[Are pulmonary Candida infections a reality?].
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Algorithms↗
Biomedical subjects
K Dalhoff
Publications and source records attributed to K Dalhoff.
Leucocyte response and anti-inflammatory cytokines in community acquired pneumonia.
BACKGROUND: In the host defence of the lung neutrophils (PMN) play a central role. Apart from antimicrobial properties, recent data indicate that PMN also exert anti-inflammatory effects by stimulation and release of cytokine antagonists such as interleukin-1 receptor antagonist (IL-1ra). METHODS: Cytokine release from lipopolysaccharide stimulated whole blood was studied in 18 patients with community acquired pneumonia (CAP) and severe co-morbidities at admission and after 24 hours. Release of IL-1ra, interleukin-1beta (IL-1beta), tumour necrosis factor alpha (TNFalpha), soluble TNF receptor type I (sTNF-RI), and IL-8 was determined by ELISA. RESULTS: The mean (SD) leucocyte level at admission was 12.5 (4.1)/nl. There was a significant correlation between the release of anti-inflammatory cytokines such as IL-1ra and sTNF-RI and the leucocyte count at admission and after 24 hours. Additional in vitro experiments showed that co-incubation of peripheral blood mononuclear cells with autologous PMN led to a marked dose dependent increase in IL-1ra and sTNF-RI release. CONCLUSION: These results indicate that PMN may be responsible for the increase in anti-inflammatory cytokines in CAP. Strategies to increase neutrophil counts may exert beneficial effects, not only by augmenting the antimicrobial activity but also by modulating the inflammatory cytokine response.
Adult↗
Intracellular cytokine repertoire in different T cell subsets from patients with sarcoidosis.
BACKGROUND: Pulmonary sarcoidosis is characterised by a mononuclear alveolitis with a predominance of CD4+ T cells and macrophages. We determined the intracellular expression of interferon (IFN)gamma, interleukin (IL)-2, tumour necrosis factor (TNF)alpha, IL-4, IL-5 and IL-10 in CD4+ and CD8+, naive and memory lymphocytes from blood and bronchoalveolar lavage (BAL) fluid using three colour flow cytometry. METHODS: Eighteen untreated patients with pulmonary sarcoidosis were evaluated and stratified according to whether they had acute or chronic disease. RESULTS: Significantly more T cells expressed Th1 than Th2 type cytokines in both BAL fluid and peripheral blood samples, regardless of clinical presentation. Significantly greater proportions of T cells secreted Th1 type cytokines in BAL fluid than in peripheral blood. Th1 type cytokines were more frequently expressed by peripheral and alveolar T cells in acute disease than in chronic disease. There were no significant differences between CD4+ and CD8+ T cells. Concerning naive and memory lymphocytes, significantly higher CD45RO:CD45RA ratios were found in BAL fluid than in blood, and increased expression of Th2 type cytokines was found in peripheral compared with alveolar memory T cells. CONCLUSIONS: Our data support the immunopathogenetic concept of Th1/Th2 imbalance and compartmentalisation in pulmonary sarcoidosis and suggest that the cytokine patterns change during the course of disease. Expression of Th2 type cytokines in memory lymphocytes is decreased in the alveolar compartment compared with peripheral blood.
Acute Disease↗
Early postoperative erythromycin breath test correlates with hepatic cytochrome P4503A activity in liver transplant recipients.
BACKGROUND: Interindividual variation in the pharmacokinetics of the immunosuppressive agents cyclosporine (INN, ciclosporin) and tacrolimus may result from differences in the activity of cytochrome P4503A (CYP3A). The erythromycin breath test is an in vivo assay of hepatic CYP3A activity, but the method has never been directly validated. The aim of the study was to investigate whether an early postoperative erythromycin breath test correlated with the hepatic CYP3A protein level and catalytic activity in liver transplant recipients. METHODS: In 18 liver transplant recipients, the erythromycin breath test was performed within 2 hours after transplantation. A graft biopsy was obtained during surgery and analyzed for the CYP3A protein level by Western blotting and for CYP3A activity with erythromycin demethylation and testosterone 6beta- hydroxylation assays. RESULTS: The erythromycin breath test values ranged from 0.14% to 1.65% of carbon 14 per hour, and the CYP3A protein level ranged from 732 to 7822 as measured by optical density. The in vitro catalytic activity determined by the erythromycin demethylation assay ranged from 94 to 902 disintegrations per minute per 5 minutes per milligram of protein, and the activity determined by testosterone 6beta-hydroxylation ranged from 0.030 to 0.627 nmol per minute per milligram of protein. Significant correlation was demonstrated between the erythromycin breath test and both the erythromycin demethylation (Spearman correlation coefficient: R = 0.76, R (2) = 0.57; P =.0004) and the testosterone 6beta-hydroxylation (Spearman correlation coefficient: R = 0.79, R (2) = 0.63; P =.0001) assays. The erythromycin breath test also correlated with the CYP3A protein level (Spearman correlation coefficient: R = 0.60, R (2) = 0.36; P =.01). CONCLUSION: Our data support the erythromycin breath test as a specific in vivo assay of CYP3A activity in humans. The test is applicable in liver transplant recipients in the early postoperative phase. Future studies should evaluate the clinical usefulness of an early postoperative erythromycin breath test as a predictor of cyclosporine-tacrolimus pharmacokinetics in liver transplantation.
