Dr. Philipp M. Lepper, FCCP Dept. of Internal Medicine V - Pneumology (Head: Prof. Dr. Dr. Robert Bals) University Hospital of Saarland 66424 Homburg Germany
- Innate Immunity - Toll-like receptor signaling - Role of (innate) immunity in cardiovascular and pulmonary disorders - Intensive Care Medicine
Editorial tasks:
- Associate Editor "Mediators of Inflammation" (http://www.hindawi.com/journals/mi) - Faculty Member "Faculty of 1000 Medicine" (http://www.f1000medicine.com)
Reviewer for Funding Organizations
- Biotechnology and Biological Sciences Research Council, UK (http://www.bbsrc.ac.uk/) - Sport Aiding Medical Research for Kids (SPARKS) Foundation, UK (http://www.sparks.org.uk/) - Meningitis Research Foundation, UK (http://www.meningitis.org/) - University of Southampton, UK - Swiss Cancer League (www.swisscancer.ch)
Ad-hoc reviewer for the following journals:
- Allergy (www.blackwellpublishing.com/journals/all) - American Journal of Respiratory and Critical Care Medicine (http://ajrccm.atsjournals.org/) - Anesthesia & Analgesia (www.anesthesia-analgesia.org/) - Arteriosclerosis Thrombosis Vascular Biology (http://atvb.ahajournals.org/) - BMC Infectious Diseases (http://www.biomedcentral.com/bmcinfectdis/) - Cerebrovascular Disease (http://www.karger.com/ced) - Chest (http://chestjournal.chestpubs.org/) - Circulation (http://circ.ahajournals.org/) - Circulation: Cardiovascular Interventions (http://circinterventions.ahajournals.org/) - Clinical Research in Cardiology (http://www.springer.com/medicine/cardiology/journal/392) - Clinical Respiratory Journal (http://www.the-crj.com) - Clinical Infectious Diseases (www.journals.uchicago.edu/CID/home.html) - Clinical Microbiology and Infection (www.blackwellpublishing.com/journals/clm) - Critical Care Medicine (http://journals.lww.com/ccmjournal/pages/default.aspx) - Hypertension (http://hyper.ahajournals.org/) - Intensive Care Medicine (http://www.springer.com/medicine/journal/134) - International Journal of Hygiene and Environmental Health (http://www.elsevier.de/ijheh) - International Journal of Infectious Diseases (http://ees.elsevier.com/ijid/) - Journal of Applied Microbiology (http://www.blackwellpublishing.com/jam) - Journal of Cellular and Molecular Medicine (http://www.blackwellpublishing.com/jcmm) - Journal of Immunology (http://www.jimmunol.org) - Letters in Applied Microbiology (http://www.blackwellpublishing.com/lam) - Mediators of Inflammation (http://www.hindawi.com/journals/mi) - Molecular and Cellular Endocrinology (http://ees.elsevier.com/mce/) - Respiratory Care (www.rcjournal.com/) - Respiratory Medicine (http://ees.elsevier.com/yrmed/) - Stroke (http://stroke.ahajournals.org/)
Memberships:
- Fellow of the "American College of Chest Physicians" (http://www.chestnet.org/) - "American Heart Association" (http://www.americanheart.org/) - "Paul Ehrlich Society" (http://www.p-e-g.de/) - "German Society for Pneumology" (http://www.pneumologie.de) - "German Sepsis Society" (http://www.sepsis-gesellschaft.de/) - "CAPNETZ Study Group" (members of the study group listed in the manuscripts` appendix)
Abstract: BACKGROUND; Hemoptysis can be an acute medical emergency, which can be localized angiographically and controlled by therapeutic intervention.
Abstract: The superior vena cava syndrome (SVCS) comprises various symptoms due to occlusion of the SVC, which can be easily obstructed by pathological conditions (eg, lung cancer, due to the low internal venous pressure within rigid structures of the thorax [trachea, right bronchus, aorta]). The resulting increased venous pressure in the upper body may cause edema of the head, neck, and upper extremities, often associated with cyanosis, plethora, and distended subcutaneous vessels. Despite the often striking clinical presentation, SVCS itself is usually not a life-threatening condition. Currently, randomized controlled trials on many clinically important aspects of SVCS are lacking. This review gives an interdisciplinary overview of the pathophysiology, etiology, clinical manifestations, diagnosis, and treatment of malignant SVCS.
Abstract: OBJECTIVE: In addition to use of a laser, argon plasma coagulation, electrocautery, or coring with a rigid bronchoscope, tumor debulking with a flexible cryoprobe is used for therapeutic bronchoscopy with an immediate effect for endobronchial pathologies. We performed this analysis to determine the usefulness, efficacy, and safety of the flexible cryorecanalization in a large population under routine conditions. METHODS: We identified 225 bronchoscopic interventions that were done as cryorecanalization with a flexible cryoprobe. All patients had symptomatic airway stenosis. We determined the endoscopic success rate and safety (bleeding and perforation) of the procedure. RESULTS: Successful cryorecanalization was achieved in 205 (91.1%) of 225 patients. The flexible cryoprobe was used with all patients, in most patients in combination with flexible bronchoscopy and only in a minority (n = 31, 13.8%) in combination with a rigid bronchoscope. Additional interventional techniques used were endobronchial stents (n = 11, 4.9%) and argon plasma coagulation (n = 37, 16.4%). Mild bleeding (if ice-cold NaCl or epinephrine solution was necessary) occurred in 9 (4.0%) patients, moderate bleeding (if argon plasma coagulation or a bronchus blocker was required) occurred in 18 (8.0%) patients, and severe bleeding (events with hemodynamic instability) never occurred. CONCLUSIONS: Cryorecanalization with the flexible cryoprobe for treatment of symptomatic endobronchial tumor stenosis is a safe technique with a high success rate and immediate treatment effect.
Abstract: In industrialized countries respiratory tract infections are one of the most common reasons for medical consultations. It is assumed that almost one third of these infections affect the lower respiratory tract (LRTI), e. g. acute bronchitis, acute exacerbation of chronic obstructive pulmonary disease (COPD), community- or hospital-acquired pneumonia and influenza. Due to a lack of sufficient and valid investigations on the epidemiology of respiratory viruses, their impact on the pathogenesis of LRTI has probably been underestimated for a long time. Therefore, there might have been many cases of needless antibiotic treatment, particularly in cases of acute bronchitis or acute exacerbations of COPD, because of an assumed bacteriological aetiology. Following the introduction of diagnostic procedures with increased sensitivity, such as polymerase chain reaction, it is possible to reliably detect respiratory viruses and to illuminate their role in the pathogenesis of LRTI of the adult. We have reviewed the current literature to elucidate the role of viruses in the pathogenesis of LRTI. The first part of this series described frequent viral pathogens, pathogenesis of viral LRTI, and diagnostic procedures. In this 2 (nd) part the aetiological role of viruses in the most frequent forms of LRTI will be highlighted, and the third and last part will provide an overview of therapeutic and preventive options.
