Seropositive erosive rheumatoid arthritis (RA).
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Biomedical subjects
Publications and source records attributed to C Matthews.
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The purpose of this study was to identify the population prevalence across the stages of change (SoC) for regular physical activity and to establish the prevalence of people at risk. With support from the National Institutes of Health, the American Heart Association, and the Robert Wood Johnson Foundation, nine Behavior Change Consortium studies with a common physical activity SoC measure agreed to collaborate and share data. The distribution pattern identified in these predominantly reactively recruited studies was Precontemplation (PC) = 5% (+/- 10), Contemplation (C) = 10% (+/- 10), Preparation (P) = 40% (+/- 10), Action = 10% (+/- 10), and Maintenance = 35% (+/- 10). With reactively recruited studies, it can be anticipated that there will be a higher percentage of the sample that is ready to change and a greater percentage of currently active people compared to random representative samples. The at-risk stage distribution (i.e., those not at criteria or PC, C, and P) was approximately 10% PC, 20% C, and 70% P in specific samples and approximately 20% PC, 10% C, and 70% P in the clinical samples. Knowing SoC heuristics can inform public health practitioners and policymakers about the population's motivation for physical activity, help track changes over time, and assist in the allocation of resources.
OBJECTIVES: To determine whether diagnostic triage by general practitioners (GPs) or rheumatology nurses (RNs) can improve the positive predictive value of referrals to early arthritis clinics (EACs). METHODS: Four GPs and two RNs were trained in the assessment of early inflammatory arthritis (IA) by four visits to an EAC supervised by hospital rheumatologists. Patients referred to one of three EACs were recruited for study and assessed independently by a GP, an RN and one of six rheumatologists. Each assessor was asked to record their clinical findings and whether they considered the patient to have IA. Each was then asked to judge the appropriateness of the referral according to predetermined guidelines. The rheumatologists had been shown previously to have a satisfactory level of agreement in the assessment of IA. RESULTS: Ninety-six patients were approached and all consented to take part in the study. In 49 cases (51%), the rheumatologist judged that the patient had IA and that the referral was appropriate. The assessments of GPs and RNs were compared with those of the rheumatologists. Levels of agreement were measured using the kappa value, where 1.0 represents total unanimity. The kappa value was 0.77 for the GPs when compared with the rheumatologists and 0.79 for the RNs. Significant stiffness in the morning or after rest and objective joint swelling were the most important clinical features enabling the GPs and RNs to discriminate between IA and non-IA conditions. CONCLUSION: Diagnostic triage by GPs or RNs improved the positive predictive value of referrals to an EAC with a degree of accuracy approaching that of a group of experienced rheumatologists.
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Linkage disequilibrium (LD) methods offer great promise for mapping complex traits, but have thus far been applied sparingly. In this paper we describe an LD mapping study of severe bipolar disorder (BP-I) in the genetically isolated population of the Central Valley of Costa Rica. This study provides the first complete screen of a chromosome for a complex trait using LD mapping and presents the first application of a new LD mapping statistic (ancestral haplotype reconstruction (AHR)) that evaluates haplotype sharing among affected individuals. The results of this chromosome-wide analysis are instructive for genome-wide LD mapping in isolated populations. Furthermore, the analysis continues to support a possible BP-I locus on 18pter, suggested by previous analyses in this population. Evidence for a possible BP-I locus on 18q12.2 is also described.
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Early environment exerts profound effects on mammalian behavioral and neural development. The aim of this study was to describe changes in adult neurochemistry in the rat following repeated neonatal maternal separation (RMS) during the preweaning period, a procedure known to induce enduring behavioral effects. Following RMS, rats show an attenuated locomotor response to novelty, to D-amphetamine, and attenuated behavioral responses for conditioned incentives as adults. These behavioral effects are broadly opposite in direction to those found following postweaning isolation rearing. Isolation rearing-induced behavioral changes are associated with profound changes in central monoamine function. Following RMS, adult rats had increased tissue levels of dopamine in both dorsal and ventral striatum. The turnover of dopamine, as determined by the ratio of DOPAC to dopamine, was decreased in the mPFC of RMS subjects. Serotonin levels were reduced in dorsal hippocampus of RMS rats of both sexes and in the mPFC of male RMS rats. Noradrenaline levels were increased in the dorsal hippocampus in female, but not in male, RMS rats. These data provide evidence that, in addition to the adult behavioral consequences, RMS leads to profound, region-, and gender-specific changes in brain monoamine content. The developmental specificity of these results is discussed with respect to their possible role in altered behavioral development and psychopathology.