Adolescent↗
[Infection hypothesis of coronary heart disease].
It is well accepted that coronary artery disease is linked to an inflammatory process. It is unproven however whether either infectious agents may cause or accelerate coronary artery disease or the inflammatory process is due to metabolic or toxic effects. Among the possible infectious agents Chlamydia pneumoniae is the most likely bacterium involved in atherosclerosis. The arguments in favour of Chlamydia pneumoniae originate from seroepidemiologic studies and from detection and isolation of bacteria from vascular lesions. This review summarises the present understanding of the role of bacterial infection for development or progression of coronary artery disease.
Animals↗
[Necrotizing enterocolitis: a historical and current review].
Enteritis necroticans, locally called "Darmbrand", is a severe and life threatening infectious disease which was epidemic in Northern Germany after World War II. Darmbrand had a limited appearance, occurring only for a few years. In Lübeck many cases were diagnosed in 1946/1948 and the book "Darmbrand, Enteritis necroticans" was published in 1949 by clinicians and pathologists. Enteritis necroticans is also known as a tropical cause of bloody diarrhea and is caused by Clostridium perfringens Type C (type beta-toxin). The disease is related to pig feasts in Papua New Guinea. Although necrotizing enterocolitis is now a rather rare disease we must be aware of the appearance of this fulminant entity. This paper represents a review on the historic and current aspects of enteritis necroticans and discusses the epidemiology, pathogenesis and treatment of this disease.
Clostridium Infections↗
Hydroxymethylglutaryl coenzyme A reductase inhibitors modify the inflammatory response of human macrophages and endothelial cells infected with Chlamydia pneumoniae.
BACKGROUND: In patients with atherosclerosis, hepatic hydroxymethylglutaryl coenzyme A reductase (CSE) inhibitors may reduce the activation of inflammation. Because Chlamydia pneumoniae infection has been linked to coronary artery disease through the induction of plaque inflammation, we investigated whether cerivastatin affects the infection rate of human macrophages and endothelial cells (ECs) and their proinflammatory activation after chlamydial infection. METHODS AND RESULTS: Macrophages were collected from the alveolar compartment of 6 volunteers and 10 patients with chronic bronchitis. ECs were obtained from 10 umbilical cords. The C. pneumoniae strain CWL was incubated with macrophages or ECs in the presence and absence of the CSE inhibitor cerivastatin. The infection rate was determined by immunofluorescence microscopy. The release of monocyte chemoattractant protein-1 (MCP-1), interleukin-8 (IL-8), and tumor necrosis factor (TNF)-alpha was quantified by ELISA. The release of oxygen radicals was determined by ferricytochrome assay. Infection rates were tendentially lower after the preincubation of macrophages with CSE inhibitors (17.2% versus 9. 3% and 18.2% versus 10.4%, respectively; P=NS). The secretion of MCP-1, IL-8, and TNF-alpha by infected macrophages from volunteers increased. Coincubation with cerivastatin resulted in significantly lower MCP-1 and IL-8 production, whereas the release of TNF-alpha remained unaffected. Similar effects regarding chemokine release were observed in ECs. CONCLUSIONS: CSE inhibitors modify the inflammatory response of human immune cells to C. pneumoniae. This finding could be relevant for the therapeutic potential of CSE statins in patients with atherosclerosis and C. pneumoniae infection.
Adult↗
Coronary artery disease: an inflammatory or infectious process.
