247 research outputs found

    The Toronto Extremity Salvage Score in unoperated controls: an age, gender, and country comparison

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    Extent: 5p.The Toronto Extremity Salvage Score (TESS) is widely used for the functional assessment of patients following surgery for musculoskeletal tumours. The aim of this study was to determine if there are gender and/or age-specific changes, unrelated to surgery, that may influence this score and the appropriateness of the questions. The TESS for lower limb was carried out in two different countries to see if there was variation between them. There were no statistically significant differences between the scores obtained between the respondents from Australia or Britain either in total or between the corresponding age groups. There were statistically significant differences in the TESS obtained between age groups with a lower score at older age groups but there was no difference between the sexes. Patients in the age group 70+ were more likely to record activities as “not applicable” and also have a lower score. This study has shown that age is the major factor in determining the TESS in both an Australian and British populations of otherwise healthy people. As there were no differences between the two populations, it supports the TESS as an international scoring system. There may be also an argument for age-specific questions.Mark Clayer, Simon Doyle, Nicole Sangha, and Robert Grime

    Dietary cholesterol directly induces acute inflammasome-dependent intestinal inflammation

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    Prolonged ingestion of a cholesterol- or saturated fatty acid-enriched diet induces chronic, often systemic, auto-inflammatory responses resulting in significant health problems worldwide. In vivo information regarding the local and direct inflammatory effect of these dietary components in the intestine and, in particular, on the intestinal epithelium is lacking. Here we report that both mice and zebrafish exposed to high-fat (HFDs) or high-cholesterol (HCDs) diets develop acute innate inflammatory responses within hours, reflected in the localized interleukin-1β-dependent accumulation of myeloid cells in the intestine. Acute HCD-induced intestinal inflammation is dependent on cholesterol uptake via Niemann-Pick C1-like 1 and inflammasome activation involving apoptosis-associated Speck-like protein containing a caspase recruitment domain, which leads to Caspase-1 activity in intestinal epithelial cells. Extended exposure to HCD results in localized, inflammation-dependent, functional dysregulation as well as systemic pathologies. Our model suggests that dietary cholesterol initiates intestinal inflammation in epithelial cells

    Analysis of complement and plasma cells in the brain of patients with anti-NMDAR encephalitis

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    OBJECTIVES: Most patients with anti-NMDA receptor (NMDAR) encephalitis have intrathecal synthesis of antibodies, which cause a decrease of cell surface and synaptic NMDAR. Antibodies are immunoglobulin G (IgG)1 and IgG3 subtypes and can potentially activate complement. We examined whether complement immunoreactivity and antibody-secreting cells (plasma cells/plasmablasts) are present in the brain of these patients. METHODS: Cultured rat hippocampal neurons were used in an immunocytochemical assay to test whether patients' antibodies can fix complement. Using the same reagents (antibodies to C9neo, C(5b-9), C3), complement immunoreactivity was determined in the brain of 5 patients, the teratoma of 21 patients, and appropriate control tissues. A set of markers for B (CD20), T (CD3, CD4, CD8) and antibody-secreting cells (plasma cells/plasmablasts, CD138) were used to examine the brain inflammatory infiltrates. RESULTS: Patients' antibodies were able to bind complement in vitro, but deposits of complement were not detected in patients' brain. Parallel experiments with teratomas showed that in contrast to the brain, the neural tissue of the tumors contained complement. Analysis of the inflammatory infiltrates in brain samples from autopsy or biopsy performed 3-4 weeks after symptom presentation demonstrated numerous antibody-secreting cells (CD138+) in perivascular, interstitial, and Virchow-Robin spaces, and B and T cells predominantly located in perivascular regions. CONCLUSIONS: Complement-mediated mechanisms do not appear to play a substantial pathogenic role in anti-NMDAR encephalitis. In contrast, there are copious infiltrates of antibody-secreting cells (plasma cells/plasmablasts) in the CNS of these patients. The demonstration of these cells provides an explanation for the intrathecal synthesis of antibodies and has implications for treatment

