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Marshall B Elam - One of the best experts on this subject based on the ideXlab platform.
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patients experiencing statin induced Myalgia exhibit a unique program of skeletal muscle gene expression following statin re challenge
PLOS ONE, 2017Co-Authors: Marshall B Elam, Gipsy Majumdar, Khyobeni Mozhui, Ivan C Gerling, Santiago Vera, Hannah Fishtrotter, Robert W Williams, Richard D Childress, Rajendra RaghowAbstract:Statins, the 3-hydroxy-3-methyl-glutaryl (HMG)-CoA reductase inhibitors, are widely prescribed for treatment of hypercholesterolemia. Although statins are generally well tolerated, up to ten percent of statin-treated patients experience Myalgia symptoms, defined as muscle pain without elevated creatinine phosphokinase (CPK) levels. Myalgia is the most frequent reason for discontinuation of statin therapy. The mechanisms underlying statin Myalgia are not clearly understood. To elucidate changes in gene expression associated with statin Myalgia, we compared profiles of gene expression in skeletal muscle biopsies from patients with statin Myalgia who were undergoing statin re-challenge (cases) versus those of statin-tolerant controls. A robust separation of case and control cohorts was revealed by Principal Component Analysis of differentially expressed genes (DEGs). To identify putative gene expression and metabolic pathways that may be perturbed in skeletal muscles of patients with statin Myalgia, we subjected DEGs to Ingenuity Pathways (IPA) and DAVID (Database for Annotation, Visualization and Integrated Discovery) analyses. The most prominent pathways altered by statins included cellular stress, apoptosis, cell senescence and DNA repair (TP53, BARD1, Mre11 and RAD51); activation of pro-inflammatory immune response (CXCL12, CST5, POU2F1); protein catabolism, cholesterol biosynthesis, protein prenylation and RAS-GTPase activation (FDFT1, LSS, TP53, UBD, ATF2, H-ras). Based on these data we tentatively conclude that persistent Myalgia in response to statins may emanate from cellular stress underpinned by mechanisms of post-inflammatory repair and regeneration. We also posit that this subset of individuals is genetically predisposed to eliciting altered statin metabolism and/or increased end-organ susceptibility that lead to a range of statin-induced myopathies. This mechanistic scenario is further bolstered by the discovery that a number of single nucleotide polymorphisms (e.g., SLCO1B1, SLCO2B1 and RYR2) associated with statin Myalgia and myositis were observed with increased frequency among patients with statin Myalgia.
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clinical and laboratory phenotype of patients experiencing statin intolerance attributable to Myalgia
Journal of Clinical Lipidology, 2011Co-Authors: Leonard Jeff Harris, Marshall B Elam, Richard D Childress, Rashmi Thapa, Michael Brown, Sabitha Pabbathi, Murray Heimberg, Ron BradenAbstract:Background Muscle pain without elevation of serum creatine phosphokinase (CPK) (Myalgia) is the most common medication-related adverse effect of statin therapy; it occurs in up to 10% of patients who are prescribed statin therapy. Although much is known regarding risk factors for overt myositis, very few studies have provided information on this common form of statin intolerance. Methods We defined a detailed clinical and laboratory phenotype of a cohort of patients referred to the lipid clinic of a governmental health maintenance organization for statin intolerance attributable to muscle pain without CPK elevation (Myalgia) and characterized their response to alternative lipid-lowering therapy. Baseline and follow-up data were analyzed for 104 patients with statin intolerance attributable to Myalgia and 211 statin-tolerant control patients identified from the referral population. Results Among patients with Myalgia, more were white and had hypertension. The prevalence of known risk factors for overt myositis, including renal disease, type 2 diabetes mellitus, thyroid disease, and electrolyte abnormalities, did not differ between statin intolerant and statin tolerant patients. Although individual cases were identified in which the addition of interacting medications was temporally associated with development of statin intolerance, overall use of interacting medications was not more frequent among statin-intolerant patients. The majority of patients were intolerant of two or more statins; however, in more than one-half the cases, successful rechallenge with an alternative statin was accomplished. Despite this and extensive use of nonstatin lipid medications after lipid clinic referral, control of plasma lipoproteins remained significantly worse in statin-intolerant patients. Conclusions Statin intolerance attributable to Myalgia is a significant barrier to effective treatment of hyperlipidemia. Conventional clinical risk factors for myositis do not appear to predictive of statin-associated Myalgia. These findings underscore the need to better define the pathophysiology of statin-induced Myalgia and develop methodologies to guide treatment of statin-intolerant patients.