It is well accepted that coronary artery disease is linked to an inflammatory process. It is unknown which agents may cause or accelerate coronary artery disease. An inflammation of the vessel wall may be caused by a number of mechanisms such as accumulation of glycosylated proteins in diabetic patients, oxidised LDL in patients with hypercholesterolemia or infectious agents. Among the possible infectious agents Chlamydia pneumoniae is the most likely microorganism involved in atherosclerosis. The arguments in favour of Chlamydia pneumoniae result from seroepidemiologic studies and from detection of chlamydial DNA in atherosclerotic plaques by polymerase chain reaction (PCR). In addition this microorganism is the only one that could be isolated from atherosclerotic tissue. This review summarises the present understanding of the role of an inflammatory process in the development or progression of coronary artery disease.
Acute-Phase Proteins↗
GM-CSF and GM-CSF beta c receptor in adult patients with pulmonary alveolar proteinosis.
Pulmonary alveolar proteinosis (PAP) is a rare disorder of unknown origin characterized by alveolar fillings with periodic acid-Schiff (PAS)-positive material mainly consisting of phospholipids. Mice defective in the granulocyte-macrophage colony-stimulating factor (GM-CSF) gene or the GM-CSF/interleukin (IL)-3/IL-5-receptor common beta chain (beta c) demonstrate a pathology resembling PAP. A recent study revealed defects in the beta c chain of the GM-CSF receptor in four out of eight paediatric patients. This study investigates the role of the GM-CSF coding region and components of the GM-CSF receptor in adult patients. Four adult patients with proven PAP were analysed for GM-CSF and GM-CSF-beta c receptor in regard to protein level, messenger ribonucleic acid (mRNA) expression and sequence composition. None of the adult patients displayed the mutation at position 1,835 of the beta c-receptor previously described in paediatric patients. Expression of the beta c receptor was found to be normal on the surface of peripheral blood cells. In three out of four patients GM-CSF release from blood cells failed to respond adequately to lipopolysaccharide (LPS). In one of these patients a heterozygous mutation was found in the GM-CSF complementary deoxyribonucleic acid (cDNA) from thymine (T) to cytosine (C) at position 382 of the published sequence putatively causing a change in the protein from isoleucine to threonine at position 117. This study indicates that the mutation of the beta chain receptors found in some of the paediatric patients suffering from pulmonary alveolar proteinosis is not a common problem in adult patients.
Adult↗
[Nosocomial pneumonia: recommendations on treatment and prevention. German Pneumology Society] .
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Anti-Bacterial Agents↗
[Clinical relevance of Chlamydia pneumoniae infection--from the respiratory tract to the vascular system].
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Cardiovascular Diseases↗
Detection of Chlamydia pneumoniae within peripheral blood monocytes of patients with unstable angina or myocardial infarction.
Because individual diagnoses of vascular infection with Chlamydia pneumoniae depend entirely on surgically removed tissues, a better assay to predict vascular infection is needed. Polymerase chain reaction detection of chlamydial DNA was applied to CD14-positive cells collected from 238 patients with angiographically identified unstable angina or acute myocardial infarction. C. pneumoniae was detected in 52 (28%) of 188 persons with unstable angina and in 13 (26%) of 50 persons with myocardial infarction. Differences between groups were not significant. C. pneumoniae is present in monocytes/macrophages of a significant proportion of persons with progressive coronary artery disease. Infarction is not accompanied by a rise in chlamydial detection rates. The potential role of chlamydiae in coronary atherosclerosis may therefore be more related to acceleration of disease or systemic effects by persistent infection than to sudden initiation of infarction by acute infection.
Adult↗
Neutrophil inflammation and activation in bronchiectasis: comparison with pneumonia and idiopathic pulmonary fibrosis.
BACKGROUND: Pulmonary inflammation in bronchiectasis, pneumonia and idiopathic pulmonary fibrosis (IPF) is dominated by neutrophils. Pathophysiologic differences are seen in the degree of airway and tissue destruction. Neutrophil activation and neutrophil proteolytic activity might differ between bronchiectasis, pneumonia and IPF. OBJECTIVE: The aim of this study was to determine whether levels of inflammatory and protective markers in bronchoalveolar lavage (BAL) differed among cases of bronchiectasis, pneumonia and IPF. METHODS: We studied 11 bronchiectasis patients (group 1), 30 pneumonia patients (group 2), 15 IPF patients (group 3) and 12 healthy volunteers (group 4). In the bronchoalveolar lavage fluid, concentrations of alpha(1)-proteinase inhibitor, myeloperoxidase (MPO) and elastase-alpha(1)PI complex were determined using immunoluminometric assays. Elastase inhibition capacity (EIC) and elastase activity were determined using a colorimetric assay. RESULTS: No EIC, but free elastase activity, was found in 82% of group 1, 20% of group 2, 20% of group 3 and 0% of group 4. Median MPO concentration was highest in group 1: 7,951 ng/ml (16th-84th percentile [16-84%]: 256-36,342) vs. 692 ng/ml (106-2,279; group 2), 332 ng/ml (98-1,657; group 3), and 0.12 ng/ml (0.08-0.26; group 4). Bronchiectasis patients with bronchial Pseudomonas infection showed higher amounts of neutrophils (p < 0.01) and higher elastase activity (p < 0.05) than patients with sterile lavage. CONCLUSION: Bronchiectasis patients show a severe imbalance between neutrophil activity and protective molecules leading to possible lung destruction. Chronic Pseudomonas infection might trigger neutrophil activation. Future research and treatment strategies should focus on increased bacterial clearance and inhibition of neutrophil toxicity.
