Stepwise approach to myopathy in systemic disease.

PubMed

Chawla, Jasvinder

2011-01-01

Muscle diseases can constitute a large variety of both acquired and hereditary disorders. Myopathies in systemic disease results from several different disease processes including endocrine, inflammatory, paraneoplastic, infectious, drug- and toxin-induced, critical illness myopathy, metabolic, and myopathies with other systemic disorders. Patients with systemic myopathies often present acutely or sub acutely. On the other hand, familial myopathies or dystrophies generally present in a chronic fashion with exceptions of metabolic myopathies where symptoms on occasion can be precipitated acutely. Most of the inflammatory myopathies can have a chance association with malignant lesions; the incidence appears to be specifically increased only in patients with dermatomyositis. In dealing with myopathies associated with systemic illnesses, the focus will be on the acquired causes. Management is beyond the scope of this chapter. Prognosis is based upon the underlying cause and, most of the time, carries a good prognosis. In order to approach a patient with suspected myopathy from systemic disease, a stepwise approach is utilized.

Centronuclear myopathy related to dynamin 2 mutations: Clinical, morphological, muscle imaging and genetic features of an Italian cohort

PubMed Central

Catteruccia, Michela; Fattori, Fabiana; Codemo, Valentina; Ruggiero, Lucia; Maggi, Lorenzo; Tasca, Giorgio; Fiorillo, Chiara; Pane, Marika; Berardinelli, Angela; Verardo, Margherita; Bragato, Cinzia; Mora, Marina; Morandi, Lucia; Bruno, Claudio; Santoro, Lucio; Pegoraro, Elena; Mercuri, Eugenio; Bertini, Enrico; D’Amico, Adele

2013-01-01

Mutations in dynamin 2 (DNM2) gene cause autosomal dominant centronuclear myopathy and occur in around 50% of patients with centronuclear myopathy. We report clinical, morphological, muscle imaging and genetic data of 10 unrelated Italian patients with centronuclear myopathy related to DNM2 mutations. Our results confirm the clinical heterogeneity of this disease, underlining some peculiar clinical features, such as severe pulmonary impairment and jaw contracture that should be considered in the clinical follow-up of these patients. Muscle MRI showed a distinct pattern of involvement, with predominant involvement of soleus and tibialis anterior in the lower leg muscles, followed by hamstring muscles and adductor magnus at thigh level and gluteus maximus. The detection of three novel DNM2 mutations and the first case of somatic mosaicism further expand the genetic spectrum of the disease. PMID:23394783

[Critical illness polyneuropathy and myopathy].

PubMed

Motomura, Masakatsu

2003-11-01

Critical Illness Polyneuropathy (CIP) and Myopathy (CIM), either singly or in combination, are a common complication of critical illness. Both disorders may lead to severe weakness and require mechanical ventilation. CIP, as initially described by Bolton et al., in 1984, is a sensorimotor polyneuropathy that is often a complication of sepsis and multiorgan failure. In Japan, Horinouchi et al., first reported a case in 1994. CIM has been referred to by a number of different terms (acute quadriplegic myopathy, thick filament myopathy, acute necrotizing myopathy of intensive care, rapidly evolving myopathy with myosin-deficiency fibers) in the literature. A variety of serious problems (e.g., pneumonia, severe asthma, and lung or liver transplantation) and the concomitant use of high-dose intravenous corticosteroids and nondepolarizing neuromuscular blocking agents predispose to CIM. In Japan, Kawada et al., reported a first case as acute quadriplegic myopathy in 2000. There is no specific treatment for CIP and CIM. Minimizing the use of corticosteroids and nondepolarizing neuromuscular blocking agents in a critical illness setting may prove helpful in preventing the occurrence of these disorders. The prognosis is directly related to the age of the patient and the seriousness of the underlying illness.

Crotalidae polyvalent immune Fab antivenom limits the decrease in perfusion pressure of the anterior leg compartment in a porcine crotaline envenomation model.

PubMed

Tanen, David A; Danish, David C; Clark, Richard F

2003-03-01

Crotalidae Polyvalent Immune Fab (CroFab; FabAV) antivenom prevents a decrease in perfusion pressures in intramuscular crotaline envenomation compared with normal saline solution. We used a randomized, blinded, controlled acute animal preparation. Twenty anesthetized and instrumented swine were injected intramuscularly with 6 mg/kg Crotalus atrox venom into the anterior tibialis muscle of each hind limb (time 0). One hour after envenomation (time 1 hour), animals were randomized to receive 8 vials of reconstituted FabAV or an equal volume of normal saline solution (control) through a central venous line. The main outcome variable was the area under the perfusion-time curve (AUC) of the anterior compartment of the hind limb measured from time 1 hour to time 8 hours. Perfusion pressure was defined as mean arterial pressure-compartment pressure. Additionally, physiologic variables, including pulse rate, prothrombin time, fibrinogen level, platelet count, hemoglobin level, and hematocrit level, were monitored. Venom injection resulted in a decrease in average perfusion pressures from 54.1 mm Hg (time 0) to 31.7 mm Hg (time 1 hour). Comparison of AUC between groups from time 1 hour (time of treatment) to the completion of the study at time 8 hours revealed a 57% greater AUC in animals that received FabAV (mean+/-SD: 211.1+/-67.9 versus 134.5+/-55.8 mm Hg/h; P =.036; 95% confidence interval for difference 5.9 to 147.3). Comparison of the time curves for the mean prothrombin time from time 1 hour to the completion of the study by means of repeated-measures analysis of variance revealed a significant increase in the control group (P =.02). No significant difference was detected in the time curves for the means of mean arterial pressure, compartment pressure, pulse rate, hemoglobin level, hematocrit level, fibrinogen level, or platelet count over the course of the study. FabAV was found to significantly increase survival time when compared with the effect of the normal

Intravital multiphoton imaging of mouse tibialis anterior muscle

PubMed Central

Lau, Jasmine; Goh, Chi Ching; Devi, Sapna; Keeble, Jo; See, Peter; Ginhoux, Florent; Ng, Lai Guan

2016-01-01

ABSTRACT Intravital imaging by multiphoton microscopy is a powerful tool to gain invaluable insight into tissue biology and function. Here, we provide a step-by-step tissue preparation protocol for imaging the mouse tibialis anterior skeletal muscle. Additionally, we include steps for jugular vein catheterization that allow for well-controlled intravenous reagent delivery. Preparation of the tibialis anterior muscle is minimally invasive, reducing the chances of inducing damage and inflammation prior to imaging. The tibialis anterior muscle is useful for imaging leukocyte interaction with vascular endothelium, and to understand muscle contraction biology. Importantly, this model can be easily adapted to study neuromuscular diseases and myopathies. PMID:28243520

A novel mutation in PNPLA2 causes neutral lipid storage disease with myopathy and triglyceride deposit cardiomyovasculopathy: a case report and literature review.

PubMed

Kaneko, Kimihiko; Kuroda, Hiroshi; Izumi, Rumiko; Tateyama, Maki; Kato, Masaaki; Sugimura, Koichiro; Sakata, Yasuhiko; Ikeda, Yoshihiko; Hirano, Ken-Ichi; Aoki, Masashi

2014-07-01

Mutations in PNPLA2 cause neutral lipid storage disease with myopathy (NLSDM) or triglyceride deposit cardiomyovasculopathy (TGCV). We report a 59-year-old patient with NLSDM/TGCV presenting marked asymmetric skeletal myopathy and cardiomyovasculopathy. Skeletal muscle and endomyocardial biopsies showed cytoplasmic vacuoles containing neutral lipid. Gene analysis revealed a novel homozygous mutation (c.576delC) in PNPLA2. We reviewed 37 genetically-proven NLSDM/TGCV cases; median age was 30 years; distribution of myopathy was proximal (69%) and distal predominant (16%); asymmetric myopathy (right>left) was reported in 41% of the patients. Frequently-affected muscles were posterior compartment of leg (75%), shoulder girdle to upper arm (50%), and paraspinal (33%). Skeletal muscle biopsies showed lipid accumulation in 100% and rimmed vacuoles in 22%. Frequent comorbidities were cardiomyopathy (44%), hyperlipidemia (23%), diabetes mellitus (24%), and pancreatitis (14%). PNPLA2 mutations concentrated in Exon 4-7 without apparent genotype-phenotype correlations. To know the characteristic features is essential for the early diagnosis of NLSDM/TGCV. Copyright © 2014 Elsevier B.V. All rights reserved.

[Descending ocular myopathy].

PubMed

de Freitas, M R; Nascimento, O J

1975-06-01

The case of a 23 years old female patient, with primary involvement of the extraocular and faringeal muscles without familiar history is reported. Electromyographic and muscular biopsy studies proved the myogenic nature of the process. A clinical comparison between the ocular myopathy and the descending ocular myopathy is made, the authors thinking that both of them would be variants of the same muscle disease.

A human cadaver fascial compartment pressure measurement model.

PubMed

Messina, Frank C; Cooper, Dylan; Huffman, Gretchen; Bartkus, Edward; Wilbur, Lee

2013-10-01

Fresh human cadavers provide an effective model for procedural training. Currently, there are no realistic models to teach fascial compartment pressure measurement. We created a human cadaver fascial compartment pressure measurement model and studied its feasibility with a pre-post design. Three faculty members, following instructions from a common procedure textbook, used a standard handheld intra-compartment pressure monitor (Stryker(®), Kalamazoo, MI) to measure baseline pressures ("unembalmed") in the anterior, lateral, deep posterior, and superficial posterior compartments of the lower legs of a fresh human cadaver. The right femoral artery was then identified by superficial dissection, cannulated distally towards the lower leg, and connected to a standard embalming machine. After a 5-min infusion, the same three faculty members re-measured pressures ("embalmed") of the same compartments on the cannulated right leg. Unembalmed and embalmed readings for each compartment, and baseline readings for each leg, were compared using a two-sided paired t-test. The mean baseline compartment pressures did not differ between the right and left legs. Using the embalming machine, compartment pressure readings increased significantly over baseline for three of four fascial compartments; all in mm Hg (±SD): anterior from 40 (±9) to 143 (±44) (p = 0.08); lateral from 22 (±2.5) to 160 (±4.3) (p < 0.01); deep posterior from 34 (±7.9) to 161 (±15) (p < 0.01); superficial posterior from 33 (±0) to 140 (±13) (p < 0.01). We created a novel and measurable fascial compartment pressure measurement model in a fresh human cadaver using a standard embalming machine. Set-up is minimal and the model can be incorporated into teaching curricula. Copyright © 2013 Elsevier Inc. All rights reserved.

Gait Mechanics in Those With/Without Medial Compartment Knee Osteoarthritis 5 Years After Anterior Cruciate Ligament Reconstruction

PubMed Central

Khandha, Ashutosh; Manal, Kurt; Wellsandt, Elizabeth; Capin, Jacob; Snyder-Mackler, Lynn; Buchanan, Thomas S.

2016-01-01

The objective of the study was to evaluate differences in gait mechanics 5 years after unilateral anterior cruciate ligament reconstruction surgery, for non-osteoarthritic (n = 24) versus osteoarthritic (n = 9) subjects. For the involved knee, the osteoarthritic group demonstrated significantly lower peak knee flexion angles (non-osteoarthritic = 24.3 ± 4.6°, osteoarthritic = 19.1 ± 2.9°, p = 0.01) and peak knee flexion moments (non-osteoarthritic = 5.3 ± 1.2% Body Weight × Height, osteoarthritic = 4.4 ± 1.2% Body Weight × Height, p = 0.05). Differences in peak knee adduction moment approached significance, with a higher magnitude for the osteoarthritic group (non-osteoarthritic = 2.4 ±0.8% Body Weight × Height, osteoarthritic = 2.9 ± 0.5% Body Weight × Height, p = 0.09). Peak medial compartment joint load was evaluated using electromyography-informed neuromusculoskeletal modeling. Peak medial compartment joint load in the involved knee for the two groups was not different (non-osteoarthritic = 2.4 ± 0.4 Body Weight, osteoarthritic = 2.3 ± 0.6 Body Weight). The results suggest that subjects with dissimilar peak knee moments can have similar peak medial compartment joint load magnitudes. There was no evidence of inter-limb asymmetry for either group. Given the presence of inter-group differences (non-osteoarthritic vs. osteoarthritic) for the involved knee, but an absence of inter-limb asymmetry in either group, it may be necessary to evaluate how symmetry is achieved, over time, and to differentiate between good versus bad inter-limb symmetry, when evaluating knee gait parameters. PMID:27082166

Genetics Home Reference: X-linked myotubular myopathy

MedlinePlus

... Twitter Home Health Conditions X-linked myotubular myopathy X-linked myotubular myopathy Printable PDF Open All Close ... Javascript to view the expand/collapse boxes. Description X-linked myotubular myopathy is a condition that primarily ...

Hereditary myopathies with early respiratory insufficiency in adults.

PubMed

Naddaf, Elie; Milone, Margherita

2017-11-01

Hereditary myopathies with early respiratory insufficiency as a predominant feature of the clinical phenotype are uncommon and underestimated in adults. We reviewed the clinical and laboratory data of patients with hereditary myopathies who demonstrated early respiratory insufficiency before the need for ambulatory assistance. Only patients with disease-causing mutations or a specific histopathological diagnosis were included. Patients with cardiomyopathy were excluded. We identified 22 patients; half had isolated respiratory symptoms at onset. The diagnosis of the myopathy was often delayed, resulting in delayed ventilatory support. The most common myopathies were adult-onset Pompe disease, myofibrillar myopathy, multi-minicore disease, and myotonic dystrophy type 1. Single cases of laminopathy, MELAS (mitochondrial encephalomyopathy with lactic acidosis and strokelike events), centronuclear myopathy, and cytoplasmic body myopathy were identified. We highlighted the most common hereditary myopathies associated with early respiratory insufficiency as the predominant clinical feature, and underscored the importance of a timely diagnosis for patient care. Muscle Nerve 56: 881-886, 2017. © 2017 Wiley Periodicals, Inc.

Localized scleroderma and regional inflammatory myopathy.

PubMed

Zivković, Saša A; Freiberg, William; Lacomis, David; Domsic, Robyn T; Medsger, Thomas A

2014-05-01

Inflammatory myopathy is rare in localized scleroderma. We report 2 new cases of regional inflammatory myopathy associated with localized scleroderma and review 10 reported cases of localized scleroderma associated with an inflammatory myopathy with regional muscle involvement, more often in the upper extremities. Serum creatine kinase was mildly elevated or normal. Histopathology often showed perimysial inflammation and plasma cell infiltration. These cases demonstrate that inflammatory myopathy should be considered in patients with localized scleroderma and regional muscle weakness, pain or atrophy. Muscle biopsy can confirm the diagnosis of myositis, which if identified, will require anti-inflammatory and/or immunosuppressive therapy. Published by Elsevier B.V.

Mitochondrial myopathies.

PubMed

DiMauro, Salvatore

2006-11-01

Our understanding of mitochondrial diseases (defined restrictively as defects of the mitochondrial respiratory chain) is expanding rapidly. In this review, I will give the latest information on disorders affecting predominantly or exclusively skeletal muscle. The most recently described mitochondrial myopathies are due to defects in nuclear DNA, including coenzyme Q10 deficiency and mutations in genes controlling mitochondrial DNA abundance and structure, such as POLG, TK2, and MPV17. Barth syndrome, an X-linked recessive mitochondrial myopathy/cardiopathy, is associated with decreased amount and altered structure of cardiolipin, the main phospholipid of the inner mitochondrial membrane, but a secondary impairment of respiratory chain function is plausible. The role of mutations in protein-coding genes of mitochondrial DNA in causing isolated myopathies has been confirmed. Mutations in tRNA genes of mitochondrial DNA can also cause predominantly myopathic syndromes and--contrary to conventional wisdom--these mutations can be homoplasmic. Defects in the mitochondrial respiratory chain impair energy production and almost invariably involve skeletal muscle, causing exercise intolerance, cramps, recurrent myoglobinuria, or fixed weakness, which often affects extraocular muscles and results in droopy eyelids (ptosis) and progressive external ophthalmoplegia.

Calf heads on a trophy sign: Miyoshi myopathy.

PubMed

Shyma, M Mundayadan; Roopchand, P Sreedharan; Ram, K Mohan; Shaji, C Velayudhan

2015-01-01

Miyoshi myopathy is an autosomal recessive distal myopathy with predominant involvement of the posterior calf muscles attributed to mutations in the dysferlin gene. We report a 26-year-old male, born of nonconsanginous parentage. He noticed weakness and atrophy of leg muscles with inability to walk on his heels. The creatine kinase concentration was high. The electromyography showed myopathic pattern and the muscle biopsy disclosed dystrophic changes with absence of dysferlin. Miyoshi myopathy may be distinct among the hereditary distal myopathies. There are only few reported cases of Miyoshi myopathy in the world literature. In India only 12 cases were reported who had classical features of Miyoshi myopathy. Our's is a typical case of Miyoshi myopathy, with an affected twin sister as well. He also had "calf heads on a trophy sign" on physical examination, which is considered to be pathognomonic of this disease.

Calf heads on a trophy sign: Miyoshi myopathy

PubMed Central

Shyma, M. Mundayadan; Roopchand, P. Sreedharan; Ram, K. Mohan; Shaji, C. Velayudhan

2015-01-01

Miyoshi myopathy is an autosomal recessive distal myopathy with predominant involvement of the posterior calf muscles attributed to mutations in the dysferlin gene. We report a 26-year-old male, born of nonconsanginous parentage. He noticed weakness and atrophy of leg muscles with inability to walk on his heels. The creatine kinase concentration was high. The electromyography showed myopathic pattern and the muscle biopsy disclosed dystrophic changes with absence of dysferlin. Miyoshi myopathy may be distinct among the hereditary distal myopathies. There are only few reported cases of Miyoshi myopathy in the world literature. In India only 12 cases were reported who had classical features of Miyoshi myopathy. Our's is a typical case of Miyoshi myopathy, with an affected twin sister as well. He also had “calf heads on a trophy sign” on physical examination, which is considered to be pathognomonic of this disease. PMID:26167036

Proton Pump Inhibitors: Risk for Myopathy?

PubMed

Colmenares, Evan W; Pappas, Ashley L

2017-01-01

The purpose of this article is to describe the relationship between proton pump inhibitors (PPIs) and symptoms of myopathy based on case reports. A literature search was conducted in PubMed (1946 to June 2016) using MeSH terms proton pump inhibitors, omeprazole, esomeprazole, lansoprazole, dexlansoprazole, rabeprazole, pantoprazole, and muscular diseases. Additionally, a search was conducted in ToxNet and EMBASE using similar search criteria. The resulting articles were scanned to assess relevance to the review. Bibliographies of all relevant articles were evaluated for additional sources; 26 articles resulted from the search of PubMed, ToxNet, and EMBASE; articles that involved medications typically considered to have myalgia-like side effects (eg, statins), or included patients who presented with a confounding disease state (eg, Guillain-Barré) were excluded. In total, 11 case reports as well as a review of an adverse event reporting database that included 292 cases were evaluated. Association of PPI use and myopathy symptoms does not have a clear etiology. Overall, the available published data do not show a high risk of myopathy with PPI use but should be considered if a patient presents with myopathy symptoms and concurrent PPI use. A limited body of published data suggests that PPI use has been associated with myopathy-like symptoms without long-term effects following discontinuation. Although myopathy is a rare adverse effect observed with PPIs, it can be a serious side effect to be considered when starting a patient on acid suppression therapy.

Improved Arthroscopic Visualization of Peripheral Compartment

PubMed Central

Suslak, Adam G.; Mather, Richard C.; Kelly, Bryan T.; Nho, Shane J.

2012-01-01

Femoroacetabular impingement is a recognized cause of hip pain and motion restrictions. Advancements in hip arthroscopy have allowed surgeons the ability to treat this condition more effectively. However, the learning curve is steep for osteochondroplasty of the femoral head-neck junction in the peripheral compartment. Therefore we present a reproducible technique that allows improved visualization of the peripheral compartment and treatment of the cam lesion with hip arthroscopy. Our technique uses the anterior portal as a viewing portal, a distal anterolateral accessory portal as a working portal, and the anterolateral portal for soft-tissue retraction. PMID:23766977

Hypothyroid myopathy: A peculiar clinical presentation of thyroid failure. Review of the literature.

PubMed

Sindoni, Alessandro; Rodolico, Carmelo; Pappalardo, Maria Angela; Portaro, Simona; Benvenga, Salvatore

2016-12-01

Abnormalities in thyroid function are common endocrine disorders that affect 5-10 % of the general population, with hypothyroidism occurring more frequently than hyperthyroidism. Clinical symptoms and signs are often nonspecific, particularly in hypothyroidism. Muscular symptoms (stiffness, myalgias, cramps, easy fatigability) are mentioned by the majority of patients with frank hypothyroidism. Often underestimated is the fact that muscle symptoms may represent the predominant or the only clinical manifestation of hypothyroidism, raising the issue of a differential diagnosis with other causes of myopathy, which sometimes can be difficult. Elevated serum creatine kinase, which not necessarily correlates with the severity of the myopathic symptoms, is certainly suggestive of muscle impairment, though it does not explain the cause. Rare muscular manifestations, associated with hypothyroidism, are rhabdomyolysis, acute compartment syndrome, Hoffman's syndrome and Kocher-Debré-Sémélaigne syndrome. Though the pathogenesis of hypothyroid myopathy is not entirely known, proposed mechanisms include altered glycogenolytic and oxidative metabolism, altered expression of contractile proteins, and neuro-mediated damage. Correlation studies of haplotype, muscle gene expression and protein characterization, could help understanding the pathophysiological mechanisms of this myopathic presentation of hypothyroidism.

Bethlem myopathy: An autosomal dominant myopathy with flexion contractures, keloids, and follicular hyperkeratosis.

PubMed

Saroja, Aralikatte Onkarappa; Naik, Karkal Ravishankar; Nalini, Atcharayam; Gayathri, Narayanappa

2013-10-01

Bethlem myopathy and Ullrich congenital muscular dystrophy form a spectrum of collagenopathies caused by genetic mutations encoding for any of the three subunits of collagen VI. Bethlem phenotype is relatively benign and is characterized by proximal dominant myopathy, keloids, contractures, distal hyperextensibility, and follicular hyperkeratosis. Three patients from a single family were diagnosed to have Bethlem myopathy based on European Neuromuscular Centre Bethlem Consortium criteria. Affected father and his both sons had slowly progressive proximal dominant weakness and recurrent falls from the first decade. Both children aged 18 and 20 years were ambulant at presentation. All had flexion contractures, keloids, and follicular hyperkeratosis without muscle hypertrophy. Creatinine kinase was mildly elevated and electromyography revealed myopathic features. Muscle imaging revealed severe involvement of glutei and vasti with "central shadow" in rectus femoris. Muscle biopsy in the father showed dystrophic changes with normal immmunostaining for collagen VI, sarcoglycans, and dysferlin.

Polyneuropathy and myopathy in beta-thalassemia major patients.

PubMed

Nemtsas, P; Arnaoutoglou, M; Perifanis, V; Koutsouraki, E; Spanos, G; Arnaoutoglou, N; Chalkia, P; Pantelidou, D; Orologas, A

2018-05-01

The thalassemias are the most common single gene disorder in the world. Nowadays, the average life expectancy of patients in developed countries has increased significantly, while, there was an increase of complications. We aimed to investigate peripheral neuropathy and myopathy in this patient group using a neurophysiological study. We performed nerve conduction studies and electromyography of upper and lower extremities on 36 beta-thalassemia major (β-thal) patients. The electrophysiological findings were correlated with demographic data and laboratory parameters of the disease. Patients with β-thal present polyneuropathy or myopathy at (50%). Polyneuropathy was detected in (38.9%) and myopathy in (27.8%), while polyneuropathy and myopathy were present at (16.7%) with an overlap of the diseases in 1/3 of the patients. There was not a statistically significant correlation of polyneuropathy and myopathy with age, sex, splenectomy, nor with respect to laboratory parameters, hemoglobin, and ferritin. However, there was a statistically significant correlation of polyneuropathy and myopathy with iron overload, as recorded by the magnetic resonance imaging (MRI) of the heart and the liver. Our findings suggest that iron overload plays a key role in the pathogenesis of polyneuropathy and myopathy in β-thal patients, and performing heart and liver MRI for the prediction of such lesions in an annual basis is warranted.

A study of nutritional myopathy in weaner sheep.

PubMed

Allen, J G; Steele, P; Masters, H G; D'Antuono, M F

1986-01-01

The effectiveness of various treatments upon, and pathological and biochemical changes in, ovine weaner nutritional myopathy were observed. Clinical myopathy was already apparent in the sheep at the start of the study, and they were fed decreasing amounts of a ration containing low levels of selenium and alpha-tocopherol, and periodically deprived of water. In spite of this management there was a spontaneous remission of the clinical myopathy in the sheep, but a subclinical myopathy was identified in some of the sheep at the end of the trail. The conclusions were that the myopathy was not caused by a low dietary intake of selenium and/or alpha-tocopherol alone, that alpha-tocopherol was involved in the aetiology, that alpha-tocopherol was completely effective and selenium possibly partially effective in treating it, and that the condition may be a Type II muscle fibre disease. Data on plasma creatine phosphokinase and erythrocyte glutathione peroxidase activities, and terminal liver selenium and alpha-tocopherol concentrations are presented, and their roles in the diagnosis of ovine weaner nutritional myopathy discussed.

Idiopathic inflammatory myopathies overlapping with systemic diseases

PubMed Central

Lepreux, Sébastien; Hainfellner, Johannes A.; Vital, Anne

2018-01-01

A muscle biopsy is currently requested to assess the diagnosis of an idiopathic inflammatory myopathy overlapping with a systemic disease. During the past few years, the classification of inflammatory myopathy subtypes has been revisited progressively on the basis of correlations between clinical phenotypes, autoantibodies and histological data. Several syndromic entities are now more clearly defined, and the aim of the present review is to clarify the contribution of muscle biopsy in a setting of idiopathic inflammatory myopathies overlapping with systemic diseases. PMID:29154752

Critical illness polyneuropathy and myopathy: a systematic review

PubMed Central

Zhou, Chunkui; Wu, Limin; Ni, Fengming; Ji, Wei; Wu, Jiang; Zhang, Hongliang

2014-01-01

Critical illness polyneuropathy and critical illness myopathy are frequent complications of severe illness that involve sensorimotor axons and skeletal muscles, respectively. Clinically, they manifest as limb and respiratory muscle weakness. Critical illness polyneuropathy/myopathy in isolation or combination increases intensive care unit morbidity via the inability or difficulty in weaning these patients off mechanical ventilation. Many patients continue to suffer from decreased exercise capacity and compromised quality of life for months to years after the acute event. Substantial progress has been made lately in the understanding of the pathophysiology of critical illness polyneuropathy and myopathy. Clinical and ancillary test results should be carefully interpreted to differentiate critical illness polyneuropathy/myopathy from similar weaknesses in this patient population. The present review is aimed at providing the latest knowledge concerning the pathophysiology of critical illness polyneuropathy/myopathy along with relevant clinical, diagnostic, differentiating, and treatment information for this debilitating neurological disease. PMID:25206749

Idiopathic Inflammatory Myopathies

PubMed Central

Barohn, Richard J.; Amato, Anthony

2014-01-01

The idiopathic inflammatory myopathies (IIM) consist of rare heterogenous autoimmune disorders that present with marked proximal and symmetric muscle weakness, except for distal and asymmetric weakness in inclusion body myositis (IBM). Besides frequent creatine kinase (CK) elevation, the electromyogram confirms the presence of an irritative myopathy. Extramuscular involvement affects a significant number of cases with interstitial lung disease (ILD), cutaneous in dermatomyositis (DM), systemic or joint manifestations and increased risk of malignancy especially in DM. Myositis specific autoantibodies influence phenotype of the IIM. Jo-1 antibodies are frequently associated with ILD and the newly described HMG-CoA reductase antibodies are characteristic of autoimmune necrotizing myopathy (NM). Muscle pathology ranges from inflammatory exudates of variable distribution, to intact muscle fiber invasion, necrosis, phagocytosis and in the case of IBM rimmed vacuoles and protein deposits. Despite many similarities, the IIM are a quite heterogeneous from the histopathological and pathogenetic standpoints in addition to some clinical and treatment-response difference. The field has witnessed significant advances in our understanding of pathophysiology and treatment of these rare disorders. In this review, we focus on DM, polymyositis (PM) and NM and examine current and promising therapies. The reader interested in more details on IBM is referred to the corresponding chapter in this issue. PMID:25037081

[Minimally invasive fasciotomy in the treatment of chronic exertional anterior compartment syndrome of the leg: personal technique].

PubMed

Bramante, Carmelo; Gandolfo, Luigi; Bosco, Vincenzo

2008-01-01

Numerous fasciotomy techniques have been proposed for the treatment of chronic exertional anterior compartment syndrome. In this work we evaluate the efficacy of a personal surgical technique whereby the fasciotomy is performed through a small cutaneous incision using endo mini-shears. From 2004 to 2006 19 patients, all professional skaters, were submitted to bilateral fasciotomy (38 legs). No complications were observed. Only two patients used pain-killers. In the follow-up (12 months), resumption of competitive activity was achieved by the fourth week in 63.2% of cases (12 patients), by the fifth week in 26.3% (5 patients), and by the sixth week in 10.5% (2 patients). All patients achieved sporting performance comparable to that present before the onset of symptoms. There were no recurrences. This technique is relatively simple to perform, is easily repeatable, does not require a long learning curve, is practically complication-free, and is characterised by a virtually painless postoperative course.

Myotilinopathy in a family with late onset myopathy.

PubMed

Pénisson-Besnier, Isabelle; Talvinen, Kati; Dumez, Catherine; Vihola, Anna; Dubas, Frédéric; Fardeau, Michel; Hackman, Peter; Carpen, Olli; Udd, Bjarne

2006-07-01

Mutations in titin are well known cause of late onset autosomal dominant distal myopathy. Mutations in another sarcomeric protein, myotilin, were first identified in two families with dominant limb girdle muscular phenotype. Recently, however, myotilin mutations have been associated with more distal phenotypes in patients with late onset myofibrillar myopathy. We report here a multigenerational French family in which gene sequencing identified a S60F myotilin mutation in all patients with full penetrance despite very late onset. The family was originally reported as a distal myopathy but intrafamilial variability was remarkable with proximal or distal muscle weakness or both. Extended morphological characteristics of muscle biopsy findings in myotilinopathy indicate that immunohistochemistry may be important for selection of molecular genetic approach in myofibrillar myopathy.

Adeno-Associated Virus–Mediated Gene Therapy for Metabolic Myopathy

PubMed Central

Mah, Cathryn S.; Soustek, Meghan S.; Todd, A. Gary; McCall, Angela; Smith, Barbara K.; Corti, Manuela; Falk, Darin J.

2013-01-01

Abstract Metabolic myopathies are a diverse group of rare diseases in which impaired breakdown of stored energy leads to profound muscle dysfunction ranging from exercise intolerance to severe muscle wasting. Metabolic myopathies are largely caused by functional deficiency of a single gene and are generally subcategorized into three major types of metabolic disease: mitochondrial, lipid, or glycogen. Treatment varies greatly depending on the biochemical nature of the disease, and unfortunately no definitive treatments exist for metabolic myopathy. Since this group of diseases is inherited, gene therapy is being explored as an approach to personalized medical treatment. Adeno-associated virus–based vectors in particular have shown to be promising in the treatment of several forms of metabolic myopathy. This review will discuss the most recent advances in gene therapy efforts for the treatment of metabolic myopathies. PMID:24164240

Statin-associated immune-mediated myopathy: biology and clinical implications.

PubMed

Christopher-Stine, Lisa; Basharat, Pari

2017-04-01

In the last 6 years, our understanding of statin-associated myopathy expanded to include not only a toxic myopathy with limited and reversible side-effects but also an autoimmune variety in which statins likely induce an autoimmune myopathy that is both associated with a specific autoantibody and responsive to immunosuppression and immune modulation. This review widens the reader's understanding of statin myopathy to include an autoimmune process. Statin-associated immune-mediated myopathy provides an example of an environmental trigger (statins) directly implicated in an autoimmune disease associated with a genetic predisposition as well as potential risk factors including concomitant diseases and specific statins. Given a median exposure to statins of 38 months, providers should be aware that anti-3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMGCR) myopathy may occur even after several years of statin exposure. It is important for the reader to understand the clinical presentation of statin-associated immune-mediated myopathy and the difference in its clinical presentation to that of statins as direct myotoxins. Prompt recognition of such an entity allows the clinician to immediately stop the offending agent if it has not already been discontinued as well as to recognize that statin rechallenge is not a likely option, and that prompt treatment with immunosuppression and/or immunomodulation is usually of enormous benefit to the patient in restoring muscle strength and physical function. VIDEO ABSTRACT.

Risk of Febuxostat-Associated Myopathy in Patients with CKD

PubMed Central

Liu, Chung-te; Chen, Chun-You; Hsu, Chien-Yi; Lin, Feng-Yen; Chen, Jaw-Wen; Lin, Shing-Jong

2017-01-01

Background and objectives Febuxostat, a nonpurine xanthine oxidase inhibitor, is widely used to treat hyperuricemia. Although febuxostat-associated rhabdomyolysis was reported in some patients with CKD, the association between CKD and febuxostat-associated myopathy remains uncertain. Design, setting, participants, & measurements Our retrospective cohort study included 1332 patients using febuxostat in Taipei Medical University–Wanfang Hospital from February of 2014 to January of 2016. The primary predictor was time-averaged eGFR as calculated by the equation proposed by the 2009 Chronic Kidney Disease Epidemiology Collaboration. The outcome was febuxostat-associated myopathy defined as elevated creatine kinase levels during febuxostat use that were not attributed to other muscular injuries. Results The median duration of febuxostat use was 224 days (25th, 75th percentiles: 86, 441.5 days). Of 1332 study participants, 1222 (91.7%) had CKD; the median eGFR was 20.8 ml/min per 1.73 m2 (25th, 75th percentiles: 9.0, 35.4 ml/min per 1.73 m2). Forty-one of the participants had febuxostat-associated myopathy (3.2%). All patients with myopathy had CKD, and the incident rate was 0.013 (95% confidence interval, 0.01 to 0.02) events per 100 patient-days in patients with CKD. Of 41 patients with myopathy, 37 had myositis, and four had rhabdomyolysis. Myopathy resolved in 17 patients who withdrew from treatment and eight patients who continued febuxostat treatment. Among the evaluated predictors, multivariate analysis showed that only the lowest eGFR tertile was significantly associated with myopathy in febuxostat users. The odds ratio of the lowest eGFR tertile to the highest tertile was 4.21 (95% confidence interval, 1.7 to 10.43). This finding remained consistent among subgroups stratified by age, sex, diabetes status, coronary artery disease, and statin or fibrate use. Conclusions Patients with severely reduced eGFR had higher risk of myopathy with treatment of febuxostat

Risk of Febuxostat-Associated Myopathy in Patients with CKD.

PubMed

Liu, Chung-Te; Chen, Chun-You; Hsu, Chien-Yi; Huang, Po-Hsun; Lin, Feng-Yen; Chen, Jaw-Wen; Lin, Shing-Jong

2017-05-08

Febuxostat, a nonpurine xanthine oxidase inhibitor, is widely used to treat hyperuricemia. Although febuxostat-associated rhabdomyolysis was reported in some patients with CKD, the association between CKD and febuxostat-associated myopathy remains uncertain. Our retrospective cohort study included 1332 patients using febuxostat in Taipei Medical University-Wanfang Hospital from February of 2014 to January of 2016. The primary predictor was time-averaged eGFR as calculated by the equation proposed by the 2009 Chronic Kidney Disease Epidemiology Collaboration. The outcome was febuxostat-associated myopathy defined as elevated creatine kinase levels during febuxostat use that were not attributed to other muscular injuries. The median duration of febuxostat use was 224 days (25th, 75th percentiles: 86, 441.5 days). Of 1332 study participants, 1222 (91.7%) had CKD; the median eGFR was 20.8 ml/min per 1.73 m 2 (25th, 75th percentiles: 9.0, 35.4 ml/min per 1.73 m 2 ). Forty-one of the participants had febuxostat-associated myopathy (3.2%). All patients with myopathy had CKD, and the incident rate was 0.013 (95% confidence interval, 0.01 to 0.02) events per 100 patient-days in patients with CKD. Of 41 patients with myopathy, 37 had myositis, and four had rhabdomyolysis. Myopathy resolved in 17 patients who withdrew from treatment and eight patients who continued febuxostat treatment. Among the evaluated predictors, multivariate analysis showed that only the lowest eGFR tertile was significantly associated with myopathy in febuxostat users. The odds ratio of the lowest eGFR tertile to the highest tertile was 4.21 (95% confidence interval, 1.7 to 10.43). This finding remained consistent among subgroups stratified by age, sex, diabetes status, coronary artery disease, and statin or fibrate use. Patients with severely reduced eGFR had higher risk of myopathy with treatment of febuxostat. Regular monitoring of creatine kinase level is suggested for early detection of febuxostat

Consensus Statement on Standard of Care for Congenital Myopathies

PubMed Central

Wang, Ching H.; Dowling, James J.; North, Kathryn; Schroth, Mary K.; Sejersen, Thomas; Shapiro, Frederic; Bellini, Jonathan; Weiss, Hali; Guillet, Marc; Amburgey, Kimberly; Apkon, Susan; Bertini, Enrico; Bonnemann, Carsten; Clarke, Nigel; Connolly, Anne M.; Estournet-Mathiaud, Brigitte; Fitzgerald, Dominic; Florence, Julaine M.; Gee, Richard; Gurgel-Giannetti, Juliana; Glanzman, Allan M.; Hofmeister, Brittany; Jungbluth, Heinz; Koumbourlis, Anastassios C.; Laing, Nigel G.; Main, Marion; Morrison, Leslie A.; Munns, Craig; Rose, Kristy; Schuler, Pamela M.; Sewry, Caroline; Storhaug, Kari; Vainzof, Mariz; Yuan, Nanci

2016-01-01

Recent progress in scientific research has facilitated accurate genetic and neuropathological diagnosis of congenital myopathies. However, given their relatively low incidence, congenital myopathies remain unfamiliar to the majority of care providers, and the levels of patient care are extremely variable. This consensus statement aims to provide care guidelines for congenital myopathies. The International Standard of Care Committee for Congenital Myopathies worked through frequent e-mail correspondences, periodic conference calls, 2 rounds of online surveys, and a 3-day workshop to achieve a consensus for diagnostic and clinical care recommendations. The committee includes 59 members from 10 medical disciplines. They are organized into 5 working groups: genetics/diagnosis, neurology, pulmonology, gastroenterology/nutrition/speech/oral care, and orthopedics/rehabilitation. In each care area the authors summarize the committee’s recommendations for symptom assessments and therapeutic interventions. It is the committee’s goal that through these recommendations, patients with congenital myopathies will receive optimal care and improve their disease outcome. PMID:22431881

Exertional myopathy in whooping cranes (Grus americana) with prognostic guidelines.

PubMed

Hanley, Christopher S; Thomas, Nancy J; Paul-Murphy, Joanne; Hartup, Barry K

2005-09-01

Exertional myopathy developed in three whooping cranes (Grus americana) secondary to routine capture, handling, and trauma. Presumptive diagnosis of exertional myopathy was based on history of recent capture or trauma, clinical signs, and elevation of aspartate aminotransferase, alanine aminotransferase, creatine kinase, lactate dehydrogenase, and serum potassium. Treatments were attempted in each case, but ultimately were not successful. Gross and microscopic lesions at necropsy confirmed the diagnosis in each case, with the leg musculature most severely affected. Guidelines for determining prognosis of exertional myopathy in cranes have been included based on the analysis of these cases and others in the literature. As treatment is largely unrewarding, prevention remains the key in controlling exertional myopathy. Identification of predisposing factors and proper handling, immobilization, and transportation techniques can help prevent development of exertional myopathy in cranes.

Exertional myopathy in whooping cranes (Grus americana) with prognostic guidlelines

USGS Publications Warehouse

Hanley, C.S.; Thomas, N.J.; Paul-Murphy, P.; Hartup, B.K.

2005-01-01

Exertional myopathy developed in three whooping cranes (Grus americana) secondary to routine capture, handling, and trauma. Presumptive diagnosis of exertional myopathy was based on history of recent capture or trauma, clinical signs, and elevation of aspartate aminotransferase, alanine aminotransferase, creatine kinase, lactate dehydrogenase, and serum potassium. Treatments were attempted in each case, but ultimately were not successful. Gross and microscopic lesions at necropsy confirmed the diagnosis in each case, with the leg musculature most severely affected. Guidelines for determining prognosis of exertional myopathy in cranes have been included based on the analysis of these cases and others in the literature. As treatment is largely unrewarding, prevention remains the key in controlling exertional myopathy. Identification of predisposing factors and proper handling, immobilization, and transportation techniques can help prevent development of exertional myopathy in cranes.

Acute Exertional Compartment Syndrome with Rhabdomyolysis: Case Report and Review of Literature

PubMed Central

Gaunder, Christopher; Schumer, Ross

2018-01-01

Patient: Male, 17 Final Diagnosis: Acute exertional compartment syndrome Symptoms: Foot drop • leg pain • paresthesia Medication: — Clinical Procedure: Fasciotomy Specialty: Orthopedics and Traumatology Objective: Rare disease Background: Acute exertional compartment syndrome (AECS) is a rare cause of leg pain often associated with a delay in diagnosis and potentially leading to irreversible muscle and nerve damage. Case Report: We present the case of a previously healthy, high-level athlete who presented with the acute onset of unilateral anterior leg pain and foot drop the day after a strenuous workout. He was diagnosed with compartment syndrome and rhabdomyolysis. His management included emergent fluid resuscitation, fasciotomies, debridement of necrotic muscle from his anterior compartment, and delayed primary closure. After six months of intensive outpatient physical therapy, including the use of blood flow restriction treatments, the patient returned to sports and received a NCAA Division I Football scholarship. Conclusions: We describe the details of this patient’s case and review the literature related to acute exertional compartment syndrome. The occurrence of acute compartment syndrome in the absence of trauma or fracture, though rare, can have devastating consequences following delays in treatment. AECS requires prompt diagnosis and surgical intervention to prevent these consequences. Diagnosis of atraumatic cases can be difficult, which is why awareness is equally as important as history and physical examination. While diagnosis is primarily clinical, it can be supported with direct intra-compartmental pressure measurements and maintaining a high index of suspicion in acute presentations of exertional limb pain. PMID:29415981

Mutation Update for GNE Gene Variants Associated with GNE Myopathy

PubMed Central

Celeste, Frank V.; Vilboux, Thierry; Ciccone, Carla; de Dios, John Karl; Malicdan, May Christine V.; Leoyklang, Petcharat; McKew, John C.; Gahl, William A.; Carrillo-Carrasco, Nuria; Huizing, Marjan

2014-01-01

The GNE gene encodes the rate-limiting, bifunctional enzyme of sialic acid biosynthesis, UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE). Biallelic GNE mutations underlie GNE myopathy, an adult-onset progressive myopathy. GNE myopathy-associated GNE mutations are predominantly missense, resulting in reduced, but not absent, GNE enzyme activities. The exact pathomechanism of GNE myopathy remains unknown, but likely involves aberrant (muscle) sialylation. Here we summarize 154 reported and novel GNE variants associated with GNE myopathy, including 122 missense, 11 nonsense, 14 insertion/deletions and 7 intronic variants. All variants were deposited in the online GNE variation database (http://www.dmd.nl/nmdb2/home.php?select_db=GNE). We report the predicted effects on protein function of all variants as well as the predicted effects on epimerase and/or kinase enzymatic activities of selected variants. By analyzing exome sequence databases, we identified three frequently occurring, unreported GNE missense variants/polymorphisms, important for future sequence interpretations. Based on allele frequencies, we estimate the world-wide prevalence of GNE myopathy to be ~ 4–21/1,000,000. This previously unrecognized high prevalence confirms suspicions that many patients may escape diagnosis. Awareness among physicians for GNE myopathy is essential for the identification of new patients, which is required for better understanding of the disorder’s pathomechanism and for the success of ongoing treatment trials. PMID:24796702

Current concepts in the pathophysiology, evaluation, and diagnosis of compartment syndrome

NASA Technical Reports Server (NTRS)

Hargens, A. R.; Mubarak, S. J.

1998-01-01

This article reviews present knowledge of the pathophysiology and diagnosis of acute compartment syndromes. Recent results using compression of legs in normal volunteers provide objective data concerning local pressure thresholds for neuromuscular dysfunction in the anterior compartment. Results with this model indicate that a progression of neuromuscular deficits occurs when IMP increases to within 35 to 40 mm Hg of diastolic blood pressure. These findings provide useful information on the diagnosis and compression thresholds for acute compartment syndromes. Time factors are also important, however, and usually are incompletely known in most cases of acute compartment syndrome. Although the slit catheter is a very good technique for monitoring IMP during rest, these catheters and their associated extracorporeal transducer systems are not ideal. Recently developed miniature transducer-tipped catheters and, perhaps, future development of noninvasive techniques may provide accurate recordings of IMP in patients with acute compartment syndromes.

Immune-mediated statin myopathy.

PubMed

Loganathan, Priyadarshini; Oddis, Chester V; Aggarwal, Rohit

2016-01-01

Statin-induced necrotizing autoimmune myopathy (SINAM) is associated with a unique clinical 5 phenotype of severe proximal muscle weakness during or after exposure to statins in patients with high creatine kinase (CK) levels. Electromyography (EMG) and muscle biopsy reveal features of a necrotizing myopathy and the anti-HMGCR autoantibody is frequently detected. Treatment requires a combination of statin discontinuation as well as immunomodulatory or immunosuppressive therapy. HLA typing (HLADRB1*1101) is strongly associated with anti-10 HMGCR autoantibody positivity in statin-exposed patients. It is well documented that statin triggers autoimmune disease in those with a genetic susceptibility. With the commercial availability of an accurate ELISA test, the natural history of the disease and its phenotypic features are becoming increasingly understood.

Genetics Home Reference: hereditary myopathy with early respiratory failure

MedlinePlus

... Home Health Conditions HMERF Hereditary myopathy with early respiratory failure Printable PDF Open All Close All Enable ... expand/collapse boxes. Description Hereditary myopathy with early respiratory failure ( HMERF ) is an inherited muscle disease that ...

Measurement of compartment elasticity using pressure related ultrasound: a method to identify patients with potential compartment syndrome.

PubMed

Sellei, R M; Hingmann, S J; Kobbe, P; Weber, C; Grice, J E; Zimmerman, F; Jeromin, S; Gansslen, A; Hildebrand, F; Pape, H C

2015-01-01

PURPOSE OF THE STUDY Decision-making in treatment of an acute compartment syndrome is based on clinical assessment, supported by invasive monitoring. Thus, evolving compartment syndrome may require repeated pressure measurements. In suspected cases of potential compartment syndromes clinical assessment alone seems to be unreliable. The objective of this study was to investigate the feasibility of a non-invasive application estimating whole compartmental elasticity by ultrasound, which may improve accuracy of diagnostics. MATERIAL AND METHODS In an in-vitro model, using an artificial container simulating dimensions of the human anterior tibial compartment, intracompartmental pressures (p) were raised subsequently up to 80 mm Hg by infusion of saline solution. The compartmental depth (mm) in the cross-section view was measured before and after manual probe compression (100 mm Hg) upon the surface resulting in a linear compartmental displacement (Δd). This was repeated at rising compartmental pressures. The resulting displacements were related to the corresponding intra-compartmental pressures simulated in our model. A hypothesized relationship between pressures related compartmental displacement and the elasticity at elevated compartment pressures was investigated. RESULTS With rising compartmental pressures, a non-linear, reciprocal proportional relation between the displacement (mm) and the intra-compartmental pressure (mm Hg) occurred. The Pearson's coefficient showed a high correlation (r2 = -0.960). The intraobserver reliability value kappa resulted in a statistically high reliability (κ = 0.840). The inter-observer value indicated a fair reliability (κ = 0.640). CONCLUSIONS Our model reveals that a strong correlation between compartmental strain displacements assessed by ultrasound and the intra-compartmental pressure changes occurs. Further studies are required to prove whether this assessment is transferable to human muscle tissue. Determining the complete

Characteristics of patients with chronic exertional compartment syndrome.

PubMed

Davis, Daniel E; Raikin, Steven; Garras, David N; Vitanzo, Peter; Labrador, Hallie; Espandar, Ramin

2013-10-01

Chronic exertional compartment syndrome (CECS) is a condition that causes reversible ischemia and lower extremity pain during exercise. To date there are few large studies examining the characteristics of patients with CECS. This study aimed to present these characteristics by examining the largest published series of patients with a confirmed diagnosis of the disorder. An IRB-approved, retrospective review was undertaken of patients with a suspected diagnosis of CECS undergoing pre- and postexercise compartment pressure testing between 2000 and 2012. Patients were evaluated for gender, age, duration of symptoms, pain level, specific compartments involved, compartment pressure measurements, and participation and type of athletics. Two-hundred twenty-six patients (393 legs) underwent compartment pressure testing. A diagnosis of CECS was made in 153 (67.7%) patients and 250 (63.6%) legs with elevated compartment measurements; average age of the patients was 24 years (range, 13-69 years). Female patients accounted for 92 (60.1%) of those with elevated pressures. Anterior and lateral compartment pressures were elevated most frequently, with 200 (42.5%) and 167 (35.5%) compartments, respectively. One hundred forty-one (92.2%) patients reported participation in sports, with running being the most common individual sport and soccer being the most common team sport. Duration of pain prior to diagnosis averaged 28 months. Although there is ample literature pertaining to the diagnostic criteria and treatment algorithm of the condition, few papers have described the type of patient most likely to develop CECS. This is the largest study to date to evaluate the type of patient likely to present with chronic exertional compartment syndrome. Level III, retrospective review.

Association between statin-associated myopathy and skeletal muscle damage

PubMed Central

Mohaupt, Markus G.; Karas, Richard H.; Babiychuk, Eduard B.; Sanchez-Freire, Verónica; Monastyrskaya, Katia; Iyer, Lakshmanan; Hoppeler, Hans; Breil, Fabio; Draeger, Annette

2009-01-01

Background Many patients taking statins often complain of muscle pain and weakness. The extent to which muscle pain reflects muscle injury is unknown. Methods We obtained biopsy samples from the vastus lateralis muscle of 83 patients. Of the 44 patients with clinically diagnosed statin-associated myopathy, 29 were currently taking a statin, and 15 had discontinued statin therapy before the biopsy (minimal duration of discontinuation 3 weeks). We also included 19 patients who were taking statins and had no myopathy, and 20 patients who had never taken statins and had no myopathy. We classified the muscles as injured if 2% or more of the muscle fibres in a biopsy sample showed damage. Using reverse transcriptase polymerase chain reaction, we evaluated the expression levels of candidate genes potentially related to myocyte injury. Results Muscle injury was observed in 25 (of 44) patients with myopathy and in 1 patient without myopathy. Only 1 patient with structural injury had a circulating level of creatine phosphokinase that was elevated more than 1950 U/L (10× the upper limit of normal). Expression of ryanodine receptor 3 was significantly upregulated in patients with biopsy evidence of structural damage (1.7, standard error of the mean 0.3). Interpretation Persistent myopathy in patients taking statins reflects structural muscle damage. A lack of elevated levels of circulating creatine phosphokinase does not rule out structural muscle injury. Upregulation of the expression of ryanodine receptor 3 is suggestive of an intracellular calcium leak. PMID:19581603

Association between statin-associated myopathy and skeletal muscle damage.

PubMed

Mohaupt, Markus G; Karas, Richard H; Babiychuk, Eduard B; Sanchez-Freire, Verónica; Monastyrskaya, Katia; Iyer, Lakshmanan; Hoppeler, Hans; Breil, Fabio; Draeger, Annette

2009-07-07

Many patients taking statins often complain of muscle pain and weakness. The extent to which muscle pain reflects muscle injury is unknown. We obtained biopsy samples from the vastus lateralis muscle of 83 patients. Of the 44 patients with clinically diagnosed statin-associated myopathy, 29 were currently taking a statin, and 15 had discontinued statin therapy before the biopsy (minimal duration of discontinuation 3 weeks). We also included 19 patients who were taking statins and had no myopathy, and 20 patients who had never taken statins and had no myopathy. We classified the muscles as injured if 2% or more of the muscle fibres in a biopsy sample showed damage. Using reverse transcriptase polymerase chain reaction, we evaluated the expression levels of candidate genes potentially related to myocyte injury. Muscle injury was observed in 25 (of 44) patients with myopathy and in 1 patient without myopathy. Only 1 patient with structural injury had a circulating level of creatine phosphokinase that was elevated more than 1950 U/L (10x the upper limit of normal). Expression of ryanodine receptor 3 was significantly upregulated in patients with biopsy evidence of structural damage (1.7, standard error of the mean 0.3). Persistent myopathy in patients taking statins reflects structural muscle damage. A lack of elevated levels of circulating creatine phosphokinase does not rule out structural muscle injury. Upregulation of the expression of ryanodine receptor 3 is suggestive of an intracellular calcium leak.

Epsilon aminocaproic acid (EACA) myopathy.

PubMed Central

Lane, R. J.; McLelland, N. J.; Martin, A. M.; Mastaglia, F. L.

1979-01-01

Two female patients developed a severe, painful proximal myopathy after taking 18--30 g of epsilon-aminocaproic acid daily for 5 weeks. Marked elevations of serum aminotransferases, creatine kinase and aldolase levels were found and the first patient had electromyographic and muscle biopsy changes of an acute monophasic, necrotising myopathy at the height of the illness. Resolution occurred in both cases on stopping the drug and the second patient had no electromyographic or muscle biopsy abnormalities 3 weeks later. Only 2 recognized cases of the condition have been reported previously but a review of the literature revealed several other possible examples. Images Fig. 1 PMID:471867

Metabolic myopathies: functional evaluation by different exercise testing approaches.

PubMed

Volpi, L; Ricci, G; Orsucci, D; Alessi, R; Bertolucci, F; Piazza, S; Simoncini, C; Mancuso, M; Siciliano, G

2011-08-01

Metabolic myopathies are a clinically and etiologically heterogeneous group of disorders due to defects in muscular energy metabolism. They include glycogen storage diseases, fatty acid oxidation defects, and mitochondrial disorders. The typical manifestations of a metabolic myopathy are exercise-induced myalgias, exercise intolerance, and cramps. Evaluating subjects with such symptoms is not easy because of the frequent lack of clinical features. Exercise tests are, therefore, reliable screening tools. Here, we discuss the possible role of such exercise testing techniques in the diagnostic approach of a patient with suspected metabolic myopathy.

Mitochondrial function is altered in horse atypical myopathy.

PubMed

Lemieux, Hélène; Boemer, François; van Galen, Gaby; Serteyn, Didier; Amory, Hélène; Baise, Etienne; Cassart, Dominique; van Loon, Gunther; Marcillaud-Pitel, Christel; Votion, Dominique-M

2016-09-01

Equine atypical myopathy in Europe is a fatal rhabdomyolysis syndrome that results from the ingestion of hypoglycin A contained in seeds and seedlings of Acer pseudoplatanus (sycamore maple). Acylcarnitine concentrations in serum and muscle OXPHOS capacity were determined in 15 atypical myopathy cases. All but one acylcarnitine were out of reference range and mitochondrial respiratory capacity was severely decreased up to 49% as compared to 10 healthy controls. The hallmark of atypical myopathy thus consists of a severe alteration in the energy metabolism including a severe impairment in muscle mitochondrial respiration that could contribute to its high death rate. Copyright © 2016 Elsevier B.V. and Mitochondria Research Society. All rights reserved.

Myopathy induced by statin-ezetimibe combination: Evaluation of potential risk factors.

PubMed

Brahmachari, Ballari; Chatterjee, Suparna

2015-01-01

Although both atorvastatin and ezetimibe may cause myopathy, statin-induced myopathy is less likely at low doses, and ezetimibe is only rarely reported to induce myopathy. Also, ezetimibe is not usually known to potentiate statin-induced myopathy. We report a case of myalgia with elevated serum creatinine phosphokinase in a patient after 2 months of therapy with fixed dose combination of atorvastatin and ezetimibe (10 mg each). At the time of the event, patient was undertaking moderate physical exertion in the form of brisk walking for 30-40 min a day and was detected to have low serum Vitamin D levels. The adverse event resolved after stopping atorvastatin-ezetimibe combination therapy. Potential risk factors, such as physical exertion and Vitamin D deficiency, co-existent in dyslipidemic patients, may exacerbate myopathy potential of these drugs, and precipitate muscular symptoms even at a low-dose.

A Brazilian family with hereditary inclusion body myopathy associated with Paget disease of bone and frontotemporal dementia.

PubMed

Fanganiello, R D; Kimonis, V E; Côrte, C C; Nitrini, R; Passos-Bueno, M R

2011-04-01

Inclusion body myopathy associated with Paget disease and frontotemporal dementia (IBMPFD) is a progressive and usually misdiagnosed autosomal dominant disorder. It is clinically characterized by a triad of features: proximal and distal myopathy, early onset Paget disease of bone (PDB), and frontotemporal dementia (FTD). It is caused by missense mutations in the valosin-containing protein (VCP) gene. We describe here the clinical and molecular findings of the first Brazilian family identified with IBMPFD. Progressive myopathy affecting the limb girdles was detected by clinical examination followed by muscle biopsy and creatine kinase measurement. PDB was suggested after anatomopathological bone examination and FTD was diagnosed by clinical, neuropsychological and language evaluations. Brain magnetic resonance revealed severe atrophy of the anterior temporal lobes, including the hippocampi. A R93C mutation in VCP was detected by direct sequencing screening in subject W (age 62) and in his mother. Four more individuals diagnosed with "dementia" were reported in this family. We also present a comprehensive genotype-phenotype correlation analysis of mutations in VCP in 182 patients from 29 families described in the literature and show that while IBM is a conspicuously penetrant symptom, PDB has a lower penetrance when associated with mutations in the AAAD1 domain and FTD has a lower penetrance when associated with mutations in the Junction (L1-D1) domain. Furthermore, the R93C mutation is likely to be associated with the penetrance of all the clinical symptoms of the triad.

Hypothyroid-induced acute compartment syndrome in all extremities.

PubMed

Musielak, Matthew C; Chae, Jung Hee

2016-12-20

Acute compartment syndrome (ACS) is an uncommon complication of uncontrolled hypothyroidism. If unrecognized, this can lead to ischemia, necrosis and potential limb loss. A 49-year-old female presented with the sudden onset of bilateral lower and upper extremity swelling and pain. The lower extremity anterior compartments were painful and tense. The extensor surface of the upper extremities exhibited swelling and pain. Motor function was intact, however, limited due to pain. Bilateral lower extremity fasciotomies were performed. Postoperative Day 1, upper extremity motor function decreased significantly and paresthesias occurred. She therefore underwent bilateral forearm fasciotomies. The pathogenesis of hypothyroidism-induced compartment syndrome is unclear. Thyroid-stimulating hormone-induced fibroblast activation results in increased glycosaminoglycan deposition. The primary glycosaminoglycan in hypothyroid myxedematous changes is hyaluronic acid, which binds water causing edema. This increases vascular permeability, extravasation of proteins and impaired lymphatic drainage. These contribute to increased intra-compartmental pressure and subsequent ACS. Published by Oxford University Press and JSCR Publishing Ltd. All rights reserved. © The Author 2016.

Congenital myopathy is caused by mutation of HACD1.

PubMed

Muhammad, Emad; Reish, Orit; Ohno, Yusuke; Scheetz, Todd; Deluca, Adam; Searby, Charles; Regev, Miriam; Benyamini, Lilach; Fellig, Yakov; Kihara, Akio; Sheffield, Val C; Parvari, Ruti

2013-12-20

Congenital myopathies are heterogeneous inherited diseases of muscle characterized by a range of distinctive histologic abnormalities. We have studied a consanguineous family with congenital myopathy. Genome-wide linkage analysis and whole-exome sequencing identified a homozygous non-sense mutation in 3-hydroxyacyl-CoA dehydratase 1 (HACD1) in affected individuals. The mutation results in non-sense mediated decay of the HACD1 mRNA to 31% of control levels in patient muscle and completely abrogates the enzymatic activity of dehydration of 3-hydroxyacyl-CoA, the third step in the elongation of very long-chain fatty acids (VLCFAs). We describe clinical findings correlated with a deleterious mutation in a gene not previously known to be associated with congenital myopathy in humans. We suggest that the mutation in the HACD1 gene causes a reduction in the synthesis of VLCFAs, which are components of membrane lipids and participants in physiological processes, leading to congenital myopathy. These data indicate that HACD1 is necessary for muscle function.

Metabolic myopathies

NASA Technical Reports Server (NTRS)

Martin, A.; Haller, R. G.; Barohn, R.; Blomqvist, C. G. (Principal Investigator)

1994-01-01

Metabolic myopathies are disorders of muscle energy production that result in skeletal muscle dysfunction. Cardiac and systemic metabolic dysfunction may coexist. Symptoms are often intermittent and provoked by exercise or changes in supply of lipid and carbohydrate fuels. Specific disorders of lipid and carbohydrate metabolism in muscle are reviewed. Evaluation often requires provocative exercise testing. These tests may include ischemic forearm exercise, aerobic cycle exercise, and 31P magnetic resonance spectroscopy with exercise.

Sialylation of Thomsen-Friedenreich antigen is a noninvasive blood-based biomarker for GNE myopathy

PubMed Central

Leoyklang, Petcharat; Malicdan, May Christine; Yardeni, Tal; Celeste, Frank; Ciccone, Carla; Li, Xueli; Jiang, Rong; Gahl, William A.; Carrillo-Carrasco, Nuria; He, Miao; Huizing, Marjan

2014-01-01

GNE myopathy is an adult-onset progressive myopathy, resulting from mutations in GNE, the key enzyme of sialic acid synthesis. The pathomechanism of GNE myopathy likely involves aberrant sialylation, since administration of sialic acid itself, or its precursor, N-acetylmannosamine (ManNAc), rescued hyposialylation of GNE myopathy mice. Recently, clinical trials for GNE myopathy patients were initiated. A robust, noninvasive biomarker is highly desirable for diagnosis of GNE myopathy and for evaluating response to therapy. Since muscle biopsies of patients with GNE myopathy demonstrated hyposialylation of predominantly O-linked glycans, we analyzed the O-linked glycome of patients’ plasma proteins using mass spectrometry. Most patients showed increased plasma levels of the core 1 O-linked glycan, Thomsen-Friedenreich (T)-antigen and/or decreased amounts of its sialylated form, ST-antigen. In addition, compared to unaffected individuals, all analyzed patients had a consistently increased ratio of T-antigen to ST-antigen. Importantly, the T/ST ratios were in the normal range in a GNE myopathy patient treated with intravenous immunoglobulins as a source of sialic acid, indicating response to therapy. Natural history and clinical trial data will reveal whether T/ST ratios can be correlated to muscle function. These findings not only highlight plasma T/ST ratios as a robust blood-based biomarker for GNE myopathy, but may also help explain the pathology and course of the disease. PMID:25123033

The expanding phenotype of mitochondrial myopathy.

