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1.
The present study was undertaken to investigate the appearance and location of Pseudomonas aeruginosa in the cystic fibrosis (CF) lung and in sputum. Samples include preserved tissues of CF patients who died due to chronic P. aeruginosa lung infection prior to the advent of intensive antibiotic therapy, explanted lungs from 3 intensively treated chronically P. aeruginosa infected CF patients and routine sputum from 77 chronically P. aeruginosa infected CF patients. All samples were investigated microscopically using hematoxylin–eosin (HE), Gram and alcian‐blue stain, PNA FISH and immunofluorescence for alginate. Investigation of the preserved tissues revealed that prior to aggressive antibiotic therapy, P. aeruginosa infection and destruction of the CF lung correlated with the occurrence of mucoid (alginate) bacteria present in aggregating structures surrounded by pronounced polymorphonuclear‐leukocyte (PMN) inflammation in the respiratory zone (9/9). Non‐mucoid bacteria were not observed here, and rarely in the conductive zone (1/9). However, in the explanted lungs, the P. aeruginosa aggregates were also mucoid but in contrast to the autopsies, they were very rare in the respiratory zone but abundant in the sputum of the conductive zone (3/3), which also contained abundances of PMNs (3/3). Non‐mucoid and planktonic P. aeruginosa were also observed here (3/3). In conclusion, the present intensive antibiotic therapy of chronic P. aeruginosa infections, at the Copenhagen CF Centre, seems to restrain but not eradicate the bacteria from the conductive zone, whereas the remaining healthy respiratory zone appears to be protected, for a long period, from massive biofilm infection. This strongly suggests that the conductive zone serves as a bacterial reservoir where the bacteria are organized in mucoid biofilms within the mucus, protected against antibiotics and host defenses. Pediatr Pulmonol. 2009; 44:547–558. © 2009 Wiley‐Liss, Inc.  相似文献   

2.
Enzyme-induced calcium carbonate precipitation (EICP) technology can improve the strength of treated soil. But it also leads to remarkable brittleness of the soil. This study used polyvinyl alcohol (PVA) fiber combined with EICP to solidify sand. Through the unconfined compressive strength (UCS) test, the effect of PVA fiber incorporation on the mechanical properties of EICP-solidified sand was investigated; the distribution of CaCO3 in the sample and the microstructure of fiber-reinforced EICP-treated sand were explored through the calcium carbonate content (CCC) test and microscopic experiment. Compared with the sand treated by EICP, the strength and stiffness of the sand reinforced by the fiber combined with EICP were greatly improved, and the ductility was also improved to a certain extent. However, the increase of CCC was extremely weak, and the inhomogeneity of CaCO3 distribution was enlarged; the influence of fiber length on the UCS and CCC of the treated sand was greater than that of the fiber content. The improvement of EICP-solidified sand by PVA fiber was mainly due to the formation of a “fiber–CaCO3–sand” spatial structure system through fiber bridging, not the increase of CCC.  相似文献   

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Antibiotic resistance causes around 700,000 deaths a year worldwide. Without immediate action, we are fast approaching a post-antibiotic era in which common infections can result in death. Pseudomonas aeruginosa is the leading cause of nosocomial infection and is also one of the three bacterial pathogens in the WHO list of priority bacteria for developing new antibiotics against. A viable alternative to antibiotics is to use phages, which are bacterial viruses. Yet, the isolation of phages that efficiently kill their target bacteria has proven difficult. Using a combination of phages and antibiotics might increase treatment efficacy and prevent the development of resistance against phages and/or antibiotics, as evidenced by previous studies. Here, in vitro populations of a Pseudomonas aeruginosa strain isolated from a burn patient were treated with a single phage, a mixture of two phages (used simultaneously and sequentially), and the combination of phages and antibiotics (at sub-minimum inhibitory concentration (MIC) and MIC levels). In addition, we tested the stability of these phages at different temperatures, pH values, and in two burn ointments. Our results show that the two-phages-one-antibiotic combination had the highest killing efficiency against the P. aeruginosa strain. The phages tested showed low stability at high temperatures, acidic pH values, and in the two ointments. This work provides additional support for the potential of using combinations of phage–antibiotic cocktails at sub-MIC levels for the treatment of multidrug-resistant P. aeruginosa infections.  相似文献   

