ORCID Profile
0000-0003-3276-9685
Current Organisations
Flinders University
,
SA Pathology
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Publisher: Oxford University Press (OUP)
Date: 15-01-2008
DOI: 10.1086/524666
Abstract: Coagulase-negative staphylococci (CoNS) are an infrequent cause of native valve endocarditis (NVE), and our understanding of NVE caused by CoNS is incomplete. The International Collaboration on Endocarditis-Prospective Cohort Study includes patients with endocarditis from 61 centers in 28 countries. Patients with definite cases of NVE caused by CoNS who were enrolled during the period June 2000-August 2006 were compared with patients with definite cases of NVE caused by Staphylococcus aureus and patients with NVE caused by viridans group streptococci. Multivariable logistic regression was used to determine factors associated with death in patients with NVE caused by CoNS. Of 1635 patients with definite NVE and no history of injection drug use, 128 (7.8%) had NVE due to CoNS. Health care-associated infection occurred in 63 patients (49%) with NVE caused by CoNS. Comorbidities, long-term intravascular catheter use, and history of recent invasive procedures were similar among patients with NVE caused by CoNS and among patients with NVE caused by S. aureus. Surgical treatment for endocarditis occurred more frequently in patients with NVE due to CoNS (76 patients [60%]) than in patients with NVE due to S. aureus (150 [33%] P=.01) or in patients with NVE due to viridans group streptococci (149 [44%] P=.01). Despite the high rate of surgical procedures among patients with NVE due to CoNS, the mortality rates among patients with NVE due to CoNS and among patients with NVE due to S. aureus were similar (32 patients [25%] and 124 patients [27%], respectively P=.44) the mortality rate among patients with NVE due to CoNS was higher than that among patients with NVE due to viridans group streptococci (24 [7.0%] P=.01). Persistent bacteremia (odds ratio, 2.65 95% confidence interval, 1.08-6.51), congestive heart failure (odds ratio, 3.35 95% confidence interval, 1.57-7.12), and chronic illness (odds ratio, 2.86 95% confidence interval, 1.34-6.06) were independently associated with death in patients with NVE due to CoNS (c index, 0.73). CoNS have emerged as an important cause of NVE in both community and health care settings. Despite high rates of surgical therapy, NVE caused by CoNS is associated with poor outcomes.
Publisher: Wiley
Date: 06-1995
Publisher: Wiley
Date: 24-01-2020
Abstract: Dengue disease is an inflammatory-driven pathology, and complement overactivation is linked to disease severity and vascular leakage. Additionally, dysregulation of complement alternative pathway (AP) components has been described, such as upregulation of complement factor D and downregulation of complement factor H (FH), which activate and inhibit the AP, respectively. Thus, the pathology of severe dengue could in part result from AP dysfunction, even though complement and AP activation usually provide protection against viral infections. In dengue virus-infected macrophages and endothelial cells (ECs), the site of replication and target for vascular pathology, respectively, the AP is activated. The AP activation, reduced FH and vascular leakage seen in dengue disease in part parallels other complement AP pathologies associated with FH deficiency, such as atypical haemolytic uraemic syndrome (aHUS). aHUS can be therapeutically targeted with inhibitors of complement terminal activity, raising the idea that strategies such as inhibition of complement or delivery of FH or other complement regulatory components to EC may be beneficial to combat the vascular leakage seen in severe dengue.
Publisher: Oxford University Press (OUP)
Date: 16-10-2012
DOI: 10.1093/CID/CIS878
Abstract: The timing of cardiac surgery after stroke in infective endocarditis (IE) remains controversial. We examined the relationship between the timing of surgery after stroke and the incidence of in-hospital and 1-year mortalities. Data were obtained from the International Collaboration on Endocarditis-Prospective Cohort Study of 4794 patients with definite IE who were admitted to 64 centers from June 2000 through December 2006. Multivariate logistic regression and Cox regression analyses were performed to estimate the impact of early surgery on hospital and 1-year mortality after adjustments for other significant covariates. Of the 857 patients with IE complicated by ischemic stroke syndromes, 198 who underwent valve replacement surgery poststroke were available for analysis. Overall, 58 (29.3%) patients underwent early surgical treatment vs 140 (70.7%) patients who underwent late surgical treatment. After adjustment for other risk factors, early surgery was not significantly associated with increased in-hospital mortality rates (odds ratio, 2.308 95% confidence interval [CI], .942-5.652). Overall, probability of death after 1-year follow-up did not differ between 2 treatment groups (27.1% in early surgery and 19.2% in late surgery group, P = .328 adjusted hazard ratio, 1.138 95% CI, .802-1.650). There is no apparent survival benefit in delaying surgery when indicated in IE patients after ischemic stroke. Further observational analyses that include detailed pre- and postoperative clinical neurologic findings and advanced imaging data (eg, ischemic stroke size), may allow for more refined recommendations on the optimal timing of valvular surgery in patients with IE and recent stroke syndromes.
Publisher: Informa UK Limited
Date: 10-2015
DOI: 10.2147/IPRP.S92850
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-2020
Publisher: Elsevier BV
Date: 03-2019
Publisher: Wiley
Date: 06-1993
DOI: 10.1038/ICB.1993.24
Abstract: Mosaic proteins consist of a group of proteins that may be comprised of one or more types of a variety of different structural modules and have a erse range of functions. We have examined primary human astrocyte cultures for the presence of three mosaic proteins, B2I and the complement proteins factor H and properdin. Using the polymerase chain reaction and an enhanced chemiluminescence detection technique, we were able to show that mRNA transcripts for each of these proteins are expressed in human astrocytes.
Publisher: Elsevier BV
Date: 05-2018
DOI: 10.1016/J.TIM.2017.10.009
Abstract: The global spread of antibiotic-resistant pathogens threatens to increase the mortality of cancer patients significantly. We propose that chemotherapy contributes to the emergence of antibiotic-resistant bacteria within the gut and, in combination with antibiotics, drives pathogen overgrowth and translocation into the bloodstream. In our model, these processes are mediated by the effects of chemotherapy on bacterial mutagenesis and horizontal gene transfer, the disruption of commensal gut microbiology, and alterations to host physiology. Clinically, this model manifests as a cycle of recurrent sepsis, with each episode involving ever more resistant organisms and requiring increasingly broad-spectrum antimicrobial therapy. Therapies that restore the gut microbiota following chemotherapy or antibiotics could provide a means to break this cycle of infection and treatment failure.
Publisher: Springer Science and Business Media LLC
Date: 28-08-2023
DOI: 10.1186/S12877-023-04215-3
Abstract: The emergence of antimicrobial-resistant bacteria represents a considerable threat to human health, particularly for vulnerable populations such as those living in residential aged care. However, antimicrobial resistance carriage and modes of transmission remain incompletely understood. The Generating evidence on antimicrobial Resistance in the Aged Care Environment (GRACE) study was established to determine principal risk factors of antimicrobial resistance carriage and transmission in residential aged care facilities (RACFs). This article describes the cohort characteristics, national representation, and planned analyses for this study. Between March 2019 and March 2020, 279 participants were recruited from five South Australian RACFs. The median age was 88.6 years, the median period in residence was 681 days, and 71.7% were female. A dementia diagnosis was recorded in 54.5% and more than two thirds had moderate to severe cognitive impairment (68.8%). 61% had received at least one course of antibiotics in the 12 months prior to enrolment. To investigate the representation of the GRACE cohort to Australians in residential aged care, its characteristics were compared to a subset of the historical cohort of the Registry of Senior Australians (ROSA). This included 142,923 in iduals who were permanent residents of RACFs on June 30th, 2017. GRACE and ROSA cohorts were similar in age, sex, and duration of residential care, prevalence of health conditions, and recorded dementia diagnoses. Differences were observed in care requirements and antibiotic exposure (both higher for GRACE participants). GRACE participants had fewer hospital visits compared to the ROSA cohort, and a smaller proportion were prescribed psycholeptic medications. We have assembled a cohort of aged care residents that is representative of the Australian aged care population, and which provides a basis for future analyses. Metagenomic data isolated from participants and built environments will be used to determine microbiome and resistome characteristics of an in idual and the facility. In idual and facility risk exposures will be aligned with metagenomic data to identify principal determinants for antimicrobial resistance carriage. Ultimately, this analysis will inform measures aimed at reducing the emergence and spread of antimicrobial resistant pathogens in this high-risk population.
Publisher: Springer Science and Business Media LLC
Date: 19-02-2021
DOI: 10.1038/S41467-021-21444-5
Abstract: The durability of infection-induced SARS-CoV-2 immunity has major implications for reinfection and vaccine development. Here, we show a comprehensive profile of antibody, B cell and T cell dynamics over time in a cohort of patients who have recovered from mild-moderate COVID-19. Binding and neutralising antibody responses, together with in idual serum clonotypes, decay over the first 4 months post-infection. A similar decline in Spike-specific CD4 + and circulating T follicular helper frequencies occurs. By contrast, S-specific IgG + memory B cells consistently accumulate over time, eventually comprising a substantial fraction of circulating the memory B cell pool. Modelling of the concomitant immune kinetics predicts maintenance of serological neutralising activity above a titre of 1:40 in 50% of convalescent participants to 74 days, although there is probably additive protection from B cell and T cell immunity. This study indicates that SARS-CoV-2 immunity after infection might be transiently protective at a population level. Therefore, SARS-CoV-2 vaccines might require greater immunogenicity and durability than natural infection to drive long-term protection.
Publisher: Wiley
Date: 12-1994
DOI: 10.1038/ICB.1994.70
Abstract: We investigated complement activation by recombinant gp120 (rgp120) treated CD4 cells and the role host complement regulatory proteins play in controlling C3 deposition. Complement activation was determined by detection of C3 on rgp120 coated cells in the presence and absence of HIV seropositive sera using flow cytometry. Treatment of rgp120 coated cells with complement resulted in C3 deposition only if HIV positive sera was included. Examination of C3 fragments on these cells demonstrated rapid cleavage of C3b to iC3b. The role of the regulatory proteins was examined by pretreating cells with mAb to block decay accelerating factor (DAF) or membrane cofactor protein (MCP) or by using factor H depleted sera as a complement source. Inhibition of DAF or use of factor H depleted sera significantly increased C3 deposition on rgp120 coated cells. In contrast, C3 deposition on rgp120 coated cells was not increased after blocking MCP. The sensitivity of rgp120 coated cells to complement lysis was unchanged after inhibition of the regulatory proteins, despite the increase in C3 deposited. These results indicate that in a model of virus infected cells, C3 deposition is regulated by DAF and factor H but MCP appears to have no role.
Publisher: Elsevier BV
Date: 11-2014
Publisher: Informa UK Limited
Date: 10-2018
DOI: 10.2147/IDR.S176519
Publisher: Springer Science and Business Media LLC
Date: 13-06-2010
DOI: 10.1007/S10096-010-0983-2
Abstract: Referral bias occurs because of the clustering of patients at tertiary care centers. This may result in the distortion of observed clinical manifestations of rare diseases. This analysis evaluates the effect of referral bias on the epidemiology of infective endocarditis (IE) in the International Collaboration on Endocarditis-Prospective Cohort Study (ICE-PCS). This is a prospective multicenter cohort study comparing transferred and non-transferred patients with IE. Factors independently associated with transfer status were evaluated using multivariable logistic regression. A total of 2,760 patients were included in the analysis, of which 1,164 (42.2%) were transferred from other medical centers. Transferred patients more often underwent surgery for IE (odds ratio [OR] = 2.5 95% confidence interval [CI] 1.9-3.2). They were also more likely to have complications such as stroke (OR = 1.5 95% CI 1.3-1.9), heart failure (OR = 1.4 95% CI 1.1-1.6), and new valvular regurgitation (OR = 1.3 95% CI 1.1-1.6). The in-hospital mortality rates were similar in both groups. Patients with IE who require surgery and suffer complications are referred to tertiary hospitals more frequently than patients with an uncomplicated course. Hospital transfer has no obvious effect on the in-hospital mortality. Referral bias should be taken into consideration when describing the clinical spectrum of IE.
Publisher: American Society for Microbiology
Date: 2007
DOI: 10.1128/JCM.01012-06
Abstract: Multilocus sequence typing (MLST) has provided important new insights into the population structure of C ylobacter jejuni and is rapidly becoming the gold standard for typing this species. However, the methodology is comparatively costly and slow to perform for the routine surveillance testing of large numbers of isolates required by public health laboratories. Restriction fragment length polymorphism analysis of the flaA gene (RFLP- flaA ) and sequencing of the variable region in the fla locus (SVR- fla ) were compared to MLST to determine if a low cost alternative could be found that reliably predicts clonal lineage (as determined by MLST). An isolate of C. jejuni from each of 153 patients from New South Wales, Australia, collected sequentially over a period of 30 months from 1999 to 2001 and comprising 40 sequence types (ST) from 15 clonal complexes (CC) was examined. Of 15 CC, 12 were represented by more than one isolate and a predominant RFLP- flaA type was found for 10 (83%). Of these, seven (70%) correctly predicted the predominant MLST CC with a probability of .8. Of 40 STs detected, 19 were reported for the first time, 9 of which were represented by more than one isolate. Eight of these were represented by a single RFLP- flaA type. Only two of eight major SVR- fla types were able to predict CC with a probability of .8, indicating that flaA -RFLP is a more reliable predictor of CC than SVR- fla and thus offers an alternative to MLST for use in routine surveillance.
Publisher: Wiley
Date: 27-12-2013
DOI: 10.1111/CEO.12252
Publisher: Springer Science and Business Media LLC
Date: 25-10-2007
DOI: 10.1007/S10096-007-0406-1
Abstract: Leptotrichia species typically colonize the oral cavity and genitourinary tract. We report the first two cases of endocarditis secondary to L. goodfellowii sp. nov. Both cases were identified using 16S rRNA gene sequencing. Review of the English literature revealed only two other cases of Leptotrichia sp. endocarditis.
Publisher: American Society for Microbiology
Date: 05-2008
DOI: 10.1128/JCM.02405-07
Abstract: Coagulase-negative staphylococci (CNS) are important causes of infective endocarditis (IE), but their microbiological profiles are poorly described. We performed DNA target sequencing and susceptibility testing for 91 patients with definite CNS IE who were identified from the International Collaboration on Endocarditis—Microbiology, a large, multicenter, multinational consortium. A hierarchy of gene sequences demonstrated great genetic ersity within CNS from patients with definite endocarditis that represented erse geographic regions. In particular, rpoB sequence data demonstrated unique genetic signatures with the potential to serve as an important tool for global surveillance.
Publisher: Elsevier BV
Date: 2008
DOI: 10.1016/J.JMB.2007.09.026
Abstract: Factor H (FH) is a plasma glycoprotein that plays a central role in regulation of the alternative pathway of complement. It is composed of 20 short complement regulator (SCR) domains. The SCR-1/5 fragment is required for decay acceleration and cofactor activity, while the SCR-16/20 fragment possesses binding sites for complement C3d and heparin. X-ray scattering and analytical ultracentrifugation showed that SCR-1/5 was monomeric, while SCR-16/20 formed dimers. The Guinier radius of gyration R(G) of 4.3 nm for SCR-1/5 and those of 4.7 nm and about 7.8 nm for monomeric and dimeric SCR-16/20, respectively, showed that their structures are partially folded back and bent. The distance distribution function P(r) showed that SCR-1/5 has a maximum dimension of 15 nm while monomeric and dimeric SCR-16/20 are 17 nm and about 27 nm long, respectively. The sedimentation coefficient of 2.4 S for SCR-1/5 showed no concentration-dependence, while that for SCR-16/20 was 2.8 S for the monomer and 3.9 S for the dimer. Sedimentation equilibrium data showed that SCR-1/5 is monomeric while SCR-16/20 exhibited a weak monomer-dimer equilibrium with a dissociation constant of 16 microM. The constrained scattering and sedimentation modelling of SCR-1/5 and SCR-16/20 showed that partially folded-back and bent flexible SCR arrangements fitted both data sets better than extended linear arrangements, and that the dimer was best modelled in the SCR-16/20 model by an end-to-end association of two SCR-20 domains. The SCR-1/5 and SCR-16/20 models were conformationally similar to the previously determined partially folded-back structure for intact wild-type FH, hence suggesting a partial explanation of the intact FH structure. Comparison of the SCR-16/20 model with the crystal structure of C3b clarified reasons for the distribution of mutations leading to atypical haemolytic uraemic syndrome.