Abstract: Objective: Besides persisting high pulmonary arterial pressure and increased pulmonary vascular resistance, remodelling of pulmonary tissues and subsequently the right heart are the key pathomechanisms of pulmonary hypertension (PH). Extracellular matrix maintenance in this context plays a central role. Methods: We tested the hypothesis that plasma concentration of matrix metalloproteinase (MMP)-2, tissue inhibitor of matrix metalloproteinases (TIMP)-4 and tenascin C (TNC) might be useful as biomarkers for assessing the severity of PH. Therefore, the concentrations of MMP-2, TIMP-4, TNC and N-terminal b-type natriuretic peptide (NT-proBNP) of 36 PH patients were compared with those of 44 age- and gender-matched healthy volunteers. Additionally, lung function, 6-min walk distance and right heart function were assessed. Results: In PH patients, significantly elevated plasma levels of MMP-2, TIMP-4, TNC and NT-proBNP were detected. In particular, TIMP-4 was significantly increased in patients with higher NYHA classification, and in patients with severe right ventricular hypertrophy. Conclusion: Monitoring of plasma TIMP-4 and to a lesser extent of MMP-2 and TNC levels in PH patients might help to assess the beneficial effects of PH pharmacotherapy on tissue remodelling.
Abstract: OBJECTIVE: Forceps biopsy is the standard method to obtain specimens in endoscopically visible lesions. It is common to combine forceps biopsy with cytology methods to increase the diagnostic yield. Although the flexible cryoprobe has been established for bronchoscopic interventions in malignant stenosis, the obtained biopsies, called "cryobiopsies," have not been investigated in a large cohort of patients. The aim of this feasibility study was to prospectively evaluate the diagnostic yield and safety of cryobiopsy and forceps biopsy. METHODS: During a 6-year period, 296 patients with visible endoluminal tumor lesions were included in the study at the bronchoscopy unit of a university hospital. In the first consecutively conducted 55 cases, both techniques, forceps biopsy and cryobiopsy, were applied simultaneously. Pathologic and quantitative image analyses were performed to evaluate the size and quality of the obtained specimens. We evaluated the safety and diagnostic yield to describe the feasibility of cryobiopsy. RESULTS: Comparative analysis of the first conducted and randomly assigned 55 cases revealed a significantly higher diagnostic yield for cryobiopsy compared with forceps biopsy (89.1% vs 65.5%, P < .05). In this cohort, quantitative image analysis showed significantly larger biopsies regarding size and artifact-free tissue sections for cryobiopsy compared with forceps biopsy (P < .0001). The overall diagnostic yield of cryobiopsy was 89.5%. Mild bleeding occurred in 11 cases (3.7%), moderate bleeding occurred in 3 cases (1.0%), and severe bleeding occurred in 1 case (0.3%). CONCLUSION: Cryobiopsy is safe and increases the diagnostic yield in endobronchial tumor lesions. The method also is feasible under routine conditions.
Abstract: In industrialized countries respiratory tract infections are one of the most common reasons for medical consultations. It is assumed that almost one third of these infections include the lower respiratory tract (LRTI), e. g. acute bronchitis, acute exacerbation of chronic obstructive pulmonary disease (COPD), community- or hospital-acquired pneumonia and influenza. Due to a lack of sufficient and valid investigations to prove the presence of respiratory viruses their impact in the pathogenesis of lower respiratory tract infection has probably been underestimated for a long time. Therefore, there might have been many cases of unnecessary antibiotic treatment, especially in cases of acute bronchitis or acute exacerbations of COPD, because of an assumed bacteriological cause. With the introduction of more sensitive investigational procedures, such as polymerase chain reaction, it is possible to sufficiently prove respiratory viruses and therefore illuminate their role in the pathogenesis of lower respiratory tract infections of the adult. We have reviewed the current literature on the impact of viruses in lower respiratory tract infections to elucidate the role of viruses in the pathogenesis of lower respiratory tract infections. The preceding parts of this series provided an introduction to the frequently found viruses, pathogenesis, and diagnostic procedures (part I) as well as common viral infections of the lower respiratory tract (part II). The present 3 (rd) part deals with therapy for and prevention of viral LRTI.
Abstract: Bacterial endotoxin is known to act as a potent trigger of disseminated coagulation and septic shock. During clinical antibiotic treatment, endotoxin may be released from Gram-negative bacteria. It is known that antibiotic classes differ in their ability to induce endotoxin release.
Abstract: BACKGROUND/AIMS: Genes encoding for some of the mitochondrial proteins are under the control of the transcriptional factor hypoxia inducible factor-1 alpha (HIF-1 alpha), which can accumulate under normoxic conditions in inflammatory states. The aim of this study was to evaluate the effects of cobalt chloride (CoCl(2), a hypoxia mimicking agent), tumour necrosis factor-alpha (TNF-alpha) and toll-like receptor (TLR) -2, -3 and -4 agonists on HIF-1 alpha accumulation, and further on HIF-1 alpha-mediated modulation of mitochondrial respiration in cultured human hepatocytes. METHODS: The human hepatoma cell line HepG2 was used in this study. Cells were treated with CoCl(2), TNF-alpha and TLR-2, -3 and -4 agonists. HIF-1 alpha was determined by Western blotting and mitochondrial respiration in stimulated cells by high-resolution respirometry. RESULTS: CoCl(2), TNF-alpha and TLR agonists induced the expression of HIF-1 alpha in a time-dependent fashion. TNF-alpha and CoCl(2), but not TLR agonists, induced a reduction in complex I-, II- and IV-dependent mitochondrial oxygen consumption. TNF-alpha-associated reduction of cellular oxygen consumption was abolished through inhibition of HIF-1 alpha activity by chetomin (CTM). Pretreatment with cyclosporine A prevented CoCl(2)-induced reduction of complex I- and II-dependent mitochondrial oxygen consumption and TNF-alpha-induced reduction of complex-I-dependent respiration, implicating the involvement of the mitochondrial permeability transition pore openings. TNF-alpha and TLR-2, -3 and -4 agonists induced the expression of vascular endothelial growth factor, which was partially abolished by the blockage of HIF-1 alpha with CTM. CONCLUSIONS: The data suggest that HIF-1 alpha modulates mitochondrial respiration during CoCl(2) and TNF-alpha stimulation, whereas it has no effect when induced with TLR-2, -3 and -4 agonists.