5.
Background and objective: Clonal strains of Pseudomonas aeruginosa have been identified in large cystic fibrosis (CF) centres. Whether such strains are more virulent or whether cross‐infection between patients explains their widespread prevalence is unknown. This study described the epidemiology of P. aeruginosa infection in CF patients in Tasmania, Australia, an area with a high CF birth incidence. Patients in Tasmania are geographically dispersed and when this study was conducted (2003) there was no central CF clinic, with patients receiving treatment in regional hospitals. Methods: P. aeruginosa isolates from CF adults aged 15 years and over in Tasmania were genotyped using random amplified polymorphic DNA (RAPD)‐PCR and clonal strains confirmed with pulsed field gel electrophoresis. Results: Airway samples were obtained from 41 patients (82% of the adult CF population). P. aeruginosa was isolated from 34 patients and nine (26%) of these individuals harboured P. aeruginosa strains with identical RAPD‐PCR and pulsed field gel electrophoresis patterns (Australian Epidemic Strain III – AES III). AES III was isolated from patients in all regions of Tasmania and was distinct from the epidemic CF strains described on mainland Australia (AES I and II). The possible link between CF adults infected with AES III was attendance at family camps more than 12 years previously. Patients harbouring AES III had suffered significantly more exacerbations requiring hospitalisation during the 2 years prior to the study compared with patients infected with unique strains (P < 0.01). AES III displayed increased multi‐antibiotic resistance compared with other strains (P < 0.001). Conclusions: Clonal strains of P. aeruginosa may arise even in isolated CF populations. The increased exacerbation rate in patients infected with AES III and its antibiotic resistance profile strongly suggest increased virulence.  相似文献   

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Pseudomonas aeruginosa forms biofilms in the cystic fibrosis lung. Quorum sensing (QS) controls biofilm maturation, immune evasion, antibiotic tolerance and virulence factor production. Garlic shows QS inhibitory activity in vitro and in animal models. We report the first clinical trial in man of a QS inhibitor. We randomized 34 patients to garlic or olive oil capsules (both 656 mg daily). Clinical outcomes and safety bloods were measured at baseline and after 8 weeks treatment. In this exploratory study, analysis was per protocol. Eight patients withdrew, leaving 26 for analysis (13 garlic). With placebo, there was a greater decline in mean (SD) percentage change from baseline FEV1 [?3.6% (11.3)] than with garlic [?2.0% (12.3)]. This was not significant (mean difference = 1.6, 95% CI ?12.7 to 15.9, P = 0.8). The mean (SD) increase in weight was greater with garlic [1.0% (2.0)] than with placebo [0.6% (2.0)]—non‐significant (mean difference = 0.4%, 95% CI ?1.3 to 2.0, P = 0.6). The median (range) change in clinical score with garlic was ?1 (?3 to 5) and 1 (?1 to 4) with placebo (negative score means improvement). This was non‐significant [median difference = ?1 (?3 to 0), P = 0.16]. In the garlic group, seven patients had IV antibiotics versus five placebo. There was a highly significant correlation between plasma and sputum measurements of the QS molecule 3‐oxo‐C12‐HSL (Pearson correlation coefficient = 0.914, P = 0.004). At the end of treatment five patients in each group had abnormal liver function or triglycerides and five garlic patients (one placebo) reported minor adverse effects. Garlic capsules were well tolerated. Although there was no significant effect of garlic compared to placebo in this pilot study, there was a suggestion of improvement with garlic which should be investigated in a larger trial. Pediatr Pulmonol. 2010; 45:356–362. © 2010 Wiley‐Liss, Inc.  相似文献   