Publisher: Elsevier BV
Date: 1988
DOI: 10.3109/00313028809066622
Abstract: The requirement for an intact thiolester bond in C3 for assembly of the membrane attack complex and bactericidal activity was demonstrated in a system permitting only alternative pathway activation. Serum depleted of C3 and C4 by treatment with potassium bromide was reconstituted with forms of C3 with an intact (native C3) or disrupted (NH3.C3) thiolester bond, and bactericidal activity against Haemophilus influenzae b was determined. For strain 885 in high-antibody-containing serum, reconstitution with native C3 was associated with marked bactericidal activity (log10 kill in 60 min 1.01 +/- 0.08) compared with reconstitution with NH3.C3 (log10 kill -0.04 +/- 0.19, p less than 0.001). Similar results were obtained with other strains of H. influenzae b. In serum lacking type-specific antibody no alternative pathway-mediated bactericidal activity was detected against any of the strains examined, even when native C3 was added to KBr serum. These experiments indicate how the biochemical structure of C3 directs its functions only forms of C3 with an intact thiolester bond, which can covalently bind to bacterial surfaces, can serve as the C5 convertase and generate bacterial activity. In addition these experiments demonstrate an absolute antibody dependence for alternative pathway-mediated bactericidal activity against H. influenzae.
Publisher: American College of Physicians
Date: 15-07-1995
DOI: 10.7326/0003-4819-123-2-199507150-00002
Abstract: To document the effects of treatment with famciclovir on the acute signs and symptoms of herpes zoster and postherpetic neuralgia. A randomized, double-blind, placebo-controlled, multicenter trial. 36 centers in the United States, Canada, and Australia. 419 immunocompetent adults with uncomplicated herpes zoster. Patients were assigned within 72 hours of rash onset to famciclovir, 500 mg famciclovir, 750 mg or placebo, three times daily for 7 days. Lesions were assessed daily for as long as 14 days until full crusting occurred and then weekly until the lesions healed. Viral cultures were obtained daily while vesicles were present. Pain was assessed at each of the visits at which lesions were examined and then monthly for 5 months after the lesions healed. Safety was assessed throughout the study. Famciclovir was well tolerated, with a safety profile similar to that of placebo. Famciclovir accelerated lesion healing and reduced the duration of viral shedding. Most importantly, famciclovir recipients had faster resolution of postherpetic neuralgia (approximately twofold faster) than placebo recipients differences between the placebo group and both the 500-mg famciclovir group (hazard ratio, 1.7 [95% CI, 1.1 to 2.7]) and the 750-mg famciclovir group (hazard ratio, 1.9 [CI, 1.2 to 2.9]) were statistically significant (P = 0.02 and 0.01, respectively). The median duration of postherpetic neuralgia was reduced by approximately 2 months. Oral famciclovir, 500 mg or 750 mg three times daily for 7 days, is an effective and well-tolerated therapy for herpes zoster that decreases the duration of the disease's most debilitating complication, postherpetic neuralgia.
Publisher: Wiley
Date: 05-2006
Publisher: Elsevier BV
Date: 2008
DOI: 10.1016/J.MOLIMM.2007.05.029
Abstract: Complement may be important for immunity to infection with parasitic helminths, by promoting the recruitment of leukocytes to infected tissues and by modulating the function of cytotoxic effector leukocytes. However, the importance of complement in vivo during helminth infection is poorly understood. In this study, mice lacking classical (C1q-deficient), alternative (factor B-deficient) or all pathways of complement activation (C3-deficient) were used to assess the role of complement in immunity to the nematode Nippostrongylus brasiliensis. Double-mutant complement-deficient/IL-5 transgenic (Tg) mice were used to determine if complement is required for the strong eosinophil-dependent resistance to this parasite. Complement activation on larvae (C3 deposition), extracellular eosinophil peroxidase activity, larval aggregation and eosinophil recruitment to the skin 30 min post-injection (p.i.) of larvae were reduced in factor B-deficient mice. Inhibition of the C5a receptor with the antagonist PMX53 impaired eosinophil and neutrophil recruitment to the skin. C3 deposition on larvae was minimal by 150 min p.i. and at this time cell adherence, larval aggregation, eosinophil recruitment and degranulation were complement-independent. Factor B and C3 deficiency were associated with higher lung larval burdens in primary infections. Complement-deficient/IL-5 Tg mice were highly resistant to N. brasiliensis, suggesting that eosinophils can limit infection in a complement-independent manner. Potent secondary immunity was similarly complement-independent. In conclusion, although the alternative pathway is important for parasite recognition and leukocyte recruitment early in N. brasiliensis infections, the parasite soon becomes resistant to complement and other factors can compensate to promote eosinophil-dependent immunity.
Publisher: Frontiers Media SA
Date: 21-01-2021
DOI: 10.3389/FIMMU.2020.601895
Abstract: Complement Factor H (CFH), with 20 short complement regulator (SCR) domains, regulates the alternative pathway of complement in part through the interaction of its C-terminal SCR-19 and SCR-20 domains with host cell-bound C3b and anionic oligosaccharides. In solution, CFH forms small amounts of oligomers, with one of its self-association sites being in the SCR-16/20 domains. In order to correlate CFH function with dimer formation and the occurrence of rare disease-associated variants in SCR-16/20, we identified the dimerization site in SCR-16/20. For this, we expressed, in Pichia pastoris , the five domains in SCR-16/20 and six fragments of this with one-three domains (SCR-19/20, SCR-18/20, SCR-17/18, SCR-16/18, SCR-17 and SCR-18). Size-exclusion chromatography suggested that SCR dimer formation occurred in several fragments. Dimer formation was clarified using analytical ultracentrifugation, where quantitative c(s) size distribution analyses showed that SCR-19/20 was monomeric, SCR-18/20 was slightly dimeric, SCR-16/20, SCR-16/18 and SCR-18 showed more dimer formation, and SCR-17 and SCR-17/18 were primarily dimeric with dissociation constants of ~5 µM. The combination of these results located the SCR-16/20 dimerization site at SCR-17 and SCR-18. X-ray solution scattering experiments and molecular modelling fits confirmed the dimer site to be at SCR-17/18, this dimer being a side-by-side association of the two domains. We propose that the self-association of CFH at SCR-17/18 enables higher concentrations of CFH to be achieved when SCR-19/20 are bound to host cell surfaces in order to protect these better during inflammation. Dimer formation at SCR-17/18 clarified the association of genetic variants throughout SCR-16/20 with renal disease.
Publisher: Wiley
Date: 10-1997
DOI: 10.1038/ICB.1997.79
Abstract: The 5' flanking region of human factor H was cloned using nested polymerase chain reaction (PCR) and the promoter finder method. A total of 1.2 kb has been sequenced and a number of putative regulatory elements identified including glucocorticoid response elements cAMP responsive element, HTF-1, and acute phase signal sequences. A 717 b.p. fragment was cloned into a CAT reporter vector and transfected into HeLa cells. A series of truncations from the 5' end of this fragment were also cloned into the CAT vector. Analysis of CAT activity of the cell lysates showed that the region from -699 to +18 is likely to contain promoter elements for the factor H gene as it was able to drive transcription of the CAT gene.
Publisher: Informa UK Limited
Date: 16-03-2017
Publisher: Elsevier BV
Date: 06-2021
Publisher: American Society for Microbiology
Date: 09-2015
DOI: 10.1128/AEM.00997-15
Abstract: The life cycles of many enteric bacterial species require a transition between two very distinct environments. Their primary habitat is the gastrointestinal tract of the host, while their secondary habitat, during transmission from one host to another, consists of environments external to the host, such as soil, water, and sediments. Consequently, both host and environmental factors shape the genetic structure of enteric bacterial populations. This study examined the distribution of four Salmonella enterica subspecies in a population of sleepy lizards, Tiliqua rugosa , in a semiarid region of South Australia. The lizards living within the 1,920-m by 720-m study site were radio tracked, and their enteric bacteria were s led at regular intervals throughout their active seasons in the years 2001, 2002, and 2006. Four of the six subspecies of S. enterica were present in this population and were nonrandomly distributed among the lizards. In particular, S. enterica subsp. diarizonae was restricted to lizards living in the most shaded parts of the study site with an overstorey of Casuarina trees. Experiments undertaken to investigate the survival of S. enterica cells under seminatural conditions revealed that cell survival decreased with increased exposure to elevated temperatures and UV light. Among the three S. enterica subspecies tested, S. enterica subsp. diarizonae consistently had an average expected life span that was shorter than that observed for the other two subspecies. There was no indication in the data that there was any competitive dominance hierarchy among the S. enterica subspecies within in idual hosts. Thus, the nonrandom distribution of S. enterica subspecies in this population of lizards appears to be driven by their different survival characteristics in the external environment.
Publisher: BMJ
Date: 12-2019
DOI: 10.1136/BMJOPEN-2019-032583
Abstract: Invasive meningococcal disease (IMD) primarily causes disease in young children and adolescents and can cause long-term disability. Many countries are considering implementation of meningococcal B and/or meningococcal ACWY vaccines to control meningococcal disease. Estimating the cost-effectiveness of meningococcal vaccine programme is h ered due to a lack of good quality costing and burden of disease data. This study aims to address this evidence gap by assessing the clinical, physical, neurocognitive, economic and societal impact of IMD on adolescents and young adults. A case–control study of 64 participants with confirmed IMD (15–24 years 11 months at time of disease) and 64 control participants (17–34 years 11 months) will be conducted in Australia from 2016 to 2020. All participants will undergo a neurocognitive assessment, full medical examination, pure tone audiometry assessment and complete quality of life and behavioural questionnaires. Meningococcal cases will be assessed 2–10 years posthospitalisation and a subset of cases will be interviewed to explore in depth their experiences of IMD and its impact on their life. Primary outcome measures include general intellectual functioning from the Wechsler Adult Intelligence Scale and overall quality of life from the Health Utilities Index. Secondary outcome measures include academic achievement, executive functioning, behaviour, hearing, psychological and physical functioning. Outcome measures will be compared between cases and controls using independent t-tests or ORs, or if any significant confounders are identified, adjusted analyses (analysis of covariance or adjusted ORs) will be conducted. Thematic analysis will be used to analyse transcribed interviews and a costing model will be used to project lifetime costs. The Adolescent MENingococcal Disease (AMEND) study has been approved by the Human Research Ethics Committee of the Women’s and Children’s Health Network (HREC/14/WCHN/024). The results will be disseminated via peer-reviewed publications, conference presentations, study participants, and meningococcal and meningitis foundations. NCT03798574 .
Publisher: Informa UK Limited
Date: 05-2016
DOI: 10.2147/IDR.S107961
Publisher: Elsevier BV
Date: 03-2022
DOI: 10.1016/J.SURVOPHTHAL.2021.06.003
Abstract: Multiple studies around the world suggest that syphilis is re-emerging. Ocular syphilis - with a wide range of presentations, most of which are subtypes of uveitis - has become an increasingly common cause of ocular inflammation over the past 20 years. Its rising incidence, diagnostic complexity, and manifestations that have only recently been characterized make ocular syphilis relevant from the public health, clinical, and scientific perspectives. We review the demographics, epidemiology, clinical features, ocular imaging findings, diagnosis, and medical management of this condition.
Publisher: Wiley
Date: 22-03-2010
DOI: 10.1111/J.1758-2229.2010.00152.X
Abstract: A total of 2489 wildlife hosts from Australia were s led in order to determine the fraction of hosts that harboured Salmonella enterica as a dominant member of the host's enteric community. Hosts s led included fish, frogs, reptiles, birds and mammals from the four main climatic regions of Australia: desert, grassland, temperate and tropical. Salmonella enterica was predominately isolated from reptiles, in particular, lizards. It was also isolated from mammals, though not from any fish, frog or bird host. Salmonella enterica was more likely to be isolated from lizards living in desert or grassland regions of Australia compared with lizards inhabiting tropical or temperate regions. The low prevalence of S. enterica isolated from wildlife hosts in Australia indicates that Australian wildlife are unlikely to play a large role in disseminating S. enterica to humans and livestock.
Publisher: American Society for Microbiology
Date: 12-2008
DOI: 10.1128/JVI.01208-08
Abstract: Human metapneumovirus (hMPV) is an important cause of lower respiratory tract disease, particularly in infants and young children. hMPV has two major glycoproteins, G and F, which are responsible for virus attachment and membrane fusion, respectively. We investigated the role of cellular glycosaminoglycans (GAGs) and G protein in hMPV infection. The pretreatment of hMPV with soluble heparin markedly inhibited the infection of HEp-2 cells. Recombinant G protein, comprising the extracellular domain of G, bound to heparin-agarose columns and also to HEp-2 cells. hMPV infection and G protein binding to HEp-2 cells was inhibited by other soluble GAGs, including chondroitin sulfates, by the enzymatic removal of cell surface GAGs with GAG lyases or by the pretreatment of cells with basic fibroblast growth factor. The role of cellular GAGs was confirmed by the binding of G protein to wild-type CHO cells but not to GAG-deficient CHO-pgsA745 cells. An analysis of the G protein sequence revealed two adjacent clusters of positively charged amino acids ( 149 EKKKTRA 155 and 159 QRRGKGKE 166 ). Truncated G fragments were expressed, and only the fragment containing these putative heparin binding domains retained heparin binding. The alanine mutagenesis of charged residues in either of these regions resulted in the loss of binding to heparin and to HEp-2 cells, suggesting that both sites are likely to be required for hMPV attachment. These results, taken together with the inhibition of hMPV infection by soluble G protein, indicate an important role for G protein and cellular GAGs in hMPV infection.
Publisher: Oxford University Press (OUP)
Date: 15-05-2006
DOI: 10.1086/503426
Abstract: Ciprofloxacin-resistant C ylobacter jejuni isolates obtained from infected patients in Australia have not been detected in studies of isolates from specific geographic areas. The Australian government has prohibited the use of fluoroquinolone in food-producing animals. To assess the impact of this policy, we have examined the antimicrobial susceptibility of isolates from 5 Australian states. We conducted a period-prevalence survey of the susceptibility of C. jejuni isolates to 10 antimicrobial agents. C. jejuni isolates obtained from 585 patients from 5 Australian states (Queensland, South Australia, Tasmania, Victoria, and Western Australia) were identified by means of notifiable disease databases and were systematically selected from September 2001 to August 2002. Among locally acquired infections, only 2% of isolates (range, 0%-8% in different states) were resistant to ciprofloxacin. The locally acquired isolates also exhibited resistance to sulfisoxazole (55%), icillin (46%), roxithromycin (38%), tetracycline (7%), nalidixic acid (6%), chlor henicol (3%), erythromycin (3%), gentamicin (2%), and kanamycin (0.2%). Treatment with antimicrobial agents in the 4 weeks before onset was not associated with ciprofloxacin resistance. The very low level of ciprofloxacin resistance in C. jejuni isolates likely reflects the success of Australia's policy of restricting use of fluoroquinolones in food-producing animals.
Publisher: Elsevier
Date: 2018
Publisher: MDPI AG
Date: 07-01-2018
Publisher: Informa UK Limited
Date: 12-2021
DOI: 10.2147/IDR.S319780
Publisher: Cambridge University Press (CUP)
Date: 21-01-2008
DOI: 10.1017/S0950268807000246
Abstract: We aimed to explore C ylobacter genotype-specific risk factors in Australia. Isolates collected prospectively from cases recruited into a case-control study were genotyped using flaA restriction fragment-length polymorphism typing ( flaA genotyping). Exposure information for cases and controls was collected by telephone interview. Risk factors were examined for major flaA genotypes using logistic and multinomial regression. Five flaA genotypes accounted for 325 of 590 (55%) cases – flaA -6b ( n =129), flaA -6 ( n =70), flaA -10 ( n =48), flaA -2 ( n =43), flaA -131 ( n =35). In Australia, infections due to flaA- 10 and flaA- 2 were found to be significantly associated with eating non-poultry meat (beef and ham, respectively) in both case-control and inter-genotype comparisons. All major genotypes apart from flaA -10 were associated with chicken consumption in the case-control comparisons. Based on several clinical criteria, infections due to flaA -2 were more severe than those due to other genotypes. Thus genotype analysis may reveal genotype-specific niches and differences in virulence and transmission routes.
Publisher: Wiley
Date: 05-2001
DOI: 10.1111/J.1479-828X.2001.TB01220.X
Abstract: We describe the case of an amoebic liver abscess (ALA) presenting in the third trimester of pregnancy which raised both diagnostic and treatment dilemmas as well as being associated with preterm labour. Amoebic liver abscess is caused by the protozoan organism Entamoeba histolytica which is endemic in many parts of the developing world. Invasion of the colonic mucosa results in the clinical syndrome of amoebic dysentery and in some cases dissemination to the liver or other organs occurs resulting in abscess formation. Amoebic liver abscess is a rare complication of pregnancy and there are few reports in the world literature, these being mostly from endemic areas. We present here the case of a caucasian female who presented with an amoebic liver abscess in the third trimester of pregnancy, thirteen months after returning to Australia from a short holiday in Bali.