BACKGROUND: Previous investigators have administered 4-aminopyridine (4AP) to dogs to evaluate the role of transient outward current (I(to)) in vivo; however, plasma concentrations of 4AP were not measured, and it is therefore uncertain which cardiac ion channels were blocked at the concentrations achieved. METHODS AND RESULTS: We applied high-performance liquid chromatography to measure 4AP concentrations produced by intravenous 4AP administration to dogs. A previously described dose regimen produced plasma concentrations that increased during the maintenance infusion but never exceeded 250 micromol/L and caused significant mortality. Whole-cell patch-clamp experiments on isolated canine myocytes showed that even the maximum 4AP concentrations achieved in vivo failed to alter ventricular I(to) and had very small effects on atrial I(to); however, concentrations achieved in vivo had a strong inhibitory effect on the dog ultrarapid delayed rectifier (I(Kur.d)), present only in atrial cells. We designed a loading and maintenance infusion regimen to produce stable 4AP plasma concentrations. At concentrations in the range of 25 and 50 micromol/L, 4AP had no effect on ventricular refractory period but increased atrial refractoriness significantly, consistent with the results of voltage clamp studies. CONCLUSIONS: The interpretation of previous studies using intravenous 4AP administration to inhibit I(to) in dogs in vivo needs to be reevaluated in light of the fact that the infusion regimens used produce plasma concentrations that are inadequate to affect ventricular I(to). Our findings also support the concept that selective inhibition of ultrarapid delayed rectifier current can prolong atrial refractory periods without affecting ventricular refractoriness.
OBJECTIVE: To undertake a qualitative study to explore the influence of role modelling on teaching by comparing faculty members recollections of their teachers' behaviours with residents perceptions of the same behaviours in a family medicine residency programme in Saudi Arabia. METHOD: Using semi-structured interviews of faculty and a questionnaire based on the issues arising from the interviews, faculty members' recollections of their medical teachers' behaviours were compared with residents' current perceptions of the same teaching behaviours. SETTING: Department of Family Medicine, King Fahad National Guard Hospital, Riyadh, Saudi Arabia. SUBJECTS: Faculty and residents. RESULTS: The four best-remembered teacher behaviours were: positive behaviour towards patients, negative behaviour towards junior colleagues, effective presentation of subject content and encouragement to participate in patient care. The residents perceived positive behaviour towards patients, positive behaviour towards junior colleagues, suboptimal skills of subject content presentation, and insufficient encouragement for trainees to actively participate in patient management. Although faculty retained many unhappy memories of teacher behaviour, it was encouraging that there was no evidence of perpetuation of the negatively perceived behaviours which provoked them. CONCLUSIONS: Discernment of the value of technical teaching skills was not a predictor of later proficiency.
Managers of health care services are seeking new opportunities to improve communication with clients who have limited English proficiency. An increase in bilingual health staff and the frequent use of their language skills in patient encounters provides opportunities but also brings with it confusion surrounding the role of interpreters and bilingual health staff. Secondary analysis of transcripts from 18 focus groups with monolingual and bilingual health staff has provided a method of distinguishing the roles of these complementary communicators. This paper clarifies the roles of interpreters and bilingual communication facilitators using seven key features: scope of language, language proficiency, nature of communication/interaction, nature of the contact and relationship, client responsibilities, and relationship with other health care providers. We discuss differences in how bilingual health staff use language when providing care, and alternative types of interactions interpreters could adopt to extend their current role. A collaborative group of communicators located within a health team is proposed, that is able to identify need and select the best communicator for the task.