8.
Continental, orogenic, and oceanic lithospheric mantle embeds sizeable parcels of exotic cratonic lithospheric mantle (CLM) derived from distant, unrelated sources. This hints that CLM recycling into the mantle and its eventual upwelling and relamination at the base of younger plates contribute to the complex structure of the growing lithosphere. Here, we use numerical modeling to investigate the fate and survival of recycled CLM in the ambient mantle and test the viability of CLM relamination under Hadean to present-day mantle temperature conditions and its role in early lithosphere evolution. We show that the foundered CLM is partially mixed and homogenized in the ambient mantle; then, as thermal negative buoyancy vanishes, its long-lasting compositional buoyancy drives upwelling, relaminating unrelated growing lithospheric plates and contributing to differentiation under cratonic, orogenic, and oceanic regions. Parts of the CLM remain in the mantle as diffused depleted heterogeneities at multiple scales, which can survive for billions of years. Relamination is maximized for high depletion degrees and mantle temperatures compatible with the early Earth, leading to the upwelling and underplating of large volumes of foundered CLM, a process we name massive regional relamination (MRR). MRR explains the complex source, age, and depletion heterogeneities found in ancient cratonic lithospheric mantle, suggesting this may have been a key component of the construction of continents in the early Earth.

Continents keep the record of the evolution of our planet and the life it hosts. How continents formed and evolved remains, to date, an outstanding question in geosciences (13). Several lines of evidence show that continents are gradually accreted from their interiors to their margins, from Precambrian cratonic cores to marginal orogens (4). However, how the cratonic cores are formed is controversial, and proposed models invoke processes related to plate margins, such as rifting, subduction and stacking, accretion, and evolution along arc-like environments, or to mantle plumes (1, 2, 57), all providing compatible petrogenetic environments. Cratons have increased buoyancy and rigidity that allowed stabilization and preservation (13); however, the heterogeneous composition supports the idea that recycling, magmatic addition, reworking, and refertilization are common during their formation (810). Evidence from the geological record of cratons shows that ancient lithospheric roots comprise large volumes of harzburgite and depleted lherzolite with highly heterogeneous ages, compositions, and sources (3, 5, 9, 11, 12). Similar heterogeneities are found in younger orogenic and oceanic regions, where evidence from geological and geophysical studies shows ancient, depleted peridotites embedded within or beneath younger fertile peridotites (1316). This provides proof that the embedding of delaminated, exotic, older, and depleted mantle in the growing lithosphere is a relevant component of the evolution of the Earth’s outer shell (13, 14, 17, 18), potentially contributing to the construction of the continents.Delamination of the older continental lithospheric mantle is a fundamental process of continental evolution, compatible with different tectonic regimes, resulting in lithospheric thinning and craton destruction and critically defining the nature and evolution of mantle heterogeneities (2, 5, 12, 17, 1922). The cycle of mantle heterogeneities is best understood as a large-scale process involving sinking and mixing of variable volumes of CLM, as well as the upwelling of CLM residue (18), driven by long-lasting chemical buoyancy, and its eventual embedding in the growing lithosphere. The subsequent upwelling of CLM residue and relamination of the new lithosphere may contribute to the characteristic source, age, and compositional heterogeneities of cratons. To date, the viability, conditions, effects, and significance of subsequent relamination through time remain poorly addressed.The conditions controlling sinking, upwelling, and relamination of foundered CLM (in other words, its fate and survival) are strictly related to the initial lithospheric buoyancy and the mantle viscosity, mainly functions of CLM size, composition, and temperature (23, 24). The majority of depleted, cold CLM is compositionally buoyant (25) but achieves negative buoyancy due to thermal contraction; thus, once decoupled, it founders into the ambient mantle. Once in the ambient mantle, compositional buoyancy may counteract the vanishing thermal negative buoyancy, opposing sinking, allowing the foundered CLM to rise and relaminate the base of the growing lithosphere (13, 17, 18). The complex feedback between mantle flow, heat transfer, viscosities, and thermal and compositional buoyancy provides key constraints on the spatiotemporal evolution of foundered CLM, including its sinking, transportation, stagnation, upwelling, relamination, and deep mixing, relevant to the interpretation of the physical and chemical mantle anomalies at different depths (17, 20, 2630).The conditions for sinking and upwelling, controlling relamination, are critically impacted by mantle temperatures and may have changed under hotter mantle conditions in the early Earth. Throughout Earth’s evolution, the mantle potential temperature (Tp) has changed; in turn, this may have affected the size of the delaminated lithosphere through its thermal as well as chemical buoyancy, function of the depletion degree (F), rheological properties of the mantle, and plate surface velocity (Vsurf) as a result of thermal convection vigor (6, 7, 25, 31). Therefore, the force balance of foundered CLM has changed accordingly, resulting in different possible scenarios for the fate of foundered CLM, ranging from complete mixing in the ambient mantle to survival and embedding in the new lithosphere (17, 23, 26, 29, 32). Here, we used thermo-chemo-mechanical modeling (SI Appendix, sections 1 and 2) to reproduce different conditions throughout Earth’s past and address cycles of CLM recycling with a focus on its relamination. We investigated the conditions for CLM relamination viability, assessing the paths and fates of foundered CLM segments in the mantle, which include upwelling, stagnation depth and timescale, and partitioning between relamination and mixing. We then focused on the complexities this process adds to the growing lithospheric lid, highlighted by the lithosphere’s heterogeneous structure, and compared the model results with realistic lithosphere structures to discuss the significance of CLM relamination in the construction of the existing lithosphere.  相似文献   