Publisher: American Society for Microbiology
Date: 15-07-2018
DOI: 10.1128/JVI.00633-18
Abstract: Severe dengue virus (DENV) infection is associated with overactivity of the complement alternative pathway (AP) in patient studies. Here, the molecular changes in components of the AP during DENV infection in vitro were investigated. mRNA for factor H (FH), a major negative regulator of the AP, was significantly increased in DENV-infected endothelial cells (EC) and macrophages, but, in contrast, production of extracellular FH protein was not. This discord was not seen for the AP activator factor B (FB), with DENV induction of both FB mRNA and protein, nor was it seen with Toll-like receptor 3 or 4 stimulation of EC and macrophages, which induces both FH and FB mRNA and protein. Surface-bound and intracellular FH protein was, however, induced by DENV, but only in DENV antigen-positive cells, while in two other DENV-susceptible immortalized cell lines (ARPE-19 and human retinal endothelial cells), FH protein was induced both intracellularly and extracellularly by DENV infection. Regardless of the cell type, there was an imbalance in AP components and an increase in markers of complement AP activity associated with DENV-infected cells, with lower FH relative to FB protein, an increased ability to promote AP-mediated lytic activity, and increased deposition of complement component C3b on the surface of DENV-infected cells. For EC in particular, these changes are predicted to result in higher complement activity in the local cellular microenvironment, with the potential to induce functional changes that may result in increased vascular permeability, a hallmark of dengue disease. IMPORTANCE Dengue virus (DENV) is a significant human viral pathogen with a global medical and economic impact. DENV may cause serious and life-threatening disease, with increased vascular permeability and plasma leakage. The pathogenic mechanisms underlying these features remain unclear however, overactivity of the complement alternative pathway has been suggested to play a role. In this study, we investigate the molecular events that may be responsible for this observed alternative pathway overactivity and provide novel findings of changes in the complement system in response to DENV infection in primary cell types that are a major target for DENV infection (macrophages) and pathogenesis (endothelial cells) in vivo . Our results suggest a new dimension of cellular events that may influence endothelial cell barrier function during DENV infection that could expand strategies for developing therapeutics to prevent or control DENV-mediated vascular disease.
Publisher: Oxford University Press (OUP)
Date: 2007
DOI: 10.1111/J.1365-2672.2006.03049.X
Abstract: Multilocus sequence typing (MLST) was used to examine the ersity and population structure of C ylobacter jejuni isolates associated with sporadic cases of gastroenteritis in Australia, and to compare these isolates with those from elsewhere. A total of 153 C . jejuni isolates were genotyped. Forty sequence types (STs) were found, 19 of which were previously undescribed and 21 identified in other countries. The 19 newly described STs accounted for 43% of isolates, 16 of which were assigned to known clonal complexes. Eighty-eight percent of isolates were assigned to a total of 15 clonal complexes. Of these, four clonal complexes accounted for 60% of isolates. Three STs accounted for nearly 40% of all isolates and appeared to be endemic, while 21 STs were represented by more than one isolate. Seven infections were acquired during international travel, and the associated isolates all had different STs, three of which were exclusive to the travel-acquired cases. Comparison of serotypes among isolates from clonal complexes revealed further ersity. Eight serotypes were identified among isolates from more than one clonal complex, while isolates from six clonal complexes displayed serotypes not previously associated with those clonal complexes. Multilocus sequence typing is a useful tool for the discrimination of subtypes and examination of the population structure of C . jejuni associated with sporadic infections. This study highlights the genotypic ersity of C . jejuni in Australia, demonstrating that STs causing disease have both a global and a local distribution evident from the typing of domestically and internationally acquired C . jejuni isolates.
Publisher: Elsevier BV
Date: 08-2019
DOI: 10.1016/J.DIAGMICROBIO.2019.02.016
Abstract: Staphylococcus aureus in blood cultures is rarely considered a contaminant. We report a case of intra-laboratory contamination between blood culture bottles which was confirmed by whole genome sequencing, highlighting the importance of molecular analysis in the clinical laboratory setting.
Publisher: Springer Science and Business Media LLC
Date: 08-08-2016
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 07-2018
DOI: 10.1097/ACM.0000000000002142
Abstract: Clinical reasoning is an essential component of a health professional’s practice. Yet clinical reasoning research has produced a notably fragmented body of literature. In this article, the authors describe the pause-and-reflect exercise they undertook during the execution of a synthesis of the literature on clinical reasoning in the health professions. Confronted with the challenge of establishing a shared understanding of the nature and relevant components of clinical reasoning, members of the review team paused to independently generate their own personal definitions and conceptualizations of the construct. Here, the authors describe the variability of definitions and conceptualizations of clinical reasoning present within their own team. Drawing on an analogy from mathematics, they hypothesize that the presence of differing “boundary conditions” could help explain in iduals’ differing conceptualizations of clinical reasoning and the fragmentation at play in the wider sphere of research on clinical reasoning. Specifically, boundary conditions refer to the practice of describing the conditions under which a given theory is expected to hold, or expected to have explanatory power. Given multiple theoretical frameworks, research methodologies, and assessment approaches contained within the clinical reasoning literature, different boundary conditions are likely at play. Open acknowledgment of different boundary conditions and explicit description of the conceptualization of clinical reasoning being adopted within a given study would improve research communication, support comprehensive approaches to teaching and assessing clinical reasoning, and perhaps encourage new collaborative partnerships among researchers who adopt different boundary conditions.
Publisher: Elsevier BV
Date: 11-1996
DOI: 10.1016/S0140-6736(05)65508-0
Abstract: Background Renal dysfunction is a potentially life-threatening condition that is commonly encountered in the emergency department (ED). This study aimed to describe the clinical profile of patients presenting with renal dysfunction to a tertiary-level hospital ED. Methods Medical records of patients presenting to the ED with renal dysfunction over a six-month period (July-December 2017) were reviewed. A descriptive analysis of the data was performed. Results Serum creatinine levels were measured in 7,442 (69.9%) of the 10,642 patients that were triaged into the ED. Of these, 208 (2.8%) were identified with renal dysfunction, of which 192 consented to study participation. The median age of study subjects was 49.5 (IQR 38.8-63.0) years 108 (56.3%) were male proteinuria on urine dipsticks was demonstrated in 108 (56.3%) 72 (37.5%) were HIV-positive 66 (39.6%) required dialysis 11 (5.7%) were admitted to the ICU and 59 (30.7%) died prior to hospital discharge. More patients presented with acute kidney injury (AKI) (46.9%) compared to chronic kidney disease (CKD) (27.6%) and acute on chronic kidney disease (AoCKD) (25.5%). Sepsis was the most common precipitant of AKI (42.2%) and AoCKD (30.6%), while chronic hypertension (35.8%) and diabetes mellitus (34.0%) were the most common comorbidities in subjects with CKD. Conclusion Patients presenting to the ED with various risk factors and comorbidities, including HIV, sepsis, hypertension, and diabetes mellitus, may have underlying renal dysfunction. ED clinicians should therefore adopt a low threshold to screen for renal dysfunction in these patients.
Publisher: Oxford University Press (OUP)
Date: 29-05-2003
DOI: 10.1046/J.1365-2249.2003.02173.X
Abstract: Rheumatoid arthritis is a chronic inflammatory disease of unknown aetiology predominantly affecting cells and tissues of synovial joints. Here we show that the two important complement regulators FHL-1 and factor H play a protective anti-inflammatory role in rheumatoid arthritis. Expression analyses at the mRNA- and protein level show in vitro expression and secretion of both regulators by synovial fibroblasts derived from patients with rheumatoid arthritis. Similarly the two regulators are synthesized in vivo in diseased synovial tissue, and in particular synovial lining cells express high levels of FHL-1. The anti-inflammatory role of these regulators in rheumatoid arthritis is highlighted by their induction with IFN-γ and dexamethasone, whilst the pro-inflammatory cytokine TNF-α had no effect. Transient transfection experiments with various FHL-1/factor H promoter-luciferase reporter constructs into cells of distinct origin show independent cell and tissue specific promoter regulated transcription of these two regulators. The inducible expression, specifically of FHL-1 has physiological consequences. By binding directly to surfaces the released proteins protect cells from inflammatory damage and complement-mediated cell lysis. This study shows a novel protective and anti-inflammatory role of the two important complement regulators FHL-1 and factor H in rheumatoid arthritis and suggests a disease controlling role of the two proteins.
Publisher: Public Library of Science (PLoS)
Date: 17-05-2013
Publisher: Oxford University Press (OUP)
Date: 06-2008
DOI: 10.1086/587896
Abstract: Telavancin is an investigational, rapidly bactericidal lipoglycopeptide with a multifunctional mechanism of action. We conducted 2 parallel, randomized, double-blind, active-control, phase 3 studies with a prespecified pooled analysis design. Patients aged > or = 18 years who had complicated skin and skin-structure infections caused by suspected or confirmed gram-positive organisms were randomized to receive either telavancin (10 mg/kg intravenously every 24 h) or vancomycin (1 g intravenously every 12 h). A total of 1867 patients were randomized and received > or = 1 dose of study medication. In the clinically evaluable population, at 7-14 days after receipt of the last antibiotic dose, success was achieved in 88% and 87% of patients who received telavancin and vancomycin, respectively (95% confidence interval for the difference, -2.1 to 4.6). Methicillin-resistant Staphylococcus aureus was isolated at baseline from s les from 579 clinically evaluable patients. Among these patients with methicillin-resistant S. aureus infection, cure rates were 91% among patients who received telavancin and 86% among patients who received vancomycin (95% confidence interval for the difference, -1.1 to 9.3). Microbiologic eradication among patients infected with methicillin-resistant S. aureus was 90% in the telavancin treatment group and 85% in the vancomycin treatment group (95% confidence interval for the difference, -0.9 to 9.8). Therapy was discontinued because of adverse events in 8% and 6% of patients who received telavancin and vancomycin, respectively. Except for mild taste disturbance, nausea, vomiting, and serum creatinine concentration elevation in the telavancin treatment group and pruritus in the vancomycin treatment group, adverse events were similar between groups with regard to type and severity. Telavancin given once daily is at least as effective as vancomycin for the treatment of patients with complicated skin and skin-structure infections, including those infected with methicillin-resistant S. aureus.
Publisher: Elsevier BV
Date: 04-1996
DOI: 10.1016/0304-4165(95)00095-X
Abstract: Thrombospondin is a trimeric glycoprotein that has several known functions, including roles in platelet aggregation, phagocytosis and an inhibitor of angiogenesis. Typically the molecule is isolated from platelet secretate by heparin affinity followed by sizing chromatography. In this study, purity is analysed by 7.5% SDS-PAGE under reducing conditions when thrombospondin monomers run as a band at around 180 kDa. Under nonreducing conditions of 7.5% SDS-PAGE, thrombospondin does not penetrate beyond the stacking gel however, under these conditions a major contaminating band can be seen which, upon reduction, merges into the thrombospondin band. Further purification of this contaminating protein was achieved by DEAE chromatography and it was identified as Factor H by peptide sequencing and immunoblotting. Factor H function was demonstrated by the ability of the protein to function as a cofactor in the Factor-I-mediated cleavage of C3b. Since Factor H has several known functions, such contamination could confound functional studies of thrombospondin thus purified and a pre-elution step of the heparin affinity column is recommended.
Publisher: MDPI AG
Date: 16-10-2013
DOI: 10.3390/V5102546
Publisher: SAGE Publications
Date: 12-2015
Abstract: Human metapneumovirus is an emerging cause of lower respiratory disease in infants, young children, and immunocompromised adults. We have previously demonstrated that human metapneumovirus infection is mediated by interaction of human metapneumovirus attachment (G) and/or fusion (F) proteins with cellular glycosaminoglycans. We report here the activity of an investigational sialidase fusion protein, DAS181, on human metapneumovirus infection of Hep-2 cells. These results suggest that human metapneumovirus infection may involve sialic acids, providing a new therapeutic strategy for human metapneumovirus for which there is currently no available treatment. Hep-2 cells were preincubated with DAS181 or control DAS185 (a mutated sialidase) prior to inoculation with human metapneumovirus strains. Infectivity was assessed by a cell-based ELISA quantitating human metapneumovirus matrix protein. The effect of DAS181 on binding of recombinant G attachment protein was also determined. DAS181 blocked infection of human metapneumovirus strains A2, B1, and B2 at low concentrations. No effect of DAS185 was observed. Binding of MPV G protein to Hep-2 cells was also markedly inhibited by preincubation of cells with DAS181. These results suggest that human metapneumovirus may utilize sialic acids as an entry cofactor. DAS181 may thus represent a new therapeutic agent useful for the treatment of human metapneumovirus.
Publisher: SAGE Publications
Date: 13-01-2015
Abstract: We describe a case of development of painful periostitis deformans in a 39-year-old woman who was receiving long-term voriconazole treatment for Aspergillus infection as a complication of orthotopic liver transplant. Measurement of fluoride levels strongly supports fluorosis to be the mechanism of the voriconazole-induced periostitis deformans and supports the concept that such measurements might be of use in predicting this complication of long-term voriconazole treatment.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 04-2013
Publisher: Wiley
Date: 03-2001
Publisher: AMPCo
Date: 03-1989
Publisher: Elsevier
Date: 2017
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 05-2008
DOI: 10.1167/IOVS.07-1297
Abstract: A Tyr-to-His (Y402H) sequence variant in the factor H (FH) and factor H-like protein (FHL-1) gene is strongly associated with an increased susceptibility for age-related macular degeneration (AMD). The purpose of this study was to understand how the Y402H variant in FH/FHL-1 contributes to the pathogenesis of AMD and, in particular, whether interactions mediated by FH/FHL-1, including binding to C-reactive protein (CRP), group A streptococcal M protein (GAS M6), heparin, and retinal pigment epithelial cells (RPE), are affected. FH was purified from sera of patients homozygous for FH(Y402) or (H402), and recombinant FH fragments representing FHL-1 were generated. Proteins were analyzed for binding to CRP, GAS M6, heparin, and RPE cells. Binding of the FH and FH1 to seven polymorphic variants to CRP and M protein was reduced. The variant did not influence the interaction of FH with heparin but did reduce binding of FHL-1. Binding of the FH and FHL-1 polymorphic variant to RPE cells was not affected. The FH Y402H polymorphism associated with AMD causes a reduction in binding of FH and FHL-1 to CRP and M protein. Both variants show comparable binding to RPE cells, indicating that AMD is unlikely to manifest as a result of impaired host cell-surface recognition. The decreased interaction between FH and CRP, which is essential for the anti-inflammatory function of CRP, provides a possible pathophysiological explanation for the association of the Y402H variant with AMD.
Publisher: Oxford University Press (OUP)
Date: 10-11-2014
DOI: 10.1093/CID/CIU871
Publisher: Elsevier BV
Date: 2019
DOI: 10.1016/J.MIMET.2018.12.001
Abstract: The efficacy of faecal microbiota transplantation (FMT) as a therapeutic intervention may depend on the viability of the microorganisms in faecal slurries (FS) prepared from donor stool. However, determining the viability of these organisms is challenging. Most microorganisms in stool are refractory to culture using standard techniques, and culture-independent PCR-based methods derive signal from both viable and non-viable cells. Propidium monoazide (PMA) treatment has been shown to be effective in preventing PCR lification of DNA from non-viable bacteria in a range of contexts. However, this methodology can be sensitive to factors such as bacterial load and s le turbidity. We describe the optimisation of a PMA treatment methodology for FS that restricts quantitative PCR-based bacterial enumeration to viable cells. When applied to concentrated FS (10-25% stool content), PMA treatment at 100 μM concentration was ineffective in preventing DNA lification from heat-killed cells. Efficacy was not significantly improved by doubling the PMA concentration. However, PMA treatment efficacy was improved markedly following 10-fold s le dilution, and was found to be optimal at 100-fold dilution. Substantial reductions in viable bacterial load could be observed following both freeze-thaw and heat-treatment of FS. This method successfully prevented DNA lification of heat-killed Pseudomonas and Staphylococcus spiked into stool and could reliably determine the proportion of live bacteria and viable E. coli counts present in fresh and heat-treated stool. With appropriate s le dilution, PMA treatment excluded >97% of non-viable cells from lification in all assays, without significantly affecting the lification of DNA from viable cells. This method can be applied to optimise s le processing of FMT donor material, and to characterise bacterial viability within faecal s les more widely.