PubMed

DiMauro, Salvatore; Gurgel-Giannetti, Juliana

2005-10-01

Our understanding of mitochondrial diseases (defined restrictively as defects in the mitochondrial respiratory chain) continues to progress apace. In this review we provide an update of information regarding disorders that predominantly or exclusively affect skeletal muscle. Most recently described mitochondrial myopathies are due to defects in nuclear DNA, including coenzyme Q10 deficiency, and mutations in genes that control mitochondrial DNA (mtDNA) abundance and structure such as POLG and TK2. Barth syndrome, an X-linked recessive mitochondrial myopathy/cardiopathy, is associated with altered lipid composition of the inner mitochondrial membrane, but a putative secondary impairment of the respiratory chain remains to be documented. Concerning the 'other genome', the role played by mutations in protein encoding genes of mtDNA in causing isolated myopathies has been confirmed. It has also been confirmed that mutations in tRNA genes of mtDNA can cause predominantly myopathic syndromes and - contrary to conventional wisdom - these mutations can be homoplasmic. Defects in the mitochondrial respiratory chain impair energy production and almost invariably involve skeletal muscle, causing exercise intolerance, myalgia, cramps, or fixed weakness, which often affects extraocular muscles and results in droopy eyelids (ptosis) and progressive external ophthalmoplegia.

Congenital myopathy is caused by mutation of HACD1

PubMed Central

Muhammad, Emad; Reish, Orit; Ohno, Yusuke; Scheetz, Todd; DeLuca, Adam; Searby, Charles; Regev, Miriam; Benyamini, Lilach; Fellig, Yakov; Kihara, Akio; Sheffield, Val C.; Parvari, Ruti

2013-01-01

Congenital myopathies are heterogeneous inherited diseases of muscle characterized by a range of distinctive histologic abnormalities. We have studied a consanguineous family with congenital myopathy. Genome-wide linkage analysis and whole-exome sequencing identified a homozygous non-sense mutation in 3-hydroxyacyl-CoA dehydratase 1 (HACD1) in affected individuals. The mutation results in non-sense mediated decay of the HACD1 mRNA to 31% of control levels in patient muscle and completely abrogates the enzymatic activity of dehydration of 3-hydroxyacyl-CoA, the third step in the elongation of very long-chain fatty acids (VLCFAs). We describe clinical findings correlated with a deleterious mutation in a gene not previously known to be associated with congenital myopathy in humans. We suggest that the mutation in the HACD1 gene causes a reduction in the synthesis of VLCFAs, which are components of membrane lipids and participants in physiological processes, leading to congenital myopathy. These data indicate that HACD1 is necessary for muscle function. PMID:23933735

Spatial influence on breast muscle morphological structure, myofiber size, and gene expression associated with the wooden breast myopathy in broilers.

PubMed

Clark, D L; Velleman, S G

2016-12-01

The wooden breast (WB) myopathy is identified by the palpation of a rigid pectoralis major (p. major) muscle and is characterized as a fibrotic, necrotic p. major disorder in broilers. The objective of the current study was to determine spatial morphological and gene expression differences at 4 locations within WB affected muscle from different genetic lines. Morphology was evaluated in 2 broiler lines expressing the WB myopathy (Lines A and B) and a line without WB (Line C) at 3 ventral locations and one anterodorsal location in the p. major muscle. In WB affected muscle of Line A, fibrosis was greatest in the anterior locations of WB affected muscle. In Line B muscle, fibrosis was greatest in the anteroventral region and minimal in the anterodorsal or posterior regions. Average p. major myofiber diameter was 30% larger in Lines A and B compared to Line C. However, in Line A there were no differences between the percentage of large fibers (diameter >70 μm) in unaffected and WB affected muscles at any sampling region. The percentage of small fibers (diameter <10 μm), likely small regenerating fibers, and expression of myogenic determination factor 1 (MYOD1) and myogenin were increased in Line A WB affected muscle compared to unaffected muscle. In Line B, the percentage of small fibers and MYOD1 expression in WB affected muscle was not different from unaffected muscle. Connective tissue organization within WB affected muscle was also different in Lines A and B, which may be attributed to decorin, a proteoglycan that mediates collagen crosslinking, growth factor signaling, and cell growth. Decorin expression was increased at all locations within Line A. However, in Line B decorin was increased only in the fibrotic regions of the p. major. The compiled results provide evidence that the WB myopathy is not uniform throughout the entire p. major muscle and the anterior end of the p. major muscle was more affected by the condition. © 2016 Poultry Science Association

Muscular MRI-based algorithm to differentiate inherited myopathies presenting with spinal rigidity.

PubMed

Tordjman, Mickael; Dabaj, Ivana; Laforet, Pascal; Felter, Adrien; Ferreiro, Ana; Biyoukar, Moustafa; Law-Ye, Bruno; Zanoteli, Edmar; Castiglioni, Claudia; Rendu, John; Beroud, Christophe; Chamouni, Alexandre; Richard, Pascale; Mompoint, Dominique; Quijano-Roy, Susana; Carlier, Robert-Yves

2018-05-25

Inherited myopathies are major causes of muscle atrophy and are often characterized by rigid spine syndrome, a clinical feature designating patients with early spinal contractures. We aim to present a decision algorithm based on muscular whole body magnetic resonance imaging (mWB-MRI) as a unique tool to orientate the diagnosis of each inherited myopathy long before the genetically confirmed diagnosis. This multicentre retrospective study enrolled 79 patients from referral centres in France, Brazil and Chile. The patients underwent 1.5-T or 3-T mWB-MRI. The protocol comprised STIR and T1 sequences in axial and coronal planes, from head to toe. All images were analyzed manually by multiple raters. Fatty muscle replacement was evaluated on mWB-MRI using both the Mercuri scale and statistical comparison based on the percentage of affected muscle. Between February 2005 and December 2015, 76 patients with genetically confirmed inherited myopathy were included. They were affected by Pompe disease or harbored mutations in RYR1, Collagen VI, LMNA, SEPN1, LAMA2 and MYH7 genes. Each myopathy had a specific pattern of affected muscles recognizable on mWB-MRI. This allowed us to create a novel decision algorithm for patients with rigid spine syndrome by segregating these signs. This algorithm was validated by five external evaluators on a cohort of seven patients with a diagnostic accuracy of 94.3% compared with the genetic diagnosis. We provide a novel decision algorithm based on muscle fat replacement graded on mWB-MRI that allows diagnosis and differentiation of inherited myopathies presenting with spinal rigidity. • Inherited myopathies are rare, diagnosis is challenging and genetic tests require specialized centres and often take years. • Inherited myopathies are often characterized by spinal rigidity. • Whole body magnetic resonance imaging is a unique tool to orientate the diagnosis of each inherited myopathy presenting with spinal rigidity. • Each inherited

Mutation Spectrum of GNE Myopathy in the Indian Sub-Continent.

PubMed

Bhattacharya, Sudha; Khadilkar, Satish V; Nalini, Atchayaram; Ganapathy, Aparna; Mannan, Ashraf U; Majumder, Partha P; Bhattacharya, Alok

GNE myopathy is an adult onset recessive genetic disorder that affects distal muscles sparing the quadriceps. GNE gene mutations have been identified in GNE myopathy patients all over the world. Homozygosity is a common feature in GNE myopathy patients worldwide. The major objective of this study was to investigate the mutation spectrum of GNE myopathy in India in relation to the population diversity in the country. We have collated GNE mutation data of Indian GNE myopathy patients from published literature and from recently identified patients. We also used data of people of Indian subcontinent from 1000 genomes database, South Asian Genome database and Strand Life Science database to determine frequency of GNE mutations in the general population. A total of 67 GNE myopathy patients were studied, of whom 21% were homozygous for GNE variants, while the rest were compound heterozygous. Thirty-five different mutations in the GNE gene were recorded, of which 5 have not been reported earlier. The most frequent mutation was p.Val727Met (65%) found mainly in the heterozygous form. Another mutation, p.Ile618Thr was also common (16%) but was found mainly in patients from Rajasthan, while p.Val727Met was more widely distributed. The latter was also seen at a high frequency in general population of Indian subcontinent in all the databases. It was also present in Thailand but was absent in general population elsewhere in the world. p.Val727Met is likely to be a founder mutation of Indian subcontinent.

Multidisciplinary Approach to the Management of Myopathies

PubMed Central

M. King, Wendy; Kissel, John T.

2013-01-01

Purpose of Review Aside from some inflammatory myopathies and very few genetic disorders, there are no therapies that make most patients with myopathies stronger. Consequently, the management of these patients can be frustrating for patients and their families as well as the clinicians taking care of them. Treatment of these patients must involve a comprehensive approach focused on limiting the secondary effects of skeletal muscle weakness, managing comorbidities associated with specific diseases, and, most importantly, optimizing patients’ functional abilities and quality of life in terms of their ability to accomplish activities of daily living. While the approach to each patient differs depending on their disease, certain common themes can be addressed in each patient. This review highlights an approach centered on four conceptual themes (“the Four S’s”): Strength therapies, Supportive care, Symptomatic therapies, and pSychological support. Recent Findings Although relatively few well-designed studies have been done that highlight conservative management of patients with various myopathies, an emerging literature helps guide the clinician in certain key areas, especially in relation to cardiac and pulmonary management of these patients. Summary While disease-altering therapies have proven elusive for many muscle diseases, a multimodal approach to the conservative and supportive care of these patients can markedly improve their quality of life. Pharmacologic treatment options for specific myopathies will not be addressed in this article but are covered elsewhere in this issue of CONTINUUM. PMID:24305452

Genetics Home Reference: Miyoshi myopathy

MedlinePlus

... Itoyama Y. Dysferlin mutations in Japanese Miyoshi myopathy: relationship to phenotype. Neurology. 2003 Jun 10;60(11): ... for Links Data Files & API Site Map Subscribe Customer Support USA.gov Copyright Privacy Accessibility FOIA Viewers & ...

Myopathy With SQSTM1 and TIA1 Variants: Clinical and Pathological Features.

PubMed

Niu, Zhiyv; Pontifex, Carly Sabine; Berini, Sarah; Hamilton, Leslie E; Naddaf, Elie; Wieben, Eric; Aleff, Ross A; Martens, Kristina; Gruber, Angela; Engel, Andrew G; Pfeffer, Gerald; Milone, Margherita

2018-01-01

The aim of this study is to identify the molecular defect of three unrelated individuals with late-onset predominant distal myopathy; to describe the spectrum of phenotype resulting from the contributing role of two variants in genes located on two different chromosomes; and to highlight the underappreciated complex forms of genetic myopathies. Clinical and laboratory data of three unrelated probands with predominantly distal weakness manifesting in the sixth-seventh decade of life, and available affected and unaffected family members were reviewed. Next-generation sequencing panel, whole exome sequencing, and targeted analyses of family members were performed to elucidate the genetic etiology of the myopathy. Genetic analyses detected two contributing variants located on different chromosomes in three unrelated probands: a heterozygous pathogenic mutation in SQSTM1 (c.1175C>T, p.Pro392Leu) and a heterozygous variant in TIA1 (c.1070A>G, p.Asn357Ser). The affected fraternal twin of one proband also carries both variants, while the unaffected family members harbor one or none. Two unrelated probands (family 1, II.3, and family 3, II.1) have a distal myopathy with rimmed vacuoles that manifested with index extensor weakness; the other proband (family 2, I.1) has myofibrillar myopathy manifesting with hypercapnic respiratory insufficiency and distal weakness. The findings indicate that all the affected individuals have a myopathy associated with both variants in SQSTM1 and TIA1 , respectively, suggesting that the two variants determine the phenotype and likely functionally interact. We speculate that the TIA1 variant is a modifier of the SQSTM1 mutation. We identify the combination of SQSTM1 and TIA1 variants as a novel genetic defect associated with myofibrillar myopathy and suggest to consider sequencing both genes in the molecular investigation of myopathy with rimmed vacuoles and myofibrillar myopathy although additional studies are needed to investigate the

Intermittent Massage as a Therapeutic Option for Compartment Syndrome after Embolectomy of the Lower Limbs.

PubMed

Pereira de Godoy, José Maria; de Fátima Guerreiro Godoy, Maria

2018-01-01

The case of a 54-year-old cardiac patient is reported, who was admitted to hospital with a complaint of sudden pain in the legs associated with edema, paresthesia, and coldness. Arterial embolism of the lower limbs was diagnosed and the patient was submitted to bilateral embolectomy. The patient evolved with a burning sensation, hypersensitivity in the right leg, swelling, and difficulty bending and stretching the sole of the foot and the knee. A physical examination detected edema and increased tension in the anterior, lateral, and posterior compartments. Treatment using intermittent massage of the leg during the evaluation of the patient was chosen in an attempt to stimulate lymphatic and venous drainage. After a few minutes of stimulation, there was significant improvement in the pain and edema. In 40 minutes, there was total reduction of the pain in the posterior and lateral compartments and improvement of over 50% in the anterior compartment. After this, the patient started to bend the knee without pain and bend the sole of the foot with slight pain. On the following day, the patient was walking around the hospital ward without difficulty. It seems that intermittent massage is a therapeutic option in selected cases of compartment syndrome.

Genetics Home Reference: Laing distal myopathy

MedlinePlus

... Muscular Dystrophy Association: Facts About Rare Muscular Dystrophies (PDF) Muscular Dystrophy Canada Muscular Dystrophy UK National Organization for Rare Disorders (NORD): Distal Myopathy Resource list ...

Genetics Home Reference: nemaline myopathy

MedlinePlus

... nemaline myopathy interact within the sarcomere to facilitate muscle contraction. When the skeletal muscle cells of people with ... The disorganized proteins cannot interact normally, which disrupts muscle contraction. Inefficient muscle contraction leads to muscle weakness and ...

Statin-Associated Autoimmune Myopathy: A Systematic Review of 100 Cases.

PubMed

Nazir, Salik; Lohani, Saroj; Tachamo, Niranjan; Poudel, Dilliram; Donato, Anthony

2017-04-01

Statins are a group of drugs that reduce the levels of triglycerides and cholesterol in blood by inhibiting HMG-CoA reductase, an enzyme involved in rate limiting step in cholesterol synthesis. About 2-20% patients on statins develop toxic myopathies, which usually resolve on discontinuation of statin. More recently, an immune-mediated necrotizing myopathy has been found to be associated with statin use which in most cases requires treatment with immunosuppressants. To perform a systematic review on published case reports and case series of statin-associated autoimmune myopathy. A comprehensive search of PUBMED, EMBASE, Cochrane library and ClinicalTrials.gov databases was performed for relevant articles from inception until March 19, 2016 to identify cases of statin-associated necrotizing myopathy and characterize their symptoms, evaluation and response to treatment. A total of 16 articles describing 100 patients with statin-associated autoimmune myopathy were identified. The mean age of presentation was 64.72 years, and 54.44% were males. The main presenting clinical feature was proximal muscle weakness, which was symmetric in 83.33% of patients. The mean creatine kinase (CK) was 6853 IU/l. Anti-HMG-CoA reductase antibody was positive in all cases tested (n = 57/57, 100%). In patients with no anti-HMG-CoA antibody results, diagnosis was established by findings of necrotizing myopathy on biopsy. Among the 83 cases where muscle biopsy information was available, 81.48% had necrosis, while 18.51% had combination of necrosis and inflammation. Most (83.82%) patients received two or more immunosuppressants to induce remission. Ninety-one percent had resolution of symptoms after treatment. Statin-associated necrotizing myopathy is a symmetric proximal muscle weakness associated with extreme elevations of CK. It is common in males and can occur after months of statin use. It is associated with necrosis on muscle biopsy and the presence of anti-HMG-CoA reductase antibodies

Absence of anti-HMG-CoA reductase autoantibodies in severe self-limited statin-related myopathy.

PubMed

Floyd, James S; Brody, Jennifer A; Tiniakou, Eleni; Psaty, Bruce M; Mammen, Andrew

2016-06-01

Patients with self-limited statin-related myopathy improve spontaneously when statins are stopped. In contrast, patients with statin-associated autoimmune myopathy have autoantibodies recognizing 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMGCR) and usually require immunosuppressive therapy to control their disease. On initial presentation, it can sometimes be difficult to distinguish between these 2 diseases, as both present with muscle pain, weakness, and elevated serum creatine kinase (CK) levels. The goal of this study was to determine whether patients with severe self-limited statin-related myopathy also make anti-HMGCR autoantibodies. We screened 101 subjects with severe self-limited cerivastatin-related myopathy for anti-HMGCR autoantibodies. No patient with severe self-limited cerivastatin-related myopathy had anti-HMGCR autoantibodies. Anti-HMGCR autoantibody testing can be used to help differentiate whether a patient has self-limited myopathy due to cerivastatin or autoimmune statin-associated myopathy; these findings may apply to other statins as well. Muscle Nerve 54: 142-144, 2016. © 2016 Wiley Periodicals, Inc.

A Rare Manifestation of Hypothyroid Myopathy: Hoffmann's Syndrome

PubMed Central

Lee, Kang Won; Kim, Kyoung Jin; Kim, Sang Hyun; Kim, Hee Young; Kim, Byung-Jo; Kim, Sin Gon; Choi, Dong Seop

2015-01-01

Hypothyroid myopathy is observed frequently and the resolution of the clinical manifestations of myopathy following thyroid hormone replacement is well known. However, a specific subtype of hypothyroid myopathy, Hoffmann's syndrome, characterized by increased muscular mass (pseudohypertrophy), proximal muscle weakness, muscle stiffness and cramps, is rarely reported. Herein, we describe a 34-year-old male who presented with proximal muscle weakness and non-pitting edema of the lower extremities. He initially visited the neurology department where he was suspected of having polymyositis. Additional laboratory evaluation revealed profound autoimmune hypothyroidism and elevated muscle enzymes including creatine kinase. The patient was started on levothyroxine treatment and, subsequently, clinical symptoms and biochemical parameters resolved with the treatment. The present case highlights that hypothyroidism should be considered in the differential diagnosis of musculoskeletal symptoms even in the absence of overt manifestations of hypothyroidism. To our knowledge, this is the first case reported in Korea. PMID:26394732

Testing of therapies in a novel nebulin nemaline myopathy model demonstrate a lack of efficacy.

PubMed

Sztal, Tamar E; McKaige, Emily A; Williams, Caitlin; Oorschot, Viola; Ramm, Georg; Bryson-Richardson, Robert J

2018-05-30

Nemaline myopathies are heterogeneous congenital muscle disorders causing skeletal muscle weakness and, in some cases, death soon after birth. Mutations in nebulin, encoding a large sarcomeric protein required for thin filament function, are responsible for approximately 50% of nemaline myopathy cases. Despite the severity of the disease there is no effective treatment for nemaline myopathy with limited research to develop potential therapies. Several supplements, including L-tyrosine, have been suggested to be beneficial and consequently self-administered by nemaline myopathy patients without any knowledge of their efficacy. We have characterized a zebrafish model for nemaline myopathy caused by a mutation in nebulin. These fish form electron-dense nemaline bodies and display reduced muscle function akin to the phenotypes observed in nemaline myopathy patients. We have utilized our zebrafish model to test and evaluate four treatments currently self-administered by nemaline myopathy patients to determine their ability to increase skeletal muscle function. Analysis of muscle pathology and locomotion following treatment with L-tyrosine, L-carnitine, taurine, or creatine revealed no significant improvement in skeletal muscle function emphasizing the urgency to develop effective therapies for nemaline myopathy.

Diagnosis and classification of Idiopathic Inflammatory Myopathies

PubMed Central

Lundberg, Ingrid E.; Miller, Frederick W.; Tjärnlund, Anna; Bottai, Matteo

2016-01-01

The idiopathic inflammatory myopathies (IIMs) are a heterogeneous group of diseases, collectively named myositis, sharing symptoms of muscle weakness and muscle fatigue and inflammation in muscle tissue. Other organs are frequently involved supporting that these are systemic inflammatory diseases. The IIMs can be sub-grouped into dermatomyositis, polymyositis and inclusion body myositis. The myositis-specific autoantibodies (MSAs) identify other and often more distinct clinical phenotypes, such as the anti-synthetase syndrome with antisynthetase autoantibodies and frequent interstitial lung disease (ILD) and anti-SRP and anti-HMGCR autoantibodies that identify necrotizing myopathy. The MSAs are important both to support myositis diagnosis and to identify subgroups with different patterns of extramuscular organ involvement such as ILD. Another cornerstone in the diagnostic procedure is muscle biopsy to identify inflammation and to exclude non-inflammatory myopathies. Treatment effect and prognosis varies by subgroup. To develop new and better therapies, validated classification criteria that identify distinct subgroups of myositis are critical.. The lack of such criteria was the main rationale for the development of new classification criteria for inflammatory myopathies, which are summarized in this review, along with an historical background on previous diagnostic and classification criteria. As these are rare diseases with a prevalence of 10 in 100 000 individuals an international collaboration was essential, as was the interdisciplinary effort including adult and paediatric experts in rheumatology, neurology, dermatology and epidemiology. The new criteria have been developed based on data from more than 1 500 patients from 47 centers world-wide and are based on clinically easily available variables. PMID:27320359

REV-ERB and ROR: therapeutic targets for treating myopathies

NASA Astrophysics Data System (ADS)

Welch, Ryan D.; Flaveny, Colin A.

2017-08-01

Muscle is primarily known for its mechanical roles in locomotion, maintenance of posture, and regulation of cardiac and respiratory function. There are numerous medical conditions that adversely affect muscle, myopathies that disrupt muscle development, regeneration and protein turnover to detrimental effect. Skeletal muscle is also a vital secretory organ that regulates thermogenesis, inflammatory signaling and directs context specific global metabolic changes in energy substrate preference on a daily basis. Myopathies differ in the causative factors that drive them but share common features including severe reduction in quality of life and significantly increased mortality all due irrefutably to the loss of muscle mass. Thus far clinically viable approaches for preserving muscle proteins and stimulating new muscle growth without unwanted side effects or limited efficacy has been elusive. Over the last few decades, evidence has emerged through in vitro and in vivo studies that suggest the nuclear receptors REV-ERB and ROR might modulate pathways involved in myogenesis and mitochondrial biogenesis. Hinting that REV-ERB and ROR might be targeted to treat myopathies. However there is still a need for substantial investigation into the roles of these nuclear receptors in in vivo rodent models of degenerative muscle diseases and acute injury. Although exciting, REV-ERB and ROR have somewhat confounding roles in muscle physiology and therefore more studies utilizing in vivo models of skeletal muscle myopathies are needed. In this review we highlight the molecular forces driving some of the major degenerative muscular diseases and showcase two promising molecular targets that may have the potential to treat myopathies: ROR and REV-ERB.

Myofibrillar myopathies: State of the art, present and future challenges.

PubMed

Béhin, A; Salort-Campana, E; Wahbi, K; Richard, P; Carlier, R-Y; Carlier, P; Laforêt, P; Stojkovic, T; Maisonobe, T; Verschueren, A; Franques, J; Attarian, S; Maues de Paula, A; Figarella-Branger, D; Bécane, H-M; Nelson, I; Duboc, D; Bonne, G; Vicart, P; Udd, B; Romero, N; Pouget, J; Eymard, B

2015-10-01

Myofibrillar myopathies (MFM) have been described in the mid-1990s as a group of diseases sharing common histological features, including an abnormal accumulation of intrasarcoplasmic proteins, the presence of vacuoles and a disorganization of the intermyofibrillar network beginning at the Z-disk. The boundaries of this concept are still uncertain, and whereas six genes (DES, CRYAB, LDB3/ZASP, MYOT, FLNC and BAG3) are now classically considered as responsible for MFM, other entities such as FHL1 myopathy or Hereditary Myopathy with Early Respiratory Failure linked to mutations of titin can now as well be included in this group. The diagnosis of MFM is not always easy; as histological lesions can be focal, and muscle biopsy may be disappointing; this has led to a growing importance of muscle imaging, and the selectivity of muscle involvement has now been described in several disorders. Due to the rarity of these myopathies, if some clinical patterns (such as distal myopathy associated with cardiomyopathy due to desmin mutations) are now well known, surprises remain possible and should lead to systematic testing of the known genes in case of a typical histological presentation. In this paper, we aim at reviewing the data acquired on the six main genes listed above as well as presenting the experience from two French reference centres, Paris and Marseilles. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Development of computer tablet software for clinical quantification of lateral knee compartment translation during the pivot shift test.

PubMed

Muller, Bart; Hofbauer, Marcus; Rahnemai-Azar, Amir Ata; Wolf, Megan; Araki, Daisuke; Hoshino, Yuichi; Araujo, Paulo; Debski, Richard E; Irrgang, James J; Fu, Freddie H; Musahl, Volker

2016-01-01

The pivot shift test is a commonly used clinical examination by orthopedic surgeons to evaluate knee function following injury. However, the test can only be graded subjectively by the examiner. Therefore, the purpose of this study is to develop software for a computer tablet to quantify anterior translation of the lateral knee compartment during the pivot shift test. Based on the simple image analysis method, software for a computer tablet was developed with the following primary design constraint - the software should be easy to use in a clinical setting and it should not slow down an outpatient visit. Translation of the lateral compartment of the intact knee was 2.0 ± 0.2 mm and for the anterior cruciate ligament-deficient knee was 8.9 ± 0.9 mm (p < 0.001). Intra-tester (ICC range = 0.913 to 0.999) and inter-tester (ICC = 0.949) reliability were excellent for the repeatability assessments. Overall, the average percent error of measuring simulated translation of the lateral knee compartment with the tablet parallel to the monitor increased from 2.8% at 50 cm distance to 7.7% at 200 cm. Deviation from the parallel position of the tablet did not have a significant effect until a tablet angle of 45°. Average percent error during anterior translation of the lateral knee compartment of 6mm was 2.2% compared to 6.2% for 2 mm of translation. The software provides reliable, objective, and quantitative data on translation of the lateral knee compartment during the pivot shift test and meets the design constraints posed by the clinical setting.

A Multi-Compartment 3-D Finite Element Model of Rectocele and Its Interaction with Cystocele

PubMed Central

Luo, Jiajia; Chen, Luyun; Fenner, Dee E.; Ashton-Miller, James A.; DeLancey, John O. L.

2015-01-01

We developed a subject-specific 3-D finite element model to understand the mechanics underlying formation of female pelvic organ prolapse, specifically a rectocele and its interaction with a cystocele. The model was created from MRI 3-D geometry of a healthy 45 year-old multiparous woman. It included anterior and posterior vaginal walls, levator ani muscle, cardinal and uterosacral ligaments, anterior and posterior arcus tendineus fascia pelvis, arcus tendineus levator ani, perineal body, perineal membrane and anal sphincter. Material properties were mostly from the literature. Tissue impairment was modeled as decreased tissue stiffness based on previous clinical studies. Model equations were solved using Abaqus v 6.11. The sensitivity of anterior and posterior vaginal wall geometry was calculated for different combinations tissue impairments under increasing intraabdominal pressure. Prolapse size was reported as POP-Q point at point Bp for rectocele and point Ba for cystocele. Results show that a rectocele resulted from impairments of the levator ani and posterior compartment support. For 20% levator and 85% posterior support impairments, simulated rectocele size (at POP-Q point: Bp) increased 0.29 mm/cm H2O without apical impairment and 0.36 mm/cm H2O with 60% apical impairment, as intraabdominal pressures increased from 0 to 150 cm H2O. Apical support impairment could result in the development of either a cystocele or rectocele. Simulated repair of posterior compartment support decreased rectocele but increased a preexisting cystocele. We conclude that development of rectocele and cystocele depend on the presence of anterior, posterior, levator and/or or apical support impairments, as well as the interaction of the prolapse with the opposing compartment. PMID:25757664

Potassium dependent rescue of a myopathy with core-like structures in mouse

PubMed Central

Hanson, M Gartz; Wilde, Jonathan J; Moreno, Rosa L; Minic, Angela D; Niswander, Lee

2015-01-01

Myopathies decrease muscle functionality. Mutations in ryanodine receptor 1 (RyR1) are often associated with myopathies with microscopic core-like structures in the muscle fiber. In this study, we identify a mouse RyR1 model in which heterozygous animals display clinical and pathological hallmarks of myopathy with core-like structures. The RyR1 mutation decreases sensitivity to activated calcium release and myoplasmic calcium levels, subsequently affecting mitochondrial calcium and ATP production. Mutant muscle shows a persistent potassium leak and disrupted expression of regulators of potassium homeostasis. Inhibition of KATP channels or increasing interstitial potassium by diet or FDA-approved drugs can reverse the muscle weakness, fatigue-like physiology and pathology. We identify regulators of potassium homeostasis as biomarkers of disease that may reveal therapeutic targets in human patients with myopathy of central core disease (CCD). Altogether, our results suggest that amelioration of potassium leaks through potassium homeostasis mechanisms may minimize muscle damage of myopathies due to certain RyR1 mutations. DOI: http://dx.doi.org/10.7554/eLife.02923.001 PMID:25564733

Compartment elasticity measured by pressure-related ultrasound to determine patients "at risk" for compartment syndrome: an experimental in vitro study.

PubMed

Sellei, Richard Martin; Hingmann, Simon Johannes; Kobbe, Philipp; Weber, Christian; Grice, John Edward; Zimmerman, Frauke; Jeromin, Sabine; Hildebrand, Frank; Pape, Hans-Christoph

2015-01-01

Decision-making in treatment of an acute compartment syndrome is based on clinical assessment, supported by invasive monitoring. Thus, evolving compartment syndrome may require repeated pressure measurements. In suspected cases of potential compartment syndromes clinical assessment alone seems to be unreliable. The objective of this study was to investigate the feasibility of a non-invasive application estimating whole compartmental elasticity by ultrasound, which may improve accuracy of diagnostics. In an in vitro model, using an artificial container simulating dimensions of the human anterior tibial compartment, intra-compartmental pressures (p) were raised subsequently up to 80 mmHg by infusion of saline solution. The compartmental depth (mm) in the cross-section view was measured before and after manual probe compression (100 mmHg) upon the surface resulting in a linear compartmental displacement (∆d). This was repeated at rising compartmental pressures. The resulting displacements were related to the corresponding intra-compartmental pressures simulated in our model. A hypothesized relationship between pressures related compartmental displacement and the elasticity at elevated compartment pressures was investigated. With rising compartmental pressures, a non-linear, reciprocal proportional relation between the displacement (mm) and the intra-compartmental pressure (mmHg) occurred. The Pearson coefficient showed a high correlation (r(2) = -0.960). The intra-observer reliability value kappa resulted in a statistically high reliability (κ = 0.840). The inter-observer value indicated a fair reliability (κ = 0.640). Our model reveals that a strong correlation between compartmental strain displacements assessed by ultrasound and the intra-compartmental pressure changes occurs. Further studies are required to prove whether this assessment is transferable to human muscle tissue. Determining the complete compartmental elasticity by ultrasound

Oxidative stress and successful antioxidant treatment in models of RYR1-related myopathy

PubMed Central

Arbogast, Sandrine; Hur, Junguk; Nelson, Darcee D.; McEvoy, Anna; Waugh, Trent; Marty, Isabelle; Lunardi, Joel; Brooks, Susan V.; Kuwada, John Y.; Ferreiro, Ana

2012-01-01

The skeletal muscle ryanodine receptor is an essential component of the excitation–contraction coupling apparatus. Mutations in RYR1 are associated with several congenital myopathies (termed RYR1-related myopathies) that are the most common non-dystrophic muscle diseases of childhood. Currently, no treatments exist for these disorders. Although the primary pathogenic abnormality involves defective excitation–contraction coupling, other abnormalities likely play a role in disease pathogenesis. In an effort to discover novel pathogenic mechanisms, we analysed two complementary models of RYR1-related myopathies, the relatively relaxed zebrafish and cultured myotubes from patients with RYR1-related myopathies. Expression array analysis in the zebrafish disclosed significant abnormalities in pathways associated with cellular stress. Subsequent studies focused on oxidative stress in relatively relaxed zebrafish and RYR1-related myopathy myotubes and demonstrated increased oxidant activity, the presence of oxidative stress markers, excessive production of oxidants by mitochondria and diminished survival under oxidant conditions. Exposure to the antioxidant N-acetylcysteine reduced oxidative stress and improved survival in the RYR1-related myopathies human myotubes ex vivo and led to significant restoration of aspects of muscle function in the relatively relaxed zebrafish, thereby confirming its efficacy in vivo. We conclude that oxidative stress is an important pathophysiological mechanism in RYR1-related myopathies and that N-acetylcysteine is a successful treatment modality ex vivo and in a vertebrate disease model. We propose that N-acetylcysteine represents the first potential therapeutic strategy for these debilitating muscle diseases. PMID:22418739

Recessive myosin myopathy with external ophthalmoplegia associated with MYH2 mutations.

PubMed

Tajsharghi, Homa; Hammans, Simon; Lindberg, Christopher; Lossos, Alexander; Clarke, Nigel F; Mazanti, Ingrid; Waddell, Leigh B; Fellig, Yakov; Foulds, Nicola; Katifi, Haider; Webster, Richard; Raheem, Olayinka; Udd, Bjarne; Argov, Zohar; Oldfors, Anders

2014-06-01

Myosin myopathies comprise a group of inherited diseases caused by mutations in myosin heavy chain (MyHC) genes. Homozygous or compound heterozygous truncating MYH2 mutations have been demonstrated to cause recessive myopathy with ophthalmoplegia, mild-to-moderate muscle weakness and complete lack of type 2A muscle fibers. In this study, we describe for the first time the clinical and morphological characteristics of recessive myosin IIa myopathy associated with MYH2 missense mutations. Seven patients of five different families with a myopathy characterized by ophthalmoplegia and mild-to-moderate muscle weakness were investigated. Muscle biopsy was performed to study morphological changes and MyHC isoform expression. Five of the patients were homozygous for MYH2 missense mutations, one patient was compound heterozygous for a missense and a nonsense mutation and one patient was homozygous for a frame-shift MYH2 mutation. Muscle biopsy demonstrated small or absent type 2A muscle fibers and reduced or absent expression of the corresponding MyHC IIa transcript and protein. We conclude that mild muscle weakness and ophthalmoplegia in combination with muscle biopsy demonstrating small or absent type 2A muscle fibers are the hallmark of recessive myopathy associated with MYH2 mutations.

Genetics Home Reference: myopathy with deficiency of iron-sulfur cluster assembly enzyme

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... Myopathy with deficiency of iron-sulfur cluster assembly enzyme Printable PDF Open All Close All Enable Javascript ... Myopathy with deficiency of iron-sulfur cluster assembly enzyme is an inherited disorder that primarily affects muscles ...

The safe zone for hip arthroscopy: a cadaveric assessment of central, peripheral, and lateral compartment portal placement.

PubMed

Robertson, William J; Kelly, Bryan T

2008-09-01

This study evaluated 11 arthroscopic portals (4 central, 4 peripheral, and 3 peritrochanteric) with regard to their proximity to neurovascular structures and the extra-articular path taken before entering their intended compartments. We established 11 standard portals in 10 cadaveric hips, under arthroscopic and fluoroscopic visualization, using 3/16-inch Steinmann pins. Each hip was dissected, and the relation of the pins to the pertinent anatomy was recorded to the nearest 1 mm. Only 2 of the 11 portals, the anterior and midanterior portals, came within 2 cm of a neurovascular structure before entering their respective compartments. The anterior portal placed the lateral femoral cutaneous nerve at risk, lying at a mean of 15.4 mm (range, 1 to 28 mm) away. The midanterior portal lies a mean of 19.2 mm (range, 5 to 42 mm) from the ascending branch of the lateral circumflex femoral artery. In addition, a small terminal branch of this artery courses a mean of 14.7 mm (range, 2 to 33 mm) and 10.1 mm (range, 1 to 23 mm) from the anterior portal and midanterior portal, respectively. This study showed that 11 arthroscopic portals can be safely inserted into the central, peripheral, and peritrochanteric compartments of the hip. The midanterior and anterior portals pass in close proximity to a small terminal branch of the ascending lateral circumflex femoral artery. The greatest risk still comes from the proximity of the anterior portal to the lateral femoral cutaneous nerve. However, a slightly more lateral location seems to provide substantial benefits. This study investigated 11 arthroscopic hip portals inserted in a standardized fashion. This knowledge should help surgeons place the necessary portals both safely and accurately.

Myopathy in Pediatric Thyroid States: A Review of the Literature.

PubMed

Dingle, Elena; Palliyil-Gopi, Resmy; Contreras, Maria; Kohn, Brenda; Brar, Preneet Cheema

2016-12-01

This review highlights the presentations of myopathy in children in both hypothyroid and hyperthyroid states with an emphasis on the pathophysiology, diagnosis and treatment. Based on our review of the literature data, myopathy should be considered in all children presenting with muscular weakness or altered muscle enzymes in the context of thyroid disease. Copyright© of YS Medical Media ltd.

The peri-esophageal connective tissue layers and related compartments: visualization by histology and magnetic resonance imaging.

PubMed

Weijs, T J; Goense, L; van Rossum, P S N; Meijer, G J; van Lier, A L H M W; Wessels, F J; Braat, M N G; Lips, I M; Ruurda, J P; Cuesta, M A; van Hillegersberg, R; Bleys, R L A W

2017-02-01

An organized layer of connective tissue coursing from aorta to esophagus was recently discovered in the mediastinum. The relations with other peri-esophageal fascias have not been described and it is unclear whether this layer can be visualized by non-invasive imaging. This study aimed to provide a comprehensive description of the peri-esophageal fascias and determine whether the connective tissue layer between aorta and esophagus can be visualized by magnetic resonance imaging (MRI). First, T2-weighted MRI scanning of the thoracic region of a human cadaver was performed, followed by histological examination of transverse sections of the peri-esophageal tissue between the thyroid gland and the diaphragm. Secondly, pretreatment motion-triggered MRI scans were prospectively obtained from 34 patients with esophageal cancer and independently assessed by two radiologists for the presence and location of the connective tissue layer coursing from aorta to esophagus. A layer of connective tissue coursing from the anterior aspect of the descending aorta to the left lateral aspect of the esophagus, with a thin extension coursing to the right pleural reflection, was visualized ex vivo in the cadaver on MR images, macroscopic tissue sections, and after histologic staining, as well as on in vivo MR images. The layer connecting esophagus and aorta was named 'aorto-esophageal ligament' and the layer connecting aorta to the right pleural reflection 'aorto-pleural ligament'. These connective tissue layers divides the posterior mediastinum in an anterior compartment containing the esophagus, (carinal) lymph nodes and vagus nerve, and a posterior compartment, containing the azygos vein, thoracic duct and occasionally lymph nodes. The anterior compartment was named 'peri-esophageal compartment' and the posterior compartment 'para-aortic compartment'. The connective tissue layers superior to the aortic arch and at the diaphragm corresponded with the currently available anatomic

Transient compartment-like syndrome and normokalaemic periodic paralysis due to a Cav1.1 mutation

PubMed Central

Fan, Chunxiang; Lehmann-Horn, Frank; Weber, Marc-André; Bednarz, Marcin; Groome, James R.; Jonsson, Malin K. B.

2013-01-01

We studied a two-generation family presenting with conditions that included progressive permanent weakness, myopathic myopathy, exercise-induced contracture before normokalaemic periodic paralysis or, if localized to the tibial anterior muscle group, transient compartment-like syndrome (painful acute oedema with neuronal compression and drop foot). 23Na and 1H magnetic resonance imaging displayed myoplasmic sodium overload, and oedema. We identified a novel familial Cav1.1 calcium channel mutation, R1242G, localized to the third positive charge of the domain IV voltage sensor. Functional expression of R1242G in the muscular dysgenesis mouse cell line GLT revealed a 28% reduced central pore inward current and a −20 mV shift of the steady-state inactivation curve. Both changes may be at least partially explained by an outward omega (gating pore) current at positive potentials. Moreover, this outward omega current of 27.5 nS/nF may cause the reduction of the overshoot by 13 mV and slowing of the upstroke of action potentials by 36% that are associated with muscle hypoexcitability (permanent weakness and myopathic myopathy). In addition to the outward omega current, we identified an inward omega pore current of 95 nS/nF at negative membrane potentials after long depolarizing pulses that shifts the R1242G residue above the omega pore constriction. A simulation reveals that the inward current might depolarize the fibre sufficiently to trigger calcium release in the absence of an action potential and therefore cause an electrically silent depolarization-induced muscle contracture. Additionally, evidence of the inward current can be found in 23Na magnetic resonance imaging-detected sodium accumulation and 1H magnetic resonance imaging-detected oedema. We hypothesize that the episodes are normokalaemic because of depolarization-induced compensatory outward potassium flux through both delayed rectifiers and omega pore. We conclude that the position of the R1242G residue

Inflammatory myopathy as the initial presentation of cryoglobulinaemic vasculitis.

PubMed

Rodríguez-Pérez, Noelia; Rodríguez-Navedo, Yerania; Font, Yvonne M; Vilá, Luis M

2013-06-03

Cryoglobulinaemic vasculitis is characterised by immunoglobulin deposition at low temperatures. The most common manifestations are cutaneous involvement, arthralgias, Raynaud's phenomenon, peripheral neuropathy and renal disease. Myopathy is unusual and only a few cases have been reported. Here, we present a 31-year-old woman who developed progressive muscle weakness involving upper and lower extremities, dysphagia, paraesthesias and palpable purpura. Diagnostic studies revealed elevated creatine kinase, diffuse myopathic and sensorimotor axonal neuropathy on electromyography and nerve conduction studies, and inflammatory myopathy on muscle biospsy. Cryoglobulin levels were elevated on two occasions. She responded favourably to cyclophosphamide and high-dose corticosteroids. Cyclophosphamide was continued for 1 year followed by methotrexate. Prednisone was gradually tapered and discontinued 1 year later. She remained in clinical remission after 4 years of follow-up. This case suggests that cryoglobulinaemia should be considered in the differential diagnosis of a patient presenting with inflammatory myopathy.

Myosin storage myopathy: slow skeletal myosin (MYH7) mutation in two isolated cases.

PubMed

Laing, N G; Ceuterick-de Groote, C; Dye, D E; Liyanage, K; Duff, R M; Dubois, B; Robberecht, W; Sciot, R; Martin, J-J; Goebel, H H

2005-02-08

Myosin storage myopathy is a congenital myopathy characterized by subsarcolemmal hyaline bodies in type 1 muscle fibers, which are ATPase positive and thus contain myosin. Mutations recently were identified in the type 1 muscle fiber myosin gene (MYH7) in Swedish and Saudi families with myosin storage myopathy. The authors have identified the arginine 1845 tryptophan mutation found in the Swedish families in two isolated Belgian cases, indicating a critical role for myosin residue arginine 1845.

Capture myopathy in a moose.

PubMed

Haigh, J C; Stewart, R R; Wobeser, G; MacWilliams, P S

1977-11-01

Of 18 moose captured by dart immobilization from a helicopter, 1 became recumbent after release. Blood samples were collected at the time of capture and on the following 2 days. Serum creatine phosphokinase and glutamic-oxalacetic transaminase activities increased, and serum potassium concentrations decreased. Necropsy revealed extensive myopathy.

SLCO1B1 variants and statin-induced myopathy--a genomewide study.

PubMed

Link, E; Parish, S; Armitage, J; Bowman, L; Heath, S; Matsuda, F; Gut, I; Lathrop, M; Collins, R

2008-08-21

Lowering low-density lipoprotein cholesterol with statin therapy results in substantial reductions in cardiovascular events, and larger reductions in cholesterol may produce larger benefits. In rare cases, myopathy occurs in association with statin therapy, especially when the statins are administered at higher doses and with certain other medications. We carried out a genomewide association study using approximately 300,000 markers (and additional fine-mapping) in 85 subjects with definite or incipient myopathy and 90 controls, all of whom were taking 80 mg of simvastatin daily as part of a trial involving 12,000 participants. Replication was tested in a trial of 40 mg of simvastatin daily involving 20,000 participants. The genomewide scan yielded a single strong association of myopathy with the rs4363657 single-nucleotide polymorphism (SNP) located within SLCO1B1 on chromosome 12 (P=4x10(-9)). SLCO1B1 encodes the organic anion-transporting polypeptide OATP1B1, which has been shown to regulate the hepatic uptake of statins. The noncoding rs4363657 SNP was in nearly complete linkage disequilibrium with the nonsynonymous rs4149056 SNP (r(2)=0.97), which has been linked to statin metabolism. The prevalence of the rs4149056 C allele in the population was 15%. The odds ratio for myopathy was 4.5 (95% confidence interval [CI], 2.6 to 7.7) per copy of the C allele, and 16.9 (95% CI, 4.7 to 61.1) in CC as compared with TT homozygotes. More than 60% of these myopathy cases could be attributed to the C variant. The association of rs4149056 with myopathy was replicated in the trial of 40 mg of simvastatin daily, which also showed an association between rs4149056 and the cholesterol-lowering effects of simvastatin. No SNPs in any other region were clearly associated with myopathy. We have identified common variants in SLCO1B1 that are strongly associated with an increased risk of statin-induced myopathy. Genotyping these variants may help to achieve the benefits of statin

Chronic exertional compartment syndrome with medial tibial stress syndrome in twins.

PubMed

Banerjee, Purnajyoti; McLean, Christopher

2011-06-14

Chronic exertional compartment syndrome and medial tibial stress syndrome are uncommon conditions that affect long-distance runners or players involved in team sports that require extensive running. We report 2 cases of bilateral chronic exertional compartment syndrome, with medial tibial stress syndrome in identical twins diagnosed with the use of a Kodiag monitor (B. Braun Medical, Sheffield, United Kingdom) fulfilling the modified diagnostic criteria for chronic exertional compartment syndrome as described by Pedowitz et al, which includes: (1) pre-exercise compartment pressure level >15 mm Hg; (2) 1 minute post-exercise pressure >30 mm Hg; and (3) 5 minutes post-exercise pressure >20 mm Hg in the presence of clinical features. Both patients were treated with bilateral anterior fasciotomies through minimal incision and deep posterior fasciotomies with tibial periosteal stripping performed through longer anteromedial incisions under direct vision followed by intensive physiotherapy resulting in complete symptomatic recovery. The etiology of chronic exertional compartment syndrome is not fully understood, but it is postulated abnormal increases in intramuscular pressure during exercise impair local perfusion, causing ischemic muscle pain. No familial predisposition has been reported to date. However, some authors have found that no significant difference exists in the relative perfusion, in patients, diagnosed with chronic exertional compartment syndrome. Magnetic resonance images of affected compartments have indicated that the pain is not due to ischemia, but rather from a disproportionate oxygen supply versus demand. We believe this is the first report of chronic exertional compartment syndrome with medial tibial stress syndrome in twins, raising the question of whether there is a genetic predisposition to the causation of these conditions. Copyright 2011, SLACK Incorporated.

Inflammatory myopathy as the initial presentation of cryoglobulinaemic vasculitis

PubMed Central

Rodríguez-Pérez, Noelia; Rodríguez-Navedo, Yerania; Font, Yvonne M; Vilá, Luis M

2013-01-01

Cryoglobulinaemic vasculitis is characterised by immunoglobulin deposition at low temperatures. The most common manifestations are cutaneous involvement, arthralgias, Raynaud's phenomenon, peripheral neuropathy and renal disease. Myopathy is unusual and only a few cases have been reported. Here, we present a 31-year-old woman who developed progressive muscle weakness involving upper and lower extremities, dysphagia, paraesthesias and palpable purpura. Diagnostic studies revealed elevated creatine kinase, diffuse myopathic and sensorimotor axonal neuropathy on electromyography and nerve conduction studies, and inflammatory myopathy on muscle biospsy. Cryoglobulin levels were elevated on two occasions. She responded favourably to cyclophosphamide and high-dose corticosteroids. Cyclophosphamide was continued for 1 year followed by methotrexate. Prednisone was gradually tapered and discontinued 1 year later. She remained in clinical remission after 4 years of follow-up. This case suggests that cryoglobulinaemia should be considered in the differential diagnosis of a patient presenting with inflammatory myopathy. PMID:23737595

Statin-induced necrotizing myositis - a discrete autoimmune entity within the "statin-induced myopathy spectrum".

PubMed

Hamann, Philip D H; Cooper, Robert G; McHugh, Neil J; Chinoy, Hector

2013-10-01

Statin-induced necrotizing myositis is increasingly being recognised as part of the "statin-induced myopathy spectrum". As in other immune-mediated necrotizing myopathies, statin-induced myositis is characterised by proximal muscle weakness with marked serum creatinine kinase elevations and histological evidence of myonecrosis, with little or no inflammatory cell infiltration. Unlike other necrotizing myopathies, statin-induced myopathy is associated with the presence of autoantibodies directed against 3-hydroxy-3-methylglutaryl- coenzyme A reductase (the enzyme target of statin therapies), and with Human Leukocyte Antigen-DRB1*11. This article summarises the clinical presentation, investigations and management of this rare, but serious complication of statin therapy. © 2013 Elsevier B.V. All rights reserved.

GNE Myopathy in Turkish Sisters with a Novel Homozygous Mutation

PubMed Central

Diniz, Gulden; Secil, Yaprak; Ceylaner, Serdar; Tokucoglu, Figen; Türe, Sabiha; Celebisoy, Mehmet; İncesu, Tülay Kurt; Akhan, Galip

2016-01-01

Background. Hereditary inclusion body myopathy is caused by biallelic defects in the GNE gene located on chromosome 9p13. It generally affects adults older than 20 years of age. Methods and Results. In this study, we present two Turkish sisters with progressive myopathy and describe a novel mutation in the GNE gene. Both sisters had slightly higher levels of creatine kinase (CK) and muscle weakness. The older sister presented at 38 years of age with an inability to climb steps, weakness, and a steppage gait. Her younger sister was 36 years old and had similar symptoms. The first symptoms of the disorder were seen when the sisters were 30 and 34 years old, respectively. The muscle biopsy showed primary myopathic features and presence of rimmed vacuoles. DNA analysis demonstrated the presence of previously unknown homozygous mutations [c.2152 G>A (p.A718T)] in the GNE genes. Conclusion. Based on our literature survey, we believe that ours is the first confirmed case of primary GNE myopathy with a novel missense mutation in Turkey. These patients illustrate that the muscle biopsy is still an important method for the differential diagnosis of vacuolar myopathies in that the detection of inclusions is required for the definitive diagnosis. PMID:27298745

Surgical treatment of chronic exertional compartment syndrome of the leg: failure rates and postoperative disability in an active patient population.

PubMed

Waterman, Brian R; Laughlin, Matthew; Kilcoyne, Kelly; Cameron, Kenneth L; Owens, Brett D

2013-04-03

Chronic exertional compartment syndrome of the leg is a frequent source of lower-extremity pain in military personnel, competitive athletes, and runners. We are not aware of any previous study in which the authors rigorously evaluated the rates of return to full activity, persistent disability, and surgical revision after operative management of chronic exertional compartment syndrome of the leg in a large, physically active population. Individuals who had undergone surgical fasciotomy of the anterior, lateral, and/or posterior compartments (current procedural terminology [CPT] codes 27600, 27601, and 27602) for nontraumatic compartment syndrome of the lower extremity (International Classification of Diseases, Ninth Revision [ICD-9] code 729.72) between 2003 and 2010 were identified from the Military Health System Management Analysis and Reporting Tool (M2). Demographic variables including age, sex, and rank were extracted, and rates of postoperative complications, activity limitations, and revision surgery or medical discharge were obtained from the electronic medical record and U.S. Army Physical Disability Agency database. A total of 611 patients underwent 754 surgical procedures. The average patient age was 28.0 years, and 91.8% of the patients were male. Of the surgical procedures, 77.4% involved only anterior and lateral compartment releases; 19.4% addressed the anterior, lateral, and posterior compartments; and 2.2% addressed the posterior compartments alone. Symptom recurrence was reported by 44.7% of the patients, and 27.7% were unable to return to full activity. Surgical complications were documented for 15.7% of the patients, 5.9% underwent surgical revision, and 17.3% were referred for medical discharge because of chronic exertional compartment syndrome. Univariate analysis of prognostic factors revealed that surgical failure was associated with bilateral involvement (odds ratio [OR], 1.64), perioperative complications (OR, 2.12), activity limitations

Elevated compartment pressures from copperhead envenomation successfully treated with antivenin.

PubMed

Mazer-Amirshahi, Maryann; Boutsikaris, Amy; Clancy, Cathleen

2014-01-01

Copperhead envenomation causes local soft tissue effects; however, associated compartment syndrome is rare. We report a case of a 17-month-old with significantly elevated compartment pressures successfully treated with antivenin and supportive care. A 17-month-old girl sustained a copperhead bite to the foot and presented with circumferential edema, erythema, and ecchymosis of the foot and distal ankle. The patient had palpable pulses and was neurologically intact. Four vials of Crotalidae polyvalent immune Fab was initiated and additional doses were administered in an attempt to achieve local control. Within 10 h of presentation, the patient's edema extended to the groin, although sensation was maintained and pulses were documented by Doppler. Lower-extremity compartment pressures were measured and were most notable for an anterior pressure of 85 mm Hg, despite having received 12 vials of antivenin. Fasciotomy was deferred and the patient received two additional six-vial doses of antivenin to achieve local control. Compartment pressures improved with a 2.2-cm mean decrease in limb diameter within 48 h. Maintenance dosing was initiated and the patient ultimately received a total of 26 vials of antivenin. The patient did not develop significant coagulopathy or thrombocytopenia. Swelling continued to improve with return of limb function. In this case, early and aggressive treatment with antivenin may have avoided invasive fasciotomy, and its use should be considered in patients with copperhead envenomation and significantly elevated compartment pressures. Copyright © 2014 Elsevier Inc. All rights reserved.

Centronuclear myopathy in a Border collie dog.

PubMed

Eminaga, S; Cherubini, G B; Shelton, G D

2012-10-01

A two-year old, male entire Border collie was presented with a one-year history of exercise-induced collapsing on the pelvic limbs. Physical examination revealed generalised muscle atrophy. Neurological examination supported a generalised neuromuscular disorder. Electromyography revealed spontaneous electrical activity in almost all muscles. Unfixed and formaldehyde-fixed biopsy samples were collected from the triceps brachii, longissimus and vastus lateralis muscles. Histopathological, histochemical and ultrastructural examinations of biopsy specimens were consistent with either centronuclear or myotubular myopathy. The dog clinically improved with supportive treatment with L-carnitine, co-enzyme Q10 and vitamin B compound. To the authors' knowledge, this is the first report of centronuclear/myotubular myopathy in a Border collie. © 2012 British Small Animal Veterinary Association.

Risk of Colchicine-Associated Myopathy in Gout: Influence of Concomitant Use of Statin.

PubMed

Kwon, Oh Chan; Hong, Seokchan; Ghang, Byeongzu; Kim, Yong-Gil; Lee, Chang-Keun; Yoo, Bin

2017-05-01

The purpose of this study was to investigate the risk of myopathy when statins are coadministered with colchicine in patients with gout. In gout patients who received colchicine with or without statin, clinical data collected included medications and history of hypertension, chronic kidney disease, and liver cirrhosis. Myopathy was defined as the presence of muscle symptoms with elevated creatine kinase or myoglobin. Multivariate analysis was performed to identify risk factors for myopathy. Inverse probability of treatment weighting (IPTW)-adjusted analysis was used to evaluate the influence of concomitant colchicine and statin use on myopathy. Of 674 patients, 486 received colchicine alone and 188 also received statin. The incidence of myopathy was not significantly higher in those on both drugs than in those on colchicine alone (2.7% vs 1.4%, P = .330). On multivariate analysis, chronic kidney disease (hazard ratio [HR] 29.056; 95% confidence interval [CI], 4.387-192.450; P <.001), liver cirrhosis (HR 10.676; 95% CI, 1.279-89.126; P = .029), higher colchicine dose (HR 20.960; 95% CI, 1.835-239.481; P = .014), and concomitant CYP3A4 inhibitor (HR 12.027; 95% CI, 2.743-52.725; P = .001) were associated with increased risk of myopathy. Concomitant use of statins, however, was not, even after adjusting for confounders (HR 1.123; 95% CI, 0.262-4.814; P = .875; IPTW-adjusted HR 0.321; 95% CI, 0.077-1.345; P = .120). Concomitant use of statin and colchicine was not associated with increased risk of myopathy. Thus, concomitant use of statin with colchicine seems to be safe from myotoxicity in gout patients. Copyright © 2017 Elsevier Inc. All rights reserved.

Myalgia as the revealing symptom of multicore disease and fibre type disproportion myopathy

PubMed Central

Sobreira*, C; Marques, W; Barreira, A

2003-01-01

Objective: To report the occurrence of myalgia as the revealing symptom of multicore disease and fibre type disproportion myopathy. Methods: The clinical cases of three patients with fibre type disproportion myopathy and one with multicore disease are described. Skeletal muscle biopsies were processed for routine histological and histochemical studies. Results: The clinical picture was unusual in that the symptoms were of late onset and the predominant complaint was muscle pain exacerbated by exercise. Muscle weakness was found in only a single patient, the mother of a patient with fibre type disproportion myopathy. Physical examination was unremarkable in the other patients. Muscle biopsies from patients 1 and 2 contained type I fibres that were considerably smaller than the type II fibres, supporting the diagnosis of fibre type disproportion myopathy. Skeletal muscle of patient 4 showed multiple areas, predominantly but not exclusively in the type I fibres, from which oxidative enzyme activities were absent, as seen in multicore disease. Conclusions: Muscle pain was the main clinical manifestation in our patients. Recognition of the broader clinical expression of these myopathies is important for prognostic reasons and for genetic counselling of the family members. PMID:12933945

Anatomical Study of Temporal Fat Compartments and its Clinical Application for Temporal Fat Grafting

PubMed Central

Huang, Ru-Lin; Xie, Yun; Wang, Wenjin; Herrler, Tanja; Zhou, Jia; Zhao, Peijuan; Pu, Lee LQ; Li, Qingfeng

2017-01-01

Abstract Background Low satisfaction rates and severe complications are two major limitations for temporal hollowing augmentation using autologous fat grafting. Despite fat compartments in temporal region have been reported, its clinical applied anatomy for fat grafting have not been the subject of studies that show its benefits objectively and statistically. Objectives To investigate temporal fat compartments and relative neurovascular structures in cadavers, developing a safe and effective fat grafting technique for temporal hollowing augmentation. Methods The study was conducted on 8 cadavers (16 temples). The tissue layers, fat compartments, ligaments, and neurovascular structures in the temporal region were analysed. The variables were the number and location of sentinel veins, perforator vessels of the middle temporal vein. Measurements were taken with a digital calliper. Results Two separate fat compartments, the lateral temporal-cheek fat compartment and lateral orbital fat compartment, were found in the subcutaneous layer, and two separate septum compartments, the upper and lower temporal compartment, were found in the loose areolar tissue layer. One sentinel vein and 1 to 6 perforator vessels were found to travel through the subcutaneous tissue layer, traverse the overlapping tissue layers in the lower temporal septum region, and finally join in the middle temporal vein. Conclusions The four fat compartments in the temporal region are ideal receipt sites for fat grafting. The medial border of the junction of the hairline and temporal line is a safe and effective cannula entry site for temporal fat grafting. The anterior half of the lower temporal compartment is a “zone of caution” for temporal fat grafting. PMID:28520850

[Application of targeted capture technology and next generation sequencing in molecular diagnosis of inherited myopathy].

PubMed

Fu, Xiaona; Liu, Aijie; Yang, Haipo; Wei, Cuijie; Ding, Juan; Wang, Shuang; Wang, Jingmin; Yuan, Yun; Jiang, Yuwu; Xiong, Hui

2015-10-01

To elucidate the usefulness of next generation sequencing for diagnosis of inherited myopathy, and to analyze the relevance between clinical phenotype and genotype in inherited myopathy. Related genes were selected for SureSelect target enrichment system kit (Panel Version 1 and Panel Version 2). A total of 134 patients who were diagnosed as inherited myopathy clinically underwent next generation sequencing in Department of Pediatrics, Peking University First Hospital from January 2013 to June 2014. Clinical information and gene detection result of the patients were collected and analyzed. Seventy-seven of 134 patients (89 males and 45 females, visiting ages from 6-month-old to 26-year-old, average visiting age was 6 years and 1 month) underwent next generation sequencing by Panel Version 1 in 2013, and 57 patients underwent next generation sequencing by Panel Version 2 in 2014. The gene detection revealed that 74 patients had pathogenic gene mutations, and the positive rate of genetic diagnosis was 55.22%. One patient was diagnosed as metabolic myopathy. Five patients were diagnosed as congenital myopathy; 68 were diagnosed as muscular dystrophy, including 22 with congenital muscular dystrophy 1A (MDC1A), 11 with Ullrich congenital muscular dystrophy (UCMD), 6 with Bethlem myopathy (BM), 12 with Duchenne muscular dystrophy (DMD) caused by point mutations in DMD gene, 5 with LMNA-related congenital muscular dystrophy (L-CMD), 1 with Emery-Dreifuss muscular dystrophy (EDMD), 7 with alpha-dystroglycanopathy (α-DG) patients, and 4 with limb-girdle muscular dystrophy (LGMD) patients. Next generation sequencing plays an important role in diagnosis of inherited myopathy. Clinical and biological information analysis was essential for screening pathogenic gene of inherited myopathy.

Myopathy and hepatic lipidosis in weaned lambs due to vitamin E deficiency.

PubMed

Menzies, Paula; Langs, Lisa; Boermans, Herman; Martin, John; McNally, John

2004-03-01

A sheep flock experienced losses in weaned lambs from myopathy and hepatic lipidosis. Investigation revealed painful ambulation, illthrift, and unexpected death in lambs with normal selenium levels, deficient vitamin E levels, and elevated muscle and liver enzyme levels. Vitamin E deficiency should be considered when investigating myopathy and illthrift in lambs.