Abstract: In industrialised countries respiratory tract infections are one of the most common reasons for medical consultations. It is assumed that almost one third of these infections include the lower respiratory tract (LRTI), e. g. acute bronchitis, acute exacerbation of chronic obstructive pulmonary disease (COPD), community- or hospital-acquired pneumonia and influenza. Due to a lack of sufficient and valid investigations on the epidemiology of respiratory viruses, their impact on the pathogenesis of LRTI has probably been underestimated for a long time. Therefore, there might have been many cases of needless antibiotic treatment, particularly in cases of acute bronchitis or acute exacerbations of COPD, because of an assumed bacteriological aetiology. Following the introduction of diagnostic procedures with increased sensitivity, such as polymerase chain reaction, it is possible to reliably detect respiratory viruses and to illuminate their role in the pathogenesis of LRTI of the adult. We have reviewed the current literature to elucidate the role of viruses in the pathogenesis of LRTI. The first part of this series deals with the relevant pathogens, pathogenesis, and diagnostic procedures. In the subsequent 2 parts of this series a review will be given on the most common variants of viral LRTI (part II), and therapeutic and preventive options (part III).
Abstract: INTRODUCTION: Several recent studies have shown that a positive fluid balance in critical illness is associated with worse outcome. We tested the effects of moderate vs. high-volume resuscitation strategies on mortality, systemic and regional blood flows, mitochondrial respiration, and organ function in two experimental sepsis models. METHODS: 48 pigs were randomized to continuous endotoxin infusion, fecal peritonitis, and a control group (n = 16 each), and each group further to two different basal rates of volume supply for 24 hours [moderate-volume (10 ml/kg/h, Ringer's lactate, n = 8); high-volume (15 + 5 ml/kg/h, Ringer's lactate and hydroxyethyl starch (HES), n = 8)], both supplemented by additional volume boli, as guided by urinary output, filling pressures, and responses in stroke volume. Systemic and regional hemodynamics were measured and tissue specimens taken for mitochondrial function assessment and histological analysis. RESULTS: Mortality in high-volume groups was 87% (peritonitis), 75% (endotoxemia), and 13% (controls). In moderate-volume groups mortality was 50% (peritonitis), 13% (endotoxemia) and 0% (controls). Both septic groups became hyperdynamic. While neither sepsis nor volume resuscitation strategy was associated with altered hepatic or muscle mitochondrial complex I- and II-dependent respiration, non-survivors had lower hepatic complex II-dependent respiratory control ratios (2.6 +/- 0.7, vs. 3.3 +/- 0.9 in survivors; P = 0.01). Histology revealed moderate damage in all organs, colloid plaques in lung tissue of high-volume groups, and severe kidney damage in endotoxin high-volume animals. CONCLUSIONS: High-volume resuscitation including HES in experimental peritonitis and endotoxemia increased mortality despite better initial hemodynamic stability. This suggests that the strategy of early fluid management influences outcome in sepsis. The high mortality was not associated with reduced mitochondrial complex I- or II-dependent muscle and hepatic respiration.
Abstract: Community-acquired pneumonia (CAP) remains a major cause of mortality in developed countries. There is much discrepancy in the literature regarding factors influencing the outcome in the elderly population.Data derived from a multicenter prospective study initiated by the German Competence network CAPNETZ.2647 patients (1298 <65 years, 1349 >65 years) with CAP were evaluated. 72.3% were hospitalised, 27.7% treated in the community.Clinical history, residence status, course of disease and antimicrobial treatment were prospectively documented. Microbiologic investigations included cultures and PCR from respiratory samples and blood cultures. Factors related to mortality were included in multivariate analysis.Overall 30-day mortality was 6.3%. Elderly patients had a significantly higher mortality rate which was associated independently with age, residence status, the CURB score, comorbidities and failure of initial therapy. Increasing age remained predictive for death in the elderly. Nursing homes residents had a fourfold increased mortality rate and an increased rate of gram-negative bacillary infections compared to patients dwelling in the community. The CURB score and cerebrovascular disease were confirmed as independent predictors of death in this subgroup.Age and residence status are independent risk factors for mortality after controlling for comorbidities and disease severity. Failure of initial therapy was the only modifiable prognostic factor.
Abstract: Recognition of bacterial lipopolysaccharide (LPS) by the innate immune system involves at least three receptor molecules: CD14, TLR4 and MD-2. Additional receptor components such as heat shock proteins, chemokine receptor 4 (CXCR4), or CD55 have been suggested to be part of this activation cluster; possibly acting as additional LPS transfer molecules. Our group has previously identified CXCR4 as a component of the "LPS-sensing apparatus". In this study we aimed to elucidate the role that CXCR4 plays in innate immune responses to LPS. Here we demonstrate that CXCR4 transfection results in responsiveness to LPS. Fluorescence correlation spectroscopy experiments further showed that LPS directly interacts with CXCR4. Our data suggest that CXCR4 is not only involved in LPS binding but is also responsible for triggering signalling, especially mitogen-activated protein kinases in response to LPS. Finally, co-clustering of CXCR4 with other LPS receptors seems to be crucial for LPS signalling, thus suggesting that CXCR4 is a functional part of the multimeric LPS "sensing apparatus".
Abstract: OBJECTIVE: Adiponectin has anti-atherogenic properties and low circulating adiponectin has been linked to coronary atherosclerosis. Yet, there is considerable evidence that the high-molecular weight (HMW) complex of adiponectin is the major active form of this adipokine. We therefore investigated whether HMW adiponectin is associated with the extent of coronary artery disease (CAD) in men. RESEARCH DESIGN AND METHODS: Associations among CAD, HMW adiponectin and the HMW/total-adiponectin ratio were assessed in 240 male patients undergoing elective coronary angiography. Total adiponectin and HMW adiponectin was measured by enzyme-linked immunosorbent assay and serum levels were correlated with defined coronary scores and established cardiovascular risk factors. RESULTS: We found significant inverse correlations between angiographic scores and HMW adiponectin [Extent Score (ES): r=-0.39; Gensini Score (GS): r=-0.35; and Severity Score (SS): r=-0.40, all P<0.001], and the HMW/total-adiponectin ratio (ES: r=-0.49; GS: r=-0.46; SS: r=-0.46; all P<0.001). Multivariable regression analyses revealed that HMW adiponectin and the HMW/total-adiponectin ratio were significantly associated with the extent of CAD (both P<0.001). ROC analyses demonstrated that the predictive value of HMW adiponectin and the HMW/total-adiponectin ratio for the extent of coronary atherosclerosis significantly exceeded that of total adiponectin (P<0.001, P=0.010, respectively). CONCLUSIONS: HMW adiponectin and the HMW/total-adiponectin ratio inversely correlate with the extent of CAD. HMW adiponectin in particular seems to be a better marker for CAD extent than total adiponectin.
