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Ladina Joos

Publications and source records attributed to Ladina Joos.

14 recordsLinked to original sources
PubMed2006

Pulmonary infections diagnosed by BAL: a 12-year experience in 1066 immunocompromised patients.

Bronchoalveolar lavage (BAL) is a useful tool in the diagnosis of pulmonary infections in immunocompromised patients. We aimed to compare the spectrum of infectious pulmonary complications diagnosed using BAL in a large consecutive cohort of immunocompromised patients. The diagnostic yield of 1066 BAL specimens was analyzed in 4 different groups of immunocompromised patients (HIV; solid organ transplants; high-dose chemotherapy and/or stem cell transplants; other immunosuppressive therapy) suffering from fever, respiratory symptoms and/or infiltrates on chest X-ray. Specimens were analyzed for bacteria, mycobacteria, fungi, Pneumocystis jiroveci, cytomegalovirus (CMV) and other viruses. Two time periods were compared (1992-1996; 1997-2003). The overall diagnostic yield of BAL was 34% for bacteria, 22% for CMV, 15% for P. jiroveci, 6% for other viruses, 6% for mycobacteria and 2% for aspergillus. There were significant changes in the pattern of opportunistic infections between the 2 time periods. Mycobacterial infections decreased considerably in the HIV group (17.9 vs. 8.5%, P=0.02), while the incidence of P. jiroveci decreased mainly in the transplant group (32.6 vs. 7.9%, P<0.00001). This study demonstrates a changed pattern of pulmonary infections in immunocompromised patients diagnosed by BAL. The overall diagnostic yield of BAL remains high in immunocompromised patients with respiratory symptoms.

Bacterial Infections↗
PubMed2006

Diagnostic yield of flexible bronchoscopy in current clinical practice.

BACKGROUND: Flexible bronchoscopy is a procedure commonly performed for diagnostic and therapeutic purposes. The aim of this study was to assess the diagnostic yield and the safety of routine bronchoscopy techniques including transbronchial needle aspiration and transbronchial biopsy at a university hospital in Switzerland. METHODS: 616 consecutive bronchoscopies performed at the Pulmonary Medicine Department (University Hospital Basel) over a period of 6 months were analysed retrospectively using bronchoscopy reports and hospital charts. Diagnostic procedures included bronchial washings, bronchoalveolar lavage, bronchial brushings, transbronchial needle aspiration and transbronchial biopsies. RESULTS: 430 bronchoscopies had a diagnostic, 186 a therapeutic indication. The overall diagnostic yield was 57% (245/430). Bronchoscopy performed for suspected tumours confirmed malignancy in 43% of cases. Bronchoscopy in suspected infection and tuberculosis identified pathogenic organisms in 46% and 27% of cases, respectively. The diagnostic yield for central and peripheral TBNA was 37.8 and 43.6%, respectively. Complications were very rare (n = 10, 1.6%) and were only minor. CONCLUSION: This study demonstrates that routine bronchoscopy techniques including transbronchial needle aspiration and transbronchial biopsy are safe and have a high diagnostic yield.

Adolescent↗
PubMed2005

Multitarget FISH analysis in the diagnosis of lung cancer.

The aim of the present study was to explore the diagnostic usefulness of the multitarget fluorescence in situ hybridization (FISH) test, LAVysion (Vysis, Downers Grove, IL), for the detection of lung cancer cells in cytologic specimens. Specimens from bronchial washings, bronchial brushings, and transbronchial fine-needle aspirates (TBNAs) from 100 patients with suspected lung cancer and from a control group of 71 patients with nonneoplastic lung disorders were analyzed. FISH positivity was defined as more than 5 cells with gains of at least 2 chromosomes or gene loci. FISH significantly improved the sensitivity of bronchial brushings from 49% to 73%. The specificities of FISH and cytologic examination were 87% and 100%, respectively. In contrast, FISH provided no additional diagnostic information in TBNAs and bronchial washings. There was no increased prevalence of genetic changes in contralateral bronchial washings from patients with lung cancer compared with the control group. The quantity of previous smoking had no effect on the prevalence of chromosomal changes.

Adult↗
PubMed2005

Breakdown of pulmonary host defense in the immunocompromised host: cancer chemotherapy.