Publisher: Royal Society of Chemistry (RSC)
Date: 2016
DOI: 10.1039/C6RA07678E
Abstract: Using a simple dip-coating mechanism, urinary catheters have been coated with poly(2-methacryloyloxyethyl)trimethylammonium chloride (pMTAC) using activator regenerated by electron transfer (ARGET)–atom transfer radical polymerization (ATRP).
Publisher: Elsevier BV
Date: 10-2017
DOI: 10.1016/J.VACCINE.2017.08.053
Abstract: Analysis of the anti-haemagglutinin serum antibody proteome from six H1N1pdm09 influenza A vaccinated subjects demonstrated restricted IgG1 heavy chain species encoded by IGHV5-51 and IGHV3-7 gene families in 2 subjects and either IGHV5-51 or IGHV3-7 in 4 in iduals. All subjects exhibited a dominant IGKV3-20 light chain, however 5 subjects also exhibited IGKV3-11 and IGKV4-1 families. Sequences were closely aligned with the matched germline sequence, with few shared mutations. This study illustrates the feasibility of using a proteomic approach to determine the expressed V region signatures of serum antibodies induced by vaccination.
Publisher: Wiley
Date: 08-1992
DOI: 10.1111/J.1440-0960.1992.TB00088.X
Abstract: A case of recurrent cutaneous cryptococcosis in an immunocompromised patient is described. The patient presented with a non-healing cutaneous ulcer due to infection with Cryptococcus neoformans. Extensive investigation failed to reveal any evidence of associated systemic cryptococcosis. Treatment with oral fluconazole resulted in complete resolution of the ulcer but after several months a second cutaneous cryptococcal lesion appeared, strongly suggesting dissemination from an underlying systemic focus. This case illustrates the hazards associated with making a diagnosis of isolated cutaneous cryptococcosis and the necessity for prolonged follow-up of patients who present in this way.
Publisher: Wiley
Date: 11-1999
DOI: 10.1046/J.1440-0960.1999.00370.X
Abstract: A bacteriology technical officer presented with episodes of burning pruritus and urticarial-like lesions on the face and forearms. Patch testing was strongly positive for epoxy resin. The exposure was occupational to the re-formulation of microscopy immersion oil.
Publisher: Elsevier BV
Date: 07-2021
Publisher: Wiley
Date: 29-10-2009
DOI: 10.1096/FJ.08-119537
Abstract: The pneumococcal histidine triad (Pht) proteins are a recently recognized family of surface proteins, comprising 4 members: PhtA, PhtB, PhtD, and PhtE. They are being promoted for inclusion in a multicomponent pneumococcal protein vaccine currently under development, but to date, their biological functions and their relative contributions to pathogenesis have not been clarified. In this study, the involvement of these proteins in pneumococcal virulence was investigated in murine models of sepsis and pneumonia by using defined, nonpolar mutants of the respective genes in Streptococcus pneumoniae D39. In either challenge model, mutagenesis of all 4 genes was required to completely abolish virulence relative to the wild-type, suggesting significant functional redundancy among Pht proteins. The in vivo expression of pht genes was significantly up-regulated in the nasopharynx and lungs compared with blood. We provide unequivocal molecular evidence for Zn(2+)-dependent, AdcR-mediated, regulation of pht gene expression by real-time reverse transcriptase-polymerase chain reaction, Western blotting, and electrophoretic mobility-shift assays. We also present the first direct evidence for the biological function of this protein family by demonstrating that Pht proteins are required for inhibition of complement deposition on the pneumococcal surface through the recruitment of complement factor H.
Publisher: Elsevier BV
Date: 05-2020
DOI: 10.1016/J.TIM.2019.12.009
Abstract: Faecal microbiota transplantation (FMT) has been shown to be effective in the treatment of a growing number of conditions, and its clinical use continues to rise. However, recent cases of antibiotic-resistant pathogen transmission through FMT, resulting in at least one case of fatal sepsis, highlight the need to reevaluate current donor screening practices. Commensal gut microbes profoundly influence infection risk but are not routinely assessed in donor stool. Extending the assessment of donor material beyond pathogen populations to include the composition and structure of the wider faecal microbiota has the potential to reduce infectious complications in FMT recipients.
Publisher: Elsevier BV
Date: 1991
DOI: 10.3109/00313029109060815
Abstract: One thousand eight hundred urine specimens were examined prospectively to determine the validity of primary sensitivity testing. Microscopic criteria assessing pyuria and microorganisms were developed for predicting the presence of urinary tract infection and thus suitability for direct sensitivity testing. The criteria selected gave a positive predictive value of 74.6% and a negative predictive value of 99.5%. Zone diameters by primary and standardized secondary methods were compared for each urinary pathogen to each antibiotic tested. Percentage agreement between primary and secondary sensitivity results varied between 100% for Enterobacteriaceae tested against Gentamicin to 95.2% for Enterococcus faecalis tested against Ampicillin. Seventeen discrepancies between primary and secondary test results were observed (error 2.0%) with only 3 of potential clinical significance (primary sensitive, secondary resistant). Although primary sensitivity testing has limitations, our study indicates that the results are, in the vast majority of cases, in agreement with secondary testing, and are probably adequate for the clinical management of uncomplicated urinary tract infections. Furthermore, as primary testing rarely produces false resistant results it may permit earlier modification of initial empiric therapy.
Publisher: Wiley
Date: 05-2012
Publisher: Oxford University Press (OUP)
Date: 12-1989
DOI: 10.1111/J.1574-6968.1989.TB02433.X
Abstract: We examined the serum requirements for surface phagocytosis of Staphylococcus epidermidis and Escherichia coli and for the subsequent chemiluminescent response of human neutrophils. Substantial surface phagocytosis of S. epidermidis occurred in the absence of opsonins, although the presence of 10% pooled or heat-inactivated serum significantly increased phagocytosis. There was no significant difference between these opsonins, indicating that surface phagocytosis of S. epidermidis did not require complement. Unopsonized E. coli were not as readily phagocytized as S. epidermidis (33% versus 57%). In contrast to S. epidermidis optimal phagocytosis of E. coli required complement as 10% heat inactivated donor serum (HHS) was significantly less effective as an opsonin than 10% pooled healthy donor serum (PHS). The time kinetics for phagocytosis of each organism were similar, with most of the phagocytosis occurring in the first 10 min. The chemiluminescent response of neutrophils produced discrepant results. Maximal chemiluminescence was observed when neutrophils were stimulated with bacteria opsonized in PHS. The response to HHS-opsonized bacteria was less, and chemiluminescence to unopsonized bacteria was only marginally higher than the control, even though there was relatively good phagocytosis. These results define the opsonic requirements for surface phagocytosis of S. epidermidis and E. coli and indicate that although complement may not be required for phagocytosis, it is necessary for generation of a maximal oxidative burst, and thus may be essential for efficient intracellular killing.
Publisher: Microbiology Society
Date: 03-2021
DOI: 10.1099/JGV.0.001547
Abstract: The complement alternative pathway (AP) is tightly regulated and changes in two important AP components, factor B (FB) and factor H (FH) are linked to severe dengue in humans. Here, a mouse model of dengue was investigated to define the changes in FB and FH and assess the utility of this model to study the role of the AP in severe dengue. Throughout the period of viremia in the AG129 IFN signalling-deficient mouse, an increase in FB and a decrease in FH was observed following dengue virus (DENV) infection, with the former only seen in a model of more severe disease associated with antibody-dependent enhancement (ADE). Terminal disease was associated with a decrease in FB and FH, with greater changes during ADE, and accompanied by increased C3 degradation consistent with complement activation. In silico analysis of NFκΒ, signal transducer and activator of transcription (STAT) and IFN-driven FB and FH promoter elements to reflect the likely impact of the lack of IFN-responses in AG129 mice, demonstrated that these elements differed markedly between human and mouse, notably with mouse FH lacking NFκΒ and key IFN-stimulated response elements (ISRE), and FB with many more NFκΒ and STAT-responsive elements than human FB. Thus, the AG129 mouse offers utility in demonstrating changes in FB and FH that, similar to humans, are associated with severe disease, but lack predicted important human-specific and IFN-dependent responses of FB and FH to DENV-infection that are likely to regulate the subtleties of the overall AP response during dengue disease in humans.
Publisher: SAGE Publications
Date: 07-2015
DOI: 10.1177/0310057X1504300407
Abstract: Prophylaxis for surgical site infection (SSI) is often at variance with guidelines, despite the prevalence of SSI and its associated cost, morbidity, and mortality. The CareTrack Australia study, undertaken by a number of the authors, demonstrated that appropriate care (in line with evidence- or consensus-based guidelines) was provided at 38% of eligible SSI healthcare encounters. Here, we report the indicator-level CareTrack Australia findings for SSI prophylaxis. Indicators were extracted from Australian and international clinical guidelines and ratified by clinical experts. A s le designed to be representative of the Australian population was recruited (n=1154). Participants’ medical records were reviewed and analysed for compliance with the five SSI indicators. The main outcome measure was the percentage of eligible healthcare encounters with documented compliance with indicators for appropriate SSI prophylaxis. Of the 35,145 CareTrack Australia encounters, 702 (2%) were eligible for scoring against the SSI indicators. Where antibiotics were recommended, compliance was 49% for contaminated surgery, 57% for clean-contaminated surgery and 85% for surgery involving a prosthesis: these fell to 8%, 10% and 14%, respectively (an average of 11%), when currently recommended timing of antibiotic administration was included. Where antibiotics were not indicated, 72% of patients still received them. SSI prophylaxis in our s le was poor over two-thirds of patients were given antibiotics, whether indicated or not, mainly at the wrong time. There is a need for national agreement on clinical standards, indicators and tools to guide, document and monitor SSI prophylaxis, with both local and national measures to increase and monitor their uptake.
Publisher: Oxford University Press (OUP)
Date: 10-1986
Abstract: We used polyclonal and monoclonal antibodies to neutrophil complement receptors CR1 and CR3 to assess the role of these receptors in the phagocytosis of virulent Streptococcus pneumoniae serotypes 3, 6A, and 14, which bear accessible C3 ligands covalently bound to the polysaccharide capsule. When the iC3b receptor (CR3) on normal polymorphonuclear leukocytes (PMNLs) was blocked by the monoclonal antibody OKM10, phagocytosis of pneumococcal serotypes 6A and 14 (which bear exclusively iC3b) was inhibited 50%-80% in pooled human serum and completely in nonimmune serum. Blockade of the PMNL C3b receptor (CR1) failed to inhibit phagocytosis for serotypes 6A and 14. For serotype 3, which bears C3b and C3d (as well as iC3b) on the capsule, CR3-mediated phagocytosis accounted for only 20% of the uptake again, there was no evidence for CR1-mediated phagocytosis. The iC3b ligand elicited consistently greater release of superoxide, myeloperoxidase, and lactoferrin than did C3b. The iC3b/CR3 interaction is thus the primary trigger for phagocytosis of iC3b-bearing pneumococci and for stimulation of intracellular bactericidal processes.
Publisher: Elsevier BV
Date: 12-2007
DOI: 10.1016/J.AHJ.2007.07.023
Abstract: Embolic events to the central nervous system are a major cause of morbidity and mortality in patients with infective endocarditis (IE). The appropriate role of valvular surgery in reducing such embolic events is unclear. The purpose of this study was to determine the relationship between the initiation of antimicrobial therapy and the temporal incidence of stroke in patients with IE and to determine if this time course differs from that shown for embolic events in previous studies. Prospective incidence cohort study involving 61 tertiary referral centers in 28 countries. Case report forms were analyzed from 1437 consecutive patients with left-sided endocarditis admitted directly to participating centers. The crude incidence of stroke in patients receiving appropriate antimicrobial therapy was 4.82/1000 patient days in the first week of therapy and fell to 1.71/1000 patient days in the second week. This rate continued to decline with further therapy. Stroke rates fell similarly regardless of the valve or organism involved. After 1 week of antimicrobial therapy, only 3.1% of the cohort experienced a stroke. The risk of stroke in IE falls dramatically after the initiation of effective antimicrobial therapy. The falling risk of stroke in patients with IE as a whole precludes stroke prevention as the sole indication for valvular surgery after 1 week of therapy.
Publisher: Microbiology Society
Date: 21-04-2021
Abstract: Background. C ylobacter curvus is a Gram-negative bacteria associated with periodontal disease in humans. Cases of extra-oral manifestations of infection are rare with only six reported cases of extra-oral infection including this report that have been identified in the current literature. Molecular methods are generally used to identify C. curvus while optimal antibiotic choice and duration to treat extra-oral infections for this pathogen is unknown. Case presentation. A 63-year-old male with a background history of alcoholic pancreatitis presented with fever and malaise who was found to have radiological intra-abdominal collections. Drainage of these collections identified C. curvus via matrix-assisted laser desorption/ionisation time of flight (MALDI-TOF) mass spectrometry with high probability and identification further confirmed by whole-genome sequencing. Antibiotic susceptibility testing to erythromycin and ciprofloxacin of C. curvus was performed using E-test diffusion methods along with investigation for the presence of resistance genes. The patient was treated with intravenous piperacillin-tazobactam followed by ciprofloxacin for 4 weeks total with good clinical recovery. Conclusions. Extra-oral manifestations with the pathogen C. curvus are rare with few cases described in the literature. There is minimal data on susceptibility patterns, optimal antibiotic treatment and duration. Treatment of extraintestinal C. curvus infections in humans should encompass both adequate source control and antibiotic therapy.
Publisher: Elsevier BV
Date: 2000
DOI: 10.1016/S0161-5890(00)00024-9
Abstract: Complement factor H (fH) is a member of a family of proteins involved in the regulation of complement activation (RCA). These proteins share a common structural motif, the Short Consensus Repeat (SCR), which is structurally conserved among related genes and between phylogenetically ergent species. fH is composed of 20 such SCRs and a variety of biological functions have been localised to specific SCR domains. The majority of in idual SCRs identified are encoded by single exons, and processes such as gene conversion, duplication and exon shuffling have been implicated in the evolution and genomic radiation of SCR-encoding genes. We have analysed two GenBank sequence entries relating to two overlapping PAC clones sequenced at the Sanger Centre which contain the entire human fH gene and two adjacent fH-related (fHR) genes, fHR-1 and fHR-3. Here, we report the detailed analysis of the assembled 221 kb of contiguous, ungapped genomic sequence from human chromosome 1q32, in part employing the RUMMAGE-DP automated annotation tool. Genomic duplications involving fH and fHR exons were identified and Alu/L1 repeat dating established that the duplications occurred after the separation of rodent and primate lineages. The analysis indicates that retrotransposition as well as single and multiple exon duplication events are likely to have been involved in SCR radiation and RCA gene evolution, facilitated by conservation of splice-phasing and the single-exon, single-SCR nature of the encoded domains.
Publisher: Wiley
Date: 26-05-2020
DOI: 10.1111/ANS.15963
Publisher: Elsevier BV
Date: 06-2004
Publisher: Elsevier BV
Date: 10-2016
Publisher: American Society for Microbiology
Date: 06-2007
DOI: 10.1128/JCM.00175-07
Abstract: Bartonella quintana is increasingly recognized as a cause of clinical disease in various geographical locations. We characterized three Australian strains associated with endocarditis, using established molecular-typing techniques, the 16S/23S rRNA intergenic spacer (ITS) region, and multispacer typing (MST). All strains examined demonstrated novel ITS and/or MST genotypes. Further characterization of Australian strains is required to determine whether there is an association between genotype and geographical location.
Publisher: AMPCo
Date: 09-1994
Publisher: AMPCo
Date: 05-1992
Publisher: American Society for Microbiology
Date: 10-2002
DOI: 10.1128/IAI.70.10.5604-5611.2002
Abstract: The innate ability of Streptococcus pneumoniae to resist complement activation and complement-mediated phagocytosis may be a direct consequence of the ability of the bacteria to bind components of the complement regulatory system. One such component, factor H (fH), is a crucial fluid-phase negative regulator of the alternative pathway of complement and is utilized by a number of pathogenic organisms to resist complement attack. The pneumococcal surface protein C (PspC [also known as CbpA] and SpsA) has been shown to bind fH, although the exact binding site within one or more of the 20 short consensus repeats (SCRs) of the molecule is not known. The purpose of the current study was to map specific SCRs on fH responsible for this binding. Initial experiments utilizing type 2 pneumococcal strain D39 and its isogenic PspC-negative derivative (D39/ pspC mutant) showed that fH binding was PspC dependent. A purified recombinant protein derivative of PspC that lacked the proline-rich region (PspCΔPro) had a reduced binding efficiency for fH, thereby directly showing the importance of this region for the fH interaction. We have specifically shown by inhibition experiments that SCRs responsible for heparin and C3b binding of fH are not involved in binding PspC and the interaction between fH and PspC is largely hydrophobic, since no inhibition was observed in the presence of high concentrations of NaCl. Construction of SCR proteins encompassing the whole fH molecule showed that SCRs 8 to 15 (SCR 8-15) mediated binding to PspC. Further localization experiments revealed that SCR 13 and SCR 15 were required for full binding, although partial binding was retained when either SCR was removed.