Björn Gerdle - One of the best experts on this subject based on the ideXlab platform.
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Protein Signature in Saliva of Temporomandibular Disorders Myalgia.
International Journal of Molecular Sciences, 2020Co-Authors: Hajer Jasim, Björn Gerdle, Malin Ernberg, Anders Carlsson, Bijar GhafouriAbstract:In the last years, several attempts have been made to study specific biological markers of temporomandibular disorders (TMD). So far, no laboratory tests have been appropriately validated for the diagnosis and prognosis of these disorders. This study aimed to investigate the proteomic profile of the whole stimulated saliva of TMD Myalgia patients in order to evaluate potential diagnostic and/or prognostic salivary candidate proteins which could be useful for the management of TMD. Twenty patients diagnosed with TMD Myalgia according to the validated Diagnostic Criteria for TMD (DC/TMD) and 20 matched healthy pain-free controls were enrolled. Saliva samples were collected in the morning. Comparative proteomic analysis was performed with two-dimensional gel electrophoresis followed by identification with liquid chromatography-tandem mass spectrometry. Statistical analysis of the quantitative proteomics data revealed that 20 proteins were significantly altered in patients compared to controls. Among these proteins, 12 showed significantly increased levels, and 8 showed significantly decreased levels in patients with TMD Myalgia compared to controls. The identified proteins are involved in metabolic processes, immune response, and stress response. This proteomic study shows that the salivary protein profile can discriminate patients with TMD Myalgia from healthy subjects, but the protein signature has no correlation with the clinical features of TMD Myalgia. Additional studies are needed to validate our observations in additional sample sets and to continue assessing the utility of saliva as a suitable sample for studying processes related to TMD Myalgia.
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algogenic substances and metabolic status in work related trapezius Myalgia a multivariate explorative study
BMC Musculoskeletal Disorders, 2014Co-Authors: Björn Gerdle, Jesper Kristiansen, Britt Larsson, Bengt Saltin, Karen Sogaard, Gisela SjogaardAbstract:Background: This study compares the levels of algesic substances between subjects with trapezius Myalgia (TM) and healthy controls (CON) and explores the multivariate correlation pattern between these substances, pain, and metabolic status together with relative blood flow changes reported in our previous paper (Eur J Appl Physiol 108:657–669, 2010). Methods: 43 female workers with (TM) and 19 females without (CON) trapezius Myalgia were – using microdialysis - compared for differences in interstitial concentrations of interleukin-6 (IL-6), bradykinin (BKN), serotonin (5-HT), lactate dehydrogenas (LDH), substance P, and N-terminal propeptide of procollagen type I (PINP) in the trapezius muscle at rest and during repetitive/stressful work. These data were also used in multivariate analyses together with previously presented data (Eur J Appl Physiol 108:657–669, 2010): trapezius muscle blood flow, metabolite accumulation, oxygenation, and pain development and sensitivity. Results: Substance P was significantly elevated in TM (p=0.0068). No significant differences were found in the classical algesic substances (p: 0.432-0.926). The multivariate analysis showed that blood flow related variables, interstitial concentrations of metabolic (pyruvate), and algesic (BKN and K + ) substances were important for the discrimination of the subjects to one of the two groups (R 2 : 0.19-0.31, p<0.05). Pain intensity was positively associated with levels of 5-HT and K + and negatively associated with oxygenation indicators and IL-6 in TM (R 2 : 0.24, p<0.05). A negative correlation existed in TM between mechanical pain sensitivity of trapezius and BKN and IL-6 (R 2 : 0.26-0.39, p<0.05). Conclusion: The present study increased understanding alterations in the myalgic muscle. When considering the system-wide aspects, increased concentrations of lactate, pyruvate and K + and decreased oxygenation characterized TM compared to CON. There are three major possible explanations for this finding: the workers with pain had relatively low severity of Myalgia, metabolic alterations preceded detectable alterations in levels of algesics, or peripheral sensitization and other muscle alterations existed in TM. Only SP of the investigated algesic substances was elevated in TM. Several of the algesics were of importance for the levels of pain intensity and mechanical pain sensitivity in TM. These results indicate peripheral contribution to maintenance of central nociceptive and pain mechanisms and may be important to consider when designing treatments.
