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Biomedical subjects

S Evans

Publications and source records attributed to S Evans.

At least 55 records · Page 3Linked to original sources

Early postmenopausal bone loss in hyperthyroidism.

OBJECTIVES: To evaluate the effect of hyperthyroidism on bone in relation to the menopausal state. METHODS: Fifty-nine hyperthyroid (HYPER), 40 hypothyroid (HYPO), and 51 control euthyroid (EUTH) women were studied. Bone mineral density (BMD) was assessed by dual X-rays absorptiometry (DXA) at the lumbar spine, and at the femoral neck. A multi-site QUS device evaluated speed of sound (SOS) at the radius (RAD), tibia (TIB), metatarsus (MTR), and phalanx (PLX). Bone markers used were serum bone specific alkaline phosphatase (BSAP) and urinary deoxypyridinoline (DPD). RESULTS: At all sites, SOS was lower in HYPER than in EUTH (RAD P<0.05, TIB P<0.01, MTR P<0.05, PLX P=0.01). The low SOS was only noted at the early postmenopausal period. BMD at the femoral neck but not at the lumbar spine was lower in HYPER as compared to EUTH (P<0.05). Both femoral neck and tibia were the sites with the highest odds ratio for being hyperthyroid (2.3 and 2.04, respectively). There was no correlation between BMD or SOS and FT(4), TT(3) or duration of hyperthyroidism. BSAP and DPD positively correlated with FT(4) and TT(3) (P<0.05). CONCLUSIONS: This study suggests that hyperthyroidism affects bone mineralization especially during the early postmenopausal period, and the effect is mainly at the cortical bone.

Absorptiometry, Photon↗

Degradation of albumin in meningococcal sepsis.

We postulate that the proteolytic degradation of albumin into fragments could link the rapidity of the shock, rash, and hypocalcaemia associated with meningococcal sepsis. We examined urine of children with meningococcal disease and urine from control children with no sepsis and found albumin fragments of about 45 kDa, 25 kDa, and less than 20 kDa only in the urine of children with meningococcal sepsis and associated purpura. Exogenous or endogenous proteases, or both, may be released in severe meningococcal sepsis and, in association with an inadequate antiprotease response, result in albumin degradation. This may be a contributory factor to the rapid shock, hypocalcaemia, and rash seen in meningococcal sepsis.

Albumins↗

Cutting edge: systemic inhibition of angiogenesis underlies resistance to tumors during acute toxoplasmosis.

The ability of various infections to suppress neoplastic growth has been well documented. This phenomenon has been traditionally attributed to infection-induced concomitant, cell-mediated antitumor immunity. We found that infection with Toxoplasma gondii effectively blocked neoplastic growth of a nonimmunogenic B16.F10 melanoma. Moreover, this effect was independent of cytotoxic T or NK cells, production of NO by macrophages, or the function of the cytokines IL-12 and TNF-alpha. These findings suggested that antitumor cytotoxicity was not the primary mechanism of resistance. However, infection was accompanied by strong, systemic suppression of angiogenesis, both in a model system and inside the nascent tumor. This suppression resulted in severe hypoxia and avascular necrosis that are incompatible with progressive neoplastic growth. Our results identify the suppression of tumor neovascularization as a novel mechanism critical for infection-induced resistance to tumors.

Acute Disease↗

Problems in the development and validation of questionnaire-based screening instruments for ascertaining cases with symptomatic knee osteoarthritis: the Framingham Study.

OBJECTIVE: To determine if screening for symptomatic knee osteoarthritis (OA) for clinical trials and epidemiologic studies could be satisfactorily done without performing knee radiographs and to develop efficient screening instruments for symptomatic knee OA based on self-reported symptoms and functional limitations. METHODS: We administered a mailed questionnaire containing many different questions on knee symptoms and functional limitations to 1,921 participants of the Framingham Study who had previously been screened for symptomatic OA with a history and knee radiographs. Recursive partitioning methods (using the Classification and Regression Trees [CART] program) were used to create a set of screening instruments for symptomatic knee OA, which was defined as knee symptoms on most days and radiographic evidence of OA. Three screening instruments were developed to maximize the sensitivity, specificity, and efficiency. RESULTS: The sensitive instrument had 84% sensitivity and 73% specificity. The specific instrument had 46% sensitivity and 94% specificity. The efficient instrument had 56% sensitivity and 85% specificity. Sensitivity was lower and specificity was higher when these instruments were used to screen for radiographic OA. All instruments had higher sensitivity but lower specificity when used for older subjects (age >60) with greater disease prevalence. However, using any of these instruments as a single-step screening mechanism resulted in considerable misclassification. CONCLUSION: We conclude that none of these instruments has adequate diagnostic test performance to serve as a single-step evaluation of the presence or absence of symptomatic knee OA.

Age Factors↗

Episodic memory in primates.