Publisher: Elsevier BV
Date: 02-2020
DOI: 10.1016/J.VACCINE.2019.10.096
Abstract: Clostridioides difficile infection is the leading cause of nosocomial diarrhoea globally. Immune responses to toxins produced by C. difficile are important in disease progression and outcome. Here, we analysed the anti-toxin A and anti-toxin B serum antibody proteomes following natural infection or vaccination with a C. difficile toxoid A/toxoid B vaccine using a modified miniaturised proteomic approach based on de novo mass spectrometric sequencing. Analysis of immunoglobulin variable region (IgV) subfamily expression in immunoprecipitated toxin A and toxin B antibodies from four and seven participants of a vaccine trial, respectively, revealed a polyclonal proteome with restricted IGHV, IGKV and IGLV subfamily usage. No dominant IGHV subfamily was observed in the toxin A response, however the dominant anti-toxin B heavy (H)-chain was encoded by IGHV3-23. Light (L)-chain usage was convergent for both anti-toxin A and anti-toxin B proteomes with IGKV3-11, 3-15, 3-20 and 4-1 shared among all subjects in both cohorts. Peptide mapping of common IgV families showed extensive public and private amino acid substitutions. The cohort responses to toxin A and toxin B showed limited similarity in shared IGHV subfamilies. L-chain subfamily usage was more similar in the anti-toxin A and anti-toxin B responses, however the mutational signatures for each subfamily were toxin-dependent. S les taken both post vaccination (n = 5) or at baseline, indicating previous exposure (n = 2), showed similar anti-toxin B IgV subfamily usage and mutational profiles. In summary, this study provides the first sequence-based proteomic analysis of the antibody response to the major disease-mediating toxins of C. difficile, toxin A and toxin B, and demonstrates that despite the potential for extreme ersity, the immunoglobulin repertoire can raise convergent responses to specific pathogens whether through natural infection or following vaccination.
Publisher: Springer Science and Business Media LLC
Date: 07-03-2020
Publisher: Wiley
Date: 06-1994
DOI: 10.1038/ICB.1994.33
Abstract: CD59 is a membrane glycoprotein that regulates the membrane attack complex of complement and protects cells from autologous complement damage. Human polymorphonuclear leucocyte (PMN) expression of CD59 was confirmed by flow cytometry following staining with mAb 1F5, and western blotting revealed staining of a 19-23 kDa band. Warming of PMN from 4 to 37 degrees C resulted in spontaneous CD59 upregulation. A dose-dependent increase in expression following PMN stimulation with FMLP was observed and occurred within minutes, indicating that new protein synthesis was not required. Treatment of PMN with calcium ionophore A23187 resulted in similar increases in CD59 expression. This occurred in the presence or absence of extracellular calcium, indicating that upregulation was dependent on release of calcium from intracellular stores. Evidence for a mobilizable intracellular pool of CD59 was obtained by detection of increased binding of 1F5 following PMN permeabilization CD59 could also be re-expressed after stripping by phosphatidylinositol specific phospholipase C (PI-PLC) by treatment with FMLP or A23187. There was a correlation between CD59 upregulation and lactoferrin release, suggesting that stores of CD59 may be associated with secondary granules. These studies indicate that PMN expression of CD59 is enhanced by cell activation and suggest the presence of an intracellular pool of CD59 which can be translocated to the cell membrane upon PMN stimulation.
Publisher: American Society for Microbiology
Date: 19-01-2022
DOI: 10.1128/JCM.03202-20
Abstract: Evaluation of penicillin and oxacillin susceptibility testing was conducted on 200 Staphylococcus lugdunensis isolates. Disc diffusion with penicillin 1 IU (P1, EUCAST) and penicillin 10 IU (P10, CLSI) was compared with nitrocefin discs (Cefinase) and automated broth microdilution (Vitek 2).
Publisher: CRC Press
Date: 02-10-2017
Publisher: Wiley
Date: 27-07-2012
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 31-12-2020
Publisher: Elsevier BV
Date: 07-2016
Publisher: Elsevier
Date: 2012
Publisher: American Society for Microbiology
Date: 11-2005
DOI: 10.1128/IAI.73.11.7442-7449.2005
Abstract: Complement activation and C3 deposition on the surface of parasitic helminths may be important for recruitment of leukocytes and for damage to the target organism via cell-mediated mechanisms. Inhibition of complement activation would therefore be advantageous to parasites, minimizing damage and enhancing migration through tissues. The aim of this study was to determine ex vivo if complement activation by, and leukocyte adherence to, the nematode Nippostrongylus brasiliensis change as the parasite matures and migrates through the murine host. Pathways of activation of complement and the mechanism of adherence of leukocytes were also defined using sera from mice genetically deficient in either C1q, factor B, C1q and factor B, C3, or C4. Substantive deposition of C3 and adherence of eosinophil-rich leukocytes were seen with infective-stage (L3) but not with lung-stage (L4) larvae. Adult intestinal worms had low to intermediate levels of both C3 and leukocyte binding. For L3 and adult worms, complement deposition was principally dependent on the alternative pathway. For lung-stage larvae, the small amount of C3 detected was dependent to similar degrees on both the lectin and alternative pathways. The classical pathway was not involved for any of the life stages of the parasite. These results suggest that in primary infections, the infective stage of N. brasiliensis is vulnerable to complement-dependent attack by leukocytes. However, within the first 24 h of infection, N. brasiliensis acquires the ability to largely avoid complement-dependent immune responses.
Publisher: American Medical Association (AMA)
Date: 22-06-2005
Abstract: The global significance of infective endocarditis (IE) caused by Staphylococcus aureus is unknown. To document the international emergence of health care-associated S aureus IE and methicillin-resistant S aureus (MRSA) IE and to evaluate regional variation in patients with S aureus IE. Prospective observational cohort study set in 39 medical centers in 16 countries. Participants were a population of 1779 patients with definite IE as defined by Duke criteria who were enrolled in the International Collaboration on Endocarditis-Prospective Cohort Study from June 2000 to December 2003. In-hospital mortality. S aureus was the most common pathogen among the 1779 cases of definite IE in the International Collaboration on Endocarditis Prospective-Cohort Study (558 patients, 31.4%). Health care-associated infection was the most common form of S aureus IE (218 patients, 39.1%), accounting for 25.9% (Australia/New Zealand) to 54.2% (Brazil) of cases. Most patients with health care-associated S aureus IE (131 patients, 60.1%) acquired the infection outside of the hospital. MRSA IE was more common in the United States (37.2%) and Brazil (37.5%) than in Europe/Middle East (23.7%) and Australia/New Zealand (15.5%, P<.001). Persistent bacteremia was independently associated with MRSA IE (odds ratio, 6.2 95% confidence interval, 2.9-13.2). Patients in the United States were most likely to be hemodialysis dependent, to have diabetes, to have a presumed intravascular device source, to receive vancomycin, to be infected with MRSA, and to have persistent bacteremia (P<.001 for all comparisons). S aureus is the leading cause of IE in many regions of the world. Characteristics of patients with S aureus IE vary significantly by region. Further studies are required to determine the causes of regional variation.
Publisher: Elsevier BV
Date: 05-2011
DOI: 10.1016/J.JINF.2011.03.002
Abstract: The aim of this study was to determine the humoral immune response to influenza A H1N1 2009 and cross reactivity against seasonal H1N1 and H3N2 strains. Baseline and convalescent sera from 88 subjects with confirmed H1N1 2009 were screened for serological responses by HAI assay. Protective antibody titres to H1N1 2009 were present in 87% post-infection, but varied with age, sex and pregnancy. Some cross reactivity with seasonal influenza strains was observed. Females and pregnant subjects had an attenuated immune response to H1N1 2009 in comparison to the rest of the study population. Antibodies from the serum of H1N1 2009 infected subjects cross reacted with seasonal H1N1 and H3N2 influenza viruses.
Publisher: MDPI AG
Date: 14-12-2012
DOI: 10.3390/V4123785
Publisher: Wiley
Date: 24-07-2020
DOI: 10.1111/TID.13392
Publisher: American Medical Association (AMA)
Date: 09-09-2013
DOI: 10.1001/JAMAINTERNMED.2013.8203
Abstract: There are limited prospective, controlled data evaluating survival in patients receiving early surgery vs medical therapy for prosthetic valve endocarditis (PVE). To determine the in-hospital and 1-year mortality in patients with PVE who undergo valve replacement during index hospitalization compared with patients who receive medical therapy alone, after controlling for survival and treatment selection bias. Participants were enrolled between June 2000 and December 2006 in the International Collaboration on Endocarditis-Prospective Cohort Study (ICE-PCS), a prospective, multinational, observational cohort of patients with infective endocarditis. Patients hospitalized with definite right- or left-sided PVE were included in the analysis. We evaluated the effect of treatment assignment on mortality, after adjusting for biases using a Cox proportional hazards model that included inverse probability of treatment weighting and surgery as a time-dependent covariate. The cohort was stratified by probability (propensity) for surgery, and outcomes were compared between the treatment groups within each stratum. Valve replacement during index hospitalization (early surgery) vs medical therapy. In-hospital and 1-year mortality. Of the 1025 patients with PVE, 490 patients (47.8%) underwent early surgery and 535 in iduals (52.2%) received medical therapy alone. Compared with medical therapy, early surgery was associated with lower in-hospital mortality in the unadjusted analysis and after controlling for treatment selection bias (in-hospital mortality: hazard ratio [HR], 0.44 [95% CI, 0.38-0.52] and lower 1-year mortality: HR, 0.57 [95% CI, 0.49-0.67]). The lower mortality associated with surgery did not persist after adjustment for survivor bias (in-hospital mortality: HR, 0.90 [95% CI, 0.76-1.07] and 1-year mortality: HR, 1.04 [95% CI, 0.89-1.23]). Subgroup analysis indicated a lower in-hospital mortality with early surgery in the highest surgical propensity quintile (21.2% vs 37.5% P = .03). At 1-year follow-up, the reduced mortality with surgery was observed in the fourth (24.8% vs 42.9% P = .007) and fifth (27.9% vs 50.0% P = .007) quintiles of surgical propensity. Prosthetic valve endocarditis remains associated with a high 1-year mortality rate. After adjustment for differences in clinical characteristics and survival bias, early valve replacement was not associated with lower mortality compared with medical therapy in the overall cohort. Further studies are needed to define the effect and timing of surgery in patients with PVE who have indications for surgery.
Publisher: Wiley
Date: 12-2000
DOI: 10.1046/J.1440-1754.2000.00565.X
Abstract: This paper provides specific guidelines on the management of tuberculosis infection and disease, covering general principles, recommended drug regimens and discuss the evidence to support these. It also covers use of corticosteroids, intermittent therapy, directly observed therapy and an approach to the management of a patient with drug-resistant tuberculosis.
Publisher: Elsevier BV
Date: 02-2017
DOI: 10.1016/J.JIAC.2017.09.010
Abstract: Despite vancomycin being in use for over half-a-century, it is still not dosed or monitored appropriately in many centers around the world. The objective of this study was to determine the effectiveness of a multifaceted intervention to implement a vancomycin dosing and monitoring guideline across multiple medical and surgical units over time. This was an observational before-and-after interventional cohort study. The pre-intervention period was August to December 2010-2011 and the post-intervention period was September to November 2012-2014. The implementation strategy comprised: face-to-face education, online continuing medical education, dissemination of pocket guideline and email reminder. Outcome measures included: appropriate prescribing of loading and maintenance doses, therapeutic drug monitoring, time to attain target range and nephrotoxicity. Post-implementation prescribing of loading doses increased (10.4%-43.6%, P=<0.001), guideline adherent first maintenance dose (44%-68.4% P = 0.04), correct dose adjustment from (53.1%-72.2%, P = 0.009). Beneficial effects pre and post-implementation were observed for adherent timing of initial concentration (43.2%-51.9%, P = 0.01), concentrations in target range (32.6%-44.1%, P = 0.001), time to target range (median 6-4 days, P=<0.001), potentially nephrotoxic concentrations (30.7%-20.9%, P=<0.001) and nephrotoxicity (10.4%-6.8%, P=<0.001). A multifaceted intervention to implement a vancomycin dosing and monitoring guideline significantly improved prescribing, monitoring, pharmacokinetic and safety outcomes for patients treated with vancomycin over an extended period. However, increased guideline adoption by clinicians is required to maximize and prolong the utility of this important agent.
Publisher: Wiley
Date: 05-07-2007
Publisher: Elsevier BV
Date: 04-2021
Publisher: Oxford University Press (OUP)
Date: 15-10-2004
DOI: 10.1086/424746
Abstract: A human immunodeficiency virus (HIV)-seronegative woman was admitted to the hospital with postpartum onset Cryptococcus neoformans var. gattii meningitis and markedly increased intracranial pressure. A poor initial response to antifungal therapy was followed, 2 months after hospital admission, by severe acute meningeal and cerebral inflammation and clearance of yeast cells from cerebrospinal fluid. This first reported case of paradoxical inflammatory reaction to C. neoformans illustrates important aspects of the host-pathogen interaction and highlights possible effects of immunomodulatory therapies.
Publisher: Elsevier BV
Date: 10-2016
Publisher: American Society for Microbiology
Date: 26-07-2018
DOI: 10.1128/MRA.00883-18
Abstract: Vibrio cholerae is the causative agent of cholera and, more rarely, nondiarrheal opportunistic infections. We report here a draft genome sequence of a non-O1/O139 V. cholerae strain isolated from the urine of a patient presenting with dysuria at a South Australian health care facility.
Publisher: Elsevier BV
Date: 02-2016
DOI: 10.1016/J.JSE.2015.08.002
Abstract: In vitro, Propionibacterium acnes (P acnes) is highly susceptible to commonly used antibiotics and antiseptics, yet in vivo, it still causes postsurgical infections of the shoulder. We hypothesized that the local environment within the pilosebaceous glands protects P acnes and that incision of the skin transects these glands, exposing viable P acnes to the wound. Fifty consecutive patients undergoing open shoulder surgery were prospectively studied. Prophylactic antibiotics were administered to all patients. Microbiologic swabs of the skin surface were taken before and after skin preparation with 70% alcoholic chlorhexidine. The skin was incised, and a further swab and dermal biopsy specimen were taken. P acnes was cultured in 21 of 50 prepreparation skin surface swabs (42%), 7 of 50 postpreparation skin surface swabs (14%), 26 of 50 dermal swabs (52%), and 20 of 50 dermal biopsy specimens (40%). There was a significantly higher incidence of P acnes growth from the skin surface (P = .009) and dermis (P = .01) of patients aged ≤50 years old and in the dermal biopsy specimens of patients undergoing revision surgery (P = .01) and a trend toward increased incidence of P acnes in men. P acnes growth from a prepreparation skin surface swab had a sensitivity of 69%, specificity of 88%, positive predictive value of 86%, and negative predictive value of 72% at predicting subsequent P acnes growth from the dermal swab or biopsy specimen. Viable P acnes persists within the skin dermis, despite standard antimicrobial precautions. These findings suggest that incising the skin is likely to lead to deep seeding of the surgical wound, which has implications for the pathogenesis and prevention of postsurgical shoulder infections.