9.
H.‐Y. Sun, R.K. Shields, T.V. Cacciarelli, R.R. Muder, N. Singh. A novel combination regimen for the treatment of refractory bacteremia due to multidrug‐resistant Pseudomonas aeruginosa in a liver transplant recipient
Transpl Infect Dis 2010: 12: 555–560. All rights reserved Abstract: Both bacteremia and biliary cast syndrome are serious post‐transplant complications in liver transplant recipients. In the setting of increasing drug resistance in the current era, management of infections caused by multidrug‐resistant (MDR) bacteria has proven challenging. We present a case of a liver transplant recipient who developed biliary cast syndrome and intractable MDR Pseudomonas bacteremia that failed to resolve with conventional antimicrobial therapy and which was finally controlled by a novel combination regimen of colistimethate, doripenem, and tobramycin. Future studies validating the clinical efficacy of this combination strategy are warranted.  相似文献   

10.
目的研究密度感应信号系统(QS)在铜绿假单胞菌(PA)致大鼠肺部感染中的作用。方法将PA制成PA藻酸盐包裹体,建立大鼠肺部感染模型,SD大鼠258只,随机分为3组;比较野生型PA菌株PAO1及QS基因缺失的PA变异株PAO1-JP2大鼠肺部感染模型中细菌学、病理学的不同,从而评价2株菌在大鼠肺部感染中的致病性差异。用刚果红法测定该2株细菌弹性蛋白酶的活性;用免疫印迹法检测外毒素A的表达。结果感染后第14天、28天,PAO1-JP2肺组织匀浆菌落计数分别为(9.6±3.3)lgCFU/g及(4.2±3.1)lgCFU/g,显著低于PAO1组的(11.3±2.8)lgCFU/g及(9.1±1.5)lgCFU/g(P<0.05)。感染后第7、14及28天,PAO1-JP2感染组大鼠肺部病理变化指数及肺组织大体病理评分、肺部脓肿/肉芽肿的平均直径及肺组织显微病理评分均显著低于PAO1组。体外实验结果表明,PAO1-JP2菌株弹性蛋白酶活性(吸光度值)为0.35±0.03,高于PAO1菌株的0.02±0.00。免疫印迹实验可见PAO1株在相对分子质量73 000处显示棕色条带,PAO1-JP2株未见棕色条带。结论QS系统缺损后由于某些致病因子如弹性蛋白酶、外毒素不能表达,其导致的肺部感染程度有所减低。  相似文献   