The number of immunocompromised patients is steadily increasing due to HIV infection, solid organ and stem cell transplantation, intensified chemotherapy, immunosuppression for autoimmune diseases, and a marked increase in the use of monoclonal antibodies. Prevention strategies for pulmonary infections and diagnostic methods have evolved and patient outcome has improved. However, therapies affecting the immune system are also given to older patients and patients with comorbidities. While the rate of pulmonary complications in HIV patients has dramatically decreased under antiretroviral therapy, we are seeing more patients with pulmonary problems after chemotherapy. Neutropenia is still the most important risk factor for bacterial and fungal infection. Flexible bronchoscopy with BAL remains an important diagnostic method with a low morbidity and high diagnostic yield in patients with pulmonary infiltrates following cancer chemotherapy.

Antineoplastic Agents↗
PubMed2004

Systemic Th1- and Th2-gene signals in atopy and asthma.

BACKGROUND: Atopic disorders have been associated with a Th-2 cytokine predominance. This study investigated Th1- and Th2-related gene expression in asthmatics, atopics and healthy individuals. METHODS: We compared Th1- and Th2-related in vivo-signals using gene expression arrays in 18 atopic asthmatics, 8 atopic non-asthmatic and 14 healthy control subjects. Purified mRNA from peripheral blood mononuclear cells was reverse-transcribed and hybridised to cDNA membranes. Group differences were assessed after standardisation with Mann-Whitney U-test. RESULTS: Atopic individuals had upregulated lymphotoxin-alpha and downregulated IFNGR1. On the other hand, they had particularly high IL-4, IL-5 and IL4R levels, together with significantly upregulated IL10. Asthmatic individuals had normal Th1-gene expression, but an upregulation og Th-2 genes. Atopic individuals had high, asthmatic individuals excessively high IL12RB1-levels. No Th-2 gene was downregulated in both atopic phenotypes. The expression of IL6R correlated with the daily dose of inhaled corticosteroids. CONCLUSIONS: Atopic individuals had a down regulation of key TH1- and Th2-genes, resulting in a balanced upregulation of Th-specific genes. In contrast, asthmatic subjects had normal Th1-gene expression but a constant upregulation of Th2-specific genes, leading to Th2-predominance.

Adolescent↗
PubMed2004

Functional genomics and prognosis in sarcoidosis--the critical role of antigen presentation.

BACKGROUND: Sarcoidosis is a systemic disorder of unknown cause, highly variable phenotype and unpredictable outcome. Antigen processing, inflammatory response and immunomodulation appear critical to development and prognosis of the disease. METHODS: We performed a comprehensive genomic analysis, applying high-density human GeneChip probe arrays (HUG95A, Affymetrix Inc.) for gene expression profiling from peripheral blood of patients with acute pulmonary sarcoidosis (n = 12) and matched healthy controls (n = 12), mean age 36 +/- 12 and 33 +/- 10 years respectively. RESULTS: At follow-up (18 [15-24] months), 7 patients had self-limited disease and 5 had persistent disease. Significantly different expression comparing patients and controls was identified for 1,860 (14.9%) and 729 (5.8%) gene products at p = 0.05 and p = 0.01 levels respectively. Genes closely associated with persistent disease included HLA-DRB1*1501 DQB1*0602, TNFA, NFKB, cyclic AMP-responsive element modulator (CREM) and T-cell activation marker CD69. IL1B, IL8, growth related (GRO)-beta/-gamma and CCR 2,5,6 were closely associated with self-limited disease. CONCLUSION: We hypothesize that, in self-limited disease, greater effector cell activation leads to successful antigen elimination/tolerance, whereas HLA-DRB1*1501 DQBI*0602-mediated, probably defective/partial T-lymphocyte activation results in an inefficient primary immune response, antigen intolerance and persistent disease.

Adult↗
PubMed2003

Functional genomics and gene microarrays--the use in research and clinical medicine.

In the year 2000, the Human Genome Project Consortium presented the first complete draft of the human genome together with Celera Genetics. Since then, the so-called "post-genome era" has started. Microarrays are capable of profiling gene expression patterns of tens of thousands of genes in a single experiment and thus allow a systematic analysis of DNA and RNA variation. They seem likely to become a standard tool of both molecular biology research and clinical diagnostics. These prospects have attracted great interest and investment from both the public and private sectors. This review introduces the principle of microarray technology and gives an overview of its current and future potential in clinical medicine.

Animals↗
PubMed2002

The role of matrix metalloproteinase polymorphisms in the rate of decline in lung function.