Publisher: American Society for Microbiology
Date: 04-2015
DOI: 10.1128/AAC.04867-14
Abstract: Candida infective endocarditis is a rare disease with a high mortality rate. Our understanding of this infection is derived from case series, case reports, and small prospective cohorts. The purpose of this study was to evaluate the clinical features and use of different antifungal treatment regimens for Candida infective endocarditis. This prospective cohort study was based on 70 cases of Candida infective endocarditis from the International Collaboration on Endocarditis (ICE)-Prospective Cohort Study and ICE-Plus databases collected between 2000 and 2010. The majority of infections were acquired nosocomially (67%). Congestive heart failure (24%), prosthetic heart valve (46%), and previous infective endocarditis (26%) were common comorbidities. Overall mortality was high, with 36% mortality in the hospital and 59% at 1 year. On univariate analysis, older age, heart failure at baseline, persistent candidemia, nosocomial acquisition, heart failure as a complication, and intracardiac abscess were associated with higher mortality. Mortality was not affected by use of surgical therapy or choice of antifungal agent. A subgroup analysis was performed on 33 patients for whom specific antifungal therapy information was available. In this subgroup, 11 patients received hotericin B-based therapy and 14 received echinocandin-based therapy. Despite a higher percentage of older patients and nosocomial infection in the echinocandin group, mortality rates were similar between the two groups. In conclusion, Candida infective endocarditis is associated with a high mortality rate that was not impacted by choice of antifungal therapy or by adjunctive surgical intervention. Additionally, echinocandin therapy was as effective as hotericin B-based therapy in the small subgroup analysis.
Publisher: Oxford University Press (OUP)
Date: 1987
Abstract: The characterization of the reactive thiolester bond in the third component of human complement has led to the identification of homologous sites in a number of proteins. In addition to the participation of the C3 thiolester in the opsonic acylation of surface components of microorganisms, new evidence is emerging to implicate thiolester disruption by physiologic nucleophiles, such as ammonia, as a potent mediator of local inflammation in the lung, the kidney, and at endothelial surfaces. Manipulation of the thiolester bonds in these related proteins should permit us to understand, and ultimately to direct, the molecular mechanisms of inflammation.
Publisher: No publisher found
Date: 2002
Publisher: Public Library of Science (PLoS)
Date: 15-06-2012
Publisher: Elsevier BV
Date: 1988
DOI: 10.3109/00313028809085203
Abstract: Subclinical amniotic fluid infection and subsequent preterm labour may occur with intact membranes. We report two cases of subclinical amniotic fluid infection with intact membranes presenting in preterm labour. Capnocytophaga species, fastidious Gram-negative bacilli normally found in oral flora, were isolated in pure culture from amniotic fluid obtained by transabdominal amniocentesis. The distinctive microbiological features and spectrum of infections associated with Capnocytophaga species, and the importance of recognition of subclinical amniotic fluid infection as a cause of preterm labour, are discussed.
Publisher: Oxford University Press (OUP)
Date: 15-11-2009
DOI: 10.1086/644769
Abstract: There are 2 once-daily, fixed-dose-combination, dual-nucleoside analogue tablets: tenofovir 300 mg-emtricitabine 200 mg (TDF-FTC) and abacavir 600 mg-lamivudine 300 mg (ABC-3TC). Which fixed-dose-combination tablet is more effective and safe is uncertain. We compared TDF-FTC and ABC-3TC in a randomized, open-label, 96-week trial in which either fixed-dose-combination was substituted for current nucleoside treatments in human leukocyte antigen-B*5701-negative adults with human immunodeficiency virus loads 400 copies/mL, by intention-to-treat). Secondary end points included death, AIDS, adverse events, serious non-AIDS events, metabolic parameters, and body composition. We used exact statistics for differences in proportions, T tests to compare means, and Cox regression for hazard ratios. Of 441 patients who were screened, 357 were treated 98% were men, the mean age was 45 years, 30% were receiving TDF, 20% were receiving ABC, and 24% were receiving a protease inhibitor. Virological failure was uncommon (5.6% for ABC-3TC and 3.9% for TDF-FTC difference, 1.7% 95% confidence interval [CI], -2.8% to 6.1% P = .62). No participant developed AIDS, whereas 18 (5%) participants developed a serious non-AIDS event (rate, 2.79 events per 100 person-years 95% CI, 1.76-4.43), of which 4 were fatal. TDF-FTC was associated with significantly fewer serious non-AIDS events than ABC-3TC (1.2 vs 4.8 events per 100 patient-years hazard ratio [HR], 0.24 95% CI, 0.08-0.73 P = .012), influenced mostly by a lower rate of cardiovascular events (0.3 vs 2.2 events per 100 patient-years HR, 0.12 95% CI, 0.02-0.98 P = .048). TDF-FTC resulted in significantly lower bone mineral density (mean difference in hip t score, 0.16 95% CI, 0.08-0.23 P < .001) but not in more fractures. In this population, TDF-FTC and ABC-3TC had similar virological efficacy, but ABC-3TC was associated with more serious non-AIDS events, particularly cardiovascular events. Clinical trials registration. NCT00192634 .
Publisher: Cambridge University Press (CUP)
Date: 25-01-2006
DOI: 10.1017/S0950268805005777
Abstract: In order to identify subtyping methods able to contribute to the surveillance or investigation of Australian C ylobacter infection, six genotypic and three phenotypic subtyping methods were evaluated on a collection of 84 clinical isolates collected over a 30-month period from one region in Australia. The aim was to compare the logistics of various subtyping methods and examine their ability to assist in finding outbreaks or common sources of sporadic infection. The genotypic subtyping methods used were sequencing of the short variable region of the flaA gene, two methods using restriction fragment length polymorphism (RFLP) of the flaA gene using either Dde I or Eco RI with Pst I, automated ribotyping, pulsed field gel electrophoresis and multilocus sequence typing. The phenotypic methods employed included Laboratory of Enteric Pathogens serotyping, Lior biotyping and antibiotic resistotyping. The level of agreement between subtyping results was determined. Phenotypic methods showed little agreement whereas genotypic typing methods showed a high level of agreement. Using the premise that five of the six genotypic typing methods were in agreement 15 genotypic groupings were identified. Sequencing of the short variable region of the flaA gene, RFLP of the flaA gene or automated ribotyping in conjunction with multilocus sequence typing best identified genotypic groupings. An alternative combination of RFLP of the flaA gene followed by ribotyping was equally satisfactory. RFLP of the flaA gene appeared to be suitable as a preliminary typing method based on ease of operation, equipment availability and cost.
Publisher: Informa UK Limited
Date: 17-07-2019
Publisher: Oxford University Press (OUP)
Date: 09-2005
DOI: 10.1086/431675
Abstract: Two phase 3, double-blind studies in hospitalized adults with complicated skin and skin-structure infections (cSSSI) determined the safety and efficacy of tigecycline versus that of vancomycin-aztreonam. Patients received tigecycline (100 mg, followed by 50 mg intravenously twice daily) or vancomycin (1 g intravenously twice daily) plus aztreonam (2 g intravenously twice daily) for up to 14 days. Populations were as follows: 1116 patients (566 treated with tigecycline, and 550 treated with vancomycin-aztreonam) constituted the modified intent-to-treat (mITT) population, 1057 patients (538 treated with tigecycline, and 519 treated with vancomycin-aztreonam) constituted the clinical mITT (c-mITT) population, and 833 patients (422 treated with tigecycline, and 411 treated with vancomycin-aztreonam) constituted the clinically evaluable population. Clinical responses to tigecycline and vancomycin-aztreonam at test-of-cure were similar: c-mITT, 79.7% (95% confidence interval [CI], 76.1%-83.1%) versus 81.9% (95% CI, 78.3%-85.1%) (P = .4183) and clinically evaluable, 86.5% (95% CI, 82.9%-89.6%) versus 88.6% (95% CI, 85.1%-91.5%) (P = .4233). Adverse events were similar, with increased nausea and vomiting in the tigecycline group and increased rash and elevated hepatic aminotransferase levels in the vancomycin-aztreonam group. Tigecycline monotherapy is as safe and efficacious as the vancomycin-aztreonam combination in treating patients with cSSSI.
Publisher: Wiley
Date: 07-06-2010
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 02-2007
Publisher: Elsevier BV
Date: 2015
DOI: 10.1016/J.IJCARD.2014.10.125
Abstract: Nearly half of patients require cardiac surgery during the acute phase of infective endocarditis (IE). We describe the characteristics of patients according to the type of valve replacement (mechanical or biological), and examine whether the type of prosthesis was associated with in-hospital and 1-year mortality. Among 5591 patients included in the International Collaboration on Endocarditis Prospective Cohort Study, 1467 patients with definite IE were operated on during the active phase and had a biological (37%) or mechanical (63%) valve replacement. Patients who received bioprostheses were older (62 vs 54years), more often had a history of cancer (9% vs 6%), and had moderate or severe renal disease (9% vs 4%) proportion of health care-associated IE was higher (26% vs 17%) intracardiac abscesses were more frequent (30% vs 23%). In-hospital and 1-year death rates were higher in the bioprosthesis group, 20.5% vs 14.0% (p=0.0009) and 25.3% vs 16.6% (p<.0001), respectively. In multivariable analysis, mechanical prostheses were less commonly implanted in older patients (odds ratio: 0.64 for every 10years), and in patients with a history of cancer (0.72), but were more commonly implanted in mitral position (1.60). Bioprosthesis was independently associated with 1-year mortality (hazard ratio: 1.298). Patients with IE who receive a biological valve replacement have significant differences in clinical characteristics compared to patients who receive a mechanical prosthesis. Biological valve replacement is independently associated with a higher in-hospital and 1-year mortality, a result which is possibly related to patient characteristics rather than valve dysfunction.
Publisher: Public Library of Science (PLoS)
Date: 21-10-2015
Publisher: American Society for Microbiology
Date: 09-2008
DOI: 10.1128/JCM.00920-08
Abstract: Identification of viridans group streptococci (VGS) to the species level is difficult because VGS exchange genetic material. We performed multilocus DNA target sequencing to assess phylogenetic concordance of VGS for a well-defined clinical syndrome. The hierarchy of sequence data was often discordant, underscoring the importance of establishing biological relevance for finer phylogenetic distinctions.
Publisher: Oxford University Press (OUP)
Date: 30-05-2020
DOI: 10.1093/CID/CIAA673
Abstract: SARS-CoV-2 is a novel coronavirus and causative pathogen to the pandemic illness COVID-19. Although RNA has been detected in various clinical s les, no reports to date have documented SARS-CoV-2 in human milk. This case report describes an actively breastfeeding patient with COVID-19 infection with detectable viral RNA in human milk.
Publisher: Springer Science and Business Media LLC
Date: 22-05-2021
DOI: 10.1186/S12885-021-08296-4
Abstract: The gut microbiota influences many aspects of host physiology, including immune regulation, and is predictive of outcomes in cancer patients. However, whether conventional myelosuppressive chemotherapy affects the gut microbiota in humans with non-haematological malignancy, independent of antibiotic exposure, is unknown. Faecal s les from 19 participants with non-haematological malignancy, who were receiving conventional chemotherapy regimens but not antibiotics, were examined prior to chemotherapy, 7–12 days after chemotherapy, and at the end of the first cycle of treatment. Gut microbiota ersity and composition was determined by 16S rRNA gene licon sequencing. Compared to pre-chemotherapy s les, s les collected 7–12 days following chemotherapy exhibited increased richness (mean 120 observed species ± SD 38 vs 134 ± 40 p = 0.007) and ersity (Shannon ersity: mean 6.4 ± 0.43 vs 6.6 ± 0.41 p = 0.02). Composition was significantly altered, with a significant decrease in the relative abundance of gram-positive bacteria in the phylum Firmicutes (pre-chemotherapy median relative abundance [IQR] 0.78 [0.11] vs 0.75 [0.11] p = 0.003), and an increase in the relative abundance of gram-negative bacteria (Bacteroidetes: median [IQR] 0.16 [0.13] vs 0.21 [0.13] p = 0.01 and Proteobacteria: 0.015 [0.018] vs 0.03 [0.03] p = 0.02). Differences in microbiota characteristics from baseline were no longer significant at the end of the chemotherapy cycle. Conventional chemotherapy results in significant changes in gut microbiota characteristics during the period of predicted myelosuppression post-chemotherapy. Further study is indicated to link microbiome changes during chemotherapy to clinical outcomes.
Publisher: Wiley
Date: 09-07-2008
DOI: 10.1111/J.1365-3024.2008.01040.X
Abstract: Survival of parasitic helminths within a host requires immune evasion and excretory/secretory (ES) proteins may contribute to this process. Eosinophils are important effector cells in immunity of mice to the nematode Nippostrongylus brasiliensis and eosinophilic interleukin-5 transgenic (IL-5 Tg) mice are highly resistant to the earliest stages of primary infections. In contrast, Toxocara canis is largely resistant to eosinophils, with viable larvae encysted in tissues often surrounded by these and other leucocytes. The aim of this study was to investigate whether T. canis ES (TES) proteins inhibit eosinophil-dependent resistance to N. brasiliensis. Mouse serum pre-treated with TES had reduced capacity to mediate the adherence of leucocytes to N. brasiliensis infective-stage larvae (L3) and this correlated with reduced complement C3 deposition on the parasite. TES did not inhibit eosinophil survival or eotaxin-dependent eosinophil migration in vitro. Cellular inflammation and eosinophil degranulation in the skin in response to injection of L3 was also not impaired by TES. However, when TES was included with L3 in an inoculum given to IL-5 Tg mice, a greatly increased number of parasites migrated to the lung. This suggests that the early eosinophil-dependent resistance in these mice was suppressed, by mechanisms yet to be determined.
Publisher: American Society for Microbiology
Date: 25-04-2018
Abstract: Recent demonstrations that long-term macrolide therapy can prevent exacerbations in chronic airways diseases have led to a dramatic increase in their use. However, little is known about the wider, potentially adverse impacts of these treatments. Substantial disruption of the upper airway commensal microbiota might reduce its contribution to host defense and local immune regulation, while increases in macrolide resistance carriage would represent a serious public health concern. Using s les from a randomized controlled trial, we show that low-dose erythromycin given over 48 weeks influences the composition of the oropharyngeal commensal microbiota. We report that macrolide therapy is associated with significant changes in the relative abundances of members of the Actinomyces genus and with significant increases in the carriage of transmissible macrolide resistance. Determining the clinical significance of these changes, relative to treatment benefit, now represents a research priority.
Publisher: MDPI AG
Date: 18-05-2020
DOI: 10.3390/V12050559
Abstract: The efficacy of phages in multispecies infections has been poorly examined. The in vitro lytic efficacies of phage cocktails AB-SA01, AB-PA01, which target Staphylococcus aureus and Pseudomonas aeruginosa, respectively, and their combination against their hosts were evaluated in S. aureus and P. aeruginosa mixed-species planktonic and biofilm cultures. Green fluorescent protein (GFP)-labelled P. aeruginosa PAO1 and mCherry-labelled S. aureus KUB7 laboratory strains and clinical isolates were used as target bacteria. During real-time monitoring using fluorescence spectrophotometry, the density of mCherry S. aureus KUB7 and GFP P. aeruginosa PAO1 significantly decreased when treated by their respective phage cocktail, a mixture of phage cocktails, and gentamicin. The decrease in bacterial density measured by relative fluorescence strongly associated with the decline in bacterial cell counts. This microplate-based mixed-species culture treatment monitoring through spectrophotometry combine reproducibility, rapidity, and ease of management. It is amenable to high-throughput screening for phage cocktail efficacy evaluation. Each phage cocktail, the combination of the two phage cocktails, and tetracycline produced significant biofilm biomass reduction in mixed-species biofilms. This study result shows that these phage cocktails lyse their hosts in the presence of non-susceptible bacteria. These data support the use of phage cocktails therapy in infections with multiple bacterial species.
Publisher: Wiley
Date: 11-2010
DOI: 10.5694/J.1326-5377.2010.TB04042.X
Abstract: Liver abscess due to Klebsiella pneumoniae infection has been widely reported in Asia, but rarely reported in Australia until now. We describe four previously well Asian-born patients who presented across Australia with community-acquired K. pneumoniae liver abscesses. With prompt recognition, appropriate antibiotics and early drainage, outcome is significantly improved, although vigilance for metastatic complications is essential.
Publisher: Springer Science and Business Media LLC
Date: 27-10-2017
Publisher: Wiley
Date: 06-1983
DOI: 10.1111/J.1445-5994.1983.TB04657.X
Abstract: A patient with severe seropositive rheumatoid arthritis and hepatic cirrhosis developed septic arthritis of his knees. Plesiomonas shigelloides was isolated from joint fluid, blood, and also from the gut. The patient's joint symptoms responded to treatment with oral trimethoprim-sulphamethoxazole, but he died of uncontrolled gastrointestinal bleeding five days later.
