Enhanced viral clearance in interleukin-18 gene-deficient mice after pulmonary infection with influenza A virus

T helper 1 driven immune responses facilitate host defence during viral infections. Because interleukin-18 (IL-18) mediates T helper 1 driven immune responses, and since mature IL-18 is up-regulated in human macrophages after influenza virus infection in vitro, it has been suggested that IL-18 plays an important role in the immune response to influenza. To determine the role of IL-18 in respiratory tract infection with influenza, IL-18 gene-deficient (IL-18(-/-)) and normal wildtype mice were intranasally inoculated with influenza A virus. Influenza resulted in an increase in constitutively expressed IL-18 in the lungs of wildtype mice. The clearance of influenza A was inhibited by IL-18, as indicated by reduced viral loads on day 8 and day 12 after infection in IL-18(-/-) mice. This enhanced viral clearance correlated with increased CD4(+) T-cell activation in the lungs as reflected by CD69 expression on the cell surface. Surprisingly, interferon-gamma (IFN-gamma) levels were similar in the lungs of IL-18(-/-) mice and wildtype mice. Intracellular IFN-gamma staining revealed similar expression levels in lung-derived natural killer cells, CD4(+) and CD8(+) T cells, indicating that IFN-gamma production is IL-18-independent during influenza virus infection. Tumour necrosis factor-alpha production by CD4(+) T cells was significantly lower in IL-18(-/-) mice than in wildtype mice. Our data indicate that endogenous IL-18 impairs viral clearance during influenza A infection.     

Basismaßnahmen zur Wiederbelebung Erwachsener (Basic Life Support)

Notfall + Rettungsmedizin - Der Europäische Rat für Wiederbelebung hat diese Leitlinie – Basismaßnahmen zur Wiederbelebung – auf Grundlage des...     

Dynamic Contrast-Enhanced MR Imaging for Soft Tissue Sarcomas

Dynamic contrast-enhanced magnetic resonance imaging has recently emerged as an important method for evaluating soft tissue sarcomas for biopsy localization, chemotherapeutic response, and long-term follow-up because of its ability to detect viable tumor. This article presents the basic principles of contrast kinetics in soft tissue sarcomas after bolus injection of contrast agent and discusses the current postprocessing methods (subtraction, first-pass image and time-intensity curves with region of interest, and color-encoded techniques) used to display these dynamic studies. Because of its excellent temporal resolution, dynamic MR imaging can delineate the early uptake of contrast agent in sarcomas within seconds after injection, almost synchronous with arterial enhancement, and thereby differentiate the rapidly enhancing viable tumor from the nonenhancing necrotic tumor and the late enhancing changes after surgery, radiation therapy, and chemotherapy.     

Influence of matching for exposure time on estimates of attributable mortality caused by nosocomial bacteremia in critically ill patients.

OBJECTIVE: To evaluate the influence of matching on exposure time on estimates of attributable mortality of nosocomial bacteremia as assessed by matched cohort studies. DESIGN: Two retrospective, pairwise-matched (1:2) cohort studies. SETTING: A 54-bed intensive care unit (ICU) in a university hospital. PATIENTS: Patients with nosocomial Escherichia coli bacteremia (n = 68) and control-patients without nosocomial bacteremia (n = 136 for each matched cohort study). INTERVENTION: In both matched cohort studies, the same set of bacteremic patients was matched with control-patients using the APACHE II system. In the first study, control-patients were required to have an ICU stay at least as long as the respective bacteremic patient prior to onset of bacteremia (matching on exposure time). In the second study, control-patients were required to have an ICU stay shorter than the stay prior to the development of bacteremia in the respective bacteremic patient (no matching on exposure time). RESULTS: For bacteremic patients, the mean ICU stay before onset of the bacteremia was 9 days (median, 6 days). In the first matched cohort study, hospital mortality was not different between bacteremic patients and control-patients (44.1% vs 43.4%; P = .999). In the second study, mortality of bacteremic patients and control-patients was also not different (44.1% vs 47.8%; P = .657). Mortality rates between control groups were not different (43.4% vs 47.8%; P = .543). CONCLUSION: Matching or not matching on exposure time did not alter the estimate of attributable mortality for ICU patients with E. coli bacteremia.     