Adult↗
Decreased apoptosis and increased activation of alveolar neutrophils in bacterial pneumonia.
STUDY OBJECTIVES: The central role of apoptosis in the regulation of lung inflammation is increasingly recognized. The aim of this study was to determine the parameters of cell activation and apoptosis on neutrophils from the circulation and the pulmonary compartment in patients with community-acquired pneumonia (CAP), and to assess the role of the Fas system and of complement-regulating molecules in this context. DESIGN AND METHODS: The study population consisted of nine patients with CAP (group 1) and six age-matched control patients without evidence of bronchopulmonary inflammation (group 2). Apoptosis rate and expression of CD11b, CD16, CD55, CD59, CD95, and CD114 surface molecules on systemic and bronchoalveolar neutrophils were assessed ex vivo using fluorescence-activated cell sorter analysis. RESULTS: In patients with CAP, we found a significant decrease of the mean apoptosis rate in pulmonary neutrophils compared to systemic neutrophils, without concomitant changes in Fas expression. In contrast, cell activation markers were significantly increased on pulmonary cells (CD11b, 288 +/- 98.2 relative mean fluorescence intensity [rMFI] vs 53.8 +/- 10.8 rMFI on peripheral cells), and similar changes were observed with respect to the expression of complement-regulating molecules. Pulmonary polymorphonuclear neutrophils of the control group showed analogous changes, compared to systemic neutrophils, but a significantly higher rate of apoptosis and a lower increase of activation-marker expression were found, compared to pulmonary neutrophils of patients with pneumonia. CONCLUSIONS: Pulmonary neutrophils from patients with CAP show a decreased rate of apoptosis and increased activation status in the alveolar compartment, which may be important for effective control of pulmonary inflammation.
Adaptor Proteins, Signal Transducing↗
1,25-dihydroxycholecalciferol stimulates ICAM-1 expression of human alveolar macrophages in healthy controls and patients with sarcoidosis.
Synthesis and release of 1,25-dihydroxycholecalciferol (1, 25-(OH)2D2) by alveolar macrophages (AM) have been shown to be increased in granulomatous lung disease. ICAM-1 plays a major part in leukocyte homing to sites of chronic inflammation, which is a crucial step during the inflammatory response. Whether 1,25-(OH)2D2 alters the ICAM-1 expression of AM in humans has not been studied. Bronchoalveolar lavage (BAL) was performed in 12 healthy volunteers, in 13 patients with sarcoidosis (active disease n = 8, inactive disease n = 5), and in 9 patients with chronic bronchitis. AM were incubated with different concentrations of 1,25-(OH)2D2 (10(-11) to 10(-6) M) with and without priming with interferon-gamma (IFN-gamma) and with and without preincubation with 10(-8) M dexamethasone. In addition, the metabolites of vitamin D, 24, 25-dihydroxycholecalciferol and 25-hydroxycholecalciferol, were used. The AM expression of ICAM-1 (cELISA) and the release of tumor necrosis factor-alpha (TNF-alpha) (bioassay) by AM were determined. In healthy volunteers the ICAM-1 expression on AM was significantly and dose-dependently increased by 1,25-(OH)2D2, but not by 24, 25-dihydroxycholecalciferol and 25-hydroxycholecalciferol. Priming with IFN-gamma resulted in an additive effect. Preincubation with dexamethasone inhibited ICAM-1 expression. Addition of 1,25-(OH)2D2 after inhibition by dexamethasone increased ICAM-1 expression significantly. TNF-alpha secretion of AM from healthy volunteers was significantly reduced by 1,25-(OH)2D2. In sarcoidosis patients ICAM-1 expression was significantly higher compared with healthy volunteers. Incubation with 1,25-(OH)2D2 resulted in a further significant increase of ICAM-1 expression. TNF-alpha secretion of AM was increased compared with healthy volunteers. 1,25-(OH)2D2 reduced TNF-alpha secretion; however, this difference was not significant. 1, 25-(OH)2D2 has an immunomodulating effect on human AM both in healthy volunteers and in sarcoidosis patients with enhanced expression of ICAM-1. It may serve as an autocrine mediator in inflammatory lung disease.