Abstract: OBJECTIVES: In Germany the estimation of a population based annual incidence of community acquired pneumonia (CAP) in adults has been referred to the denominator problem. To estimate a population based annual incidence of CAP in an urban German area we compared the incidence estimated on four different approaches. METHODS: We estimated the annual incidence on the basis of the covered population of sentinel practices from Luebeck participating in the German competence network CAPNETZ. We estimated the incidence on the basis of a population based survey, on the basis of the mortality and lethality in Luebeck, and on the basis of data of the regional Association of Statutory Health Insurance Physicians ("Kassenärztliche Vereinigung (KV) Schleswig-Holstein"). RESULTS: The annual incidence of CAP in Luebeck was 3.7/1000 inhabitants (95% confidence interval (CI) 2.4-5.5), 6.0/1000 inhabitants, 8.7/1000 inhabitants (95% CI 8.2-9.1), or 10.1/1000 inhabitants (95% CI 9.6-10.5) depending on the approach of estimation. According to this, in Germany we would expect 400,000-680,000 new CAP cases per year. CONCLUSIONS: The true incidence of CAP in Luebeck might range between 3.7 and 10 per 1000 inhabitants. Comparisons with the rates in the literature are difficult due to the differences in the applied methods.
Abstract: Community Acquired Pneumonia (CAP) is a frequent and potentially fatal infectious disease which, in the majority of cases, needs an antibiotic intervention. OBJECTIVES: Aim was to evaluate antibiotic treatment patterns regarding all types of mono- and combination-therapy throughout the local clinical centres (LCCs) represented in the German competence network CAPNETZ (=Community Acquired Pneumonia Network) and to identify clinical indicators for regional differences. METHODS: We analysed outpatients and inpatients recruited between March 2003 and April 2005. Patient and treatment details were registered online using standardised data entry forms. A logistic regression model was issued for the 4 most frequently applied antibiotics, adjusting for potentially relevant confounders. RESULTS: The study sample consisted of 3221 patients at the age of 18 to 102 years. Overall, aminopenicillins plus betalactamase inhibitor (20.4%), fluoroquinolone (17.0%), macrolides combined with cephalosporins third generation (10.6%) and cephalosporins third generation (8.9%) were most frequently prescribed. After control for potential confounders, significant treatment differences remained between study sites. Regional variability of antibiotic CAP-treatment could not be attributed to a number of clinical or sociodemographic factors. CONCLUSIONS: The presented treatment variability ranges within given guidelines, but indicates the need for an ongoing implementation of evidence-based guidelines in order to avoid potential negative clinical or economic consequences.
Abstract: The objective of this case-control study was to identify the main risk factors for community-acquired pneumonia (CAP) in a German adult population. A self-administered questionnaire was given to CAP cases provided by the German competence network CAPNETZ and population-based, randomly selected controls (sex- and age-matched). Multivariate analysis showed that in addition to known risk factors such as previous CAP [odds ratio (OR) 1.6, 95% confidence interval (CI) 1.3-2.1], more than one respiratory infection during the previous year (OR 3.6, 95% CI 2.9-4.5), chronic pulmonary diseases (OR 2.3, 95% CI 1.7-3.0), number of comorbidities (OR 1.6, 95% CI 1.4-1.9), and number of children in the household (2 children: OR 2.2, 95% CI 1.5-3.4; > or = 3 children: OR 3.2, 95% CI 1.5-7.0) were independent risk factors for CAP. This was pronounced in particular in people aged < or = 65 years. The most likely explanation for this finding is higher exposure to infectious agents.
Abstract: OBJECTIVES: In this study we tested the hypothesis that lipopolysaccharide-binding protein (LBP) might be able to be used as a biomarker for coronary artery disease (CAD). BACKGROUND: The mechanisms by which the innate immune recognition of pathogens could lead to atherosclerosis remain unclear. Lipopolysaccharide-binding protein is the first protein to encounter lipopolysaccharide and to deliver it to its cellular targets, toll-like receptors; therefore, its presence might be a reliable biomarker that indicates activation of innate immune responses. METHODS: A total of 247 men undergoing elective coronary angiography were studied, and the extent of coronary atherosclerosis was assessed by 2 established scores: "extent score" and "severity score." Levels of LBP, markers of inflammation, and traditional risk factors for CAD were assessed. RESULTS: Serum LBP concentration was significantly increased in 172 patients with angiographically confirmed CAD compared with 75 individuals without coronary atherosclerosis (20.6 +/- 8.7 pg/ml vs. 17.1 +/- 6.0 pg/ml, respectively; p = 0.002). Moreover in multivariable logistic regression analyses, adjusted for established cardiovascular risk factors and markers of systemic inflammation, LBP was a significant and independent predictor of prevalent CAD (p < 0.05 in all models). CONCLUSIONS: Lipopolysaccharide-binding protein might serve as a novel marker for CAD in men. The present results underlie the potential importance of innate immune mechanisms for CAD. Further studies are warranted to bolster the data and to identify pathogenetic links between innate immune system activation and atherosclerosis.
Abstract: BACKGROUNDS: Cyclophosphamide and high-dose steroids have been used as limited induction therapy in progressive IgA nephropathy (IgAN) to reduce the loss of renal function and proteinuria. We evaluated the effect of cyclophosphamide pulses (CyP) and mycophenolic acid (MPA) as sequential therapy on renal function in patients with progressive IgAN. METHODS: Twenty patients with progressive IgAN and advanced renal failure (median GFR 22 ml/min per 1.73 m2) and further disease activity (triangle downGFR -0.8 ml/min per month) after cyclophosphamide (CyP; n = 18) or steroid pulse therapy (n = 2) were treated with mycophenolate mofetil 1 g per day for a median of 27 months. RESULTS: The monthly loss of renal function was significantly reduced in linear regression analysis from -2.4 ml/min before CyP to -0.12 ml/min with CyP/MPA (p = 0.0009). Estimated renal survival time was significantly prolonged by a median of 65 months (p = 0.0014). Proteinuria decreased significantly from 1.7 to 0.4 g/l during MPA treatment (p = 0.015). In Cox regression analysis, only proteinuria >1.0 g/l was an independent risk factor for doubling of creatinine during CyP/MPA treatment (p = 0.03). CONCLUSION: A sequential therapy with CyP/MPA may arrest or slow down the loss of renal function and reduces proteinuria even in patients who passed the so called 'point of no return' with progressive IgAN.