Synergistic Effects of BAY 60‐4552 and Vardenafil on Relaxation of Corpus Cavernosum Tissue of Patients with Erectile Dysfunction and Clinical Phosphodiesterase Type 5 Inhibitor Failure

IntroductionOverall efficacy rates of phosphodiesterase type 5 inhibitors (PDE5‐i) for erectile dysfunction (ED) are 60–70%. PDE5‐i treatment failures currently have to resort to invasive treatment options for restoration of erectile function.AimsTo assess changes in the nitric oxide (NO)/cyclic guanosine monophosphate (cGMP)/protein kinase (PKG) pathway in human corpus cavernosum (HCC) of PDE5‐i nonresponders compared with healthy controls. To evaluate the effects of BAY 60‐4552, a stimulator of soluble guanylate cyclase (sGC), and vardenafil on relaxation of HCC strips from PDE5‐i nonresponders.Main Outcome MeasuresmRNA expression, morphological localization of the NO/cGMP/PKG pathway, and relaxant capacity of both compounds alone or combined. Analysis of variance, t‐test or Mann–Whitney test based upon number of groups and normality of data.MethodsHCC tissues were harvested after consent from individuals undergoing penile prosthesis implantation (patients) and potent patients undergoing transurethral surgery (healthy controls, needle biopsy). HCC tissues of patients were compared with those of healthy controls for the expression of mRNA coding for PDE5A, eNOS, PKGα1, PKG2, sGCα1, sGCα2, sGCβ1, sGCβ2, α‐smooth muscle actin (aSMA) and β‐actin by quantitative polymerase chain reaction (qPCR). The respective proteins were localized using immunofluorescence. Tissue strips of patients were precontracted with phenylepinephrine followed by incubation with 1 μM of either vardenafil or BAY 60‐4552, or both simultaneously.ResultsThe main targets in the NO/cGMP/sGC pathway were downregulated in PDE5‐i nonresponders. The pathway was morphologically located to HCC smooth muscle, of which the overall content was preserved in ED patients based on aSMA expression. BAY 60‐4552 and vardenafil have synergistic effects on relaxation of HCC of PDE5‐i nonresponders. The main limitation is the small amount of control tissue precluding functional testing on these samples.ConclusionDespite downregulation of the NO/cGMP/PKG pathway, combining BAY 60‐4552 with vardenafil significantly enhanced relaxation HCC strips of PDE5‐i nonresponders.     

Forensic age estimation based on magnetic resonance imaging of third molars: converting 2D staging into 3D staging

Background: Established methods to stage development of third molars for forensic age estimation are based on the evaluation of radiographs, which show a 2D projection. It has not been investigated whether these methods require any adjustments in order to apply them to stage third molars on magnetic resonance imaging (MRI), which shows 3D information.

Aim: To prospectively study root stage assessment of third molars in age estimation using 3 Tesla MRI and to compare this with panoramic radiographs, in order to provide considerations for converting 2D staging into 3D staging and to determine the decisive root.

Subjects and methods: All third molars were evaluated in 52 healthy participants aged 14–26 years using MRI in three planes. Three staging methods were investigated by two observers. In sixteen of the participants, MRI findings were compared with findings on panoramic radiographs.

Results: Decisive roots were palatal in upper third molars and distal in lower third molars. Fifty-seven per cent of upper third molars were not assessable on the radiograph, while 96.9% were on MRI. Upper third molars were more difficult to evaluate on radiographs than on MRI (p?p?=?.375). Inter- and intra-observer agreement for evaluation was higher in MRI than in radiographs. In both imaging techniques lower third molars showed greater inter- and intra-observer agreement compared to upper third molars. MR images in the sagittal plane proved to be essential for staging.

Conclusion: In age estimation, 3T MRI of third molars could be valuable. Some considerations are, however, necessary to transfer known staging methods to this 3D technique.