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Comparative metabolomics of muscle interstitium fluid in human trapezius Myalgia: an in vivo microdialysis study
European Journal of Applied Physiology, 2013Co-Authors: J. Hadrévi, Björn Gerdle, B. Ghafouri, A. Sjörs, H. Antti, B. Larsson, A. G. Crenshaw, F. HellströmAbstract:Purpose The mechanisms behind trapezius Myalgia are unclear. Many hypotheses have been presented suggesting an altered metabolism in the muscle. Here, muscle microdialysate from healthy and myalgic muscle is analysed using metabolomics. Metabolomics analyse a vast number of metabolites, enabling a comprehensive explorative screening of the cellular processes in the muscle. Methods Microdialysate samples were obtained from the shoulder muscle of healthy and myalgic subjects that performed a work and stress test. Samples from the baseline period and from the recovery period were analysed using gas chromatography—mass spectrometry (GC–MS) together with multivariate analysis to detect differences in extracellular content of metabolites between groups. Systematic differences in metabolites between groups were identified using multivariate analysis and orthogonal partial least square discriminate analysis (OPLS-DA). A complementary Mann–Whitney U test of group difference in individual metabolites was also performed. Results A large number of metabolites were detected and identified in this screening study. At baseline, no systematic differences between groups were observed according to the OPLS-DA. However, two metabolites, l -leucine and pyroglutamic acid, were significantly more abundant in the myalgic muscle compared to the healthy muscle. In the recovery period, systematic difference in metabolites between the groups was observed according to the OPLS-DA. The groups differed in amino acids, fatty acids and carbohydrates. Myristic acid and putrescine were significantly more abundant and beta- d -glucopyranose was significantly less abundant in the myalgic muscle. Conclusion This study provides important information regarding the metabolite content, thereby presenting new clues regarding the pathophysiology of the myalgic muscle.
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Muscle performance, electromyography and fibre type composition in fibroMyalgia and work-related Myalgia.
Scandinavian Journal of Rheumatology, 2009Co-Authors: Jessica Elert, S. B. Rantapää-dahlqvist, Karin Henriksson-larsén, Ronny Lorentzon, Björn GerdleAbstract:Elert JE, Rantapaa-Dahlqvist SB, Henriksson-Larsen K, Lorentzon R, Gerdle BUC. Muscle Performance, Electromyography and Fibre Type Composition in FibroMyalgia and Work-related Myalgia. Scand J Rheumatol 1992; 21: 28–34.Muscle performance and fibre type composition were investigated in women with fibroMyalgia, work-related trapezius Myalgia and healthy volunteers. Each subject performed 100 repetitive shoulder flexions using an is kinetic dynamometer during simultaneous registration of surface electromyography. A biopsy from the trapezius muscle was obtained. The groups differed neither in mechanical performance nor in fibre type proportions. An inability to relax between contractions was found in all registered muscles in patients with fibroMyalgia. The patients with work-related Myalgia displayed an inability to relax only in the myalgic trapezius muscle. An inability to relax during repetitive movements might play an important role both in initiating and upholding muscle pain.
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blood supply and oxidative metabolism in muscle biopsies of female cleaners with and without Myalgia
The Clinical Journal of Pain, 2004Co-Authors: Britt Larsson, Fawzi Kadi, Jonas Bjork, Rolf Lindman, Björn GerdleAbstract:OBJECTIVES: Pathomechanisms of work-related Myalgia are poorly understood. Myalgia is thought to be caused by excitation of nociceptors present in the muscular tissue but not in the muscle fiber it ...
Larseric Thornell - One of the best experts on this subject based on the ideXlab platform.