Abstract: Infection with bacteria such as Chlamydia pneumonia, Helicobacter pylori or Porphyromonas gingivalis may be triggering the secretion of inflammatory cytokines that leads to atherogenesis. The mechanisms by which the innate immune recognition of these pathogens could lead to atherosclerosis remain unclear. In this study, using human vascular endothelial cells or HEK-293 cells engineered to express pattern-recognition receptors (PRRs), we set out to determine Toll-like receptors (TLRs) and functionally associated PRRs involved in the innate recognition of and response to lipopolysaccharide (LPS) from H. pylori or P. gingivalis. Using siRNA interference or recombinant expression of cooperating PRRs, we show that H. pylori and P. gingivalis LPS-induced cell activation is mediated through TLR2. Human vascular endothelial cell activation was found to be lipid raft-dependent and to require the formation of heterotypic receptor complexes comprising of TLR2, TLR1, CD36 and CD11b/CD18. In addition, we report that LPS from these bacterial strains are able to antagonize TLR4. This antagonistic activity of H. pylori or P. gingivalis LPS, as well as their TLR2 activation capability may be associated with their ability to contribute to atherosclerosis.
Abstract: Dieses Positionspapier ist eine Stellungnahme der Deutschen Gesellschaft für Kardiologie – Herz- und Kreislaufforschung (DGK) und der Paul-Ehrlich Gesellschaft für Chemotherapie, die den gegenwärtigen
Erkenntnisstand wiedergibt und allen Ärzten und ihren Patienten die Entscheidungsfindung erleichtern soll. Es werden bisher publizierte, relevante Studien herangezogen, gelöste Fragen beantwortet
und ungelöste aufgezeigt. Es wird eine Empfehlung abgegeben, für welche Patienten das vorgestellte (diagnostische und/oder therapeutische) Verfahren infrage kommt. Der Zusammenhang zwischen
der jeweiligen Empfehlung und dem zugehörigen Evidenzgrad ist gekennzeichnet.
Das Positionspapier ersetzt nicht die ärztliche Evaluation des individuellen Patienten
und die Anpassung der Diagnostik und Therapie an dessen spezifische Situation.
Abstract: AIMS/HYPOTHESIS: Retinol-binding protein 4 (RBP4) has recently been reported to be associated with insulin resistance and the metabolic syndrome. This study tested the hypothesis that RBP4 is a marker of insulin resistance and the metabolic syndrome in patients with type 2 diabetes or coronary artery disease (CAD) or in non-diabetic control subjects without CAD. METHODS: Serum RBP4 was measured in 365 men (126 with type 2 diabetes, 143 with CAD and 96 control subjects) and correlated with the homeostasis model assessment of insulin resistance index (HOMA-IR), components of the metabolic syndrome and lipoprotein metabolism. RBP4 was detected by ELISA and validated by quantitative Western blotting. RESULTS: RBP4 concentrations detected by ELISA were shown to be strongly associated with the results gained in quantitative Western blots. There were no associations of RBP4 with HOMA-IR or HbA(1c) in any of the groups studied. In patients with type 2 diabetes there were significant positive correlations of RBP4 with total cholesterol, LDL-cholesterol, VLDL-cholesterol, plasma triacylglycerol and hepatic lipase activity. In patients with CAD, there were significant associations of RBP4 with VLDL-cholesterol, plasma triacylglycerol and hepatic lipase activity, while non-diabetic control subjects without CAD showed positive correlations of RBP4 with VLDL-cholesterol and plasma triacylglycerol. CONCLUSIONS/INTERPRETATION: RBP4 does not seem to be a valuable marker for identification of the metabolic syndrome or insulin resistance in male patients with type 2 diabetes or CAD. Independent associations of RBP4 with pro-atherogenic lipoproteins and enzymes of lipoprotein metabolism indicate a possible role of RBP4 in lipid metabolism.
Abstract: We present a case of severe sepsis due to Streptococcus pneumoniae, serotype 22F treated with recombinant human activated protein C (drotrecogin alpha activated) (DrotAA). APACHE II score at admission was 34 with a predicted mortality of 81%. A wide range of cytokines, chemokines and receptors was measured before and after DrotAA treatment. Soon after infusion of 24 microg DrotAA per kg bodyweight and h (microg/kg/h) over a period of 96 h, cytokine levels fell markedly. The patient survived and was discharged after 6 weeks of hospitalization. In conclusion, administration of DrotAA in a case of Streptococcus pneumoniae-induced septic shock was followed by dramatic changes in serum levels of immuno-regulatory cytokines.
Abstract: INTRODUCTION: Since 2002, the German competence network CAPNETZ has been collecting data from inpatients and outpatients with community acquired pneumonia (CAP) at eight local clinical centres. Contrary to the literature reports, the proportion of outpatients in CAPNETZ averages out at 28 %. Therefore, this study determines whether an active reporting system can increase the number of cases reported in medical practices. METHOD: In ten medical practices in Lübeck, the passive reporting system was changed to an active reporting system consisting of a) a weekly announcement of CAP cases including negative reporting, b) a study nurse who was responsible for the reporting, c) additional payment, d) a telephone call after two weeks by absent announcements and e) incentives like benchmarking or additional information. The number of the reported cases between the active reporting period (2004) and the same period in the year before was recorded. RESULTS: The number of reported cases increased in eight of the ten medical practices. Overall 72 CAP cases were reported, 33 % more than in the period of passive reporting. The number of patients encompassed in CAPNETZ increased from 17 to 34. CONCLUSION: We did not find a comparable increase of CAP cases either in Lübeck overall (including inpatients) or in all the local clinical centres together. Thus, it is assumed that the increase of reported cases depends on the methodical effect.
Abstract: Infection with Helicobacter pylori may be associated with a variety of gastroduodenal diseases. Although H. pylori infection is common, peptic ulcer disease and gastric cancer occur in only a small minority of infected persons. This work was intended to correlate the pathological findings with the serological response to certain H. pylori antigens. Serum samples were taken from 285 patients who underwent gastroscopy. H. pylori infection was diagnosed by histology, culture or rapid urease test (RUT). Serum IgG reactivity against H. pylori-specific antigens was studied by Western blot. There was a significant association between the diagnosis of gastric cancer and the presence of IgG antibodies against the 19.5, 33 and 136 kDa (CagA) antigens. Comparing all H. pylori-positive patients with the gastric cancer group for the presence of the 19.5, 33 and 136 kDa (CagA) antigens, the results were as follows: chi2: 17.482, p < 0.001, power P = 0.994, odds ratio (OR) for the presence of gastric cancer: 19.5 (95% confidence interval (CI): 4.11-92.56). Antibodies against CagA alone or other bands (except 33 and 19.5 kDa antigens), as well as the age of patients were not related to a diagnosis of gastric cancer. Male patients were more likely to develop duodenal ulcer. IgG antibodies against the 19.5, 33 and 136 kDa (CagA) antigens could be helpful to identify patients at enhanced risk for the development of gastric cancer.