Muscle-specific AMPK β1β2-null mice display a myopathy due to loss of capillary density in nonpostural muscles

PubMed Central

Thomas, Melissa M.; Wang, David C.; D'Souza, Donna M.; Krause, Matthew P.; Layne, Andrew S.; Criswell, David S.; O'Neill, Hayley M.; Connor, Michael K.; Anderson, Judy E.; Kemp, Bruce E.; Steinberg, Gregory R.; Hawke, Thomas J.

2014-01-01

AMP-activated protein kinase (AMPK) is a master regulator of metabolism. While muscle-specific AMPK β1β2 double-knockout (β1β2M-KO) mice display alterations in metabolic and mitochondrial capacity, their severe exercise intolerance suggested a secondary contributor to the observed phenotype. We find that tibialis anterior (TA), but not soleus, muscles of sedentary β1β2M-KO mice display a significant myopathy (decreased myofiber areas, increased split and necrotic myofibers, and increased centrally nucleated myofibers. A mitochondrial- and fiber-type-specific etiology to the myopathy was ruled out. However, β1β2M-KO TA muscles displayed significant (P<0.05) increases in platelet aggregation and apoptosis within myofibers and surrounding interstitium (P<0.05). These changes correlated with a 45% decrease in capillary density (P<0.05). We hypothesized that the β1β2M-KO myopathy in resting muscle resulted from impaired AMPK-nNOSμ signaling, causing increased platelet aggregation, impaired vasodilation, and, ultimately, ischemic injury. Consistent with this hypothesis, AMPK-specific phosphorylation (Ser1446) of nNOSμ was decreased in β1β2M-KO compared to wild-type (WT) mice. The AMPK-nNOSμ relationship was further demonstrated by administration of 5-aminoimidazole-4-carboxamide 1-β-d-ribofuranoside (AICAR) to β1β2-MKO muscles and C2C12 myotubes. AICAR significantly increased nNOSμ phosphorylation and nitric oxide production (P<0.05) within minutes of administration in WT muscles and C2C12 myotubes but not in β1β2M-KO muscles. These findings highlight the importance of the AMPK-nNOSμ pathway in resting skeletal muscle.—Thomas, M. M., Wang, D. C., D'Souza, D. M., Krause, M. P., Layne, A. S., Criswell, D. S., O'Neill, H. M., Connor, M. K., Anderson, J. E., Kemp, B. E., Steinberg, G. R., and Hawke, T. J. Muscle-specific AMPK β1β2-null mice display a myopathy due to loss of capillary density in nonpostural muscles. PMID:24522207

Severe polysaccharide storage myopathy in Belgian and Percheron draught horses.

PubMed

Valentine, B A; Credille, K M; Lavoie, J P; Fatone, S; Guard, C; Cummings, J F; Cooper, B J

1997-05-01

A severe myopathy leading to death or euthanasia was identified in 4 Belgian and 4 Percheron draught horses age 2-21 years. Clinical signs ranged from overt weakness and muscle atrophy in 2 horses age 2 and 3 years, to recumbency with inability to rise in 6 horses age 4-21 years. In 5 horses there was mild to severe increases in muscle enzyme levels. Clinical diagnoses included equine motor neuron disease (2 horses), post anaesthetic myopathy (2 horses), exertional myopathy (2 horses), myopathy due to unknown (one horse), and equine protozoal myelitis (one horse). Characteristic histopathology of muscle from affected horses was the presence of excessive complex polysaccharide and/or glycogen, revealed by periodic acid-Schiff staining in all cases and by electron microscopy in one case. Evaluation of frozen section histochemistry performed on 2 cases indicated that affected fibres were Type 2 glycolytic fibres. Subsarcolemmal and intracytoplasmic vacuoles were most prominent in 3 horses age 2-4 years, and excessive glycogen, with little or no complex polysaccharide, was the primary compound stored in affected muscle in these young horses. Myopathic changes, including fibre size variation, fibre hypertrophy, internal nuclei, and interstitial fat infiltration, were most prominent in 5 horses age 6-21 years, and the accumulation of complex polysaccharide appeared to increase with age. Mild to moderate segmental myofibre necrosis was present in all cases.

Myopathy and hepatic lipidosis in weaned lambs due to vitamin E deficiency

PubMed Central

2004-01-01

Abstract A sheep flock experienced losses in weaned lambs from myopathy and hepatic lipidosis. Investigation revealed painful ambulation, illthrift, and unexpected death in lambs with normal selenium levels, deficient vitamin E levels, and elevated muscle and liver enzyme levels. Vitamin E deficiency should be considered when investigating myopathy and illthrift in lambs. PMID:15072198

Search for Pompe disease among patients with undetermined myopathies.

PubMed

Lindberg, C; Anderson, B; Engvall, M; Hult, M; Oldfors, A

2015-07-20

Pompe disease is a rare treatable glycogen storage disease with in adults - a limb-girdle muscle weakness. Muscle biopsy may fail to show the typical vacuolar myopathy. We asked if we had un-diagnosed patients with Pompe disease in western Sweden. We searched the muscle biopsy registry during the time period 1986 until 2006 including 3665 biopsies and included patients at our Neuromuscular Center with unspecified myopathy or limb-girdle muscular dystrophy. The dry blood spot test was used to identify patients with Pompe disease. A total of 82 patients (46 from the biopsy register and 36 from our center) were seen and dry blood spot test was obtained. No patient with Pompe disease was found. The dry blood spot test was low in three cases (11, 16, and 18% of normal) but a second blood sample showed a normal result based on GAA enzyme activity in lymphocytes in all three patients. In one patient with low normal result of the analysis in lymphocytes a genetic test showed no pathogenic mutations. Further investigation gave a definite diagnose of another myopathy in 12 patients. The prevalence of Pompe disease in western Sweden (3 in 1.27 million or 0.24 per 100.000 inhabitants) is lower than in the Netherlands and New York. Re-evaluation of patients with myopathies but without definite diagnosis is rewarding since 12 of 82 patients in our study had a definite molecular diagnosis after workup. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

[Biologic therapy in idiopathic inflammatory myopathy].

PubMed

Selva-O'Callaghan, Albert; Ramos Casals, Manel; Grau Junyent, Josep M

2014-09-15

The aim of this article is to study the evidence-based knowledge related to the use of biological therapies in patients diagnosed with idiopathic inflammatory myopathy (dermatomyositis, polymyositis and inclusion body myositis). In this review the leading published studies related to the use of biological therapy in patients with myositis are analysed; mainly those with high methodological standards, that means randomized and controlled studies. Methodological drawbacks due to the rarity and heterogeneity of these complex diseases are also addressed. Up to now is not possible to ascertain the biologics as a recommended therapy in patients with myositis, at least based in the current evidence-based knowledge, although it can not be neglected as a therapeutic option in some clinical situations, taking into account the scarce of effective treatments in those patients, especially in refractory myositis. Future studies probably will help to better define the role of biological therapies in patients with idiopathic inflammatory myopathy. Copyright © 2013 Elsevier España, S.L.U. All rights reserved.

Targeted Re-Sequencing Emulsion PCR Panel for Myopathies: Results in 94 Cases.

PubMed

Punetha, Jaya; Kesari, Akanchha; Uapinyoying, Prech; Giri, Mamta; Clarke, Nigel F; Waddell, Leigh B; North, Kathryn N; Ghaoui, Roula; O'Grady, Gina L; Oates, Emily C; Sandaradura, Sarah A; Bönnemann, Carsten G; Donkervoort, Sandra; Plotz, Paul H; Smith, Edward C; Tesi-Rocha, Carolina; Bertorini, Tulio E; Tarnopolsky, Mark A; Reitter, Bernd; Hausmanowa-Petrusewicz, Irena; Hoffman, Eric P

2016-05-27

Molecular diagnostics in the genetic myopathies often requires testing of the largest and most complex transcript units in the human genome (DMD, TTN, NEB). Iteratively targeting single genes for sequencing has traditionally entailed high costs and long turnaround times. Exome sequencing has begun to supplant single targeted genes, but there are concerns regarding coverage and needed depth of the very large and complex genes that frequently cause myopathies. To evaluate efficiency of next-generation sequencing technologies to provide molecular diagnostics for patients with previously undiagnosed myopathies. We tested a targeted re-sequencing approach, using a 45 gene emulsion PCR myopathy panel, with subsequent sequencing on the Illumina platform in 94 undiagnosed patients. We compared the targeted re-sequencing approach to exome sequencing for 10 of these patients studied. We detected likely pathogenic mutations in 33 out of 94 patients with a molecular diagnostic rate of approximately 35%. The remaining patients showed variants of unknown significance (35/94 patients) or no mutations detected in the 45 genes tested (26/94 patients). Mutation detection rates for targeted re-sequencing vs. whole exome were similar in both methods; however exome sequencing showed better distribution of reads and fewer exon dropouts. Given that costs of highly parallel re-sequencing and whole exome sequencing are similar, and that exome sequencing now takes considerably less laboratory processing time than targeted re-sequencing, we recommend exome sequencing as the standard approach for molecular diagnostics of myopathies.

Zidovudine-induced myopathy: A study in Indian patients.

PubMed

Sagar, Amitabh; Mohanty, Ambika P; Bahal, Ashish

2010-07-01

Literature is replete with studies on zidovudine-induced myopathy after prolonged use (use beyond 270 days on an average). However, all these studies have been done on patients of Caucasian, American and African ethnic origin. No such study has been carried out in Indian patients to our knowledge. To determine the correlation of zidovudine usage with serum creatine phosphokinase (CK) levels, clinical muscular weakness and muscle histology in Indian patients, we studied 147 physically active, Human Immunodeficiency Virus infected men on prolonged zidovudine-based antiretroviral therapy (ART). Cross-sectional study on hospital follow-up patients of HIV infection. All cases on ART who reported to our canter during a period of 18 months were evaluated for symptoms (muscle fatigue, myalgia), objective muscle strength (testing clinically) and serum CK levels, and a select group was evaluated by muscle biopsy. These patients were on zidovudine for 1 to 7 years. None of the patients studied had significant symptoms or objective muscle weakness and only a small fraction (10.8% of cases) had marginally raised serum CK levels. All muscle biopsies were normal on light microscopy. Zidovudine myopathy may be a constraint for use of the drug in the western population; however, it is a well-tolerated drug as regards myopathy in our study on Indian patients.

Myopathy in hyperthyroidism as a consequence of rapid reduction of thyroid hormone

PubMed Central

Li, Qianrui; Liu, Yuping; Zhang, Qianying; Tian, Haoming; Li, Jianwei; Li, Sheyu

2017-01-01

Abstract Rationale: Myalgia and elevated creatine kinase (CK) are occasionally observed during the treatment of hyperthyroid patients. Relative hypothyroidism resulted from rapid thyroid hormone reduction had been promoted as a plausible cause of these myopathic changes, however rarely reported. Patient concerns: We hereby presented a 20-year-old female with Grave's disease, who developed myopathy and elevated CK during rapid correction of thyroid hormone. Diagnoses: Relative hypothyroidism-induced myopathy. Interventions: Antithyroid drug (ATD) dosage was reduced without levothyroxine replacement. Outcomes: The muscular symptoms were recovered with CK level returned to normal after adoption of the euthyroid status. Lessons: Differentiation of relative hypothyroidism from other causes of myopathy, especially with the effect of ATD, is important for clinical practice, although difficult in many cases. PMID:28746208

Acute quadriplegic myopathy with loss of thick (myosin) filaments following heart transplantation.

PubMed

Perea, M; Picón, M; Miró, O; Orús, J; Roig, E; Grau, J M

2001-10-01

Acute quadriplegic myopathy with loss of thick (myosin) filaments (AQM-LTF) is an acute toxic myopathy observed in critically ill patients and is characterized by proximal or diffuse weakness of extremities and difficulty in weaning from mechanical ventilation. In recent years, this myopathy has been described in transplanted patients, although only 5 cases have been reported following heart transplantation. We present 3 new cases and review the previous literature. We conclude that the clinical picture and outcome of AQM-LTF in heart-transplanted patients do not differ from those observed in other critically ill patients (transplanted and non-transplanted). Therefore, because AQM-LTF is often clinically suspected muscle biopsy should be quickly performed to confirm the diagnosis so that physical therapy may begin as soon as possible.

Role of Autophagy in Glycogen Breakdown and Its Relevance to Chloroquine Myopathy

PubMed Central

Zirin, Jonathan; Nieuwenhuis, Joppe; Perrimon, Norbert

2013-01-01

Several myopathies are associated with defects in autophagic and lysosomal degradation of glycogen, but it remains unclear how glycogen is targeted to the lysosome and what significance this process has for muscle cells. We have established a Drosophila melanogaster model to study glycogen autophagy in skeletal muscles, using chloroquine (CQ) to simulate a vacuolar myopathy that is completely dependent on the core autophagy genes. We show that autophagy is required for the most efficient degradation of glycogen in response to starvation. Furthermore, we show that CQ-induced myopathy can be improved by reduction of either autophagy or glycogen synthesis, the latter possibly due to a direct role of Glycogen Synthase in regulating autophagy through its interaction with Atg8. PMID:24265594

Kinematically aligned total knee arthroplasty limits high tibial forces, differences in tibial forces between compartments, and abnormal tibial contact kinematics during passive flexion.

PubMed

Roth, Joshua D; Howell, Stephen M; Hull, Maury L

2018-06-01

Following total knee arthroplasty (TKA), high tibial forces, large differences in tibial forces between the medial and lateral compartments, and anterior translation of the contact locations of the femoral component on the tibial component during passive flexion indicate abnormal knee function. Because the goal of kinematically aligned TKA is to restore native knee function without soft tissue release, the objectives were to determine how well kinematically aligned TKA limits high tibial forces, differences in tibial forces between compartments, and anterior translation of the contact locations of the femoral component on the tibial component during passive flexion. Using cruciate retaining components, kinematically aligned TKA was performed on thirteen human cadaveric knee specimens with use of manual instruments without soft tissue release. The tibial forces and tibial contact locations were measured in both the medial and lateral compartments from 0° to 120° of passive flexion using a custom tibial force sensor. The average total tibial force (i.e. sum of medial + lateral) ranged from 5 to 116 N. The only significant average differences in tibial force between compartments occurred at 0° of flexion (29 N, p = 0.0008). The contact locations in both compartments translated posteriorly in all thirteen kinematically aligned TKAs by an average of 14 mm (p < 0.0001) and 18 mm (p < 0.0001) in the medial and lateral compartments, respectively, from 0° to 120° of flexion. After kinematically aligned TKA, average total tibial forces due to the soft tissue restraints were limited to 116 N, average differences in tibial forces between compartments were limited to 29 N, and a net posterior translation of the tibial contact locations was observed in all kinematically aligned TKAs during passive flexion from 0° to 120°, which are similar to what has been measured previously in native knees. While confirmation in vivo is warranted, these findings give

Hereditary inclusion-body myopathies.

PubMed

Broccolini, Aldobrando; Mirabella, Massimiliano

2015-04-01

The term hereditary inclusion-body myopathies (HIBMs) defines a group of rare muscle disorders with autosomal recessive or dominant inheritance and presence of muscle fibers with rimmed vacuoles and collection of cytoplasmic or nuclear 15-21 nm diameter tubulofilaments as revealed by muscle biopsy. The most common form of HIBM is due to mutations of the GNE gene that codes for a rate-limiting enzyme in the sialic acid biosynthetic pathway. This results in abnormal sialylation of glycoproteins that possibly leads to muscle fiber degeneration. Mutations of the valosin containing protein are instead responsible for hereditary inclusion-body myopathy with Paget's disease of the bone and frontotemporal dementia (IBMPFD), with these three phenotypic features having a variable penetrance. IBMPFD probably represents a disorder of abnormal cellular trafficking of proteins and maturation of the autophagosome. HIBM with congenital joint contractures and external ophthalmoplegia is due to mutations of the Myosin Heavy Chain IIa gene that exerts a pathogenic effect through interference with filament assembly or functional defects in ATPase activity. This review illustrates the clinical and pathologic characteristics of HIBMs and the main clues available to date concerning the possible pathogenic mechanisms and therapeutic perspectives of these disorders. This article is part of a Special Issue entitled: Neuromuscular Diseases: Pathology and Molecular Pathogenesis. Copyright © 2014 Elsevier B.V. All rights reserved.

Myosin storage myopathy associated with a heterozygous missense mutation in MYH7.

PubMed

Tajsharghi, Homa; Thornell, Lars-Eric; Lindberg, Christopher; Lindvall, Björn; Henriksson, Karl-Gösta; Oldfors, Anders

2003-10-01

Myosin constitutes the major part of the thick filaments in the contractile apparatus of striated muscle. MYH7 encodes the slow/beta-cardiac myosin heavy chain (MyHC), which is the main MyHC isoform in slow, oxidative, type 1 muscle fibers of skeletal muscle. It is also the major MyHC isoform of cardiac ventricles. Numerous missense mutations in the globular head of slow/beta-cardiac MyHC are associated with familial hypertrophic cardiomyopathy. We identified a missense mutation, Arg1845Trp, in the rod region of slow/beta-cardiac MyHC in patients with a skeletal myopathy from two different families. The myopathy was characterized by muscle weakness and wasting with onset in childhood and slow progression, but no overt cardiomyopathy. Slow, oxidative, type 1 muscle fibers showed large inclusions consisting of slow/beta-cardiac MyHC. The features were similar to a previously described entity: hyaline body myopathy. Our findings indicate that the mutated residue of slow/beta-cardiac MyHC is essential for the assembly of thick filaments in skeletal muscle. We propose the term myosin storage myopathy for this disease.

A rat model of spontaneous myopathy and malignant hyperthermia.

PubMed Central

Gonzalez, L. E.; Meléndez-Vásquez, C. V.; Gregson, N. A.; File, S. E.

1998-01-01

Malignant hyperthermia is a main cause of death during general anesthesia, particularly in children. However, research has been hampered by the lack of a convenient animal model, the only one available being a special strain of pig. In this study, we describe spontaneous myopathy and a fatal syndrome of generalized muscle rigidity triggered by halothane in an outbred strain of rat. Histological examination of skeletal muscle reveals severe abnormalities indicating chronic underlying myopathy. The association of histological abnormalities with an acute, fatal syndrome clinically resembling malignant hyperthermia provides a strong basis for a new and extremely useful animal model to study this fatal disorder. Images Figure 1 Figure 2 PMID:9546371

Elucidation of the mechanism of atorvastatin-induced myopathy in a rat model.

PubMed

El-Ganainy, Samar O; El-Mallah, Ahmed; Abdallah, Dina; Khattab, Mahmoud M; Mohy El-Din, Mahmoud M; El-Khatib, Aiman S

2016-06-01

Myopathy is among the well documented and the most disturbing adverse effects of statins. The underlying mechanism is still unknown. Mitochondrial dysfunction related to coenzyme Q10 decline is one of the proposed theories. The present study aimed to investigate the mechanism of atorvastatin-induced myopathy in rats. In addition, the mechanism of the coenzyme Q10 protection was investigated with special focus of mitochondrial alterations. Sprague-Dawely rats were treated orally either with atorvastatin (100mg/kg) or atorvastatin and coenzyme Q10 (100mg/kg). Myopathy was assessed by measuring serum creatine kinase (CK) and myoglobin levels together with examination of necrosis in type IIB fiber muscles. Mitochondrial dysfunction was evaluated by measuring muscle lactate/pyruvate ratio, ATP level, pAkt as well as mitochondrial ultrastructure examination. Atorvastatin treatment resulted in a rise in both CK (2X) and myoglobin (6X) level with graded degrees of muscle necrosis. Biochemical determinations showed prominent increase in lactate/pyruvate ratio and a decline in both ATP (>80%) and pAkt (>50%) levels. Ultrastructure examination showed mitochondrial swelling with disrupted organelle membrane. Co-treatment with coenzyme Q10 induced reduction in muscle necrosis as well as in CK and myoglobin levels. In addition, coenzyme Q10 improved all mitochondrial dysfunction parameters including mitochondrial swelling and disruption. These results presented a model for atorvastatin-induced myopathy in rats and proved that mitochondrial dysfunction is the main contributor in statin-myopathy pathophysiology. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Anterior pelvic organ prolapse repair using synthetic mesh.

PubMed

Patel, Bhavin N; Lucioni, Alvaro; Kobashi, Kathleen C

2012-06-01

Since the U.S. Food and Drug Administration (FDA) statement on mesh in July of 2011, there has been controversy regarding synthetic mesh repairs for vaginal prolapse. In this article, we review the biochemical basis for the use of synthetic mesh in prolapse repair as well as clinical results of anterior compartment prolapse repair with synthetic mesh. Finally, we discuss the FDA warning regarding mesh.

Myopathy including polymyositis: a likely class adverse effect of proton pump inhibitors?

PubMed

Clark, David W J; Strandell, Johanna

2006-06-01

Polymyositis occurring in patients treated with omeprazole has been signalled as a possible adverse drug reaction (ADR) by the New Zealand Intensive Medicines Monitoring Programme (IMMP) and the WHO Collaborating Centre for International Drug Monitoring: the Uppsala Monitoring Centre (UMC). Polymyositis and other myopathies have also been reported in post-marketing data and in the medical literature in association with proton pump inhibitor (PPI) use. We wished to follow-up these signals and investigate the evidence of causality for the association of polymyositis and other myopathy with PPI use. Spontaneously reported ADRs from national monitoring centres are sent to the WHO ADR database (VigiBase). VigiBase was searched for case reports of the PPIs, omeprazole, pantoprazole, lansoprazole, esomeprazole and rabeprazole, with terms indicative of myopathy, and further information was elicited from the national centres to help establish causality. Literature sources were reviewed for the occurrence of the above terms in combination with PPIs. In total, there were 292 reports of various myopathies with PPIs, excluding 868 cases of 'myalgia'. In this analysis, 69 patients recovered when the drug was withdrawn and, in 15 patients, the reaction re-occurred when the drug was reinstated. In one-third of the 292 cases, the PPI was the single administered drug, and the PPI was the single suspected drug by the reporter in 57% of reports where concomitant medication was used. In this analysis, three index cases are documented. One involves the same patient taking three different PPIs (lansoprazole, esomeprazole and rabeprazole) at different time periods, with myalgia and muscle weakness occurring with all three drugs. In the two other index cases, myopathies with esomeprazole and omeprazole were reported with positive rechallenge, and causality was assessed as 'possible' and 'certain' by the reporting centres. In 27 cases myositis or polymyositis was reported. Other myopathies

Flaccid quadriplegia due to thyrotoxic myopathy.

PubMed

Couillard, Philippe; Wijdicks, Eelco F M

2014-04-01

Acute flaccid paralysis is an important clinical problem in neurological critical care. After implementing life-supporting measures, it is imperative to identify the correct diagnosis to provide timely appropriate care. Thyrotoxicosis is a recognized cause of myopathy, but rarely of quadriplegia. Here, we report a case of hyperthyroidism with severe weakness. Case report and video demonstration of clinical examination. We describe a case of a 59-year-old woman with Grave's disease who presented to the hospital with progressive shortness of breath secondary to atrial fibrillation with rapid ventricular response. Following contrast administration, she had a pulseless electrical activity arrest from which she recovered without cognitive sequelae, but with flaccid quadriplegia, facial diplegia, and hypophonia. CK was mildly elevated and electrolytes were essentially normal. Nerve conduction studies and electromyography demonstrated features supporting an acute myopathy without evidence of neuromuscular junction conduction abnormality. Normalization of thyroid hormones resulted in slow, but steady improvement over months after which she regained ambulation. Acute flaccid quadriplegia can result from thyrotoxicosis. With normalization of thyroid function, recovery can be expected.

c-Kit-positive cardiac stem cells nested in hypoxic niches are activated by stem cell factor reversing the aging myopathy.

PubMed

Sanada, Fumihiro; Kim, Junghyun; Czarna, Anna; Chan, Noel Yan-Ki; Signore, Sergio; Ogórek, Barbara; Isobe, Kazuya; Wybieralska, Ewa; Borghetti, Giulia; Pesapane, Ada; Sorrentino, Andrea; Mangano, Emily; Cappetta, Donato; Mangiaracina, Chiara; Ricciardi, Mario; Cimini, Maria; Ifedigbo, Emeka; Perrella, Mark A; Goichberg, Polina; Choi, Augustine M; Kajstura, Jan; Hosoda, Toru; Rota, Marcello; Anversa, Piero; Leri, Annarosa

2014-01-03

Hypoxia favors stem cell quiescence, whereas normoxia is required for stem cell activation, but whether cardiac stem cell (CSC) function is regulated by the hypoxic/normoxic state of the cell is currently unknown. A balance between hypoxic and normoxic CSCs may be present in the young heart, although this homeostatic control may be disrupted with aging. Defects in tissue oxygenation occur in the old myocardium, and this phenomenon may expand the pool of hypoxic CSCs, which are no longer involved in myocyte renewal. Here, we show that the senescent heart is characterized by an increased number of quiescent CSCs with intact telomeres that cannot re-enter the cell cycle and form a differentiated progeny. Conversely, myocyte replacement is controlled only by frequently dividing CSCs with shortened telomeres; these CSCs generate a myocyte population that is chronologically young but phenotypically old. Telomere dysfunction dictates their actual age and mechanical behavior. However, the residual subset of quiescent young CSCs can be stimulated in situ by stem cell factor reversing the aging myopathy. Our findings support the notion that strategies targeting CSC activation and growth interfere with the manifestations of myocardial aging in an animal model. Although caution has to be exercised in the translation of animal studies to human beings, our data strongly suggest that a pool of functionally competent CSCs persists in the senescent heart and that this stem cell compartment can promote myocyte regeneration effectively, partly correcting the aging myopathy.

NCAM is hyposialylated in hereditary inclusion body myopathy due to GNE mutations.

PubMed

Ricci, E; Broccolini, A; Gidaro, T; Morosetti, R; Gliubizzi, C; Frusciante, R; Di Lella, G M; Tonali, P A; Mirabella, M

2006-03-14

The authors found that the neural cell adhesion molecule (NCAM) is hyposialylated in hereditary inclusion body myopathy (HIBM) muscle, as suggested by its decreased molecular weight by Western blot. This abnormality represented the only pathologic feature differentiating HIBM due to GNE mutations from other myopathies with similar clinical and pathologic characteristics. If further confirmed in larger series of patients, this may be a useful diagnostic marker of GNE-related HIBM.

Near-Infrared Monitoring of Model Chronic Compartment Syndrome In Exercising Skeletal Muscle

NASA Technical Reports Server (NTRS)

Hargens, Alan R.; Breit, G. A.; Gross, J. H.; Watenpaugh, D. E.; Chance, B.

1995-01-01

Chronic compartment syndrome (CCS) is characterized by muscle ischemia, usually in the anterior oompartment of the leg, caused by high intramuscular pressure during exercise. Dual-wave near-infrared (NIR) spectroscopy is an optical technique that allows noninvasive tracking of variations in muscle tissue oxygenation (Chance et al., 1988). We hypothesized that with a model CCS, muscle tissue oxygenation will show a greater decline during exercise and a slower recovery post-exercise than under normal conditions.

Idiopathic Inflammatory Myopathies: Clinical Approach and Management

PubMed Central

Malik, Asma; Hayat, Ghazala; Kalia, Junaid S.; Guzman, Miguel A.

2016-01-01

Idiopathic inflammatory myopathies (IIM) are a group of chronic, autoimmune conditions affecting primarily the proximal muscles. The most common types are dermatomyositis (DM), polymyositis (PM), necrotizing autoimmune myopathy (NAM), and sporadic inclusion body myositis (sIBM). Patients typically present with sub-acute to chronic onset of proximal weakness manifested by difficulty with rising from a chair, climbing stairs, lifting objects, and combing hair. They are uniquely identified by their clinical presentation consisting of muscular and extramuscular manifestations. Laboratory investigations, including increased serum creatine kinase (CK) and myositis specific antibodies (MSA) may help in differentiating clinical phenotype and to confirm the diagnosis. However, muscle biopsy remains the gold standard for diagnosis. These disorders are potentially treatable with proper diagnosis and initiation of therapy. Goals of treatment are to eliminate inflammation, restore muscle performance, reduce morbidity, and improve quality of life. This review aims to provide a basic diagnostic approach to patients with suspected IIM, summarize current therapeutic strategies, and provide an insight into future prospective therapies. PMID:27242652

Approach to critical illness polyneuropathy and myopathy.

PubMed

Pati, S; Goodfellow, J A; Iyadurai, S; Hilton-Jones, D

2008-07-01

A newly acquired neuromuscular cause of weakness has been found in 25-85% of critically ill patients. Three distinct entities have been identified: (1) critical illness polyneuropathy (CIP); (2) acute myopathy of intensive care (itself with three subtypes); and (3) a syndrome with features of both 1 and 2 (called critical illness myopathy and/or neuropathy or CRIMYNE). CIP is primarily a distal axonopathy involving both sensory and motor nerves. Electroneurography and electromyography (ENG-EMG) is the gold standard for diagnosis. CIM is a proximal as well as distal muscle weakness affecting both types of muscle fibres. It is associated with high use of non-depolarising muscle blockers and corticosteroids. Avoidance of systemic inflammatory response syndrome (SIRS) is the most effective way to reduce the likelihood of developing CIP or CIM. Outcome is variable and depends largely on the underlying illness. Detailed history, careful physical examination, review of medication chart and analysis of initial investigations provides invaluable clues towards the diagnosis.

Riboflavin transporter deficiency mimicking mitochondrial myopathy caused by complex II deficiency.

PubMed

Nimmo, Graeme A M; Ejaz, Resham; Cordeiro, Dawn; Kannu, Peter; Mercimek-Andrews, Saadet

2018-02-01

Biallelic likely pathogenic variants in SLC52A2 and SLC52A3 cause riboflavin transporter deficiency. It is characterized by muscle weakness, ataxia, progressive ponto-bulbar palsy, amyotrophy, and sensorineural hearing loss. Oral riboflavin halts disease progression and may reverse symptoms. We report two new patients whose clinical and biochemical features were mimicking mitochondrial myopathy. Patient 1 is an 8-year-old male with global developmental delay, axial and appendicular hypotonia, ataxia, and sensorineural hearing loss. His muscle biopsy showed complex II deficiency and ragged red fibers consistent with mitochondrial myopathy. Whole exome sequencing revealed a homozygous likely pathogenic variant in SLC52A2 (c.917G>A; p.Gly306Glu). Patient 2 is a 14-month-old boy with global developmental delay, respiratory insufficiency requiring ventilator support within the first year of life. His muscle biopsy revealed combined complex II + III deficiency and ragged red fibers consistent with mitochondrial myopathy. Whole exome sequencing identified a homozygous likely pathogenic variant in SCL52A3 (c.1223G>A; p.Gly408Asp). We report two new patients with riboflavin transporter deficiency, caused by mutations in two different riboflavin transporter genes. Both patients presented with complex II deficiency. This treatable neurometabolic disorder can mimic mitochondrial myopathy. In patients with complex II deficiency, riboflavin transporter deficiency should be included in the differential diagnosis to allow early treatment and improve neurodevelopmental outcome. © 2017 Wiley Periodicals, Inc.

Lower Leg Anterior and Lateral Intracompartmental Pressure Changes Before and After Classic Versus Skate Nordic Rollerskiing.

PubMed

Woods, Katherine M; Petron, David J; Shultz, Barry B; Hicks-Little, Charlie A

2015-08-01

Chronic exertional compartment syndrome (CECS) is a debilitating condition resulting in loss of function and a decrease in athletic performance. Cases of CECS are increasing among Nordic skiers; therefore, analysis of intracompartmental pressures (ICPs) before and after Nordic skiing is warranted. To determine if lower leg anterior and lateral ICPs and subjective lower leg pain levels increased after a 20-minute Nordic rollerskiing time trial and to examine if differences existed between postexercise ICPs for the 2 Nordic rollerskiing techniques, classic and skate. Crossover study. Outdoor paved loop. Seven healthy Division I Nordic skiers (3 men, 4 women; age = 22.71 ± 1.38 y, height = 175.36 ± 6.33 cm, mass = 70.71 ± 6.58 kg). Participants completed two 20-minute rollerskiing time trials using the classic and skate technique in random order. The time trials were completed 7 days apart. Anterior and lateral ICPs and lower leg pain scores were obtained at baseline and at minutes 1 and 5 after rollerskiing. Anterior and lateral ICPs (mm Hg) were measured using a Stryker Quic STIC handheld monitor. Subjective measures of lower leg pain were recorded using the 11-point Numeric Rating Scale. Increases in both anterior (P = .000) and lateral compartment (P = .002) ICPs were observed, regardless of rollerskiing technique used. Subjective lower leg pain increased after the classic technique for the men from baseline to 1 minute postexercise and after the skate technique for the women. Significant 3-way interactions (technique × time × sex) were observed for the anterior (P = .002) and lateral (P = .009) compartment ICPs and lower leg pain (P = .005). Postexercise anterior and lateral ICPs increased compared with preexercise ICPs after both classic and skate rollerskiing techniques. Lower leg pain is a primary symptom of CECS. The subjective lower leg pain 11-point Numeric Rating Scale results indicate that increases in lower leg ICPs sustained during Nordic

Lipid Storage Myopathy in Behçet's Disease: A Rare Cause of Elevated Serum Creatine Kinases Levels

PubMed Central

Yilmaz, Sedat; Cinar, Muhammet; Karslioglu, Yıldırım; Simsek, Ismail; Erdem, Hakan; Pay, Salih; Dinc, Ayhan

2012-01-01

Muscular involvement in Behçet's disease is rare and there are only a few case reports in the literature. The causes of elevated muscle enzymes in a patient with Behcet's disease are many, including myositis, drug-induced myopathy, metabolic myopathy, and the disease itself. We herein have defined an algorithmic approach to a patient with Behcet's disease and elevated muscle enzymes and report a case of coexisting of lipid storage myopathy. PMID:22937450

Myopathy in Childhood Muscle-Specific Kinase Myasthenia Gravis.

PubMed

Kirzinger, Lukas; Khomenko, Andrei; Schulte-Mattler, Wilhelm; Backhaus, Roland; Platen, Sabine; Schalke, Berthold

2016-12-01

Adult and pediatric patients suffering from MuSK (muscle-specific kinase) -antibody positive myasthenia gravis exhibit similar features to individuals with acetylcholine receptor (AChR) antibodies, but they differ in several characteristics such as a predominant bulbar, respiratory and neck weakness, a generally worse disease severity and a tendency to develop muscle atrophy. Muscle atrophy is a rare phenomenon that is usually restricted to the facial muscles. We describe a girl with MuSK-antibody positive myasthenia gravis who developed a myopathy with severe generalized muscular weakness, muscle atrophy, and myopathic changes on electromyography. This is the first published example of a generalized myopathic syndrome in myasthenia gravis. We review the relevant literature and discuss the hypothesis of a mitochondrial myopathy as a pathogenic mechanism in MuSK-antibody positive myasthenia gravis. Copyright © 2016 Elsevier Inc. All rights reserved.

The Impact of Exercise on Statin-Associated Skeletal Muscle Myopathy

PubMed Central

Chung, Hae R.; Vakil, Mayand; Munroe, Michael; Parikh, Alay; Meador, Benjamin M.; Wu, Pei T.; Jeong, Jin H.; Woods, Jeffrey A.; Wilund, Kenneth R.; Boppart, Marni D.

2016-01-01

HMG-CoA reductase inhibitors (statins) are the most effective pharmacological means of reducing cardiovascular disease risk. The most common side effect of statin use is skeletal muscle myopathy, which may be exacerbated by exercise. Hypercholesterolemia and training status are factors that are rarely considered in the progression of myopathy. The purpose of this study was to determine the extent to which acute and chronic exercise can influence statin-induced myopathy in hypercholesterolemic (ApoE-/-) mice. Mice either received daily injections of saline or simvastatin (20 mg/kg) while: 1) remaining sedentary (Sed), 2) engaging in daily exercise for two weeks (novel, Nov), or 3) engaging in daily exercise for two weeks after a brief period of training (accustomed, Acct) (2x3 design, n = 60). Cholesterol, activity, strength, and indices of myofiber damage and atrophy were assessed. Running wheel activity declined in both exercise groups receiving statins (statin x time interaction, p<0.05). Cholesterol, grip strength, and maximal isometric force were significantly lower in all groups following statin treatment (statin main effect, p<0.05). Mitochondrial content and myofiber size were increased and 4-HNE was decreased by exercise (statin x exercise interaction, p<0.05), and these beneficial effects were abrogated by statin treatment. Exercise (Acct and Nov) increased atrogin-1 mRNA in combination with statin treatment, yet enhanced fiber damage or atrophy was not observed. The results from this study suggest that exercise (Nov, Acct) does not exacerbate statin-induced myopathy in ApoE-/- mice, yet statin treatment reduces activity in a manner that prevents muscle from mounting a beneficial adaptive response to training. PMID:27936249

Compartment syndromes

NASA Technical Reports Server (NTRS)

Mubarak, S. J.; Pedowitz, R. A.; Hargens, A. R.

1989-01-01

The compartment syndrome is defined as a condition in which high pressure within a closed fascial space (muscle compartment) reduces capillary blood perfusion below the level necessary for tissue viability'. This condition occurs in acute and chronic (exertional) forms, and may be secondary to a variety of causes. The end-result of an extended period of elevated intramuscular pressure may be the development of irreversible tissue injury and Volkmann's contracture. The goal of treatment of the compartment syndrome is the reduction of intracompartmental pressure thus facilitating reperfusion of ischaemic tissue and this goal may be achieved by decompressive fasciotomy. Controversy exists regarding the critical pressure-time thresholds for surgical decompression and the optimal diagnostic methods of measuring intracompartmental pressures. This paper will update and review some current knowledge regarding the pathophysiology, aetiology, diagnosis, and treatment of the acute compartment syndrome.

Facial Contouring by Targeted Restoration of Facial Fat Compartment Volume: The Midface.

PubMed

Wang, Wenjin; Xie, Yun; Huang, Ru-Lin; Zhou, Jia; Tanja, Herrler; Zhao, Peijuan; Cheng, Chen; Zhou, Sizheng; Pu, Lee L Q; Li, Qingfeng

2017-03-01

Recent anatomical findings have suggested that facial fat distribution is complex and changes with age. Here, the authors developed a grafting technique based on the physiologic distribution and volume changes of facial fat compartments to achieve a youthful and natural-appearing face. Forty cadaveric hemifaces were used for the dissection of fat compartments and neurovascular structures in the midface area. Seventy-eight patients were treated for cheek atrophy using the authors' targeted restoration of midface fat compartment volume. The outcome was evaluated by a two-dimensional assessment, malar lipoatrophy assessment, and a satisfaction survey. The medial and lateral parts of the deep medial cheek fat compartment were separated by a septum arising from the lateral border of the levator anguli oris muscle. The angular vein traveled between the deep medial cheek fat compartment and the buccal fat pad, 12 mm from the maxilla. A total volume of 29.3 ml of fat was grafted per cheek for each patient. A 12-month follow-up revealed an average volume augmentation rate of 27.1 percent. Pleasing and elevated anterior projection of the cheek and ameliorated nasolabial groove were still obvious by 12 months after the procedure. In total, 95.2 percent of the patients were satisfied with their results. The present study provides the anatomical and clinical basis for the concept of compartmentally based fat grafting. It allows for the restoration of facial fat volume close to the physiologic state. With this procedure, a natural and youthful facial contour could be rebuilt with a high satisfaction rate. Therapeutic, IV.

Prominent subcutaneous oedema as a masquerading symptom of an underlying inflammatory myopathy.

PubMed

Anantharajah, Anthea; Vucic, Steve; Tarafdar, Surjit; Vongsuvanh, Roslyn; Wilcken, Nicholas; Swaminathan, Sanjay

2017-02-01

The inflammatory myopathies are a group of immune-mediated inflammatory muscle disorders that typically present with marked proximal muscle weakness. We report four cases of inflammatory myopathies with marked subcutaneous oedema as their main complaint. Three of the four patients had normal or low levels of creatine kinase, an enzyme often markedly elevated in these disorders. Magnetic resonance imaging of the muscles, followed by a muscle biopsy were used to make a definitive diagnosis. © 2017 Royal Australasian College of Physicians.

Mutation-specific effects on thin filament length in thin filament myopathy.

PubMed

Winter, Josine M de; Joureau, Barbara; Lee, Eun-Jeong; Kiss, Balázs; Yuen, Michaela; Gupta, Vandana A; Pappas, Christopher T; Gregorio, Carol C; Stienen, Ger J M; Edvardson, Simon; Wallgren-Pettersson, Carina; Lehtokari, Vilma-Lotta; Pelin, Katarina; Malfatti, Edoardo; Romero, Norma B; Engelen, Baziel G van; Voermans, Nicol C; Donkervoort, Sandra; Bönnemann, C G; Clarke, Nigel F; Beggs, Alan H; Granzier, Henk; Ottenheijm, Coen A C

2016-06-01

Thin filament myopathies are among the most common nondystrophic congenital muscular disorders, and are caused by mutations in genes encoding proteins that are associated with the skeletal muscle thin filament. Mechanisms underlying muscle weakness are poorly understood, but might involve the length of the thin filament, an important determinant of force generation. We investigated the sarcomere length-dependence of force, a functional assay that provides insights into the contractile strength of muscle fibers as well as the length of the thin filaments, in muscle fibers from 51 patients with thin filament myopathy caused by mutations in NEB, ACTA1, TPM2, TPM3, TNNT1, KBTBD13, KLHL40, and KLHL41. Lower force generation was observed in muscle fibers from patients of all genotypes. In a subset of patients who harbor mutations in NEB and ACTA1, the lower force was associated with downward shifted force-sarcomere length relations, indicative of shorter thin filaments. Confocal microscopy confirmed shorter thin filaments in muscle fibers of these patients. A conditional Neb knockout mouse model, which recapitulates thin filament myopathy, revealed a compensatory mechanism; the lower force generation that was associated with shorter thin filaments was compensated for by increasing the number of sarcomeres in series. This allowed muscle fibers to operate at a shorter sarcomere length and maintain optimal thin-thick filament overlap. These findings might provide a novel direction for the development of therapeutic strategies for thin filament myopathy patients with shortened thin filament lengths. Ann Neurol 2016;79:959-969. © 2016 American Neurological Association.

Mutation-Specific Effects on Thin Filament Length in Thin Filament Myopathy

PubMed Central

de Winter, Josine M.; Joureau, Barbara; Lee, Eun-Jeong; Kiss, Balázs; Yuen, Michaela; Gupta, Vandana A.; Pappas, Christopher T.; Gregorio, Carol C.; Stienen, Ger J. M.; Edvardson, Simon; Wallgren-Pettersson, Carina; Lehtokari, Vilma-Lotta; Pelin, Katarina; Malfatti, Edoardo; Romero, Norma B.; van Engelen, Baziel G.; Voermans, Nicol C.; Donkervoort, Sandra; Bönnemann, C. G.; Clarke, Nigel F.; Beggs, Alan H.; Granzier, Henk; Ottenheijm, Coen A. C.

2016-01-01

Objective Thin filament myopathies are among the most common nondystrophic congenital muscular disorders, and are caused by mutations in genes encoding proteins that are associated with the skeletal muscle thin filament. Mechanisms underlying muscle weakness are poorly understood, but might involve the length of the thin filament, an important determinant of force generation. Methods We investigated the sarcomere length-dependence of force, a functional assay that provides insights into the contractile strength of muscle fibers as well as the length of the thin filaments, in muscle fibers from 51 patients with thin filament myopathy caused by mutations in NEB, ACTA1, TPM2, TPM3, TNNT1, KBTBD13, KLHL40, and KLHL41. Results Lower force generation was observed in muscle fibers from patients of all genotypes. In a subset of patients who harbor mutations in NEB and ACTA1, the lower force was associated with downward shifted force–sarcomere length relations, indicative of shorter thin filaments. Confocal microscopy confirmed shorter thin filaments in muscle fibers of these patients. A conditional Neb knockout mouse model, which recapitulates thin filament myopathy, revealed a compensatory mechanism; the lower force generation that was associated with shorter thin filaments was compensated for by increasing the number of sarcomeres in series. This allowed muscle fibers to operate at a shorter sarcomere length and maintain optimal thin–thick filament overlap. Interpretation These findings might provide a novel direction for the development of therapeutic strategies for thin filament myopathy patients with shortened thin filament lengths. PMID:27074222

A new mitochondria-related disease showing myopathy with episodic hyper-creatine kinase-emia.

PubMed

Okamoto, Yuji; Higuchi, Itsuro; Sakiyama, Yusuke; Tokunaga, Shoko; Watanabe, Osamu; Arimura, Kimiyoshi; Nakagawa, Masanori; Takashima, Hiroshi

2011-09-01

To elucidate the relationship between mitochondrial DNA (mtDNA) alterations and a mitochondrial disease with a distinct combination of characteristic symptoms, namely episodic hyper-creatine kinase (CK)-emia and mild myopathy. We selected 9 patients with mtDNA np8291 alteration from 586 patients suspected to have a mitochondrial disease, and assessed them clinically, pathologically, and genetically. These 9 patients had undiagnosed mitochondrial myopathy with episodic hyper-CK-emia, all showing similar symptoms and progression. Patients had mild muscle weakness and episodic hyper-CK-emia triggered by infections or drugs. Five of 9 patients were initially diagnosed with other conditions, such as myasthenia gravis, polymyositis, viral myositis, and drug-induced myopathy, because these conditions were acute or subacute, and 9 patients showed the same 16 mtDNA alterations, which have been reported to be nonpathological polymorphisms. Muscle biopsy revealed ragged-red fibers, highly expressed succinate dehydrogenase staining fibers, and cytochrome c oxidase-deficient fibers. Because their mitochondrial sequence data was almost the same, and 9 patients live in widely separated cities in Japan, the alterations may have arisen from a single source. These findings suggest that mild myopathy with episodic hyper-CK-emia associated with some of the 16 mtDNA alterations or at least with their mitochondria, could be a novel mitochondrial disease. Therefore, we propose that this disease be named as "mitochondrial myopathy with episodic hyper-CK-emia (MIMECK)." These alterations could work concomitantly and probably modify the impact of medications or other environmental factors. We believe these findings provide an insight into a novel aspect of mitochondrial disease pathogenesis. Copyright © 2011 American Neurological Association.

Patient reported outcomes in GNE myopathy: incorporating a valid assessment of physical function in a rare disease.

PubMed

Slota, Christina; Bevans, Margaret; Yang, Li; Shrader, Joseph; Joe, Galen; Carrillo, Nuria

2018-05-01

The aim of this analysis was to evaluate the psychometric properties of three patient reported outcome (PRO) measures characterizing physical function in GNE myopathy: the Human Activity Profile, the Inclusion Body Myositis Functional Rating Scale, and the Activities-specific Balance Confidence scale. This analysis used data from 35 GNE myopathy subjects participating in a natural history study. For construct validity, correlational and known-group analyses were between the PROs and physical assessments. Reliability of the PROs between baseline and 6 months was evaluated using the intra-class correlation coefficient model; internal consistency was tested with Cronbach's alpha. The hypothesized moderate positive correlations for construct validity were supported; the strongest correlation was between the human activity profile adjusted activity score and the adult myopathy assessment endurance subscale score (r = 0.81; p < 0.0001). The PROs were able to discriminate between known high and low functioning groups for the adult myopathy assessment tool. Internal consistency of the PROs was high (α > 0.8) and there was strong reliability (ICC >0.62). The PROs are valid and reliable measures of physical function in GNE myopathy and should be incorporated in investigations to better understand the impact of progressive muscle weakness on physical function in this rare disease population. Implications for Rehabilitation GNE myopathy is a rare muscle disease that results in slow progressive muscle atrophy and weakness, ultimately leading to wheelchair use and dependence on a caregiver. There is limited knowledge on the impact of this disease on the health-related quality of life, specifically physical function, of this rare disease population. Three patient reported outcomes have been shown to be valid and reliable in GNE myopathy subjects and should be incorporated in future investigations to better understand how progressive muscle weakness impacts physical

Immune checkpoint failures in inflammatory myopathies: An overview.

PubMed

Herbelet, Sandrine; De Bleecker, Jan L

2018-06-06

Dermatomyositis (DM), polymyositis (PM), inclusion body myositis (IBM), immune mediated necrotizing myopathy (IMNM) and overlap myositis (OM) are classified as inflammatory myopathies (IM) with involvement of autoimmune features such as autoreactive lymphocytes and autoantibodies. Autoimmunity can be defined as a loss in self-tolerance and attack of autoantigens by the immune system. Self-tolerance is achieved by a group of immune mechanisms occurring in central and periphal lymphoid organs and tissues, called immune checkpoints, that work in synergy to protect the body from harmful immune reactions. Autoimmune disorders appear when immune checkpoints fail. In this review, the different immune checkpoint failures are discussed in DM, PM, IBM and IMNM. Exploring research contribution in each of these immune checkpoints might help to highlight research perspectives in the field and obtain a more complete picture of IM disease pathology. Copyright © 2018 Elsevier B.V. All rights reserved.

Hypothyroid myopathy. A clinical and pathologaical study.

PubMed

McKeran, R O; Slavin, G; Ward, P; Paul, E; Mair, W G

1980-09-01

Ten patients with varying degrees of hypothroid myopathy were studied clinically and by serial percutaneous needle muscle biopsies before and during treatment with L-thyroxine. The biochemical evidence of hypothyroidism was related to the severity of the myopathic and signs before treatment. The severity of myopathic symptoms before and during treatment correlated with the biochemical evidence of hypothyrodism, a type II fibre atrophy and increased central nuclear counts. Likewise, the clinical evidence of a myopathy before and during treatment was correlated with both a type II fibre atrophy and loss and increased central nuclear counts but was not related to the biochemical parameters of hypothyroidism, except the level of thyroid stimulating hormone. In the muscle, before and during treatment, of the two most severely affected patients, intracellular glycogen inclusions were seen in scattered muscle fibres. On light microscopy and on electronmicroscopy, numerous mitochondria were seen responding to L-thyroxine with accumulations of subsarcolemmal honey-combing. Vesicular abnormalities, an electron dense matrix or occasional crystalline deposits were seen in muscle mitochondria from less severely azffected patients. Severely myopathic muscle contained excessive glycogen, membrane bound glycogen and excess lipid in a mainly perinuclear distribution. Occasional myelin and membranous bodies were seen and satellite cells during the recovery phase. A group of patients with hypothyroid myopathy who are likely to have a delayed recovery of full muscle strength on L-thyroxine may be recognised by the presence of severe proximal muscle weakness and characteristic changes on histochemical and electronmicroscopic examination of muscle. The spectrum of histochemical and electronmicroscopic abnormalities of muscle revealed with increasing degree of hypothyrodism, suggests that a generally reversible acquired glycogen storage and mictochondrial disorder is an important feature

Extra- and intramuscular nerve supply of the muscles of the anterior antebrachial compartment: applications for selective neurotomy and for botulinum toxin injection.

PubMed

Lepage, D; Parratte, B; Tatu, L; Vuiller, F; Monnier, G

2005-12-01

Hypertonia of the upper limb due to spasticity causes pronation of the forearm and flexion of wrist and fingers. Nowadays this spasticity is often treated with injections of botulinum toxin and sometimes with selective fascicular neurotomy. To correctly perform this microsurgical technique, it is necessary to get precise knowledge of the extramuscular nerve branching in order to be better able to select the motor branches which supply the muscles involved in spasticity. The same knowledge is required for botulinum toxin injections which must be made as near as possible to the zones where intramuscular nerve endings are the densest, which is also where neuromuscular junctions are the most numerous. Thus, it is necessary to better know these zones, but their knowledge remains today imprecise. The muscles of the anterior compartment of 30 forearms were dissected, first macroscopically, then microscopically, to study the extra- and intramuscular nerve supply and the distribution of terminal nerve ramifications. The results were then linked to surface topographical landmarks to indicate the precise location of motor branches for each muscle with the aim of proposing appropriate surgical approaches for selective neurotomies. Then for each muscle, the zones with the highest density of nerve endings were divided into segments, thus determining the optimal zones for botulinim toxin injections.

Forefoot running improves pain and disability associated with chronic exertional compartment syndrome.

PubMed

Diebal, Angela R; Gregory, Robert; Alitz, Curtis; Gerber, J Parry

2012-05-01

Anterior compartment pressures of the leg as well as kinematic and kinetic measures are significantly influenced by running technique. It is unknown whether adopting a forefoot strike technique will decrease the pain and disability associated with chronic exertional compartment syndrome (CECS) in hindfoot strike runners. For people who have CECS, adopting a forefoot strike running technique will lead to decreased pain and disability associated with this condition. Case series; Level of evidence, 4. Ten patients with CECS indicated for surgical release were prospectively enrolled. Resting and postrunning compartment pressures, kinematic and kinetic measurements, and self-report questionnaires were taken for all patients at baseline and after 6 weeks of a forefoot strike running intervention. Run distance and reported pain levels were recorded. A 15-point global rating of change (GROC) scale was used to measure perceived change after the intervention. After 6 weeks of forefoot run training, mean postrun anterior compartment pressures significantly decreased from 78.4 ± 32.0 mm Hg to 38.4 ± 11.5 mm Hg. Vertical ground-reaction force and impulse values were significantly reduced. Running distance significantly increased from 1.4 ± 0.6 km before intervention to 4.8 ± 0.5 km 6 weeks after intervention, while reported pain while running significantly decreased. The Single Assessment Numeric Evaluation (SANE) significantly increased from 49.9 ± 21.4 to 90.4 ± 10.3, and the Lower Leg Outcome Survey (LLOS) significantly increased from 67.3 ± 13.7 to 91.5 ± 8.5. The GROC scores at 6 weeks after intervention were between 5 and 7 for all patients. One year after the intervention, the SANE and LLOS scores were greater than reported during the 6-week follow-up. Two-mile run times were also significantly faster than preintervention values. No patient required surgery. In 10 consecutive patients with CECS, a 6-week forefoot strike running intervention led to decreased

Chronic exertional compartment syndrome of the superficial posterior compartment: Soleus syndrome.

PubMed

Gross, Christopher E; Parekh, Bela J; Adams, Samuel B; Parekh, Selene G

2015-01-01

Chronic exertional compartment syndrome (CECS) represents the second most-common cause of exertional leg pain with incidence of 27-33%. CECS of the superficial posterior compartment, or soleus syndrome, is rare and has only been discussed briefly in the literature. We discuss the management of two patients with bilateral soleus syndrome or CECS of the superficial posterior compartment.

A novel perspective for burn-induced myopathy: Membrane repair defect

PubMed Central

Wang, Chao; Wang, Hongyu; Wu, Dan; Hu, Jianhong; Wu, Wei; Zhang, Yong; Peng, Xi

2016-01-01

Myopathy is a common complication of severe burn patients. One potential cause of this myopathy could be failure of the plasma membrane to undergo repair following injuries generated from toxin or exercise. The aim of this study is to assess systemic effect on muscle membrane repair deficiency in burn injury. Skeletal muscle fibers isolated from burn-injured mice were damaged with a UV laser and dye influx imaged confocally to evaluate membrane repair capacity. Membrane repair failure was also tested in burn-injured mice subjected to myotoxin or treadmill exercise. We further used C2C12 myotubules and animal models to investigate the role of MG53 in development of burn-induced membrane repair defect. We demonstrated that skeletal muscle myofibers in burn-injured mice showed significantly more dye uptake after laser damage than controls, indicating a membrane repair deficiency. Myotoxin or treadmill exercise also resulted in a higher-grade repair defect in burn-injured mice. Furthermore, we observed that burn injury induced a significant decrease in MG53 levels and its dimerization in skeletal muscles. Our findings highlight a new mechanism that implicates membrane repair failure as an underlying cause of burn-induced myopathy. And, the disorders in MG53 expression and MG53 dimerization are involved in this cellular pathology. PMID:27545095

Compound RYR1 heterozygosity resulting in a complex phenotype of malignant hyperthermia susceptibility and a core myopathy.

PubMed

Kraeva, N; Heytens, L; Jungbluth, H; Treves, S; Voermans, N; Kamsteeg, E; Ceuterick-de Groote, C; Baets, J; Riazi, S

2015-07-01

Malignant hyperthermia (MH) is a potentially fatal pharmacogenetic myopathy triggered by exposure to volatile anesthetics and/or depolarizing muscle relaxants. Susceptibility to MH is primarily associated with dominant mutations in the ryanodine receptor type 1 gene (RYR1). Recent genetic studies have shown that RYR1 variants are the most common cause of dominant and recessive congenital myopathies - central core and multi-minicore disease, congenital fiber type disproportion, and centronuclear myopathy. However, the MH status of many patients, especially with recessive RYR1-related myopathies, remains uncertain. We report the occurrence of a triplet of RYR1 variants, c.4711A>G (p.Ile1571Val), c.10097G>A (p.Arg3366His), c.11798A>G (p.Tyr3933Cys), found in cis in four unrelated families, one from Belgium, one from The Netherlands and two from Canada. Phenotype-genotype correlation analysis indicates that the presence of the triplet allele alone confers susceptibility to MH, and that the presence of this allele in a compound heterozygous state with the MH-associated RYR1 variant c.14545G>A (p.Val4849Ile) results in the MH susceptibility phenotype and a congenital myopathy with cores and rods. Our study underlines the notion that assigning pathogenicity to individual RYR1 variants or combination of variants, and counseling in RYR1-related myopathies may require integration of clinical, histopathological, in vitro contracture testing, MRI and genetic findings. Copyright © 2015 Elsevier B.V. All rights reserved.

Myopathy in hyperthyroidism as a consequence of rapid reduction of thyroid hormone: A case report.

PubMed

Li, Qianrui; Liu, Yuping; Zhang, Qianying; Tian, Haoming; Li, Jianwei; Li, Sheyu

2017-07-01

Myalgia and elevated creatine kinase (CK) are occasionally observed during the treatment of hyperthyroid patients. Relative hypothyroidism resulted from rapid thyroid hormone reduction had been promoted as a plausible cause of these myopathic changes, however rarely reported. We hereby presented a 20-year-old female with Grave's disease, who developed myopathy and elevated CK during rapid correction of thyroid hormone. Relative hypothyroidism-induced myopathy. Antithyroid drug (ATD) dosage was reduced without levothyroxine replacement. The muscular symptoms were recovered with CK level returned to normal after adoption of the euthyroid status. Differentiation of relative hypothyroidism from other causes of myopathy, especially with the effect of ATD, is important for clinical practice, although difficult in many cases.

A novel mutation in PNPLA2 leading to neutral lipid storage disease with myopathy.

PubMed

Ash, Daniel B; Papadimitriou, Dimitra; Hays, Arthur P; Dimauro, Salvatore; Hirano, Michio

2012-09-01

Mutations in PNPLA2, a gene encoding adipose triglyceride lipase, lead to neutral lipid storage disease with myopathy. To report the clinical and molecular features of a case of neutral lipid storage disease with myopathy resulting from a novel mutation in PNPLA2. Case report. University hospital. A 65-year-old man with progressive muscle weakness and high serum creatine kinase levels. Direct sequencing of the PNPLA2 gene. Identification of a novel homozygous mutation in the patient's PNPLA2 gene confirmed the suspected diagnosis of neutral lipid storage disease with myopathy. Screening of the PNPLA2 gene should be considered for patients presenting with high levels of creatine kinase, progressive muscle weakness, and systemic lipid accumulation. The presence of Jordans anomaly can be a strong diagnostic clue.

[Value of MRI in the treatment of Grave's disease orbital myopathy].

PubMed

Oğuz, V; Yolar, M; Yetik, H; Cakirer, D; Uysal, O; Pazarli, H

2001-10-01

In order to evaluate the predictability of the results in the treatment of myopathy in cases with the clinical signs of muscle involvement, 177 extraocular muscles of 27 cases whose oedematous status was detected by MRI and who were given antiinflammatory treatment according to the data of this method, were studied. The nature of involvement was detected in respect with the signal intensity and thickness of each rectus muscle prior to the treatment and at the end of the sixth month following a three months' application of combined treatment of steroids and irradiation of 2000 rads. When the initial and final results were compared, the signal intensities of four involved recti showed significant decrease at the end of the treatment, as they were evaluated separately or together. Besides the thicknesses of these groups of involved recti which were evaluated separately showed significant decrease. The evaluation of the signal intensities by MRI is a way that enables noninvasive detection of the edema and prediction of the anti-inflammatory treatment's results of dysthyroid myopathy. Therefore a systematic follow up by MRI is recommended for the treatment choice in dysthyroid myopathy.

Rod distribution and muscle fiber type modification in the progression of nemaline myopathy.

PubMed

Gurgel-Giannetti, Juliana; Reed, Umbertina C; Marie, Sueli K; Zanoteli, Edmar; Fireman, Moacir A T; Oliveira, Acary S B; Werneck, Lineu C; Beggs, Alan H; Zatz, Mayana; Vainzof, Mariz

2003-03-01

Nemaline myopathy is a structural congenital myopathy associated with the presence of rodlike structures inside the muscle fibers and type I predominance. It may be caused by mutations in at least five genes: slow alpha-tropomyosin 3 (chromosome 1q22-23), nebulin (chromosome 2q21.1-q22), actin (chromosome 1q42), tropomyosin 2 (chromosome 9p13), and troponin T1 (chromosome 19q13.4). The effect of these mutations in the expression of the protein and the mechanism of rod formation is still under investigation. We analyzed the possibility of progressive alterations with time and/or disease evolution, such as transformation of type I to type II fiber and rod pattern and distribution in muscle fibers from patients with nemaline myopathy, through a morphometric and immunohistochemical analysis of different muscle protein isoforms. A tendency of diffuse rods to be organized in the subsarcolemmal region was observed in two patients who were submitted to subsequent biopsies after 10 and 13 years. Additionally, we observed the expression of type II protein isoforms in type I fibers and a higher proportion of type II fibers in the younger patient of a pair of affected sibs, giving further support to the hypothesis of progressive conversion of type II to type I fibers in nemaline myopathy.