Publisher: Oxford University Press (OUP)
Date: 15-03-2015
DOI: 10.1093/JAC/DKV069
Publisher: Elsevier BV
Date: 08-2012
Publisher: Elsevier BV
Date: 04-2006
DOI: 10.1016/J.MOLIMM.2005.09.012
Abstract: Complement factor H (fH) plays a pivotal role in regulating the alternative pathway, allowing complement activation to proceed on foreign surfaces, whilst protecting surrounding host cell surfaces from complement-mediated damage. Host cell recognition is mediated by polyanions such as sialic acid and glycosaminoglycans (GAGs), which promote a high affinity interaction between fH and C3b deposited on host cell surfaces. Factor H is composed of 20 short consensus repeats (SCRs) two heparin-binding sites have been identified within SCR 7 and SCR 20 and a third site is thought to exist within or near SCR 13. Using an extensive series of recombinant fH fragments and heparin affinity chromatography, we have localized the third heparin-binding domain to SCR 9. A recombinant fH fragment containing both SCR 7 and SCR 9 exhibited higher affinity for heparin than SCR 7 alone, suggesting that the in idual heparin-binding sites interact simultaneously with heparin to create a higher avidity interaction. Recombinant fragments containing SCR 9 bound to endothelial cells, indicating that this domain is capable of interacting with polyanions within a physiologically relevant environment. In addition, the three heparin-binding sites exhibited differences in their specificity for certain GAGs, suggesting that the in idual binding domains may possess separate GAG recognition functions.
Publisher: Elsevier BV
Date: 06-2014
Publisher: Future Medicine Ltd
Date: 02-2021
Abstract: The ability of influenza A virus to evolve, coupled with increasing antimicrobial resistance, could trigger an influenza pandemic with great morbidity and mortality. Much of the 1918 influenza pandemic mortality was likely due to bacterial coinfection, including Staphylococcus aureus pneumonia. S. aureus resists many antibiotics. The lack of new antibiotics suggests alternative antimicrobials, such as bacteriophages, are needed. Potential delivery routes for bacteriophage therapy (BT) include inhalation and intravenous injection. BT has recently been used successfully in compassionate access pulmonary infection cases. Phage lysins, enzymes that hydrolyze bacterial cell walls and which are bactericidal, are efficacious in animal pneumonia models. Clinical trials will be needed to determine whether BT can ameliorate disease in influenza and S. aureus coinfection.
Publisher: Wiley
Date: 06-04-2015
Abstract: To analyse the association between time from triage to administration of initial antibiotics and mortality in all patients presenting with sepsis to a tertiary hospital ED. A retrospective review of patients presenting to the ED with sepsis from January to December 2012 was conducted at Flinders Medical Centre, South Australia. Outcome measures were: time elapsed from triage to administration of initial antibiotic therapy and in-hospital mortality. A total of 220 patients presented with sepsis, comprising 102 cases of uncomplicated sepsis and 118 severe sepsis. The median time to antibiotic administration was 3.5 h (interquartile range [IQR] 1.7-6.6) and in-hospital mortality was 28.6% (95% CI 22.6-34.6%). There was no association observed between delays to antibiotics and mortality in the total patient population. When stratified by presenting severity, patients with severe sepsis demonstrated a trend towards increased mortality when delays to antibiotics exceeded 6 h from triage (HR = 2.25, 95% CI 0.91-5.59, P = 0.08) in comparison with <1 h. Significant delays to antibiotic administration occurred when initial agents were charted as a 'regular medicine' (9.4 h, IQR 5.1-16.6) in comparison with a 'once only order' (3.4 h, IQR 1.7-6.7), P < 0.001. Early administration of antibiotics specifically in patients with severe sepsis might be beneficial. Further studies within the ED are warranted to establish the effect of delayed antibiotics in a generalised sepsis cohort.
Publisher: Elsevier BV
Date: 05-2009
DOI: 10.1016/J.JINF.2009.03.006
Abstract: To assess the influence of acetyl-salicylic acid (ASA) on clinical outcomes in Staphylococcus aureus infective endocarditis (SA-IE). The International Collaboration on Endocarditis - Prospective Cohort Study database was used in this observational study. Multivariable analysis of the SA-IE cohort compared outcomes in patients with and without ASA use, adjusting for other predictive variables, including: age, diabetes, hemodialysis, cancer, pacemaker, intracardiac defibrillator and methicillin resistance. Data were analysed from 670 patients, 132 of whom were taking ASA at the time of SA-IE diagnosis. On multivariable analysis, ASA usage was associated with a significantly decreased overall rate of acute valve replacement surgery (OR 0.58 [95% CI 0.35-0.97] p<0.04), particularly where valvular regurgitation, congestive heart failure or periannular abscess was the indication for such surgery (OR 0.46 [0.25-0.86] p<0.02). There was no reduction in the overall rates of clinically apparent embolism with prior ASA usage, and no increase in hemorrhagic strokes in ASA-treated patients. In this multinational prospective observational cohort, recent ASA usage was associated with a reduced occurrence of acute valve replacement surgery in SA-IE patients. Future investigations should focus on ASA's prophylactic and therapeutic use in high-risk and newly diagnosed patients with SA bacteremia and SA-IE, respectively.
Publisher: Korea Health Personnel Licensing Examination Institute
Date: 07-06-2017
Abstract: Purpose: We aimed to assess the preparedness of junior doctors to use vancomycin, and to determine whether attending an educational session and being provided pocket guidelines were associated with self-reported confidence and objective knowledge. Methods: This was a 2-component cross-sectional study. A 60-minute educational session was implemented and pocket guidelines were provided. Preparedness was evaluated by a self-reported confidence survey in the early and late stages of each training year, and by continuing medical education (CME) knowledge scores. Results: Self-confidence was higher among those later in the training year (n=75) than in those earlier (n=120) in the year for all questions. In the late group, vancomycin education was associated with higher self-confidence regarding the frequency of therapeutic drug monitoring (P=0.02) and dose amendment (P=0.05) however, the confidence for initial monitoring was lower (P .05). Those with pocket guidelines were more confident treating patients with vancomycin (P .001), choosing initial (P=0.01) and maintenance doses (P .001), and knowing the monitoring frequency (P=0.03). The 85 respondents who completed the knowledge assessment scored a mean±standard deviation of 8.55±1.55 on 10 questions, and the interventions had no significant effect. Conclusion: Attending an educational session and possessing pocket guidelines were associated with preparedness, as measured by higher self-reported confidence using vancomycin. High knowledge scores were attained following CME however attending an educational session or possessing pocket guidelines did not significantly increase the knowledge scores. Our findings support providing educational sessions and pocket guidelines to increase self-confidence in prescribing vancomycin, yet also highlight the importance of evaluating content, format, and delivery when seeking to improve preparedness to use vancomycin through education.
Publisher: Springer Science and Business Media LLC
Date: 2009
DOI: 10.1186/CC7964
Publisher: Mary Ann Liebert Inc
Date: 02-2013
Abstract: Monitoring HIV subtype distribution is important for understanding transmission dynamics. Subtype B has historically been dominant in Australia, but in recent years new clades have appeared. Since 2000, clade data have been collected as part of HIV surveillance in South Australia. The aim of this study was to evaluate the prevalence of and risk factors for HIV-1 non-B subtypes. The study population was composed of newly diagnosed, genotyped HIV subjects in South Australia between 2000 and 2010. We analyzed time trends and subtype patterns in this cohort notification data were aggregated into three time periods (2000-2003, 2004-2006, and 2007-2010). Main outcome measures were number of new non-B infections by year, exposure route, and other demographic characteristics. There were 513 new HIV diagnoses 425 had information on subtype. The majority (262/425) were in men who have sex with men (MSM), predominantly subtype B and acquired in Australia. Infections acquired in Australia decreased from 77% (2000-2003) to 64% (2007-2010) (p=0.007) and correspondingly the proportion of subtype B declined from 85% to 68% (p=0.002). Non-B infections were predominantly (83%) heterosexual contacts, mostly acquired overseas (74%). The majority (68%) of non-B patients were born outside of Australia. There was a nonsignificant increase from 1.6% to 4.2% in the proportion of locally transmitted non-B cases (p=0.3). Three non-B subtypes and two circulating recombinant forms (CRFs) were identified: CRF_AE (n=41), C (n=36), CRF_AG (n=13), A (n=9), and D (n=2). There has been a substantial increase over the past decade in diagnosed non-B infections, primarily through cases acquired overseas.
Publisher: American Society for Microbiology
Date: 05-2011
DOI: 10.1128/AEM.02764-10
Abstract: Multilocus sequence typing of 56 Salmonella enterica subsp. enterica strains isolated from Australian wildlife hosts was performed. The results of population assignment algorithms revealed that the 56 strains could be sub ided into two distinct clades. Strains belonging to the two clades were further distinguished phenotypically, genotypically, and with respect to host distribution.
Publisher: American Society for Microbiology
Date: 04-2006
DOI: 10.1128/IAI.74.4.2007-2014.2006
Abstract: Borrelia hermsii , the primary etiological agent of tick-borne relapsing fever in North America, binds the complement regulatory protein factor H (FH) as a means of evading opsonophagocytosis and the alternative complement pathway. The ability of FH-binding protein A (FhbA) to bind FH-like protein 1 (FHL-1) has not been assessed previously. In this study, using a whole-cell absorption assay, we demonstrated that B. hermsii absorbs both FH and FHL-1 from human serum. Consistent with this, affinity ligand binding immunoblot analyses revealed that FH constructs spanning short consensus repeats 1 to 7 and 16 to 20 bind to FhbA. To investigate the molecular basis of the interaction of FhbA with FH/FHL-1, recombinant FhbA truncated proteins were generated and tested for FH/FHL-1 binding. Binding required determinants located in both the N- and C-terminal domains of FhbA, suggesting that long-range intramolecular interactions are involved in the formation and presentation of the FH/FHL-1-binding pocket. To identify specific FhbA residues involved in binding, random mutagenesis was performed. These analyses identified a loop region of FhbA that may serve as a contact point for FH/FHL-1. The data presented here expand our understanding of the pathogenic mechanisms of the relapsing fever spirochetes and of the molecular nature of the interaction between FH/FHL-1 and FhbA.
Publisher: The Journal of Rheumatology
Date: 12-2011
Abstract: In acute monoarthritis, the presence of crystals in synovial fluid may lead to a diagnosis of crystal arthritis (CA) before septic arthritis (SA) can be excluded by culture. We aimed to identify the frequency of coexistence of CA with SA and to compare these with regard to synovial fluid microscopy, C-reactive protein (CRP), and blood culture. We examined 1612 synovial aspirates from 2004 to 2009 retrospectively. Of these, 104 patients with clinically significant SA were identified. These were compared to 295 patients with isolated CA. Five percent of joints with CA had concomitant infection. A high synovial white blood cell (WBC) count and elevated CRP ( 100 mg/l) were predictive of concomitant SA with a sensitivity of 86.4%, specificity of 48.3% and 54.6%, and negative predictive values of 98.5% and 98.7%, respectively. In patients with SA who had a blood culture, 42.5% were positive with a matching organism. SA of the shoulder had a 90% rate of bacteremia. Crystals alone in synovial fluid from acute monoarthritis cannot exclude SA, as CA and SA frequently coexist. High WBC counts and elevated CRP are common to both SA and CA. Blood cultures should be collected and septic arthritis considered, even when crystals are present, particularly if the shoulder is affected. The exception is when Gram stain is negative and the CRP is 100 mg/l and joint WBC count is 10,000/μl. In these circumstances it is very unlikely that there will be concomitant SA.
Publisher: Wiley
Date: 04-2003
Abstract: The complement inhibitor factor H (fH) interacts via its seventh short consensus repeat (SCR) domain with multiple ligands including heparin, streptococcal M protein and C-reactive protein (CRP). The aim of this study was to localize the residues in SCR 7 required for these interactions. We initially built a homology model of fH SCR 6-7 using the averaged NMR structures of fH SCR 15-16 and vaccinia control protein SCR 3-4 as templates. Electrostatic potentials of the model's surface demonstrated a co-localization of three clusters of positively charged residues on SCR 7, labeled site A (R369 and K370), site B (R386 and K387) and site C (K392). These residues, localized to the linker region preceding SCR 7 and to the end of a "hypervariable loop" in SCR 7, were systematically replaced with uncharged alanine residues in an fH construct containing SCR 1-7. The resulting proteins were expressed in the methylotrophic yeast, Pichia pastoris. By ELISA analysis we demonstrated: first, that substituting site A inhibited heparin and CRP binding secondly, that substituting site B inhibited binding to heparin, CRP and M protein and thirdly, that substituting site C clearly inhibited only heparin binding.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 06-2019
DOI: 10.1097/ACM.0000000000002618
Abstract: An evidence-based approach to assessment is critical for ensuring the development of clinical reasoning (CR) competence. The wide array of CR assessment methods creates challenges for selecting assessments fit for the purpose thus, a synthesis of the current evidence is needed to guide practice. A scoping review was performed to explore the existing menu of CR assessments. Multiple databases were searched from their inception to 2016 following PRISMA guidelines. Articles of all study design types were included if they studied a CR assessment method. The articles were sorted by assessment methods and reviewed by pairs of authors. Extracted data were used to construct descriptive appendixes, summarizing each method, including common stimuli, response formats, scoring, typical uses, validity considerations, feasibility issues, advantages, and disadvantages. A total of 377 articles were included in the final synthesis. The articles broadly fell into three categories: non-workplace-based assessments (e.g., multiple-choice questions, extended matching questions, key feature examinations, script concordance tests) assessments in simulated clinical environments (objective structured clinical examinations and technology-enhanced simulation) and workplace-based assessments (e.g., direct observations, global assessments, oral case presentations, written notes). Validity considerations, feasibility issues, advantages, and disadvantages differed by method. There are numerous assessment methods that align with different components of the complex construct of CR. Ensuring competency requires the development of programs of assessment that address all components of CR. Such programs are ideally constructed of complementary assessment methods to account for each method’s validity and feasibility issues, advantages, and disadvantages.
Publisher: Elsevier BV
Date: 06-2003
Abstract: Pulmonary infection by Nocardia is an uncommon opportunistic infection in humans. Thirty-five patients with pulmonary nocardiosis were identified in two tertiary referral hospitals. A retrospective review of the patient characteristics, clinical and laboratory features including antimicrobial susceptibility at diagnosis was carried out. Radiological features derived from chest radiographs and CT scans were also documented. In our population, the predominant risk factors were immuno-compromised state, corticosteroid therapy, and underlying pulmonary pathology. The presenting features were similar to those previously described but disseminated infection was not common. The radiological changes were erse and non-specific. Nocardia asteroides was the commonest species. Most Nocardia isolates were susceptible to imipenem, ceftriaxone, amikacin, and cotrimoxazole. Co-existing microbial agents are common and reflect the underlying complex disorders.
Publisher: BMJ
Date: 08-08-2017
DOI: 10.1136/THORAXJNL-2016-208775
Abstract: To assess whether Induced sputum s les were obtained from 112 adult patients with high-resolution CT scan-proven bronchiectasis and at least two exacerbations in the previous year, as part of an unrelated randomised control trial. Presence of null Patients were grouped by ACTRN12609000578202 (anzctr.org.au) Pre-results.
Publisher: Oxford University Press (OUP)
Date: 2008
DOI: 10.1086/523723
Publisher: Elsevier BV
Date: 04-2017
Publisher: Wiley
Date: 07-2012
DOI: 10.1111/J.1445-5994.2012.02798.X
Abstract: Hepatitis C treatment is successful in 40-80% of patients in drug sponsored registration trials. However, few studies have examined treatment outcomes in non-trial, routine clinical practice settings. The aim of this study was to investigate the treatment outcomes and predictors of a sustained virological response in a routine clinical setting. Data were collected retrospectively on patients treated for hepatitis C between January 2004 and March 2010 in a tertiary hospital setting. Demographics, treatment outcomes and potential predictors of outcome (viral genotype, viral load, virological response, platelet count, alanine transaminase level, glucose, ferritin, weight, fibrosis and cirrhosis, compliance, dose reductions, adverse events, psychiatric and alcohol history) were recorded. Univariate and multiple logistic regressions were performed. A total of 405 patients was treated during the study period. On an intention to treat basis, sustained virological response rates were 55%, 82% and 72% in genotypes 1, 2 and 3 respectively. Predictors of response were gender, age, genotype, weight, fibrosis, cirrhosis, platelet count and alanine transaminase on univariate analysis. Age, genotype, cirrhosis and platelet count were independently associated with sustained virological response on multiple logistic regression. In our cohort, treatment outcomes for genotype 1 and 2 were similar to results from clinical trials but results for genotype 3 were inferior. Clinicians should not assume that results from registration trials are transferable to their own clinical practice. This has particular relevance for the new era of triple therapy regimens containing direct antivirals.