Abstract: The epidemiology of Pseudomonas aeruginosa infections and colonizations was studied prospectively on a 12-bed medical intensive care unit. Patients were monitored for P. aeruginosa colonization by performing throat swabs or tracheal aspirates on admission and weekly thereafter over a period of 6 months. Cultures of possibly infected sites were taken as clinically indicated. Water samples from all patient care-related tap water outlets were collected in 2-weekly intervals and examined for the presence of P. aeruginosa. Strains isolated from patients and water samples were analysed by serotyping and random amplified polymorphic DNA polymerase chain reaction (RAPD-PCR) typing. During the 6-month period, 60 of 143 (42%) water samples contained P. aeruginosa at various levels ranging from 1 to >100 colony-forming units per 100ml sample. Genotypically, water samples contained 8 different clonotypes. Nine patients had infections due to P. aeruginosa and 7 patients were colonized. Isolates from patients showed a similar distribution of genotypes as did tap water isolates, and strains of identical genotype as patient strains had been isolated previously from tap water outlets in 8 out of 16 (50%) infection or colonization episodes. However, patients also harboured strains not previously isolated from tap water. Thus, in addition to tap water, other environmental or unknown reservoirs appeared to play a role for the epidemiology of P. aeruginosa infections on this ward. However, because tap water played a significant role for strain transmissions, we conclude that intensified water site care is justified.
Abstract: OBJECTIVE: The study was performed to validate the CURB, CRB and CRB-65 scores for the prediction of death from community-acquired pneumonia (CAP) in both the hospital and out-patient setting. DESIGN: Data were derived from a large multi-centre prospective study initiated by the German competence network for community-acquired pneumonia (CAPNETZ) which started in March 2003 and were censored for this analysis in October 2004. SETTING: Out- and in-hospital patients in 670 private practices and 10 clinical centres. SUBJECTS: Analysis was done for n = 1343 patients (n = 208 out-patients and n = 1135 hospitalized) with all data sets completed for the calculation of CURB and repeated for n = 1967 patients (n = 482 out-patients and n = 1485 hospitalized) with complete data sets for CRB and CRB-65. INTERVENTION: None. 30-day mortality from CAP was determined by personal contacts or a structured interview. RESULTS: Overall 30-day mortality was 4.3% (0.6% in out-patients and 5.5% in hospitalized patients, P < 0.0001). Overall, the CURB, CRB and CRB-65 scores provided comparable predictions for death from CAP as determined by receiver-operator-characteristics (ROC) curves. However, in hospitalized patients, CRB misclassified 26% of deaths as low risk patients. Availability of the CRB-65 score (90%) was far superior to that of CURB (65%), due to missing blood urea nitrogen values (P < 0.001). CONCLUSIONS: Both the CURB and CRB-65 scores can be used in the hospital and out-patients setting to assess pneumonia severity and the risk of death. Given that the CRB-65 is easier to handle, we favour the use of CRB-65 where blood urea nitrogen is unavailable.
Abstract: As a noninvasive method, exhaled breath condensate (EBC) has gained importance to improve monitoring of lung diseases and to detect biomarkers. The aim of the study was to investigate, whether erythropoietin (EPO) is detectable in EBC. EBC was collected from 22 consecutive patients as well as from healthy individuals. Using a multiplex fluorescent bead immunoassay, we detected EPO in EBC, as well as tumour necrosis factor-alpha (TNF-alpha) in 13 out of 22 patients simultaneously (EPO 0.21 +/- 0.03 in U/mL and TNF-alpha 34.6 +/- 4.2 in pg/mL, mean +/- SEM). No significant differences for EPO levels or correlation between EPO and TNF-alpha were found but TNF-alpha was significantly higher in patients with chronic obstructive pulmonary disease (COPD) than in non-COPD (obstructive sleep apnoea, OSA, and lung healthy patients). This is the first report of detection of EPO in EBC. Due to the small study size more data is needed to clarify the role of EPO in EBC.
Abstract: In progressive immunoglobulin A nephropathy (IgAN), intravenous immunoglobulin (IVIg) treatment has been used to delay disease progression, but the long-term efficacy is largely unknown. We report the clinical outcomes after IVIg therapy in six male patients with progressive IgAN [median glomerular filtration rate (GFR) 31 ml/min per 1.73 m(2)] followed for a median observation period of 8 years. In this single-arm, non-randomized study, IVIg was given monthly at a dose of 2 g/kg body weight for 6 months. The course of renal function was assessed by linear regression analysis of GFR and proteinuria, and was compared to eight patients with IgAN (median GFR 29 ml/min per 1.73 m(2)) without IVIg as a contemporaneous control group. IgAN disease progression was delayed after IVIg therapy on average for 3 years. The mean loss of renal function decreased from -1.05 ml/min per month to -0.15 ml/min per month (P = 0.024) and proteinuria decreased from 2.4 g/l to 1.0 g/l (P = 0.015). The primary end-point (GFR < 10 ml/min or relapse) occurred 5.2 years (median; range 0.4-8.8) after the first IVIg pulse, and after 1.3 years (median; range 0.8-2.4) in the control group (P = 0.043). In Kaplan-Meier analysis, the median renal survival time with IVIg was prolonged by 3.5 years (IVIg 4.7 years versus control 1.2 years; P = 0.006). IVIg pulse therapy may be considered as a treatment option to reduce the loss of renal function and improve proteinuria in patients with progressive IgAN.
Abstract: In spite of the significant changes in the spectrum of organisms causing intensive care unit (ICU)-associated infections, Pseudomonas aeruginosa has held a nearly unchanged position in the rank order of pathogens causing ICU-related infections during the last 4 decades. Horizontal transmissions between patients have long been considered the most frequent source of P aeruginosa colonizations/infections. The application of molecular typing methods made it possible, during the last approximately 7 years, to identify ICU tap water as a significant source of exogenous P aeruginosa isolates. A review of prospective studies published between 1998 and 2005 showed that between 9.7% and 68.1% of randomly taken tap water samples on different types of ICUs were positive for P aeruginosa , and between 14.2% and 50% of infection/colonization episodes in patients were due to genotypes found in ICU water. Faucets are easily accessible for preventive measures, and the installation of single-use filters on ICU water outlets appears to be an effective concept to reduce water-to-patient transmissions of this important nosocomial pathogen.
