Post-cardiac arrest syndrome (PCAS) is often associated with disseminated intravascular coagulation (DIC), thus leading to the development of multiple organ dysfunction syndrome (MODS). The aim of this study was to examine the pathophysiological relationships between coagulation, fibrinolysis and fibrinolytic shutdown by evaluating the levels of coagulofibrinolytic markers, including soluble fibrin, thrombin-activatable fibrinolysis inhibitor (TAFI), tissue plasminogen activator-plasminogen activator inhibitor-1 complex (tPAIC), plasmin-alpha2 plasmin inhibitor complex (PPIC), neutrophil elastase and fibrin degradation product by neutrophil elastase (EXDP).
Materials and Methods
Fifty-two resuscitated patients were divided into two groups: 22 DIC and 30 non-DIC patients.
Results
The levels of soluble fibrin, PPIC, tPAIC, EXDP and neutrophil elastase in the DIC patients with PCAS were significantly higher than those observed in the non-DIC patients. The values of the tPAIC and JAAM DIC scores were found to be independent predictors of increased SOFA scores in the DIC patients. The MODS patients demonstrated significantly higher levels of soluble fibrin and tPAIC; however, the levels of TAFI and EXDP were identical between the patients with and without MODS. In addition, positive correlations were observed between the levels of tPAIC and EXDP in the patients with non-MODS; however, no correlations were observed between these markers in the MODS patients.
Conclusions
Thrombin activation and fibrinolytic shutdown play important roles in the development of organ dysfunction in PCAS patients. Neutrophil elastase-mediated fibrinolysis cannot overcome the fibrinolytic shutdown that occurs in DIC patients with PCAS, thus resulting in the development of MODS. 相似文献
The physiological significance of canonical transient receptor potential (TRPC) ion channels in sensory systems is rapidly emerging. Heterologous expression studies show that TRPC3 is a significant Ca2+ entry pathway, with dual activation via G protein‐coupled receptor (GPCR)–phospholipase C–diacylglycerol second messenger signaling, and through negative feedback, whereby a fall in cytosolic Ca2+ releases Ca2+–calmodulin channel block. We hypothesised that the latter process contributes to cochlear hair cell cytosolic Ca2+ homeostasis. Confocal microfluorimetry with the Ca2+ indicator Fluo‐4 acetoxymethylester showed that, when cytosolic Ca2+ was depleted, Ca2+ re‐entry was significantly impaired in mature TRPC3?/? inner and outer hair cells. The impact of this disrupted Ca2+ homeostasis on sound transduction was assessed with the use of distortion product otoacoustic emissions (DPOAEs), which constitute a direct measure of the outer hair cell transduction that underlies hearing sensitivity and frequency selectivity. TRPC3?/? mice showed significantly stronger DPOAE (2f1 ? f2) growth functions than wild‐type (WT) littermates within the frequency range of best hearing acuity. This translated to hyperacusis (decreased threshold) measured by the auditory brainstem response (ABR). TRPC3?/? and WT mice did not differ in the levels of temporary and permanent threshold shift arising from noise exposure, indicating that potential GPCR signaling via TRPC3 is not pronounced. Overall, these data suggest that the Ca2+ set‐point in the hair cell, and hence membrane conductance, is modulated by TRPC3s through their function as a negative feedback‐regulated Ca2+ entry pathway. This TPRC3‐regulated Ca2+ homeostasis shapes the sound transduction input–output function and auditory neurotransmission. 相似文献
PurposeTo assess the incidence and risk factors for chronic radiodermatitis after fluoroscopically guided interventions (FGIs) in high-risk patients.Materials and MethodsBetween 2010 and 2016, of 55,782 patients who underwent FGIs, 359 had a risk procedure for skin injury (maximal skin dose > 3 Gy, air kerma > 5 Gy, dose area product [DAP] > 500 Gy.cm2, or fluoroscopy time > 60 minutes). Ninety-one of these patients were examined by a dermatologist for radiodermatitis (median time after procedure, 31.2 months [95% confidence interval, 14.2–50.7]). In each case, the clinical features and topography of the skin lesions were recorded and their incidence calculated. The characteristics of the patients and of the FGIs were tested as risk factors.ResultsEight patients (8.8%) had chronic radiodermatitis; 19 (20.9%) had acute radiodermatitis. Body mass index, DAP value, and air kerma were the only risk factors identified.ConclusionsThis study shows that chronic radiodermatitis may be considered a frequent side effect in an at-risk population. The lesions are commonly benign, but extensive sclerosis can occur. Patients should be better informed about the side effects and offered a skin exam periodically. 相似文献
In recent years, development of rheumatoid arthritis (RA) drug therapy has been more directly targeted to counteract specific
mechanisms of inflammation, and it is now believed that early aggressive treatment with disease modifying drugs is important
to inhibit future structural joint damage. The development of these new treatments has increased the need for methodologies
to assess disease activity in RA and monitor the effectiveness of drug therapy. Unlike X-ray, which shows only structural