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structural changes in male trapezius muscle with work related Myalgia
Acta Neuropathologica, 1998Co-Authors: Fawzi Kadi, G Hagg, R Hakansson, Staffan Holmner, Gillian Butlerbrowne, Larseric ThornellAbstract:Muscular changes in male forest machine operators with work-related neck and shoulder Myalgia were studied. Enzyme cyto- and immunohistochemical analysis was carried on muscle biopsies obtained from ten myalgic subjects (M), nine non-myalgic selected in the same work place (NM) and six healthy young men (C). The M group displayed a significant increase in type IIA fibres in comparison to the C group. This hypertrophy was accompanied by a parallel increase in the capillary bed. Both the M and NM groups exhibited an increase in fibres with a disorganised mitochondrial pattern. Interestingly, fibres lacking cytochrome c oxidase occurred in the M group (0.9%) but also in the NM group (0.5%), suggesting a mitochondrial defect. Central nuclei (5.2%) and developmental myosin (3%) were also more frequent in the M group. These changes are probably related to injury-regeneration cycles. These data support the association between the work conditions and muscle changes in work-related trapezius Myalgia.
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structural changes in male trapezius muscle with work related Myalgia
Acta Neuropathologica, 1998Co-Authors: Fawzi Kadi, G Hagg, R Hakansson, Staffan Holmner, Gillian Butlerbrowne, Larseric ThornellAbstract:Muscular changes in male forest machine operators with work-related neck and shoulder Myalgia were studied. Enzyme cyto- and immunohistochemical analysis was carried on muscle biopsies obtained from ten myalgic subjects (M), nine non-myalgic selected in the same work place (NM) and six healthy young men (C). The M group displayed a significant increase in type IIA fibres in comparison to the C group. This hypertrophy was accompanied by a parallel increase in the capillary bed. Both the M and NM groups exhibited an increase in fibres with a disorganised mitochondrial pattern. Interestingly, fibres lacking cytochrome c oxidase occurred in the M group (0.9%) but also in the NM group (0.5%), suggesting a mitochondrial defect. Central nuclei (5.2%) and developmental myosin (3%) were also more frequent in the M group. These changes are probably related to injury-regeneration cycles. These data support the association between the work conditions and muscle changes in work-related trapezius Myalgia.
Fawzi Kadi - One of the best experts on this subject based on the ideXlab platform.
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blood supply and oxidative metabolism in muscle biopsies of female cleaners with and without Myalgia
The Clinical Journal of Pain, 2004Co-Authors: Britt Larsson, Fawzi Kadi, Jonas Bjork, Rolf Lindman, Björn GerdleAbstract:OBJECTIVES: Pathomechanisms of work-related Myalgia are poorly understood. Myalgia is thought to be caused by excitation of nociceptors present in the muscular tissue but not in the muscle fiber it ...
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structural changes in male trapezius muscle with work related Myalgia
Acta Neuropathologica, 1998Co-Authors: Fawzi Kadi, G Hagg, R Hakansson, Staffan Holmner, Gillian Butlerbrowne, Larseric ThornellAbstract:Muscular changes in male forest machine operators with work-related neck and shoulder Myalgia were studied. Enzyme cyto- and immunohistochemical analysis was carried on muscle biopsies obtained from ten myalgic subjects (M), nine non-myalgic selected in the same work place (NM) and six healthy young men (C). The M group displayed a significant increase in type IIA fibres in comparison to the C group. This hypertrophy was accompanied by a parallel increase in the capillary bed. Both the M and NM groups exhibited an increase in fibres with a disorganised mitochondrial pattern. Interestingly, fibres lacking cytochrome c oxidase occurred in the M group (0.9%) but also in the NM group (0.5%), suggesting a mitochondrial defect. Central nuclei (5.2%) and developmental myosin (3%) were also more frequent in the M group. These changes are probably related to injury-regeneration cycles. These data support the association between the work conditions and muscle changes in work-related trapezius Myalgia.
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structural changes in male trapezius muscle with work related Myalgia
Acta Neuropathologica, 1998Co-Authors: Fawzi Kadi, G Hagg, R Hakansson, Staffan Holmner, Gillian Butlerbrowne, Larseric ThornellAbstract:Muscular changes in male forest machine operators with work-related neck and shoulder Myalgia were studied. Enzyme cyto- and immunohistochemical analysis was carried on muscle biopsies obtained from ten myalgic subjects (M), nine non-myalgic selected in the same work place (NM) and six healthy young men (C). The M group displayed a significant increase in type IIA fibres in comparison to the C group. This hypertrophy was accompanied by a parallel increase in the capillary bed. Both the M and NM groups exhibited an increase in fibres with a disorganised mitochondrial pattern. Interestingly, fibres lacking cytochrome c oxidase occurred in the M group (0.9%) but also in the NM group (0.5%), suggesting a mitochondrial defect. Central nuclei (5.2%) and developmental myosin (3%) were also more frequent in the M group. These changes are probably related to injury-regeneration cycles. These data support the association between the work conditions and muscle changes in work-related trapezius Myalgia.