Severe myopathy in mice lacking the MEF2/SRF-dependent gene leiomodin-3

PubMed Central

Cenik, Bercin K.; Garg, Ankit; McAnally, John R.; Shelton, John M.; Richardson, James A.; Bassel-Duby, Rhonda; Olson, Eric N.; Liu, Ning

2015-01-01

Maintenance of skeletal muscle structure and function requires a precise stoichiometry of sarcomeric proteins for proper assembly of the contractile apparatus. Absence of components of the sarcomeric thin filaments causes nemaline myopathy, a lethal congenital muscle disorder associated with aberrant myofiber structure and contractility. Previously, we reported that deficiency of the kelch-like family member 40 (KLHL40) in mice results in nemaline myopathy and destabilization of leiomodin-3 (LMOD3). LMOD3 belongs to a family of tropomodulin-related proteins that promote actin nucleation. Here, we show that deficiency of LMOD3 in mice causes nemaline myopathy. In skeletal muscle, transcription of Lmod3 was controlled by the transcription factors SRF and MEF2. Myocardin-related transcription factors (MRTFs), which function as SRF coactivators, serve as sensors of actin polymerization and are sequestered in the cytoplasm by actin monomers. Conversely, conditions that favor actin polymerization de-repress MRTFs and activate SRF-dependent genes. We demonstrated that the actin nucleator LMOD3, together with its stabilizing partner KLHL40, enhances MRTF-SRF activity. In turn, SRF cooperated with MEF2 to sustain the expression of LMOD3 and other components of the contractile apparatus, thereby establishing a regulatory circuit to maintain skeletal muscle function. These findings provide insight into the molecular basis of the sarcomere assembly and muscle dysfunction associated with nemaline myopathy. PMID:25774500

Lower Leg Anterior and Lateral Intracompartmental Pressure Changes Before and After Classic Versus Skate Nordic Rollerskiing

PubMed Central

Woods, Katherine M.; Petron, David J.; Shultz, Barry B.; Hicks-Little, Charlie A.

2015-01-01

Context Chronic exertional compartment syndrome (CECS) is a debilitating condition resulting in loss of function and a decrease in athletic performance. Cases of CECS are increasing among Nordic skiers; therefore, analysis of intracompartmental pressures (ICPs) before and after Nordic skiing is warranted. Objective To determine if lower leg anterior and lateral ICPs and subjective lower leg pain levels increased after a 20-minute Nordic rollerskiing time trial and to examine if differences existed between postexercise ICPs for the 2 Nordic rollerskiing techniques, classic and skate. Design Crossover study. Setting Outdoor paved loop. Patients or Other Participants Seven healthy Division I Nordic skiers (3 men, 4 women; age = 22.71 ± 1.38 y, height = 175.36 ± 6.33 cm, mass = 70.71 ± 6.58 kg). Intervention(s) Participants completed two 20-minute rollerskiing time trials using the classic and skate technique in random order. The time trials were completed 7 days apart. Anterior and lateral ICPs and lower leg pain scores were obtained at baseline and at minutes 1 and 5 after rollerskiing. Main Outcome Measure(s) Anterior and lateral ICPs (mm Hg) were measured using a Stryker Quic STIC handheld monitor. Subjective measures of lower leg pain were recorded using the 11-point Numeric Rating Scale. Results Increases in both anterior (P = .000) and lateral compartment (P = .002) ICPs were observed, regardless of rollerskiing technique used. Subjective lower leg pain increased after the classic technique for the men from baseline to 1 minute postexercise and after the skate technique for the women. Significant 3-way interactions (technique × time × sex) were observed for the anterior (P = .002) and lateral (P = .009) compartment ICPs and lower leg pain (P = .005). Conclusions Postexercise anterior and lateral ICPs increased compared with preexercise ICPs after both classic and skate rollerskiing techniques. Lower leg pain is a primary symptom of CECS. The subjective

A new de novo missense mutation in MYH2 expands clinical and genetic findings in hereditary myosin myopathies.

PubMed

D'Amico, A; Fattori, F; Bellacchio, E; Catteruccia, M; Servidei, S; Bertini, E

2013-05-01

Congenital myopathy related to mutations in myosin MyHC IIa gene (MYH2) is a rare neuromuscular disease. A single dominant missense mutation has been reported so far in a family in which the affected members had congenital joint contractures at birth, external ophthalmoplegia and proximal muscle weakness. Afterward only additional 4 recessive mutations have been identified in 5 patients presenting a mild non-progressive early-onset myopathy associated with ophthalmoparesis. We report a new de novo MYH2 missense mutation in a baby affected by a congenital myopathy characterized by severe dysphagia, respiratory distress at birth and external ophthalmoplegia. We describe clinical, histopathological and muscle imaging findings expanding the clinical and genetic spectrum of MYH2-related myopathy. Copyright © 2013 Elsevier B.V. All rights reserved.

Aerobic Exercise and Pharmacological Therapies for Skeletal Myopathy in Heart Failure: Similarities and Differences

PubMed Central

Bacurau, Aline V.; Cunha, Telma F.; Souza, Rodrigo W.; Voltarelli, Vanessa A.; Gabriel-Costa, Daniele; Brum, Patricia C.

2016-01-01

Skeletal myopathy has been identified as a major comorbidity of heart failure (HF) affecting up to 20% of ambulatory patients leading to shortness of breath, early fatigue, and exercise intolerance. Neurohumoral blockade, through the inhibition of renin angiotensin aldosterone system (RAS) and β-adrenergic receptor blockade (β-blockers), is a mandatory pharmacological therapy of HF since it reduces symptoms, mortality, and sudden death. However, the effect of these drugs on skeletal myopathy needs to be clarified, since exercise intolerance remains in HF patients optimized with β-blockers and inhibitors of RAS. Aerobic exercise training (AET) is efficient in counteracting skeletal myopathy and in improving functional capacity and quality of life. Indeed, AET has beneficial effects on failing heart itself despite being of less magnitude compared with neurohumoral blockade. In this way, AET should be implemented in the care standards, together with pharmacological therapies. Since both neurohumoral inhibition and AET have a direct and/or indirect impact on skeletal muscle, this review aims to provide an overview of the isolated effects of these therapeutic approaches in counteracting skeletal myopathy in HF. The similarities and dissimilarities of neurohumoral inhibition and AET therapies are also discussed to identify potential advantageous effects of these combined therapies for treating HF. PMID:26904163

An Italian family with inclusion-body myopathy and frontotemporal dementia due to mutation in the VCP gene.

PubMed

Gidaro, Teresa; Modoni, Anna; Sabatelli, Mario; Tasca, Giorgio; Broccolini, Aldobrando; Mirabella, Massimiliano

2008-01-01

Mutations of the valosin-containing protein gene (VCP) are responsible for autosomal-dominant hereditary inclusion-body myopathy associated with frontotemporal dementia and Paget's disease of bone. We identified the p.R155C missense mutation in the VCP gene segregating in an Italian family with three affected siblings, two of whom had a progressive myopathy associated with dementia, whereas one exhibited a progressive myopathy and preclinical signs of Paget's disease of bone. Our study demonstrates that VCP mutations are found in patients of Italian background and may lead to a variable clinical phenotype even within the same kinship.

A descriptive study of potential effect of anterior tibial translation, femoral tunnel and anterior cruciate ligament graft inclination on clinical outcome and degenerative changes.

PubMed

Snoj, Žiga; Zupanc, Oskar; Stražar, Klemen; Salapura, Vladka

2017-04-01

There is no evidence that anatomically correct anterior cruciate ligament reconstruction (ACLR) offers lower rate of degenerative changes development or that it would lead to a better outcome. The significance and understanding of the abnormal anterior tibial translation (ATT) in ACLR patients is yet to be established. Sixty subjects (40 patients at 5.9 years after ACLR, 20 healthy controls) underwent 3 T MRI. Quantitative cartilage T2 mapping and morphological whole organ magnetic resonance imaging score (WORMS) evaluation was performed. Self-reported questionnaires were used for subjective clinical evaluation. Correlations were calculated with the following MRI measurements; femoral tunnel inclination, ACL graft inclination, lateral and medial compartment ATT. In the ACLR group positive correlation was found between the patellar cartilage T2 values and sagittal ACL graft inclination. In the ACLR group lateral compartment ATT showed negative correlation with ACL graft inclination and subjective clinical evaluation, and positive correlation with morphological degenerative changes. Femoral tunnel showed positive correlation with ACL graft inclination in the same plane. Increased ATT offers worse clinical outcome and increased rate of degenerative changes. Furthermore, ATT is affected by the ACL inclination. Inclination of the drilling tunnel affects ACL graft inclination; thereby independent drilling techniques provide superior results of anatomical ACL graft positioning.

The estimated sensitivity and specificity of compartment pressure monitoring for acute compartment syndrome.

PubMed

McQueen, Margaret M; Duckworth, Andrew D; Aitken, Stuart A; Court-Brown, Charles M

2013-04-17

The aim of our study was to document the estimated sensitivity and specificity of continuous intracompartmental pressure monitoring for the diagnosis of acute compartment syndrome. From our prospective trauma database, we identified all patients who had sustained a tibial diaphyseal fracture over a ten-year period. A retrospective analysis of 1184 patients was performed to record and analyze the documented use of continuous intracompartmental pressure monitoring and the use of fasciotomy. A diagnosis of acute compartment syndrome was made if there was escape of muscles at fasciotomy and/or color change in the muscles or muscle necrosis intraoperatively. A diagnosis of acute compartment syndrome was considered incorrect if it was possible to close the fasciotomy wounds primarily at forty-eight hours. The absence of acute compartment syndrome was confirmed by the absence of neurological abnormality or contracture at the time of the latest follow-up. Of 979 monitored patients identified, 850 fit the inclusion criteria with a mean age of thirty-eight years (range, twelve to ninety-four years), and 598 (70.4%) were male (p < 0.001). A total of 152 patients (17.9%) underwent fasciotomy for the treatment of acute compartment syndrome: 141 had acute compartment syndrome (true positives), six did not have it (false positives), and five underwent fasciotomy despite having a normal differential pressure reading, with subsequent operative findings consistent with acute compartment syndrome (false negatives). Of the 698 patients (82.1%) who did not undergo fasciotomy, 689 had no evidence of any late sequelae of acute compartment syndrome (true negatives) at a mean follow-up time of fifty-nine weeks. The estimated sensitivity of intracompartmental pressure monitoring for suspected acute compartment syndrome was 94%, with an estimated specificity of 98%, an estimated positive predictive value of 93%, and an estimated negative predictive value of 99%. The estimated sensitivity and

Myosin Storage Myopathy in C. elegans and Human Cultured Muscle Cells

PubMed Central

Dahl-Halvarsson, Martin; Pokrzywa, Malgorzata; Rauthan, Manish; Pilon, Marc

2017-01-01

Myosin storage myopathy is a protein aggregate myopathy associated with the characteristic subsarcolemmal accumulation of myosin heavy chain in muscle fibers. Despite similar histological findings, the clinical severity and age of onset are highly variable, ranging from no weakness to severe impairment of ambulation, and usually childhood-onset to onset later in life. Mutations located in the distal end of the tail of slow/ß-cardiac myosin heavy chain are associated with myosin storage myopathy. Four missense mutations (L1793P, R1845W, E1883K and H1901L), two of which have been reported in several unrelated families, are located within or closed to the assembly competence domain. This location is critical for the proper assembly of sarcomeric myosin rod filaments. To assess the mechanisms leading to protein aggregation in myosin storage myopathy and to evaluate the impact of these mutations on myosin assembly and muscle function, we expressed mutated myosin proteins in cultured human muscle cells and in the nematode Caenorhabditis elegans. While L1793P mutant myosin protein efficiently incorporated into the sarcomeric thick filaments, R1845W and H1901L mutants were prone to formation of myosin aggregates without assembly into striated sarcomeric thick filaments in cultured muscle cells. In C. elegans, mutant alleles of the myosin heavy chain gene unc-54 corresponding to R1845W, E1883K and H1901L, were as effective as the wild-type myosin gene in rescuing the null mutant worms, indicating that they retain functionality. Taken together, our results suggest that the basis for the pathogenic effect of the R1845W and H1901L mutations are primarily structural rather than functional. Further analyses are needed to identify the primary trigger for the histological changes seen in muscle biopsies of patients with L1793P and E1883K mutations. PMID:28125727

Myosin Storage Myopathy in C. elegans and Human Cultured Muscle Cells.

PubMed

Dahl-Halvarsson, Martin; Pokrzywa, Malgorzata; Rauthan, Manish; Pilon, Marc; Tajsharghi, Homa

2017-01-01

Myosin storage myopathy is a protein aggregate myopathy associated with the characteristic subsarcolemmal accumulation of myosin heavy chain in muscle fibers. Despite similar histological findings, the clinical severity and age of onset are highly variable, ranging from no weakness to severe impairment of ambulation, and usually childhood-onset to onset later in life. Mutations located in the distal end of the tail of slow/ß-cardiac myosin heavy chain are associated with myosin storage myopathy. Four missense mutations (L1793P, R1845W, E1883K and H1901L), two of which have been reported in several unrelated families, are located within or closed to the assembly competence domain. This location is critical for the proper assembly of sarcomeric myosin rod filaments. To assess the mechanisms leading to protein aggregation in myosin storage myopathy and to evaluate the impact of these mutations on myosin assembly and muscle function, we expressed mutated myosin proteins in cultured human muscle cells and in the nematode Caenorhabditis elegans. While L1793P mutant myosin protein efficiently incorporated into the sarcomeric thick filaments, R1845W and H1901L mutants were prone to formation of myosin aggregates without assembly into striated sarcomeric thick filaments in cultured muscle cells. In C. elegans, mutant alleles of the myosin heavy chain gene unc-54 corresponding to R1845W, E1883K and H1901L, were as effective as the wild-type myosin gene in rescuing the null mutant worms, indicating that they retain functionality. Taken together, our results suggest that the basis for the pathogenic effect of the R1845W and H1901L mutations are primarily structural rather than functional. Further analyses are needed to identify the primary trigger for the histological changes seen in muscle biopsies of patients with L1793P and E1883K mutations.

Compartmented electrode structure

DOEpatents

Vissers, Donald R.; Shimotake, Hiroshi; Gay, Eddie C.; Martino, Fredric J.

1977-06-14

Electrodes for secondary electrochemical cells are provided with compartments for containing particles of the electrode reactant. The compartments are defined by partitions that are generally impenetrable to the particles of reactant and, in some instances, to the liquid electrolyte used in the cell. During cycling of the cell, reactant material initially loaded into a particular compartment is prevented from migrating and concentrating within the lower portion of the electrode or those portions of the electrode that exhibit reduced electrical resistance.

Technological quality, mineral profile, and sensory attributes of broiler chicken breasts affected by White Striping and Wooden Breast myopathies.

PubMed

Tasoniero, G; Cullere, M; Cecchinato, M; Puolanne, E; Dalle Zotte, A

2016-11-01

The aim of the research was to study the impact of white striping and wooden breast myopathies on the technological quality, mineral, and sensory profile of poultry meat. With this purpose, a total of 138 breasts were selected for a control group with normal breasts (N), a group of breasts characterised by white striping (WS) myopathy, and a group of breasts having both white striping and wooden breast myopathies (WSWB). Data revealed that the simultaneous presence of the two myopathies, with respect to the WS lesion individually considered, had a further detrimental effect on pH (6.04 vs. 5.96; P < 0.05), yellowness (11.4 vs. 10.3; P < 0.01), cooking losses (30.4 vs. 27.6%; P < 0.05), toughness instrumental values (22.8 vs. 20.0 N; P < 0.01), and perception (6.22 vs. 5.56; P < 0.01). In addition, mineral contents suggest that a defective ions regulation is also present in white striping and wooden breast myopathies. © 2016 Poultry Science Association Inc.

Dysferlinopathy in Switzerland: clinical phenotypes and potential founder effects.

PubMed

Petersen, Jens A; Kuntzer, Thierry; Fischer, Dirk; von der Hagen, Maja; Huebner, Angela; Kana, Veronika; Lobrinus, Johannes A; Kress, Wolfram; Rushing, Elisabeth J; Sinnreich, Michael; Jung, Hans H

2015-10-06

Dysferlin is reduced in patients with limb girdle muscular dystrophy type 2B, Miyoshi myopathy, distal anterior compartment myopathy, and in certain Ethnic clusters. We evaluated clinical and genetic patient data from three different Swiss Neuromuscular Centers. Thirteen patients from 6 non-related families were included. Age of onset was 18.8 ± 4.3 years. In all patients, diallelic disease-causing mutations were identified in the DYSF gene. Nine patients from 3 non-related families from Central Switzerland carried the identical homozygous mutation, c.3031 + 2 T>C. A possible founder effect was confirmed by haplotype analysis. Three patients from two different families carried the heterozygous mutation, c.1064_1065delAA. Two novel mutations were identified (c.2869 C>T (p.Gln957Stop), c.5928 G>A (p.Trp1976Stop)). Our study confirms the phenotypic heterogeneity associated with DYSF mutations. Two mutations (c.3031 + 2 T>C, c.1064_1065delAA) appear common in Switzerland. Haplotype analysis performed on one case (c. 3031 + 2 T>C) suggested a possible founder effect.

Spinning-induced Rhabdomyolysis and the Risk of Compartment Syndrome and Acute Kidney Injury

PubMed Central

DeFilippis, Ersilia M.; Kleiman, David A.; Derman, Peter B.; DiFelice, Gregory S.; Eachempati, Soumitra R.

2014-01-01

Exercise-induced rhabdomyolysis related to military training, marathon running, and other forms of strenuous exercise has been reported. The incidence of acute kidney injury appears to be lower in exercise-induced cases. We present 2 cases of exercise-induced rhabdomyolysis following spinning classes, one of which was further complicated by acute compartment syndrome requiring bilateral fasciotomies of the anterior thigh and acute kidney injury. With vigorous hydration and urine pH monitoring, both patients exhibited good mobility, sensation, and renal function on discharge. PMID:24982706

Spacecraft compartment venting

NASA Astrophysics Data System (ADS)

Scialdone, John J.

1998-10-01

At various times, concerns have been expressed that rapid decompressions of compartments of gas pockets and thermal blankets during spacecraft launches may have caused pressure differentials across their walls sufficient to cause minor structural failures, separations of adhesively-joined parts, ballooning, and flapping of blankets. This paper presents a close form equation expressing the expected pressure differentials across the walls of a compartment as a function of the external to the volume pressure drops, the pressure at which the rates occur and the vent capability of the compartment. The pressure profiles measured inside the shrouds of several spacecraft propelled by several vehicles and some profiles obtained from ground vacuum systems have been included. The equation can be used to design the appropriate vent, which will preclude excessive pressure differentials. Precautions and needed approaches for the evaluations of the expected pressures have been indicated. Methods to make a rapid assessment of the response of the compartment to rapid external pressure drops have been discussed. These are based on the evaluation of the compartment vent flow conductance, the volume and the length of time during which the rapid pressure drop occurs.

Spacecraft Compartment Venting

NASA Technical Reports Server (NTRS)

Scialdone, John J.

1998-01-01

At various time concerns have been expressed that rapid decompressions of compartments of gas pockets and thermal blankets during spacecraft launches may have caused pressure differentials across their walls sufficient to cause minor structural failures, separations of adhesively-joined parts, ballooning, and flapping of blankets. This paper presents a close form equation expressing the expected pressure differentials across the walls of a compartment as a function of the external to the volume pressure drops, the pressure at which the rates occur and the vent capability of the compartment. The pressure profiles measured inside the shrouds of several spacecraft propelled by several vehicles and some profiles obtained from ground vacuum systems have been included. The equation can be used to design the appropriate vent, which will preclude excessive pressure differentials. Precautions and needed approaches for the evaluations of the expected pressures have been indicated. Methods to make a rapid assessment of the response of the compartment to rapid external pressure drops have been discussed. These are based on the evaluation of the compartment vent flow conductance, the volume and the length of time during which the rapid pressure drop occurs.

Hereditary vacuolar internal anal sphincter myopathy causing proctalgia fugax and constipation: a new case contribution.

PubMed

de la Portilla, Fernando; Borrero, Juan José; Rafel, Enrique

2005-03-01

Hereditary anal sphincter myopathy is rare. We present a family with one affected member with proctalgia fugax, constipation and internal anal sphincter hypertrophy. Ultrastructural findings show vacuolization of smooth muscle cells without the characteristic polyglucosan inclusion. Further relief of symptoms was obtained using an oral calcium antagonist. Based on clinical presentation, endosonography and morphological findings, we consider our case is a histological variant of the vacuolar myopathy originally described.

Paraneoplastic necrotizing myopathy in a woman with breast cancer: a case report.

PubMed

Silvestre, Joana; Santos, Luis; Batalha, Vitor; Del Rio, Ana; Lima, Carlos; Carvalho, Antonio; Martins, Ana; Miranda, Helena; Cabral, Fatima; Felix, Adelia; Aleixo, Ana

2009-11-02

Paraneoplastic necrotizing myopathy is a rare disorder, described as a proximal, symmetrical, and rapidly progressing myopathy that is manifested as a paraneoplastic syndrome. Diagnosis is established via histological examination of the muscle biopsy. We present the case of a 53-year-old woman, born in Guinea-Bissau, with a history of locally advanced breast cancer, diagnosed ten months previously. The patient had experienced a progressively proximal muscle weakness of the lower extremities, which led to a total inability to walk. Upon neurological examination, the patient showed muscle weakness and atrophy in both proximal lower extremities without myalgia. Muscle strength was graded according to the Medical Research Council Scale as 2 out of 5 in the bilateral iliopsoas muscle, and 4 out of 5 in the bilateral quadriceps femoris. The deep-tendon reflexes were hypoactive. The laboratory examination showed increased values of serum creatinine kinase and myoglobin. An electromyogram showed an incomplete interference pattern during voluntary contraction in the iliopsoas and quadriceps femoris. The motor nerve conduction was 44.1 m/s and 44.3 m/s in the right and left tibial nerves, respectively, and 46.5 m/s and 46.1 m/s in the right and left peroneal nerves, respectively. The sensory motor nerve conductions and the compound motor action potential amplitudes were normal. These findings, despite not being specific, suggested a myopathy. Consequently, a muscle biopsy was performed. A biopsy specimen showed myopathic changes that were characteristic of a necrotizing myopathy. Treatment for this syndrome consists of controlling the tumor, and providing corticoid therapy. This led to the partial remission of the neurological manifestations.

Antisense oligonucleotide therapeutics for iron-sulphur cluster deficiency myopathy.

PubMed

Kollberg, Gittan; Holme, Elisabeth

2009-12-01

Iron-sulphur cluster deficiency myopathy is caused by a deep intronic mutation in ISCU resulting in inclusion of a cryptic exon in the mature mRNA. ISCU encodes the iron-sulphur cluster assembly protein IscU. Iron-sulphur clusters are essential for most basic redox transformations including the respiratory-chain function. Most patients are homozygous for the mutation with a phenotype characterized by a non-progressive myopathy with childhood onset of early fatigue, dyspnoea and palpitation on trivial exercise. A more severe phenotype with early onset of a slowly progressive severe muscle weakness, severe exercise intolerance and cardiomyopathy is caused by a missense mutation in compound with the intronic mutation. Treatment of cultured fibroblasts derived from three homozygous patients with an antisense phosphorodiamidate morpholino oligonucleotide for 48 h resulted in 100% restoration of the normal splicing pattern. The restoration was stable and after 21 days the correctly spliced mRNA still was the dominating RNA species.

Statin myopathy: the fly in the ointment for the prevention of cardiovascular disease in the 21st century?

PubMed

Keen, Helen I; Krishnarajah, Janakan; Bates, Timothy R; Watts, Gerald F

2014-09-01

Cardiovascular disease (CVD) remains the leading cause of death in industrialized nations. Despite clear evidence of CVD risk reduction with HMG-CoA reductase inhibitors (statins), the side effects of these medications, particularly myopathy, limit their effectiveness. Studies into the mechanisms, aetiology and management of statin myopathy are limited by lack of an internationally agreed clinical definition and tools for assessing outcomes. Currently there is a paucity of evidence to guide the management of patients affected by statin myopathy; with the exception of dose reduction, there is little evidence that other strategies can improve statin tolerance, and even less evidence to suggest these alternate dosing strategies reduce cardiovascular risk. This review will cover current definitions, clinical presentations, risk factors, pathogenesis and management. PubMed was searched (English language, to 2014) for key articles pertaining to statin myopathy. This review then briefly describes our experience of managing this condition in a tertiary lipid disorders clinic, in the setting of limited guiding evidence. Knowledge gaps in the field of statin myopathy are identified and future research directions are suggested. We urge the need for international attention to address this important, but largely neglected clinical problem, that if unresolved will remain an impediment to the effective prevention and treatment of CVD.

Capture myopathy in an endangered sandhill crane (Grus canadensis pulla)

USGS Publications Warehouse

Carpenter, J.W.; Thomas, N.J.; Reeves, S.

1991-01-01

Despite precautions to protect cranes, a 3-year-old endangered Mississippi sandhill crane (Grus canadensis pulla) was found caught in a leghold trap in Gautier, Mississippi, on 11 November 1987. The bird could have been in the trap for up to 16 hr and was standing and struggling to escape when it was discovered. Serum chemistries of the crane on 12 November revealed elevated lactic dehydrogenase (2,880 IU/L), alanine aminotransferase (ALT) (152 IU/L), and aspartate aminotransferase (AST) (>1,000 IU/L) values. Following surgical amputation of a fractured toe, the bird never attempted to stand and was unable to stand even when manually supported. Radiographic and physical examination of both legs did not reveal any anatomical abnormalities. Despite medical care, including supportive therapy, no improvement was observed in the bird's ability to stand and to support itself, and the bird died on 19 November. Serum chemistries and the postmortem and histopathologic findings were compatible with capture myopathy described in other species. Because of the possible susceptibility of long-legged birds such as the Mississippi sandhill crane to capture myopathy, special care must be taken when trapping, handling, chemically immobilizing, and transporting these species. In addition, precautions must be taken when conducting a predator-control program to ensure that nontarget wildlife are unlikely to encounter traps. Capture myopathy has only rarely been observed in wild birds, and this case represents the first report in a Mississippi sandhill crane.

A novel MYH7 mutation links congenital fiber type disproportion and myosin storage myopathy.

PubMed

Ortolano, Saida; Tarrío, Rosa; Blanco-Arias, Patricia; Teijeira, Susana; Rodríguez-Trelles, Francisco; García-Murias, María; Delague, Valerie; Lévy, Nicolas; Fernández, José M; Quintáns, Beatriz; Millán, Beatriz San; Carracedo, Angel; Navarro, Carmen; Sobrido, María-Jesús

2011-04-01

This study aimed to identify the genetic defect in a multigenerational family presenting an autosomal dominant myopathy with histological features of congenital fiber type disproportion. Linkage analysis and genetic sequencing identified, in all affected members of the family, the c.5807A>G heterozygous mutation in MYH7, which encodes the slow/β-cardiac myosin heavy chain. This mutation causes skeletal but not cardiac involvement. Myosin heavy chain expression pattern was also characterized by immunohistochemistry, western blot and q-PCR in muscle biopsies from two patients aged 25 and 62, respectively. While only congenital fiber type disproportion was observed in the younger patient, older patient's biopsy presented aggregates of slow myosin heavy chains, in fiber sub-sarcolemmal region. These clinico-pathologic findings suggest a novel phenotype within the emerging group of hereditary myosin myopathies, which in this family presents typical characteristics of congenital fiber type disproportion in early stages and later evolves to myosin storage myopathy. Copyright © 2011 Elsevier B.V. All rights reserved.

MCT1, MCT4 and CD147 gene polymorphisms in healthy horses and horses with myopathy.

PubMed

Mykkänen, A K; Koho, N M; Reeben, M; McGowan, C M; Pösö, A R

2011-12-01

Polymorphisms in human lactate transporter proteins (monocarboxylate transporters; MCTs), especially the MCT1 isoform, can affect lactate transport activity and cause signs of exercise-induced myopathy. Muscles express MCT1, MCT4 and CD147, an ancillary protein, indispensable for the activity of MCT1 and MCT4. We sequenced the coding sequence (cDNA) of horse MCT4 for the first time and examined polymorphisms in the cDNA of MCT1, MCT4 and CD147 of 16 healthy horses. To study whether signs of myopathy are linked to the polymorphisms, biopsy samples were taken from 26 horses with exercise-induced recurrent myopathy. Two polymorphisms that cause a change in amino acid sequence were found in MCT1 (Val(432)Ile and Lys(457)Gln) and one in CD147 (Met(125)Val). All polymorphisms in MCT4 were silent. Mutations in MCT1 or CD147 in equine muscle were not associated with myopathy. In the future, a functional study design is needed to evaluate the physiological role of the polymorphisms found. Copyright © 2010 Elsevier Ltd. All rights reserved.

Evaluating the Atrial Myopathy Underlying Atrial Fibrillation: Identifying the Arrhythmogenic and Thrombogenic Substrate

PubMed Central

Goldberger, Jeffrey J.; Arora, Rishi; Green, David; Greenland, Philip; Lee, Daniel C.; Lloyd-Jones, Donald M.; Markl, Michael; Ng, Jason; Shah, Sanjiv J.

2015-01-01

Atrial disease or myopathy forms the substrate for atrial fibrillation (AF) and underlies the potential for atrial thrombus formation and subsequent stroke. Current diagnostic approaches in patients with AF focus on identifying clinical predictors with evaluation of left atrial size by echocardiography serving as the sole measure specifically evaluating the atrium. Although the atrial substrate underlying AF is likely developing for years prior to the onset of AF, there is no current evaluation to identify the pre-clinical atrial myopathy. Atrial fibrosis is one component of the atrial substrate that has garnered recent attention based on newer MRI techniques that have been applied to visualize atrial fibrosis in humans with prognostic implications regarding success of treatment. Advanced ECG signal processing, echocardiographic techniques, and MRI imaging of fibrosis and flow provide up-to-date approaches to evaluate the atrial myopathy underlying AF. While thromboembolic risk is currently defined by clinical scores, their predictive value is mediocre. Evaluation of stasis via imaging and biomarkers associated with thrombogenesis may provide enhanced approaches to assess risk for stroke in patients with AF. Better delineation of the atrial myopathy that serves as the substrate for AF and thromboembolic complications might improve treatment outcomes. Furthermore, better delineation of the pathophysiologic mechanisms underlying the development of the atrial substrate for AF, particularly in its earlier stages, could help identify blood and imaging biomarkers that could be useful to assess risk for developing new onset AF and suggest specific pathways that could be targeted for prevention. PMID:26216085

Automatic segmentation of abdominal organs and adipose tissue compartments in water-fat MRI: Application to weight-loss in obesity.

PubMed

Shen, Jun; Baum, Thomas; Cordes, Christian; Ott, Beate; Skurk, Thomas; Kooijman, Hendrik; Rummeny, Ernst J; Hauner, Hans; Menze, Bjoern H; Karampinos, Dimitrios C

2016-09-01

To develop a fully automatic algorithm for abdominal organs and adipose tissue compartments segmentation and to assess organ and adipose tissue volume changes in longitudinal water-fat magnetic resonance imaging (MRI) data. Axial two-point Dixon images were acquired in 20 obese women (age range 24-65, BMI 34.9±3.8kg/m(2)) before and after a four-week calorie restriction. Abdominal organs, subcutaneous adipose tissue (SAT) compartments (abdominal, anterior, posterior), SAT regions along the feet-head direction and regional visceral adipose tissue (VAT) were assessed by a fully automatic algorithm using morphological operations and a multi-atlas-based segmentation method. The accuracy of organ segmentation represented by Dice coefficients ranged from 0.672±0.155 for the pancreas to 0.943±0.023 for the liver. Abdominal SAT changes were significantly greater in the posterior than the anterior SAT compartment (-11.4%±5.1% versus -9.5%±6.3%, p<0.001). The loss of VAT that was not located around any organ (-16.1%±8.9%) was significantly greater than the loss of VAT 5cm around liver, left and right kidney, spleen, and pancreas (p<0.05). The presented fully automatic algorithm showed good performance in abdominal adipose tissue and organ segmentation, and allowed the detection of SAT and VAT subcompartments changes during weight loss. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Oral monosaccharide therapies to reverse renal and muscle hyposialylation in a mouse model of GNE myopathy

PubMed Central

Niethamer, Terren K.; Yardeni, Tal; Leoyklang, Petcharat; Ciccone, Carla; Astiz-Martinez, Adrian; Jacobs, Katherine; Dorward, Heidi M.; Zerfas, Patricia M.; Gahl, William A.; Huizing, Marjan

2012-01-01

GNE myopathy, previously termed hereditary inclusion body myopathy (HIBM), is an adult-onset neuromuscular disorder characterized by progressive muscle weakness. The disorder results from biallelic mutations in GNE, encoding UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase, the key enzyme of sialic acid synthesis. GNE myopathy, associated with impaired glycan sialylation, has no approved therapy. Here we test potential sialylation-increasing monosaccharides for their effectiveness in prophylaxis (at the embryonic and neonatal stages) and therapy (after the onset of symptoms) by evaluating renal and muscle hyposialylation in a knock-in mouse model (Gne p.M712T) of GNE myopathy. We demonstrate that oral mannosamine (ManN), but not sialic acid (Neu5Ac), mannose (Man), galactose (Gal), or glucosamine (GlcN), administered to pregnant female mice has a similar prophylactic effect on renal hyposialylation, pathology and neonatal survival of mutant offspring, as previously shown for N-acetylmannosamine (ManNAc) therapy. ManN may be converted to ManNAc by a direct, yet unknown, pathway, or may act through another mode of action. The other sugars (Man, Gal, GlcN) may either not cross the placental barrier (Neu5Ac) and/or may be able to directly increase sialylation. Because GNE myopathy patients will likely require treatment in adulthood after onset of symptoms, we also administered ManNAc (1 or 2 g/kg/day for 12 weeks), Neu5Ac (2g/kg/day for 12 weeks), or ManN (2g/kg/day for 6 weeks) in drinking water to 6 month old mutant Gne p.M712T mice. All three therapies markedly improved the muscle and renal hyposialylation, as evidenced by lectin histochemistry for overall sialylation status and immunoblotting of specific sialoproteins. These preclinical data strongly support further evaluation of oral ManNAc, Neu5Ac and ManN as therapy for GNE myopathy and conceivably for certain glomerular diseases with hyposialylation. PMID:23122659

Distinct muscle apoptotic pathways are activated in muscles with different fiber types in a rat model of critical illness myopathy.

PubMed

Barnes, Benjamin T; Confides, Amy L; Rich, Mark M; Dupont-Versteegden, Esther E

2015-06-01

Critical illness myopathy (CIM) is associated with severe muscle atrophy and fatigue in affected patients. Apoptotic signaling is involved in atrophy and is elevated in muscles from patients with CIM. In this study we investigated underlying mechanisms of apoptosis-related pathways in muscles with different fiber type composition in a rat model of CIM using denervation and glucocorticoid administration (denervation and steroid-induced myopathy, DSIM). Soleus and tibialis anterior (TA) muscles showed severe muscle atrophy (40-60% of control muscle weight) and significant apoptosis in interstitial as well as myofiber nuclei that was similar between the two muscles with DSIM. Caspase-3 and -8 activities, but not caspase-9 and -12, were elevated in TA and not in soleus muscle, while the caspase-independent proteins endonuclease G (EndoG) and apoptosis inducing factor (AIF) were not changed in abundance nor differentially localized in either muscle. Anti-apoptotic proteins HSP70, -27, and apoptosis repressor with a caspase recruitment domain (ARC) were elevated in soleus compared to TA muscle and ARC was significantly decreased with induction of DSIM in soleus. Results indicate that apoptosis is a significant process associated with DSIM in both soleus and TA muscles, and that apoptosis-associated processes are differentially regulated in muscles of different function and fiber type undergoing atrophy due to DSIM. We conclude that interventions combating apoptosis with CIM may need to be directed towards inhibiting caspase-dependent as well as -independent mechanisms to be able to affect muscles of all fiber types.

Disease Severity and Thin Filament Regulation in M9R TPM3 Nemaline Myopathy

PubMed Central

Ilkovski, Biljana; Mokbel, Nancy; Lewis, Raymond A.; Walker, Kendall; Nowak, Kristen J.; Domazetovska, Ana; Laing, Nigel G.; Fowler, Velia M.; North, Kathryn N.; Cooper, Sandra T.

2009-01-01

The mechanism of muscle weakness was investigated in an Australian family with a M9R mutation in TPM3 (α-tropomyosinslow). Detailed protein analyses of five muscle samples from two patients showed that nemaline bodies are restricted to atrophied type 1 (slow) fibers in which the TPM3 gene is expressed. Developmental expression studies showed that α-tropomyosinslow is not expressed at significant levels until after birth, thereby likely explaining the childhood (rather than congenital) disease onset in TPM3 nemaline myopathy. Isoelectric focusing demonstrated that α-tropomyosinslow dimers, comprised of equal ratios of wild-type and M9R-α-tropomyosinslow, are the dominant tropomyosin species in three separate muscle groups from an affected patient. These findings suggest that myopathy-related slow fiber predominance likely contributes to the severity of weakness in TPM3 nemaline myopathy because of increased proportions of fibers that express the mutant protein. Using recombinant proteins and far Western blot we demonstrated a higher affinity of tropomodulin for α-tropomyosinslow compared to β-tropomyosin; the M9R substitution within α-tropomyosinslow greatly reduced this interaction. Finally, transfection of the M9R mutated and wild-type α-tropomyosinslow into myoblasts revealed reduced incorporation into stress fibers and disruption of the filamentous actin network by the mutant protein. Collectively, these results provide insights into the clinical features and pathogenesis of M9R-TPM3 nemaline myopathy. PMID:18716557

An analysis of the sensitivity and specificity of MHC-I and MHC-II immunohistochemical staining in muscle biopsies for the diagnosis of inflammatory myopathies.

PubMed

Rodríguez Cruz, Pedro M; Luo, Yue-Bei; Miller, James; Junckerstorff, Reimar C; Mastaglia, Frank L; Fabian, Victoria

2014-12-01

Although there have been several previous reports of immunohistochemical staining for MHC antigens in muscle biopsies, there appears to be a lack of consensus about its routine use in the diagnostic evaluation of biopsies from patients with suspected inflammatory myopathy. Positive MHC-I staining is nonspecific but is widely used as a marker for inflammatory myopathy, whilst the role of MHC-II staining is not clearly defined. We investigated the sensitivity and specificity of MHC-I and MHC-II immunostaining for the diagnosis of inflammatory myopathy in a large group of biopsies from a single reference laboratory. Positive staining for MHC-I was found to have a high sensitivity in biopsies from patients with inflammatory myopathy but a very low specificity, as it was also common in other non-inflammatory myopathies and neurogenic disorders. On the other hand, MHC-II positivity had a much higher specificity in all major subgroups of inflammatory myopathy, especially inclusion body myositis. The findings indicate that the combination of MHC-I and MHC-II staining results in a higher degree of specificity for the diagnosis of inflammatory myopathy and that in biopsies with inflammation, positive MHC-II staining strongly supports the diagnosis of an immune-mediated myopathy. We recommend that immunohistochemical staining for both MHC-I and MHC-II should be included routinely in the diagnostic evaluation of muscle biopsies from patients with suspected inflammatory myopathy. However, as the sensitivity and interpretation of MHC staining may depend on the technique used, further studies are needed to compare procedures in different centres and develop standardised protocols. Copyright © 2014 Elsevier B.V. All rights reserved.

Hereditary inclusion-body myopathy: clues on pathogenesis and possible therapy.

PubMed

Broccolini, Aldobrando; Gidaro, Teresa; Morosetti, Roberta; Mirabella, Massimiliano

2009-09-01

Hereditary inclusion-body myopathy (h-IBM), or distal myopathy with rimmed vacuoles (DMRV), is an autosomal recessive disorder with onset in early adult life and a progressive course leading to severe disability. h-IBM/DMRV is due to mutations of a gene (GNE) that codes for a rate-limiting enzyme in the sialic acid biosynthetic pathway. Despite the identification of the causative gene defect, it has not been unambiguously clarified how GNE gene mutations impair muscle metabolism. Although numerous studies have indicated a key role of hyposialylation of glycoproteins in h-IBM/DMRV pathogenesis, others have demonstrated new and unpredicted functions of the GNE gene, outside the sialic acid biosynthetic pathway, that may also be relevant. This review illustrates the clinical and pathologic characteristics of h-IBM/DMRV and the main clues available to date concerning the possible pathogenic mechanisms and therapeutic perspectives of this disorder.

Near-infrared spectroscopy for monitoring of tissue oxygenation of exercising skeletal muscle in a chronic compartment syndrome model

NASA Technical Reports Server (NTRS)

Breit, G. A.; Gross, J. H.; Watenpaugh, D. E.; Chance, B.; Hargens, A. R.

1997-01-01

Variations in the levels of muscle hemoglobin and of myoglobin oxygen saturation can be detected non-invasively with near-infrared spectroscopy. This technique could be applied to the diagnosis of chronic compartment syndrome, in which invasive testing has shown increased intramuscular pressure associated with ischemia and pain during exercise. We simulated chronic compartment syndrome in ten healthy subjects (seven men and three women) by applying external compression, through a wide inflatable cuff, to increase the intramuscular pressure in the anterior compartment of the leg. The tissue oxygenation of the tibialis anterior muscle was measured with near-infrared spectroscopy during gradual inflation of the cuff to a pressure of forty millimeters of mercury (5.33 kilopascals) during fourteen minutes of cyclic isokinetic dorsiflexion and plantar flexion of the ankle. The subjects exercised with and without external compression. The data on tissue oxygenation for each subject then were normalized to a scale of 100 per cent (the baseline value, or the value at rest) to 0 per cent (the physiological minimum, or the level of oxygenation achieved by exercise to exhaustion during arterial occlusion of the lower extremity). With external compression, tissue oxygenation declined at a rate of 1.4 +/- 0.3 per cent per minute (mean and standard error) during exercise. After an initial decrease at the onset, tissue oxygenation did not decline during exercise without compression. The recovery of tissue oxygenation after exercise was twice as slow with compression (2.5 +/- 0.6 minutes) than it was without the use of compression (1.3 +/- 0.2 minutes).

Opening the medial tibiofemoral compartment by pie-crusting the superficial medial collateral ligament at its tibial insertion: a cadaver study.

PubMed

Roussignol, X; Gauthe, R; Rahali, S; Mandereau, C; Courage, O; Duparc, F

2015-09-01

Arthroscopic treatment of tears in the middle and posterior parts of the medial meniscus can be difficult when the medial tibiofemoral compartment is tight. Passage of the instruments may damage the cartilage. The primary objective of this cadaver study was to perform an arthroscopic evaluation of medial tibiofemoral compartment opening after pie-crusting release (PCR) of the superficial medial collateral ligament (sMCL) at its distal insertion on the tibia. The secondary objective was to describe the anatomic relationships at the site of PCR (saphenous nerve, medial saphenous vein). We studied 10 cadaver knees with no history of invasive procedures. The femur was held in a vise with the knee flexed at 45°, and the medial aspect of the knee was dissected. PCR of the sMCL was performed under arthroscopic vision, in the anteroposterior direction, at the distal tibial insertion of the sMCL, along the lower edge of the tibial insertion of the semi-tendinosus tendon. Continuous 300-N valgus stress was applied to the ankle. Opening of the medial tibiofemoral compartment was measured arthroscopically using graduated palpation hooks after sequential PCR of the sMCL. The compartment opened by 1mm after release of the anterior third, 2.3mm after release of the anterior two-thirds, and 3.9mm after subtotal release. A femoral fracture occurred in 1 case, after completion of all measurements. Both the saphenous nerve and the medial saphenous vein were located at a distance from the PCR site in all 10 knees. PCR of the sMCL is chiefly described as a ligament-balancing method during total knee arthroplasty. This procedure is usually performed at the joint line, where it opens the compartment by 4-6mm at the most, with some degree of unpredictability. PCR of the sMCL at its distal tibial insertion provides gradual opening of the compartment, to a maximum value similar to that obtained with PCR at the joint space. The lower edge of the semi-tendinosus tendon is a valuable landmark

Reasons for and Against Use of Non-absorbable, Synthetic Mesh During Pelvic Organ Prolapse Repair, According to the Prolapsed Compartment.

PubMed

Kontogiannis, Stavros; Goulimi, Evangelia; Giannitsas, Konstantinos

2017-01-01

Awareness and reporting of mesh-related complications of pelvic organ prolapse repairs have increased in recent years. As a result, deciding whether to use a mesh or not has become a difficult task for urogynecologists. Our aim was to summarize reasons for and against the use of mesh in prolapse repair based on a review of relevant literature. Scopus and PubMed databases were searched for papers reporting on the efficacy and safety of native tissue versus non-absorbable, synthetic mesh prolapse repairs. Randomized controlled trials, systematic reviews, and meta-analyses were included. Evidence is presented for each vaginal compartment separately. In the anterior compartment, mesh repairs seem to offer clearly superior efficacy and durability of results compared to native tissue repairs, but with an equally clear increase in complication rates. In the isolated posterior compartment prolapse, high-quality evidence is sparse. As far as the apical compartment is concerned, sacrocolpopexy is the most efficacious, yet the most invasive procedure. Data on the comparison of transvaginal mesh versus native tissue repairs of the apical compartment are somewhat ambiguous. Given the inevitable coexistence of advantages and disadvantages of mesh use in each of the prolapsed vaginal compartments, an individualized treatment decision, based on weighing risks against benefits for each patient, seems to be the most rational approach.

Genetic risk factors associated with lipid-lowering drug-induced myopathies.

PubMed

Vladutiu, Georgirene D; Simmons, Zachary; Isackson, Paul J; Tarnopolsky, Mark; Peltier, Wendy L; Barboi, Alexandru C; Sripathi, Naganand; Wortmann, Robert L; Phillips, Paul S

2006-08-01

Lipid-lowering drugs produce myopathic side effects in up to 7% of treated patients, with severe rhabdomyolysis occurring in as many as 0.5%. Underlying metabolic muscle diseases have not been evaluated extensively. In a cross-sectional study of 136 patients with drug-induced myopathies, we report a higher prevalence of underlying metabolic muscle diseases than expected in the general population. Control groups included 116 patients on therapy with no myopathic symptoms, 100 asymptomatic individuals from the general population never exposed to statins, and 106 patients with non-statin-induced myopathies. Of 110 patients who underwent mutation testing, 10% were heterozygous or homozygous for mutations causing three metabolic myopathies, compared to 3% testing positive among asymptomatic patients on therapy (P = 0.04). The actual number of mutant alleles found in the test group patients was increased fourfold over the control group (P < 0.0001) due to an increased presence of mutation homozygotes. The number of carriers for carnitine palmitoyltransferase II deficiency and for McArdle disease was increased 13- and 20-fold, respectively, over expected general population frequencies. Homozygotes for myoadenylate deaminase deficiency were increased 3.25-fold with no increase in carrier status. In 52% of muscle biopsies from patients, significant biochemical abnormalities were found in mitochondrial or fatty acid metabolism, with 31% having multiple defects. Variable persistent symptoms occurred in 68% of patients despite cessation of therapy. The effect of statins on energy metabolism combined with a genetic susceptibility to triggering of muscle symptoms may account for myopathic outcomes in certain high-risk groups.

A case of adult-onset reducing body myopathy presenting a novel clinical feature, asymmetrical involvement of the sternocleidomastoid and trapezius muscles.

PubMed

Fujii, Takayuki; Hayashi, Shintaro; Kawamura, Nobutoshi; Higuchi, Masa-Aki; Tsugawa, Jun; Ohyagi, Yasumasa; Hayashi, Yukiko K; Nishino, Ichizo; Kira, Jun-Ichi

2014-08-15

We herein report a 32-year-old woman with adult-onset reducing body myopathy (RBM) who had a mutation in the four-and-a-half LIM domain 1 gene (FHL1) and showed a marked asymmetrical involvement of sternocleidomastoid and trapezius muscles. At 30 years of age she noticed bilateral foot drop, and over the next two years developed difficulty raising her right arm. At 32 years of age she was admitted to our hospital for a diagnostic evaluation. Neurological examination showed moderate weakness and atrophy of her right sternocleidomastoid muscle, right trapezius muscle, and bilateral upper proximal muscles. There were severe weakness and atrophy of her bilateral tibialis anterior muscles. Her deep tendon reflexes were hypoactive in her upper extremities. Her serum creatine kinase level was mildly increased. Muscle biopsy specimens from the left tibialis anterior muscle revealed marked variation in fiber size, some necrotic or regenerating fibers, and reducing bodies. Gene analysis of FHL1 demonstrated a mutation: a heterozygous missense mutation of c.377G>A (p. C126T) in FHL1. Compared with previous adult-onset RBM cases harboring mutations in FHL1, our case was characterized by asymmetrical atrophy of the sternocleidomastoid and trapezius muscles. Copyright © 2014 Elsevier B.V. All rights reserved.

Architectural differences in the anterior and middle compartments of the pelvic floor of young-adult and postmenopausal females.

PubMed

Wu, Yi; Dabhoiwala, Noshir F; Hagoort, Jaco; Tan, Li-Wen; Zhang, Shao-Xiang; Lamers, Wouter H

2017-05-01

The pelvic floor guards the passage of the pelvic organs to the exterior. The near-epidemic prevalence of incontinence in women continues to generate interest in the functional anatomy of the pelvic floor. However, due to its complex architecture and poor accessibility, the classical 'dissectional' approach has been unable to come up with a satisfactory description, so that many aspects of its anatomy continue to raise debate. For this reason, we opted for a 'sectional' approach, using the Chinese Visible Human project (four females, 21-35 years) and the Visible Human Project (USA; one female, 59 years) datasets to investigate age-related changes in the architecture of the anterior and middle compartments of the pelvic floor. The puborectal component of the levator ani muscle defined the levator hiatus boundary. The urethral sphincter complex consisted of a circular proximal portion (urethral sphincter proper), a sling that passed on the vaginal wall laterally to attach to the puborectal muscle (urethral compressor), and a circular portion that surrounded the distal urethra and vagina (urethrovaginal sphincter). The exclusive attachment of the urethral sphincter to soft tissues implies dependence on pelvic-floor integrity for optimal function. The vagina was circular at the introitus and gradually flattened between bladder and rectum. Well-developed fibrous tissue connected the inferior vaginal wall with urethra, rectum and pelvic floor. With eight-muscle insertions, the perineal body was a strong, irregular fibrous node that guarded the levator hiatus. Only loose areolar tissue comprising a remarkably well developed venous plexus connecting the middle and superior parts of the vagina with the lateral pelvic wall. The posterolateral boundary of the putative cardinal and sacrouterine ligaments coincided with the adventitia surrounding the mesorectum. The major difference between the young-adult and postmenopausal pelvic floor was the expansion of fat in between

The cnm locus, a canine homologue of human autosomal forms of centronuclear myopathy, maps to chromosome 2.

PubMed

Tiret, Laurent; Blot, Stéphane; Kessler, Jean-Louis; Gaillot, Hugues; Breen, Matthew; Panthier, Jean-Jacques

2003-09-01

Myotubular/centronuclear myopathies are a nosological group of hereditary disorders characterised by severe architectural and metabolic remodelling of skeletal muscle fibres. In most myofibres, nuclei are found at an abnormal central position within a halo devoid of myofibrillar proteins. The X-linked form (myotubular myopathy) is the most prevalent and severe form in human, leading to death during early postnatal life. Maturation of fibres is not completed and fibres resemble myotubes. Linkage analysis in human has helped to identify MTM1 as the morbid gene. MTM1 encodes myotubularin, a dual protein phosphatase. In families in which myotubular myopathy segregates, detected mutations in MTM1 abolish the specific phosphatase activity targeting the second messenger phosphatidylinositol 3-phosphate. Autosomal forms (centronuclear) have a later onset and are often compatible with life. At birth, fibres are normally constituted but progressively follow remodelling with a secondary centralisation of nuclei. Their prevalence is low; hence, no linkage data can be performed and no molecular aetiology is known. In the Labrador Retriever, a spontaneous disorder strikingly mimics the clinical evolution of the human centronuclear myopathy. We have established a canine pedigree and show that the disorder segregates as an autosomal recessive trait in that pedigree. We have further mapped the dog locus to a region on chromosome 2 that is orthologous to human chromosome 10p. To date, no human MTM1 gene member has been mapped to this genetic region. This report thus describes the first spontaneous mammalian model of centronuclear myopathy and defines a new locus for this group of diseases.

Evaluation of inflammatory biomarkers associated with oxidative stress and histological assessment of magnetic therapy on experimental myopathy in rats.

PubMed

Vignola, María Belén; Dávila, Soledad; Cremonezzi, David; Simes, Juan C; Palma, José A; Campana, Vilma R

2012-12-01

The effect of pulsed electromagnetic field (PEMF) therapy, also called magnetic therapy, upon inflammatory biomarkers associated with oxidative stress plasma fibrinogen, nitric oxide (NO), L-citrulline, carbonyl groups, and superoxide dismutase (SOD) was evaluated through histological assessment, in rats with experimental myopathy. The groups studied were: (A) control (intact rats that received PEMF sham exposures); (B) rats with myopathy and sacrificed 24 h later; (C) rats with myopathy; (D) rats with myopathy and treated with PEMF; and (E) intact rats treated with PEMF. Groups A, C, D, and E were sacrificed 8 days later. Myopathy was induced by injecting 50 μl of 1% carrageenan λ (type IV) once sub-plantar. Treatment was carried out with PEMF emitting equipment with two flat solenoid disks for 8 consecutive days in groups D and E, at 20 mT and 50 Hz for 30 min/day/rat. The biomarkers were determined by spectrophotometry. The muscles (5/8) were stained with Hematoxylin-Eosin and examined by optic microscopy. Quantitative variables were statistically analyzed by the Fisher test, and categorical applying Pearson's Chi Squared test at p < 0.05 for all cases. In Groups B and C, the biomarkers were significantly increased compared to A, D, and E groups: fibrinogen (p < 0.001); NO, L-citrulline and carbonyl groups (p < 0.05); SOD (p < 0.01) as well as the percentage of area with inflammatory infiltration (p < 0.001). PEMF caused decreased levels of fibrinogen, L-citrulline, NO, SOD, and carbonyl groups and significant muscle recovery in rats with experimental myopathies.

Juvenile-onset distal myopathy in Rottweiler dogs.

PubMed

Hanson, S M; Smith, M O; Walker, T L; Shelton, G D

1998-01-01

Two juvenile Rottweiler siblings were presented with the complaint of decreased activity and various postural abnormalities, including plantigrade and palmigrade stance and splayed forepaw digits. The neurologic examinations were otherwise normal. Electromyography revealed rare fibrillation potentials and positive sharp waves. Motor nerve conduction velocities were normal, whereas compound muscle action potentials from the interosseous muscles were decreased. These findings were consistent with a primary myopathy. A 3rd pup from a different litter and a 4th pup from a litter with 3 of 8 affected dogs had similar clinical presentations. Histopathologic changes in fresh-frozen muscle biopsy samples were similar in all pups and consisted of myofiber atrophy with mild myonecrosis, endomysial fibrosis and replacement of muscle with fatty tissue. These changes were more severe in distal muscles than in proximal muscles. Plasma carnitine concentrations (total and free) were decreased in all pups. Muscle carnitine concentrations (total and free) were decreased in 3 of 4 pups and the least affected pup had a borderline low free muscle carnitine concentration. Abnormalities involving major metabolic pathways were not found on quantification of organic and amino acids. Dystrophin immunocytochemistry was normal in 2 dogs tested. Distal myopathies in humans are classified under the dystrophic group of muscle disorders. These 4 cases represent a form of muscular dystrophy apparently not previously reported in dogs.

Novel duplication mutation in the patatin domain of adipose triglyceride lipase (PNPLA2) in neutral lipid storage disease with severe myopathy.

PubMed

Akiyama, Masashi; Sakai, Kaori; Ogawa, Masaya; McMillan, James R; Sawamura, Daisuke; Shimizu, Hiroshi

2007-12-01

Recently, mutations in PNPLA2 encoding adipose triglyceride lipase (ATGL) were reported to underlie a neutral lipid storage disease (NLSD) subgroup characterized by mild myopathy and the absence of ichthyosis. In the present study a novel homozygous PNPLA2 mutation c.475_478dupCTCC (p.Gln160ProfsX19) in the patatin domain, the ATGL active site, was detected in a woman with NLSD and severe myopathy. The present results suggest that a premature truncation mutation in the patatin domain causes NLSD with severe myopathy.

Myopathy in a patient with systemic AA amyloidosis possibly induced by psoriasis vulgaris: An autopsy case.

PubMed

Tanabe, Hajime; Maki, Yoshimitsu; Urabe, Shogo; Higuchi, Itsuro; Obayashi, Konen; Hokezu, Youichi

2015-12-01

Amyloid myopathy is a rare manifestation of primary systemic amyloid light-chain (AL) amyloidosis, but it has not been reported to occur in secondary amyloid A (AA) amyloidosis. We describe a 46-year-old man with psoriasis vulgaris who presented with idiopathic upper and lower limb weakness and was eventually diagnosed with hypertrophic cardiomyopathy. Muscle biopsy findings were compatible with mild inflammatory myopathy. He died of cardiopulmonary arrest, and an autopsy was performed. The autopsy revealed amyloid plaques immunopositive for AA (but not AL or transthyretin) in the perimysial, perivascular, and endomysial regions of the iliopsoas muscle. The final diagnosis was systemic AA amyloidosis with muscle amyloid angiopathy, possibly induced by psoriasis vulgaris. This is an extremely rare autopsy case of myopathy in a patient with systemic AA amyloidosis. The reason for the unusually large amount of amyloid deposition in muscle blood vessel walls remains unclear. © 2015 Wiley Periodicals, Inc.

Cardiovascular magnetic resonance imaging (CMR) reveals characteristic pattern of myocardial damage in patients with mitochondrial myopathy.

PubMed

Yilmaz, Ali; Gdynia, Hans-Jürgen; Ponfick, Matthias; Rösch, Sabine; Lindner, Alfred; Ludolph, Albert C; Sechtem, Udo

2012-04-01

Mitochondrial myopathy comprises various clinical subforms of neuromuscular disorders that are characterised by impaired mitochondrial energy metabolism due to dysfunction of the mitochondrial respiratory chain. No comprehensive and targeted cardiovascular magnetic resonance (CMR) studies have been performed so far in patients with mitochondrial disorders. The present study aimed at characterising cardiac disease manifestations in patients with mitochondrial myopathy and elucidating the in vivo cardiac damage pattern of patients with different subforms of mitochondrial disease by CMR studies. In a prospective study, 37 patients with mitochondrial myopathy underwent comprehensive neurological and cardiac evaluations including physical examination, resting ECG and CMR. The CMR studies comprised cine-CMR, T2-weighted "edema" imaging and T1-weighted late-gadolinium-enhancement (LGE) imaging. Various patterns and degrees of skeletal myopathy were present in the participants of this study, whereas clinical symptoms such as chest pain symptoms (in eight (22%) patients) and various degrees of dyspnea (in 16 (43%) patients) were less frequent. Pathological ECG findings were documented in eight (22%) patients. T2-weighted "edema" imaging was positive in one (3%) patient with MELAS (mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes) only. LGE imaging demonstrated the presence of non-ischemic LGE in 12 (32%) patients: 10 out of 24 (42%) patients with CPEO (chronic progressive external ophthalmoplegia) or KSS (Kearns-Sayre syndrome) and 2 of 3 (67%) patients with MELAS were LGE positive. All 10 LGE-positive patients with CPEO or KSS demonstrated a potentially typical pattern of diffuse intramural LGE in the left-ventricular (LV) inferolateral segments. Cardiac involvement is a frequent finding in patients with mitochondrial myopathy. A potentially characteristic pattern of diffuse intramural LGE in the LV inferolateral segments was identified in

[Acute leg compartment syndrome after exertion].

PubMed

Misović, Sidor; Kronja, Goran; Ignjatović, Dragan; Tomić, Aleksandar

2005-03-01

A case of a 22-year old soldier, with a history of pain in the leg during heavy exercise, which desisted at rest, was presented. One day before admission, the patient had felt an extreme exertion-induced pain in his right leg which had not lessenned at rest. At the same time, the patient noticed persistent severe leg edema. On physical examination, the intracompartmental pressure was 62 mmHg (> 30 mmHg). The patient was urgently operated on, and fasciotomy according to Mubarak was used. At second surgery, the debridement of the muscles of the posterior group of the leg, and the evacuation of hemathoma from the anterior and lateral group of the right leg muscles were perfomed. Postoperative recovery was uneventful. Fasciotomy wounds were closed within 14 days of the surgery. The complete physical treatment was done. Follow-up examinations 1, 3, and 6 months afterwards were satisfactory. The soldier completed his compulsory military service without any sequelae. Laboratory results were normal. Overlooked, unrecognized or surgically untreated compartment syndrome can cause severe damage, including even the loss of the extremity.

[Rhabdomyolysis - may it be a metabolic myopathy? Case report and diagnostic algorithm].

PubMed

Sebők, Ágnes; Pál, Endre; Molnár, Gergő Attila; Wittmann, István; Berenténé Bene, Judit; Melegh, Béla; Komoly, Sámuel; Hidvégi, Tibor; Balogh, Lídia; Szabó, Attila; Zsidegh, Petra

2017-11-01

We report the case of a 46-year-old female patient with recurrent rhabdomyolysis. In the background of her metabolic myopathy an inherited metabolic disorder of the fatty acid oxidation, very long-chain acyl-coenzyme A-dehydrogenase deficiency was diagnosed. The diagnosis was based on abnormal acyl-carnitine- and urine organic-acid profile in addition to low residual enzyme activity, and was confirmed by genetic testing. After introduction of dietotherapy metabolic crisis necessitating hospital admission has not occurred neither have fixed myopathic changes developed. We present here the differential diagnosis of rhabdomyolysis and exertional muscle complaints, with the metabolic myopathies in focus. The main features of fatty acid oxidation disorders are highlighted, acute and chronic managements of very long-chain acyl-coenzyme A-dehydrogenase deficiency are discussed. Metabolic myopathies respond well to treatment, so good quality of life can be achieved. However, especially in fatty acid oxidation disorders, a metabolic crisis may develop quickly and can be fatal, albeit rarely. Some of these disorders can be identified by newborn screening, but occasionally the symptoms may manifest only in adulthood. With the presentation of this case we would like to point out that in the differential diagnosis of recurrent rhabdomyolysis inherited metabolic disorders should be considered regardless of the patient's age. Orv Hetil. 2017; 158(46): 1873-1882.