    Development and validation of an index of musculoskeletal functional limitations

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    BACKGROUND: While musculoskeletal problems are leading sources of disability, there has been little research on measuring the number of functionally limiting musculoskeletal problems for use as predictor of outcome in studies of chronic disease. This paper reports on the development and preliminary validation of a self administered musculoskeletal functional limitations index. METHODS: We developed a summary musculoskeletal functional limitations index based upon a six-item self administered questionnaire in which subjects indicate whether they are limited a lot, a little or not at all because of problems in six anatomic regions (knees, hips, ankles and feet, back, neck, upper extremities). Responses are summed into an index score. The index was completed by a sample of total knee replacement recipients from four US states. Our analyses examined convergent validity at the item and at the index level as well as discriminant validity and the independence of the index from other correlates of quality of life. RESULTS: 782 subjects completed all items of the musculoskeletal functional limitations index and were included in the analyses. The mean age of the sample was 75 years and 64% were female. The index demonstrated anticipated associations with self-reported quality of life, activities of daily living, WOMAC functional status score, use of walking support, frequency of usual exercise, frequency of falls and dependence upon another person for assistance with chores. The index was strongly and independently associated with self-reported overall health. CONCLUSION: The self-reported musculoskeletal functional limitations index appears to be a valid measure of musculoskeletal functional limitations, in the aspects of validity assessed in this study. It is useful for outcome studies following TKR and shows promise as a covariate in studies of chronic disease outcomes.National Institutes of Health (NIH P60 AR 47782; NIH K24 AR 02123

    Relationship of literacy and heart failure in adults with diabetes

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    <p>Abstract</p> <p>Background</p> <p>Although reading ability may impact educational strategies and management of heart failure (HF), the prevalence of limited literacy in patients with HF is unknown.</p> <p>Methods</p> <p>Subjects were drawn from the Vermont Diabetes Information System Field Survey, a cross-sectional study of adults with diabetes in primary care. Participants' self-reported characteristics were subjected to logistic regression to estimate the association of heart failure and literacy while controlling for social and economic factors. The Short Test of Functional Health Literacy was used to measure literacy.</p> <p>Results</p> <p>Of 172 subjects with HF and diabetes, 27% had limited literacy compared to 15% of 826 subjects without HF (OR 2.05; 95% CI 1.39, 3.02; <it>P </it>< 0.001). Adjusting for age, sex, race, income, marital status and health insurance, HF continued to be significantly associated with limited literacy (OR 1.55, 95% CI 1.00, 2.41, <it>P </it>= .05).</p> <p>After adjusting for education, however, HF was no longer independently associated with literacy (OR 1.31; 95% CI 0.82 – 2.08; <it>P </it>= 0.26).</p> <p>Conclusion</p> <p>Over one quarter of diabetic adults with HF have limited literacy. Although this association is no longer statistically significant when adjusted for education, clinicians should be aware that many of their patients have important limitations in dealing with written materials.</p

    INSPIRE: A phase III study of the BLP25 liposome vaccine (L-BLP25) in Asian patients with unresectable stage III non-small cell lung cancer

