[Pulmonary infections in human human lung tissue models].
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Humans↗
Biomedical subjects
M Maass
Publications and source records attributed to M Maass.
CD14 promoter polymorphism -159C>T is associated with susceptibility to chronic Chlamydia pneumoniae infection in peripheral blood monocytes.
Chlamydia pneumoniae uses peripheral blood monocytes (PBMC) for systemic dissemination and has been linked to atherogenesis by inflammation mediated via TLR2/4 and CD14. We found 12.8% of 610 coronary artery disease (CAD) patients of Central European background to be chronically infected with C. pneumoniae based on the repeated detection of chlamydial DNA in PBMC. Among those the -159C>T CD14 promoter polymorphism was more frequent (OR 1.7, 95% CI 1.08-2.65, P=0.0224) than among C. pneumoniae-negative subjects matched for age and gender. The Arg753Gln TLR2 and Asp299Gly TLR4 polymorphisms were not related to chlamydial infection. Susceptibility for chronic chlamydial infection of PBMC in CAD patients appears associated with the CD14-159C>T promoter polymorphism encoding for enhanced CD14 expression.
Antibodies, Bacterial↗
Differences in cell activation by Chlamydophila pneumoniae and Chlamydia trachomatis infection in human endothelial cells.
Seroepidemiological studies and demonstration of viable bacteria in atherosclerotic plaques have linked Chlamydophila pneumoniae infection to the development of chronic vascular lesions and coronary heart disease. In this study, we characterized C. pneumoniae-mediated effects on human endothelial cells and demonstrated enhanced phosphorylation and activation of the endothelial mitogen-activated protein kinase (MAPK) family members extracellular receptor kinase (ERK1/2), p38-MAPK, and c-Jun-NH2 kinase (JNK). Subsequent interleukin-8 (IL-8) expression was dependent on p38-MAPK and ERK1/2 activation as demonstrated by preincubation of endothelial cells with specific inhibitors for the p38-MAPK (SB202190) or ERK (U0126) pathway. Inhibition of either MAPK had almost no effect on intercellular cell adhesion molecule 1 (ICAM-1) expression. While Chlamydia trachomatis was also able to infect endothelial cells, it did not induce the expression of endothelial IL-8 or ICAM-1. These effects were specific for a direct stimulation with viable C. pneumoniae and independent of paracrine release of endothelial cell-derived mediators like platelet-activating factor, NO, prostaglandins, or leukotrienes. Thus, C. pneumoniae triggers an early signal transduction cascade in target cells that could lead to endothelial cell activation, inflammation, and thrombosis, which in turn may result in or promote atherosclerosis.
Chlamydia trachomatis↗
Antibacterial resistance of community-acquired respiratory tract pathogens recovered from patients in Germany and activity of the Ketolide Telithromycin: results from the PROTEKT surveillance study (1999-2000).
BACKGROUND: The Prospective Resistant Organism Tracking and Epidemiology for the Ketolide Telithromycin (PROTEKT) longitudinal global surveillance study examines the antibacterial susceptibility of community-acquired respiratory pathogens. METHODS AND RESULTS: Data from isolates collected in Germany in 1999-2000 in the PROTEKT study show that 8.3% of pneumococcal isolates (n = 325) had reduced susceptibility to penicillin and 2.2% were fully resistant. Erythromycin resistance was 15.7% overall and particularly high in Leipzig (31.6%). All penicillin- and erythromycin-resistant strains were inhibited by telithromycin (MIC < or =0.5 mg/l) and linezolid (MIC < or =2 mg/l). Beta-lactamase was produced by 3.2% of Haemophilus influenzae (9/284) and 89.5% of Moraxella catarrhalis strains (111/124). All Streptococcus pyogenes isolates (n = 87) were susceptible to penicillin, although 9.2% were resistant to macrolides. CONCLUSIONS: Penicillin resistance in Germany remains low; however, the prevalence of antimicrobial resistance among common respiratory pathogens is rising, particularly against macrolides. Continued surveillance is necessary to guide optimal empirical therapy, and new antimicrobials, like telithromycin, need to be developed with improved potency against target pathogens and low propensity for the development of resistance.