Exertional compartment syndrome of the medial foot compartment--diagnosis and treatment: a case report.

PubMed

Izadi, Faye E; Richie, Douglas H

2014-07-01

Exertional compartment syndrome in the foot is rarely reported and often confused with plantar fasciitis as a cause of arch pain in the running athlete. We describe a case involving a 19-year-old competitive collegiate runner who developed a chronic case of bilateral medial arch pain during training, which was initially diagnosed as plantar fasciitis but failed to respond to conventional treatment. After symptoms began to suggest exertional compartment syndrome, the diagnosis was confirmed by measuring an elevated resting pressure in the medial compartment of both feet. The patient underwent a bilateral medial compartment fasciotomy, which allowed a full return to activity, and has remained pain free after a 1-year follow-up.

A novel large deletion in the RYR1 gene in a Belgian family with late-onset and recessive core myopathy.

PubMed

Remiche, Gauthier; Kadhim, Hazim; Abramowicz, Marc; Mavroudakis, Nicolas; Monnier, Nicole; Lunardi, Joël

2015-05-01

We report a novel and particularly unusual type of mutation, namely, large deletion in the RYR1 gene, in a Belgian family with myopathy: Patients were found to be compound heterozygous and presented a clinico-pathological phenotype characterized by late-onset and recessive myopathy with cores. We depict the clinical, electrophysiological, pathological and molecular genetic characteristics of family members. To date, large deletions in the RYR1 gene have been reported in only two cases. Both involved different mutations and, in sharp contrast to our cases, presented with a very early-onset, neonatal, and a very severe or lethal phenotype. Overview of reported clinico-pathologic phenotypes, also highlights the rarity of combined late-onset/recessive co-occurrence in this group of myopathies with cores. Finally, this report underlines the broadening spectrum in this group of myopathologic disorders and highlights the concept of 'RYR1-associated/related core myopathies'. Copyright © 2015 Elsevier B.V. All rights reserved.

Suspected myofibrillar myopathy in Arabian horses with a history of exertional rhabdomyolysis.

PubMed

Valberg, S J; McKenzie, E C; Eyrich, L V; Shivers, J; Barnes, N E; Finno, C J

2016-09-01

Although exertional rhabdomyolysis (ER) is common in Arabian horses, there are no dedicated studies describing histopathological characteristics of muscle from Arabian horses with ER. To prospectively identify distinctive histopathological features of muscle from Arabian endurance horses with a history of ER (pro-ER) and to retrospectively determine their prevalence in archived samples from Arabian horses with exertional myopathies (retro-ER). Prospective and retrospective histopathological description. Middle gluteal muscle biopsies obtained from Arabian controls (n = 14), pro-ER (n = 13) as well as archived retro-ER (n = 25) muscle samples previously classified with type 2 polysaccharide storage myopathy (15/25), recurrent exertional rhabdomyolysis (7/25) and no pathology (3/25) were scored for histopathology and immunohistochemical staining of cytoskeletal proteins. Glutaraldehyde-fixed samples (2 pro-ER, one control) were processed for electron microscopy. Pro-ER and retro-ER groups were compared with controls using Mann-Whitney U and Fisher's exact tests. Centrally located myonuclei in mature myofibres were found in significantly more (P<0.05) pro-ER (12/13) and retro-ER (21/25) horses than controls (4/14). Degenerating myofibres were not evident in any biopsies. Retro-ER horses had amylase-resistant polysaccharide (6/25, P<0.05) and higher scores for cytoplasmic glycogen, rimmed vacuoles and rod-like bodies. A few control horses (3/14) and significantly (P<0.05) more pro-ER (12/13) and retro-ER (18/25) horses had disrupted myofibrillar alignment and large desmin and αβ-crystallin positive cytoplasmic aggregates. Prominent Z-disc degeneration and focal myofibrillar disruption with regional accumulation of β-glycogen particles were identified on electron microscopy of the 2 pro-ER samples. In a subset of Arabian horses with intermittent episodes of exertional rhabdomyolysis, ectopic accumulation of cytoskeletal proteins and Z-disc degeneration bear a

Muscle spindles exhibit core lesions and extensive degeneration of intrafusal fibers in the Ryr1{sup I4895T/wt} mouse model of core myopathy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zvaritch, Elena; MacLennan, David H., E-mail: david.maclennan@utoronto.ca

Muscle spindles from the hind limb muscles of adult Ryr1{sup I4895T/wt} (IT/+) mice exhibit severe structural abnormalities. Up to 85% of the spindles are separated from skeletal muscle fascicles by a thick layer of connective tissue. Many intrafusal fibers exhibit degeneration, with Z-line streaming, compaction and collapse of myofibrillar bundles, mitochondrial clumping, nuclear shrinkage and pyknosis. The lesions resemble cores observed in the extrafusal myofibers of this animal model and of core myopathy patients. Spindle abnormalities precede those in extrafusal fibers, indicating that they are a primary pathological feature in this murine Ryr1-related core myopathy. Muscle spindle involvement, if confirmedmore » for human core myopathy patients, would provide an explanation for an array of devastating clinical features characteristic of these diseases and provide novel insights into the pathology of RYR1-related myopathies. - Highlights: • Muscle spindles exhibit structural abnormalities in a mouse model of core myopathy. • Myofibrillar collapse and mitochondrial clumping is observed in intrafusal fibers. • Myofibrillar degeneration follows a pattern similar to core formation in extrafusal myofibers. • Muscle spindle abnormalities are a part of the pathological phenotype in the mouse model of core myopathy. • Direct involvement of muscle spindles in the pathology of human RYR1-related myopathies is proposed.« less

[Role of C5b-9 expression in skeletal muscle blood vessels in necrotizing myopathy].

PubMed

Cong, Lu; Pu, Chuanqiang; Mao, Yanling; Liu, Jiexiao; Lu, Xianghui; Wang, Qian

2012-05-01

To investigate the expression of C5b-9 in the skeletal muscle blood vessels in patients with necrotizing myopathy and explore its role in the pathogenesis of this disease. The expression of C5b-9 and MHC-I in the skeletal muscular fibers and blood vessels in 4 patients with necrotizing myopathy was detected using enzymohistochemistry and immunohistochemistry. Focal or dispersive necrotic muscle fibers with obvious phagocytosis were observed in all the 4 patients. No inflammatory cell infiltration was found in the perimysium or perivascular regions. HE staining showed a decreased number of local small blood vessels, and the some small blood vessels showed thickened vascular walls. Immunohistochemistry detected prominent C5b-9 expression in the necrotic muscle fibers and the blood vessels, and diffuse strong C5b-9 expression was found in the vascular walls, vascular endothelial cells and the smooth muscle layer. No MHC-I deposition was detected in the muscular fibers and blood vessels. C5b-9 contributes to the pathogenesis of necrotizing myopathy mediated by pathologies in the blood vessels.

Capture myopathy in a free-flying greater sandhill crane (Grus canadensis tabida) from Wisconsin

USGS Publications Warehouse

Windingstad, R.M.; Hurley, S.S.; Sileo, L.

1983-01-01

Capture myopathy has been reported Frequently in wild mammals (Bartsch et al., 1977, Vet. Pathol. 14: 314-324). There are, however, fewer reports of this disease in wild birds (Young, 1967, mt. Zoo Yearb. 7: 226-227; Bartsch et al., 1977, op. cit. ; Henschel and Low, 1978, S. Afr. J. Sci. 74: 305-306; Wobeser, 1981, Diseases of Wild Waterfowl, Plenum Press, New York, 300 pp.). We are reporting a case of skeletal muscle necrosis in a greater sandhill crane found dead 5 days after its capture, radio-tagging, and release. We believe this is the first case of capture myopathy to be reported for this species.

The Sick and the Weak: Neuropathies/Myopathies in the Critically Ill

PubMed Central

Friedrich, O.; Reid, M. B.; Van den Berghe, G.; Vanhorebeek, I.; Hermans, G.; Rich, M. M.; Larsson, L.

2015-01-01

Critical illness polyneuropathies (CIP) and myopathies (CIM) are common complications of critical illness. Several weakness syndromes are summarized under the term intensive care unit-acquired weakness (ICUAW). We propose a classification of different ICUAW forms (CIM, CIP, sepsis-induced, steroid-denervation myopathy) and pathophysiological mechanisms from clinical and animal model data. Triggers include sepsis, mechanical ventilation, muscle unloading, steroid treatment, or denervation. Some ICUAW forms require stringent diagnostic features; CIM is marked by membrane hypoexcitability, severe atrophy, preferential myosin loss, ultrastructural alterations, and inadequate autophagy activation while myopathies in pure sepsis do not reproduce marked myosin loss. Reduced membrane excitability results from depolarization and ion channel dysfunction. Mitochondrial dysfunction contributes to energy-dependent processes. Ubiquitin proteasome and calpain activation trigger muscle proteolysis and atrophy while protein synthesis is impaired. Myosin loss is more pronounced than actin loss in CIM. Protein quality control is altered by inadequate autophagy. Ca2+ dysregulation is present through altered Ca2+ homeostasis. We highlight clinical hallmarks, trigger factors, and potential mechanisms from human studies and animal models that allow separation of risk factors that may trigger distinct mechanisms contributing to weakness. During critical illness, altered inflammatory (cytokines) and metabolic pathways deteriorate muscle function. ICUAW prevention/treatment is limited, e.g., tight glycemic control, delaying nutrition, and early mobilization. Future challenges include identification of primary/secondary events during the time course of critical illness, the interplay between membrane excitability, bioenergetic failure and differential proteolysis, and finding new therapeutic targets by help of tailored animal models. PMID:26133937

Method and apparatus to assess compartment syndrome

NASA Technical Reports Server (NTRS)

Hargens, Alan R. (Inventor); Yost, William T. (Inventor); Ueno, Toshiaki (Inventor)

2008-01-01

A method and apparatus for measuring pressure buildup in a body compartment that encases muscular tissue. The method includes assessing the body compartment configuration and identifying the effect of pulsatile components on at least one compartment dimension. This process is used in preventing tissue necrosis, and in decisions of whether to perform surgery on the body compartment for prevention of Compartment Syndrome. An apparatus is used for measuring excess pressure in the body compartment having components for imparting ultrasonic waves such as a transducer, placing the transducer to impart the ultrasonic waves, capturing the reflected imparted ultrasonic waves, and converting them to electrical signals, a pulsed phase-locked loop device for assessing a body compartment configuration and producing an output signal, and means for mathematically manipulating the output signal to thereby categorize pressure build-up in the body compartment from the mathematical manipulations.

The effect of coenzyme Q10 in statin myopathy.

PubMed

Zlatohlavek, Lukas; Vrablik, Michal; Grauova, Barbora; Motykova, Eva; Ceska, Richard

2012-01-01

Statins significantly reduce CV morbidity and mortality. Unfortunately, one of the side effects of statins is myopathy, for which statins cannot be administered in sufficient doses or administered at all. The aim of this study was to demonstrate the effect of coenzyme Q10 in patients with statin myopathy. Twenty eight patients aged 60.6±10.7 years were monitored (18 women and 10 men) and treated with different types and doses of statin. Muscle weakness and pain was monitored using a scale of one to ten, on which patients expressed the degree of their inconvenience. Examination of muscle problems was performed prior to administration of CQ10 and after 3 and 6 months of dosing. Statistical analysis was performed using Friedman test, Annova and Students t-test. Pain decreased on average by 53.8% (p<0.0001), muscle weakness by 44.4% (p<0.0001). The CQ10 levels were increased by more than 194% (from 0,903 μg/ml to 2.66 μg/ml; p<0.0001). After a six-month administration of coenzyme Q10, muscle pain and sensitivity statistically significantly decreased.

Constitutive activation of MAPK cascade in acute quadriplegic myopathy.

PubMed

Di Giovanni, Simone; Molon, Annamaria; Broccolini, Aldobrando; Melcon, Gisela; Mirabella, Massimiliano; Hoffman, Eric P; Servidei, Serenella

2004-02-01

Acute quadriplegic myopathy (AQM; also called "critical illness myopathy") shows acute muscle wasting and weakness and is experienced by some patients with severe systemic illness, often associated with administration of corticosteroids and/or neuroblocking agents. Key aspects of AQM include muscle atrophy and myofilament loss. Although these features are shared with neurogenic atrophy, myogenic atrophy in AQM appears mechanistically distinct from neurogenic atrophy. Using muscle biopsies from AQM, neurogenic atrophy, and normal controls, we show that both myogenic and neurogenic atrophy share induction of myofiber-specific ubiquitin/proteosome pathways (eg, atrogin-1). However, AQM patient muscle showed a specific strong induction of transforming growth factor (TGF)-beta/MAPK pathways. Atrophic AQM myofibers showed coexpression of TGF-beta receptors, p38 MAPK, c-jun, and c-myc, including phosphorylated active forms, and these same fibers showed apoptotic features. Our data suggest a model of AQM pathogenesis in which stress stimuli (sepsis, corticosteroids, pH imbalance, osmotic imbalance) converge on the TGF-beta pathway in myofibers. The acute stimulation of the TGF-beta/MAPK pathway, coupled with the inactivity-induced atrogin-1/proteosome pathway, leads to the acute muscle loss seen in AQM patients.

Intramuscular pressure varies with depth. The tibialis anterior muscle studied in 12 volunteers

NASA Technical Reports Server (NTRS)

Nakhostine, M.; Styf, J. R.; van Leuven, S.; Hargens, A. R.; Gershuni, D. H.

1993-01-01

Pressures in the tibialis anterior muscle were recorded at rest and during exercise with transducer-tipped catheters in 12 volunteers while they were supine or standing. The recordings were repeated with venous stasis created by an inflated tourniquet cuff on the thigh. Catheters were placed at 3 different sites in the muscle: catheter I adjacent to the deep surface of the fascia over the anterior compartment; catheter II between the fascia and the central tendon; and catheter III deep in the muscle close to the interosseous membrane. In both the supine and standing positions the intramuscular pressure at rest and the muscle relaxation pressure during exercise, obtained by catheter II, were greater than the corresponding pressures measured by the superficially located catheter I in the normal as well as in the volume loaded limb. The same conditions for pressure measurement consistently revealed lower pressures recorded by catheter III compared to II, but the difference was not significant. Our results indicate that intramuscular pressure increases centripetally, as the centrally lying tendon is approached. We conclude that pressure measurements for diagnosis of acute and chronic compartment syndromes and in ergonomic studies should be based on recordings from a standard location of the catheter within the muscle and a standard posture of the subject.

Skeletal muscle-specific HMG-CoA reductase knockout mice exhibit rhabdomyolysis: A model for statin-induced myopathy.

PubMed

Osaki, Yoshinori; Nakagawa, Yoshimi; Miyahara, Shoko; Iwasaki, Hitoshi; Ishii, Akiko; Matsuzaka, Takashi; Kobayashi, Kazuto; Yatoh, Shigeru; Takahashi, Akimitsu; Yahagi, Naoya; Suzuki, Hiroaki; Sone, Hirohito; Ohashi, Ken; Ishibashi, Shun; Yamada, Nobuhiro; Shimano, Hitoshi

2015-10-23

HMG-CoA reductase (HMGCR) catalyzes the conversion of HMG-CoA to mevalonic acid (MVA); this is the rate-limiting enzyme of the mevalonate pathway that synthesizes cholesterol. Statins, HMGCR inhibitors, are widely used as cholesterol-reducing drugs. However, statin-induced myopathy is the most adverse side effect of statins. To eludicate the mechanisms underlying statin the myotoxicity and HMGCR function in the skeletal muscle, we developed the skeletal muscle-specific HMGCR knockout mice. Knockout mice exhibited postnatal myopathy with elevated serum creatine kinase levels and necrosis. Myopathy in knockout mice was completely rescued by the oral administration of MVA. These results suggest that skeletal muscle toxicity caused by statins is dependent on the deficiencies of HMGCR enzyme activity and downstream metabolites of the mevalonate pathway in skeletal muscles rather than the liver or other organs. Copyright © 2015 Elsevier Inc. All rights reserved.

Relationship of Skeletal Muscle Development and Growth to Breast Muscle Myopathies: A Review.

PubMed

Velleman, Sandra G

2015-12-01

Selection in meat-type birds has focused on growth rate, muscling, and feed conversion. These strategies have made substantial improvements but have affected muscle structure, repair mechanisms, and meat quality, especially in the breast muscle. The increase in muscle fiber diameters has reduced available connective tissue spacing, reduced blood supply, and altered muscle metabolism in the breast muscle. These changes have increased muscle fiber degeneration and necrosis but have limited muscle repair mechanisms mediated by the adult myoblast (satellite cell) population of cells, likely resulting in the onset of myopathies. This review focuses on muscle growth mechanisms and how changes in the cellular development of the breast muscle may be associated with breast muscle myopathies occurring in meat-type birds.

[Cardiac myopathy due to overt hypothyroidism].

PubMed

Harbeck, B; Berndt, M J; Lehnert, H

2014-03-01

A 51-year-old man presented with progressive tiredness, proximal muscle weakness, hair loss and weight gain for months. The patient showed mild pretibial myxedema and dry skin. Laboratory findings revealed strongly elevated cardiac enzymes as well as marked hypothyroidism. The electrocardiogram, echocardiography, abdominal sonography and chest X-ray were unremarkable. Thyroid ultrasound demonstrated features of Hashimoto thyroiditis. The findings supported the diagnosis of an overt hypothyroidism with myxedema and rhabdomyolysis. After starting levothyroxine and volume substitution laboratory parameters and clinical condition slowly normalized. Severe overt hypothyroidism may rarely present primarily as myopathy with myositis and cardiac involvement. © Georg Thieme Verlag KG Stuttgart · New York.

[Insight into the training of patients with idiopathic inflammatory myopathy].

PubMed

Váncsa, Andrea

2016-09-01

Using current recommended treatment, a majority of patients with idiopathic inflammatory myopathy develop muscle impairment and poor health. Beneficial effects of exercise have been reported on muscle performance, aerobic capacity and health in chronic polymyositis and dermatomyositis, as well as in active disease and inclusion body myositis to some extent. Importantly, randomized controlled trials indicate that improved health and decreased clinical disease activity could be mediated through increased aerobic capacity. Recently, reports seeking pathomechanisms of the underlying effects of exercise on skeletal muscle indicate increased aerobic capacity (i.e. increased mitochondrial capacity and capillary density, reduced lactate levels), activation of genes of aerobic phenotype and muscle growth programs and down regulation of genes related to inflammation. Exercise contributes to both systemic and within-muscle adaptations demonstrating that it is fundamental for improving muscle performance and health in patients with idiopathic inflammatory myopathy. There is a need for randomized controlled trials to study the effects of exercise in patients with active disease and inclusion body myositis. Orv. Hetil., 2016, 157(39), 1557-1562.

Clinical Utility of LC3 and p62 Immunohistochemistry in Diagnosis of Drug-Induced Autophagic Vacuolar Myopathies: A Case-Control Study

PubMed Central

Lee, Han S.; Daniels, Brianne H.; Salas, Eduardo; Bollen, Andrew W.; Debnath, Jayanta; Margeta, Marta

2012-01-01

Background Some patients treated with chloroquine, hydroxychloroquine, or colchicine develop autophagic vacuolar myopathy, the diagnosis of which currently requires electron microscopy. The goal of the current study was to develop an immunohistochemical diagnostic marker for this pathologic entity. Methodology Microtubule-associated protein light chain 3 (LC3) has emerged as a robust marker of autophagosomes. LC3 binds p62/SQSTM1, an adapter protein that is selectively degraded via autophagy. In this study, we evaluated the utility of immunohistochemical stains for LC3 and p62 as diagnostic markers of drug-induced autophagic vacuolar myopathy. The staining was performed on archival muscle biopsy material, with subject assignment to normal control, drug-treated control, and autophagic myopathy groups based on history of drug use and morphologic criteria. Principal Findings In all drug-treated subjects, but not in normal controls, LC3 and p62 showed punctate staining characteristic of autophagosome buildup. In the autophagic myopathy subjects, puncta were coarser and tended to coalesce into linear structures aligned with the longitudinal axis of the fiber, often in the vicinity of vacuoles. The percentage of LC3- and p62-positive fibers was significantly higher in the autophagic myopathy group compared to either the normal control (p<0.001) or the drug-treated control group (p<0.05). With the diagnostic threshold set between 8% and 15% positive fibers (depending on the desired level of sensitivity and specificity), immunohistochemical staining for either LC3 or p62 could be used to identify subjects with autophagic vacuolar myopathy within the drug-treated subject group (p≤0.001). Significance Immunohistochemistry for LC3 and p62 can facilitate tissue-based diagnosis of drug-induced autophagic vacuolar myopathies. By limiting the need for electron microscopy (a time consuming and costly technique with high specificity, but low sensitivity), clinical use of these

Clinical utility of LC3 and p62 immunohistochemistry in diagnosis of drug-induced autophagic vacuolar myopathies: a case-control study.

PubMed

Lee, Han S; Daniels, Brianne H; Salas, Eduardo; Bollen, Andrew W; Debnath, Jayanta; Margeta, Marta

2012-01-01

Some patients treated with chloroquine, hydroxychloroquine, or colchicine develop autophagic vacuolar myopathy, the diagnosis of which currently requires electron microscopy. The goal of the current study was to develop an immunohistochemical diagnostic marker for this pathologic entity. Microtubule-associated protein light chain 3 (LC3) has emerged as a robust marker of autophagosomes. LC3 binds p62/SQSTM1, an adapter protein that is selectively degraded via autophagy. In this study, we evaluated the utility of immunohistochemical stains for LC3 and p62 as diagnostic markers of drug-induced autophagic vacuolar myopathy. The staining was performed on archival muscle biopsy material, with subject assignment to normal control, drug-treated control, and autophagic myopathy groups based on history of drug use and morphologic criteria. In all drug-treated subjects, but not in normal controls, LC3 and p62 showed punctate staining characteristic of autophagosome buildup. In the autophagic myopathy subjects, puncta were coarser and tended to coalesce into linear structures aligned with the longitudinal axis of the fiber, often in the vicinity of vacuoles. The percentage of LC3- and p62-positive fibers was significantly higher in the autophagic myopathy group compared to either the normal control (p<0.001) or the drug-treated control group (p<0.05). With the diagnostic threshold set between 8% and 15% positive fibers (depending on the desired level of sensitivity and specificity), immunohistochemical staining for either LC3 or p62 could be used to identify subjects with autophagic vacuolar myopathy within the drug-treated subject group (p ≤ 0.001). Immunohistochemistry for LC3 and p62 can facilitate tissue-based diagnosis of drug-induced autophagic vacuolar myopathies. By limiting the need for electron microscopy (a time consuming and costly technique with high specificity, but low sensitivity), clinical use of these markers will improve the speed and accuracy of

14 CFR 25.787 - Stowage compartments.

Code of Federal Regulations, 2010 CFR

2010-01-01

... STANDARDS: TRANSPORT CATEGORY AIRPLANES Design and Construction Personnel and Cargo Accommodations § 25.787 Stowage compartments. (a) Each compartment for the stowage of cargo, baggage, carry-on articles, and... to compartments located below, or forward, of all occupants in the airplane. If the airplane has a...

Compartment syndrome of the foot.

PubMed

Andermahr, J; Helling, H J; Tsironis, K; Rehm, K E; Koebke, J

2001-05-01

The hindfoot compartment syndrome occurs in 10% of cases after calcaneal fracture. We analyzed the pathological anatomical reasons for this syndrome using the 10 feet from cadavers plastinated and cut into 4-mm thick sequential sections. CT scans of patients with calcaneal fractures were then compared with the anatomical findings. The key component of this compartment syndrome is the quadratus plantae muscle. The sustentacular calcaneal fragment causes bleeding from the bone or the medial calcaneal arteries into this compartment. The medial and lateral plantar nerves and vessels are then compressed between the quadratus plantae muscle and the short flexor digitorum muscle. Relieving pressure by surgical decompression of the quadratus plantae compartment via a medial or plantar approach is the recommended treatment. Copyright 2001 Wiley-Liss, Inc.

Proteomics identification of differentially expressed proteins in the muscle of dysferlin myopathy patients.

PubMed

De la Torre, Carolina; Illa, Isabel; Faulkner, Georgine; Soria, Laura; Robles-Cedeño, Rene; Dominguez-Perles, Raul; De Luna, Noemí; Gallardo, Eduard

2009-04-01

The muscular dystrophies are a large and heterogeneous group of neuromuscular disorders that can be classified according to the mode of inheritance, the clinical phenotype and the molecular defect. To better understand the pathological mechanisms of dysferlin myopathy we compared the protein-expression pattern in the muscle biopsies of six patients with this disease with six patients with limb girdle muscular dystrophy 2A, five with facioscapulohumeral dystrophy and six normal control subjects. To investigate differences in the expression levels of skeletal muscle proteins we used 2-DE and MS. Western blot or immunohistochemistry confirmed relevant results. The study showed specific increase expression of proteins involved in fast-to-slow fiber type conversion (ankyrin repeat protein 2), type I predominance (phosphorylated forms of slow troponin T), sarcomere stabilization (actinin-associated LIM protein), protein ubiquitination (TRIM 72) and skeletal muscle differentiation (Rho-GDP-dissociation inhibitor ly-GDI) in dysferlin myopathy. As anticipated, we also found differential expression of proteins common to all the muscular dystrophies studied. This comparative proteomic analysis suggests that in dysferlin myopathy (i) the type I fiber predominance is an active process of fiber type conversion rather than a selective loss of type II fibers and (ii) the dysregulation of proteins involved in muscle differentiation further confirms the role of dysferlin in this process. Copyright © 2009 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Fatal hepatic hemorrhage by peliosis hepatis in X-linked myotubular myopathy: a case report.

PubMed

Motoki, T; Fukuda, M; Nakano, T; Matsukage, S; Fukui, A; Akiyoshi, S; Hayashi, Y K; Ishii, E; Nishino, I

2013-11-01

We report a 5-year-old boy with X-linked myotubular myopathy complicated by peliosis hepatis. At birth, he was affected with marked generalized muscle hypotonia and weakness, which required permanent ventilatory support, and was bedridden for life. He died of acute fatal hepatic hemorrhage after using a mechanical in-exsufflator. Peliosis hepatis, defined as multiple, variable-sized, cystic blood-filled spaces through the liver parenchyma, was confirmed by autopsy. To avoid fatal hepatic hemorrhage by peliosis hepatis, routine hepatic function tests and abdominal imaging tests should be performed for patients with X-linked myotubular myopathy, especially at the time of using artificial respiration. Copyright © 2013 Elsevier B.V. All rights reserved.

Rehabilitation of Critical Illness Polyneuropathy and Myopathy Patients: An Observational Study

ERIC Educational Resources Information Center

Novak, Primoz; Vidmar, Gaj; Kuret, Zala; Bizovicar, Natasa

2011-01-01

Critical illness polyneuropathy and myopathy (CIPNM) frequently develops in patients hospitalized in intensive care units. The number of patients with CIPNM admitted to inpatient rehabilitation is increasing. The aim of this study was to comprehensively evaluate the outcome of their rehabilitation. Twenty-seven patients with CIPNM were included in…

14 CFR 23.771 - Pilot compartment.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 14 Aeronautics and Space 1 2011-01-01 2011-01-01 false Pilot compartment. 23.771 Section 23.771... Cargo Accommodations § 23.771 Pilot compartment. For each pilot compartment— (a) The compartment and its equipment must allow each pilot to perform his duties without unreasonable concentration or fatigue; (b...

14 CFR 29.771 - Pilot compartment.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 14 Aeronautics and Space 1 2011-01-01 2011-01-01 false Pilot compartment. 29.771 Section 29.771... Pilot compartment. For each pilot compartment— (a) The compartment and its equipment must allow each pilot to perform his duties without unreasonable concentration or fatigue; (b) If there is provision for...

14 CFR 29.771 - Pilot compartment.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Pilot compartment. 29.771 Section 29.771... Pilot compartment. For each pilot compartment— (a) The compartment and its equipment must allow each pilot to perform his duties without unreasonable concentration or fatigue; (b) If there is provision for...

BAG3-related myopathy, polyneuropathy and cardiomyopathy with long QT syndrome.

PubMed

Kostera-Pruszczyk, Anna; Suszek, Małgorzata; Płoski, Rafał; Franaszczyk, Maria; Potulska-Chromik, Anna; Pruszczyk, Piotr; Sadurska, Elżbieta; Karolczak, Justyna; Kamińska, Anna M; Rędowicz, Maria Jolanta

2015-12-01

BAG3 belongs to BAG family of molecular chaperone regulators interacting with HSP70 and anti-apoptotic protein Bcl-2. It is ubiquitously expressed with strong expression in skeletal and cardiac muscle, and is involved in a panoply of cellular processes. Mutations in BAG3 and aberrations in its expression cause fulminant myopathies, presenting with progressive limb and axial muscle weakness, and respiratory insufficiency and neuropathy. Herein, we report a sporadic case of a 15-years old girl with symptoms of myopathy, demyelinating polyneuropathy and asymptomatic long QT syndrome. Genetic testing demonstrated heterozygous mutation Pro209Leu (c.626C > T) in exon 3 of BAG3 gene causing severe myopathy and neuropathy, often associated with restrictive cardiomyopathy. We did not find a mutation in any known LQT syndrome genes. Analysis of muscle biopsy revealed profound disintegration of Z-discs with extensive accumulation of granular debris and large inclusions within fibers. We demonstrated profound alterations in BAG3 distribution as the protein localized to long filamentous structures present across the fibers that were positively stained not only for α-actinin but also for desmin and filamin indicating that those disintegrated Z-disc regions contained also other sarcomeric proteins. The mutation caused a decrease in the content of BAG3 and HSP70, and also of α-actinin desmin, filamin and fast myosin heavy chain, confirming its severe effect on the muscle fiber morphology and thus function. We provide further evidence that BAG3 is associated with Z-disc maintenance, and the Pro209Leu mutation may occur worldwide. We also provide a summary of cases associated with this mutation reported so far.

Orbiter Crew Compartment Integration-Stowage

NASA Technical Reports Server (NTRS)

Morgan, L. Gary

2007-01-01

This viewgraph presentation describes the Orbiter Crew Compartment Integration (CCI) stowage. The evolution of orbiter crew compartment stowage volume is also described, along with photographs presented of the on-orbit volume stowage capacity.

Correction of the Middle Eastern M712T mutation causing GNE myopathy by trans-splicing.

PubMed

Tal-Goldberg, Tzukit; Lorain, Stéphanie; Mitrani-Rosenbaum, Stella

2014-06-01

GNE myopathy is a rare neuromuscular autosomal recessive disease, resulting from mutations in the gene UDP N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE). The most frequent mutation is the single homozygous missense mutation, M712T-the Middle Eastern mutation-located ten amino acids before the end of the protein. We have used an adeno-associated virus (AAV)-based trans-splicing (TS) vector as a gene therapy tool to overcome this mutation by replacing the mutated last exon of GNE by the wild-type exon while preserving the natural endogenous regulatory machinery. We have designed relevant plasmids directed either to mouse or to human GNE. Following transfection of C2C12 murine muscle cells with the mouse TS vectors, we have been able to detect by nested RT-PCR trans-spliced molecules carrying the wild-type exon 12 of GNE. Similarly, transfection of HEK293 human cells with the human-directed TS vectors resulted in the generation of trans-spliced human GNE RNA molecules. Furthermore, infection of primary muscle cells from a GNE myopathy patient carrying the homozygous M712T mutation, with an AAV8-based viral vector carrying a human-directed TS construct, resulted in the generation of wild-type GNE transcripts in addition to the mutated ones. These studies provide a proof of concept that the TS approach could be used to partially correct the Middle Eastern mutation in GNE myopathy patients. These results provide the basis for in vivo research in animal models using the AAV platform with TS plasmids as a potential genetic therapy for GNE myopathy.

Reducing body myopathy and desmin storage in skeletal muscle: morphological and biochemical findings.

PubMed

Bertini, E; Salviati, G; Apollo, F; Ricci, E; Servidei, S; Broccolini, A; Papacci, M; Tonali, P

1994-01-01

We describe clinical, morphological and biochemical findings of a patient with reducing body myopathy (RBM). This 15-year-old patient was affected by severe limb-girdle progressive myopathy with asymmetric distribution. Muscle biopsy showed many fibers with cytoplasmic polymorphic masses, which stained dark purple with modified Gomori's trichrome, associated with proliferation of cytoplasmic bodies. Cytoplasmic polymorphic masses showed marked reducing activity with menadione-nitro blue tetrazolium reaction. Ultrastructurally, there was great amount of highly electron-dense tubular-filamentous structures of 16-17 nm in diameter. Immunohistochemistry showed that many fibers were positive for desmin. Sodium dodecyl sulfate-electrophoresis disclosed an increase in two bands of approximately 53 and 70 kDa, and Western blot demonstrated that the 53-kDa band was desmin. It was not possible to characterize the 70-kDa protein further.

Suspected myofibrillar myopathy in Arabian horses with a history of exertional rhabdomyolysis

PubMed Central

VALBERG, S. J.; McKENZIE, E. C.; EYRICH, L. V.; SHIVERS, J.; BARNES, N. E.; FINNO, C. J.

2016-01-01

Summary Reasons for performing study Although exertional rhabdomyolysis (ER) is common in Arabian horses, there are no dedicated studies describing histopathological characteristics of muscle from Arabian horses with ER. Objectives To prospectively identify distinctive histopathological features of muscle from Arabian endurance horses with a history of ER (pro-ER) and to retrospectively determine their prevalence in archived samples from Arabian horses with exertional myopathies (retro-ER). Study design Prospective and retrospective histopathological description. Methods Middle gluteal muscle biopsies obtained from Arabian controls (n = 14), pro-ER (n = 13) as well as archived retro-ER (n = 25) muscle samples previously classified with type 2 polysaccharide storage myopathy (15/25), recurrent exertional rhabdomyolysis (7/25) and no pathology (3/25) were scored for histopathology and immunohistochemical staining of cytoskeletal proteins. Glutaraldehyde-fixed samples (2 pro-ER, one control) were processed for electron microscopy. Pro-ER and retro-ER groups were compared with controls using Mann–Whitney U and Fisher's exact tests. Results Centrally located myonuclei in mature myofibres were found in significantly more (P<0.05) pro-ER (12/13) and retro-ER (21/25) horses than controls (4/14). Degenerating myofibres were not evident in any biopsies. Retro-ER horses had amylase-resistant polysaccharide (6/25, P<0.05) and higher scores for cytoplasmic glycogen, rimmed vacuoles and rod-like bodies. A few control horses (3/14) and significantly (P<0.05) more pro-ER (12/13) and retro-ER (18/25) horses had disrupted myofibrillar alignment and large desmin and αβ-crystallin positive cytoplasmic aggregates. Prominent Z-disc degeneration and focal myofibrillar disruption with regional accumulation of β-glycogen particles were identified on electron microscopy of the 2 pro-ER samples. Conclusions In a subset of Arabian horses with intermittent episodes of exertional

Fluid balance within the canine anterolateral compartment and its relationship to compartment syndromes.

PubMed

Hargens, A R; Akeson, W H; Mubarak, S J; Owen, C A; Evans, K L; Garetto, L P; Gonsalves, M R; Schmidt, D A

1978-06-01

Fluid homeostasis within muscle compartments is maintained by four pressures: capillary blood pressure, capillary blood oncotic pressure, tissue-fluid pressure, and tissue fluid oncotic pressure. As determined in the canine anterolateral compartment, capillary blood pressure is 25 +/- 3 millimeters of mercury; capillary blood oncotic pressure, 26 +/- 3 millimeters of mercury, tissue-pbessure, -2 +/- 2 millimeters of mercury; and tissue-fluid oncotic pressure, 11 +/- 1 millimeters of mercury. The wick technique allows direct measurement of tissue-fluid pressure in skeletal muscle and, with minor modifications, is adapted to collect microsamples of interstitial fluid for determinations of tissue-fluid oncotic pressure. The wick technique detects very slight fluctuations in intracompartmental pressure such as light finger compression, injection of small volumes of fluid, and even pulsation due to adjacent arterial pressure. Adjacent muscle compartments may contain different tissue-fluid pressure due to impermeable osseofascial barriers. Our results obtained in canine muscle compartments pressurized by infusion of autologous plasma suggest that risks of muscle damage are significant at intracompartmental pressures greater than thirty millimeters of mercury.

Advances in serological diagnostics of inflammatory myopathies.

PubMed

Benveniste, Olivier; Stenzel, Werner; Allenbach, Yves

2016-10-01

Inflammatory myopathies are rare diseases. Their diagnosis criteria are historically based on their clinical phenotype (topography of the muscle weakness, presence of skin lesions and/or of extra-skin/muscle signs) and the presence of inflammatory infiltrates on muscle biopsy. However, the recent discovery of different myositis-specific antibodies (MSA) or myositis-associated antibodies (MAA) permitted to revisit these old classifications. This review covers recent findings in clinical and pathological phenotypes regarding prognosis, associated cancer and response to the treatment based on MSA/MAA categorization. Since the mid-1970s, about 20 MSA or MAA were discovered year after year (by immunoprecipitation). Now commercial kits (mainly dot line assays) permit their detection routinely which is clearly a help for the diagnosis but also give some key indications on clinical features, risk of associated cancers and response to the treatments. Overlap myositis is associated with antisynthetase antibodies (Abs) or those associated with sclerodermia (anti-RNP, Ku and PM-ScL). Dermatomyositis is associated with anti-Mi2, small ubiquitin-like modifier activating enzyme (SAE), nuclear matrix protein-2 (NXP2), TIF-1γ or melanoma differentiation-associated gene 5 (MDA5) Abs. Immune-mediated necrotizing myopathies are associated with anti-signal recognition particle (SRP) or 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) Abs. One third of inclusion body myositis' patients also presented anti-cytosolic 5'-nucleotidase 1A (cN1A) Abs. The risk of associated cancers is elevated with anti-TIF-1γ, NXP2 or HMGCR Abs.

24 CFR 3280.111 - Toilet compartments.

Code of Federal Regulations, 2012 CFR

2012-04-01

... line of the toilet shall not be less than 12 inches. At least 21 inches of clear space shall be... 24 Housing and Urban Development 5 2012-04-01 2012-04-01 false Toilet compartments. 3280.111... Toilet compartments. Each toilet compartment shall be a minimum of 30 inches in width, except, when the...

24 CFR 3280.111 - Toilet compartments.

Code of Federal Regulations, 2010 CFR

2010-04-01

... line of the toilet shall not be less than 12 inches. At least 21 inches of clear space shall be... 24 Housing and Urban Development 5 2010-04-01 2010-04-01 false Toilet compartments. 3280.111... Toilet compartments. Each toilet compartment shall be a minimum of 30 inches in width, except, when the...

24 CFR 3280.111 - Toilet compartments.

Code of Federal Regulations, 2013 CFR

2013-04-01

... line of the toilet shall not be less than 12 inches. At least 21 inches of clear space shall be... 24 Housing and Urban Development 5 2013-04-01 2013-04-01 false Toilet compartments. 3280.111... Toilet compartments. Each toilet compartment shall be a minimum of 30 inches in width, except, when the...

24 CFR 3280.111 - Toilet compartments.

Code of Federal Regulations, 2011 CFR

2011-04-01

... line of the toilet shall not be less than 12 inches. At least 21 inches of clear space shall be... 24 Housing and Urban Development 5 2011-04-01 2011-04-01 false Toilet compartments. 3280.111... Toilet compartments. Each toilet compartment shall be a minimum of 30 inches in width, except, when the...

Muscle contributions to medial tibiofemoral compartment contact loading following ACL reconstruction using semitendinosus and gracilis tendon grafts.

PubMed

Konrath, Jason M; Saxby, David J; Killen, Bryce A; Pizzolato, Claudio; Vertullo, Christopher J; Barrett, Rod S; Lloyd, David G

2017-01-01

The muscle-tendon properties of the semitendinosus (ST) and gracilis (GR) are substantially altered following tendon harvest for the purpose of anterior cruciate ligament reconstruction (ACLR). This study adopted a musculoskeletal modelling approach to determine how the changes to the ST and GR muscle-tendon properties alter their contribution to medial compartment contact loading within the tibiofemoral joint in post ACLR patients, and the extent to which other muscles compensate under the same external loading conditions during walking, running and sidestep cutting. Motion capture and electromyography (EMG) data from 16 lower extremity muscles were acquired during walking, running and cutting in 25 participants that had undergone an ACLR using a quadruple (ST+GR) hamstring auto-graft. An EMG-driven musculoskeletal model was used to estimate the medial compartment contact loads during the stance phase of each gait task. An adjusted model was then created by altering muscle-tendon properties for the ST and GR to reflect their reported changes following ACLR. Parameters for the other muscles in the model were calibrated to match the experimental joint moments. The medial compartment contact loads for the standard and adjusted models were similar. The combined contributions of ST and GR to medial compartment contact load in the adjusted model were reduced by 26%, 17% and 17% during walking, running and cutting, respectively. These deficits were balanced by increases in the contribution made by the semimembranosus muscle of 33% and 22% during running and cutting, respectively. Alterations to the ST and GR muscle-tendon properties in ACLR patients resulted in reduced contribution to medial compartment contact loads during gait tasks, for which the semimembranosus muscle can compensate.

24 CFR 3280.111 - Toilet compartments.

Code of Federal Regulations, 2014 CFR

2014-04-01

... inches. At least 21 inches of clear space shall be provided in front of each toilet. [40 FR 58752, Dec... compartments. Each toilet compartment must have a minimum width of 30 inches, with a minimum clear space of 21... 24 Housing and Urban Development 5 2014-04-01 2014-04-01 false Toilet compartments. 3280.111...

A distinctive type of infantile inflammatory myopathy with abnormal myonuclei.

PubMed

Sripathi, N; Karpati, G; Carpenter, S

1996-03-01

Four infants developed progressive muscle weakness after a normal initial postnatal development. All patients had a moderate elevation of serum creatine kinase (CK) activity. Muscle biopsies revealed, in addition to myopathic features, endomysial and perivascular inflammation. Electron microscopy disclosed prominent myonuclear abnormalities. Corticosteroids in 3 patients were moderately beneficial. This appears to be a clinicopathologically distinct form of inflammatory myopathy of infants.

Acute quadriplegic myopathy in a 17-month-old boy.

PubMed

Salviati, L; Laverda, A M; Zancan, L; Fanin, M; Angelini, C; Meznaric-Petrusa, M

2000-01-01

Acute quadriplegic myopathy is a rare condition associated with the use of nondepolarizing muscle-blocking agents and corticosteroids in the course of severe systemic illness. A 17-month-old boy underwent liver transplantation for fulminant hepatitis. He was intubated for 24 days and treated with vecuronium bromide and high-dose methylprednisolone. The child was weaned from the ventilator and presented extreme weakness in the upper limbs and total paralysis of the lower limbs. Serum creatine kinase level was normal and electromyography showed myopathic abnormalities. Muscle biopsy showed severe type-1 fiber atrophy and selective loss of myosin thick filaments was seen on electron microscopy. Scattered regenerating fetal myosin-positive fibers were present, mu calpain was absent, while m calpain was diffusely expressed. Physical therapy was immediately started and the child recovered even though corticosteroids were not discontinued. The pathogenesis of acute quadriplegic myopathy is still unknown. We suggest that it could be due to abnormal protein turnover in the muscle. Several independent factors, such as corticosteroid treatment, immobilization, or cytokines, could take part in a cascade of events that leads to an excessive yet selective degradation of proteins involving myosin thick filaments and possibly components of sarcolemma, causing muscle inexcitability.

Inflammatory myopathies in Nigerians: case series and literature review.

PubMed

Adelowo, O O; Edomwonyi, U; Olaosebikan, H

2013-06-01

Idiopathic Inflammatory myopathies (IIM) are rare connective tissue diseases and have been rarely reported among Nigerians: To study the clinical, laboratory and electromyographic characteristics of Nigerian patients with polymyositis and dermatomyositis. In a retrospective study, patients attending a private practice rheumatology clinic in Lagos and fulfilling the Bohan and Peter's criteria for polymyositis and dermatomyositis were examined and common causes of proximal muscle weakness were excluded. Haematological, biochemical, serological and electromyographic studies were carried out. Patients were treated with standard drugs. Fourteen patients (F-13, M-1) were diagnosed with Polymyositis (PM) and Dermatomyositis (DM). Seven had probable PM, 4 with possible PM and 3 with probable DM. Mean age was 35 years (range 22-54) ESR was markedly raised mean 105/min (26-150). Muscle and liver enzymes were raised in all patients. Creatinine kinase median 1134 (29-10,166); lactic dehydrogenase median 477 (209-787); ALT 43 (19-233); AST 136 (25-725). Serology for ANF was positive in eight patients; Anti Jo1 in 1 out of 9 while Anti Mi2 was negative in all tested. EMG in 6 tested showed myopathic pattern. Inflammatory myopathies are rare among Nigerians but a heightened awareness is needed for diagnosis and management.

Reduced step length reduces knee joint contact forces during running following anterior cruciate ligament reconstruction but does not alter inter-limb asymmetry.

PubMed

Bowersock, Collin D; Willy, Richard W; DeVita, Paul; Willson, John D

2017-03-01

Anterior cruciate ligament reconstruction is associated with early onset knee osteoarthritis. Running is a typical activity following this surgery, but elevated knee joint contact forces are thought to contribute to osteoarthritis degenerative processes. It is therefore clinically relevant to identify interventions to reduce contact forces during running among individuals after anterior cruciate ligament reconstruction. The primary purpose of this study was to evaluate the effect of reducing step length during running on patellofemoral and tibiofemoral joint contact forces among people with a history of anterior cruciate ligament reconstruction. Inter limb knee joint contact force differences during running were also examined. 18 individuals at an average of 54.8months after unilateral anterior cruciate ligament reconstruction ran in 3 step length conditions (preferred, -5%, -10%). Bilateral patellofemoral, tibiofemoral, and medial tibiofemoral compartment peak force, loading rate, impulse, and impulse per kilometer were evaluated between step length conditions and limbs using separate 2 factor analyses of variance. Reducing step length 5% decreased patellofemoral, tibiofemoral, and medial tibiofemoral compartment peak force, impulse, and impulse per kilometer bilaterally. A 10% step length reduction further decreased peak forces and force impulses, but did not further reduce force impulses per kilometer. Tibiofemoral joint impulse, impulse per kilometer, and patellofemoral joint loading rate were lower in the previously injured limb compared to the contralateral limb. Running with a shorter step length is a feasible clinical intervention to reduce knee joint contact forces during running among people with a history of anterior cruciate ligament reconstruction. Copyright © 2017 Elsevier Ltd. All rights reserved.

A Case of Myopathy, Encephalopathy, Lactic Acidosis and Stroke-Like Episodes (MELAS) Syndrome with Intracardiac Thrombus [corrected].

PubMed

Joo, Jung-Chul; Seol, Myung Do; Yoon, Jin Won; Lee, Young Soo; Kim, Dong-Keun; Choi, Yong Hoon; Ahn, Hyo Seong; Cho, Wook Hyun

2013-03-01

Myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) is a multisystem clinical syndrome manifested by mitochondrial myopathy, encephalopathy, lactic acidosis and recurrent stroke-like episodes. A 27-year-old female with MELAS syndrome presented with cerebral infarction. Echocardiography revealed a thrombus attached to the apex of the hypertrophied left ventricle, with decreased systolic function. The embolism of the intracardiac thrombus might have been the cause of stroke. There should be more consideration given to the increased possibility of intracardiac thrombus formation when a MELAS patient with cardiac involvement is encountered.

A NON-OPERATIVE APPROACH TO THE MANAGEMENT OF CHRONIC EXERTIONAL COMPARTMENT SYNDROME IN A TRIATHLETE: A CASE REPORT.

PubMed

Collins, Cristiana Kahl; Gilden, Brad

2016-12-01

Chronic Exertional Compartment Syndrome (CECS) causes significant exercise related pain secondary to increased intra-compartmental pressure (ICP) in the lower extremities. CECS is most often treated with surgery with minimal information available on non-operative approaches to care. This case report presents a case of CECS successfully managed with physical therapy. Case report. A 34-year-old competitive triathlete experienced bilateral anterior and posterior lower leg pain measured with a numerical pain rating scale of 7/10 at two miles of running. Pain decreased to resting levels of 4/10 two hours post exercise. The patient was diagnosed with bilateral CECS with left lower extremity ICP at rest measured at 36 mmHg (deep posterior), 36-38 mmHg (superficial posterior), and 25 mmHg (anterior). Surgery was recommended. The patient chose non-operative care and was treated with physical therapy using the Functional Manual Therapy approach aimed at addressing myofascial restrictions, neuromuscular function and motor control deficits throughout the lower quadrant for 23 visits over 3.5 months. At discharge the patient had returned to running pain free and training for an Olympic distance triathlon. The Lower Extremity Functional Scale improved from 62 to 80. The patient reported minimal post exercise tightness in bilateral lower extremities. Left lower extremity compartment pressure measurements at rest were in normal ranges measuring at 11 mmHg (deep posterior), 8 mmHg (superficial posterior), 19 mmHg (anterior), and 10 mmHg (lateral). Three-years post intervention the patient remained pain free with a Global Rating of Change of 6. This case report describes the successful treatment of a triathlete with Functional Manual Therapy resulting in a return to competitive sports without pain. Level 4.

Ultrasonic Apparatus and Method to Assess Compartment Syndrome

NASA Technical Reports Server (NTRS)

Yost, William T. (Inventor); Ueno, Toshiaki (Inventor); Hargens, Alan R. (Inventor)

2009-01-01

A process and apparatus for measuring pressure buildup in a body compartment that encases muscular tissue. The method includes assessing the body compartment configuration and identifying the effect of pulsatible components on compartment dimensions and muscle tissue characteristics. This process is used in preventing tissue necrosis, and in decisions of whether to perform surgery on the body compartment for prevention of Compartment Syndrome. An apparatus is used for measuring pressure build-up in the body compartment having components for imparting ultrasonic waves such as a transducer, placing the transducer to impart the ultrasonic waves, capturing the imparted ultrasonic waves, mathematically manipulating the captured ultrasonic waves and categorizing pressure build-up in the body compartment from the mathematical manipulations.

Interposition of the Posterior Cruciate Ligament into the Medial Compartment of the Knee Joint on Coronal Magnetic Resonance Imaging.

PubMed

Kim, Hyun Su; Yoon, Young Cheol; Park, Ki Jeong; Wang, Joon Ho; Choe, Bong-Keun

2016-01-01

The purpose of our study was to evaluate the overall prevalence and clinical significance of interposition of the posterior cruciate ligament (PCL) into the medial compartment of the knee joint in coronal magnetic resonance imaging (MRI). We retrospectively reviewed 317 consecutive patients referred for knee MRI at our institution between October 2009 and December 2009. Interposition of the PCL into the medial compartment of the knee joint on proton coronal MRI was evaluated dichotomously (i.e., present or absent). We analyzed the interposition according to its prevalence as well as its relationship with right-left sidedness, gender, age, and disease categories (osteoarthritis, anterior cruciate ligament tear, and medial meniscus tear). Prevalence of interposition of PCL into the medial compartment of the knee joint was 47.0% (149/317). There was no right (50.0%, 83/166) to left (43.7%, 66/151) or male (50.3%, 87/173) to female (43.1%, 62/144) differences in the prevalence. There was no significant association between the prevalence and age, or the disease categories. Interposition of the PCL into the medial compartment of the knee joint is observed in almost half of patients on proton coronal MRI of the knee. Its presence is not associated with any particular factors including knee pathology and may be regarded as a normal MR finding.

Genetic factors affecting statin concentrations and subsequent myopathy: a HuGENet systematic review

PubMed Central

Canestaro, William J.; Austin, Melissa A.; Thummel, Kenneth E.

2015-01-01

Statins, 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibitors, have proven efficacy in both lowering low-density-lipoprotein levels and preventing major coronary events, making them one of the most commonly prescribed drugs in the United States. Statins exhibit a class-wide side effect of muscle toxicity and weakness, which has led regulators to impose both dosage limitations and a recall. This review focuses on the best-characterized genetic factors associated with increased statin muscle concentrations, including the genes encoding cytochrome P450 enzymes (CYP2D6, CYP3A4, and CYP3A5), a mitochondrial enzyme (GATM), an influx transporter (SLCO1B1), and efflux transporters (ABCB1 and ABCG2). A systematic literature review was conducted to identify relevant research evaluating the significance of genetic variants predictive of altered statin concentrations and subsequent statin-related myopathy. Studies eligible for inclusion must have incorporated genotype information and must have associated it with some measure of myopathy, either creatine kinase levels or self-reported muscle aches and pains. After an initial review, focus was placed on seven genes that were adequately characterized to provide a substantive review: CYP2D6, CYP3A4, CYP3A5, GATM, SLCO1B1, ABCB1, and ABCG2. All statins were included in this review. Among the genetic factors evaluated, statin-related myopathy appears to be most strongly associated with variants in SLCO1B1. PMID:24810685

Differential synaptology of vGluT2-containing thalamostriatal afferents between the patch and matrix compartments in rats.

PubMed

Raju, Dinesh V; Shah, Deep J; Wright, Terrence M; Hall, Randy A; Smith, Yoland

2006-11-10

The striatum is divided into two compartments named the patch (or striosome) and the matrix. Although these two compartments can be differentiated by their neurochemical content or afferent and efferent projections, the synaptology of inputs to these striatal regions remains poorly characterized. By using the vesicular glutamate transporters vGluT1 and vGluT2, as markers of corticostriatal and thalamostriatal projections, respectively, we demonstrate a differential pattern of synaptic connections of these two pathways between the patch and the matrix compartments. We also demonstrate that the majority of vGluT2-immunolabeled axon terminals form axospinous synapses, suggesting that thalamic afferents, like corticostriatal inputs, terminate preferentially onto spines in the striatum. Within both compartments, more than 90% of vGluT1-containing terminals formed axospinous synapses, whereas 87% of vGluT2-positive terminals within the patch innervated dendritic spines, but only 55% did so in the matrix. To characterize further the source of thalamic inputs that could account for the increase in axodendritic synapses in the matrix, we undertook an electron microscopic analysis of the synaptology of thalamostriatal afferents to the matrix compartments from specific intralaminar, midline, relay, and associative thalamic nuclei in rats. Approximately 95% of PHA-L-labeled terminals from the central lateral, midline, mediodorsal, lateral dorsal, anteroventral, and ventral anterior/ventral lateral nuclei formed axospinous synapses, a pattern reminiscent of corticostriatal afferents but strikingly different from thalamostriatal projections arising from the parafascicular nucleus (PF), which terminated onto dendritic shafts. These findings provide the first evidence for a differential pattern of synaptic organization of thalamostriatal glutamatergic inputs to the patch and matrix compartments. Furthermore, they demonstrate that the PF is the sole source of significant

Retinal and anterior eye compartments derive from a common progenitor pool in the avian optic cup

PubMed Central

Venters, Sara J.; Cuenca, Paulina D.

2011-01-01

Purpose The optic cup is created through invagination of the optic vesicle. The morphogenetic rearrangement creates a double-layered cup, with a hinge (the Optic Cup Lip) where the epithelium bends back upon itself. Shortly after the optic cup forms, it is thought to be sub-divided into separate lineages: i) pigmented epithelium in the outer layer; ii) presumptive iris and ciliary body at the most anterior aspect of the inner layer; and iii) presumptive neural retina in the remainder of the inner layer. We test the native developmental potential of the anterior cup to determine if it normally contributes to the retina. Methods Vital dye and green fluorescent protein (GFP) expressing replication-incompetent retroviral vectors were used to label cells in the nascent optic cup and follow their direct progeny throughout development. Label was applied to either the optic cup lip (n=40), or to the domain just posterior to the lip (n=20). Retroviral labeling is a permanent lineage marker and enabled the analysis of advanced stages of development. Results Labeling within the optic cup gave rise to labeled progeny in the posterior optic cup that differentiated as neural retina (20 of 20). In contrast, labeling cells in the optic cup lip gave rise to progeny of labeled cells arrayed in a linear progression, from the lip into the neural retina (36 of 40). Label was retained in cells at the optic cup lip, regardless of age at examination. In older embryos, labeled progeny delaminated from the optic cup lip to differentiate as muscle of the pupillary margin. Conclusions The data show that the cells at the optic cup lip are a common progenitor population for pigmented epithelium, anterior eye tissues (ciliary body, iris, and pupillary muscle) and retinal neurons. The findings are supportive of an interpretation where the optic cup lip is a specialized niche containing a multipotent progenitor population. PMID:22219630

Apparent diffusion coefficient (ADC) does not correlate with different serological parameters in myositis and myopathy.

PubMed

Meyer, Hans-Jonas; Ziemann, Oliver; Kornhuber, Malte; Emmer, Alexander; Quäschling, Ulf; Schob, Stefan; Surov, Alexey

2018-06-01

Background Magnetic resonance imaging (MRI) is widely used in several muscle disorders. Diffusion-weighted imaging (DWI) is an imaging modality, which can reflect microstructural tissue composition. The apparent diffusion coefficient (ADC) is used to quantify the random motion of water molecules in tissue. Purpose To investigate ADC values in patients with myositis and non-inflammatory myopathy and to analyze possible associations between ADC and laboratory parameters in these patients. Material and Methods Overall, 17 patients with several myositis entities, eight patients with non-inflammatory myopathies, and nine patients without muscle disorder as a control group were included in the study (mean age = 55.3 ± 14.3 years). The diagnosis was confirmed by histopathology in every case. DWI was obtained in a 1.5-T scanner using two b-values: 0 and 1000 s/mm 2 . In all patients, the blood sample was acquired within three days to the MRI. The following serological parameters were estimated: C-reactive protein, lactate dehydrogenase, alanine aminotransferase, aspartate aminotransferase, creatine kinase, and myoglobine. Results The estimated mean ADC value for the myositis group was 1.89 ± 0.37 × 10 -3  mm 2 /s and for the non-inflammatory myopathy group was 1.79 ± 0.33 × 10 -3  mm 2 /s, respectively. The mean ADC values (1.15 ± 0.37 × 10 -3  mm 2 /s) were significantly higher to unaffected muscles (vs. myositis P = 0.0002 and vs. myopathy P = 0.0021). There were no significant correlations between serological parameters and ADC values. Conclusion Affected muscles showed statistically significantly higher ADC values than normal muscles. No linear correlations between ADC and serological parameters were identified.

Forearm Compartment Syndrome: Evaluation and Management.

PubMed

Kistler, Justin M; Ilyas, Asif M; Thoder, Joseph J

2018-02-01

Compartment syndrome of the forearm is uncommon but can have devastating consequences. Compartment syndrome is a result of osseofascial swelling leading to decreased tissue perfusion and tissue necrosis. There are numerous causes of forearm compartment syndrome and high clinical suspicion must be maintained to avoid permanent disability. The most widely recognized symptoms include pain out of proportion and pain with passive stretch of the wrist and digits. Early diagnosis and decompressive fasciotomy are essential in the treatment of forearm compartment syndrome. Closure of fasciotomy wounds can often be accomplished by primary closure but many patients require additional forms of soft tissue coverage procedures. Copyright © 2017 Elsevier Inc. All rights reserved.

Metabolic Myopathies and Physical Activity: When Fatigue Is More Than Simple Exertion.

ERIC Educational Resources Information Center

Tarnopolsky, Mark A.

2002-01-01

When patients experience fatigue and muscle cramps beyond exercise adaptation, physicians should consider metabolic myopathies. The most common conditions seen in active patients are myoadenylate deaminase deficiency and disorders such as McArdle's disease. Targeted family histories and basic laboratory studies help rule out conditions mimicking…

Leiomodin-3 dysfunction results in thin filament disorganization and nemaline myopathy

PubMed Central

Yuen, Michaela; Sandaradura, Sarah A.; Dowling, James J.; Kostyukova, Alla S.; Moroz, Natalia; Quinlan, Kate G.; Lehtokari, Vilma-Lotta; Ravenscroft, Gianina; Todd, Emily J.; Ceyhan-Birsoy, Ozge; Gokhin, David S.; Maluenda, Jérome; Lek, Monkol; Nolent, Flora; Pappas, Christopher T.; Novak, Stefanie M.; D’Amico, Adele; Malfatti, Edoardo; Thomas, Brett P.; Gabriel, Stacey B.; Gupta, Namrata; Daly, Mark J.; Ilkovski, Biljana; Houweling, Peter J.; Davidson, Ann E.; Swanson, Lindsay C.; Brownstein, Catherine A.; Gupta, Vandana A.; Medne, Livija; Shannon, Patrick; Martin, Nicole; Bick, David P.; Flisberg, Anders; Holmberg, Eva; Van den Bergh, Peter; Lapunzina, Pablo; Waddell, Leigh B.; Sloboda, Darcée D.; Bertini, Enrico; Chitayat, David; Telfer, William R.; Laquerrière, Annie; Gregorio, Carol C.; Ottenheijm, Coen A.C.; Bönnemann, Carsten G.; Pelin, Katarina; Beggs, Alan H.; Hayashi, Yukiko K.; Romero, Norma B.; Laing, Nigel G.; Nishino, Ichizo; Wallgren-Pettersson, Carina; Melki, Judith; Fowler, Velia M.; MacArthur, Daniel G.; North, Kathryn N.; Clarke, Nigel F.

2014-01-01

Nemaline myopathy (NM) is a genetic muscle disorder characterized by muscle dysfunction and electron-dense protein accumulations (nemaline bodies) in myofibers. Pathogenic mutations have been described in 9 genes to date, but the genetic basis remains unknown in many cases. Here, using an approach that combined whole-exome sequencing (WES) and Sanger sequencing, we identified homozygous or compound heterozygous variants in LMOD3 in 21 patients from 14 families with severe, usually lethal, NM. LMOD3 encodes leiomodin-3 (LMOD3), a 65-kDa protein expressed in skeletal and cardiac muscle. LMOD3 was expressed from early stages of muscle differentiation; localized to actin thin filaments, with enrichment near the pointed ends; and had strong actin filament-nucleating activity. Loss of LMOD3 in patient muscle resulted in shortening and disorganization of thin filaments. Knockdown of lmod3 in zebrafish replicated NM-associated functional and pathological phenotypes. Together, these findings indicate that mutations in the gene encoding LMOD3 underlie congenital myopathy and demonstrate that LMOD3 is essential for the organization of sarcomeric thin filaments in skeletal muscle. PMID:25250574

Glutaric aciduria type II presenting as myopathy and rhabdomyolysis in a teenager.