Episodic memory refers to a system of memory with the capacity to recollect specific events from an individual's life. Some psychologists have suggested that episodic memory is a uniquely human phenomenon. We challenge that idea and present evidence that great apes and other primates may possess episodic-like memory. We review criteria developed to assess episodic-like memory in nonhumans, and how they apply to primates. In particular, we discuss the criteria of Clayton et al. [2001], who stated that episodic-like memory is based on the retrieval of multiple and integrated components of an event. We then review eight studies examining memory in great apes and apply the Clayton et al. criteria to each of them. We summarize the evidence that is compatible with the existence of episodic-like memory, although none of the data completely satisfy the Clayton et al. criteria. Morover, feelings of pastness and feelings of confidence, which mark episodic memory in humans, have not been empirically addressed in nonhuman primates. Future studies should be directed at these aspects of memory in primates. We speculate on the functional significance of episodic memory in nonhuman primates.

Animals↗

Managing severe mental illness in the community using the Mental Health Act 1983: a comparison of Supervised Discharge and Guardianship in England.

BACKGROUND: Two measures in the English Mental Health Act allow requirements to be imposed upon patients living in the community. These are Guardianship (Section 7) and Supervised Discharge (Section 25A). AIMS: The paper aims to compare patients with mental illnesses, made subject to Guardianship or Supervised Discharge. METHOD: Data on patient characteristics, impairment, needs and interventions were collected from keyworkers in a random national sample of Trusts and local authorities. Ratings were obtained on standardised measures of disability, impairment and needs. RESULTS: Patients placed on Supervised Discharge were more likely to have problems of treatment compliance and drug misuse, whilst those on Guardianship were more likely to have problems of social welfare and higher ratings of disability and impairment. Supervised Discharge has a higher proportion of African-Caribbean patients. Interventions delivered are rated as effective for both measures. CONCLUSIONS: Legal changes proposed in England include a single power for supervision in the community. This should not mean a focus on risk management to the neglect of social welfare interventions.

Adult↗

Quality of life outcome in a randomized controlled trial of case management.

BACKGROUND: This paper presents the quality of life (QOL) outcome results from the UK700 randomised controlled trial of case management. METHOD: A total of 708 patients with severe mental illness were randomly assigned to intensive and standard forms of case management in four sites in the UK. QOL was assessed using the Lancashire Quality of Life Profile, which provides a self-reported objective and subjective appraisal of eight life domains (finances, work, leisure, family, social relations, living situation, safety and health). The outcome after 2 years was examined using univariate and multivariate analyses. RESULTS: Significant improvements in QOL over the 2 years were observed. The QOL outcome did not differ significantly by case management treatment conditions or by diagnosis. A better outcome was associated with improvements in depression and with the location (site) of treatment. In one site there were significant improvements in all eight domains and overall QOL, with moderate or better effect sizes (> 0.4) in three domains and overall QOL. CONCLUSIONS: Depression should be assessed when subjective QOL measures are used. Better means for describing service organisations and the context/place in which they operate should be developed in order to explain more of the variance in QOL outcomes.

Adolescent↗

Environmental enrichment enhances recovery of function but exacerbates ischemic cell death.

Prior exposure to brief 'conditioning' episodes of ischemia protects hippocampal CA1 neurons against a subsequent more severe ischemic insult. However, protected cells exhibit abnormal function and as survival times are extended this ischemic tolerance dissipates and cells begin to die. In this study, we sought to determine whether environmental enrichment could alter the above pattern of delayed cell death and functional impairment in a gerbil model of ischemic tolerance. Gerbils received either ischemic preconditioning, 5 min of ischemia without preconditioning or sham surgery. Three days after ischemia, gerbils were placed in either an enriched environment or standard laboratory housing. Open field habituation was assessed 3, 7, 10, 30 and 60 days after ischemia. Subsequently, animals were trained in two versions (win-shift and win-stay) of a T-maze task. Following behavioral testing, extracellular CA1 field potential amplitudes and CA1 cell counts were determined. Initial open field activity was significantly higher in all experimental groups compared to sham animals (P<0.001). By 60 days, enriched ischemic preconditioned and enriched ischemic gerbils were not different than shams whereas non-enriched, ischemic preconditioned and ischemic gerbils continued to have higher activity scores (P<0.05). Preconditioned and enriched ischemic animals learned the win-shift T-maze problem as quickly as shams while non-enriched ischemic gerbils were severely impaired compared with all other groups (P<0.001). Only the sham and enriched preconditioned groups readily acquired the win-stay paradigm. CA1 field potential amplitudes were lower (P<0.05) in ischemic than sham gerbils irrespective of treatment. Surprisingly, CA1 cell counts were significantly lower (P<0.01) in enriched versus non-enriched ischemic preconditioned animals. These data demonstrate that early, intensive intervention after ischemia can improve functional outcome but that this is accompanied by increased brain damage. Careful consideration needs to be given to the timing of rehabilitation after stroke and related types of brain injury.