Abstract: The group B coxsackieviruses are single-stranded RNA viruses that have been implicated in viral myocarditis. Viral infection of the myocardium, as well as the associated inflammatory response are important determinants of the virus-associated myocardial damage. Although these viruses are known as cytopathic viruses that cause death of the host cell, their viral RNA has been shown to persist in cardiac muscle contributing to a chronic inflammatory cardiomyopathy. Thus, it is essential that we understand the mechanism by which Coxasckie B viruses (CBVs) trigger this inflammatory response. In this study we investigated the involvement of Toll-like receptors (TLRs) in the recognition of CBV virions as well as CBV single-stranded RNA. Here we report that the CBV-induced inflammatory response is mediated through TLR8 and to a lesser extent through TLR7.
Abstract: BACKGROUND: We investigated whether myocardial biopsy analysis for inflammation and viruses correlates with outcome in dilated cardiomyopathy. METHODS: Myocardial biopsies of 82 patients were analyzed for HLAI, HLAII, CD54, CD2, CD68 and entero-/adenovirus. Ejection fraction was determined by left ventriculography. NYHA classification, electrocardiogram (ECG) and echocardiography were analyzed at first admission and for follow up. Patients were attributed to three groups: (A) no inflammation/no virus (B) inflammation/no virus (C) virus with/without inflammation. Patients not responding to conventional treatment of heart failure received interferon beta1b (group C) or prednisolone (group B). Median follow up was 7 months (group A), 11 months (group B) and 14.5 months (group C). RESULTS: Thirty nine patients (48%) belonged to group A, 33 patients (40%) to group B, 10 patients (12%) to group C. Only enterovirus was detected. Ejection fraction at admission was worse for group B compared to group A (p=0.003). Groups A and B improved for echocardiography and NYHA (p< or =0.001). Group C improved for echocardiography only (p=0.031). Group B showed a better outcome for echocardiography (p=0.014) and NYHA (p=0.023) than group A. CONCLUSIONS: Inflammatory cardiomyopathy shows the best outcome. Antiinflammatory or antiviral treatment may be an option in patients not responding to conventional therapy.
Abstract: Toll-like receptors (TLR) have a key role in regulating immunity against microbial agents. Engagement of TLR by bacterial, viral or fungal components leads to the production and release of inflammatory cytokines. In this study we show that mainly TLR8 and also TLR7 act as the host sensors for human parechovirus 1, a single-stranded RNA (ssRNA) virus. Furthermore, we see that the viral ssRNA genome is detected in endosomal compartments by these TLR, which activate signalling that lead to the synthesis of pro-inflammatory molecules by the host.
Abstract: Infection with Helicobacter pylori, a Gram-negative bacterium, is strongly associated with gastric ulcers and adenocarcinoma. The mechanisms by which the innate immune system recognizes H. pylori lipopolysaccharide (LPS) remain unclear. Contradictory reports exist that suggest that Toll-like receptors are involved. In this study we evaluated the interactions of Toll-like receptors with LPS from different strains of H. pylori. Using reporter cell lines, as well as HEK293 cells transfected with either CD14 and TLR4, or CD14 and TLR2, we show that H. pylori LPS-induced cell activation is mediated through TLR2. In addition, for the first time, we report that LPS from some H. pylori strains are able to antagonize TLR4. The antagonistic activity of H. pylori LPS from certain strains, as well as the activation via TLR2, might give H. pylori an advantage over the host that may be associated with the clinical outcome of H. pylori infection.
Abstract: Spontaneous coronary artery dissection is a very rare event and occurs most often in young women following childbirth. It is also known as a rare focal complication in Churg-Strauss syndrome. Here, we present the case of a 43-year-old woman who died after spontaneous dissection of all three coronary arteries. The microscopic examination of coronary vessels showed severe eosinophilic infiltrations, whereas all extracardiac (medium-vessel and large-vessel) arteries were intact and free of inflammatory cells. Her history did not reveal allergy, asthma, or eosinophilia. To the best of our knowledge, this is the first case of spontaneous coronary dissection involving all coronary arteries without a history of Churg-Strauss syndrome or hypereosinophilic syndrome.
Abstract: BACKGROUND: The tested device is a new connecting tool for infusion systems that has been designed to replace conventional single-use stopcocks. Because outbreaks of bloodstream infections have been observed during the use of similar connectors in the United States, we examined the microbiological safety of the connecting device after artificial contamination in the laboratory setting and during routine clinical use. METHODS: In the first part of the study, the new device was tested in 3 types of in vitro experiments. In the second part of the study, surgical intensive care patients had their entry ports capped with novel devices (n=27) or with conventional stopcocks (n=32), and samples of infusion fluids and swabs from entry ports were taken after completion of infusion periods. RESULTS: The new device did not perpetuate bacterial contaminations in spite of high artificial inocula in the in vitro experiments. Microbial contamination rates after 96 hours of infusion therapy for the novel connecting tool versus conventional stopcock groups were as follows: swabs from 3-way ports, 6/129 versus 1/111; rest fluid from infusion lines, 0/20 versus 1/22; rest fluid from infusion bottles, 2/196 versus 2/208; rest fluid from perfusor syringes, 7/180 versus 6/142 (all differences not significant). CONCLUSION: The novel connecting device was microbiologically safe and did not increase microbial contamination rates of intravenous infusion systems.
Abstract: Gastric infection with Helicobacter pylori is one of the most common chronic infections in humans, causing substantial morbidity and mortality. The diagnosis of H. pylori infection usually involves upper endoscopy with biopsy since the only noninvasive method of comparable accuracy, the [(13)C]urea breath test, requires technical equipment that is not available in most gastroenterological units. Serological methods for detection of H. pylori infection have reached sufficient accuracy to be used as screening tests before endoscopy or for seroepidemiological surveys. In the present study we evaluated different interpretation criteria for use with immunoglobulin G immunoblotting for the diagnosis of H. pylori infection. We applied five different sets of interpretation criteria, four of which had been published previously, to the Western blot results of 294 patients with different gastrointestinal symptoms. Since it is known that less than 2% of patients who are infected with H. pylori fail to seroconvert, an optimally sensitive Western blotting system should be able to detect approximately 98% of active infections. When the different criteria were applied to our patient population, it became apparent that the abilities of the systems to detect active H. pylori infection were quite varied. The results for the sensitivity and specificity, according to the different applied criteria, ranged from 62.8 to 95.9% and from 85.7 to 100.0%, respectively. Positive predictive values and negative predictive values, according to the published criteria, ranged from 97.2 to 100.0% and from 37.7 to 82.4%, respectively. Recommendations for the optimal use of the different interpretation criteria are discussed.