11.
In recent years, recycled aggregate concrete (RAC) has become a research hotspot in the field of urban construction because of its resource utilization of construction waste. However, compared with original concrete, its strength is still low, which requires additional nano-SiO2 (NS) and fiber. In order to study the mechanism of strength improvement of RAC, this paper takes NS and polyvinyl alcohol (PVA) fiber as variable parameters; uniaxial and triaxial compression tests were carried out on RAC with PVA fiber and NS, and the mechanical properties of RAC were investigated The result shows that within the range of 3% NS content, an increase in the NS substitution rate causes the mechanical properties of RAC to improve significantly. The compressive strength of RAC increases again after adding PVA fiber; through a SEM (scanning electron microscopy) analysis of the specimen, it was found that the NS filled the micro-pores and micro-cracks in the RAC, and the PVA fiber changed the contact range between recycled aggregate and mortar, so the microstructure of the material was more compact. The mechanism of RAC strength improvement is explained in the microcosmic view.  相似文献   

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There is considerable evidence that autophagy in cardiomyocytes is activated by hypoxia/reoxygenation (H/R) or in hearts by ischemia/reperfusion (I/R). Depending upon the experimental model and duration of ischemia, increases in autophagy in this setting maybe beneficial (cardioprotective) or deleterious (exacerbate I/R injury). Besides the conundrum as to whether or not autophagy is an adaptive process, it is clearly regulated by a number of diverse molecules, including reactive oxygen species (ROS), various kinases, hydrogen sulfide (H2S) and nitric oxide (NO). The purpose of this review was to address briefly the controversy regarding the role of autophagy in this setting and to examine a variety of disparate molecules that are involved in its regulation.  相似文献   

15.
This article summarizes the contents of Alcohol: No Ordinary Commodity (2nd edn). The first part of the book describes why alcohol is not an ordinary commodity, and reviews epidemiological data that establish alcohol as a major contributor to the global burden of disease, disability and death in high‐, middle‐ and low‐income countries. This section also documents how international beer and spirits production has been consolidated recently by a small number of global corporations that are expanding their operations in Eastern Europe, Asia, Africa and Latin America. In the second part of the book, the scientific evidence for strategies and interventions that can prevent or minimize alcohol‐related harm is reviewed critically in seven key areas: pricing and taxation, regulating the physical availability of alcohol, modifying the drinking context, drink‐driving countermeasures, restrictions on marketing, education and persuasion strategies, and treatment and early intervention services. Finally, the book addresses the policy‐making process at the local, national and international levels and provides ratings of the effectiveness of strategies and interventions from a public health perspective. Overall, the strongest, most cost‐effective strategies include taxation that increases prices, restrictions on the physical availability of alcohol, drink‐driving countermeasures, brief interventions with at risk drinkers and treatment of drinkers with alcohol dependence.  相似文献   

16.
Objectives—To assess death rates among patients waiting for cardiac valve surgery or isolated coronary artery bypass surgery (CABG), and to determine independent risk factors for death while waiting for isolated CABG.
Design—Prospective cohort analysis based on an inclusive registry.
Setting—Nine cardiac surgical units in Ontario, Canada.
Patients—29 293 consecutive patients scheduled for cardiac surgery between October 1991 and June 1995.
Main outcome measures—Death rates while waiting for surgery were determined among patients scheduled for isolated CABG, isolated valve surgery, or combined procedures. Predictors of death among patients with isolated CABG were determined from multivariate analysis.
Results—There were 141 deaths (0.48%) among 29 293 patients. Adjusting for age, sex, and waiting time, patients waiting for valve surgery had a significantly increased risk of death compared with patients waiting for CABG alone (adjusted odds ratio 1.88, 95% confidence interval (CI) 1.23 to 2.88, p = 0.004). Results were similar for patients waiting for combined valve and CABG procedures compared with those who were waiting for isolated CABG. Independent risk factors for death while waiting for isolated CABG included: impaired left ventricular function (odds ratio 2.47, 95% CI 1.59 to 3.84, p < 0.001); advancing age (for each decade, odds ratio 1.41, 95% CI 1.10 to 1.80, p = 0.007); male sex (odds ratio 1.95, 95% CI 1.00 to 3.81, p = 0.05); and waiting longer than the maximum time recommended in Canadian guidelines for a patient's clinical profile (odds ratio 1.59, 95% CI 1.01 to 2.51, p = 0.044). After scaling waiting time to surgery or death continuously in days, the same predictors emerged.
Conclusions—Patients waiting for valve surgery have a higher risk of death than patients waiting for isolated CABG. Guidelines to promote safer and fairer queuing for non-CABG cardiac surgery are needed. Shorter waiting lists, better compliance with existing guidelines, and guideline revisions to upgrade patients with left ventricular dysfunction could generate additional reductions in the already low risk of death for patients waiting for isolated CABG.