Publisher: American Society for Microbiology
Date: 11-2005
DOI: 10.1128/IAI.73.11.7126-7132.2005
Abstract: Treponema denticola is an important contributor to periodontal disease. In this study we investigated the ability of T. denticola to bind the complement regulatory proteins factor H and factor H-like protein 1 (FHL-1). The binding of these proteins has been demonstrated to facilitate evasion of the alternative complement cascade and/or to play a role in adherence and invasion. Here we demonstrate that T. denticola specifically binds FHL-1 via a 14-kDa, surface-exposed protein that we designated FhbB. Consistent with its FHL-1 binding specificity, FhbB binds only to factor H recombinant fragments spanning short consensus repeats (SCRs) 1 to 7 (H7 construct) and not to SCR constructs spanning SCRs 8 to 15 and 16 to 20. Binding of H7 to FhbB was inhibited by heparin. The specific involvement of SCR 7 in the interaction was demonstrated using an H7 mutant (H7AB) in which specific charged residues in SCR 7 were replaced by alanine. This construct lost FhbB binding ability. Analyses of the ability of FHL-1 bound to the surface of T. denticola to serve as a cofactor for factor I-mediated cleavage of C3b revealed that C3b is cleaved in an FHL-1/factor I-independent manner, perhaps by an unidentified protease. Based on the data presented here, we hypothesize that the primary function of FHL-1 binding by T. denticola might be to facilitate adherence to FHL-1 present on anchorage-dependent cells and in the extracellular matrix.
Publisher: Elsevier BV
Date: 08-2012
Publisher: American Medical Association (AMA)
Date: 28-03-2007
Abstract: Prosthetic valve endocarditis (PVE) is associated with significant mortality and morbidity. The contemporary clinical profile and outcome of PVE are not well defined. To describe the prevalence, clinical characteristics, and outcome of PVE, with attention to health care-associated infection, and to determine prognostic factors associated with in-hospital mortality. Prospective, observational cohort study conducted at 61 medical centers in 28 countries, including 556 patients with definite PVE as defined by Duke University diagnostic criteria who were enrolled in the International Collaboration on Endocarditis-Prospective Cohort Study from June 2000 to August 2005. In-hospital mortality. Definite PVE was present in 556 (20.1%) of 2670 patients with infective endocarditis. Staphylococcus aureus was the most common causative organism (128 patients [23.0%]), followed by coagulase-negative staphylococci (94 patients [16.9%]). Health care-associated PVE was present in 203 (36.5%) of the overall cohort. Seventy-one percent of health care-associated PVE occurred within the first year of valve implantation, and the majority of cases were diagnosed after the early (60-day) period. Surgery was performed in 272 (48.9%) patients during the index hospitalization. In-hospital death occurred in 127 (22.8%) patients and was predicted by older age, health care-associated infection (62/203 [30.5%] adjusted odds ratio [OR], 1.62 95% confidence interval [CI], 1.08-2.44 P = .02), S aureus infection (44/128 [34.4%] adjusted OR, 1.73 95% CI, 1.01-2.95 P = .05), and complications of PVE, including heart failure (60/183 [32.8%] adjusted OR, 2.33 95% CI, 1.62-3.34 P<.001), stroke (34/101 [33.7%] adjusted OR, 2.25 95% CI, 1.25-4.03 P = .007), intracardiac abscess (47/144 [32.6%] adjusted OR, 1.86 95% CI, 1.10-3.15 P = .02), and persistent bacteremia (27/49 [55.1%] adjusted OR, 4.29 95% CI, 1.99-9.22 P<.001). Prosthetic valve endocarditis accounts for a high percentage of all cases of infective endocarditis in many regions of the world. Staphylococcus aureus is now the leading cause of PVE. Health care-associated infection significantly influences the clinical characteristics and outcome of PVE. Complications of PVE strongly predict in-hospital mortality, which remains high despite prompt diagnosis and the frequent use of surgical intervention.
Publisher: Informa UK Limited
Date: 2007
DOI: 10.1080/00365540701367793
Abstract: Propionibacterium species are occasionally associated with serious systemic infections such as infective endocarditis. In this study, we examined the clinical features, complications and outcome of 15 patients with Propionibacterium endocarditis using the International Collaboration on Endocarditis Merged Database (ICE-MD) and Prospective Cohort Study (ICE-PCS), and compared the results to 28 cases previously reported in the literature. In the ICE database, 11 of 15 patients were male with a mean age of 52 y. Prosthetic valve endocarditis occurred in 13 of 15 cases and 3 patients had a history of congenital heart disease. Clinical findings included valvular vegetations (9 patients), cardiac abscesses (3 patients), congestive heart failure (2 patients), and central nervous system emboli (2 patients). Most patients were treated with beta-lactam antibiotics alone or in combination for 4 to 6 weeks. 10 of the 15 patients underwent valve replacement surgery and 2 patients died. Similar findings were noted on review of the literature. The results of this paper suggest that risk factors for Propionibacterium endocarditis include male gender, presence of prosthetic valves and congenital heart disease. The clinical course is characterized by complications such as valvular dehiscence, cardiac abscesses and congestive heart failure. Treatment may require a combination of medical and surgical therapy.
Publisher: Springer Science and Business Media LLC
Date: 06-12-2005
Publisher: Wiley
Date: 10-2006
Publisher: Wiley
Date: 10-07-2018
DOI: 10.1111/JVH.12943
Abstract: In March 2016, the Australian government offered unrestricted access to direct-acting antiviral (DAA) therapy for chronic hepatitis C virus (HCV) to the entire population. This included prescription by any medical practitioner in consultation with specialists until sufficient experience was attained. We sought to determine the outcomes and experience over the first twelve months for the entire state of South Australia. We performed a prospective, observational study following outcomes of all treatments associated with the state's four main tertiary centres. A total of 1909 subjects initiating DAA therapy were included, representing an estimated 90% of all treatments in the state. Overall, SVR12 was 80.4% in all subjects intended for treatment and 95.7% in those completing treatment and follow-up. 14.2% were lost to follow-up (LTFU) and did not complete SVR12 testing. LTFU was independently associated with community treatment via remote consultation (OR 1.50, 95% CI 1.04-2.18, P = .03), prison-based treatment (OR 2.02, 95% CI 1.08-3.79, P = .03) and younger age (OR 0.98, 95% CI 0.97-0.99, P = .05). Of the 1534 subjects completing treatment and follow-up, decreased likelihood of SVR12 was associated with genotype 2 (OR 0.23, 95% CI 0.07-0.74, P = .01) and genotype 3 (OR 0.23, 95% CI 0.12-0.43, P ≤ .01). A significant decrease in treatment initiation was observed over the twelve-month period in conjunction with a shift from hospital to community-based treatment. Our findings support the high responses observed in clinical trials however, a significant gap exists in SVR12 in our real-world cohort due to LTFU. A declining treatment initiation rate and shift to community-based treatment highlight the need to explore additional strategies to identify, treat and follow-up remaining patients in order to achieve elimination targets.
Publisher: Elsevier BV
Date: 07-1993
DOI: 10.1016/S0196-0644(05)80983-7
Abstract: We tested the hypotheses that blood culture positivity and contamination rates were not increased by not changing needles between venipuncture and inoculation of blood culture bottles or by taking blood for culture by freshly inserted IV cannulae. A prospective study of blood cultures collected by venipuncture or IV cannulae taken from an emergency department population. Venipuncture s les were randomized into needle change (standard method) or no needle change before inoculation into blood culture bottles. Nine hundred forty patients requiring blood cultures after assessment in the ED. A standard disinfection procedure using 0.5% chlorhexidine in 70% alcohol was used. Blood was collected by venipuncture and inoculated with or without needle change. Blood collected by IV cannula was inoculated with a fresh needle applied to the collection syringe. There was no statistically significant difference in contamination rates for blood collected by venipuncture with no needle change (6.4%) compared with needle change (4.2%, P > .30). No significant difference in contamination rates was noted for blood taken by freshly inserted IV cannulae (4.3%) compared with venipuncture with needle change after s ling (4.2%, P > .90). Some problems with randomization resulted in unequal numbers in the needle-change (286) versus no-needle-change (141) subgroups, and this may have introduced bias. A higher rate of pathogen growth was observed in blood taken by IV cannula (11.4%) compared with the standard method (6.3%) (P < .025). A significantly greater rate of Gram-negative sepsis was noted in the IV cannula group (6.6%) compared with direct venipuncture with needle change (1.1%) and no needle change (4.2%, P < .01). The results of this study do not support the practice of changing needles before inoculating blood s les into blood culture bottles. Collection of blood for culture through freshly inserted IV cannulae is associated with a low contamination rate and is an acceptable alternative to direct venipuncture. Sources of bias in this study suggest that further research is needed to determine the optimal technique for collecting blood cultures.
Publisher: Wiley
Date: 10-04-2007
DOI: 10.1002/IJC.22662
Publisher: Institution of Engineering and Technology (IET)
Date: 2010
Publisher: Elsevier BV
Date: 08-2009
DOI: 10.1016/J.JMB.2009.06.013
Abstract: Activation of C3 to C3b signals the start of the alternative complement pathway. The C-terminal short complement regulator (SCR)-20 domain of factor H (FH), the major serum regulator of C3b, possesses a binding site for C3d, a 35-kDa physiological fragment of C3b. Size distribution analyses of mixtures of SCR-16/20 or FH with C3d by analytical ultracentrifugation in 50 and 137 mM NaCl buffer revealed a range of discrete peaks, showing that multimeric complexes had formed at physiologically relevant concentrations. Surface plasmon resonance studies showed that native FH binds C3d in two stages. An equilibrium dissociation constant K(D)(1) of 2.6 microM in physiological buffer was determined for the first stage. Overlay experiments indicated that C3d formed multimeric complexes with FH. X-ray scattering showed that the maximum dimension of the C3d complexes with SCR-16/20 at 29 nm was not much longer than that of the unbound SCR-16/20 dimer. Molecular modelling suggested that the ultracentrifugation and scattering data are most simply explained in terms of associating dimers of each of SCR-16/20 and C3d. We conclude that the physiological interaction between FH and C3d is not a simple 1:1 binding stoichiometry between the two proteins that is often assumed. Because the multimers involve the C-terminus of FH, which is bound to host cell surfaces, our results provide new insight on FH regulation during excessive complement activation, both in the fluid phase and at host cell surfaces decorated by C3d.
Publisher: Elsevier BV
Date: 04-2013
Publisher: Informa UK Limited
Date: 09-2016
DOI: 10.2147/IDR.S114942
Publisher: Wiley
Date: 04-1987
DOI: 10.1111/J.1440-0960.1987.TB00324.X
Abstract: Patient reported outcome measures (PROMs) are increasingly being used to compare the performance of health care providers. Our objectives were to determine the relative frequency of use of different metrics that can be derived from PROMs, explore clinicians' and patients' views of the options available, and make recommendations. First a rapid review of the literature on metrics derived from two generic (EQ-5D and EQ-VAS) and three disease-specific (Oxford Hip Score Oxford Knee Score Aberdeen Varicose Vein Questionnaire) PROMs was conducted. Next, the findings of the literature review were mapped onto our typology of metrics to determine their relative frequency of use, Finally, seven group meetings with surgical clinicians (n = 107) and six focus groups with patients (n = 45) were held which were audio-taped, transcribed and analysed thematically. Only nine studies (9.3% of included papers) used metrics for comparing providers. These were derived from using either the follow-up PROM score (n = 3) or the change in score as an outcome (n = 5), both adjusted for pre-intervention score. There were no recorded uses of the proportion reaching a specified ('good') threshold and only two studies used the proportion reaching a minimally important difference (MID).Surgical clinicians wanted multiple outcomes, with most support expressed for the mean change in score, perceiving it to be more interpretable there was also some support for the MID. For patients it was apparent that rather than the science behind these measures, the most important aspects were the use of language that would make the metrics personally meaningful and linking the metric to a familiar scale. For clinicians the recommended metrics are the mean change in score and the proportion achieving a MID, both adjusted for pre-intervention score. Both need to be clearly described and explained. For patients we recommend the proportion achieving a MID or proportion achieving a significant improvement in hip function, both adjusted for pre-intervention score.
Publisher: Oxford University Press (OUP)
Date: 04-1988
Abstract: C3b and iC3b, opsonic fragments of C3, interact with specific receptors on phagocytic cells. After bacterial opsonization, C3 fragments were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, western blotting, and immunodetection. For bacteria opsonized in 50% pooled human serum (PHS), C3 deposition and cleavage to iC3b occurred rapidly. C3b, iC3b, and C3d made up 17%, 64%, and 19%, respectively, of the C3 on Staphylococcus aureus and 53%, 44%, and 2% respectively, on Escherichia coli. Residual C3b was refractory to factor I cleavage, an occurrence enabling alternative pathway activation to continue. C3 deposited was quantitated by enzyme-linked immunosorbent assay with 50% PHS, greater than 50% and 90% of total C3 deposition occurred within 5 and 10 min, respectively. With a lower percentage of PHS, maximal deposition required up to 60 min and was not achieved in less than 10% PHS. Ester-bound fragments represented 34% and 82% of covalently bound C3 on S. aureus and E. coli, respectively.
Publisher: Oxford University Press (OUP)
Date: 03-2007
DOI: 10.1086/511637
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 13-01-2015
DOI: 10.1161/CIRCULATIONAHA.114.012461
Abstract: Use of surgery for the treatment of infective endocarditis (IE) as related to surgical indications and operative risk for mortality has not been well defined. The International Collaboration on Endocarditis–PLUS (ICE-PLUS) is a prospective cohort of consecutively enrolled patients with definite IE from 29 centers in 16 countries. We included patients from ICE-PLUS with definite left-sided, non–cardiac device–related IE who were enrolled between September 1, 2008, and December 31, 2012. A total of 1296 patients with left-sided IE were included. Surgical treatment was performed in 57% of the overall cohort and in 76% of patients with a surgical indication. Reasons for nonsurgical treatment included poor prognosis (33.7%), hemodynamic instability (19.8%), death before surgery (23.3%), stroke (22.7%), and sepsis (21%). Among patients with a surgical indication, surgical treatment was independently associated with the presence of severe aortic regurgitation, abscess, embolization before surgical treatment, and transfer from an outside hospital. Variables associated with nonsurgical treatment were a history of moderate/severe liver disease, stroke before surgical decision, and Staphyloccus aureus etiology. The integration of surgical indication, Society of Thoracic Surgeons IE score, and use of surgery was associated with 6-month survival in IE. Surgical decision making in IE is largely consistent with established guidelines, although nearly one quarter of patients with surgical indications do not undergo surgery. Operative risk assessment by Society of Thoracic Surgeons IE score provides prognostic information for survival beyond the operative period. S aureus IE was significantly associated with nonsurgical management.
Publisher: Springer Netherlands
Date: 2010
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-04-2016
Abstract: Host factors and complications have been associated with higher mortality in infective endocarditis ( IE ). We sought to develop and validate a model of clinical characteristics to predict 6‐month mortality in IE . Using a large multinational prospective registry of definite IE (International Collaboration on Endocarditis [ ICE ]–Prospective Cohort Study [ PCS ], 2000–2006, n=4049), a model to predict 6‐month survival was developed by Cox proportional hazards modeling with inverse probability weighting for surgery treatment and was internally validated by the bootstrapping method. This model was externally validated in an independent prospective registry ( ICE ‐ PLUS , 2008–2012, n=1197). The 6‐month mortality was 971 of 4049 (24.0%) in the ICE ‐ PCS cohort and 342 of 1197 (28.6%) in the ICE ‐ PLUS cohort. Surgery during the index hospitalization was performed in 48.1% and 54.0% of the cohorts, respectively. In the derivation model, variables related to host factors (age, dialysis), IE characteristics (prosthetic or nosocomial IE , causative organism, left‐sided valve vegetation), and IE complications (severe heart failure, stroke, paravalvular complication, and persistent bacteremia) were independently associated with 6‐month mortality, and surgery was associated with a lower risk of mortality (Harrell's C statistic 0.715). In the validation model, these variables had similar hazard ratios (Harrell's C statistic 0.682), with a similar, independent benefit of surgery (hazard ratio 0.74, 95% CI 0.62–0.89). A simplified risk model was developed by weight adjustment of these variables. Six‐month mortality after IE is ≈25% and is predicted by host factors, IE characteristics, and IE complications. Surgery during the index hospitalization is associated with lower mortality but is performed less frequently in the highest risk patients. A simplified risk model may be used to identify specific risk subgroups in IE .
No related grants have been discovered for David Gordon.