Abstract: Infections due to Klebsiella pneumoniae and other Klebsiella spp. are a leading cause of hospital-associated morbidity, especially in the intensive care setting. In this study, the hypothesis that normal human sera contain sufficient concentrations of K-antigen-specific antibodies to promote phagocytic killing of encapsulated, highly virulent Klebsiella organisms was tested. K2-antigen-specific IgG and IgM antibodies were detected in each of 10 normal sera, and such antibodies were functionally active in a phagocytic killing assay. Phagocytosis depended critically on sufficient numbers of neutrophils and was impaired by the presence of soluble Klebsiella capsular polysaccharide (CPS). Thus, insufficient numbers of neutrophils and circulation of soluble CPS but not lack of K-specific antibodies may be detrimental in Klebsiella sepsis. The efficacy of hyperimmune sera might be based not on enhancement of phagocytosis but on the neutralization of these detrimental effects of circulating CPS and LPS.
Abstract: It is generally assumed that the antibiotic prescription policy of a hospital has a significant impact on bacterial resistance rates; however, few studies are available to support this concept with valid statistical data. During a 3-year period from 1997 to 2000, we monitored the consumption of beta-lactam and other antibiotics with known activity against Pseudomonas aeruginosa in a 600-bed community hospital. Monthly isolations of P. aeruginosa were assessed, and resistance rates were recorded. Partial correlation coefficients between consumption and resistance rates were determined, taking into account possible associations with other variables such as seasonal effects and transfers from other hospitals. A total of 30 +/- 7 novel P. aeruginosa strains per month were isolated without epidemic clustering. Prescriptions of imipenem varied significantly during the study period, while prescriptions of other antipseudomonal agents were stable, with the exception of an increase in piperacillin-tazobactam prescriptions. Rates of resistance of P. aeruginosa to the antimicrobial agents used showed a time course similar to figures for imipenem consumption. Monthly rates of resistance to imipenem (partial correlation coefficient [cc], 0.63), piperacillin-tazobactam (cc, 0.57), and ceftazidime (cc, 0.56) were significantly associated with imipenem prescription rates in the same or the preceding month, while consumption of ceftazidime or piperacillin-tazobactam had no apparent association with resistance. Among the variables investigated, imipenem consumption was identified as the major factor associated with both carbapenem and beta-lactam resistance in endemic P. aeruginosa. Periods of extensive imipenem use were associated with significant increases in resistance. Our data support the concept that a written antibiotic policy which balances the use of various antibiotic classes may help to avoid disturbances of a hospital's microbial sensitivity patterns.
Abstract: During a 3-year period, three cases of bacterial meningitis developing after spinal or epidural anesthesia were observed at one hospital in Germany. The causative organisms were Streptococcus salivarius (2 cases) and Staphylococcus aureus (1 case). In the first two cases, contamination of the needle by oropharyngeal flora of the anesthesiological team was likely but remained unproven. In the third case, a nasal swab obtained from the operating anesthesiologist yielded a Staphylococcus aureus strain whose genotypic profile was identical to that of the patient's strain. Infection control procedures for spinal anesthesia are discussed.
Abstract: Antibiotic-induced release of bacterial cell wall components can have immediate adverse effects for the patient. This article reviews the data on endotoxin release after initiation of antibiotic therapy and its role in the pathogenesis of sepsis and septic shock. Antibiotics differ in their potential to liberate endotoxins from bacterial cell walls. When used for treatment of systemic Gram-negative infection, some classes of beta-lactam antibiotics lead to markedly increased levels of free endotoxins while treatment with carbapenems and aminoglycosides produces relatively low amounts of endotoxins. Antibiotics that induce the formation of long, aberrant bacterial cells before effectively killing the microorganisms show the highest degree of endotoxin liberation. There is increasing evidence from animal models and clinical studies of sepsis that the antibiotic-mediated release of biologically active cell wall components derived from Gram-positive, Gram-negative or fungal organisms is associated with a rapid clinical deterioration.
Abstract: During a 3-year period, a clinical diagnosis of invasive candidosis was made in 8 out of 2054 consecutive surgical intensive care unit (ICU) patients. These patients were retrospectively matched with 16 control patients who underwent similar surgical procedures and had a similar clinical course except for negative Candida cultures. In all patients, Candida antigen (Ramco CandTec serum antigen test) and antibody serology (Candida HA test) were determined at least once a week during their stay. The antigen test was positive in 1/8 patients and 4/16 controls and thus did not differentiate patients with candidosis from non-infected controls. The HA antibody titer results fulfilled the manufacturer's criteria for positivity in 7/8 patients with candidosis and 2/16 control patients. Thus, the Candida HA antibody test, but not the Ramco antigen test, can be recommended to confirm a clinical diagnosis of invasive candidosis.
Abstract: OBJECTIVE: Establishment of a case definition for invasive candidosis in postsurgical intensive care patients. METHODS: During the period of 1996-1999, 8 cases of invasive candidosis were observed on a surgical intensive care unit. Patient records were evaluated with respect to diagnostic criteria and response to antimycotic therapy. RESULTS: Patients included 3 women and 5 men with a mean age of 62.7 (37-85) years. Candida peritonitis (n = 6) occurred after surgery or perforation of the intestinal tract, and Candida pneumonia was due to artificial ventilation (n = 3). C. albicans was isolated in all 8 cases, but mixed infections with other Candida spp. occurred in 3 cases. The Candida serum antigen test yielded a positive result in only 2/8 cases. I.v. therapy with fluconazole was successful in 7 cases, one patient with severe initial disease died with ongoing infection. With the exception of the lethal case, all patients showed a diagnostic serum antibody test, proving systemic candida infection. CONCLUSION: Based on the case descriptions, we propose the following definition of invasive candidosis: (1) Clinical signs of infection after surgery, (2) absence of bacterial pathogens and/or failure to respond to systemic antibiotics, (3) cultivation of Candida spp. from normally sterile sites or abundant growth in tracheal aspirate, (4) response to antimycotic therapy and (5) diagnostic serum antibody test. This definition proved to be valid for our patients and could be used as an inclusion criterion for future clinical studies of serodiagnosis of Candida infection or antimycotic chemotherapy.