PubMed

Prasad, Manish; Hussain, Shanawaz

2015-01-01

Late-onset glutaric aciduria type II has been described recently as a rare but treatable cause of proximal myopathy in teenagers and adults. It is an autosomal recessive disease affecting fatty acid, amino acid, and choline metabolism. This is usually a result of 2 defective flavoproteins: either electron transfer flavoprotein (ETF) or electron transfer flavoprotein-ubiquinone oxidoreductase (ETF:QO). We present a 14-year-old boy with a background of autistic spectrum disorder who presented with severe muscle weakness and significant rhabdomyolysis. Before the onset of muscle weakness, he was very active but was completely bedridden at presentation. Diagnosis was established quickly by urine organic acid and plasma acylcarnitine analysis. He has shown significant improvement after starting oral riboflavin supplementation and is now fully mobile. This case highlights that late-onset glutaric aciduria type II is an important differential diagnosis to consider in teenagers presenting with proximal myopathy and rhabdomyolysis and it may not be associated with hypoglycemia. © The Author(s) 2014.

Effective treatment of mitochondrial myopathy by nicotinamide riboside, a vitamin B3

PubMed Central

Khan, Nahid A; Auranen, Mari; Paetau, Ilse; Pirinen, Eija; Euro, Liliya; Forsström, Saara; Pasila, Lotta; Velagapudi, Vidya; Carroll, Christopher J; Auwerx, Johan; Suomalainen, Anu

2014-01-01

Nutrient availability is the major regulator of life and reproduction, and a complex cellular signaling network has evolved to adapt organisms to fasting. These sensor pathways monitor cellular energy metabolism, especially mitochondrial ATP production and NAD+/NADH ratio, as major signals for nutritional state. We hypothesized that these signals would be modified by mitochondrial respiratory chain disease, because of inefficient NADH utilization and ATP production. Oral administration of nicotinamide riboside (NR), a vitamin B3 and NAD+ precursor, was previously shown to boost NAD+ levels in mice and to induce mitochondrial biogenesis. Here, we treated mitochondrial myopathy mice with NR. This vitamin effectively delayed early- and late-stage disease progression, by robustly inducing mitochondrial biogenesis in skeletal muscle and brown adipose tissue, preventing mitochondrial ultrastructure abnormalities and mtDNA deletion formation. NR further stimulated mitochondrial unfolded protein response, suggesting its protective role in mitochondrial disease. These results indicate that NR and strategies boosting NAD+ levels are a promising treatment strategy for mitochondrial myopathy. PMID:24711540

Elevated Cardiac Troponin T in Patients With Skeletal Myopathies.

PubMed

Schmid, Johannes; Liesinger, Laura; Birner-Gruenberger, Ruth; Stojakovic, Tatjana; Scharnagl, Hubert; Dieplinger, Benjamin; Asslaber, Martin; Radl, Roman; Beer, Meinrad; Polacin, Malgorzata; Mair, Johannes; Szolar, Dieter; Berghold, Andrea; Quasthoff, Stefan; Binder, Josepha S; Rainer, Peter P

2018-04-10

Cardiac troponins are often elevated in patients with skeletal muscle disease who have no evidence of cardiac disease. The goal of this study was to characterize cardiac troponin concentrations in patients with myopathies and derive insights regarding the source of elevated troponin T measurements. Cardiac troponin T (cTnT) and cardiac troponin I (cTnI) concentrations were determined by using high sensitivity assays in 74 patients with hereditary and acquired skeletal myopathies. Patients underwent comprehensive cardiac evaluation, including 12-lead electrocardiogram, 24-h electrocardiogram, cardiac magnetic resonance imaging, and coronary artery computed tomography. cTnT and cTnI protein expression was determined in skeletal muscle samples of 9 patients and in control tissues derived from autopsy using antibodies that are used in commercial assays. Relevant Western blot bands were subjected to liquid chromatography tandem mass spectrometry for protein identification. Levels of cTnT (median: 24 ng/l; interquartile range: 11 to 54 ng/l) were elevated (>14 ng/l) in 68.9% of patients; cTnI was elevated (>26 ng/l) in 4.1% of patients. Serum cTnT levels significantly correlated with creatine kinase and myoglobin (r = 0.679 and 0.786, respectively; both p < 0.001). Based on cTnT serial testing, 30.1% would have fulfilled current rule-in criteria for myocardial infarction. Noncoronary cardiac disease was present in 23%. Using cTnT antibodies, positive bands were found in both diseased and healthy skeletal muscle at molecular weights approximately 5 kDa below cTnT. Liquid chromatography tandem mass spectrometry identified the presence of skeletal troponin T isoforms in these bands. Measured cTnT concentrations were chronically elevated in the majority of patients with skeletal myopathies, whereas cTnI elevation was rare. Our data indicate that cross-reaction of the cTnT immunoassay with skeletal muscle troponin isoforms was the likely cause. Copyright © 2018 The

Congenital myotonic myopathy in the miniature schnauzer: an autosomal recessive trait.

PubMed

Vite, C H; Melniczek, J; Patterson, D; Giger, U

1999-01-01

Myotonia is a clinical sign characterized by a delay in skeletal muscle relaxation following electrical or mechanical stimulation. A series of related miniature schnauzer dogs with congenital myotonic myopathy were studied. A composite pedigree of six affected litters and the results of a planned breeding between two affected animals are consistent with an autosomal recessive mode of inheritance.

Compartment syndrome after tibial plateau fracture☆

PubMed Central

Pitta, Guilherme Benjamin Brandão; dos Santos, Thays Fernanda Avelino; dos Santos, Fernanda Thaysa Avelino; da Costa Filho, Edelson Moreira

2014-01-01

Fractures of the tibial plateau are relatively rare, representing around 1.2% of all fractures. The tibia, due to its subcutaneous location and poor muscle coverage, is exposed and suffers large numbers of traumas, not only fractures, but also crush injuries and severe bruising, among others, which at any given moment, could lead compartment syndrome in the patient. The case is reported of a 58-year-old patient who, following a tibial plateau fracture, presented compartment syndrome of the leg and was submitted to decompressive fasciotomy of the four right compartments. After osteosynthesis with internal fixation of the tibial plateau using an L-plate, the patient again developed compartment syndrome. PMID:26229779

Acute quadriplegia caused by necrotizing myopathy in a renal transplant recipient with severe pneumonia: acute onset and complete recovery.

PubMed

Tu, Guo-Wei; Song, Jie-Qiong; Ting, Simon Kang Seng; Ju, Min-Jie; He, Hong-Yu; Dong, Ji-Hong; Luo, Zhe

2015-02-03

Critical illness polyneuropathy and myopathy are multifaceted complications that follow severe illnesses involving the sensorimotor axons and proximal skeletal muscles. These syndromes have rarely been reported among renal transplant recipients. In this paper, we report a case of acute quadriplegia caused by necrotizing myopathy in a renal transplant recipient with severe pneumonia. The muscle strength in the patient's extremities improved gradually after four weeks of comprehensive treatment, and his daily life activities were normal a year after being discharged.

Myopericarditis in a case of anti-signal recognition particle (anti-SRP) antibody-positive myopathy.

PubMed

Tanaka, Mariko; Gamou, Naoki; Shizukawa, Hirohiko; Tsuda, Emiko; Shimohama, Shun

2016-12-28

A 79 year-old female was admitted to our hospital because of high serum creatine kinase level together with proximal muscle weakness and pain on grasping. MRI revealed inflammatory changes in femoral muscles on both sides. Muscle biopsy showed size irregularity of muscle cells, and necrosis and regeneration of fibers. Study of antibodies was also consistent with the diagnostic criteria of anti-signal recognition particle (anti-SRP) antibody-positive myopathy. On admission, the patient required pericardiocentesis for the management of exudative pericarditis. Accompanying the aggravation of myositis, negative T wave in precordial leads on ECG, ventricular extrasystoles and non-sustained ventricular tachycardia were observed. These abnormalities were resolved with the improvement of myositis by immunosuppressive treatment. These observations suggest that the myopericarditis was associated with anti-SRP antibody-positive myopathy.

Acute compartment syndrome caused by uncontrolled hypothyroidism.

PubMed

Modi, Anar; Amin, Hari; Salzman, Matthew; Morgan, Farah

2017-06-01

Acute compartment syndrome is increased tissue pressure exceeding perfusion pressure in a closed compartment resulting in nerve and muscle ischemia. Common precipitating causes are crush injuries, burns, substance abuse, osseous or vascular limb trauma. This is a case of 42year old female with history of hypothyroidism who presented to emergency room with acute onset of severe pain and swelling in right lower extremity. Physical examination was concerning for acute compartment syndrome of right leg which was confirmed by demonstration of elevated compartmental pressures. No precipitating causes were readily identified. Further laboratory testing revealed uncontrolled hypothyroidism. Management included emergent fasciotomy and initiating thyroid hormone replacement. This case represents a rare association between acute compartment syndrome and uncontrolled hypothyroidism. We also discuss the pathogenesis of compartment syndrome in hypothyroid patients and emphasize the importance of evaluating for less common causes, particularly in setting of non-traumatic compartment syndrome. Copyright © 2016 Elsevier Inc. All rights reserved.

Characterization of sarcoplasmic reticulum Ca(2+) ATPase pumps in muscle of patients with myotonic dystrophy and with hypothyroid myopathy.

PubMed

Guglielmi, V; Oosterhof, A; Voermans, N C; Cardani, R; Molenaar, J P; van Kuppevelt, T H; Meola, G; van Engelen, B G; Tomelleri, G; Vattemi, G

2016-06-01

Sarcoplasmic/endoplasmic reticulum Ca(2+) ATPase (SERCA) pumps play the major role in lowering cytoplasmic calcium concentration in skeletal muscle by catalyzing the ATP-dependent transport of Ca(2+) from the cytosol to the lumen of the sarcoplasmic reticulum (SR). Although SERCA abnormalities have been hypothesized to contribute to the dysregulation of intracellular Ca(2+) homeostasis and signaling in muscle of patients with myotonic dystrophy (DM) and hypothyroid myopathy, the characterization of SERCA pumps remains elusive and their impairment is still unclear. We assessed the activity of SR Ca(2+)-ATPase, expression levels and fiber distribution of SERCA1 and SERCA2, and oligomerization of SERCA1 protein in muscle of patients with DM type 1 and 2, and with hypothyroid myopathy. Our data provide evidence that SR Ca(2+) ATPase activity, protein levels and muscle fiber distribution of total SERCA1 and SERCA2, and SERCA1 oligomerization pattern are similar in patients with both DM1 and DM2, hypothyroid myopathy and in control subjects. We prove that SERCA1b, the neonatal isoform of SERCA1, is expressed at protein level in muscle of patients with DM2 and, in lower amount, of patients with DM1. Our present study demonstrates that SERCA function is not altered in muscle of patients with DM and with hypothyroid myopathy. Copyright © 2016 Elsevier B.V. All rights reserved.

14 CFR 29.773 - Pilot compartment view.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 14 Aeronautics and Space 1 2011-01-01 2011-01-01 false Pilot compartment view. 29.773 Section 29... Accommodations § 29.773 Pilot compartment view. (a) Nonprecipitation conditions. For nonprecipitation conditions, the following apply: (1) Each pilot compartment must be arranged to give the pilots a sufficiently...

14 CFR 29.773 - Pilot compartment view.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Pilot compartment view. 29.773 Section 29... Accommodations § 29.773 Pilot compartment view. (a) Nonprecipitation conditions. For nonprecipitation conditions, the following apply: (1) Each pilot compartment must be arranged to give the pilots a sufficiently...

14 CFR 25.773 - Pilot compartment view.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 14 Aeronautics and Space 1 2011-01-01 2011-01-01 false Pilot compartment view. 25.773 Section 25... § 25.773 Pilot compartment view. (a) Nonprecipitation conditions. For nonprecipitation conditions, the following apply: (1) Each pilot compartment must be arranged to give the pilots a sufficiently extensive...

14 CFR 25.773 - Pilot compartment view.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Pilot compartment view. 25.773 Section 25... § 25.773 Pilot compartment view. (a) Nonprecipitation conditions. For nonprecipitation conditions, the following apply: (1) Each pilot compartment must be arranged to give the pilots a sufficiently extensive...

[Idiopathic inflammatory myopathies in childhood. A study of 7 patients].

PubMed

Colomer Oferil, J; Vidal Sanahuja, R; Pineda Marfa, M; Prat, M; Fernández Alvarez, E

1988-09-01

Five patients with dermatomyositis and 2 with polymyositis between 3 and 12 years old are reviewed. All of them fulfil the Bohan and Peter diagnostic criteria. Five presented misery before weakness. Two presented acute renal failure. The pathologic muscular study was not always specific of inflammatory myopathy and without correlation with the degree of symptoms. Treatment which prednisone and in one patient also azathioprine resulted with complete remission in 4 patients.

Identification of a mutation in the MTM1 gene, associated with X-linked myotubular myopathy, in a Greek family

PubMed Central

Fidani, L; Karagianni, P; Tsakalidis, C; Mitsiako, G; Hatziioannidis, I; Biancalana, V; Nikolaidis, N

2011-01-01

X-linked myotubular myopathy (XLMTM) is a rare congenital myopathy, usually characterized by severe hypotonia and respiratory insufficiency at birth, in affected, male infants. The disease is causally associated with mutations in the MTM1 gene, coding for phosphatase myotubularin. We report a severe case of XLMTM with a novel mutation, at a donor splicing site (c.1467+1G) previously associated with severe phenotype. The mutation was also identified in the patient's mother, providing an opportunity for sound genetic counseling. PMID:22435031

Identification of a mutation in the MTM1 gene, associated with X-linked myotubular myopathy, in a Greek family.

PubMed

Fidani, L; Karagianni, P; Tsakalidis, C; Mitsiako, G; Hatziioannidis, I; Biancalana, V; Nikolaidis, N

2011-07-01

X-linked myotubular myopathy (XLMTM) is a rare congenital myopathy, usually characterized by severe hypotonia and respiratory insufficiency at birth, in affected, male infants. The disease is causally associated with mutations in the MTM1 gene, coding for phosphatase myotubularin. We report a severe case of XLMTM with a novel mutation, at a donor splicing site (c.1467+1G) previously associated with severe phenotype. The mutation was also identified in the patient's mother, providing an opportunity for sound genetic counseling.

14 CFR 23.773 - Pilot compartment view.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 14 Aeronautics and Space 1 2011-01-01 2011-01-01 false Pilot compartment view. 23.773 Section 23... Personnel and Cargo Accommodations § 23.773 Pilot compartment view. (a) Each pilot compartment must be— (1) Arranged with sufficiently extensive, clear and undistorted view to enable the pilot to safely taxi...

Long-term outcomes of synthetic transobturator nonabsorbable anterior mesh versus anterior colporrhaphy in symptomatic, advanced pelvic organ prolapse surgery.

PubMed

Lo, Tsia-Shu; Pue, Leng Boi; Tan, Yiap Loong; Wu, Pei-Ying

2014-02-01

Anterior vaginal mesh (AVM) combined with sacrospinous ligament fixation (SSF) yields better long-term success rates over anterior colporrhaphy (AC) in advanced pelvic organ prolapse (POP) surgery, with a low rate of mesh-related complications. Medical records of 198 patients who underwent surgery for POP between January 2006 and March 2010 were reviewed retrospectively. Patients' assessment at baseline and third-year postoperative follow-up were analyzed. SSF plus AC or AVM was performed for apical and anterior compartment repair. Primary outcome was objective cure [Pelvic Organ Prolapse Quantification (POP-Q) stage ≤ 1)], and subjective cure defined as negative response to questions 2 and 3 on the POPDI-6. Secondary outcomes were complications, symptoms severity and quality of life as measured with validated questionnaires. Post-operative data were available for 186 patients, 72 in AC group and 114 in AVM group were analyzed. The mean age, parity and operating time in AVM group were significantly higher as compared to AC group. The overall objective and subjective cure rate in AVM group was significantly higher than AC group (90.3 % and 88.6 % versus 73.6 % and 70.8 %, with P value = 0.003 and 0.002 respectively). Mesh exposure rate was 3.5 %. Improvement in both POPDI-6 and PISQ-12 in AVM group was statistically significant compared to AC group. Transobturator synthetic nonabsorbable AVM combined with SSF yielded a favorable and sustainable result over 5 years as compared to traditional AC, both in anatomical and subjective success rate. Mesh related morbidities were low and acceptable.

A Newly Defined Area of the Mouse Anterior Hypothalamus Involved in Septohypothalamic Circuit: Perifornical Area of the Anterior Hypothalamus, PeFAH.

PubMed

Horii-Hayashi, Noriko; Nishi, Mayumi

2018-02-27

Although the hypothalamus is classified into more than 10 compartments, it still contains uncharacterized areas. In this study, we identified a new triangular-shaped area between the paraventricular hypothalamic nucleus (PVN) and the fornix area in the mouse anterior hypothalamus, which is enriched in chondroitin sulfate proteoglycans (CSPGs). We designated this region as the perifornical area of the anterior hypothalamus (PeFAH) based on its anatomical location. As evidenced by Nissl staining, the PeFAH was distinguishable as an area of relatively low density. Immunohistochemical and DNA microarray analyses indicated that PeFAH contains sparsely distributed calretinin-positive neurons and densely clustered enkephalin-positive neurons. Furthermore, the PeFAH was shown to have bidirectional neural connections with the lateral septum. Indeed, we confirmed enkephalinergic projections from PeFAH neurons to the lateral septum, and inversely, calbindin-positive lateral septum neurons as afferents to the PeFAH. Finally, c-Fos expression analysis revealed that the activity of certain PeFAH neuronal populations tended to be increased by psychological stressors, but not that of enkephalinergic neurons. We proposed PeFAH as a new region in the AH.

Clinical Manifestation and a New "ISCU" Mutation in Iron-Sulphur Cluster Deficiency Myopathy

ERIC Educational Resources Information Center

Kollberg, Gittan; Tulinius, Mar; Melberg, Atle; Darin, Niklas; Andersen, Oluf; Holmgren, Daniel; Oldfors, Anders; Holme, Elisabeth

2009-01-01

Myopathy with deficiency of succinate dehydrogenase and aconitase is a recessively inherited disorder characterized by childhood-onset early fatigue, dyspnoea and palpitations on trivial exercise. The disease is non-progressive, but life-threatening episodes of widespread weakness, severe metabolic acidosis and rhabdomyolysis may occur. The…

36 CFR 1192.127 - Sleeping compartments.

Code of Federal Regulations, 2012 CFR

2012-07-01

... Intercity Rail Cars and Systems § 1192.127 Sleeping compartments. (a) Sleeping compartments required to be... controls, call buttons, electrical outlets, etc.) shall be mounted no more than 48 inches, and no less than...

36 CFR 1192.127 - Sleeping compartments.

Code of Federal Regulations, 2014 CFR

2014-07-01

... Intercity Rail Cars and Systems § 1192.127 Sleeping compartments. (a) Sleeping compartments required to be... controls, call buttons, electrical outlets, etc.) shall be mounted no more than 48 inches, and no less than...

36 CFR 1192.127 - Sleeping compartments.

Code of Federal Regulations, 2010 CFR

2010-07-01

... Intercity Rail Cars and Systems § 1192.127 Sleeping compartments. (a) Sleeping compartments required to be... controls, call buttons, electrical outlets, etc.) shall be mounted no more than 48 inches, and no less than...

36 CFR 1192.127 - Sleeping compartments.

Code of Federal Regulations, 2011 CFR

2011-07-01

... Intercity Rail Cars and Systems § 1192.127 Sleeping compartments. (a) Sleeping compartments required to be... controls, call buttons, electrical outlets, etc.) shall be mounted no more than 48 inches, and no less than...

14 CFR 25.772 - Pilot compartment doors.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 14 Aeronautics and Space 1 2011-01-01 2011-01-01 false Pilot compartment doors. 25.772 Section 25... § 25.772 Pilot compartment doors. For an airplane that has a lockable door installed between the pilot... pilot compartment if the cockpit door becomes jammed. (c) There must be an emergency means to enable a...

14 CFR 25.772 - Pilot compartment doors.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Pilot compartment doors. 25.772 Section 25... § 25.772 Pilot compartment doors. For an airplane that has a lockable door installed between the pilot... pilot compartment if the cockpit door becomes jammed. (c) There must be an emergency means to enable a...

Evaluation of the thoraco-laryngeal reflex ('slap test') as an indicator of laryngeal adductor myopathy in the horse.

PubMed

Newton-Clarke, M J; Divers, T J; Valentine, B A

1994-09-01

A study was conducted over a 12 month period to assess the accuracy of the 'slap test' in the diagnosis of laryngeal adductor myopathy. The thoraco-laryngeal reflexes of 15 horses with no clinical signs of idiopathic laryngeal hemiplegia (ILH) were recorded using a video-endoscope. These 'slap test' responses were examined independently by 3 assessors. The horses were subsequently subjected to euthanasia and samples taken from the cricoarytenoideus lateralis (CAL) muscles for histopathological examination and assessment of denervation atrophy. Despite normal adductory responses, moderate to severe atrophy of the left CAL muscles was seen in 5 horses. The remaining horses had varying degrees of adductor myopathy, invariably worse in the left side of the larynx. The 'slap test' as performed in this study was therefore unable to differentiate between horses with moderate to severe muscle changes and those without, making it useless as a diagnostic test for adductor myopathy. The reason for the preservation in adductor function despite advanced histological atrophy of the muscle may lie in the degree of reinnervation found in the muscles.

Autoantibodies against 3-Hydroxy-3-Methylglutaryl-Coenzyme A Reductase (HMGCR) in Patients with Statin-Associated Autoimmune Myopathy

PubMed Central

Mammen, Andrew L.; Chung, Tae; Christopher-Stine, Lisa; Rosen, Paul; Rosen, Antony; Casciola-Rosen, Livia A.

2010-01-01

Objective In addition to inducing a self-limited myopathy, statin use is associated with an immune-mediated necrotizing (IMNM) myopathy with autoantibodies recognizing ~ 200 and ~100 kDa autoantigens. Identifying these molecules will clarify disease mechanism and facilitate diagnosis. Methods The effect of statin treatment on autoantigen expression was addressed by immunoprecipitation using patient sera. The identity of the ~100 kDa autoantigen was confirmed by immunoprecipitating in vitro-translated HMGCR protein. HMGCR expression in muscle was analyzed by immunofluorescence. A cohort of myopathy patients was screened for anti-HMGCR autoantibodies by ELISA and genotyped for the rs4149056 C allele, a predictor of self-limited statin myopathy. Results Statin exposure induced expression of the ~200/~100 kDa autoantigens in cultured cells. HMGCR was identified as the ~100 kDa autoantigen. Competition experiments demonstrated no distinct autoantibodies recognizing the ~200 kDa protein. In muscle biopsies from anti-HMGCR positive patients, HMGCR expression was up-regulated in cells expressing NCAM, a marker of muscle regeneration. Anti-HMGCR autoantibodies were found in 45 of 750 patients presenting to the Johns Hopkins Myositis Center (6%). Among patients age 50 or older, 92% were exposed to statins. The prevalence of the rs4149056 C allele was not increased in anti-HMGCR subjects. Conclusion Statins up-regulate expression of HMGCR, the major target of autoantibodies in statin-associated IMNM. Regenerating muscle cells express high levels of HMGCR, which may sustain the immune response even after statins are discontinued. These studies demonstrate a mechanistic link between an environmental trigger and the development of sustained autoimmunity. Detection of anti-HMGCR autoantibodies may facilitate diagnosis and direct therapy. PMID:21360500

Schistosomiasis and nutritional myopathy in a Brazilian tapir (Tapirus terrestris).

PubMed

Yamini, B; Schillhorn van Veen, T W

1988-10-01

Gross lesions suggestive of severe hepatoenteropathy and myopathy were noted in a 4.5-yr-old Brazilian tapir (Tapirus terrestris) from a zoo in Michigan (USA). The major microscopic lesions were granulomatous hepatitis and hemorrhagic enteritis associated with non-operculated eggs compatible with those of the Schistosomatidae (Digenea). Skeletal muscle and tongue contained foci of severe acute myodegeneration and necrosis. The hepatic vitamin E value of 1.3 ppm dry weight was considered critically low.

The Anterior Interosseus Artery Perforator Flap: Anatomical Dissections and Clinical Study.

PubMed

Panse, Nikhil S; Joshi, Sheetal B; Sahasrabudhe, Parag B; Bahetee, B; Gurude, Pradnya; Chandanwale, Ajay

2017-05-01

Reconstruction of upper extremity deformities continues to be a challenge to the reconstructive surgeon. Various loco regional, distant and free flaps are available for reconstruction. However, each has its own set of advantages and disadvantages. Of the commonly performed local flaps, radial artery forearm flap, and the posterior interosseus artery flap stand out prominently. Recently, perforator propeller flaps have been used for resurfacing the upper extremity. The anterior interosseus artery perforator flap is an uncommonly used and described flap. This study was divided into anatomical study and clinical application in a IV level of evidence. In the anatomical study, five upper extremities were studied. Clinically, 12 patients underwent reconstruction using the anterior interosseus artery perforator flap. Flaps were performed by a single surgeon. A retrospective review of these cases from November 2008 to May 2014 is presented. The anterior interosseus artery perforator was identified in four out of five cadaver limbs. The septocutaneous perforator was in the fifth extensor compartment around 4 cm proximal to the wrist joint. Of the twelve flaps, there was complete necrosis in one flap, and partial necrosis in one flap. The patient with complete necrosis underwent skin grafting at a later date. The wound healed secondarily in case of partial flap necrosis. Anterior interosseus artery perforator flap must be considered as an important reconstructive option in the armamentarium of the plastic surgeon, while managing hand and wrist defects.

The Anterior Interosseus Artery Perforator Flap: Anatomical Dissections and Clinical Study

PubMed Central

Panse, Nikhil S; Joshi, Sheetal B; Sahasrabudhe, Parag B; Bahetee, B; Gurude, Pradnya; Chandanwale, Ajay

2017-01-01

BACKGROUND Reconstruction of upper extremity deformities continues to be a challenge to the reconstructive surgeon. Various loco regional, distant and free flaps are available for reconstruction. However, each has its own set of advantages and disadvantages. Of the commonly performed local flaps, radial artery forearm flap, and the posterior interosseus artery flap stand out prominently. Recently, perforator propeller flaps have been used for resurfacing the upper extremity. The anterior interosseus artery perforator flap is an uncommonly used and described flap. METHODS This study was divided into anatomical study and clinical application in a IV level of evidence. In the anatomical study, five upper extremities were studied. Clinically, 12 patients underwent reconstruction using the anterior interosseus artery perforator flap. Flaps were performed by a single surgeon. A retrospective review of these cases from November 2008 to May 2014 is presented. RESULTS The anterior interosseus artery perforator was identified in four out of five cadaver limbs. The septocutaneous perforator was in the fifth extensor compartment around 4 cm proximal to the wrist joint. Of the twelve flaps, there was complete necrosis in one flap, and partial necrosis in one flap. The patient with complete necrosis underwent skin grafting at a later date. The wound healed secondarily in case of partial flap necrosis. CONCLUSION Anterior interosseus artery perforator flap must be considered as an important reconstructive option in the armamentarium of the plastic surgeon, while managing hand and wrist defects. PMID:28713704

[Inclusion body myopathy with Paget's disease of bone and frontotemporal dementia].

PubMed

Hayashi, Yukiko

2013-01-01

Inclusion body myopathy with Paget's disease of bone and frontotemporal dementia (IBMPFD) is an autosomal dominant disease caused by mutations in the VCP gene. VCP encodes a well-conserved multifunctional protein, valosin containing protein (VCP), which has important roles in protein quality control via proteasome and autophagy, protein aggregation, quality control of mitochondria, cell proliferation, and so on. Clinically, muscle weakness is the most common symptom of which disease onset is around 40 years. Affected muscles are variable, and the patients are sometimes diagnosed as limb girdle muscular dystrophy or GNE myopathy. Muscle pathology shows characteristic features including cytoplasmic/nuclear inclusions, rimmed vacuoles, and disorganized myofibrills, together with neurogenic changes. Paget's disease of bone is reported to be observed in a half of the patients around the age of 40 years, but less common in Japanese patients. Frontotemporal dementia is seen around one third of the patients which appears nearly 10 years later than muscle or bone disease. In addition to cognitive dysfunctions, motor neuron involvement and cerebellar signs were also seen in our series. IBMPFD is not so rare disease as previously thought, but complicate clinical findings may make its diagnosis difficult.

Genetics Home Reference: hereditary fibrosing poikiloderma with tendon contractures, myopathy, and pulmonary fibrosis

MedlinePlus

... which scar tissue forms in the lungs . Pulmonary fibrosis eventually causes difficulty breathing and can be life-threatening within ... Keavney B, Bézieau S, Mayosi BM. Mutations in FAM111B cause hereditary fibrosing ... myopathy, and pulmonary fibrosis. Am J Hum Genet. 2013 Dec 5;93( ...

A Peculiar Formula of Essential Amino Acids Prevents Rosuvastatin Myopathy in Mice

PubMed Central

D'Antona, Giuseppe; Tedesco, Laura; Ruocco, Chiara; Corsetti, Giovanni; Ragni, Maurizio; Fossati, Andrea; Saba, Elisa; Fenaroli, Francesca; Montinaro, Mery; Carruba, Michele O.; Valerio, Alessandra

2016-01-01

Abstract Aims: Myopathy, characterized by mitochondrial oxidative stress, occurs in ∼10% of statin-treated patients, and a major risk exists with potent statins such as rosuvastatin (Rvs). We sought to determine whether a peculiar branched-chain amino acid-enriched mixture (BCAAem), found to improve mitochondrial function and reduce oxidative stress in muscle of middle-aged mice, was able to prevent Rvs myopathy. Results: Dietary supplementation of BCAAem was able to prevent the structural and functional alterations of muscle induced by Rvs in young mice. Rvs-increased plasma 3-methylhistidine (a marker of muscular protein degradation) was prevented by BCAAem. This was obtained without changes of Rvs ability to reduce cholesterol and triglyceride levels in blood. Rather, BCAAem promotes de novo protein synthesis and reduces proteolysis in cultured myotubes. Morphological alterations of C2C12 cells induced by statin were counteracted by amino acids, as were the Rvs-increased atrogin-1 mRNA and protein levels. Moreover, BCAAem maintained mitochondrial mass and density and citrate synthase activity in skeletal muscle of Rvs-treated mice beside oxygen consumption and ATP levels in C2C12 cells exposed to statin. Notably, BCAAem assisted Rvs to reduce oxidative stress and to increase the anti-reactive oxygen species (ROS) defense system in skeletal muscle. Innovation and Conclusions: The complex interplay between proteostasis and antioxidant properties may underlie the mechanism by which a specific amino acid formula preserves mitochondrial efficiency and muscle health in Rvs-treated mice. Strategies aimed at promoting protein balance and controlling mitochondrial ROS level may be used as therapeutics for the treatment of muscular diseases involving mitochondrial dysfunction, such as statin myopathy. Antioxid. Redox Signal. 25, 595–608. PMID:27245589

Altered Splicing of the BIN1 Muscle-Specific Exon in Humans and Dogs with Highly Progressive Centronuclear Myopathy

PubMed Central

Böhm, Johann; Vasli, Nasim; Maurer, Marie; Cowling, Belinda; Shelton, G. Diane; Kress, Wolfram; Toussaint, Anne; Prokic, Ivana; Schara, Ulrike; Anderson, Thomas James; Weis, Joachim; Tiret, Laurent; Laporte, Jocelyn

2013-01-01

Amphiphysin 2, encoded by BIN1, is a key factor for membrane sensing and remodelling in different cell types. Homozygous BIN1 mutations in ubiquitously expressed exons are associated with autosomal recessive centronuclear myopathy (CNM), a mildly progressive muscle disorder typically showing abnormal nuclear centralization on biopsies. In addition, misregulation of BIN1 splicing partially accounts for the muscle defects in myotonic dystrophy (DM). However, the muscle-specific function of amphiphysin 2 and its pathogenicity in both muscle disorders are not well understood. In this study we identified and characterized the first mutation affecting the splicing of the muscle-specific BIN1 exon 11 in a consanguineous family with rapidly progressive and ultimately fatal centronuclear myopathy. In parallel, we discovered a mutation in the same BIN1 exon 11 acceptor splice site as the genetic cause of the canine Inherited Myopathy of Great Danes (IMGD). Analysis of RNA from patient muscle demonstrated complete skipping of exon 11 and BIN1 constructs without exon 11 were unable to promote membrane tubulation in differentiated myotubes. Comparative immunofluorescence and ultrastructural analyses of patient and canine biopsies revealed common structural defects, emphasizing the importance of amphiphysin 2 in membrane remodelling and maintenance of the skeletal muscle triad. Our data demonstrate that the alteration of the muscle-specific function of amphiphysin 2 is a common pathomechanism for centronuclear myopathy, myotonic dystrophy, and IMGD. The IMGD dog is the first faithful model for human BIN1-related CNM and represents a mammalian model available for preclinical trials of potential therapies. PMID:23754947

Effective treatment of mitochondrial myopathy by nicotinamide riboside, a vitamin B3.

PubMed

Khan, Nahid A; Auranen, Mari; Paetau, Ilse; Pirinen, Eija; Euro, Liliya; Forsström, Saara; Pasila, Lotta; Velagapudi, Vidya; Carroll, Christopher J; Auwerx, Johan; Suomalainen, Anu

2014-06-01

Nutrient availability is the major regulator of life and reproduction, and a complex cellular signaling network has evolved to adapt organisms to fasting. These sensor pathways monitor cellular energy metabolism, especially mitochondrial ATP production and NAD(+)/NADH ratio, as major signals for nutritional state. We hypothesized that these signals would be modified by mitochondrial respiratory chain disease, because of inefficient NADH utilization and ATP production. Oral administration of nicotinamide riboside (NR), a vitamin B3 and NAD(+) precursor, was previously shown to boost NAD(+) levels in mice and to induce mitochondrial biogenesis. Here, we treated mitochondrial myopathy mice with NR. This vitamin effectively delayed early- and late-stage disease progression, by robustly inducing mitochondrial biogenesis in skeletal muscle and brown adipose tissue, preventing mitochondrial ultrastructure abnormalities and mtDNA deletion formation. NR further stimulated mitochondrial unfolded protein response, suggesting its protective role in mitochondrial disease. These results indicate that NR and strategies boosting NAD(+) levels are a promising treatment strategy for mitochondrial myopathy. © 2014 The Authors. Published under the terms of the CC BY license.

The Effect of the Wooden Breast Myopathy on Sarcomere Structure and Organization.

PubMed

Velleman, Sandra G; Clark, Daniel L; Tonniges, Jeffrey R

2018-03-01

The wooden breast (WB) has been classically identified by the phenotypic presence of a wood-like pectoralis major (p. major) muscle. The WB-affected p. major muscle is characterized by necrotic muscle fibers and the replacement of muscle with connective tissue, water, and fat. The objective of the current study was to determine the effect of the WB myopathy on sarcomere organization by transmission electron microscopy. Sarcomere structure and organization were examined in two broiler lines with a high incidence of WB (Lines A and B) and another broiler line without WB (Line C). Affected muscle had an increase in smaller myofibers with diameters of 20 μm or less. Sarcomere organization decreased with fiber diameter in both Lines A and B. The structure and organization of sarcomeres in Line C were similar to WB-unaffected muscle in Lines A and B. Taken together, these data demonstrate that the WB myopathy detrimentally affects sarcomere organization in a broiler line-specific manner. Disorganization of sarcomere structure will affect the function of the p. major muscle as well as meat quality.

EFFECTS OF FOREFOOT RUNNING ON CHRONIC EXERTIONAL COMPARTMENT SYNDROME: A CASE SERIES

PubMed Central

Gregory, Robert; Alitz, Curtis; Gerber, J. Parry

2011-01-01

Introduction: Chronic exertional compartment syndrome (CECS) is a condition that occurs almost exclusively with running whereby exercise increases intramuscular pressure compromising circulation, prohibiting muscular function, and causing pain in the lower leg. Currently, a lack of evidence exists for the effective conservative management of CECS. Altering running mechanics by adopting forefoot running as opposed to heel striking may assist in the treatment of CECS, specifically with anterior compartment symptoms. Case Description: The purpose of this case series is to describe the outcomes for subjects with CECS through a systematic conservative treatment model focused on forefoot running. Subject one was a 21 y/o female with a 4 year history of CECS and subject two was a 21 y/o male, 7 months status-post two-compartment right leg fasciotomy with a return of symptoms and a new onset of symptoms on the contralateral side. Outcome: Both subjects modified their running technique over a period of six weeks. Kinematic and kinetic analysis revealed increased step rate while step length, impulse, and peak vertical ground reaction forces decreased. In addition, leg intracompartmental pressures decreased from pre-training to post-training. Within 6 weeks of intervention subjects increased their running distance and speed absent of symptoms of CECS. Follow-up questionnaires were completed by the subjects at 7 months following intervention; subject one reported running distances up to 12.87 km pain-free and subject two reported running 6.44 km pain-free consistently 3 times a week. Discussion: This case series describes a potentially beneficial conservative management approach to CECS in the form of forefoot running instruction. Further research in this area is warranted to further explore the benefits of adopting a forefoot running technique for CECS as well as other musculoskeletal overuse complaints. PMID:22163093

Effects of forefoot running on chronic exertional compartment syndrome: a case series.

PubMed

Diebal, Angela R; Gregory, Robert; Alitz, Curtis; Gerber, J Parry

2011-12-01

Chronic exertional compartment syndrome (CECS) is a condition that occurs almost exclusively with running whereby exercise increases intramuscular pressure compromising circulation, prohibiting muscular function, and causing pain in the lower leg. Currently, a lack of evidence exists for the effective conservative management of CECS. Altering running mechanics by adopting forefoot running as opposed to heel striking may assist in the treatment of CECS, specifically with anterior compartment symptoms. The purpose of this case series is to describe the outcomes for subjects with CECS through a systematic conservative treatment model focused on forefoot running. Subject one was a 21 y/o female with a 4 year history of CECS and subject two was a 21 y/o male, 7 months status-post two-compartment right leg fasciotomy with a return of symptoms and a new onset of symptoms on the contralateral side. Both subjects modified their running technique over a period of six weeks. Kinematic and kinetic analysis revealed increased step rate while step length, impulse, and peak vertical ground reaction forces decreased. In addition, leg intracompartmental pressures decreased from pre-training to post-training. Within 6 weeks of intervention subjects increased their running distance and speed absent of symptoms of CECS. Follow-up questionnaires were completed by the subjects at 7 months following intervention; subject one reported running distances up to 12.87 km pain-free and subject two reported running 6.44 km pain-free consistently 3 times a week. This case series describes a potentially beneficial conservative management approach to CECS in the form of forefoot running instruction. Further research in this area is warranted to further explore the benefits of adopting a forefoot running technique for CECS as well as other musculoskeletal overuse complaints.

SLCO1B1 polymorphism is not associated with risk of statin-induced myalgia/myopathy in a Czech population.

PubMed

Hubáček, Jaroslav A; Dlouhá, Dana; Adámková, Vera; Zlatohlavek, Lukáš; Viklický, Ondřej; Hrubá, Petra; Češka, Richard; Vrablík, Michal

2015-05-20

Gene SLCO1B1, encoding solute organic anionic transport polypeptide OATP1B1, belongs to the group of candidates potentially influencing statin treatment safety. OATP1B1 regulates (not only) the hepatic uptake of statins. Its genetic variation was described as an important predictor of statin-associated myopathy in a cohort of patients treated with a maximum dose of simvastatin. However, the impact of SLCO1B1 gene polymorphism on this risk in patients treated with other statins or lower doses of simvastatin needs to be assessed. Therefore, we performed the present study. SLCO1B1 tagging rs4363657 polymorphism was analyzed in 2 groups of patients with dyslipidemia (treated with simvastatin or atorvastatin, 10 or 20 mg per day), subgroup with statin-induced myalgia (N=286), and subgroup (N=707) without myalgia/myopathy, and in 2301 population controls without lipid-lowering treatment. Frequency of the individual genotypes in patients with myalgia/myopathy (TT=62.3%, CT=34.5%, CC=2.8%) did not significantly differ (both P values over 0.19) from that in patients without muscle symptoms (TT=61.4%, CT=32.9%, CC=5.7%) or from the population controls (TT=63.9%, CT=32.5%, CC=3.6%). Null results were also obtained for the dominant and recessive models of the analysis. In Czech patients treated with low statin doses, there is no association between SLCO1B1 gene polymorphism and risk of myalgia/myopathy.

Radiographic Findings in Revision Anterior Cruciate Ligament Reconstructions from the MARS Cohort

PubMed Central

2013-01-01

The Multicenter ACL (anterior cruciate ligament) Revision Study (MARS) group was developed to investigate revision ACL reconstruction outcomes. An important part of this is obtaining and reviewing radiographic studies. The goal for this radiographic analysis is to establish radiographic findings for a large revision ACL cohort to allow comparison with future studies. The study was designed as a cohort study. Various established radiographic parameters were measured by three readers. These included sagittal and coronal femoral and tibial tunnel position, joint space narrowing, and leg alignment. Inter- and intraobserver comparisons were performed. Femoral sagittal position demonstrated 42% were more than 40% anterior to the posterior cortex. On the sagittal tibia tunnel position, 49% demonstrated some impingement on full-extension lateral radiographs. Limb alignment averaged 43% medial to the medial edge of the tibial plateau. On the Rosenberg view (45-degree flexion view), the minimum joint space in the medial compartment averaged 106% of the opposite knee, but it ranged down to a minimum of 4.6%. Lateral compartment narrowing at its minimum on the Rosenberg view averaged 91.2% of the opposite knee, but it ranged down to a minimum of 0.0%. On the coronal view, verticality as measured by the angle from the center of the tibial tunnel aperture to the center of the femoral tunnel aperture measured 15.8 degree ± 6.9% from vertical. This study represents the radiographic findings in the largest revision ACL reconstruction series ever assembled. Findings were generally consistent with those previously demonstrated in the literature. PMID:23404491

Homozygous MYH7 R1820W mutation results in recessive myosin storage myopathy: scapuloperoneal and respiratory weakness with dilated cardiomyopathy.

PubMed

Yüceyar, Nur; Ayhan, Özgecan; Karasoy, Hatice; Tolun, Aslıhan

2015-04-01

Myosin storage myopathy (MSM) is a protein aggregate myopathy caused by the accumulation of myosin in muscle fibres and results from MYH7 mutation. Although MYH7 mutation is also an established cause of variable cardiomyopathy with or without skeletal myopathy, cardiomyopathy with MSM is a rare combination. Here, we update the clinical findings in the two brothers that we previously reported as having recessively inherited MSM characterized by scapuloperoneal distribution of weakness and typical hyaline-like bodies in type 1 muscle fibres. One of the patients, weak from childhood but not severely symptomatic until 28 years of age, had an unusual combination of MSM, severe dilated cardiomyopathy, and respiratory impairment at the age of 44 years. We identified homozygous missense mutation c.5458C>T (p.R1820W) in exon 37 in these patients as the second recessive MYH7 mutation reported to date. Copyright © 2015 Elsevier B.V. All rights reserved.

An epidemiological investigation of an idiopathic myopathy in hunting dogs in New Zealand.

PubMed

Hunt, H; Cave, N J; Gartrell, B D; Cogger, N; Petersen, J A; Roe, W D

2018-07-01

To conduct an epidemiological investigation of an idiopathic myopathy, known as "Go Slow" (GSM), which was initially recognised in dogs used for pig hunting. A secondary aim was to describe the hunting activities, diet and health of dogs used for pig hunting in New Zealand. A retrospective cohort study was conducted between June 2014-June 2017. Cases of GSM in dogs were diagnosed by veterinarians using a combination of clinical history, physical examination findings, serum biochemistry and/or skeletal muscle histology. A telephone interview was conducted with the owner or primary veterinarian to provide information regarding the dog's diet and exercise over the 7 days preceding the onset of clinical signs. In August 2015, a separate online survey of owners of dogs used for pig hunting was conducted to characterise the normal hunting activities, diet and health of these dogs. A total of 86 cases of GSM were recruited, of which 58 (67%) were pig hunting dogs, 16 (19%) pet dogs and 12 (14%) working farm dogs. Cases were most commonly reported in the upper North Island, and 65 (76 (95% CI=67-85)%) were from the Northland region. Processed commercial dog food had been fed to 93 (95% CI=88-98)% of affected dogs. Ingestion of raw, frozen or cooked wild pig in the preceding week was reported for 76 (88 (95% CI=82-95)%) dogs with the myopathy. In the survey of owners of healthy pig hunting dogs, 203 eligible responses were received; pig hunting was reported to most commonly occur in Northland (20.2%), Waikato (22.3%) and Bay of Plenty (23.2%) regions. Commercial dog food was fed to 172 (85 (95% CI=80-90)%) of the dogs included in this survey, and 55 (27 (95% CI=20-33)%) had eaten wild pig in the preceding week. The most common reported health problem in pig hunting dogs was traumatic wounds. Cases of GSM were most commonly recognised in dogs used for pig hunting, but also occurred in pet and working farm dogs. The disease was most frequently reported in the upper North

The renal compartment: a hydraulic view.

PubMed

Cruces, Pablo; Salas, Camila; Lillo, Pablo; Salomon, Tatiana; Lillo, Felipe; Hurtado, Daniel E

2014-12-01

The hydraulic behavior of the renal compartment is poorly understood. In particular, the role of the renal capsule on the intrarenal pressure has not been thoroughly addressed to date. We hypothesized that pressure and volume in the renal compartment are not linearly related, similar to other body compartments. The pressure-volume curve of the renal compartment was obtained by injecting fluid into the renal pelvis and recording the rise in intrarenal pressure in six anesthetized and mechanically ventilated piglets, using a catheter Camino 4B® inserted into the renal parenchyma. In healthy kidneys, pressure has a highly nonlinear dependence on the injected volume, as revealed by an exponential fit to the data (R (2) = 0.92). On the contrary, a linear relation between pressure and volume is observed in decapsulated kidneys. We propose a biomechanical model for the renal capsule that is able to explain the nonlinear pressure-volume dependence for moderate volume increases. We have presented experimental evidence and a theoretical model that supports the existence of a renal compartment. The mechanical role of the renal capsule investigated in this work may have important implications in elucidating the role of decompressive capsulotomy in reducing the intrarenal pressure in acutely injured kidneys.

Salvaging hope: Is increasing NAD(+) a key to treating mitochondrial myopathy?

PubMed

Lightowlers, Robert N; Chrzanowska-Lightowlers, Zofia M A

2014-06-01

Mitochondrial diseases can arise from mutations either in mitochondrial DNA or in nuclear DNA encoding mitochondrially destined proteins. Currently, there is no cure for these diseases although treatments to ameliorate a subset of the symptoms are being developed. In this issue of EMBO Molecular Medicine, Khan et al (2014) use a mouse model to test the efficacy of a simple dietary supplement of nicotinamide riboside to treat and prevent mitochondrial myopathies.

Dietary nitrate does not reduce oxygen cost of exercise or improve muscle mitochondrial function in patients with mitochondrial myopathy.

PubMed

Nabben, Miranda; Schmitz, Joep P J; Ciapaite, Jolita; le Clercq, Carlijn M P; van Riel, Natal A; Haak, Harm R; Nicolay, Klaas; de Coo, Irenaeus F M; Smeets, Hubert; Praet, Stephan F; van Loon, Luc J; Prompers, Jeanine J

2017-05-01

Muscle weakness and exercise intolerance negatively affect the quality of life of patients with mitochondrial myopathy. Short-term dietary nitrate supplementation has been shown to improve exercise performance and reduce oxygen cost of exercise in healthy humans and trained athletes. We investigated whether 1 wk of dietary inorganic nitrate supplementation decreases the oxygen cost of exercise and improves mitochondrial function in patients with mitochondrial myopathy. Ten patients with mitochondrial myopathy (40 ± 5 yr, maximal whole body oxygen uptake = 21.2 ± 3.2 ml·min -1 ·kg body wt -1 , maximal work load = 122 ± 26 W) received 8.5 mg·kg body wt -1 ·day -1 inorganic nitrate (~7 mmol) for 8 days. Whole body oxygen consumption at 50% of the maximal work load, in vivo skeletal muscle oxidative capacity (evaluated from postexercise phosphocreatine recovery using 31 P-magnetic resonance spectroscopy), and ex vivo mitochondrial oxidative capacity in permeabilized skinned muscle fibers (measured with high-resolution respirometry) were determined before and after nitrate supplementation. Despite a sixfold increase in plasma nitrate levels, nitrate supplementation did not affect whole body oxygen cost during submaximal exercise. Additionally, no beneficial effects of nitrate were found on in vivo or ex vivo muscle mitochondrial oxidative capacity. This is the first time that the therapeutic potential of dietary nitrate for patients with mitochondrial myopathy was evaluated. We conclude that 1 wk of dietary nitrate supplementation does not reduce oxygen cost of exercise or improve mitochondrial function in the group of patients tested. Copyright © 2017 the American Physiological Society.

SLCO1B1 Polymorphism is not associated with Risk of Statin-Induced Myalgia/Myopathy in a Czech Population

PubMed Central

Hubáček, Jaroslav A.; Dlouhá, Dana; Adámková, Vera; Zlatohlávek, Lukáš; Viklický, Ondřej; Hrubá, Petra; Češka, Richard; Vrablík, Michal

2015-01-01

Background Gene SLCO1B1, encoding solute organic anionic transport polypeptide OATP1B1, belongs to the group of candidates potentially influencing statin treatment safety. OATP1B1 regulates (not only) the hepatic uptake of statins. Its genetic variation was described as an important predictor of statin-associated myopathy in a cohort of patients treated with a maximum dose of simvastatin. However, the impact of SLCO1B1 gene polymorphism on this risk in patients treated with other statins or lower doses of simvastatin needs to be assessed. Therefore, we performed the present study. Material/Methods SLCO1B1 tagging rs4363657 polymorphism was analyzed in 2 groups of patients with dyslipidemia (treated with simvastatin or atorvastatin, 10 or 20 mg per day), subgroup with statin-induced myalgia (N=286), and subgroup (N=707) without myalgia/myopathy, and in 2301 population controls without lipid-lowering treatment. Results Frequency of the individual genotypes in patients with myalgia/myopathy (TT=62.3%, CT=34.5%, CC=2.8%) did not significantly differ (both P values over 0.19) from that in patients without muscle symptoms (TT=61.4%, CT=32.9%, CC=5.7%) or from the population controls (TT=63.9%, CT=32.5%, CC=3.6%). Null results were also obtained for the dominant and recessive models of the analysis. Conclusions In Czech patients treated with low statin doses, there is no association between SLCO1B1 gene polymorphism and risk of myalgia/myopathy. PMID:25992810

Smad4 SUMOylation is essential for memory formation through upregulation of the skeletal myopathy gene TPM2.

PubMed

Hsu, Wei L; Ma, Yun L; Liu, Yen C; Lee, Eminy H Y

2017-11-28

Smad4 is a critical effector of TGF-β signaling that regulates a variety of cellular functions. However, its role in the brain has rarely been studied. Here, we examined the molecular mechanisms underlying the post-translational regulation of Smad4 function by SUMOylation, and its role in spatial memory formation. In the hippocampus, Smad4 is SUMOylated by the E3 ligase PIAS1 at Lys-113 and Lys-159. Both spatial training and NMDA injection enhanced Smad4 SUMOylation. Inhibition of Smad4 SUMOylation impaired spatial learning and memory in rats by downregulating TPM2, a gene associated with skeletal myopathies. Similarly, knockdown of TPM2 expression impaired spatial learning and memory, while TPM2 mRNA and protein expression increased after spatial training. Among the TPM2 mutations associated with skeletal myopathies, the TPM2E122K mutation was found to reduce TPM2 expression and impair spatial learning and memory in rats. We have identified a novel role of Smad4 SUMOylation and TPM2 in learning and memory formation. These results suggest that patients with skeletal myopathies who carry the TPM2E122K mutation may also have deficits in learning and memory functions.

In vivo imaging of skeletal muscle in mice highlights muscle defects in a model of myotubular myopathy

PubMed Central

Mercier, Luc; Böhm, Johann; Fekonja, Nina; Allio, Guillaume; Lutz, Yves; Koch, Marc; Goetz, Jacky G.; Laporte, Jocelyn

2016-01-01

ABSTRACT Skeletal muscle structure and function are altered in different myopathies. However, the understanding of the molecular and cellular mechanisms mainly rely on in vitro and ex vivo investigations in mammalian models. In order to monitor in vivo the intracellular structure of the neuromuscular system in its environment under normal and pathological conditions, we set-up and validated non-invasive imaging of ear and leg muscles in mice. This original approach allows simultaneous imaging of different cellular and intracellular structures such as neuromuscular junctions and sarcomeres, reconstruction of the 3D architecture of the neuromuscular system, and video recording of dynamic events such as spontaneous muscle fiber contraction. Second harmonic generation was combined with vital dyes and fluorescent-coupled molecules. Skin pigmentation, although limiting, did not prevent intravital imaging. Using this versatile toolbox on the Mtm1 knockout mouse, a model for myotubular myopathy which is a severe congenital myopathy in human, we identified several hallmarks of the disease such as defects in fiber size and neuromuscular junction shape. Intravital imaging of the neuromuscular system paves the way for the follow-up of disease progression or/and disease amelioration upon therapeutic tests. It has also the potential to reduce the number of animals needed to reach scientific conclusions. PMID:28243519

The Relationship between Anterior Cruciate Ligament Injury and Osteoarthritis of the Knee

PubMed Central

Simon, David; Saltzman, Bryan M.; Rollins, Meaghan; Bach, Bernard R.; MacDonald, Peter

2015-01-01

Anterior cruciate ligament (ACL) tears are a common injury, particularly in the athletic and youth populations. The known association between ACL injury and subsequent osteoarthritis (OA) of the knee merits a more in-depth understanding of the relationship between the ACL-injured knee and osteoarthritis. ACL injury, especially with concomitant meniscal or other ligamentous pathology, predisposes the knee to an increased risk of osteoarthritis. ACL insufficiency results in deterioration of the normal physiologic knee bending culminating in increased anterior tibial translation and increased internal tibial rotation. This leads to increased mean contact stresses in the posterior medial and lateral compartments under anterior and rotational loading. However, surgical reconstruction of the ACL has not been shown to reduce the risk of future OA development back to baseline and has variability based on operative factors of graft choice, timing of surgery, presence of meniscal and chondral abnormalities, and surgical technique. Known strategies to prevent OA development are applicable to patients with ACL deficiency or after ACL reconstruction and include weight management, avoidance of excessive musculoskeletal loading, and strength training. Reconstruction of the ACL does not necessarily prevent osteoarthritis in many of these patients and may depend on several external variables. PMID:25954533

Structural dynamics of the mitochondrial compartment.

PubMed

Thorsness, P E

1992-09-01

The metabolic activities of mitochondria have been extensively characterized. However, there is much less known about the morphogenic changes of the mitochondrial compartment during growth, development and aging of the cell and the consequences of those structural changes on cellular metabolism. There is a growing body of evidence for interactions of mitochondria with cytoskeletal components and changes of mitochondrial structure during development and in response to changing environmental conditions. Segregation and recombination of mitochondrial genomes are also processes dependent upon the dynamic nature of the mitochondrial compartment. These regulatory and structural aspects of mitochondrial compartment dynamics will play an important role in the analysis of mitochondrial function and pathology.

Inclusion-body myositis and myopathies: different etiologies, possibly similar pathogenic mechanisms.

PubMed

Askanas, Valerie; Engel, W King

2002-10-01

Sporadic inclusion-body myositis (s-IBM) and hereditary inclusion body myopathies are progressive muscle diseases that lead to severe disability. We discuss recent advances in illuminating their pathogenic mechanism(s). We emphasize how different etiologies might lead to the strikingly similar pathology and possibly similar pathogenic cascade. Our basic hypothesis is that over-expression of amyloid-beta precursor protein within aging muscle fibers is an early upstream event causing the subsequent pathogenic cascade. On the basis of our research, several processes seem to be important in relation to the still speculative pathogenesis: (a) increased transcription and accumulation of amyloid-beta precursor protein, and accumulation of its proteolytic fragment Abeta; (b) accumulations of phosphorylated tau and other Alzheimer-related proteins; (c) accumulation of cholesterol and low-density lipoprotein receptors, the cholesterol accumulation possibly due to its abnormal trafficking; (d) oxidative stress; and (e) a milieu of muscle cellular aging in which these changes occur. We discuss unfolded and/or misfolded proteins as a possible mechanism in formation of the inclusion bodies and their consequences. The remarkable pathologic similarities between s-IBM muscle and Alzheimer disease brain are discussed. Unfolding knowledge of the various pathogenetic aspects of the s-IBMs and hereditary inclusion body myopathies may lead to new therapeutic avenues.

Topographical investigation of changes in depth-wise proteoglycan distribution in rabbit femoral articular cartilage at 4 weeks after transection of the anterior cruciate ligament.

PubMed

Arokoski, Mikko E A; Tiitu, Virpi; Jurvelin, Jukka S; Korhonen, Rami K; Fick, James M

2015-09-01

In this study, we explore topographical changes in proteoglycan distribution from femoral condylar cartilage in early osteoarthritis, acquired from both the lateral and medial condyles of anterior cruciate ligament transected (ACLT) and contralateral (CNTRL) rabbit knee joints, at 4 weeks post operation. Four sites across the cartilage surface in a parasagittal plane were defined across tissue sections taken from femoral condyles, and proteoglycan (PG) content was quantified using digital densitometry. The greatest depth-wise change in PG content due to an ACLT (compared to the CNTRL group) was observed anteriorly (site C) from the most weight-bearing location within the lateral compartment. In the medial compartment, the greatest change was observed in the most weight-bearing location (site B). The depth-wise changes in PG content were observed up to 48% and 28% depth from the tissue surface at these aforementioned sites, respectively (p < 0.05). The smallest depth-wise change in PG content was observed posteriorly (site A) from the most weight-bearing location within both femoral condyles (up to 20% and up to 5% depth from the tissue surface at lateral and medial compartments, respectively). This study gives further insight into how early cartilage deterioration progresses across the parasagittal plane of the femoral condyle. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Evaluation of subchondral bone marrow lipids of acute anterior cruciate ligament (ACL)-injured patients at 3 T.

PubMed

Wang, Ligong; Salibi, Nouha; Chang, Gregory; Bencardino, Jenny T; Babb, James S; Rokito, Andrew; Jazrawi, Laith; Sherman, Orrin; Regatte, Ravinder R

2014-06-01

The objectives of this study were to investigate the changes in compartment-specific subchondral bone marrow lipids of femoral-tibial bone in acute anterior cruciate ligament (ACL)-injured patients compared to that of healthy volunteers and patients with osteoarthritis (OA) (Kellgren-Lawrence [KL] grade 2-3). A total of 55 subjects were recruited in the study and subdivided into three subgroups: 17 healthy controls (4 females, 13 males; mean age = 41 ± 16, age range 24-78 years), 17 patients with acute ACL injury (3 females, 14 males; mean age = 30 ± 11, age range 18-61 years), and 21 patients with KL2-3 OA (12 females, 9 males; mean age = 65 ± 12, age range 44-89 years). Routine clinical proton density-weighted fast spin echo images in sagittal (without fat saturation), axial, and coronal (fat saturation) planes were acquired on a 3 T clinical scanner for cartilage morphology using Whole-Organ Magnetic Resonance Imaging Score grading. A voxel of 10 × 10 × 10 mm(3) was positioned in the medial and lateral compartments of the tibia and femur for proton magnetic resonance spectroscopy measurements using the single voxel stimulated echo acquisition mode pulse sequence. All proton magnetic resonance data were processed with Java-based magnetic resonance user interface. Wilcoxon rank sum test and mixed model two-way analysis of variance were performed to determine significant differences between different compartments and examine the effect of ACL injury, OA grade and compartment, and their interactions. The index of unsaturation in lateral tibial compartment in ACL-injured patients was significantly higher (P < .05) than all compartments except lateral femoral in patients with KL2-3 OA. Significantly lower values (P < .05) were also identified in saturated lipids at 2.03 ppm in all compartments in ACL-injured patients than those of all compartments in patients with KL2-3 OA. The preliminary results suggest that the indices of unsaturation in the lateral tibial

Neutral lipid-storage disease with myopathy and extended phenotype with novel PNPLA2 mutation.

PubMed

Massa, Roberto; Pozzessere, Simone; Rastelli, Emanuele; Serra, Laura; Terracciano, Chiara; Gibellini, Manuela; Bozzali, Marco; Arca, Marcello

2016-04-01

Neutral lipid-storage disease with myopathy is caused by mutations in PNPLA2, which produce skeletal and cardiac myopathy. We report a man with multiorgan neutral lipid storage and unusual multisystem clinical involvement, including cognitive impairment. Quantitative brain MRI with voxel-based morphometry and extended neuropsychological assessment were performed. In parallel, the coding sequences and intron/exon boundaries of the PNPLA2 gene were screened by direct sequencing. Neuropsychological assessment revealed global cognitive impairment, and brain MRI showed reduced gray matter volume in the temporal lobes. Molecular characterization revealed a novel homozygous mutation in exon 5 of PNPLA2 (c.714C>A), resulting in a premature stop codon (p.Cys238*). Some PNPLA2 mutations, such as the one described here, may present with an extended phenotype, including brain involvement. In these cases, complete neuropsychological testing, combined with quantitative brain MRI, may help to characterize and quantify cognitive impairment. © 2016 Wiley Periodicals, Inc.

Craniopharyngioma presenting with severe hyponatremia, hyponatremia-induced myopathy, and panhypopituitarism: a case report.