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    <p>Abstract</p> <p>Background</p> <p>Previous research suggests the therapeutic cancer vaccine L-BLP25 potentially provides a survival benefit in patients with locally advanced unresectable stage III non-small cell lung carcinoma (NSCLC). These promising findings prompted the phase III study, INSPIRE, in patients of East-Asian ethnicity. East-Asian ethnicity is an independent favourable prognostic factor for survival in NSCLC. The favourable prognosis is most likely due to a higher incidence of EGFR mutations among this patient population.</p> <p>Methods/design</p> <p>The primary objective of the INSPIRE study is to assess the treatment effect of L-BLP25 plus best supportive care (BSC), as compared to placebo plus BSC, on overall survival time in East-Asian patients with unresectable stage III NSCLC and either documented stable disease or an objective response according to the Response Evaluation Criteria in Solid Tumors (RECIST) criteria following primary chemoradiotherapy. Those in the L-BLP25 arm will receive a single intravenous infusion of cyclophosphamide (300 mg/m<sup>2</sup>) 3 days before the first L-BLP25 vaccination, with a corresponding intravenous infusion of saline to be given in the control arm. A primary treatment phase of 8 subcutaneous vaccinations of L-BLP25 930 Îźg or placebo at weekly intervals will be followed by a maintenance treatment phase of 6-weekly vaccinations continued until disease progression or discontinuation from the study.</p> <p>Discussion</p> <p>The ongoing INSPIRE study is the first large study of a therapeutic cancer vaccine specifically in an East-Asian population. It evaluates the potential of maintenance therapy with L-BLP25 to prolong survival in East-Asian patients with stage III NSCLC where there are limited treatment options currently available.</p> <p>Study number</p> <p>EMR 63325-012</p> <p>Trial Registration</p> <p>Clinicaltrials.gov reference: <a href="http://www.clinicaltrials.gov/ct2/show/NCT01015443">NCT01015443</a></p

    Role of Androgen Receptor CAG Repeat Polymorphism and X-Inactivation in the Manifestation of Recurrent Spontaneous Abortions in Indian Women

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    The aim of the present study was to investigate the role of CAG repeat polymorphism and X-chromosome Inactivation (XCI) pattern in Recurrent Spontaneous Abortions among Indian women which has not been hitherto explored. 117 RSA cases and 224 Controls were included in the study. Cases were recruited from two different hospitals - Lakshmi Fertility Clinic, Nellore and Fernandez Maternity Hospital, Hyderabad. Controls were roughly matched for age, ethnicity and socioeconomic status. The CAG repeats of the Androgen Receptor gene were genotyped using a PCR-based assay and were analysed using the GeneMapper software to determine the CAG repeat length. XCI analysis was also carried out to assess the inactivation percentages. RSA cases had a significantly greater frequency of allele sizes in the polymorphic range above 19 repeats (p = 0.006), which is the median value of the controls, and in the biallelic mean range above 21 repeats (p = 0.002). We found no evidence of abnormal incidence of skewed X-inactivation. We conclude that longer CAG repeat lengths are associated with increased odds for RSA with statistical power estimated to be ∼90%

    Harpgophytum procumbens for osteoarthritis and low back pain: A systematic review

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    BACKGROUND: The objective of this review is to determine the effectiveness of Harpagophytum procumbens preparations in the treatment of various forms of musculoskeletal pain. METHODS: Several databases and other sources were searched to identify randomized controlled trials, quasi-randomized controlled trials, and controlled clinical trials testing Harpagophytum preparations in adults suffering from pain due to osteoarthritis or low back pain. RESULTS: Given the clinical heterogeneity and insufficient data for statistical pooling, trials were described in a narrative way, taking into consideration methodological quality scores. Twelve trials were included with six investigating osteoarthritis (two were identical trials), four low back pain, and three mixed-pain conditions. CONCLUSIONS: There is limited evidence for an ethanolic Harpagophytum extract containing less than <30 mg harpagoside per day in the treatment of knee and hip osteoarthritis. There is moderate evidence of effectiveness for (1) the use of a Harpagophytum powder at 60 mg harpagoside in the treatment of osteoarthritis of the spine, hip and knee; (2) the use of an aqueous Harpagophytum extract at a daily dose of 100 mg harpagoside in the treatment of acute exacerbations of chronic non-specific low back pain; and (3) the use of an aqueous extract of Harpagophytum procumbens at 60 mg harpagoside being non-inferior to 12.5 mg rofecoxib per day for chronic non-specific low-back pain (NSLBP) in the short term. Strong evidence exists for the use of an aqueous Harpagophytum extract at a daily dose equivalent of 50 mg harpagoside in the treatment of acute exacerbations of chronic NSLBP
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