Anti-Bacterial Agents↗
Phagocytes transmit Chlamydia pneumoniae from the lungs to the vasculature.
Chlamydia pneumoniae, a major cause of community-acquired pneumonia, primarily infects the respiratory tract. Chronic infection of nonrespiratory sites, such as the vascular wall, the brain or blood monocytes, requires evasion from the lungs and spreading via the bloodstream. The cell types involved in dissemination are insufficiently characterised. In this study, New Zealand White rabbits were infected intratracheally with C. pneumoniae, and lung manifestation and systemic dissemination were monitored by polymerase chain reaction and immunohistochemistry. Infection of the lungs was characterised by an early phase dominated by granulocytes and a late phase dominated by alveolar macrophages (AM). Granulocytes, AM and alveolar epithelial cells acted as host cells for chlamydiae, which remained detectable for up to 8 weeks. AM transported the pathogen to the peribronchiolar lymphatic tissue, and subsequently C. pneumoniae entered the spleen and the aorta via dissemination by peripheral blood monocytes. In conclusion, Chlamydia pneumoniae-infected alveolar macrophages transmigrate through the mucosal barrier, and give the pathogen access to the lymphatic system and the systemic circulation. Infected peripheral blood monocytes are the vector system within the bloodstream and transmit the infection to the vascular wall. This is the first description of granulocytes acting as a reservoir for Chlamydia pneumoniae early in infection.
Animals↗
Vasculitic purpura with antineutrophil cytoplasmic antibody-positive acute renal failure in a patient with Streptococcus bovis case and Neisseria subflava bacteremia and subacute endocarditis.
Subacute bacterial endocarditis is frequently associated with extracardiac manifestations and renal failure. Clinical variety of endocarditis manifestation is wide and has the potential to mimic vasculitis. Whereas Streptococcus bovis is often isolated and associated with colonic tumors, Neisseriaceae are rarely found. An association of subacute bacterial endocarditis and antineutrophil cytoplasmic antibodies has been described. We report on a 62-year-old man who was admitted to our hospital with acute oliguric renal failure and a nonpruritic purpural rush without fever. Antineutrophil cytoplasmic antibody diagnostic revealed perinuclear staining with a titre of 1 : 512 and antiproteinase-3 specificity. Immune complex-mediated glomerulonephritis without extracapillary proliferation was diagnosed in renal biopsy. Finally, blood cultures became positive for Streptococcus bovis and Neisseria flava. Echocardiography showed mobile vegetations on tricuspid valve. Under treatment with penicillin G and gentamicin, skin efflorescences and renal function recovered, but vegetations increased. A colonic tumor could be excluded, a disastrous dental status may have been a predisposal factor. When classical findings of subacute bacterial endocarditis are less clear, the presence of renal failure and antineutrophil cytoplasmic antibodies in absence of fever may lead to misdiagnosis and deleterious immunosuppressive therapy. Neisseria subflava, an upper respiratory tract commensal, may cause subacute bacterial endocarditis without typical symptoms.
Acute Kidney Injury↗
Chlamydia pneumoniae in children with MS: frequency and quantity of intrathecal antibodies.
The authors investigated the frequency and quantity of intrathecal antibody synthesis against Chlamydia pneumoniae and the presence of C pneumoniae antigen in 25 children with MS. C pneumoniae genome was present in two children. In seven children an intrathecal synthesis of C pneumoniae antibodies was detected, representing only a small part of the total intrathecal immunoglobulin G, suggesting that this intrathecal synthesis is part of a polyspecific, oligoclonal immune response.
Adolescent↗
Imbalanced secretion of IL-1beta and IL-1RA in Chlamydia pneumoniae-infected mononuclear cells from COPD patients.