bone damage, magnetic resonance imaging (MRI) can depict soft tissue damage and synovitis, the primary pathology of RA. Recent
studies have also indicated that MRI is sensitive to pathophysiologic changes that may predate radiographic erosions and may
predict future joint damage. In this study, we have developed a computer automated analysis technique for MR wrist images
that provides an objective measure of RA synovitis. This method applies a two-compartment pharmacokinetic model to every voxel
of a dynamic contrast-enhanced MRI (DCE-MRI) dataset and outputs resulting parametric images. The aim of this technique is
to not only objectively quantify the severity of rheumatoid synovitis, but to also locally determine where areas of serious
disease activity are situated through kinetic modeling of blood-tissue exchange. Preliminary results show good correlation
to early enhancement rate, which has previously been shown to be a useful clinical marker of RA activity. However, the use
of tracer kinetic modeling methods potentially provides more specific information regarding underlying RA physiology. This
approach could provide a useful new tool in RA patient management and could substantially improve RA therapeutic studies by
calculating objective biomarkers of the disease state. 相似文献
Aims: Alcohol advertising, in the form of product placement, has been shown to influence the viewer’s alcohol consumption. However, it is not just the portrayal itself that affects behavioural outcomes; the particular message that is conveyed in an alcohol portrayal may actually influence consumer behaviour in a manner known as “framing”. Therefore, the prevalence and framing of alcohol portrayals in movies was investigated by focussing on product placement strategies, several portrayal characteristics and compliance with relevant guidelines/laws. Furthermore, a comparison is made between movies sponsored by an alcohol brand and non-sponsored movies.
Methods: Sixteen Dutch movies (of which 50% were sponsored) underwent content analysis using a four-category, 21-item coding scheme. Alcohol was present in every movie and a total of 937 alcohol portrayals were analysed.
Findings: The results show that the alcohol portrayals were predominantly positive. In the sponsored movies, more liquor was consumed and alcohol portrayals had a lower plot connection.
Conclusions: In general, the differences between alcohol portrayals in movies sponsored by an alcohol brand compared with non-sponsored movies were rather small. However, the portrayals sometimes offend the legislation regarding regular alcohol commercials, and given the effects of alcohol portrayals on young viewers, this needs attention. 相似文献
In many countries, health insurers or health plans choose to contract either with any willing providers or with preferred providers. We compare these mechanisms when two medical services are imperfect substitutes in demand and are supplied by two different firms. In both cases, the reimbursement is higher when patients select the in‐network provider(s). We show that these mechanisms yield lower prices, lower providers' and insurer's profits, and lower expense than in the uniform‐reimbursement case. Whatever the degree of product differentiation, a not‐for‐profit insurer should prefer selective contracting and select a reimbursement such that the out‐of‐pocket expense is null. Although all providers join the network under any‐willing‐provider contracting in the absence of third‐party payment, an asymmetric equilibrium may exist when this billing arrangement is implemented. 相似文献
BackgroundTo inform national healthcare authorities whether quadrivalent influenza vaccines (QIVs) provide better value for money than trivalent influenza vaccines (TIVs), we assessed the cost-effectiveness of TIV and QIV in low-and-middle income communities based in South Africa and Vietnam and contrasted these findings with those from a high-income community in Australia.MethodsIndividual based dynamic simulation models were interfaced with a health economic analysis model to estimate the cost-effectiveness of vaccinating 15% of the population with QIV or TIV in each community over the period 2003–2013. Vaccination was prioritized for HIV-infected individuals, before elderly aged 65+ years and young children. Country or region-specific data on influenza-strain circulation, clinical outcomes and costs were obtained from published sources. The societal perspective was used and outcomes were expressed in International$ (I$) per quality-adjusted life-year (QALY) gained.ResultsWhen compared with TIV, we found that QIV would provide a greater reduction in influenza-related morbidity in communities in South Africa and Vietnam as compared with Australia. The incremental cost-effectiveness ratio of QIV versus TIV was estimated at I$4183/QALY in South Africa, I$1505/QALY in Vietnam and I$80,966/QALY in Australia.ConclusionsThe cost-effectiveness of QIV varied between communities due to differences in influenza epidemiology, comorbidities, and unit costs. Whether TIV or QIV is the most cost-effective alternative heavily depends on influenza B burden among subpopulations targeted for vaccination in addition to country-specific willingness-to-pay thresholds and budgetary impact. 相似文献