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      Intravenous immunoglobulin for postpolio syndrome: a systematic review and meta-analysis

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          Abstract

          Background

          Postpolio syndrome (PPS) is characterized by progressive disabilities that develop decades after prior paralytic poliomyelitis. Because chronic inflammation may be the process underlying the development of PPS, immunomodulatory management, such as intravenous immunoglobulin (IVIg) administration, may be beneficial.

          Methods

          We performed a systematic review and meta-analysis of published randomized controlled trials (RCTs) and prospective studies that evaluated the efficacy of IVIg in managing PPS. Electronic databases, including PubMed, EMBASE, CINAHL, and the Cochrane Central Register of Controlled Trials, were searched for articles on PPS published before December 2014. The primary outcomes were pain severity, fatigue scores, and muscle strength. The secondary outcomes were physical performance, quality of life (QoL), and cytokine expression levels.

          Results

          We identified 3 RCTs involving 241 patients and 5 prospective studies involving 267 patients. The meta-analysis of pain severity (weighted mean difference [WMD] = −1.02, 95% confidence interval [CI] = −2.51 to 0.47), fatigue scores (WMD = 0.28, 95% CI −0.56 to 1.12), and muscle strength revealed no significant differences between the IVIg and the placebo group. Regarding QoL, the RCTs yielded controversial outcomes, with improvement in only certain domains of the Short Form 36 (SF-36). Moreover, one prospective study reported significant improvement on SF-36, particularly in patients aged younger than 65 years, those with paresis of the lower limbs, and high pain intensity.

          Conclusion

          The present review indicated that IVIg is unlikely to produce significant improvements in pain, fatigue, or muscle strength. Thus, routinely administering IVIg to patients with PPS is not recommended based on RCTs. However, a potential effect in younger patients with lower limbs weakness and intense pain requires confirmation from further well-structured trials.

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          Most cited references22

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          The physical activity scale for the elderly (PASE): evidence for validity.

          We assessed the validity of the Physical Activity Scale for the Elderly (PASE) in a sample of sedentary adults (56 men, 134 women, mean age +/- [SD] 66.5+/-5.3 years) who volunteered to participate in a randomized controlled trial on the effect of aerobic conditioning on psychological function. Construct validity was established by correlating PASE scores with physiologic and performance characteristics: peak oxygen uptake, resting heart rate and blood pressure, percent body fat, and balance. The mean PASE scores were higher in men than in women (men = 145.8+/-78.0; women = 123.9+/-66.3, P<0.05), and in those age 55-64 years compared with those age 65 years and over (55-64 = 144.2+/-75.8; 65 and over = 118.9+/-63.9, P<0.05). PASE scores were also significantly higher in those who did not report a chronic health condition (cardiovascular disease, hypertension, cancer, or recent surgery). PASE scores were significantly associated (P<0.05) with peak oxygen uptake (r = 0.20), systolic blood pressure (r = -0.18) and balance score (r = 0.20). No significant associations of PASE score and diastolic blood pressure, resting heart rate, or percent body fat were noted. These results provide additional evidence for the validity of the PASE as a measure of physical activity suitable for use in epidemiology studies on the association of physical activity, health, and physical function in older individuals.
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            Mobility-related function in older adults: assessment with a 6-minute walk test.

            To determine the usefulness of the 6-minute walk test as an integrated measure of mobility in older adults. Observational study. Community centers and retirement homes in the Los Angeles area. Eighty-six older adults without significant disease. None. Assessments included the 6-minute walk, chair stands, standing balance, gait speed, body mass index, and self-reported physical functioning and general health perceptions. One-week test-retest reliability of the 6-minute walk was .95. As hypothesized, the 6-minute walk distance was significantly greater for active than for inactive older adults (p < .0001), moderately correlated with chair stands (r = .67), standing balance (r = .52), and gait speed (r = -.73). It had a low correlation with body mass index (r = -.07). The correlation of the 6-minute walk with self-reported physical functioning was .55, and its correlation with general health perceptions was .39. Self-report and performance measures explained 69% of the variance in 6-minute walk scores. The 6-minute walk test is reliable and is valid in relation to the performance and self-reported indicators of physical functioning tested in this study. It could serve as a useful integrated measure of mobility.
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              Intravenous immunoglobulin expands regulatory T cells via induction of cyclooxygenase-2-dependent prostaglandin E2 in human dendritic cells.