The cardiorespiratory and thermal responses of two intensities of treadmill exercise were compared for brief periods (12 min) in fire ensemble (FE) but without self contained breathing apparatus, and sports ensemble (SE), in a temperature environment. A further experiment explored the responses of subjects exercising in FE over a prolonged period (60 min). Eighteen male fire-fighters wearing either FE or SE walked on a level treadmill for 6 min at 5 km x h(-1) increasing to 7 km x h(-1) for 6 min. Following a recovery interval of 1 h, the exercise protocol was repeated in the second ensemble; the order of ensemble was balanced. Heart rate (HR), rectal temperature (Tre), VO2 max and rating of perceived exertion (RPE) were monitored continuously under both ensembles. At 7 km x h(-1), VO2 was significantly higher (p<0.05) in FE (36.1 and 39.9 ml x kg(-1) x min(-1)) than in SE and represented 74% VO2 max. There were no changes Tre. In experiment 2, following a rest interval of at least 36 h, eight subjects in FE walked on the treadmill at 6 km x h (gradient 10%) for 60 min also in temperate conditions, where HR, Tre and RPE were recorded at 10-min intervals. During the 60-min exercise in FE, HR reached 161 beats x min(-1) and Tre increased to 38.3 degrees C. Despite considerable subject discomfort, Tre remained below dangerous levels (38.4 degrees C). When RPE were compared with a physiological strain index (PSI) calculated from Tre and HR data over 60 min, there was no significant difference (p<0.05) with a correlation coefficient (r) of 0.98. The results suggest that RPE and PSI are closely related when exercise is sufficiently prolonged or intense to elevate Tre and HR in fire-fighters wearing FE in temperate conditions. If further investigation confirms this relationship for hot humid conditions in which fire-fighters operate, then with training, it may provide individuals with a valid measure of dangerous levels of perceived heat strain.
1. The absorption changes associated with the formation of P+QBred (QBred stands for the semiquinone state of the secondary quinone acceptor) were investigated in chromatophores of Rhodobacter capsulatus. Marked modifications of the semiquinone spectrum were observed when the pH was lowered from 7 to 5. These modifications match those expected for a complete conversion of QBred from the anionic state QB- at pH 7 to the neutral protonated state QBH at pH 5. Similar modifications were observed in chromatophores from Rb. sphaeroides, but not in purified reaction centers from Rb. capsulatus, suggesting that the environment of the reaction center (native membrane vs detergent micelle) is the crucial parameter. 2. The recombination reaction P+QBred --> PQB was investigated as a function of pH. No particular kinetic heterogeneity was observed at low pH, showing that QBH remains mostly bound to the reaction center. The rate constant reaches a minimum value of 0.08 s-1 at pH 6, suggesting that the direct route for recombination prevails in chromatophores below this pH, instead of the usual pathway via QA-. 3. The proton uptake caused by QBred is about 1 below pH 7 and decreases at higher pH. It is suggested that the pH dependence of the conversion of QB- to QBH, occurring in a range where the uptake is constant, cannot be accommodated by a purely electrostatic model, but probably involves a conformational change. 4. The kinetics of the electron-transfer reaction QA-QB-->QAQBred were investigated. A 2-fold acceleration was observed between pH 7 and pH 5 (t1/2 approximately 30 and 15 microseconds, respectively). A fast (<<10 microseconds) unresolved phase appears to be present at both pHs. The second electron-transfer QA-QBred-->QAQBH2 proceeds with a similar rate as the first electron transfer (15-30 microseconds phase). Consequences for the rate-limiting step are discussed. 5. The carotenoid shift, indicative of the membrane potential, displays a rising phase concomitant with the QA-QB-->QAQBred electron transfer. Its relative extent is markedly increased at pH 5, with part of the kinetics occurring during the unresolved fast phase. 6. The extent of the electrochromic shift of bacteriopheophytin around 750 nm associated with formation of QBred decreases toward acidic pH, reflecting the charge compensation due to proton uptake and the formation of neutral QBH.