Keywords: cardiac surgery;  waiting lists;  rationing  相似文献   

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The goal of this study is to assess Ziziphus lotus’s potential for producing carboxymethylcellulose adsorption membranes with the ability to adsorb methyl green from wastewaters by the revalorization of its cellulosic fraction. The cellulose from this feedstock was extracted by an alkaline process and TAPPI standard technique T 203 cm-99 and afterwards they were carboxymethylated. The obtained carboxymethylcelluloses were deeply characterized, being observed that the carboxymethylcellulose produced from the alkaline cellulose presented the higher solubility due to its lower crystallinity degree (53.31 vs. 59.4%) and its higher substitution degree (0.85 vs. 0.74). This carboxymethylcellulose was cross-linked with citric acid in an aqueous treatment in order to form an adsorption membrane. The citric acid provided rigidity to the membrane and although it was hydrophilic it was not soluble in water. By evaluating the potential of the produced membrane for the removal of pollutant dyes from wastewater, it was observed that the adsorption membrane prepared from the carboxymethylcellulose’s produced from the Ziziphus lotus was able to remove 99% of the dye, methyl green, present in the wastewater. Thus, this work demonstrates the potential of the Ziziphus lotus for the production of a novel and cost-effective carboxymethylcellulose adsorption membrane with high capacity to treat wastewaters.  相似文献   

19.
BACKGROUND AND AIMS: New lesions of Crohn's disease occur early after ileal or ileocolonic resection and ileocolonic anastomosis. We performed a double blind controlled trial to evaluate the safety and tolerance of recombinant human interleukin 10 (IL-10; Tenovil) in subjects operated on for Crohn's disease. We also assessed the effect of Tenovil in preventing endoscopic recurrence 12 weeks after surgery. METHODS: Patients with Crohn's disease who underwent curative ileal or ileocolonic resection and primary anastomosis were randomised within two weeks after surgery to receive subcutaneous Tenovil 4 microg/kg once daily (QD) (n=22) or 8 microg/kg twice weekly (TIW) (n=21), or placebo (QD or TIW) (n=22). An ileocolonoscopy was performed after 12 weeks of treatment. RESULTS: Compliance was excellent. The most frequently observed adverse events were mild and moderate in severity and equally distributed across treatment groups. Thirty seven patients in the pooled Tenovil group and 21 patients in the pooled placebo group were evaluable by endoscopy. At 12 weeks, 11 of 21 patients (52%) in the placebo group had recurrent lesions compared with 17 of 37 patients (46%) in the Tenovil group (ns). The incidence of severe endoscopic recurrence was similar in both groups (9%). CONCLUSION: Tenovil treatment for 12 consecutive weeks in patients with Crohn's disease after intestinal resection was safe and well tolerated. No evidence of prevention of endoscopic recurrence of Crohn's disease by Tenovil was observed.  相似文献   

20.
This study aimed to assess the effects of aging on mind wandering (MW) using a sustained attention to response task (SART) with a low cognitive demand. All task-unrelated thoughts (TUTs) and the subcategory of stimulus-independent thoughts (SITUTs) were examined across the adult life span. The relationship between MW, cognitive variables (attention, inhibition, working memory), and non-cognitive variables (mindfulness, psychological well-being, and anxiety) was investigated. The sample included 210 healthy participants from 20 to 89 years old. The overall results showed few or no age-related changes in both TUTs and SITUTs. Path analyses revealed that the effect of age on both TUTs and SITUTs was only indirect and mediated by attentional resources, as well as by some aspects of psychological well-being (i.e., emotional competence), which had a direct effect, however. These findings raise doubts about any age-related differences between young and older adults’ MW. Changes in MW across the adult life span are thus discussed along with the method and tasks used to assess it and different variables affecting it.  相似文献   

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