Balanced secretion of pro- and anti-inflammatory cytokines is essential in limiting pulmonary inflammation in respiratory infections. It was hypothesised that, in acute infection with Chlamydia pneumoniae, mononuclear cells from chronic obstructive pulmonary disease (COPD) patients lack the opportunity to compensate for the inflammatory immune response by secreting adequate amounts of anti-inflammatory cytokines. Alveolar macrophages (AMs) and peripheral blood mononuclear cells (PBMCs) from eight COPD patients and eight healthy controls were infected with C. pneumoniae in order to determine interleukin (IL)-1beta, IL-1 receptor antagonist (IL-1RA) and IL-8 expression and messenger ribonucleic acid levels. Secretion of IL-1beta was significantly enhanced in AMs (six-fold) and PBMCs (four-fold) from COPD patients after infection with C. pneumoniae. Compared to the control group, release of its anti-inflammatory counterpart IL-1RA was diminished in COPD patients, resulting in a significantly higher IL-1beta/IL-1RA ratio in C. pneumoniae-infected AMs and PBMCs from COPD patients. Mononuclear cells from chronic obstructive pulmonary disease patients have less capacity for balancing the pro-inflammatory immune response caused by Chlamydia pneumoniae infection than those from healthy controls. These findings suggest that, during acute exacerbation with intracellular pathogens, chronic obstructive pulmonary disease patients are predisposed to inflammatory changes in the lungs.
Adult↗
[Recommendations for the diagnosis, therapy and prevention of pneumonia in the immunocompromised host].
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Germany↗
Detection of Chlamydia pneumoniae in unexplained pulmonary hypertension.
The pathogenesis of primary pulmonary hypertension is still unclear. The case of a 68-yr-old female patient who complained of recurrent dizzy spells and collapses over a period of 6 weeks and died of global cardiac failure is presented. Autopsy revealed severe pulmonary hypertension, slight chronic bronchitis, and bronchiolitis as well as intra-alveolar accumulation of macrophages. Chlamydiae were detected within the pulmonary arteries and in intramural and intra-alveolar macrophages by immunofluorescence, confocal laser scanning microscopy, scanning and transmission electron microscopy. Nested-polymerase chain reaction (PCR) and nonradioactive deoxyribonucleic acid (DNA) hybridization of PCR products from pulmonary arteries revealed Chlamydia pneumoniae DNA. Chlamydia pneumoniae has already been detected in atherosclerosis and in pulmonary emphysema. It can induce proliferation of smooth muscle cells. Chlamydia pneumoniae might be relevant in aggravation of primary pulmonary hypertension and might perhaps be a trigger factor in some cases.
Aged↗
Standardizing Chlamydia pneumoniae assays: recommendations from the Centers for Disease Control and Prevention (USA) and the Laboratory Centre for Disease Control (Canada).
Chlamydia pneumoniae has been associated with atherosclerosis and several other chronic diseases, but reports from different laboratories are highly variable and "gold standards" are lacking, which has led to calls for more standardized approaches to diagnostic testing. Using leading researchers in the field, we reviewed the available approaches to serological testing, culture, DNA amplification, and tissue diagnostics to make specific recommendations. With regard to serological testing, only use of microimmunofluorescence is recommended, standardized definitions for "acute infection" and "past exposure" are proposed, and the use of single immunoglobulin (Ig) G titers for determining acute infection and IgA for determining chronic infection are discouraged. Confirmation of a positive culture result requires propagation of the isolate or confirmation by use of polymerase chain reaction (PCR). Four of 18 PCR assays described in published reports met the proposed validation criteria. More consistent use of control antibodies and tissues and improvement in skill at identifying staining artifacts are necessary to avoid false-positive results of immunohistochemical staining. These standards should be applied in future investigations and periodically modified as indicated.
Bacteriological Techniques↗
[Mitral valve endocarditis caused by Erysipelothrix rhusiopathiae].