In vivo gene transfer with recombinant adenovirus vectors can be hindered by the immunogenicity of the adenovirus capsid proteins. Previous work showed that formulation of the vector with biodegradable polymers such as poly-lactic-glycolic acid (PLGA), polyethylene glycol (PEG), or lipids, may shield the virus from inhibition by neutralizing antibodies. Formulation of adenovirus in PLGA microspheres also allowed for extended release in vitro. In experiments described here, we found that the surfactant used in the formation of the primary emulsion could significantly improve the overall yield of virus released. We also tested the effects of adding poly-L-lysine to adenovirus before encapsulation with PLGA. Our results show that although PLL did not effect the yield of virus encapsulated or released from the microspheres, it significantly improved the efficiency of gene transfer after release from the polymer.
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The study of atherogenesis in humans has been restricted by the limited availability and brief in vitro life span of plaque smooth muscle cells (SMCs). We describe plaque SMC lines with extended life spans generated by the expression of the human papillomavirus (HPV)-16 E6 and E7 genes, which has been shown to extend the life span of normal adult human aortic SMCs. Resulting cell lines (pdSMC1A and 2) demonstrated at least 10-fold increases in life span; pdSMC1A became immortal. The SMC identity of both pdSMC lines was confirmed by SM22 mRNA expression. pdSMC2 were generally diploid but with various structural and numerical alterations; pdSMC1A demonstrated several chromosomal abnormalities, most commonly -Y, +7, -13, anomalies previously reported in both primary pdSMCs and atherosclerotic tissue. Confluent pdSMC2 appeared grossly similar to HPV-16 E6/E7-expressing normal adult aortic SMCs (AASMCs), exhibiting typical SMC morphology/growth patterns; pdSMC1A displayed irregular cell shape/organization with numerous mitotic figures. Dedifferentiation to a synthetic/proliferative phenotype has been hypothesized as a critical step in atherogenesis, because rat neonatal SMCs and adult intimal SMCs exhibit similar gene expression patterns. To confirm that our pdSMC lines likewise express this apparent plaque phenotype, osteopontin, platelet-derived growth factor B, and elastin mRNA levels were determined in pdSMC1A, pdSMC2, and AASMCs. However, no significant increases in osteopontin or platelet-derived growth factor B expression levels were observed in either pdSMC compared with AASMCs. pdSMC2 alone expressed high levels of elastin mRNA. Lower levels of SM22 mRNA in pdSMC1A suggested greater dedifferentiation and/or additional population doublings in pdSMC1A relative to pdSMC2. Both pdSMC lines (particularly 1A) demonstrated high message levels for matrix Gla protein, previously reported to be highly expressed by human neointimal SMCs in vitro. These results describe 2 novel plaque cell lines exhibiting various features of plaque SMC biology; pdSMC2 may represent an earlier plaque SMC phenotype, whereas pdSMC1A may be representative of cells comprising an advanced atherosclerotic lesion.
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The presence of diverse language skills within health staff provides opportunities to better meet the needs of a multicultural population. A cross-sectional survey of all staff within the South Western Sydney Area Health Service was undertaken to compare language skills with population needs and examine the context of language use. Thirty-one per cent of staff (n = 964) were bilingual or multilingual, with the predominant languages spoken being Tagalog (Filipino), Cantonese, Hindi, Spanish, Vietnamese and Italian. Thirty-seven per cent of bilingual staff used their language skills at least weekly, predominantly in situations of simple conversation and giving directions. Bilingual staff are a valuable resource for the organisation and the presence of a similar overall proportion of bilingual and bicultural staff may engender tolerance and adaptability in providing care to a diverse population. However, supply does not directly match community demand. This mismatch will continue unless recruitment is focused towards identified language groups. The high proportion of staff who rarely used their language skills (37%) may be due to lack of opportunity or limited need, and suggests that further research needs to examine service models that locate bilingual workers close to client need. This study takes a crucial first step towards realising equitable and culturally appropriate care utilising the principles of productive diversity.