Kees G Hovingh - One of the best experts on this subject based on the ideXlab platform.
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analysis of vitamin d levels in patients with and without statin associated Myalgia a systematic review and meta analysis of 7 studies with 2420 patients
International Journal of Cardiology, 2015Co-Authors: Marta Michalskakasiczak, Amirhossein Sahebkar, Dimitri P Mikhailidis, Jacek Rysz, Paul Muntner, Peter P Toth, Steven R Jones, Manfredi Rizzo, Kees G HovinghAbstract:article i nfo Introduction: VitaminD (vitD)deficiencymay beassociatedwith anincreased riskof statin-related symptomatic Myalgia in statin-treated patients. The aim of this meta-analysis was to substantiate the role of serum vitamin D levels in statin-associated Myalgia. Methods: The search included PUBMED, Cochrane Library, Scopus, and EMBASE from January 1, 1987 to April 1, 2014 to identify studies that investigated the impact of vit D levels in statin-treated subjects with and without Myalgia. Two independent reviewers extracted data on study characteristics, methods and outcomes. Quantita- tive data synthesis was performed using a fixed-effect model. Results: The electronic search yielded 437 articles; of those 20 were scrutinized as full texts and 13 studies were considered unsuitable. The final analysis included 7 studies with 2420 statin-treated patients divided into sub- groups of patients with (n = 666 (27.5%)) or without (n = 1754) Myalgia. Plasma vit D concentrations in the symptomatic and asymptomatic subgroups were 28.4 ± 13.80 ng/mL and 34.86 ± 11.63 ng/mL, respectively. ThecombinationofdatafromindividualobservationalstudiesshowedthatvitDplasmaconcentrationsweresig- nificantly lower in patients with statin-associated Myalgia compared with patients not manifesting this side ef- fect (weighted mean difference −9.41 ng/mL; 95% confidence interval: −10.17 to −8.64; p b 0.00001). Conclusions:Thismeta-analysis providesevidencethat low vit D levelsare associated with Myalgiainpatientson statin therapy. Randomized controlled trials are necessary to establish whether vitamin D supplementation re- duces the risk for statin-associated Myalgia.
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abstract 18967 analysis of vitamin d levels in patients with and without statin induced Myalgia a systematic review and meta analysis of 7 studies with 2416 patients
Circulation, 2014Co-Authors: Marta Michalskakasiczak, Amirhossein Sahebkar, Dimitri P Mikhailidis, Jacek Rysz, Paul Muntner, Peter P Toth, Steven R Jones, Manfredi Rizzo, Kees G Hovingh, Michel FarnierAbstract:Introduction: Vitamin D (vit D) deficiency may be associated with an increased risk of statin-related muscle complaints, and symptomatic Myalgia in statin-treated patients. Hypothesis: The aim of this meta-analysis was to investigate whether subjects with statin-induced Myalgia have lower serum vit D levels compared with those who are asymptomatic. Methods: We searched PubMed, Web of Science, Cochrane Library, Scopus and EMBASE (up to March 2014) to identify studies that investigated the impact of vit D levels in statin-treated subjects with and without Myalgia. Two independent reviewers extracted data on study characteristics, methods and outcomes. Results: The electronic search yielded 437 articles, of those 20 were scrutinized in the full text, of which 13 studies were considered unsuitable. The final analysis included 7 studies with 2416 statin-treated patients divided to subgroups of patients with (n = 666 [27.6%]) or without (n = 1750) Myalgia. The combination of data from individual observational studies revealed a significantly lower vit D plasma concentration in the statin-induced Myalgia compared with the asymptomatic subgroup with weighted mean difference -9.41 ng/mL(95% confidence interval (Cl): -10.17 to -8.64; p (figure) . Conclusions: This meta-analysis provides evidence that low vit D levels are associated with Myalgia in patients on statin therapy. Well-designed, randomized controlled trials are necessary to establish whether vitamin D supplementation reduces risk for statin Myalgia in patients with vitamin D deficiency.