              CD4(+)CD25(+)FoxP3(+) regulatory T cells (Tregs) play a critical role in the maintenance of immune tolerance. Intravenous immunoglobulin (IVIg), a therapeutic preparation of normal pooled human IgG, expands Tregs in various experimental models and in patients. However, the cellular and molecular mechanisms by which IVIg expands Tregs are relatively unknown. As Treg expansion in the periphery requires signaling by antigen-presenting cells such as dendritic cells (DCs) and IVIg has been demonstrated to modulate DC functions, we hypothesized that IVIg induces distinct signaling events in DCs that subsequently mediate Treg expansion. We demonstrate that IVIg expands Tregs via induction of cyclooxygenase (COX)-2-dependent prostaglandin E2 (PGE2) in human DCs. However, costimulatory molecules of DCs such as programmed death ligands, OX40 ligand, and inducible T-cell costimulator ligands were not implicated. Inhibition of PGE2 synthesis by COX-2 inhibitors prevented IVIg-mediated Treg expansion in vitro and significantly diminished IVIg-mediated Treg expansion in vivo and protection from disease in experimental autoimmune encephalomyelitis model. IVIg-mediated COX-2 expression, PGE2 production, and Treg expansion were mediated in part via interaction of IVIg and F(ab')2 fragments of IVIg with DC-specific intercellular adhesion molecule-3-grabbing nonintegrin. Our results thus uncover novel cellular and molecular mechanism by which IVIg expands Tregs.
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                Author and article information

                Contributors
                hyh0103@gmail.com
                10462@s.tmu.edu.tw
                kwhuang3@gmail.com
                euphemus2003@msn.com
                chaurjongh@tmu.edu.tw
                chingpiaotsai@gmail.com
                kelvintam@h.tmu.edu.tw
                yckuang2@gmail.com
                Journal
                BMC Neurol
                BMC Neurol
                BMC Neurology
                BioMed Central (London )
                1471-2377
                22 March 2015
                22 March 2015
                2015
                : 15
                : 39
                Affiliations
                [ ]Department of Neurology, Taipei Medical University-Shuang Ho Hospital, New Taipei City, Taiwan
                [ ]Center for Evidence-Based Health Care, Taipei Medical University-Shuang Ho Hospital, New Taipei City, Taiwan
                [ ]Department of Physical Medicine and Rehabilitation, Taipei Medical University-Shuang Ho Hospital, New Taipei City, Taiwan
                [ ]Department of Gastroenterology, College of Medicine, Taipei Medical University, Taipei, Taiwan
                [ ]Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan
                [ ]Department of Gastroenterology, Taipei Medical University-Shuang Ho Hospital, New Taipei City, Taiwan
                [ ]College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan
                [ ]Department of Neurology, School of Medicine, Taipei Medical University, Taipei, Taiwan
                [ ]Department of Neurology, Neurological Institute, Taipei Veterans General Hospital, Taipei, Taiwan
                [ ]Department of Surgery, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
                [ ]Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
                [ ]Division of General Surgery, Department of Surgery, Taipei Medical University-Shuang Ho Hospital, Taipei, Taiwan
                [ ]Center for Evidence-Based Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
                [ ]Taipei Medical University-Shuang Ho Hospital, 291 Zhongzheng Road, Zhonghe District, New Taipei City, 23561 Taiwan
                Article
                301
                10.1186/s12883-015-0301-9
                4379590
                d3265508-3eb2-437e-863a-6fa64ee98651
                © Huang et al.; licensee BioMed Central. 2015

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 15 October 2014
                : 11 March 2015
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2015

                Neurology
                post-polio syndrome,intravenous immunoglobulin,fatigue,meta-analysis,muscle strength,quality of life

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