Pneumococcal meningitis: development of a new animal model.

HYPOTHESIS: The rat is a suitable animal to establish a model for the study of pneumococcal meningitis postcochlear implantation. BACKGROUND: There has been an increase in the number of cases of cochlear implant-related meningitis. The most common organism identified was Streptococcus pneumoniae. Whether cochlear implantation increases the risk of pneumococcal meningitis in healthy subjects without other risk factors remains to be determined. Previous animal studies do not focus on the pathogenesis and risk of pneumococcal meningitis postimplantation and are based on relatively small animal numbers, making it difficult to assess the cause-and-effect relationship. There is, therefore, a need to develop a new animal model allowing direct examination of the pathogenesis of meningitis in the presence of a cochlear implant. METHODS: Eighteen nonimplanted rats were infected with 1 x 10 and 1 x 10 colony-forming units (CFU) of a clinical isolate of S. pneumoniae via three different inoculation routes (middle ear, inner ear, and i.p.) to examine for evidence of meningitis during 24 hours. Six implanted rats were infected with the highest amount of bacteria possible for each route of inoculation (4 x 10 CFU i.p., 3 x 10 CFU middle ear, and 1 x 10 CFU inner ear) to examine for evidence of meningitis with the presence of an implant. The histological pattern of cochlear infections for each of the three different inoculating routes were examined. RESULTS: Pneumococcal meningitis was evident in all 6 implanted animals for each of the three different routes of inoculation. Once in the inner ear, bacteria were found to enter the central nervous system via either the cochlear aqueduct or canaliculi perforantes of the osseous spiral lamina, reaching the perineural and perivascular space then the internal acoustic meatus. The rate, extent, and pattern of infection within the cochleae depended on the route of inoculation. Finally, there was no evidence of pneumococcal meningitis observed in 18 nonimplanted rats inoculated at a lower concentration of S. pneumoniae when observed for 24 hours postinoculation. CONCLUSION: Meningitis in implanted rats after inoculation with a clinical isolate of S. pneumoniae is possible via all three potential routes of infection via the upper respiratory tract. The lack of meningitis observed in the 18 nonimplanted rats suggests that longer postinoculation monitoring periods are required to ensure whether or not meningitis will develop. Based on this work, we have developed a new animal model that will allow quantitative risk assessment of meningitis postcochlear implantation, and the assessment of the efficacy of potential interventional strategies in future studies.     

Bench to bedside review: Extracorporeal carbon dioxide removal,past present and future

Acute respiratory distress syndrome (ARDS) has a substantial mortality rate and annually affects more than 140,000 people in the USA alone. Standard management includes lung protective ventilation but this impairs carbon dioxide clearance and may lead to right heart dysfunction or increased intracranial pressure. Extracorporeal carbon dioxide removal has the potential to optimize lung protective ventilation by uncoupling oxygenation and carbon dioxide clearance. The aim of this article is to review the carbon dioxide removal strategies that are likely to be widely available in the near future. Relevant published literature was identified using PubMed and Medline searches. Queries were performed by using the search terms ECCOR, AVCO2R, VVCO2R, respiratory dialysis, and by combining carbon dioxide removal and ARDS. The only search limitation imposed was English language. Additional articles were identified from reference lists in the studies that were reviewed. Several novel strategies to achieve carbon dioxide removal were identified, some of which are already commercially available whereas others are in advanced stages of development.     

Development and validation of the Workplace Interruptions Measure

In 3 studies, we developed and tested the first comprehensive, self‐report measure of workplace interruptions. The Workplace Interruptions Measure (WIM) is based on a typology of interruptions that included intrusions, distractions, discrepancy detections, and breaks. The four‐factor structure was reduced to a 12‐item measure in Study 1 (N = 317) and confirmed in a diverse sample of employees in Study 2 (N = 160). Study 3 (N = 323) further examined the psychometric properties of the WIM in a sample of university faculty and staff. Studies 2 and 3 demonstrated that both effort‐enhancing interruptions (intrusions, distractions, and discrepancy detections) and recovery‐enhancing interruptions (breaks) were associated with stressors and strains. Distractions, discrepancy detections, and breaks uniquely predicted strain outcomes beyond other workplace stressors (i.e., quantitative workload, interpersonal conflict, and role conflict). We discuss implications of the WIM for the theory and practice of interruptions research.     

Targeting the “Cytokine Storm” for Therapeutic Benefit

Inflammation is the body''s first line of defense against infection or injury, responding to challenges by activating innate and adaptive responses. Microbes have evolved a diverse range of strategies to avoid triggering inflammatory responses. However, some pathogens, such as the influenza virus and the Gram-negative bacterium Francisella tularensis, do trigger life-threatening “cytokine storms” in the host which can result in significant pathology and ultimately death. For these diseases, it has been proposed that downregulating inflammatory immune responses may improve outcome. We review some of the current candidates for treatment of cytokine storms which may prove useful in the clinic in the future and compare them to more traditional therapeutic candidates that target the pathogen rather than the host response.     

Inversion recovery ultrashort echo time imaging of ultrashort T2 tissue components in ovine brain at 3 T: a sequential D2O exchange study

Inversion recovery ultrashort echo time (IR‐UTE) imaging holds the potential to directly characterize MR signals from ultrashort T₂ tissue components (STCs), such as collagen in cartilage and myelin in brain. The application of IR‐UTE for myelin imaging has been challenging because of the high water content in brain and the possibility that the ultrashort T₂* signals are contaminated by water protons, including those associated with myelin sheaths. This study investigated such a possibility in an ovine brain D₂O exchange model and explored the potential of IR‐UTE imaging for the quantification of ultrashort T₂* signals in both white and gray matter at 3 T. Six specimens were examined before and after sequential immersion in 99.9% D₂O. Long T₂ MR signals were measured using a clinical proton density‐weighted fast spin echo (PD‐FSE) sequence. IR‐UTE images were first acquired with different inversion times to determine the optimal inversion time to null the long T₂ signals (TI_null). Then, at this TI_null, images with echo times (TEs) of 0.01–4 ms were acquired to measure the T₂* values of STCs. The PD‐FSE signal dropped to near zero after 24 h of immersion in D₂O. A wide range of TI_null values were used at different time points (240–330 ms for white matter and 320–350 ms for gray matter at TR = 1000 ms) because the T₁ values of the long T₂ tissue components changed significantly. The T₂* values of STCs were 200–300 μs in both white and gray matter (comparable with the values obtained from myelin powder and its mixture with D₂O or H₂O), and showed minimal changes after sequential immersion. The ultrashort T₂* signals seen on IR‐UTE images are unlikely to be from water protons as they are exchangeable with deuterons in D₂O. The source is more likely to be myelin itself in white matter, and might also be associated with other membranous structures in gray matter.