HISTORY AND CLINICAL FINDINGS: A 67 year-old country woman was admitted to the hospital because of a four weeks history of continuous catarrh, arthralgia and fever. Recently, she had also developed upper abdominal pain after oral ibuprofen treatment. The clinical examination showed a patient of impaired general condition. The heart and lungs were auscultatory normal and there were no signs of dyspnea, cyanosis or inflammatory skin lesions. EXAMINATIONS: Physical examination of heart and lung, electrocardiography and transthoracic echocardiography were without pathological findings. CLINICAL COURSE: Gastroscopy revealed acute antral gastritis and duodenitis with presence of Helicobacter pylori. Eradication therapy resolved the abdominal symptoms but fever returned after the antibiotic therapy was stopped. The patient developed a severe endocarditis with progressive mitral regurgitation within a few days. Erysipelothrix rhusiopathiae was isolated from blood cultures and identified by conventional and molecular methods. The patient was treated successfully with 3 x 2 g ampicillin daily, applied parenterally for six weeks, and a mitral valve replacement. CONCLUSION: This was an unusual manifestation of systemic Erysipelothrix rhusiopathiae infection. The bacterium Erysipelothrix rhusiopathiae has still to be considered in the diagnosis and treatment of endocarditis in patients with increased risk of exposure (e.g. farmers, butchers and fishermen).
Aged↗
Chlamydia pneumoniae infection in circulating human monocytes is refractory to antibiotic treatment.
BACKGROUND: Recovery of the intracellular bacterium Chlamydia pneumoniae from atherosclerotic plaques has initiated large studies on antimicrobial therapy in coronary artery disease. The basic concept that antibiotic therapy may eliminate and prevent vascular infection was evaluated in vitro and in vivo by examining the antibiotic susceptibility of C pneumoniae in circulating human monocytes, which are thought to transport chlamydiae from the respiratory tract to the vascular wall. METHODS AND RESULTS: Blood monocytes (CD14+) from 2 healthy volunteers were obtained before and after oral treatment with azithromycin or rifampin and then inoculated with a vascular C pneumoniae strain and continuously cultured in the presence of the respective antibiotic. Progress of infection and chlamydial viability was assessed by immunogold-labeling and detection of C pneumoniae-specific mRNA transcripts. Circulating monocytes from patients undergoing treatment with experimental azithromycin for coronary artery disease were examined for C pneumoniae infection by cell culture. Antibiotics did not inhibit chlamydial growth within monocytes. Electron microscopy showed development of chlamydial inclusion bodies. Reverse transcription-polymerase chain reaction demonstrated continuous synthesis of chlamydial mRNA for 10 days without lysis of the monocytes. The in vivo presence of viable pathogen not eliminated by azithromycin was shown by cultural recovery of C pneumoniae from the circulating monocytes of 2 patients with coronary artery disease. CONCLUSIONS: C pneumoniae uses monocytes as a transport system for systemic dissemination and enters a persistent state not covered by an otherwise effective antichlamydial treatment. Prevention of vascular infection by antichlamydial treatment may be problematic: circulating monocytes carrying a pathogen with reduced antimicrobial susceptibility might initiate reinfection or promote atherosclerosis by the release of proinflammatory mediators.
Aged↗
Cost analysis of Turku University Central Hospital PACS in 1998.
Introduction of a picture archiving and communication system (PACS) into an old hospital poses several problems since the system cannot be implemented instantaneously. We analysed the costs of a halfway implemented PACS in Turku University Central Hospital (TUCH) during 1998. Manual and digital archiving in 1998 continued parallel so that only 10% reduction of film usage was achieved. A 21% increase in image manipulation and storage expenses occurred. A calculation based on potential 90% reduction of film usage and changes in the amount of personnel suggest some direct savings. Also, indirect savings due to more efficient patient treatment and the reduction of time spent in the hospital, and overhead costs of information handling are expected to lead to savings. However, these savings were not included in our calculations. When full-scale PACS is installed, equipment investments, network and digital ware maintenance costs will drop from 121 to 116% compared with traditional film archiving activity costs.
Academic Medical Centers↗
In vitro susceptibility and eradication of Chlamydia pneumoniae cardiovascular strains from coronary artery endothelium and smooth muscle cells.