The matrix metalloproteinases (MMPs) comprise a family of at least 20 proteolytic enzymes that play an essential role in tissue remodeling. MMP1 (interstitial collagenase), MMP9 (gelatinase B) and MMP12 (macrophage elastase) are thought to be important in the development of emphysema. A number of naturally occurring polymorphisms of human MMP gene promoters have been identified and found to alter transcriptional activity. Additionally, we detected a novel polymorphism in the MMP12 coding region (Asn357Ser). The aim of this study was to investigate the role of MMP polymorphisms in the development of chronic obstructive lung disease. We determined the prevalence of these polymorphisms in 590 continuing smokers chosen from the National Heart Lung and Blood Institute, Lung Health Study for having the fastest (n = 284) and slowest (n = 306) 5 year rate of decline of lung function. Of the five polymorphisms, only G-1607GG was associated with a rate of decline in lung function. The -1607GG allele was associated with a fast rate of decline (P = 0.02) [corrected]. However, haplotypes consisting of alleles from the MMP1 G-1607GG and MMP12 Asn357Ser polymorphisms were associated with rate of decline of lung function (P = 0.0007). These data suggest that polymorphisms in the MMP1 and MMP12 genes, but not MMP9, are either causative factors in smoking-related lung injury or are in linkage disequilibrium with causative polymorphisms.

Base Sequence↗
PubMed2002

Genetic risk factors of chronic obstructive pulmonary disease.

Cigarette smoking is the major risk factor for chronic obstructive pulmonary disease (COPD). However, only a minority of cigarette smokers develop symptomatic disease. Family and twin studies suggest that genetic factors also contribute to the development of COPD. We present a detailed literature review of the genes which have been investigated as potential risk factors for this disease.

Cystic Fibrosis Transmembrane Conductance Regulato↗
PubMed2002

Array-based diagnostic gene-expression score for atopy and asthma.

Whether gene expression is useful in discriminating different atopic phenotypes is unclear. The aim of the study was to evaluate a gene-expression score for the diagnosis of atopy and asthma and to assess disease activity as a guide for therapeutic decisions. Purified mRNA from PBMCs of 18 atopic asthmatic subjects, 8 atopic nonasthmatic subjects, and 14 healthy control subjects was hybridized to cDNA membranes. A composite atopy gene expression (CAGE) score was determined by using 10 genes dysregulated in atopic individuals according to a specific algorithm. The CAGE score was better than total IgE in differentiating atopic from nonatopic subjects (sensitivity, 96%; specificity, 92%). Correlation between the CAGE score and total IgE (P <.001) was found, and there was a trend for correlation with asthma severity (P =.051). The CAGE score was able to quantify phenotype-specific alteration in gene expression of atopic individuals. The CAGE score might be used as a diagnostic tool or to monitor the effects and side effects of therapy.

Adolescent↗
PubMed2002

Genotype predictors of response to asthma medications.

The search for the genetic basis of asthma and other allergic diseases has identified many candidate genes. Some of these genes have been investigated to determine whether they influence a person's response to asthma medication. Several studies have shown that polymorphisms in the beta 2 -adrenergic receptor gene influence responsiveness to beta-agonists. Polymorphisms in the 5-lipoxygenase gene and the leukotriene C 4 synthase gene have been associated with response to medications that target leukotriene metabolism. Results such as these suggest the potential for pharmacogenetic tailoring of therapy for individual asthmatic patients. To date, no polymorphisms have been identified that influence response to anticholinergics or are involved in steroid resistance.

5-Lipoxygenase-Activating Proteins↗
PubMed2002

Genetic risk factors for chronic obstructive pulmonary disease.

Cigarette smoking is clearly the major risk factor for chronic obstructive pulmonary disease. However, only a minority of cigarette smokers develops chronic obstructive pulmonary disease, indicating that other factors are involved. Family and twin studies suggest that at least some of those factors are genetic. This article reviews the genes investigated as potential risk factors for this disease, focusing on the recent literature. The only established genetic risk factor for chronic obstructive pulmonary disease is homozygosity for the Z allele of the alpha1 -antitrypsin gene. There is increasing evidence that heterozygotes for the Z allele may also be at increased risk. Variants in genes involved in xenobiotic metabolism, antioxidation, and the inflammatory response have also been associated with chronic obstructive pulmonary disease. Thus, the genetic basis for chronic obstructive pulmonary disease has begun to be elucidated, and it is likely that several genes will be implicated in the pathogenesis of this disease.

Alleles↗