Animals↗

Anti-PF4-heparin immunoglobulin G is the major class of heparin-induced thrombocytopenia antibody: findings of an enzyme-linked immunofiltration assay using membrane-bound hPF4-heparin.

An enzyme-linked immunofiltration assay (ELIFA) was developed for detecting anti-human platelet factor 4 (hPF4)-heparin antibody in sera of patients with heparin-induced thrombocytopenia (HIT). The immunofiltration assay was developed to capture HIT antibody by hPF4-heparin complex adsorbed onto a positively charged nylon membrane, as an alternative to plastic bound hPF4. Of 75 sera with a positive serotonin-release assay (SRA), anti-PF4-heparin of the immunoglobulin (Ig)G class was detected in 72 (96%) sera. With SRA-negative sera from thrombocytopenic patients treated with heparin, anti-hPF4-heparin IgG and IgA were detected in 16% (n = 126) and 14% (n = 74) of sera respectively; 6% (n = 71) of SRA-negative sera contained both IgG and IgA anti-hPF4-heparin antibodies. The detection of anti-hPF4-heparin IgG in all HIT sera supports the assay of anti-PF4-heparin IgG as being a sensitive screening test for HIT. Alternatively, the absence of anti-hPF4-heparin IgA cannot be used as a test for excluding HIT, as it was detected in only 48% of SRA-positive HIT sera. However, it may be used to support the diagnosis of HIT, when HIT IgG is weak. This study emphasized the need to use different immobilizing media for the capture of anti-PF4-heparin antibody.

Antibodies↗

Ethical issues regarding fee-for-service-funded research within a complementary medicine context.

Ethical issues are presented concerning the appropriate use of a fee-for-service strategy to fund clinical research assessing preventive complementary medicine approaches, particularly the effectiveness of dietary supplements for disease prevention. Reasons for the need for such an alternative funding approach are identified and historical precedents are noted. Presuming a priori key desiderata of doing no harm, not taking advantage of the ill, and pursuing recognized useful purposes, six key ethical questions from the relevant literature are identified and discussed. Arguments are advanced that there is a sound rational, ethical basis (1) to ask patients to pay for clinical experimentation in the focused area of supplement-directed disease prevention; (2) to accept the reality that those who cannot pay may not participate; (3) to permit moderate profit from the ongoing research; (4) to allow researchers to receive fees for their support of such clinical research; (5) to pursue this alternative funding strategy in addition to conventional sources; and (6) to expect that patients can give informed consent in such settings. It is demonstrated that patient-funded research has been an integral component of clinical research for decades and that there is no inherent reason why explicit patient payment of fees need be less ethical than any other commonly accepted funding models. Accordingly, an ethical case is made for the appropriateness and value of significantly expanded fee-for-service-funded research within a complementary medicine context, particularly the assessment of dietary supplements for disease prevention.

Clinical Trials as Topic↗

cis-acting sequences required for coronavirus infectious bronchitis virus defective-RNA replication and packaging.

The parts of the RNA genome of infectious bronchitis virus (IBV) required for replication and packaging of the RNA were investigated using deletion mutagenesis of a defective RNA (D-RNA) CD-61 (6.1 kb) containing a chloramphenicol acetyltransferase reporter gene. A D-RNA with the first 544, but not as few as 338, nucleotides (nt) of the 5' terminus was replicated; the 5' untranslated region (UTR) comprises 528 nt. Region I of the 3' UTR, adjacent to the nucleocapsid protein gene, comprised 212 nt and could be removed without impairment of replication or packaging of D-RNAs. A D-RNA with the final 338 nt, including the 293 nt in the highly conserved region II of the 3' UTR, was replicated. Thus, the 5'-terminal 544 nt and 3'-terminal 338 nt contained the necessary signals for RNA replication. Phylogenetic analysis of 19 strains of IBV and 3 strains of turkey coronavirus predicted a conserved stem-loop structure at the 5' end of region II of the 3' UTR. Removal of the predicted stem-loop structure abolished replication of the D-RNAs. D-RNAs in which replicase gene 1b-derived sequences had been removed or replaced with all the downstream genes were replicated well but were rescued poorly, suggesting inefficient packaging. However, no specific part of the 1b gene was required for efficient packaging.

3' Untranslated Regions↗

Evaluating the impact of a locality based social policy intervention on mental health: conceptual and methodological issues.

Urban regeneration initiatives provide an opportunity for examining the impact of changes in socio-economic circumstances on the mental health of different groups and individuals within localities. This paper sets out the conceptual and methodological bases for evaluating the impact of a population based social policy intervention on mental health. We suggest the need to integrate a range of disciplinary and methodological developments in research on health inequalities in exploring the impact of urban regeneration on mental health. A combination of multi-level modelling, subjective indicators and narrative accounts of individuals about mental health in the context of locality and personal changes are central for developing theories and methods appropriate for exploring the action and interaction of effects operating between structural and individual/agency levels.

Evaluation Studies as Topic↗