PubMed

Dilrukshi, M D S A; Sandakumari, G V N; Abeysundara, P K; Chang, T

2017-02-05

Craniopharyngiomas are rare intracranial tumors commonly presenting with neurological symptoms. Reports of severe hyponatremia as a presenting manifestation of a craniopharyngioma and hyponatremia-induced myopathy are rare. We report the case of a patient with craniopharyngioma presenting with severe hyponatremia, panhypopituitarism, and hyponatremia-induced myopathy. A 52-year-old Sri Lankan man presented with anorexia, nausea, fatigue, generalized muscle weakness, and cramps for 1 week. The onset of his illness had been preceded by vomiting and diarrhea for 1 day which he attributed to food poisoning. On examination, he had an apathetic disposition with a generalized "sallow complexion." He was not dehydrated. Apart from reduced muscle power (4/5) and hyporeflexia, the neurological examination was normal. His serum sodium was 102 mmol/l; potassium 4.1 mmol/l; chloride 63 mmol/l; plasma osmolality 272 mosm/KgH 2 O; urine osmolality 642 mosm/KgH 2 O; and urine sodium 79 mmol/l. His creatine phosphokinase was 12,400 U/l, lactate dehydrogenase 628 U/l, aspartate aminotransferase 360 U/l, and alanine aminotransferase 64 U/l. His hormone profile revealed panhypopituitarism. An electromyogram showed nonspecific abnormalities while a muscle biopsy did not show any pathology. Magnetic resonance imaging of his brain demonstrated a well-defined craniopharyngioma with suprasellar extension. His pituitary gland was compressed and the pituitary stalk was displaced by the tumor. He had marked improvement in muscle power and rapid reduction of serum creatine phosphokinase levels paralleling the correction of severe hyponatremia, even before the initiation of hormone replacement. This case illustrates the rare presentation of severe hyponatremia and hyponatremia-induced myopathy in patients with craniopharyngioma, awareness of which would facilitate early appropriate investigations and treatment.

[Progress of midfacial fat compartments and related clinical applications].

PubMed

Wen, Lihong; Wang, Jinhuang; Li, Yang; Liu, Dalie

2018-02-01

To review the research progress of midfacial fat compartments, and to thoroughly understand its current state of the anatomy and the aging morphologic characters of midfacial fat compartments, as well as the current status of clinical applications. The recent literature concerning the midfacial fat compartments and related clinical applications were extensively reviewed and analyzed. Midfacial fat layer has been considered as a fusion and a continuous layer, experiencing a global atrophy when aging. As more anatomical researches have done, recent studies have shown that midfacial fat layer is broadly divided into superficial and deep layers, which are both divided into different fat compartments by fascia, ligaments, or muscles. Midfacial fat compartments tend to atrophy with age, specifically in the deep fat compartments while hypertrophy in the superficial fat compartments. Clinical applications show that fat volumetric restoration with deep medial cheek fat and Ristow's space can restore the appearance of midface effectively. In recent years, the researches of midfacial fat compartments have achieved obvious progress, which will provide new ideas and basis for fat volumetric restoration. Corresponding treatments are selected based on different sites and different layers with different aging changes, reshaping a more youthful midface.

14 CFR 91.613 - Materials for compartment interiors.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 14 Aeronautics and Space 2 2010-01-01 2010-01-01 false Materials for compartment interiors. 91.613... compartment interiors. (a) No person may operate an airplane that conforms to an amended or supplemental type... SFAR the airplane meets the compartment interior requirements set forth in § 25.853 (a), (b), (b-1), (b...

Salvaging hope: Is increasing NAD+ a key to treating mitochondrial myopathy?

PubMed Central

Lightowlers, Robert N; Chrzanowska-Lightowlers, Zofia MA

2014-01-01

Mitochondrial diseases can arise from mutations either in mitochondrial DNA or in nuclear DNA encoding mitochondrially destined proteins. Currently, there is no cure for these diseases although treatments to ameliorate a subset of the symptoms are being developed. In this issue of EMBO Molecular Medicine, Khan et al (2014) use a mouse model to test the efficacy of a simple dietary supplement of nicotinamide riboside to treat and prevent mitochondrial myopathies. PMID:24838280

Novel autosomal dominant TNNT1 mutation causing nemaline myopathy.

PubMed

Konersman, Chamindra G; Freyermuth, Fernande; Winder, Thomas L; Lawlor, Michael W; Lagier-Tourenne, Clotilde; Patel, Shailendra B

2017-11-01

Nemaline myopathy (NEM) is one of the three major forms of congenital myopathy and is characterized by diffuse muscle weakness, hypotonia, respiratory insufficiency, and the presence of nemaline rod structures on muscle biopsy. Mutations in troponin T1 (TNNT1) is 1 of 10 genes known to cause NEM. To date, only homozygous nonsense mutations or compound heterozygous truncating or internal deletion mutations in TNNT1 gene have been identified in NEM. This extended family is of historical importance as some members were reported in the 1960s as initial evidence that NEM is a hereditary disorder. Proband and extended family underwent Sanger sequencing for TNNT1. We performed RT-PCR and immunoblot on muscle to assess TNNT1 RNA expression and protein levels in proband and father. We report a novel heterozygous missense mutation of TNNT1 c.311A>T (p.E104V) that segregated in an autosomal dominant fashion in a large family residing in the United States. Extensive sequencing of the other known genes for NEM failed to identify any other mutant alleles. Muscle biopsies revealed a characteristic pattern of nemaline rods and severe myofiber hypotrophy that was almost entirely restricted to the type 1 fiber population. This novel mutation alters a residue that is highly conserved among vertebrates. This report highlights not only a family with autosomal dominant inheritance of NEM, but that this novel mutation likely acts via a dominant negative mechanism. © 2017 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.

36 CFR § 1192.127 - Sleeping compartments.

Code of Federal Regulations, 2013 CFR

2013-07-01

... Intercity Rail Cars and Systems § 1192.127 Sleeping compartments. (a) Sleeping compartments required to be... controls, call buttons, electrical outlets, etc.) shall be mounted no more than 48 inches, and no less than...

T2 -Mapping evaluation of early cartilage alteration of talus for chronic lateral ankle instability with isolated anterior talofibular ligament tear or combined with calcaneofibular ligament tear.

PubMed

Tao, Hongyue; Hu, Yiwen; Qiao, Yang; Ma, Kui; Yan, Xu; Hua, Yinghui; Chen, Shuang

2018-01-01

To quantitatively evaluate the cartilage alteration of talus for chronic lateral ankle instability (LAI) with isolated anterior talofibular ligament (ATFL) tear and combined ATFL and calcaneofibular ligament (CFL) tear using T 2 -mapping at 3.0T. In all, 27 patients including 17 with isolated ATFL tear and 10 with ATFL+CFL tear, and 21 healthy subjects were recruited. All participants underwent T 2 -mapping scan at 3T and patients completed American Orthopaedic Foot and Ankle Society (AOFAS) scoring. The total talar cartilage (TTC) was segmented into six compartments: medial anterior (MA), medial center (MC), medial posterior (MP), lateral anterior (LA), lateral center (LC), and lateral posterior (LP). The T 2 value of each compartment was measured from T 2 -mapping images. Data were analyzed with one-way analysis of variance (ANOVA), Student's t-test, and Pearson's correlation coefficient. The T 2 values of MA, MC, MP, TTC in the ATFL group and MA, MC, MP, LC, LP, TTC in the ATFL+CFL group were higher than those in the control group (P < 0.05). Moreover, the T 2 values of MC, MP, LC, and TTC in the ATFL+CFL group were higher than those in the ATFL group (P < 0.05). The T 2 values of MA in both patient groups were negatively correlated with AOFAS scores (r = -0.596, r = -0.690, P < 0.05). Chronic LAI with ATFL tear had a trend of increasing cartilage T 2 values in talar trochlea, mainly involving medial cartilage compartments. Chronic LAI with ATFL+CFL tear might result in higher T 2 values in a much larger cartilage region than with ATFL tear. MA could be the main cartilage compartment that may affect the patient's clinical symptoms. 1 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2018;47:69-77. © 2017 International Society for Magnetic Resonance in Medicine.

Hydrogen Peroxide Probes Directed to Different Cellular Compartments

PubMed Central

Malinouski, Mikalai; Zhou, You; Belousov, Vsevolod V.; Hatfield, Dolph L.; Gladyshev, Vadim N.

2011-01-01

Background Controlled generation and removal of hydrogen peroxide play important roles in cellular redox homeostasis and signaling. We used a hydrogen peroxide biosensor HyPer, targeted to different compartments, to examine these processes in mammalian cells. Principal Findings Reversible responses were observed to various redox perturbations and signaling events. HyPer expressed in HEK 293 cells was found to sense low micromolar levels of hydrogen peroxide. When targeted to various cellular compartments, HyPer occurred in the reduced state in the nucleus, cytosol, peroxisomes, mitochondrial intermembrane space and mitochondrial matrix, but low levels of the oxidized form of the biosensor were also observed in each of these compartments, consistent with a low peroxide tone in mammalian cells. In contrast, HyPer was mostly oxidized in the endoplasmic reticulum. Using this system, we characterized control of hydrogen peroxide in various cell systems, such as cells deficient in thioredoxin reductase, sulfhydryl oxidases or subjected to selenium deficiency. Generation of hydrogen peroxide could also be monitored in various compartments following signaling events. Conclusions We found that HyPer can be used as a valuable tool to monitor hydrogen peroxide generated in different cellular compartments. The data also show that hydrogen peroxide generated in one compartment could translocate to other compartments. Our data provide information on compartmentalization, dynamics and homeostatic control of hydrogen peroxide in mammalian cells. PMID:21283738

The genetic basis of pectoralis major myopathies in modern broiler chicken lines

PubMed Central

Bailey, Richard A.; Watson, Kellie A.; Bilgili, S. F.; Avendano, Santiago

2015-01-01

This is the first report providing estimates of the genetic basis of breast muscle myopathies (BMM) and their relationship with growth and yield in broiler chickens. In addition, this paper addresses the hypothesis that genetic selection for increase breast yield has contributed to the onset of BMM. Data were analyzed from ongoing recording of BMM within the Aviagen breeding program. This study focused on three BMM: deep pectoral myopathy (DPM; binary trait), white striping (WS; 4 categories) and wooden breast (WB; 3 categories). Data from two purebred commercial broiler lines (A and B) were utilized providing greater than 40,000 meat quality records per line. The difference in selection history between these two lines has resulted in contrasting breast yield (BY): 29% for Line A and 21% for Line B. Data were analyzed to estimate genetic parameters using a multivariate animal model including six traits: body weight (BW), processing body weight (PW), BY, DPM, WB, and WS, in addition to the appropriate fixed effects and permanent environmental effect of the dam. Results indicate similar patterns of heritability and genetic correlations for the two lines. Heritabilities (h2) of BW, PW and BY ranged from 0.271–0.418; for DPM and WB h2 <0.1; and for WS h2 ≤0.338. Genetic correlations between the BMM and BW, PW, or BY were ≤0.132 in Line A and ≤0.248 in Line B. This paper demonstrates the polygenic nature of these traits and the low genetic relationships with BW, PW, and BY, which facilitates genetic improvement across all traits in a balanced breeding program. It also highlights the importance of understanding the environmental and/or management factors that contribute greater than 65% of the variance in the incidence of white striping of breast muscle and more than 90% of the variance of the incidence of wooden breast and deep pectoral myopathy in broiler chickens. PMID:26476091

The genetic basis of pectoralis major myopathies in modern broiler chicken lines.

PubMed

Bailey, Richard A; Watson, Kellie A; Bilgili, S F; Avendano, Santiago

2015-12-01

This is the first report providing estimates of the genetic basis of breast muscle myopathies (BMM) and their relationship with growth and yield in broiler chickens. In addition, this paper addresses the hypothesis that genetic selection for increase breast yield has contributed to the onset of BMM. Data were analyzed from ongoing recording of BMM within the Aviagen breeding program. This study focused on three BMM: deep pectoral myopathy (DPM; binary trait), white striping (WS; 4 categories) and wooden breast (WB; 3 categories). Data from two purebred commercial broiler lines (A and B) were utilized providing greater than 40,000 meat quality records per line. The difference in selection history between these two lines has resulted in contrasting breast yield (BY): 29% for Line A and 21% for Line B. Data were analyzed to estimate genetic parameters using a multivariate animal model including six traits: body weight (BW), processing body weight (PW), BY, DPM, WB, and WS, in addition to the appropriate fixed effects and permanent environmental effect of the dam. Results indicate similar patterns of heritability and genetic correlations for the two lines. Heritabilities (h2) of BW, PW and BY ranged from 0.271-0.418; for DPM and WB h2<0.1; and for WS h2≤0.338. Genetic correlations between the BMM and BW, PW, or BY were ≤0.132 in Line A and ≤0.248 in Line B. This paper demonstrates the polygenic nature of these traits and the low genetic relationships with BW, PW, and BY, which facilitates genetic improvement across all traits in a balanced breeding program. It also highlights the importance of understanding the environmental and/or management factors that contribute greater than 65% of the variance in the incidence of white striping of breast muscle and more than 90% of the variance of the incidence of wooden breast and deep pectoral myopathy in broiler chickens. © The Author 2015. Published by Oxford University Press on behalf of Poultry Science Association.

The pseudo-compartment method for coupling partial differential equation and compartment-based models of diffusion.

PubMed

Yates, Christian A; Flegg, Mark B

2015-05-06

Spatial reaction-diffusion models have been employed to describe many emergent phenomena in biological systems. The modelling technique most commonly adopted in the literature implements systems of partial differential equations (PDEs), which assumes there are sufficient densities of particles that a continuum approximation is valid. However, owing to recent advances in computational power, the simulation and therefore postulation, of computationally intensive individual-based models has become a popular way to investigate the effects of noise in reaction-diffusion systems in which regions of low copy numbers exist. The specific stochastic models with which we shall be concerned in this manuscript are referred to as 'compartment-based' or 'on-lattice'. These models are characterized by a discretization of the computational domain into a grid/lattice of 'compartments'. Within each compartment, particles are assumed to be well mixed and are permitted to react with other particles within their compartment or to transfer between neighbouring compartments. Stochastic models provide accuracy, but at the cost of significant computational resources. For models that have regions of both low and high concentrations, it is often desirable, for reasons of efficiency, to employ coupled multi-scale modelling paradigms. In this work, we develop two hybrid algorithms in which a PDE in one region of the domain is coupled to a compartment-based model in the other. Rather than attempting to balance average fluxes, our algorithms answer a more fundamental question: 'how are individual particles transported between the vastly different model descriptions?' First, we present an algorithm derived by carefully redefining the continuous PDE concentration as a probability distribution. While this first algorithm shows very strong convergence to analytical solutions of test problems, it can be cumbersome to simulate. Our second algorithm is a simplified and more efficient implementation of

Barefoot plantar pressure measurement in Chronic Exertional Compartment Syndrome.

PubMed

Roscoe, D; Roberts, A J; Hulse, D; Shaheen, A; Hughes, M P; Bennett, A

2018-04-09

Patients with Chronic Exertional Compartment Syndrome (CECS) have exercise-limiting pain that subsides at rest. Diagnosis is confirmed by intramuscular compartment pressure (IMCP) measurement. Accompanying CECS, subjective changes to gait (foot slap) are frequently reported by patients. This has not previously been investigated. The aim of this study was to investigate differences in barefoot plantar pressure (BFPP) between CECS cases and asymptomatic controls prior to the onset of painful symptoms. 40 male military volunteers, 20 with symptoms of CECS and 20 asymptomatic controls were studied. Alternative diagnoses were excluded with rigorous inclusion criteria, magnetic resonance imaging and dynamic IMCP measurement. BFPP was measured during walking and marching. Data were analysed for: Stance Time (ST); foot progression angle (FPA); centre of force; plantarflexion rate after heel strike (IFFC-time); the distribution of pressure under the heel; and, the ratio between inner and outer metatarsal loading. Correlation coefficients of each variable with speed and leg length were calculated followed by ANCOVA or t-test. Receiver operating characteristic (ROC) curves were constructed for IFFC-time. Caseshad shorter ST and IFFC-times than controls. FPA was inversely related to walking speed (WS) in controls only. The area under the ROC curve for IFFC-time ranged from 0.746 (95%CI: 0.636-0.87) to 0.773 (95%CI: 0.671-0.875) representing 'fair predictive validity'. Patients with CECS have an increased speed of ankle plantarflexion after heel strike that precedes the onset of painful symptoms likely resulting from a mechanical disadvantage of Tibialis Anterior. These findings provide further insight into the pathophysiology of CECS and support further investigation of this non-invasive diagnostic. The predictive value of IFFC-time in the diagnosis of CECS is comparable to post-exercise IMCP but falls short of dynamic IMCP measured during painful symptoms. Copyright © 2018

Recommended standardized terminology of the anterior female pelvis based on a structured medical literature review.

PubMed

Jeppson, Peter C; Balgobin, Sunil; Washington, Blair B; Hill, Audra Jolyn; Lewicky-Gaupp, Christina; Wheeler, Thomas; Ridgeway, Beri; Mazloomdoost, Donna; Balk, Ethan M; Corton, Marlene M; DeLancey, John

2018-07-01

The use of imprecise and inaccurate terms leads to confusion amongst anatomists and medical professionals. We sought to create recommended standardized terminology to describe anatomic structures of the anterior female pelvis based on a structured review of published literature and selected text books. We searched MEDLINE from its inception until May 2, 2016, using 11 medical subject heading terms to identify studies reporting on anterior female pelvic anatomy; any study type published in English was accepted. Nine textbooks were also included. We screened 12,264 abstracts, identifying 200 eligible studies along with 13 textbook chapters from which we extracted all pertinent anatomic terms. In all, 67 unique structures in the anterior female pelvis were identified. A total of 59 of these have been previously recognized with accepted terms in Terminologia Anatomica, the international standard on anatomical terminology. We also identified and propose the adoption of 4 anatomic regional terms (lateral vaginal wall, pelvic sidewall, pelvic bones, and anterior compartment), and 2 structural terms not included in Terminologia Anatomica (vaginal sulcus and levator hiatus). In addition, we identified 2 controversial terms (pubourethral ligament and Grafenberg spot) that require additional research and consensus from the greater medical and scientific community prior to adoption or rejection of these terms. We propose standardized terminology that should be used when discussing anatomic structures in the anterior female pelvis to help improve communication among researchers, clinicians, and surgeons. Copyright © 2018 Elsevier Inc. All rights reserved.

Becker muscular dystrophy-like myopathy regarded as so-called "fatty muscular dystrophy" in a pig: a case report and its diagnostic method.

PubMed

Horiuchi, Noriyuki; Aihara, Naoyuki; Mizutani, Hiroshi; Kousaka, Shinichi; Nagafuchi, Tsuneyuki; Ochiai, Mariko; Ochiai, Kazuhiko; Kobayashi, Yoshiyasu; Furuoka, Hidefumi; Asai, Tetsuo; Oishi, Koji

2014-03-01

We describe a case of human Becker muscular dystrophy (BMD)-like myopathy that was characterized by the declined stainability of dystrophin at sarcolemma in a pig and the immunostaining for dystrophin on the formalin-fixed, paraffin-embedded (FFPE) tissue. The present case was found in a meat inspection center. The pig looked appeared healthy at the ante-mortem inspection. Muscular abnormalities were detected after carcass dressing as pale, discolored skeletal muscles with prominent fat infiltrations and considered so-called "fatty muscular dystrophy". Microscopic examination revealed following characteristics: diffused fat infiltration into the skeletal muscle and degeneration and regeneration of the remaining skeletal muscle fibers. Any lesions that were suspected of neurogenic atrophy, traumatic muscular degeneration, glycogen storage disease or other porcine muscular disorders were not observed. The immunostaining for dystrophin was conducted and confirmed to be applicable on FFPE porcine muscular tissues and revealed diminished stainability of dystrophin at the sarcolemma in the present case. Based on the histological observations and immunostaining results, the present case was diagnosed with BMD-like myopathy associated with dystrophin abnormality in a pig. Although the genetic properties were not clear, the present BMD-like myopathy implied the occurrence of dystrophinopathy in pigs. To the best of our knowledge, this is the first report of a natural case of myopathy associated with dystrophin abnormalities in a pig.

Autosomal dominant myopathy: missense mutation (Glu-706 --> Lys) in the myosin heavy chain IIa gene.

PubMed

Martinsson, T; Oldfors, A; Darin, N; Berg, K; Tajsharghi, H; Kyllerman, M; Wahlstrom, J

2000-12-19

We here report on a human myopathy associated with a mutation in a fast myosin heavy chain (MyHC) gene, and also the genetic defect in a hereditary inclusion body myopathy. The disorder has previously been described in a family with an "autosomal dominant myopathy, with joint contractures, ophthalmoplegia, and rimmed vacuoles." Linkage analysis and radiation hybrid mapping showed that the gene locus (Human Genome Map locus name: IBM3) is situated in a 2-Mb region of chromosome 17p13, where also a cluster of MyHC genes is located. These include the genes encoding embryonic, IIa, IIx/d, IIb, perinatal, and extraocular MyHCs. Morphological analysis of muscle biopsies from patients from the family indicated to us that the type 2A fibers frequently were abnormal, whereas other fiber types appeared normal. This observation prompted us to investigate the MyHC-IIa gene, since MyHC-IIa is the major isoform in type 2A fibers. The complete genomic sequence for this gene was deduced by using an "in silico" strategy. The gene, found to consist of 38 exons, was subjected to a complete mutation scan in patients and controls. We identified a missense mutation, Glu-706 --> Lys, which is located in a highly conserved region of the motor domain, the so-called SH1 helix region. By conformational changes this region communicates activity at the nucleotide-binding site to the neck region, resulting in the lever arm swing. The mutation in this region is likely to result in a dysfunctional myosin, compatible with the disorder in the family.

Autism in the Son of a Woman with Mitochondrial Myopathy and Dysautonomia: A Case Report.

PubMed

Brown, Bradley D; Rais, Theodore

2015-01-01

The relationship between autism spectrum disorders and mitochondrial dysfunction, including mitochondrial myopathies and other mitochondrial diseases, is an area of ongoing research. All autism spectrum disorders are known to be heritable, via genetic and/or epigenetic mechanisms, but specific modes of inheritance are not well characterized. Nevertheless, autism spectrum disorders have been linked to many specific genes associated with mitochondrial function, especially to genes involved in mitochondrial tRNA and the electron transport chain, both particularly vulnerable to point mutations, and clinical research also supports a relationship between the two pathologies. Although only a small minority of patients with autism have a mitochondrial disease, many patients with mitochondrial myopathies have autism spectrum disorder symptoms, and these symptoms may be the presenting symptoms, which presents a diagnostic challenge for clinicians. The authors report the case of a 15-year-old boy with a history of autism spectrum disorder and neurocardiogenic syncope, admitted to the inpatient unit for self-injury, whose young mother, age 35, was discovered to suffer from mitochondrial myopathy, dysautonomia, neurocardiogenic syncope, Ehler-Danlos syndrome, and other uncommon multisystem pathologies likely related to mitochondrial dysfunction. This case illustrates the need for a high index of suspicion for mitochondrial disease in patients with autism, as they have two orders of magnitude greater risk for such diseases than the general population. The literature shows that mitochondrial disease is underdiagnosed in autism spectrum disorder patients and should not be viewed as a "zebra" (i.e., an obscure diagnosis that is made when a more common explanation is more likely).

Autism in the Son of a Woman with Mitochondrial Myopathy and Dysautonomia: A Case Report

PubMed Central

Rais, Theodore

2015-01-01

The relationship between autism spectrum disorders and mitochondrial dysfunction, including mitochondrial myopathies and other mitochondrial diseases, is an area of ongoing research. All autism spectrum disorders are known to be heritable, via genetic and/or epigenetic mechanisms, but specific modes of inheritance are not well characterized. Nevertheless, autism spectrum disorders have been linked to many specific genes associated with mitochondrial function, especially to genes involved in mitochondrial tRNA and the electron transport chain, both particularly vulnerable to point mutations, and clinical research also supports a relationship between the two pathologies. Although only a small minority of patients with autism have a mitochondrial disease, many patients with mitochondrial myopathies have autism spectrum disorder symptoms, and these symptoms may be the presenting symptoms, which presents a diagnostic challenge for clinicians. The authors report the case of a 15-year-old boy with a history of autism spectrum disorder and neurocardiogenic syncope, admitted to the inpatient unit for self-injury, whose young mother, age 35, was discovered to suffer from mitochondrial myopathy, dysautonomia, neurocardiogenic syncope, Ehler-Danlos syndrome, and other uncommon multisystem pathologies likely related to mitochondrial dysfunction. This case illustrates the need for a high index of suspicion for mitochondrial disease in patients with autism, as they have two orders of magnitude greater risk for such diseases than the general population. The literature shows that mitochondrial disease is underdiagnosed in autism spectrum disorder patients and should not be viewed as a “zebra” (i.e., an obscure diagnosis that is made when a more common explanation is more likely). PMID:26634179

The myositis autoantibody phenotypes of the juvenile idiopathic inflammatory myopathies.

PubMed

Rider, Lisa G; Shah, Mona; Mamyrova, Gulnara; Huber, Adam M; Rice, Madeline Murguia; Targoff, Ira N; Miller, Frederick W

2013-07-01

The juvenile idiopathic inflammatory myopathies (JIIM) are systemic autoimmune diseases characterized by skeletal muscle weakness, characteristic rashes, and other systemic features. In follow-up to our study defining the major clinical subgroup phenotypes of JIIM, we compared demographics, clinical features, laboratory measures, and outcomes among myositis-specific autoantibody (MSA) subgroups, as well as with published data on adult idiopathic inflammatory myopathy patients enrolled in a separate natural history study. In the present study, of 430 patients enrolled in a nationwide registry study who had serum tested for myositis autoantibodies, 374 had either a single specific MSA (n = 253) or no identified MSA (n = 121) and were the subject of the present report. Following univariate analysis, we used random forest classification and exact logistic regression modeling to compare autoantibody subgroups. Anti-p155/140 autoantibodies were the most frequent subgroup, present in 32% of patients with juvenile dermatomyositis (JDM) or overlap myositis with JDM, followed by anti-MJ autoantibodies, which were seen in 20% of JIIM patients, primarily in JDM. Other MSAs, including anti-synthetase, anti-signal recognition particle (SRP), and anti-Mi-2, were present in only 10% of JIIM patients. Features that characterized the anti-p155/140 autoantibody subgroup included Gottron papules, malar rash, "shawl-sign" rash, photosensitivity, cuticular overgrowth, lowest creatine kinase (CK) levels, and a predominantly chronic illness course. The features that differed for patients with anti-MJ antibodies included muscle cramps, dysphonia, intermediate CK levels, a high frequency of hospitalization, and a monocyclic disease course. Patients with anti-synthetase antibodies had higher frequencies of interstitial lung disease, arthralgia, and "mechanic's hands," and had an older age at diagnosis. The anti-SRP group, which had exclusively juvenile polymyositis, was characterized by high

Skeletal muscle repair in a mouse model of nemaline myopathy

PubMed Central

Sanoudou, Despina; Corbett, Mark A.; Han, Mei; Ghoddusi, Majid; Nguyen, Mai-Anh T.; Vlahovich, Nicole; Hardeman, Edna C.; Beggs, Alan H.

2012-01-01

Nemaline myopathy (NM), the most common non-dystrophic congenital myopathy, is a variably severe neuromuscular disorder for which no effective treatment is available. Although a number of genes have been identified in which mutations can cause NM, the pathogenetic mechanisms leading to the phenotypes are poorly understood. To address this question, we examined gene expression patterns in an NM mouse model carrying the human Met9Arg mutation of alpha-tropomyosin slow (Tpm3). We assessed five different skeletal muscles from affected mice, which are representative of muscles with differing fiber-type compositions, different physiological specializations and variable degrees of pathology. Although these same muscles in non-affected mice showed marked variation in patterns of gene expression, with diaphragm being the most dissimilar, the presence of the mutant protein in nemaline muscles resulted in a more similar pattern of gene expression among the muscles. This result suggests a common process or mechanism operating in nemaline muscles independent of the variable degrees of pathology. Transcriptional and protein expression data indicate the presence of a repair process and possibly delayed maturation in nemaline muscles. Markers indicative of satellite cell number, activated satellite cells and immature fibers including M-Cadherin, MyoD, desmin, Pax7 and Myf6 were elevated by western-blot analysis or immunohistochemistry. Evidence suggesting elevated focal repair was observed in nemaline muscle in electron micrographs. This analysis reveals that NM is characterized by a novel repair feature operating in multiple different muscles. PMID:16877500

Skeletal muscle repair in a mouse model of nemaline myopathy.

PubMed

Sanoudou, Despina; Corbett, Mark A; Han, Mei; Ghoddusi, Majid; Nguyen, Mai-Anh T; Vlahovich, Nicole; Hardeman, Edna C; Beggs, Alan H

2006-09-01

Nemaline myopathy (NM), the most common non-dystrophic congenital myopathy, is a variably severe neuromuscular disorder for which no effective treatment is available. Although a number of genes have been identified in which mutations can cause NM, the pathogenetic mechanisms leading to the phenotypes are poorly understood. To address this question, we examined gene expression patterns in an NM mouse model carrying the human Met9Arg mutation of alpha-tropomyosin slow (Tpm3). We assessed five different skeletal muscles from affected mice, which are representative of muscles with differing fiber-type compositions, different physiological specializations and variable degrees of pathology. Although these same muscles in non-affected mice showed marked variation in patterns of gene expression, with diaphragm being the most dissimilar, the presence of the mutant protein in nemaline muscles resulted in a more similar pattern of gene expression among the muscles. This result suggests a common process or mechanism operating in nemaline muscles independent of the variable degrees of pathology. Transcriptional and protein expression data indicate the presence of a repair process and possibly delayed maturation in nemaline muscles. Markers indicative of satellite cell number, activated satellite cells and immature fibers including M-Cadherin, MyoD, desmin, Pax7 and Myf6 were elevated by western-blot analysis or immunohistochemistry. Evidence suggesting elevated focal repair was observed in nemaline muscle in electron micrographs. This analysis reveals that NM is characterized by a novel repair feature operating in multiple different muscles.

Fibrillar Collagen Organization Associated with Broiler Wooden Breast Fibrotic Myopathy.

PubMed

Velleman, Sandra G; Clark, Daniel L; Tonniges, Jeffrey R

2017-12-01

Wooden breast (WB) is a fibrotic myopathy affecting the pectoralis major (p. major) muscle in fast-growing commercial broiler lines. Birds with WB are phenotypically detected by the palpation of a hard p. major muscle. A primary feature of WB is the fibrosis of muscle with the replacement of muscle fibers with extracellular matrix proteins, such as collagen. The ability of a tissue to be pliable and stretch is associated with the organization of collagen fibrils in the connective tissue areas surrounding muscle fiber bundles (perimysium) and around individual muscle fibers (endomysium). The objective of this study was to compare the structure and organization of fibrillar collagen by using transmission electron microscopy in two fast-growing broiler lines (Lines A and B) with incidence of WB to a slower growing broiler Line C with no phenotypically detectable WB. In Line A, the collagen fibrils were tightly packed in a parallel organization, whereas in Line B, the collagen fibrils were randomly aligned. Tightly packed collagen fibrils arranged in parallel are associated with nonpliable collagen that is highly cross-linked. This will lead to a phenotypically hard p. major muscle. In Line C, the fibrillar collagen was sparse in its distribution. Furthermore, the average collagen fibril diameter and banding D-period length were altered in Line A p. major muscles affected with WB. Taken together, these data are suggestive of different fibrotic myopathies beyond just what is classified as WB in fast-growing broiler lines.

A de novo mutation of the MYH7 gene in a large Chinese family with autosomal dominant myopathy

PubMed Central

Oda, Tetsuya; Xiong, Hui; Kobayashi, Kazuhiro; Wang, Shuo; Satake, Wataru; Jiao, Hui; Yang, Yanling; Cha, Pei-Chieng; Hayashi, Yukiko K; Nishino, Ichizo; Suzuki, Yutaka; Sugano, Sumio; Wu, Xiru; Toda, Tatsushi

2015-01-01

Laing distal myopathy (LDM) is an autosomal dominant myopathy that is caused by mutations in the slow/beta cardiac myosin heavy-chain (MYH7) gene. It has been recently reported that LDM presents with a wide range of clinical manifestations. We herein report a large Chinese family with autosomal dominant myopathy. The affected individuals in the family presented with foot drop in early childhood, along with progressive distal and proximal limb weakness. Their characteristic symptoms include scapular winging and scoliosis in the early disease phase and impairment of ambulation in the advanced phase. Although limb-girdle muscle dystrophy (LGMD) was suspected initially, a definite diagnosis could not be reached. As such, we performed linkage analysis and detected four linkage regions, namely 1q23.2-24.1, 14q11.2-12, 15q26.2-26.3 and 17q24.3. Through subsequent whole exome sequencing, we found a de novo p.K1617del causative mutation in the MYH7 gene and diagnosed the disease as LDM. This is the first LDM case in China. Our patients have severe clinical manifestations that mimic LGMD in comparison with the patients with the same mutation reported elsewhere. PMID:27081534

Role of Exercise Therapy in Prevention of Decline in Aging Muscle Function: Glucocorticoid Myopathy and Unloading

PubMed Central

Seene, Teet; Kaasik, Priit

2012-01-01

Changes in skeletal muscle quantity and quality lead to disability in the aging population. Physiological changes in aging skeletal muscle are associated with a decline in mass, strength, and inability to maintain balance. Glucocorticoids, which are in wide exploitation in various clinical scenarios, lead to the loss of the myofibrillar apparatus, changes in the extracellular matrix, and a decrease in muscle strength and motor activity, particularly in the elderly. Exercise therapy has shown to be a useful tool for the prevention of different diseases, including glucocorticoid myopathy and muscle unloading in the elderly. The purpose of the paper is to discuss the possibilities of using exercise therapy in the prevention of glucocorticoid caused myopathy and unloading in the elderly and to describe relationships between the muscle contractile apparatus and the extracellular matrix in different types of aging muscles. PMID:22778959

Abnormal tibiofemoral contact stress and its association with altered kinematics after center-center anterior cruciate ligament reconstruction: an in vitro study.

PubMed

Imhauser, Carl; Mauro, Craig; Choi, Daniel; Rosenberg, Eric; Mathew, Stephen; Nguyen, Joseph; Ma, Yan; Wickiewicz, Thomas

2013-04-01

Abnormal tibiofemoral contact stress and aberrant kinematics may influence the progression of osteoarthritis in the anterior cruciate ligament (ACL)-deficient and the ACL-reconstructed knee. However, relationships between contact stress and kinematics after ACL reconstruction are poorly understood. Therefore, we posed the following research questions: (1) How do ACL deficiency and reconstruction affect the kinematics of and contact stress in the tibiofemoral joint? (2) What kinematic differences are associated with abnormal contact stress after ACL reconstruction? Center-center ACL reconstruction will not restore knee kinematics and contact stress. Correlations will exist between abnormal contact stress and aberrant kinematics after ACL reconstruction. Controlled laboratory study. Clinical tests of anterior and rotational stability were simulated on 11 cadaveric knees using an industrial robot. Tests were conducted with the ACL intact, sectioned, and after single-bundle ACL reconstruction using a quadrupled hamstring autograft with tunnels drilled through the center of the native footprints. Kinematics were recorded during the tests. Contact stress was continuously recorded from a stress transducer fixed to the tibial plateau, and mean contact stress was calculated regionally. ACL deficiency resulted in increased mean contact stress in the posterior sectors of the medial and lateral compartments under anterior and rotational loads, respectively. Reconstruction reduced stress in these locations; however, contact stress abnormalities remained. On average, kinematics were overconstrained after ACL reconstruction (≤1.8 mm and ≤2.6° in all directions). However, combinations of overconstrained and underconstrained motions in abduction/adduction and medial-lateral translation in response to combined moments, and anterior-posterior translation, medial-lateral translation, and axial rotation in response to an anterior load were associated with abnormal mean contact

Muscle weakness in TPM3-myopathy is due to reduced Ca2+-sensitivity and impaired acto-myosin cross-bridge cycling in slow fibres

PubMed Central

Yuen, Michaela; Cooper, Sandra T.; Marston, Steve B.; Nowak, Kristen J.; McNamara, Elyshia; Mokbel, Nancy; Ilkovski, Biljana; Ravenscroft, Gianina; Rendu, John; de Winter, Josine M.; Klinge, Lars; Beggs, Alan H.; North, Kathryn N.; Ottenheijm, Coen A.C.; Clarke, Nigel F.

2015-01-01

Dominant mutations in TPM3, encoding α-tropomyosinslow, cause a congenital myopathy characterized by generalized muscle weakness. Here, we used a multidisciplinary approach to investigate the mechanism of muscle dysfunction in 12 TPM3-myopathy patients. We confirm that slow myofibre hypotrophy is a diagnostic hallmark of TPM3-myopathy, and is commonly accompanied by skewing of fibre-type ratios (either slow or fast fibre predominance). Patient muscle contained normal ratios of the three tropomyosin isoforms and normal fibre-type expression of myosins and troponins. Using 2D-PAGE, we demonstrate that mutant α-tropomyosinslow was expressed, suggesting muscle dysfunction is due to a dominant-negative effect of mutant protein on muscle contraction. Molecular modelling suggested mutant α-tropomyosinslow likely impacts actin–tropomyosin interactions and, indeed, co-sedimentation assays showed reduced binding of mutant α-tropomyosinslow (R168C) to filamentous actin. Single fibre contractility studies of patient myofibres revealed marked slow myofibre specific abnormalities. At saturating [Ca2+] (pCa 4.5), patient slow fibres produced only 63% of the contractile force produced in control slow fibres and had reduced acto-myosin cross-bridge cycling kinetics. Importantly, due to reduced Ca2+-sensitivity, at sub-saturating [Ca2+] (pCa 6, levels typically released during in vivo contraction) patient slow fibres produced only 26% of the force generated by control slow fibres. Thus, weakness in TPM3-myopathy patients can be directly attributed to reduced slow fibre force at physiological [Ca2+], and impaired acto-myosin cross-bridge cycling kinetics. Fast myofibres are spared; however, they appear to be unable to compensate for slow fibre dysfunction. Abnormal Ca2+-sensitivity in TPM3-myopathy patients suggests Ca2+-sensitizing drugs may represent a useful treatment for this condition. PMID:26307083

Muscle weakness in TPM3-myopathy is due to reduced Ca2+-sensitivity and impaired acto-myosin cross-bridge cycling in slow fibres.

PubMed

Yuen, Michaela; Cooper, Sandra T; Marston, Steve B; Nowak, Kristen J; McNamara, Elyshia; Mokbel, Nancy; Ilkovski, Biljana; Ravenscroft, Gianina; Rendu, John; de Winter, Josine M; Klinge, Lars; Beggs, Alan H; North, Kathryn N; Ottenheijm, Coen A C; Clarke, Nigel F

2015-11-15

Dominant mutations in TPM3, encoding α-tropomyosinslow, cause a congenital myopathy characterized by generalized muscle weakness. Here, we used a multidisciplinary approach to investigate the mechanism of muscle dysfunction in 12 TPM3-myopathy patients. We confirm that slow myofibre hypotrophy is a diagnostic hallmark of TPM3-myopathy, and is commonly accompanied by skewing of fibre-type ratios (either slow or fast fibre predominance). Patient muscle contained normal ratios of the three tropomyosin isoforms and normal fibre-type expression of myosins and troponins. Using 2D-PAGE, we demonstrate that mutant α-tropomyosinslow was expressed, suggesting muscle dysfunction is due to a dominant-negative effect of mutant protein on muscle contraction. Molecular modelling suggested mutant α-tropomyosinslow likely impacts actin-tropomyosin interactions and, indeed, co-sedimentation assays showed reduced binding of mutant α-tropomyosinslow (R168C) to filamentous actin. Single fibre contractility studies of patient myofibres revealed marked slow myofibre specific abnormalities. At saturating [Ca(2+)] (pCa 4.5), patient slow fibres produced only 63% of the contractile force produced in control slow fibres and had reduced acto-myosin cross-bridge cycling kinetics. Importantly, due to reduced Ca(2+)-sensitivity, at sub-saturating [Ca(2+)] (pCa 6, levels typically released during in vivo contraction) patient slow fibres produced only 26% of the force generated by control slow fibres. Thus, weakness in TPM3-myopathy patients can be directly attributed to reduced slow fibre force at physiological [Ca(2+)], and impaired acto-myosin cross-bridge cycling kinetics. Fast myofibres are spared; however, they appear to be unable to compensate for slow fibre dysfunction. Abnormal Ca(2+)-sensitivity in TPM3-myopathy patients suggests Ca(2+)-sensitizing drugs may represent a useful treatment for this condition. © The Author 2015. Published by Oxford University Press. All rights reserved

Arthroscopic pullout repair of posterior root tear of the medial meniscus: the anterior approach using medial collateral ligament pie-crusting release.

PubMed

Park, Young-Sik; Moon, Hong-Kyo; Koh, Yong-Gon; Kim, Yong-Chan; Sim, Dong-Sik; Jo, Seung-Bae; Kwon, Se-Kwang

2011-08-01

Posterior root tears of the medial meniscus are frequently encountered and should be repaired if possible to prevent osteoarthritis of the medial compartment. Various surgical techniques have been proposed to repair posterior root tears. The anterior arthroscopic approach can cause an iatrogenic chondral injury due to the narrow medial joint space. The posterior approaches might be technically unfamiliar to many surgeons because they require the establishment of a posteromedial or trans-septal portal. This paper describes the medial collateral ligament pie-crusting release technique for arthroscopic double transosseous pullout repair of posterior root tears of the medial meniscus through the anterior approach to provide the good visualization of the footprint and sufficient working space.

Myopathy-inducing mutation H40Y in ACTA1 hampers actin filament structure and function

DOE PAGES

Chan, Chun; Fan, Jun; Messer, Andrew E.; ...

2016-04-22

In humans, more than 200 missense mutations have been identified in the ACTA1 gene. The exact molecular mechanisms by which, these particular mutations become toxic and lead to muscle weakness and myopathies remain obscure. To address this, here, we performed a molecular dynamics simulation, and we used a broad range of biophysical assays to determine how the lethal and myopathy-related H40Y amino acid substitution in actin affects the structure, stability, and function of this protein. Interestingly, our results showed that H40Y severely disrupts the DNase I-binding-loop structure and actin filaments. In addition, we observed that normal and mutant actin monomersmore » are likely to form distinctive homopolymers, with mutant filaments being very stiff, and not supporting proper myosin binding. Lastly, these phenomena underlie the toxicity of H40Y and may be considered as important triggering factors for the contractile dysfunction, muscle weakness and disease phenotype seen in patients.« less

Myopathy-inducing mutation H40Y in ACTA1 hampers actin filament structure and function

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chan, Chun; Fan, Jun; Messer, Andrew E.

In humans, more than 200 missense mutations have been identified in the ACTA1 gene. The exact molecular mechanisms by which, these particular mutations become toxic and lead to muscle weakness and myopathies remain obscure. To address this, here, we performed a molecular dynamics simulation, and we used a broad range of biophysical assays to determine how the lethal and myopathy-related H40Y amino acid substitution in actin affects the structure, stability, and function of this protein. Interestingly, our results showed that H40Y severely disrupts the DNase I-binding-loop structure and actin filaments. In addition, we observed that normal and mutant actin monomersmore » are likely to form distinctive homopolymers, with mutant filaments being very stiff, and not supporting proper myosin binding. Lastly, these phenomena underlie the toxicity of H40Y and may be considered as important triggering factors for the contractile dysfunction, muscle weakness and disease phenotype seen in patients.« less

Correlation of Clinicoserologic and Pathologic Classifications of Inflammatory Myopathies

PubMed Central

Fernandez, Carla; Bardin, Nathalie; De Paula, André Maues; Salort-Campana, Emmanuelle; Benyamine, Audrey; Franques, Jérôme; Schleinitz, Nicolas; Weiller, Pierre-Jean; Pouget, Jean; Pellissier, Jean-François; Figarella-Branger, Dominique

2013-01-01

Abstract The idiopathic inflammatory myopathies (IIM) are acquired muscle diseases characterized by muscle weakness and inflammation on muscle biopsy. Clinicoserologic classifications do not take muscle histology into account to distinguish the subsets of IIM. Our objective was to determine the pathologic features of each serologic subset of IIM and to correlate muscle biopsy results with the clinicoserologic classification defined by Troyanov et al, and with the final diagnoses. We retrospectively studied a cohort of 178 patients with clinicopathologic features suggestive of IIM with the exclusion of inclusion body myositis. At the end of follow-up, 156 of 178 cases were still categorized as IIM: pure dermatomyositis, n = 44; pure polymyositis, n = 14; overlap myositis, n = 68; necrotizing autoimmune myopathy, n = 8; cancer-associated myositis, n = 18; and unclassified IIM, n = 4. The diagnosis of IIM was ruled out in the 22 remaining cases. Pathologic dermatomyositis was the most frequent histologic picture in all serologic subsets of IIM, with the exception of patients with anti-Ku or anti-SRP autoantibodies, suggesting that it supports the histologic diagnosis of pure dermatomyositis, but also myositis of connective tissue diseases and cancer-associated myositis. Unspecified myositis was the second most frequent histologic pattern. It frequently correlated with overlap myositis, especially with anti-Ku or anti-PM-Scl autoantibodies. Pathologic polymyositis was rare and more frequently correlated with myositis mimickers than true polymyositis. The current study shows that clinicoserologic and pathologic data are complementary and must be taken into account when classifying patients with IIM patients. We propose guidelines for diagnosis according to both clinicoserologic and pathologic classifications, to be used in clinical practice. PMID:23269233

19 CFR 123.24 - Sealing of conveyances or compartments.

Code of Federal Regulations, 2011 CFR

2011-04-01

... in the same manner as less than load or compartment lots; (3) Live animals identifiable by specific... of the parties in interest, in unsealed conveyances or compartments. (b) Seals to be affixed. The carrier shall affix blue in-transit seals to all openings of conveyances and compartments containing in...

Association of Common Variants in the Human Eyes Shut Ortholog, EYS, with Statin-Induced Myopathy: Evidence for Additional Functions of EYS

PubMed Central

Isackson, Paul J.; Ochs-Balcom, Heather M.; Ma, Changxing; Harley, John B.; Peltier, Wendy; Tarnopolsky, Mark; Sripathi, Naganand; Wortmann, Robert L.; Simmons, Zachary; Wilson, Jon D.; Smith, Stephen A.; Barboi, Alexandru; Fine, Edward; Baer, Alan; Baker, Steven; Kaufman, Kenneth; Cobb, Beth; Kilpatrick, Jeffrey R.; Vladutiu, Georgirene D.

2011-01-01

Introduction Of nearly 38 million people in the U.S. receiving statin therapy, 0.1–0.5% experience severe or life-threatening myopathic side effects. Methods We performed a genome-wide association study (GWAS) in patients with severe statin myopathy versus a statin-tolerant group to identify genetic susceptibility loci. Results Replication studies in independent groups of severe statin myopathy (n=190) and statintolerant controls (n=130) resulted in the identification of three SNPs, rs9342288, rs1337512 and rs3857532, in the eyes shut homolog (EYS) on chromosome 6 suggestive of an association with risk for severe statin myopathy (p=0.0003–0.0008). Analysis of EYS cDNA demonstrated that EYS gene products are complex and expressed with relative abundance in the spinal cord as well as in the retina. Discussion Structural similarities of these EYS gene products to members of the Notch signaling pathway and to agrin suggest a possible functional role in the maintenance and regeneration of the structural integrity of skeletal muscle. PMID:21826682

Association of common variants in the human eyes shut ortholog (EYS) with statin-induced myopathy: evidence for additional functions of EYS.

PubMed

Isackson, Paul J; Ochs-Balcom, Heather M; Ma, Changxing; Harley, John B; Peltier, Wendy; Tarnopolsky, Mark; Sripathi, Naganand; Wortmann, Robert L; Simmons, Zachary; Wilson, Jon D; Smith, Stephen A; Barboi, Alexandru; Fine, Edward; Baer, Alan; Baker, Steven; Kaufman, Kenneth; Cobb, Beth; Kilpatrick, Jeffrey R; Vladutiu, Georgirene D

2011-10-01

Of the nearly 38 million people in the USA who receive statin therapy, 0.1-0.5% experience severe or life-threatening myopathic side effects. We performed a genome-wide association study (GWAS) in a group of patients with severe statin myopathy versus a statin-tolerant group to identify genetic susceptibility loci. Replication studies in independent groups of severe statin myopathy (n = 190) and statin-tolerant controls (n = 130) resulted in the identification of three single-nucleotide polymorphisms (SNPs), rs9342288, rs1337512, and rs3857532, in the eyes shut homolog (EYS) on chromosome 6 suggestive of an association with risk for severe statin myopathy (P = 0.0003-0.0008). Analysis of EYS cDNA demonstrated that EYS gene products are complex and expressed with relative abundance in the spinal cord as well as in the retina. Structural similarities of these EYS gene products to members of the Notch signaling pathway and to agrin suggest a possible functional role in the maintenance and regeneration of the structural integrity of skeletal muscle. Copyright © 2011 Wiley Periodicals, Inc.

Intensive care unit acquired weakness in children: Critical illness polyneuropathy and myopathy

PubMed Central

Kukreti, Vinay; Shamim, Mosharraf; Khilnani, Praveen

2014-01-01

Background and Aims: Intensive care unit acquired weakness (ICUAW) is a common occurrence in patients who are critically ill. It is most often due to critical illness polyneuropathy (CIP) or to critical illness myopathy (CIM). ICUAW is increasingly being recognized partly as a consequence of improved survival in patients with severe sepsis and multi-organ failure, partly related to commonly used agents such as steroids and muscle relaxants. There have been occasional reports of CIP and CIM in children, but little is known about their prevalence or clinical impact in the pediatric population. This review summarizes the current understanding of pathophysiology, clinical presentation, diagnosis and treatment of CIP and CIM in general with special reference to published literature in the pediatric age group. Subjects and Methods: Studies were identified through MedLine and Embase using relevant MeSH and Key words. Both adult and pediatric studies were included. Results: ICUAW in children is a poorly described entity with unknown incidence, etiology and unclear long-term prognosis. Conclusions: Critical illness polyneuropathy and myopathy is relatively rare, but clinically significant sequelae of multifactorial origin affecting morbidity, length of intensive care unit (ICU) stay and possibly mortality in critically ill children admitted to pediatric ICU. PMID:24678152

19 CFR 123.24 - Sealing of conveyances or compartments.

Code of Federal Regulations, 2010 CFR

2010-04-01

... loads or lots in the same manner as less than load or compartment lots; (3) Live animals identifiable by... the expense of the parties in interest, in unsealed conveyances or compartments. (b) Seals to be affixed. The carrier shall affix blue in-transit seals to all openings of conveyances and compartments...

Evaluation of Subchondral Bone Marrow Lipids of Acute Anterior Cruciate Ligament (ACL)-Injured Patients at 3 T

PubMed Central

Wang, Ligong; Salibi, Nouha; Chang, Gregory; Bencardino, Jenny T.; Babb, James S.; Rokito, Andrew; Jazrawi, Laith; Sherman, Orrin; Regatte, Ravinder R.

2014-01-01

Rationale and Objectives The objectives of this study were to investigate the changes in compartment-specific subchondral bone marrow lipids of femoral–tibial bone in acute anterior cruciate ligament (ACL)-injured patients compared to that of healthy volunteers and patients with osteoarthritis (OA) (Kellgren–Lawrence [KL] grade 2–3). Materials and Methods A total of 55 subjects were recruited in the study and subdivided into three subgroups: 17 healthy controls (4 females, 13 males; mean age = 41 ± 16, age range 24–78 years), 17 patients with acute ACL injury (3 females, 14 males; mean age = 30 ± 11, age range 18–61 years), and 21 patients with KL2–3 OA (12 females, 9 males; mean age = 65 ± 12, age range 44–89 years). Routine clinical proton density–weighted fast spin echo images in sagittal (without fat saturation), axial, and coronal (fat saturation) planes were acquired on a 3 T clinical scanner for cartilage morphology using Whole-Organ Magnetic Resonance Imaging Score grading. A voxel of 10 × 10 × 10 mm3 was positioned in the medial and lateral compartments of the tibia and femur for proton magnetic resonance spectroscopy measurements using the single voxel stimulated echo acquisition mode pulse sequence. All proton magnetic resonance data were processed with Java-based magnetic resonance user interface. Wilcoxon rank sum test and mixed model two-way analysis of variance were performed to determine significant differences between different compartments and examine the effect of ACL injury, OA grade and compartment, and their interactions. Results The index of unsaturation in lateral tibial compartment in ACL-injured patients was significantly higher (P < .05) than all compartments except lateral femoral in patients with KL2–3 OA. Significantly lower values (P < .05) were also identified in saturated lipids at 2.03 ppm in all compartments in ACL-injured patients than those of all compartments in patients with KL2–3 OA. Conclusions The

Organophosphate-induced intermediate syndrome: aetiology and relationships with myopathy.

PubMed

Karalliedde, Lakshman; Baker, David; Marrs, Timothy C

2006-01-01

-15 days and even up to 21 days. Weaning from ventilatory care is best carried out in stages, with provision of continuous positive airway pressure prior to complete weaning. Continuous and close monitoring of respiratory function (arterial oxygen saturation, partial pressure of oxygen in arterial blood, partial pressure of carbon dioxide in arterial blood) and acid-base status are an absolute necessity. Prophylactic antibiotics are usually not required unless there has been evidence of aspiration of material into the lungs. Close monitoring of fluid and electrolyte balance is mandatory in view of the profuse offensive diarrhoea that most patients develop. Maintenance of nutrition, physiotherapy, prevention of bed sores and other routine measures to minimise discomfort during ventilatory care are necessary. Recovery from the intermediate syndrome is normally complete and without any sequelae. The usefulness of oximes during the IMS remains uncertain. In animal experiments, very early administration of oximes has prevented the occurrence of myopathy. There are reports from developed countries where administration of oximes at recommended doses and within 2 hours of ingestion of OP insecticide did not prevent the onset of the IMS. Controlled randomised clinical studies are necessary to evaluate the efficacy of oximes in combating the IMS. Electrophysiological studies following OP poisoning have revealed three characteristic phenomena: (i) repetitive firing following a single stimulus; (ii) gradual reduction in twitch height or compound muscle action potential followed by an increase with repetitive stimulation (the 'decrement-increment response'); and (iii) continued reduction in twitch height or compound muscle action potential with repetitive simulation ('decrementing response'). Of these, the decrementing response is the most frequent finding during the IMS, whilst repetitive firing is observed during the acute cholinergic syndrome. The distribution of the weakness in

49 CFR 179.220-9 - Compartment tanks.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 49 Transportation 3 2014-10-01 2014-10-01 false Compartment tanks. 179.220-9 Section 179.220-9... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) SPECIFICATIONS FOR TANK CARS Specifications for Non-Pressure Tank Car Tanks (Classes DOT-111AW and 115AW) § 179.220-9 Compartment tanks. (a) The inner...

49 CFR 179.220-9 - Compartment tanks.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 2 2010-10-01 2010-10-01 false Compartment tanks. 179.220-9 Section 179.220-9... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION HAZARDOUS MATERIALS REGULATIONS SPECIFICATIONS FOR TANK CARS Specifications for Non-Pressure Tank Car Tanks (Classes DOT-111AW and 115AW) § 179.220-9 Compartment tanks. (a...

49 CFR 179.220-9 - Compartment tanks.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 49 Transportation 3 2013-10-01 2013-10-01 false Compartment tanks. 179.220-9 Section 179.220-9... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) SPECIFICATIONS FOR TANK CARS Specifications for Non-Pressure Tank Car Tanks (Classes DOT-111AW and 115AW) § 179.220-9 Compartment tanks. (a) The inner...

14 CFR 25.365 - Pressurized compartment loads.

Code of Federal Regulations, 2010 CFR

2010-01-01

... Pressurized compartment loads. For airplanes with one or more pressurized compartments the following apply: (a... differential loads from zero up to the maximum relief valve setting. (b) The external pressure distribution in... zero up to the maximum allowed during landing. (d) The airplane structure must be designed to be able...

Equine atypical myopathy caused by hypoglycin A intoxication associated with ingestion of sycamore maple tree seeds.

PubMed

Żuraw, A; Dietert, K; Kühnel, S; Sander, J; Klopfleisch, R

2016-07-01

Evidence suggest there is a link between equine atypical myopathy (EAM) and ingestion of sycamore maple tree seeds. To further evaluate the hypothesis that the ingestion of hypoglycin A (HGA) containing sycamore maple tree seeds causes acquired multiple acyl-CoA dehydrogenase deficiency and might be associated with the clinical and pathological signs of EAM. Case report. Necropsy and histopathology, using hematoxylin and eosin and Sudan III stains, were performed on a 2.5-year-old mare that died following the development of clinical signs of progressive muscle stiffness and recumbency. Prior to death, the animal ingested sycamore maple tree seeds (Acer pseudoplatanus). Detection of metabolites in blood and urine obtained post mortem was performed by rapid ultra-performance liquid chromatography-tandem mass spectrometry. Data from this case were compared with 3 geldings with no clinical history of myopathy. Macroscopic examination revealed fragments of maple tree seeds in the stomach and severe myopathy of several muscle groups including Mm. intercostales, deltoidei and trapezii. Histologically, the affected muscles showed severe, acute rhabdomyolysis with extensive accumulation of finely dispersed fat droplets in the cytoplasm of degenerated skeletal muscle cells not present in controls. Urine and serum concentrations of several acyl carnitines and acyl glycines were increased, and both contained metabolites of HGA, a toxic amino acid present in sycamore maple tree seeds. The study supports the hypothesis that ingestion of HGA-containing maple tree seeds may cause EAM due to acquired multiple acyl-CoA dehydrogenase deficiency. © 2015 EVJ Ltd.

46 CFR 174.075 - Compartments assumed flooded: general.

Code of Federal Regulations, 2012 CFR

2012-10-01

... Units § 174.075 Compartments assumed flooded: general. The individual flooding of each of the... § 174.065 (a). Simultaneous flooding of more than one compartment must be assumed only when indicated in...

46 CFR 174.075 - Compartments assumed flooded: general.

Code of Federal Regulations, 2011 CFR

2011-10-01

... Units § 174.075 Compartments assumed flooded: general. The individual flooding of each of the... § 174.065 (a). Simultaneous flooding of more than one compartment must be assumed only when indicated in...

46 CFR 174.075 - Compartments assumed flooded: general.

Code of Federal Regulations, 2014 CFR

2014-10-01

... Units § 174.075 Compartments assumed flooded: general. The individual flooding of each of the... § 174.065 (a). Simultaneous flooding of more than one compartment must be assumed only when indicated in...

[Fenofibrate--induced myopathy in a patient with undiagnosed hypothyroidism--case report and a review of the literature].

PubMed

Lukjanowicz, Małgorzata; Trzcińska-Butkiewicz, Beata; Brzosko, Marek

2006-01-01

Hypothyroidism is one of the common causes of the secondary hypercholesterolemia. The prevalence of hypothyroidism in the general population is estimated to be as high as about 1.5%. Frequency of the hypothyroidism in patients with hyperlipidemia is high, and can be observed in 4.2-10% in different populations. Most commonly, there is no need to treat the hypothyroid patients with the hypolipidemic drugs. Substitution treatment with the thyroid hormones usually results in either normalization or significant decreasing of the lipid levels. Hypothyroidism with symptoms of involvement of skeletal muscles is referred as to hypothyroid myopathy in English literature, and can be present in 30-80% patients with deficiency of the thyroid hormones. Hypothyroidism is a risk factor of developing of toxic injury of muscles, what is thought to be related to hypolipidemic drug intake. We report a case of a patient with undiagnosed hypothyroidism with muscle involvement manifestation, who was treated with fenofibrate due to accidentally diagnosed hypercholesterolemia. Hypolipidemic management resulted in rapid exacerbation of previously moderate myopathy. High concentrations of muscle enzymes and moderate increasing of creatinine concentration were detected. Improvement was observed after discontinuation of fenofibrate administration, but muscle symptoms and elevation of muscle enzymes and creatinine persisted. After administration of levothyroxin, muscle weakness and laboratory abnormalities were observed no longer. After several months of follow-up we believe that treatment with fenofibrate in our patient was complicated with muscle tissue damage and exacerbated symptoms of myopathy originally related to decompensated hypothyroidism.

Activating mutations in STIM1 and ORAI1 cause overlapping syndromes of tubular myopathy and congenital miosis

PubMed Central

Nesin, Vasyl; Wiley, Graham; Kousi, Maria; Ong, E-Ching; Lehmann, Thomas; Nicholl, David J.; Suri, Mohnish; Shahrizaila, Nortina; Katsanis, Nicholas; Gaffney, Patrick M.; Wierenga, Klaas J.; Tsiokas, Leonidas

2014-01-01

Signaling through the store-operated Ca2+ release-activated Ca2+ (CRAC) channel regulates critical cellular functions, including gene expression, cell growth and differentiation, and Ca2+ homeostasis. Loss-of-function mutations in the CRAC channel pore-forming protein ORAI1 or the Ca2+ sensing protein stromal interaction molecule 1 (STIM1) result in severe immune dysfunction and nonprogressive myopathy. Here, we identify gain-of-function mutations in the cytoplasmic domain of STIM1 (p.R304W) associated with thrombocytopenia, bleeding diathesis, miosis, and tubular myopathy in patients with Stormorken syndrome, and in ORAI1 (p.P245L), associated with a Stormorken-like syndrome of congenital miosis and tubular aggregate myopathy but without hematological abnormalities. Heterologous expression of STIM1 p.R304W results in constitutive activation of the CRAC channel in vitro, and spontaneous bleeding accompanied by reduced numbers of thrombocytes in zebrafish embryos, recapitulating key aspects of Stormorken syndrome. p.P245L in ORAI1 does not make a constitutively active CRAC channel, but suppresses the slow Ca2+-dependent inactivation of the CRAC channel, thus also functioning as a gain-of-function mutation. These data expand our understanding of the phenotypic spectrum of dysregulated CRAC channel signaling, advance our knowledge of the molecular function of the CRAC channel, and suggest new therapies aiming at attenuating store-operated Ca2+ entry in the treatment of patients with Stormorken syndrome and related pathologic conditions. PMID:24591628

Hip joint biomechanics in those with and without post-traumatic knee osteoarthritis after anterior cruciate ligament injury.

