2 2009Jun Yan Summary Marginal mean models of temporal processes in event time data analysis are gaining more attention for their milder assumptions than the traditional intensity models. Recent work on fully functional temporal process regression (TPR) offers great flexibility by allowing all the regression coefficients to be nonparametrically time varying. The existing estimation procedure, however, prevents successive goodness-of-fit test for covariate coefficients in comparing a sequence of nested models. This article proposes a partly functional TPR model in the line of marginal mean models. Some covariate effects are time independent while others are completely unspecified in time. This class of models is very rich, including the fully functional model and the semiparametric model as special cases. To estimate the parameters, we propose semiparametric profile estimating equations, which are solved via an iterative algorithm, starting at a consistent estimate from a fully functional model in the existing work. No smoothing is needed, in contrast to other varying-coefficient methods. The weak convergence of the resultant estimators are developed using the empirical process theory. Successive tests of time-varying effects and backward model selection procedure can then be carried out. The practical usefulness of the methodology is demonstrated through a simulation study and a real example of recurrent exacerbation among cystic fibrosis patients. [source] Differential modulation of innate immune cell functions by the Burkholderia cepacia complex: Burkholderia cenocepacia but not Burkholderia multivorans disrupts maturation and induces necrosis in human dendritic cellsCELLULAR MICROBIOLOGY, Issue 10 2008Kelly L. MacDonald Summary Burkholderia cepacia complex (BCC) bacteria cause pulmonary infections that can evolve into fatal overwhelming septicemia in chronic granulomatous disease or cystic fibrosis patients. Burkholderia cenocepacia and Burkholderia multivorans are responsible for the majority of BCC infections in cystic fibrosis patients, but B. cenocepacia is generally associated with a poorer prognosis than B. multivorans. The present study investigated whether these pathogens could modulate the normal functions of primary human monocyte-derived dendritic cells (DCs), important phagocytic cells that act as critical orchestrators of the immune response. Effects of the bacteria on maturation of DCs were determined using flow cytometry. DCs co-incubated for 24 h with B. cenocepacia, but not B. multivorans, had reduced expression of costimulatory molecules when compared with standard BCC lipopolysaccharide-matured DCs. B. cenocepacia, but not B. multivorans, also induced necrosis in DCs after 24 h, as determined by annexin V and propidium iodide staining. DC necrosis only occurred after phagocytosis of live B. cenocepacia; DCs exposed to heat-killed bacteria, bacterial supernatant or those pre-treated with cytochalasin D then exposed to live bacteria remained viable. The ability of B. cenocepacia to interfere with normal DC maturation and induce necrosis may contribute to its pathogenicity in susceptible hosts. [source] Nasal polyps in patients with and without cystic fibrosis: a differentiation by innate markers and inflammatory mediatorsCLINICAL & EXPERIMENTAL ALLERGY, Issue 4 2005S. Claeys Summary Background The dysfunction of the mucosal interface of the upper respiratory tract in cystic fibrosis (CF) patients is clinically visible by the development of nasal polyps (NP) at a young age. Innate defence markers and inflammatory mediators in NP from patients with CF were compared with non-cystic fibrosis nasal polyps (non-CF-NP) to determine a possible different immunological background in macroscopically similar tissue. Methods Surgical samples were obtained from patients with non-CF-NP, cystic fibrosis patients with nasal polyps (CF-NP) and control patients (CO). With real time PCR, the mRNA expression of human , defensins (HBD) 2 and 3, toll-like receptors (TLR) 2 and 4 and the macrophage mannose receptor (MMR) were measured. On homogenates of the surgical samples eotaxin, myeloperoxidase (MPO), IL-5 and IL-8 protein content was measured using commercial ELISA kits; IgE and eosinophilic cationic protein (ECP) were measured by the Unicap system. Results In CF-NP we found a statistically significant higher mRNA expression of HBD 2 compared with non-CF-NP and CO and of TLR 2 compared with non-CF-NP. In the non-CF-NP group, MMR mRNA expression was significantly elevated compared with CO and CF-NP. For TLR 4 mRNA expression no statistically significant differences were found between groups. IL-5 was below detection level in all CO and CF-NP, but was measurable in 80% of the non-CF-NP. MPO and IL-8 concentrations were significantly higher in CF-NP compared with CO and non-CF-NP, whereas ECP, eotaxin and IgE were significantly higher in the non-CF-NP group. Conclusions We here demonstrate that CF-NP and non-CF-NP not only differ in terms of inflammatory mediator profile, but also in terms of innate markers. [source] Liver disease as risk factor for cystic fibrosis-related diabetes developmentACTA PAEDIATRICA, Issue 5 2007L Minicucci Abstract Aim: To evaluate clinical and genetic factors, besides pancreatic insufficiency, associated with increased risk of cystic fibrosis-related diabetes. Methods: Case-control (1:1) study on 138 cystic fibrosis patients. Data were collected on gender, age at diagnosis, reason for cystic fibrosis diagnosis, family history of type 1 or 2 diabetes mellitus, pre-existing severe liver disease, and class of cystic fibrosis transmembrane regulation mutation. Moreover, information was obtained on lung involvement and degree of exocrine pancreatic insufficiency evaluated 1 year before the diagnosis of cystic fibrosis-related diabetes in patients and age-matched controls. Results: Compared to controls, patients with cystic fibrosis-related diabetes had a higher probability of having already been diagnosed with liver disease (16.7% versus 1.7%, OR = 11.6, 95% CI 1.43,93.0). Moreover, in the year before diabetes onset, cases had slightly worse pulmonary function compared to controls (FEV1= 58.4 ± 27% predicted versus 67.4 ± 21% predicted; p = 0.05). No significant effects related to the other factors considered were found. Conclusion: Severe liver disease was found to significantly increase the risk of developing cystic fibrosis-related diabetes. Patients with liver disease should be scheduled for earlier diabetes screening in order to identify and possibly treat glucose intolerance. [source] | ||||||||||||||||||||||||||||