Adult↗
Impaired neutrophil exocytosis in patients with severe pneumonia.
OBJECTIVE: Polymorphonuclear neutrophils (PMN) are one of the major effector cells of pulmonary defence against bacterial infection. To determine whether neutrophil function is impaired in patients with severe pneumonia, we assessed the two main partial functions exocytosis and oxidative response (ROS production) in isolated neutrophils from the peripheral venous blood of pneumonia patients and healthy volunteers. In addition, pulmonary neutrophils and peripheral neutrophils were compared in pneumonia patients. PATIENTS AND METHODS: Twenty-one patients with severe pneumonia were enrolled in the study. Eleven patients were mechanically ventilated, ten patients breathed spontaneously. For comparison, ten healthy adults were studied. The release of two markers of neutrophil exocytosis, lactoferrin and myeloperoxidase (MPO), with and without stimulation by phorbol-myristate-acetate (PMA), was determined using immunoluminometric assays. ROS production was quantified using luminol-enhanced chemiluminescence. In addition, the clinical severity of pneumonia was correlated to neutrophil exocytosis. RESULTS: With regard to blood neutrophils, both basal and PMA-stimulated exocytosis were significantly impaired in pneumonia patients compared to healthy volunteers (basal lactoferrin secretion in pneumonia patients: 0.25+/-0.36 pg/PMN versus controls: 1.17+/-0.78 pg/PMN, p<0.01). In contrast, both basal and PMA-stimulated ROS production were increased in patients compared to controls (spontaneous chemiluminescence in pneumonia patients: 13.6x10(5) cpm versus controls: 5.5x10(5) cpm). In pneumonia patients, the pulmonary neutrophils released significantly more lactoferrin, MPO and ROS compared to blood neutrophils (basal lactoferrin secretion of pulmonary neutrophils: 1.19+/-1.55 pg/PMN; p<0,01). However, after stimulation with PMA the exocytosis of pulmonary and blood neutrophils was similar. The severity of pneumonia and prognostic indices like albumin were inversely correlated to the release of lactoferrin in blood neutrophils (p<0,05). CONCLUSION: In patients with severe pneumonia, the exocytosis of blood neutrophils was significantly impaired. In contrast to this, the oxidative response was increased. Impaired bone marrow maturation of neutrophils during severe infection, perhaps due to shortened maturation time, could explain these findings.
Adult↗
[German Society of Pneumology. Recommendations for the diagnosis of nosocomial infections].
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Cross Infection↗
Endovascular presence of Chlamydia pneumoniae DNA is a generalized phenomenon in atherosclerotic vascular disease.
The common respiratory pathogen Chlamydia pneumoniae has been implicated in the pathogenesis of coronary artery disease and acute myocardial infarction. In order to verify the endovascular presence of potentially viable chlamydia by detection of genomic DNA, we examined atherosclerotic arteries from various vascular regions using a C. pneumoniae specific nested polymerase chain reaction (PCR). The samples were obtained during surgical revascularization procedures or at autopsy. Chlamydial DNA was detected in 51/238 (21%) atherosclerotic samples. A total of 17 non-atherosclerotic control samples were PCR-negative. Chlamydial presence was detected in 36/140 (26%) vascular samples obtained at coronary revascularization procedures, in 9/61 (15%) samples from carotid artery stenosis, 3/17 (18%) samples from the aorta, and 3/20 (15%) iliac artery samples. Histomorphological discrimination of infected and non-infected arterial samples was not possible. Antichlamydial IgG and IgM response as examined by microimmunofluorescence assay did not aid identification of individual endovascular infection. C. pneumoniae is present in a significant proportion of atherosclerotic arteries. Its occurrence in atheromatous plaques is not limited to coronary arteries and may be considered indicative of an infectious component in atherosclerosis. However, it remains unclear whether chlamydia actually initiates atherosclerotic injury, facilitates its progression, or merely colonizes pre-existing atheromata.
Adult↗