Severe pneumonia remains an important cause of morbidity and mortality. Polymerase chain reaction (PCR) has been shown to be more sensitive than current standard microbiological methods – particularly in patients with prior antibiotic treatment – and therefore, may improve the accuracy of microbiological diagnosis for hospitalized patients with pneumonia. Conventional detection techniques and multiplex PCR for 14 typical bacterial pneumonia-associated pathogens were performed on respiratory samples collected from adult hospitalized patients enrolled in a prospective multi-center study. Patients were enrolled from March until September 2012. A total of 739 fresh, native samples were eligible for analysis, of which 75 were sputa, 421 aspirates, and 234 bronchial lavages. 276 pathogens were detected by microbiology for which a valid PCR result was generated (positive or negative detection result by Curetis prototype system). Among these, 120 were identified by the prototype assay, 50 pathogens were not detected. Overall performance of the prototype for pathogen identification was 70.6% sensitivity (95% confidence interval (CI) lower bound: 63.3%, upper bound: 76.9%) and 95.2% specificity (95% CI lower bound: 94.6%, upper bound: 95.7%). Based on the study results, device cut-off settings were adjusted for future series production. The overall performance with the settings of the CE series production devices was 78.7% sensitivity (95% CI lower bound: 72.1%) and 96.6% specificity (95% CI lower bound: 96.1%). Time to result was 5.2 hours (median) for the prototype test and 43.5 h for standard-of-care. The Pneumonia Application provides a rapid and moderately sensitive assay for the detection of pneumonia-causing pathogens with minimal hands-on time.Trial RegistrationDeutsches Register Klinischer Studien (DRKS) DRKS00005684
One hundred ninety-two workers in a German pesticide factory who were exposed to polychlorinated dibenzodioxins and -furans (PCDD/PCDF) were investigated for former and present diseases and laboratory changes of the immune system. Moreover, in a subgroup of 29 highly exposed and 28 control persons, proliferation studies were performed. In addition to assays such as blood count, immunoglobulins, serum electrophoresis, monoclonal bands, surface markers, autoantibodies, and lymphocyte proliferation, two new methods, the rise of tetanus antibody concentration after vaccination and the in vitro resistance of lymphocytes to chromate, were used to diagnose the morphologic and functional state of the immune system. There was no stringent correlation of actual PCDD/PCDF concentrations with the occurrence of infections or with one of the immune parameters. In addition, outcomes of the tetanus vaccination and the chromate resistance test were not correlated with PCDD/PCDF. However, the chromate resistance of lymphocytes stimulated by phytohemagglutinin of highly exposed persons was significantly lower than that for the control group. These findings indicate that the function of lymphocytes can be stressed and possibly impaired by high exposure to PCDD/PCDF.ImagesFigure 2
A computer program has been developed for computer‐assisted diagnosis (including subclassification) of flow cytometry data of acute leukaemias and non‐Hodgkin lymphomas by means of artificial intelligence. The knowledge base for the system has been formulatedas semantic networks that describe physiological hematopoiesisas well as the pathological situation (eg., aberrant antigen expression) of hematological disorders. The semantic networks reflect the hierarchy of cells and their occurrence in diseases, the normal and pathological antigen expression patterns of cells, cell maturation, and the frequency of cell populations in normal blood and bone marrow. Using these semantic networks, the diagnosis algorithm compares the characteristic antigen expression pattern of a disease with the actual findings in the blood or bone marrow sample. The algorithm can separate mixed populations by taking double staining findings into account. Finally, a diagnosis text is generated that describes all identified cell populations and the resulting diagnosis. The validationof the program showed a correct diagnosis (disease group and subclassification) in 97% of the cases (n = 633) with slight differences between the disease groups (e.g., B‐NHL: 99%, B‐cell ALL: 84%). © 1996 Wiley‐Liss, Inc.
One hundred ninety-two workers in a German pesticide factory who were exposed to polychlorinated dibenzodioxins and -furans (PCDD/PCDF) were investigated for former and present diseases and laboratory changes of the immune system. Moreover, in a subgroup of 29 highly exposed and 28 control persons, proliferation studies were performed. In addition to assays such as blood count, immunoglobulins, serum electrophoresis, monoclonal bands, surface markers, autoantibodies, and lymphocyte proliferation, two new methods, the rise of tetanus antibody concentration after vaccination and the in vitro resistance of lymphocytes to chromate, were used to diagnose the morphologic and functional state of the immune system. There was no stringent correlation of actual PCDD/PCDF concentrations with the occurrence of infections or with one of the immune parameters. In addition, outcomes of the tetanus vaccination and the chromate resistance test were not correlated with PCDD/PCDF. However, the chromate resistance of lymphocytes stimulated by phytohemagglutinin of highly exposed persons was significantly lower than that for the control group. These findings indicate that the function of lymphocytes can be stressed and possibly impaired by high exposure to PCDD/PCDF. Environ Health Perspect 1 06(Suppl 2):689-695 (1998). http.//ehpnetl.niehs.nih.gov/docs/1998/Suppl-2/689-695jung/abstract.html
The present study was designed to investigate in vivo immunomodulatory properties of hematopoietic growth factors. The influence on the activation of cytokine synthesis and on the expression of surface antigens associated with cellular activation of G-CSF or GM-CSF was investigated in cancer patients receiving these factors. One single dose of growth factor was administered to patients with bladder cancer (G-CSF group) or small cell lung cancer (GM-CSF group) before chemotherapy. After cytoreductive chemotherapy patients received supportive therapy with G-CSF or GM-CSF. Peripheral blood mononuclear cells and plasma samples were obtained for flow cytometry, Northern blot analysis, and assessment of cytokine protein levels after single-dose as well as after continuous cytokine administration. Our results demonstrate differences in the induction of biological activities by GM-CSF and G-CSF in vivo which correlate well with in vitro findings. Among mature hematopoietic cells the effect of G-CSF is restricted to the granulocyte lineage. With GM-CSF moderate but unequivocal modulation of monocyte function was observed. On peripheral blood monocytes expression of MHC class-II molecules and CD44 was markedly stimulated. After one single dose of GM-CSF, plasma levels of sCD25 and IL-1RA were significantly induced (p < 0.0001, p = 0.032, respectively) and a trend to increased IL-8 levels was observed. The changes in plasma proteins were not correlated with shifts of mRNA expression for IL-8 and IL-1RA. T-cell activation was not observed with either cytokine. These results suggest that immunomodulatory features are differentially regulated by G-CSF and GM-CSF. The clinical relevance of a selective use of both hematopoietic growth factors in various disease settings remains to be determined.
In this randomised prospective study we investigated whether treatment results of maximal androgen blockade (MAB) in patients with metastatic prostatic cancer can be further improved by additional Methotrexate therapy (MTX). A total number of 61 patients (stage T1 or '1"2) have been included and 31 were randomised to arm A receiving MAB, i.e. orchiectemy + flutamide (3x250 rag/d). In group B 30 patients were treated with MAB + 50 mg{m 2 MTX (once weekly for 4 months). 53 patients are evahiable for response criteria.
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