Laboratory investigation; a journal of technical methods and pathology
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Pathology is both a medical specialty and an investigative scientific discipline, concerned with understanding the essential nature of human disease. Ultimately, pathology is accountable as well, as measured by the accuracy of our diagnoses and the resultant patient care outcomes. As such, we must consider the evidence base underlying our practices. ⋯ A survey of six North American academic pathology departments reveals that 26% of all papers published in 2005 came from 'unfunded' clinical faculty. While it is likely that their academic productivity is lower than that of 'funded' research faculty, the contribution of clinical faculty to the knowledge base for the practice of modern medicine, and to the academic reputation of the department, must not be overlooked. The ability of clinical faculty in academic departments of pathology to pursue original scholarship must be supported if our specialty is to retain its preeminence as an investigative scientific discipline in the age of EBM.
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Community-acquired (CA) methicillin-resistant Staphylococcus aureus (MRSA) infection among individuals without healthcare-associated (HA) risk factors was first recognized about a decade ago. It has now emerged as an epidemic that is responsible for rapidly progressive, fatal diseases including necrotizing pneumonia, severe sepsis and necrotizing fasciitis. Unlike HA-MRSA, CA-MRSA are usually pan-susceptible to non-beta-lactam antimicrobials. ⋯ The tight association between the novel methicillin resistance cassettes and PVL phage cannot be explained, as they integrate into distinct sites on the S. aureus chromosome. This paper presents the evidence that CA-MRSA isolates are distinct strains emerging de novo from CA-methicillin susceptible isolates rather than from HA-MRSA isolates that have escaped from the hospital setting and that these novel CA-MRSA isolates may be more virulent than HA-MRSA. The second aim is to outline the progress in understanding the role of PVL in CA-MRSA pathogenesis.
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Mechanical ventilation (MV) is frequently employed for the management of critically ill patients with respiratory failure. A major complication of mechanical ventilation (MV) is the development of ventilator-associated pneumonia (VAP), in which Staphylococcus aureus is a prominent pathogen. Moreover, previous studies suggest that MV may be an important cofactor in the development of acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS). ⋯ MV also induced proinflammatory cytokine expression in peripheral blood, associated with extrapulmonary hepatic and renal dysfunction. Surprisingly, bacterial clearance in the lungs and extrapulmonary bacterial dissemination was not affected by MV. These data indicate that MV exacerbates both pulmonary and systemic inflammation in response to bacteria and contributes to the pathogenesis of both ALI and the multiple organ dysfunction syndrome, without necessarily affecting bacterial clearance or extra-pulmonary bacterial dissemination.
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Heme oxygenase-1 (HO-1) is the inducible isoform of an enzyme family responsible for heme degradation and was suggested to be involved in the acute phase response in the liver. However, the mechanisms of the HO-1 regulation under inflammatory conditions are poorly understood. Therefore, the purpose of the current work was to study the expression of HO-1 in the liver and other organs of rats with a localized inflammation after intramuscular injection of turpentine oil (TO). ⋯ In the liver of control rats HO-1 protein was detected in Kupffer cells, while in TO-injected rats also hepatocytes became strongly HO-1 positive. Conversely, in the injured muscle, HO-1 immunoreactivity was attributed only to macrophages. Our data demonstrate that during localized inflammation HO-1 expression was rapidly and strongly induced in macrophages of injured muscle and in hepatocytes, and IL-6 derived from injured muscle seems to be responsible for the HO-1 induction in the liver.
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To assess the role of Toll-like receptor (TLR) signalling in host response to mycobacterial infection, mice deficient in the TLR adaptor molecule myeloid differentiation factor 88 (MyD88) were infected with the vaccine strain Mycobacterium bovis (BCG), and the immune response and bacterial burden were investigated. Macrophages and dendritic cells from MyD88-deficient mice stimulated in vitro with BCG mycobacterial antigens produced very low levels of proinflammatory cytokines, while the expression of costimulatory molecules such as CD40 and CD86 was preserved. ⋯ Lung infiltrating cells showed IFNgamma production by pulmonary CD4+ T cells upon specific restimulation, and a reduced capacity to produce nitric oxide and IL-10. In summary, despite the dramatic reduction of the innate immune response, MyD88-deficient mice were able to mount an efficient T-cell response to mycobacterial antigens, which was however insufficient to control infection in the lung, resulting in chronic pneumonia in MyD88-deficient mice.