UNLABELLED: Recovery of viable Chlamydia pneumoniae from atheromas of coronary heart diseases patients has initiated pilot studies to eradicate C. pneumoniae from vascular tissue by antibiotic treatment. To provide data for the selection of effective antibiotics, we investigated the in vitro activity of anti-chlamydial antibiotics to eliminate vascular strains of C. pneumoniae from coronary endothelial and smooth muscle cells, celltypes that are involved in the pathogenesis of atherosclerosis. METHODS: The susceptibility of the obligate intracellular chlamydiae was studied in primary coronary endothelial cells, smooth muscle cells and immortalized epithelial cells. Minimal inhibitory concentrations (MICs) were determined for ofloxacin, levofloxacin, trovafloxacin, moxifloxacin, erythromycin, azithromycin, roxithromycin, rifapentin and rifampin. RESULTS: In vitro, rifampin was the most effective drug overall. Moxifloxacin and trovafloxacin were as effective as the macrolides of which roxithromycin was the most active one. CONCLUSIONS: Actively replicating C. pneumoniae can be eliminated in vitro from cell types, involved in the pathogenesis of atherosclerosis by various antibiotics. These data provide an experimental background for the selection of antibiotics in clinical eradication studies and will help to assess the potential success of prevention and eradication therapies.
Anti-Bacterial Agents↗
Radiological image data migration. Practical experience and comparison of the costs of work.
PURPOSE: To identify costs deriving from data migration of obsolete digital archives by measuring the workload, and to analyse migration-associated problems. MATERIAL AND METHODS: Two digital archives were used (DTL and MOD) and the capacity of these archives could no longer support the needs of the Medical Imaging Centre. The entire content of the DLT archive and selected data from the MOD archive were transferred to the current higher capacity (17 TB) tape archive. The running time of work processes was measured by self-reporting, and the cost of work was calculated. RESULTS: The transfer of 43,096 studies required 314 working hours over the course of 15 months in total. The work was partly manual, partly automatic. The percentage of non-retrievable MOD images was 35. Less than 0.2% of the DLT image transfers failed due to incorrect patient or image data. The MOD - DLT transfer cost was six times higher per study than the DLT - DLT transmission cost. CONCLUSION: At present, data migration may be inevitable as the amount of data increases and technology advances. The data transfer proved to be labour intensive, with high fault sensitivity regarding the MOD archive. The cost of work of data migration was 0.4% of estimated digital archiving total yearly cost. Automated data migration is preferable.
Costs and Cost Analysis↗
Effectiveness of radiological image data compression.
This study was designed to evaluate effectiveness of radiological image data compression in terms of image quality and archiving material costs using DLT tapes, and to assess the relationship between loss of quality and cost savings. Six radiologists used Subjective Fidelity Criteria (SFC) in random fashion to evaluate the quality of 105 digitally acquired radiological images. In addition, 5 radiologists and 2 nonradiologists evaluated at random three phantom images exposed in conditions mimicking chest, bone, and colon examinations, displayed in five modes (a total of 15 images). Both patient images and phantom images were submitted to 3:1 (Ziv-Lempel method) and 10:1 compression (wavelet-based compression method). Cost information on material cost savings and the effect of compression on tape space requirements were compared. The results indicate that image quality was not degraded using either of the compression ratios. The interobserver proportion of agreement exceeded overwhelmingly the limit of a good proportion of agreement regarding each compression ratio and each image type. The divergence in the rest of the assessments was not consistent. The adoption of 10:1 compression would not bring a substantial decrease of archiving costs as compared to the total yearly operating costs, and especially as considering the consequences of possible image quality deterioration.
Chi-Square Distribution↗
Multicenter comparison trial of DNA extraction methods and PCR assays for detection of Chlamydia pneumoniae in endarterectomy specimens.
The reported rate of detection of Chlamydia pneumoniae DNA within atherosclerotic lesions by PCR varies between 0 and 100%. In this study, identical sets of coded experimental atheroma samples (n = 15) and spiked controls (n = 5) were analyzed by 16 test methods in nine centers by means of PCR. The positive controls were correctly identified to levels of 1, 0.1, and 0.01 inclusion bodies of C. pneumoniae/ml of tissue homogenate by 16 (100%), 11 (69%), and 3 (19%) of the test methods, respectively. Three out of 16 negative controls (19%) were rated positive. Positivity rates for atheroma samples varied between 0 and 60% for the different test methods, with the maximum concordant result for positivity being only 25% for one carotid artery sample. There was no consistent pattern of positive results among the various laboratories, and there was no correlation between the detection rates and the sensitivity of the assay used.
Arteriosclerosis↗