PubMed

Wellsandt, E; Zeni, J A; Axe, M J; Snyder-Mackler, L

2017-12-01

Anterior cruciate ligament injury results in altered kinematics and kinetics in the knee and hip joints that persist despite surgical reconstruction and rehabilitation. Abnormal movement patterns and a history of osteoarthritis are risk factors for articular cartilage degeneration in additional joints. The purpose of this study was to determine if hip joint biomechanics early after anterior cruciate ligament injury and reconstruction differ between patients with and without post-traumatic knee osteoarthritis 5years after reconstruction. The study's rationale was that individuals who develop knee osteoarthritis after anterior cruciate ligament injury may also demonstrate large alterations in hip joint biomechanics. Nineteen athletes with anterior cruciate ligament injury completed standard gait analysis before (baseline) and after (post-training) extended pre-operative rehabilitation and at 6months, 1year, and 2years after reconstruction. Weightbearing knee radiographs were completed 5years after reconstruction to identify medial compartment osteoarthritis. Five of 19 patients had knee osteoarthritis at 5years after anterior cruciate ligament reconstruction. Patients with knee osteoarthritis at 5years walked with smaller sagittal plane hip angles (P: 0.043) and lower sagittal (P: 0.021) and frontal plane (P: 0.042) external hip moments in the injured limb before and after reconstruction compared to those without knee osteoarthritis. The current findings suggest hip joint biomechanics may be altered in patients who develop post-traumatic knee osteoarthritis. Further study is needed to confirm whether the risk of non-traumatic hip pathology is increased after anterior cruciate ligament injury and if hip joint biomechanics influence its development. Copyright © 2017 Elsevier Ltd. All rights reserved.

Abdominal Compartment Syndrome After Hip Arthroscopy

DTIC Science & Technology

2010-01-01

00-00-2010 to 00-00-2010 4. TITLE AND SUBTITLE Abdominal Compartment Syndrome After Hip Arthroscopy 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c...Hip Arthroscopy Justin Fowler, M.D., and Brett D. Owens, M.D. Abstract: As hip arthroscopy becomes a more common procedure, more complications may occur...We present a case of abdominal compartment syndrome resulting from fluid extravasation in a 42-year-old man who underwent routine hip arthroscopy

Internal anal sphincter myopathy causing proctalgia fugax and constipation: further clinical and radiological characterization in a patient.

PubMed

Guy, R J; Kamm, M A; Martin, J E

1997-02-01

We report a case of a distinctive familial internal anal sphincter myopathy with unique histological and radiological features. A 67-year-old woman presented with a 20-year history of proctalgia fugax and outlet obstruction; other family members were similarly affected. Computed tomograpy and magnetic resonance imaging demonstrated a grossly hypertrophied internal anal sphincter. Strip myectomy of the sphincter was carried out with improvement in evacuation but little relief of proctalgia. Further relief of symptoms was obtained using oral and transdermal nitrates and a calcium antagonist. Histological examination of the excised muscle revealed hypertrophy and an abnormal arrangement of fibres in whorls; many fibres contained vacuoles with inclusion bodies positive for periodic acid-Schiff. This description of a specific anal sphincter myopathy illustrates the potential importance of histopathological studies of smooth muscle in functional disorders of the gut.

Influence of the fire location and the size of a compartment on the heat and smoke flow out of the compartment

NASA Astrophysics Data System (ADS)

Wegrzyński, Wojciech; Konecki, Marek

2018-01-01

This paper presents results of CFD and scale modelling of the flow of heat and smoke inside and outside of a compartment, in case of fire. Estimation of mass flow out of a compartment is critical, as it is the boundary condition in further considerations related to the exhaust of the smoke from a building - also in analysis related to the performance of natural ventilation in wind conditions. Both locations of the fire and the size of compartment were addressed as possible variables, which influence the mass and the temperature of smoke that leaves the room engulfed in fire. Results of the study show small to none influence of both size of the compartment and the location of the fire, on the mass flow of smoke exiting the room. On the same time, both of these parameters influence the temperature of the smoke - in larger compartments lower average temperatures of the smoke layer, but higher maximum values were observed. Results of this study may be useful also in the determination of the worst case scenarios for structural analysis, or in the investiga tion of the spread of fire through the compartment. Based on the results presented in this study, researchers can attribute an expert judgement choice of fire location, as a single scenario that is representative of a larger amount of probable scenarios.

Image-guided spatial localization of heterogeneous compartments for magnetic resonance

PubMed Central

An, Li; Shen, Jun

2015-01-01

Purpose: Image-guided localization SPectral Localization Achieved by Sensitivity Heterogeneity (SPLASH) allows rapid measurement of signals from irregularly shaped anatomical compartments without using phase encoding gradients. Here, the authors propose a novel method to address the issue of heterogeneous signal distribution within the localized compartments. Methods: Each compartment was subdivided into multiple subcompartments and their spectra were solved by Tikhonov regularization to enforce smoothness within each compartment. The spectrum of a given compartment was generated by combining the spectra of the components of that compartment. The proposed method was first tested using Monte Carlo simulations and then applied to reconstructing in vivo spectra from irregularly shaped ischemic stroke and normal tissue compartments. Results: Monte Carlo simulations demonstrate that the proposed regularized SPLASH method significantly reduces localization and metabolite quantification errors. In vivo results show that the intracompartment regularization results in ∼40% reduction of error in metabolite quantification. Conclusions: The proposed method significantly reduces localization errors and metabolite quantification errors caused by intracompartment heterogeneous signal distribution. PMID:26328977

Increased capillaries in mitochondrial myopathy: implications for the regulation of oxygen delivery.

PubMed

Taivassalo, Tanja; Ayyad, Karen; Haller, Ronald G

2012-01-01

Human skeletal muscle respiratory chain defects restrict the ability of working muscle to extract oxygen from blood, and result in a hyperkinetic circulation during exercise in which oxygen delivery is excessive relative to oxygen uptake and oxygen levels within contracting muscle are abnormally high. To investigate the role of the muscle microcirculation in this anomalous circulatory response and possible implications for the regulation of muscle angiogenesis, we assessed muscle oxidative capacity during cycle exercise and determined capillary levels and distribution and vascular endothelial growth factor expression in quadriceps muscle biopsies in patients with mitochondrial myopathy attributable to heteroplasmic mitochondrial DNA mutations. We found that in patients with mitochondrial myopathy, muscle capillary levels were twice that of sedentary healthy subjects (3.0 ± 0.9% compared with 1.4 ± 0.3%, P < 0.001) despite the fact that oxygen utilization during peak cycle exercise was half that of control subjects (11.1 ± 4.0 ml/kg/min compared with 20.7 ± 7.9 ml/kg/min, P < 0.01); that capillary area was greatest in patients with the most severe muscle oxidative defects and was more than two times higher around muscle fibre segments with defective (i.e. cytochrome oxidase negative/succinic dehydrogenase-positive or 'ragged-red' fibres) compared with more preserved respiratory chain function; and that vascular endothelial growth factor expression paralleled capillary distribution. The increased muscle capillary levels in patients correlated directly (r(2) = 0.68, P < 0.05) with the severity of the mismatch between systemic oxygen delivery (cardiac output) and oxygen utilization during cycle exercise. Our results suggest that capillary growth is increased as a result of impaired muscle oxidative phosphorylation in mitochondrial myopathy, thus promoting increased blood flow to respiration-incompetent muscle fibres and a

The Myositis Autoantibody Phenotypes of the Juvenile Idiopathic Inflammatory Myopathies

PubMed Central

Shah, Mona; Mamyrova, Gulnara; Huber, Adam M.; Rice, Madeline Murguia; Targoff, Ira N.; Miller, Frederick W.

2013-01-01

Abstract The juvenile idiopathic inflammatory myopathies (JIIM) are systemic autoimmune diseases characterized by skeletal muscle weakness, characteristic rashes, and other systemic features. In follow-up to our study defining the major clinical subgroup phenotypes of JIIM, we compared demographics, clinical features, laboratory measures, and outcomes among myositis-specific autoantibody (MSA) subgroups, as well as with published data on adult idiopathic inflammatory myopathy patients enrolled in a separate natural history study. In the present study, of 430 patients enrolled in a nationwide registry study who had serum tested for myositis autoantibodies, 374 had either a single specific MSA (n = 253) or no identified MSA (n = 121) and were the subject of the present report. Following univariate analysis, we used random forest classification and exact logistic regression modeling to compare autoantibody subgroups. Anti-p155/140 autoantibodies were the most frequent subgroup, present in 32% of patients with juvenile dermatomyositis (JDM) or overlap myositis with JDM, followed by anti-MJ autoantibodies, which were seen in 20% of JIIM patients, primarily in JDM. Other MSAs, including anti-synthetase, anti-signal recognition particle (SRP), and anti-Mi-2, were present in only 10% of JIIM patients. Features that characterized the anti-p155/140 autoantibody subgroup included Gottron papules, malar rash, “shawl-sign” rash, photosensitivity, cuticular overgrowth, lowest creatine kinase (CK) levels, and a predominantly chronic illness course. The features that differed for patients with anti-MJ antibodies included muscle cramps, dysphonia, intermediate CK levels, a high frequency of hospitalization, and a monocyclic disease course. Patients with anti-synthetase antibodies had higher frequencies of interstitial lung disease, arthralgia, and “mechanic’s hands,” and had an older age at diagnosis. The anti-SRP group, which had exclusively juvenile polymyositis, was

Incidence and treatment of intra-articular lesions associated with anterior cruciate ligament tears.

PubMed

Todor, Adrian; Nistor, Dan; Buescu, Cristian; Pojar, Adina; Lucaciu, Dan

2014-01-01

The aim of the study is to retrospectively review the patients admitted and treated in the "Alexandru Rădulescu" Orthopedics and Traumatology Clinic, Cluj-Napoca for an anterior cruciate ligament tear over a 2-year period and document the intra-articular lesions found at arthroscopy as well as the treatment used for these associated lesions. The case records of 88 patients operated for anterior cruciate ligament tear over a period of 2 years were reviewed. There were 67 males and 21 females with a mean age of 28.9 years, ranging from 14 to 49 years. After recording the patient demographics, we documented all the intra-articular lesions found during knee arthroscopy, as well as all procedures undertaken concomitant with the ACL reconstruction. 50 of the 88 patients (56.8%) had associated intra-articular lesions at the time of anterior cruciate ligament reconstruction. The most common injury found was a meniscus tear, 48 patients (54.5%) had a meniscal pathology at the time of ligament reconstruction, medial meniscus being the most frequent injured one, found in 37 patients. Meniscectomy and meniscus suture were the procedures performed for these lesions, meniscectomy being more frequent. Chondral defects were the next associated injuries found with an incidence of 15.9% of the cases. The medial side of the knee was the most common site of chondral pathology. ACL tears are frequently associated with other intra-articular lesions, especially medial meniscus tears and chondral defects affecting the medial compartment. Such pathology most often needs surgical attention during the anterior cruciate ligament reconstruction.

TNNT1 nemaline myopathy: Natural history and therapeutic frontier.

PubMed

Fox, Michael D; Carson, Vincent J; Feng, Han-Zhong; Lawlor, Michael W; Gray, John T; Brigatti, Karlla W; Jin, J-P; Strauss, Kevin A

2018-06-20

We describe the natural history of 'Amish' nemaline myopathy (ANM), an infantile-onset, lethal disease linked to a pathogenic c.505G>T nonsense mutation of TNNT1, which encodes the slow fiber isoform of troponin T (TNNT1; a.k.a TnT). The TNNT1 c.505G>T allele has a carrier frequency of 6.5% within Old Order Amish settlements of North America. We collected natural history data for 106 ANM patients born between 1923 and 2017. Over the last two decades, mean age of molecular diagnosis was 16 ± 27 days. TNNT1 c.505G>T homozygotes were normal weight at birth but failed to thrive by age 9 months. Presenting neonatal signs were axial hypotonia, hip and shoulder stiffness, and tremors, followed by progressive muscle weakness, atrophy, and contractures. Affected children developed thoracic rigidity, pectus carinatum, and restrictive lung disease during infancy, and all succumbed to respiratory failure by 6 years of age (median survival 18 months, range 0.2-66 months). Muscle histology from two affected children showed marked fiber size variation due to both type 1 myofiber smallness (hypotrophy) and type 2 fiber hypertrophy, with evidence of nemaline rods, myofibrillar disarray, and vacuolar pathology in both fiber types. The truncated slow TNNT1 (TnT) fragment (p.Glu180Ter) was undetectable in ANM muscle, reflecting its rapid proteolysis and clearance from sarcoplasm. Similar functional and histological phenotypes were observed in other human cohorts and two transgenic murine models (Tnnt1-/- and Tnnt1 c.505G>T). These findings have implications for emerging molecular therapies, including the suitably of TNNT1 gene replacement for newborns with ANM or other TNNT1-associated myopathies.

Acute compartment syndrome complicating an intramuscular haemangiosarcoma in a dog.

PubMed

Radke, H; Spreng, D; Sigrist, N; Lang, J; Bornand, V; Schawalder, P

2006-05-01

Acute compartment syndrome in dogs is a rare complication of muscle trauma, but it has not been previously reported as a consequence of neoplasia in dogs. This case report describes the occurrence of a compartment syndrome of the femoral compartment in an 11-year-old, male, mixed-breed dog caused by acute bleeding of an intramuscular haemangiosarcoma. The compartment syndrome was relieved by immediate fasciotomy. The dog was euthanased following acute recurrence of clinical signs seven weeks after surgery.

Chronic Exertional Compartment Syndrome

MedlinePlus

... Sometimes chronic exertional compartment syndrome is mistaken for shin splints, a more common cause of leg pain in ... such as running. If you think you have shin splints but they don't get better with self- ...

Coping with the diagnostic complexities of the compartment syndrome

NASA Technical Reports Server (NTRS)

Mubarak, S. J.; Hargens, A. R.; Karkal, S. S.

1988-01-01

This review recognizes that, given the various complexities associated with the condition, no pat answers can be given to fit every patient with the compartment syndrome. The authors first give a definition of the syndrome, together with a brief account of how this self-perpetuating pathologic cycle is triggered. Next, they delineate specific anatomical features of compartments that are likely to be involved, and follow this with an inventory of symptoms and signs to look for in suspected cases. After sorting out the entities that can mimic the compartment syndrome, the authors describe three essential techniques of measuring tissue pressure, which can prove invaluable in diagnosing the compartment syndrome.

Muscle MRI in neutral lipid storage disease with myopathy carrying mutation c.187+1G>A.

PubMed

Xu, Chunxiao; Zhao, Yawen; Liu, Jing; Zhang, Wei; Wang, Zhaoxia; Yuan, Yun

2015-06-01

We describe the clinical and muscle MRI changes in 2 siblings with neutral lipid storage disease with myopathy (NLSDM) carrying the mutation c.187+1G>A. Peripheral blood smears, genetic tests, and muscle biopsies were performed. Thigh MRI was performed to observe fatty replacement, muscle edema, and muscle bulk from axial sections. Both siblings had similar fatty infiltration and edema. T1-weighted images of the gluteus maximus, adductor magnus, semitendinosus, and semimembranosus revealed marked and diffuse fatty infiltration. There was asymmetric involvement in biceps femoris and quadriceps. There was extensive fatty infiltration in the quadriceps, except for the rectus femoris. Gracilis and sartorius were relatively spared. Thigh muscle volume was decreased, while the gracilis and sartorius appeared to show compensatory hypertrophy. Compared with previous reports in NLSDM, MRI changes in this myopathy tended to be more severe. Asymmetry and relatively selective fatty infiltration were characteristics. © 2014 Wiley Periodicals, Inc.

Combined unicompartmental knee arthroplasty and anterior cruciate ligament reconstruction in knees with osteoarthritis and deficient anterior cruciate ligament.

PubMed

Tian, Shaoqi; Wang, Bin; Wang, Yuanhe; Ha, Chengzhi; Liu, Lun; Sun, Kang

2016-08-05

Relative young and more active patients with osteoarthritis (OA) of the isolated medial femorotibial compartment in conjunction with anterior cruciate ligament (ACL) deficiency are difficult to treat. The aim of this study was to explore the early clinical outcomes of combined Oxford unicompartmental knee arthroplasty (UKA) and ACL reconstruction for the patients presenting ACL deficiency and isolated OA of the medial compartment. Twenty-eight patients were included into the study. All patients were treated by combined Oxford UKA and ACL reconstruction. Plain radiographs in the antero-posterior and lateral view and long-leg standing radiographs were routinely performed prior to and after surgery. Stress radiographs in valgus were additionally available in order to verify the well-preserved lateral compartment. The varus deformity of the knee prior to surgery and the valgus degree after surgery, the posterior slope of the tibial component and the range of motion (ROM) of the knee after surgery were measured and recorded. Clinical evaluations include Oxford Knee Score (OKS), Knee Society Score (KSS-clinical score; KSS-function score) and Tegner activity score. All the patients were followed up for 52 ± 8 months. The leg alignment showed 3.1 ± 0.6° of varus deformity prior to surgery and 4.0 ± 0.7° of valgus after surgery. The OKS, KSS and Tegner activity score improved significantly after surgery (P < 0.05). The mean ROM of the operated knee was 123.5 ± 2.8° at the last follow-up. The posterior slope of the tibial component was 3.9 ± 1.2°. A significant correlation was found between them according to the Pearson's correlation (r = 0.39, P = 0.03). There were 2 patients (7 %) with the complication of mobile bearing dislocation, and a second operation of replacing a thicker mobile bearing was performed for them. The early clinical data have shown that combined surgery of UKA and ACL reconstruction has revealed promising

Endurance training and detraining in mitochondrial myopathies due to single large-scale mtDNA deletions.

PubMed

Taivassalo, Tanja; Gardner, Julie L; Taylor, Robert W; Schaefer, Andrew M; Newman, Jane; Barron, Martin J; Haller, Ronald G; Turnbull, Douglass M

2006-12-01

At present there are limited therapeutic interventions for patients with mitochondrial myopathies. Exercise training has been suggested as an approach to improve physical capacity and quality of life but it is uncertain whether it offers a safe and effective treatment for patients with heteroplasmic mitochondrial DNA (mtDNA) mutations. The objectives of this study were to assess the effects of exercise training and detraining in eight patients with single, large-scale mtDNA deletions to determine: (i) the efficacy and safety of endurance training (14 weeks) in this patient population; (ii) to determine the effect of more prolonged (total of 28 weeks) exercise training upon muscle and cardiovascular function and (iii) to evaluate the effect of discontinued training (14 weeks) upon muscle and cardiovascular function. Our results show that: (i) 14 weeks of exercise training significantly improved tolerance of submaximal exercise and peak capacity for work, oxygen utilization and skeletal muscle oxygen extraction with no change in the level of deleted mtDNA; (ii) continued training for an additional 14 weeks maintained these beneficial adaptations; (iii) the cessation of training (detraining) resulted in loss of physiological adaptation to baseline capacity with no overall change in mutation load. Patients' self assessment of quality of life as measured by the SF-36 questionnaire improved with training and declined with detraining. Whilst our findings of beneficial effects of training on physiological outcome and quality of life without increases in the percentage of deleted mtDNA are encouraging, we did not observe changes in mtDNA copy number. Therefore there remains a need for longer term studies to confirm that endurance exercise is a safe and effective treatment for patients with mitochondrial myopathies. The effects of detraining clearly implicate physical inactivity as an important mechanism in reducing exercise capacity and quality of life in patients with

Contamination control of the space shuttle Orbiter crew compartment

NASA Technical Reports Server (NTRS)

Bartelson, Donald W.

1986-01-01

Effective contamination control as applied to manned space flight environments is a discipline characterized and controlled by many parameters. An introduction is given to issues involving Orbiter crew compartment contamination control. An effective ground processing contamination control program is an essential building block to a successful shuttle mission. Personnel are required to don cleanroom-grade clothing ensembles before entering the crew compartment and follow cleanroom rules and regulations. Prior to crew compartment entry, materials and equipment must be checked by an orbiter integrity clerk stationed outside the white-room entrance for compliance to program requirements. Analysis and source identification of crew compartment debris studies have been going on for two years. The objective of these studies is to determine and identify particulate generating materials and activities in the crew compartment. Results show a wide spectrum of many different types of materials. When source identification is made, corrective action is implemented to minimize or curtail further contaminate generation.

Mice Lacking TR4 Nuclear Receptor Develop Mitochondrial Myopathy with Deficiency in Complex I

PubMed Central

Liu, Su; Lee, Yi-Fen; Chou, Samuel; Uno, Hideo; Li, Gonghui; Brookes, Paul; Massett, Michael P.; Wu, Qiao; Chen, Lu-Min

2011-01-01

The estimated incidence of mitochondrial diseases in humans is approximately 1:5000 to 1:10,000, whereas the molecular mechanisms for more than 50% of human mitochondrial disease cases still remain unclear. Here we report that mice lacking testicular nuclear receptor 4 (TR4−/−) suffered mitochondrial myopathy, and histological examination of TR4−/− soleus muscle revealed abnormal mitochondrial accumulation. In addition, increased serum lactate levels, decreased mitochondrial ATP production, and decreased electron transport chain complex I activity were found in TR4−/− mice. Restoration of TR4 into TR4−/− myoblasts rescued mitochondrial ATP generation capacity and complex I activity. Further real-time PCR quantification and promoter studies found TR4 could modulate complex I activity via transcriptionally regulating the complex I assembly factor NDUFAF1, and restoration of NDUFAF1 level in TR4−/− myoblasts increased mitochondrial ATP generation capacity and complex I activity. Together, these results suggest that TR4 plays vital roles in mitochondrial function, which may help us to better understand the pathogenesis of mitochondrial myopathy, and targeting TR4 via its ligands/activators may allow us to develop better therapeutic approaches. PMID:21622535

Turbofan Engine Core Compartment Vent Aerodynamic Configuration Development Methodology

NASA Technical Reports Server (NTRS)

Hebert, Leonard J.

2006-01-01

This paper presents an overview of the design methodology used in the development of the aerodynamic configuration of the nacelle core compartment vent for a typical Boeing commercial airplane together with design challenges for future design efforts. Core compartment vents exhaust engine subsystem flows from the space contained between the engine case and the nacelle of an airplane propulsion system. These subsystem flows typically consist of precooler, oil cooler, turbine case cooling, compartment cooling and nacelle leakage air. The design of core compartment vents is challenging due to stringent design requirements, mass flow sensitivity of the system to small changes in vent exit pressure ratio, and the need to maximize overall exhaust system performance at cruise conditions.

Modern Therapies for Idiopathic Inflammatory Myopathies (IIMs): Role of Biologics

PubMed Central

Moghadam-Kia, Siamak; Oddis, Chester V.

2016-01-01

Despite the lack of placebo-controlled trials, glucocorticoids are considered the mainstay of initial treatment for idiopathic inflammatory myopathy (IIMs) and myositis-associated ILD (MA-ILD). Glucocorticoid-sparing agents are often given concomitantly with other immunosuppressive agents, particularly in patients with moderate or severe disease. As treatment of refractory cases of idiopathic inflammatory myopathies has been challenging, there is growing interest in evaluating newer therapies including biologics that target various pathways involved in the pathogenesis of IIMs. In a large clinical trial of rituximab in adult and juvenile myositis, the primary outcome was not met, but the definition of improvement was met by most of this refractory group of myositis patients. Rituximab use was also associated with a significant glucocorticoid-sparing effect. Intravenous immune globulin (IVIg) can be used for refractory IIMs or those with severe dysphagia or concomitant infections. Anti-tumor necrosis factor (anti-TNF) utility in IIMs is generally limited by previous negative studies along with recent reports suggesting their potential for inducing myositis. Further research is required to assess the role of new therapies such as tocilizumab (anti-IL6), ACTH gel, sifalimumab (anti-IFNα), and abatacept (inhibition of T cell co-stimulation) given their biological plausibility and encouraging small case series results. Other potential novel therapies include alemtuzumab (a humanized monoclonal antibody which binds CD52 on B and T lymphocytes), fingolimod (a sphingosine 1-phosphate receptor modulator that traps T lymphocytes in the lymphoid organs), eculizumab, and basiliximab. The future investigations in IIMs will depend on well-designed controlled clinical trials using validated consensus core set measures and improvements in myositis classification schemes based on serologic and histopathologic features. PMID:26767526

Performance, meat quality, and pectoral myopathies of broilers fed either corn or sorghum based diets supplemented with guanidinoacetic acid.

PubMed

Córdova-Noboa, H A; Oviedo-Rondón, E O; Sarsour, A H; Barnes, J; Ferzola, P; Rademacher-Heilshorn, M; Braun, U

2018-04-13

One experiment was conducted to evaluate the effects of guanidinoacetic acid (GAA) supplementation in broilers fed corn or sorghum-based diets on live performance, carcass and cut up yields, meat quality, and pectoral myopathies. The treatments consisted of corn or sorghum-based diets with or without the addition of GAA (600 g/ton). A total of 800 one-d-old male Ross 708 broiler chicks were randomly placed in 40 floor pens with 10 replicates (20 birds per pen) per each of the four treatments. At hatch, 14, 35, and 50 d, BW and feed intake were recorded. BW gain and FCR were calculated at the end of each phase. Four broilers per pen were selected and slaughtered at 51d and 55d of age to determine carcass and cut up yields, meat quality and myopathies (spaghetti muscle, white striping, and wooden breast) severity in the Pectoralis major. Data were analyzed as a randomized complete block design in a 2 × 2 factorial arrangement with grain type and GAA supplementation as main effects. At 50 d, diets containing GAA improved (P < 0.01) FCR (1.682 vs. 1.724 g: g) independently of grain type. At 55 d, broilers fed corn diets with GAA had higher breast meat yield (P < 0.05) compared to corn without GAA. Drip and cook loss, and shear force (Warner-Bratzler) were not affected (P > 0.05) by GAA supplementation at any slaughter ages. However, GAA decreased (P < 0.05) the ultimate pH at 51 and 55 d in breast meat samples compared to unsupplemented diets. At 51 d, broilers supplemented with GAA had double (P < 0.05) breast meat fillets without wooden breast (score 1) compared with broilers fed non-supplemented diets, therefore reducing the severity of this myopathy. In conclusion, GAA supplementation improved broiler live performance in broilers raised up to 50 d independently of grain source, increased breast meat yield in corn-based diets and reduced the severity of wooden breast myopathy.

Vehicle hydraulic system that provides heat for passenger compartment

DOEpatents

Bartley, Bradley E.; Blass, James R.; Gibson, Dennis H.

2001-01-01

A vehicle includes a vehicle housing which defines a passenger compartment. Attached to the vehicle housing is a hydraulic system, that includes a hydraulic fluid which flows through at least one passageway within the hydraulic system. Also attached to the vehicle housing is a passenger compartment heating system. The passenger compartment heating system includes a heat exchanger, wherein a portion of the heat exchanger is a segment of the at least one passageway of the hydraulic system.

Desmin myopathy with severe cardiomyopathy in a Uruguayan family due to a codon deletion in a new location within the desmin 1A rod domain.

PubMed

Vernengo, Luis; Chourbagi, Oussama; Panuncio, Ana; Lilienbaum, Alain; Batonnet-Pichon, Sabrina; Bruston, Francine; Rodrigues-Lima, Fernando; Mesa, Rosario; Pizzarossa, Carlos; Demay, Laurence; Richard, Pascale; Vicart, Patrick; Rodriguez, Maria-Mirta

2010-03-01

Desmin myopathy is a heterogeneous neuromuscular disorder characterized by skeletal myopathy and cardiomyopathy, inherited mostly in an autosomal dominant pattern. We report a five generation Uruguayan family with severe cardiomyopathy and skeletal myopathy. Its most striking features are: atrial dilation, arrhythmia, conduction block and sudden death due to conduction impairment. Affected skeletal muscle shows alteration of mitochondria with paracrystallin inclusions and granulofilamentous material scattered in the muscle fibres. This family carries an unusual deletion p.E114del within the 1A rod domain of desmin. Transfected cells expressing the mutated desmin show punctuated and speckled cytoplasmic aggregates. The mutation causes a local conformational change in heptads a/d residues and charge positions. These findings lead to the hypothesis that coiled-coil interactions may be impaired, resulting in severe alterations in the desmin network. This is the first time that a mutation affecting this domain in the desmin molecule is described in a desminopathy. Copyright 2010. Published by Elsevier B.V.

14 CFR 23.1192 - Engine accessory compartment diaphragm.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Engine accessory compartment diaphragm. 23... Powerplant Powerplant Fire Protection § 23.1192 Engine accessory compartment diaphragm. For aircooled radial engines, the engine power section and all portions of the exhaust sytem must be isolated from the engine...

14 CFR 23.1192 - Engine accessory compartment diaphragm.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 14 Aeronautics and Space 1 2011-01-01 2011-01-01 false Engine accessory compartment diaphragm. 23... Powerplant Powerplant Fire Protection § 23.1192 Engine accessory compartment diaphragm. For aircooled radial engines, the engine power section and all portions of the exhaust sytem must be isolated from the engine...

14 CFR 23.1192 - Engine accessory compartment diaphragm.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 14 Aeronautics and Space 1 2014-01-01 2014-01-01 false Engine accessory compartment diaphragm. 23... Powerplant Powerplant Fire Protection § 23.1192 Engine accessory compartment diaphragm. For aircooled radial engines, the engine power section and all portions of the exhaust sytem must be isolated from the engine...

Acute Monocular Blindness Due to Orbital Compartment Syndrome Following Pterional Craniotomy.

PubMed

Habets, Jeroen G V; Haeren, Roel H L; Lie, Suen A N; Bauer, Noel J C; Dings, Jim T A

2018-06-01

We present a case of orbital compartment syndrome (OCS) leading to monocular irreversible blindness following a pterional craniotomy for clipping of an anterior communicating artery aneurysm. OCS is an uncommon but vision-threatening entity requiring urgent decompression to reduce the risk of permanent visual loss. Iatrogenic orbital roof defects are a common finding following pterional craniotomies. However, complications related to these defects are rarely reported. A 65-year-old female who underwent an anterior communicating artery clipping via a pterional approach 4 days before developed proptosis, ocular movement paresis, and irreversible visual impairment following an orthopedic surgery. Computed tomography images revealed an intraorbital cerebrospinal fluid (CSF) collection, which was evacuated via an acute recraniotomy. The next day, proptosis and intraorbital CSF collection on computed tomography images reoccurred and an oral and maxillofacial surgeon evacuated the collection via a blepharoplasty incision and blunt dissection. In addition, the patient was treated with acetazolamide and an external lumbar CSF drainage during 12 days. Hereafter, the CSF collection did not reoccur. Unfortunately, monocular blindness was persistent. We hypothesize the CSF collection occurred due to the combination of a postoperative orbital roof defect and a temporarily increased intracranial pressure during the orthopedic surgery. We plead for more awareness of this severe complication after pterional surgeries and emphasize the importance of 1) strict ophthalmologic examination after pterional craniotomies in case of intracranial pressure increasing events, 2) immediate consultation of an oral and maxillofacial surgeon, and 3) consideration of CSF-draining interventions since symptoms are severely invalidating and irreversible within a couple of hours. Copyright © 2018 Elsevier Inc. All rights reserved.

An arthroscopic safety zone for the medial compartment of the hip joint.

PubMed

Lee, Je-Hun; Lee, Jung-Bum; Lee, Nam Seob; Han, Seung Yun; Kim, In-Beom; Han, Seung-Ho

2015-10-01

The purpose of this study was to investigate the safety zone without any neurovascular injury to the medial compartment of hip joint through an anatomical method and describe the relationship of the extra-articular anatomic structures from the surface of the hip joint. Thirty-two fresh specimens from 17 adult Korean cadavers (8 males and 9 females, age range 54-79 years at death) were used for this study. For the measurements, the most superolateral point of the pubic symphysis (PS) and prominent point of the anterior superior iliac spine (ASIS) were identified before dissection. The line connecting the PS and ASIS was defined as a reference line and the PS was a starting point for measurements. All 19 variables measured in this study were related to the femoral head, neck, and surrounding neurovascular structures. The variables were measured according to the x- and y-coordinates in relation to the reference line. The femoral head was generally located 39.5-71.0 mm on the x-coordinate and located 33.5-34.6 mm on the y-coordinate. The junction of the femoral neck and body was located at 52.8 mm on the x-coordinate, and 65.3 mm on the y-coordinate. The junction of the femoral head and neck was located at 47.1 mm on the x-coordinate, and 51.4 mm on the y-coordinate. The location of the medial compartment of the hip joint was located from 38.0 to 43.0 % on the x-coordinate and located from 5.1 to 6.5 cm. These results of this study provide detailed anatomy for arthroscopic hip surgeons.

Specific binding of Ulex europaeus agglutinin I lectin to sarcolemma of distal myopathy with rimmed vacuole formation.

PubMed

Yatabe, K; Kawai, M

1997-08-01

Ulex europaeus agglutinin I (UEA I) binding was studied in 83 patients with various neuromuscular disorders. UEA I labelled endomysial capillaries and endothelial cells of perimysial blood vessels in all the examined muscles. There was no UEA I binding to muscle fibres except for all (9) cases of distal myopathy with rimmed vacuole formation (DMRV), 1 of 5 cases of inclusion body myositis and 1 of 36 cases of inflammatory myopathies. The UEA I binding was completely eliminated by preincubation of UEA I solution with L-fucose. Using electron microscopy, the UEA I binding was localized to sarcolemma and intrasarco-plasmic membranous organelles other than mitochondria. Myosatellite cells were not labelled. These findings revealed the existence of fucosylated proteins or lipids in a subset of skeletal muscles suffering from DMRV. Biochemical identification of the fucosylated substance and further detailed study on subcellular localization of UEA I binding may yield important clues to the unknown pathogenesis of DMRV.

Hereditary internal anal sphincter myopathy causing proctalgia fugax and constipation: further clinical and histological characterization in a patient.

PubMed

König, P; Ambrose, N S; Scott, N

2000-01-01

Hereditary internal anal sphincter myopathy is a very rare condition, only three families have so far been described in the literature. In this case report further clinical and histological findings of one affected member of one of the above families are presented.

Coupling volume-excluding compartment-based models of diffusion at different scales: Voronoi and pseudo-compartment approaches

PubMed Central

Taylor, P. R.; Baker, R. E.; Simpson, M. J.; Yates, C. A.

2016-01-01

Numerous processes across both the physical and biological sciences are driven by diffusion. Partial differential equations are a popular tool for modelling such phenomena deterministically, but it is often necessary to use stochastic models to accurately capture the behaviour of a system, especially when the number of diffusing particles is low. The stochastic models we consider in this paper are ‘compartment-based’: the domain is discretized into compartments, and particles can jump between these compartments. Volume-excluding effects (crowding) can be incorporated by blocking movement with some probability. Recent work has established the connection between fine- and coarse-grained models incorporating volume exclusion, but only for uniform lattices. In this paper, we consider non-uniform, hybrid lattices that incorporate both fine- and coarse-grained regions, and present two different approaches to describe the interface of the regions. We test both techniques in a range of scenarios to establish their accuracy, benchmarking against fine-grained models, and show that the hybrid models developed in this paper can be significantly faster to simulate than the fine-grained models in certain situations and are at least as fast otherwise. PMID:27383421

Effect of repeated passive anterior loading on human knee anterior laxity.

PubMed

Vauhnik, Renata; Perme, Maja Pohar; Barcellona, Massimo G; Morrissey, Matthew C; Sevšek, France; Rugelj, Darja

2015-10-01

Increased knee anterior laxity results when the anterior cruciate ligament is injured. This increased laxity can cause knee dysfunction. Until recently this laxity was believed to be only diminished through surgery. But recent findings indicate that knee anterior laxity may be decreased with repeated loading of the knee. The purpose of this study was to test the hypothesis that regular passive anterior loading of the uninjured human knee would enhance its stiffness. Randomized controlled trial. Knee anterior laxity was tested using an arthrometer in 22 young, uninjured females before, during and after a 3 month period during which passive anterior loading was applied by a trained physiotherapist over 5 sessions per week to a randomly assigned knee. Knee anterior laxity was not affected by the passive anterior loading of the knee. Given that in this study repeated passive loading of the knee did not change knee anterior laxity, it would be easy to conclude that this training is ineffective and no further research is required. We caution against this given the relatively short duration and possibly insufficient intensity of the training and the population studied; individuals with normal joint laxity. We recommend that future research be performed that consists of individuals with lax joints who receive training for prolonged periods. Copyright © 2015 Elsevier Ltd. All rights reserved.

Effects of aerobic training on exercise-related oxidative stress in mitochondrial myopathies.

PubMed

Siciliano, Gabriele; Simoncini, Costanza; Lo Gerfo, Annalisa; Orsucci, Daniele; Ricci, Giulia; Mancuso, Michelangelo

2012-12-01

In mitochondrial myopathies with respiratory chain deficiency impairment of energy cell production may lead to in excess reactive oxygen species generation with consequent oxidative stress and cell damage. Aerobic training has been showed to increase muscle performance in patients with mitochondrial myopathies. Aim of this study has been to evaluate, in 7 patients (6 F e 1M, mean age 44.9 ± 12.1 years) affected by mitochondrial disease, concomitantly to lactate exercise curve, the occurrence of oxidative stress, as indicated by circulating levels of lipoperoxides, in rest condition and as effect of exercise, and also, to verify if an aerobic training program is able to modify, in these patients, ox-redox balance efficiency. At rest and before training blood level of lipoperoxides was 382.4 ± 37.8 AU, compared to controls (318.7 ± 63.8; P<0.05), this corresponding to a moderate oxidative stress degree according to the adopted scale. During incremental exercise blood level of lipoperoxides did not increase, but maintained significantly higher compared to controls. After an aerobic training of 10 weeks the blood level of lipoperoxides decreased by 13.7% at rest (P<0.01) and 10.4%, 8.6% and 8.5% respectively at the corresponding times during the exercise test (P=0.06). These data indicate that, in mitochondrial patients, oxidative stress occurs and that an aerobic training is useful in partially reverting this condition. Copyright © 2012 Elsevier B.V. All rights reserved.

Aircraft Cargo Compartment Fire Test Simulation Program

NASA Technical Reports Server (NTRS)

Blumke, R. E.

1977-01-01

The objective of the test was to assess fire containment and fire extinguishment in the cargo by reducing the ventilation through the cargo compartment. Parameters which were measured included ignition time, burnthrough time, and physical damage to the cargo liner, composition of selected combustible gases, temperature-time histories, heat flux, and detector response. The ignitor load was made of a typical cargo consisting of filled cardboard cartons occupying 50% of the compartment volume.

Nemaline myopathy and distal arthrogryposis associated with an autosomal recessive TNNT3 splice variant.

PubMed

Sandaradura, Sarah A; Bournazos, Adam; Mallawaarachchi, Amali; Cummings, Beryl B; Waddell, Leigh B; Jones, Kristi J; Troedson, Christopher; Sudarsanam, Annapurna; Nash, Benjamin M; Peters, Gregory B; Algar, Elizabeth M; MacArthur, Daniel G; North, Kathryn N; Brammah, Susan; Charlton, Amanda; Laing, Nigel G; Wilson, Meredith J; Davis, Mark R; Cooper, Sandra T

2018-03-01

A male neonate presented with severe weakness, hypotonia, contractures and congenital scoliosis. Skeletal muscle specimens showed marked atrophy and degeneration of fast fibers with striking nemaline rods and hypertrophy of slow fibers that were ultrastructurally normal. A neuromuscular gene panel identified a homozygous essential splice variant in TNNT3 (chr11:1956150G > A, NM_006757.3:c.681+1G > A). TNNT3 encodes skeletal troponin-T fast and is associated with autosomal dominant distal arthrogryposis. TNNT3 has not previously been associated with nemaline myopathy (NM), a rare congenital myopathy linked to defects in proteins associated with thin filament structure and regulation. cDNA studies confirmed pathogenic consequences of the splice variant, eliciting exon-skipping and intron retention events leading to a frameshift. Western blot showed deficiency of troponin-T fast protein with secondary loss of troponin-I fast . We establish a homozygous splice variant in TNNT3 as the likely cause of severe congenital NM with distal arthrogryposis, characterized by specific involvement of Type-2 fibers and deficiency of troponin-T fast . © 2017 Wiley Periodicals, Inc.

Space Shuttle crew compartment debris-contamination

NASA Technical Reports Server (NTRS)

Goodman, Jerry R.; Villarreal, Leopoldo J.

1992-01-01

Remedial actions undertaken to reduce debris during manned flights and ground turnaround operations at Kennedy Space Center and Palmdale are addressed. They include redesign of selected ground support equipment and Orbiter hardware to reduce particularization/debris generation; development of new detachable filters for air-cooled avionics boxes; application of tape-on screens to filter debris; and implementation of new Orbiter maintenance and turnaround procedures to clean filters and the crew compartment. Most of these steps were implemented before the return-to-flight of STS-26 in September 1988 which resulted in improved crew compartment habitability and less potential for equipment malfunction.

Creatine kinase elevation, lactacidemia, and metabolic myopathy in adult patients with diabetes mellitus.

PubMed

Frank, Marlies; Finsterer, Josef

2012-01-01

To determine the frequency of elevated creatine kinase (CK) levels among patients with diabetes mellitus and to determine how often elevated CK is attributable to primary myopathy. In this prospective study, we investigated how often CK, aspartate amino-transferase, alanine aminotransferase, and resting lactate were elevated among consecutive diabetic patients attending our clinic. Those with elevated CK values were offered a neurologic workup. Ninety-nine patients with diabetes mellitus, aged 19 to 87 years, were assessed between May 2008 and April 2010. Seven patients had type 1 diabetes and 92 patients had type 2 diabetes. CK, aspartate aminotransferase, alanine aminotransferase, and resting lactate were elevated in 19 of 99, 25 of 99, 22 of 99, and 24 of 98 patients, respectively. Eleven of 19 patients with increased CK were self-injecting insulin. Ten of 24 patients with elevated serum lactate took metformin. Seven of 19 patients with elevated CK consented to neurologic workup. Two of the 7 had elevated resting lactate. In all 7 patients, the findings from neurologic investigation were indicative of a metabolic defect and further diagnostic evaluation was recommended. In diabetic patients attending our clinic, elevated CK levels occur in one-fifth and lactacidemia occurs in one-quarter. Elevated CK levels are attributable to a primary metabolic myopathy in most cases. Elevated CK levels in the setting of diabetes mellitus require further neurologic evaluation.

Hypoxic ischemic encephalopathy in a case of intranuclear rod myopathy without any prenatal sentinel event.

PubMed

Kawase, Koya; Nishino, Ichizo; Sugimoto, Mari; Kouwaki, Masanori; Koyama, Norihisa; Yokochi, Kenji

2015-02-01

Intranuclear rod myopathy (IRM), a variant of nemaline myopathy, is characterized by the presence of nemaline bodies in myonuclei. We report a case of IRM presenting with hypoxic ischemic encephalopathy (HIE). There were no prenatal complications caused by fetal brain injury. Although no nemaline bodies were observed in the cytoplasm, intranuclear rods were observed in some fibers under light and electron microscopy. Molecular analysis identified a heterozygous variant, c.449C>T (p.Thr150Ile), in ACTA1. On magnetic resonance imaging at 9days of age, injuries to the basal ganglia, thalamus, and brainstem consistent with perinatal HIE were seen. Respiratory insufficiency at birth was strongly suspected to be the cause of HIE. Our case highlights that a patient with a congenital neuromuscular disorder who presents with severe respiratory dysfunction requiring substantial resuscitative efforts at birth can be complicated by HIE without any prenatal sentinel event. Prenatal detection of neuromuscular disorders, careful management of delivery, and neonatal resuscitation and adequate respiratory management are important in preventing irreversible brain injury in these patients. Copyright © 2014 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Congenital myopathy results from misregulation of a muscle Ca2+ channel by mutant Stac3

PubMed Central

Linsley, Jeremy W.; Hsu, I-Uen; Groom, Linda; Yarotskyy, Viktor; Lavorato, Manuela; Horstick, Eric J.; Linsley, Drew; Wang, Wenjia; Franzini-Armstrong, Clara; Dirksen, Robert T.; Kuwada, John Y.

2017-01-01

Skeletal muscle contractions are initiated by an increase in Ca2+ released during excitation–contraction (EC) coupling, and defects in EC coupling are associated with human myopathies. EC coupling requires communication between voltage-sensing dihydropyridine receptors (DHPRs) in transverse tubule membrane and Ca2+ release channel ryanodine receptor 1 (RyR1) in the sarcoplasmic reticulum (SR). Stac3 protein (SH3 and cysteine-rich domain 3) is an essential component of the EC coupling apparatus and a mutation in human STAC3 causes the debilitating Native American myopathy (NAM), but the nature of how Stac3 acts on the DHPR and/or RyR1 is unknown. Using electron microscopy, electrophysiology, and dynamic imaging of zebrafish muscle fibers, we find significantly reduced DHPR levels, functionality, and stability in stac3 mutants. Furthermore, stac3NAM myofibers exhibited increased caffeine-induced Ca2+ release across a wide range of concentrations in the absence of altered caffeine sensitivity as well as increased Ca2+ in internal stores, which is consistent with increased SR luminal Ca2+. These findings define critical roles for Stac3 in EC coupling and human disease. PMID:28003463

Should asymptomatic anterior pelvic organ prolapse be corrected to treat irritative urinary symptoms?

PubMed

Sutherland, Suzette E

2010-09-01

In clinical practice, women seen with pelvic organ prolapse (POP) often present with a variety of pelvic floor symptoms: urinary incontinence, irritative or overactive bladder symptoms, fecal urgency or incontinence, obstructive voiding, sexual disorders, pelvic and perineal pain, and vaginal bulging. Among these, the only symptom reliably associated with clinically relevant POP that will resolve following vaginal reconstructive surgery is the visualization and/or sensation of a vaginal bulge. Most other symptoms often attributed to POP at best have only weak correlations with worsening pelvic anatomical support. Specifically, with respect to the anterior and/or apical vaginal compartment, there does not appear to be a correlation between irritative overactive bladder symptoms and the presence or degree of anterior vaginal wall prolapse. Furthermore, no other symptoms, urinary or otherwise, are reliably influenced by correction of anatomical defects of pelvic support, especially in the otherwise asymptomatic patient with POP without vaginal bulge. A review of the recent literature underscores the realization that the relationship between pelvic floor symptoms and anatomy is incompletely and poorly understood. With this in mind, there does not seem to be any absolute justification for the surgical correction of otherwise asymptomatic pelvic support defects.

Exploring Water-Tight Compartments.

ERIC Educational Resources Information Center

Fishman, Steve

John Dewey employed the phrase "water-tight compartments" to mark deficiencies of integration within an individual's personality. For Dewey, the self is complex, but a strong personality integrates its various habits so that they reinforce rather than conflict with one another. Dewey's focus on this problem of personality has relevance…

Fire safety arrangement of inhabited pressurized compartments of manned spacecraft

NASA Astrophysics Data System (ADS)

Bolodian, Ivan; Melikhov, Anatoliy; Tanklevskiy, Leonid

2017-06-01

The article deals with innovative technical solutions that provide fire safety in inhabited pressurized compartments of manned spacecraft by means of a fireproof device of inhabited pressurized compartments via application of engineering means of fire prevention and fire spreading prevention by lowering fire load in an inhabited pressurized module up to the point when the maximum possible levels of fire factors in an inhabited pressurized compartment of a manned spacecraft are prevented. Represented technical solutions are used at the present time according to stated recommendations during provision of fire safety of equipment created by a number of Russian organizations for equipage of inhabited pressurized compartments of spacecraft of the Russian segment of International space station.

A Comprehensive Overview on Myositis-Specific Antibodies: New and Old Biomarkers in Idiopathic Inflammatory Myopathy

PubMed Central

Satoh, Minoru; Tanaka, Shin; Ceribelli, Angela; Calise, S. John; Chan, Edward K. L.

2018-01-01

Autoantibodies specific for idiopathic inflammatory myopathy (myositis-specific autoantibodies (MSAs)) are clinically useful biomarkers to help the diagnosis of polymyositis/dermatomyositis (PM/DM). Many of these are also associated with a unique clinical subset of PM/DM, making them useful in predicting and monitoring certain clinical manifestations. Classic MSAs known for over 30 years include antibodies to Jo-1 (histidyl transfer RNA (tRNA) synthetase) and other aminoacyl tRNA synthetases (ARS), anti-Mi-2, and anti-signal recognition particle (SRP). Anti-Jo-1 is the first autoantibodies to ARS detected in 15–25 % of patients. In addition to anti-Jo-1, antibodies to seven other aminoacyl tRNA synthetases (ARS) have been reported with prevalence, usually 1–5 % or lower. Patients with any antiARS antibodies are associated with anti-synthetase syndrome characterized by myositis, interstitial lung disease (ILD), arthritis, Raynaud’s phenomenon, and others. Several recent studies suggested heterogeneity in clinical features among different anti-ARS antibody-positive patients and anti-ARS may also be found in idiopathic ILD without myositis. Anti-Mi-2 is a classic marker for DM and associated with good response to steroid treatment and good prognosis. Anti-SRP is specific for PM and associated with treatment-resistant myopathy histologically characterized as necrotizing myopathy. In addition to classic MSAs, several new autoantibodies with strong clinical significance have been described in DM. Antibodies to transcription intermediary factor 1γ/α (TIF1γ/α, p155/140) are frequently found in DM associated with malignancy while anti-melanoma differentiation-associated gene 5 (MDA5; CADM140) are associated with clinically amyopathic DM (CADM) complicated by rapidly progressive ILD. Also, anti-MJ/nuclear matrix protein 2 (NXP-2) and anti-small ubiquitin-like modifier-1 (SUMO-1) activating enzyme (SAE) are recognized as new DM-specific autoantibodies. Addition of

Modulatory compartments in cortex and local regulation of cholinergic tone.

PubMed

Coppola, Jennifer J; Ward, Nicholas J; Jadi, Monika P; Disney, Anita A

2016-09-01

Neuromodulatory signaling is generally considered broad in its impact across cortex. However, variations in the characteristics of cortical circuits may introduce regionally-specific responses to diffuse modulatory signals. Features such as patterns of axonal innervation, tissue tortuosity and molecular diffusion, effectiveness of degradation pathways, subcellular receptor localization, and patterns of receptor expression can lead to local modification of modulatory inputs. We propose that modulatory compartments exist in cortex and can be defined by variation in structural features of local circuits. Further, we argue that these compartments are responsible for local regulation of neuromodulatory tone. For the cholinergic system, these modulatory compartments are regions of cortical tissue within which signaling conditions for acetylcholine are relatively uniform, but between which signaling can vary profoundly. In the visual system, evidence for the existence of compartments indicates that cholinergic modulation likely differs across the visual pathway. We argue that the existence of these compartments calls for thinking about cholinergic modulation in terms of finer-grained control of local cortical circuits than is implied by the traditional view of this system as a diffuse modulator. Further, an understanding of modulatory compartments provides an opportunity to better understand and perhaps correct signal modifications that lead to pathological states. Copyright © 2016 Elsevier Ltd. All rights reserved.

Architectural properties of the neuromuscular compartments in selected forearm skeletal muscles

PubMed Central

Liu, An-Tang; Liu, Ben-Li; Lu, Li-Xuan; Chen, Gang; Yu, Da-Zhi; Zhu, Lie; Guo, Rong; Dang, Rui-Shan; Jiang, Hua

2014-01-01

The purposes f this study were to (i) explore the possibility of splitting the selected forearm muscles into separate compartments in human subjects; (ii) quantify the architectural properties of each neuromuscular compartment; and (iii) discuss the implication of these properties in split tendon transfer procedures. Twenty upper limbs from 10 fresh human cadavers were used in this study. Ten limbs of five cadavers were used for intramuscular nerve study by modified Sihler's staining technique, which confirmed the neuromuscular compartments. The other 10 limbs were included for architectural analysis of neuromuscular compartments. The architectural features of the compartments including muscle weight, muscle length, fiber length, pennation angle, and sarcomere length were determined. Physiological cross-sectional area and fiber length/muscle length ratio were calculated. Five of the selected forearm muscles were ideal candidates for splitting, including flexor carpi ulnaris, flexor carpi radials, extensor carpi radialis brevis, extensor carpi ulnaris and pronator teres. The humeral head of pronator teres contained the longest fiber length (6.23 ± 0.31 cm), and the radial compartment of extensor carpi ulnaris contained the shortest (2.90 ± 0.28 cm). The ulnar compartment of flexor carpi ulnaris had the largest physiological cross-sectional area (5.17 ± 0.59 cm2), and the ulnar head of pronator teres had the smallest (0.67 ± 0.06 cm2). Fiber length/muscle length ratios of the neuromuscular compartments were relatively low (average 0.27 ± 0.09, range 0.18–0.39) except for the ulnar head of pronator teres, which had the highest one (0.72 ± 0.05). Using modified Sihler's technique, this research demonstrated that each compartment of these selected forearm muscles has its own neurovascular supply after being split along its central tendon. Data of the architectural properties of each neuromuscular compartment provide insight into the ‘design’ of their

Epidemic Spreading in a Multi-compartment System

NASA Astrophysics Data System (ADS)

Gao, Zong-Mao; Gu, Jiao; Li, Wei

2012-02-01

We introduce the variant rate and white noise into the susceptible-infected-removed (SIR) model for epidemics, discuss the epidemic dynamics of a multiple-compartment system, and describe this system by using master equations. For both the local epidemic spreading system and the whole multiple-compartment system, we find that a threshold could be useful in forecasting when the epidemic vanishes. Furthermore, numerical simulations show that a model with the variant infection rate and white noise can improve fitting with real SARS data.

Compartment A126 port side. Note ash hoist for boiler room ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

Compartment A-126 port side. Note ash hoist for boiler room compartment B-1 and compartment B-2. Scuttlebutt (drinking water fountain) is at right center of photograph. Manikin wearing WWII wave uniform is in display case at left center. (045) - USS Olympia, Penn's Landing, 211 South Columbus Boulevard, Philadelphia, Philadelphia County, PA

Lower limb compartment syndrome following laparoscopic colorectal surgery: a review.

PubMed

Rao, M M; Jayne, D

2011-05-01

  In spite of recent advances in technology and technique, laparoscopic colorectal surgery is associated with increased operating times when compared with open surgery. This increases the risk of acute lower limb compartment syndrome. The aim of this review was to gain a better understanding of postoperative lower limb compartment syndrome following laparoscopic colorectal surgery and to suggest strategies to avoid its occurrence. A MEDLINE search was performed using the keywords 'compartment syndrome', 'laparoscopic surgery' and 'Lloyd-Davies position' between 1970 and 2008. All relevant articles were retrieved and reviewed. A total of 54 articles were retrieved. Of the 30 articles in English, five were reviews, six were original articles and 19 were case reports, of which only one was following laparoscopic colorectal surgery. The remaining 24 were non-English articles. Of these, two were reviews and 22 were case reports, of which only one was following laparoscopic colorectal surgery. The incidence of acute compartment syndrome following laparoscopic colorectal surgery is unknown. The following are believed to be risk factors for acute lower limb compartment syndrome: the Lloyd-Davies operating position with exaggerated Trendelenburg tilt, prolonged operative times and improper patient positioning. Simple strategies are suggested to reduce its occurrence. Simple preventative measures have been identified which may help to reduce the incidence of acute lower limb compartment syndrome. However, if suspected, timely surgical intervention with four-compartment fasciotomy remains the standard of care. © 2011 The Authors. Colorectal Disease © 2011 The Association of Coloproctology of Great Britain and Ireland.

46 CFR 169.627 - Compartments containing diesel fuel tanks.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 7 2011-10-01 2011-10-01 false Compartments containing diesel fuel tanks. 169.627 Section 169.627 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) NAUTICAL SCHOOLS SAILING SCHOOL VESSELS Machinery and Electrical Ventilation § 169.627 Compartments containing diesel fuel tanks...

46 CFR 169.627 - Compartments containing diesel fuel tanks.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 7 2010-10-01 2010-10-01 false Compartments containing diesel fuel tanks. 169.627 Section 169.627 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) NAUTICAL SCHOOLS SAILING SCHOOL VESSELS Machinery and Electrical Ventilation § 169.627 Compartments containing diesel fuel tanks...

46 CFR 171.017 - One and two compartment standards of flooding.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 7 2011-10-01 2011-10-01 false One and two compartment standards of flooding. 171.017... standards of flooding. (a) One compartment standard of flooding. A vessel is designed to a one compartment standard of flooding if the margin line is not submerged when the total buoyancy between each set of two...

46 CFR 171.017 - One and two compartment standards of flooding.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 7 2013-10-01 2013-10-01 false One and two compartment standards of flooding. 171.017... standards of flooding. (a) One compartment standard of flooding. A vessel is designed to a one compartment standard of flooding if the margin line is not submerged when the total buoyancy between each set of two...

46 CFR 171.017 - One and two compartment standards of flooding.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 7 2012-10-01 2012-10-01 false One and two compartment standards of flooding. 171.017... standards of flooding. (a) One compartment standard of flooding. A vessel is designed to a one compartment standard of flooding if the margin line is not submerged when the total buoyancy between each set of two...

46 CFR 171.017 - One and two compartment standards of flooding.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 46 Shipping 7 2014-10-01 2014-10-01 false One and two compartment standards of flooding. 171.017... standards of flooding. (a) One compartment standard of flooding. A vessel is designed to a one compartment standard of flooding if the margin line is not submerged when the total buoyancy between each set of two...

46 CFR 171.017 - One and two compartment standards of flooding.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 7 2010-10-01 2010-10-01 false One and two compartment standards of flooding. 171.017... standards of flooding. (a) One compartment standard of flooding. A vessel is designed to a one compartment standard of flooding if the margin line is not submerged when the total buoyancy between each set of two...

Management of abdominal compartment syndrome after transurethral resection of the prostate.

PubMed

Gaut, Megan M; Ortiz, Jaime

2015-01-01

Acute abdominal compartment syndrome is most commonly associated with blunt abdominal trauma, although it has been seen after ruptured abdominal aortic aneurysm, liver transplantation, pancreatitis, and massive volume resuscitation. Acute abdominal compartment syndrome develops once the intra-abdominal pressure increases to 20-25 mmHg and is characterized by an increase in airway pressures, inadequate ventilation and oxygenation, altered renal function, and hemodynamic instability. This case report details the development of acute abdominal compartment syndrome during transurethral resection of the prostate with extra- and intraperitoneal bladder rupture under general anesthesia. The first signs of acute abdominal compartment syndrome in this patient were high peak airway pressures and difficulty delivering tidal volumes. Management of the compartment syndrome included re-intubation, emergent exploratory laparotomy, and drainage of irrigation fluid. Difficulty with ventilation should alert the anesthesiologist to consider abdominal compartment syndrome high in the list of differential diagnoses during any endoscopic bladder or bowel case. Copyright © 2013 Sociedade Brasileira de Anestesiologia. Published by Elsevier Editora Ltda. All rights reserved.

[Management of abdominal compartment syndrome after transurethral resection of the prostate].

PubMed

Gaut, Megan M; Ortiz, Jaime

2015-01-01

Acute abdominal compartment syndrome is most commonly associated with blunt abdominal trauma, although it has been seen after ruptured abdominal aortic aneurysm, liver transplantation, pancreatitis, and massive volume resuscitation. Acute abdominal compartment syndrome develops once the intra-abdominal pressure increases to 20-25mmHg and is characterized by an increase in airway pressures, inadequate ventilation and oxygenation, altered renal function, and hemodynamic instability. This case report details the development of acute abdominal compartment syndrome during transurethral resection of the prostate with extra- and intraperitoneal bladder rupture under general anesthesia. The first signs of acute abdominal compartment syndrome in this patient were high peak airway pressures and difficulty delivering tidal volumes. Management of the compartment syndrome included re-intubation, emergent exploratory laparotomy, and drainage of irrigation fluid. Difficulty with ventilation should alert the anesthesiologist to consider abdominal compartment syndrome high in the list of differential diagnoses during any endoscopic bladder or bowel case. Copyright © 2013 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.

POST‐SURGICAL REHABILITATION FOLLOWING FASCIOTOMIES FOR BILATERAL CHRONIC EXERTIONAL COMPARTMENT SYNDROME IN A SPECIAL FORCES SOLDIER: A CASE REPORT

PubMed Central

Miller, Joseph

2013-01-01

Background and Purpose: The etiology of Chronic Exertional Compartment Syndrome (CECS) is still unclear. The most commonly accepted theory suggests that it is a transient but debilitating process where there is an abnormally increased intracompartmental pressure during exercise/exertion due to non‐compliant expansion of the osteofascial tissues. This most commonly occurs in the lower leg. Surgical intervention is often performed for symptom relief. However, there has been limited scientifically‐based publication on post‐surgical rehabilitation, especially with regard to return to function in the military population. The purpose of this case report is to demonstrate the utilization of a recommended post‐operative protocol in a Special Forces Soldier. Case Description: The subject presented as a 25‐year‐old US Army Special Forces Soldier, who failed 8 weeks of conservative management for the diagnosis of CECS and subsequently underwent bilateral lower leg fasciotomies of the anterior and lateral compartments. Outcomes: Following recommended protocol guidelines he was progressed rapidly and within three months deployed without restriction or complications in a demanding combat zone. Discussion: This case report illustrates that following clearly defined, scientifically‐based rehabilitation guidelines helped in addressing all of the involved structures and musculoskeletal dysfunctions that presented following the surgical intervention for CECS in a unique subject. Level of Evidence: 5 PMID:24175149

Mutation Update and Genotype–Phenotype Correlations of Novel and Previously Described Mutations in TPM2 and TPM3 Causing Congenital Myopathies

PubMed Central

Marttila, Minttu; Lehtokari, Vilma-Lotta; Marston, Steven; Nyman, Tuula A.; Barnerias, Christine; Beggs, Alan H.; Bertini, Enrico; Ceyhan-Birsoy, OÖzge; Cintas, Pascal; Gerard, Marion; Gilbert-Dussardier, Brigitte; Hogue, Jacob S.; Longman, Cheryl; Eymard, Bruno; Frydman, Moshe; Kang, Peter B.; Klinge, Lars; Kolski, Hanna; Lochmüller, Hans; Magy, Laurent; Manel, Véronique; Mayer, Michèle; Mercuri, Eugenio; North, Kathryn N.; Peudenier-Robert, Sylviane; Pihko, Helena; Probst, Frank J.; Reisin, Ricardo; Stewart, Willie; Taratuto, Ana Lia; de Visser, Marianne; Wilichowski, Ekkehard; Winer, John; Nowak, Kristen; Laing, Nigel G.; Winder, Tom L.; Monnier, Nicole; Clarke, Nigel F.; Pelin, Katarina; Grönholm, Mikaela; Wallgren-Pettersson, Carina

2014-01-01

Mutations affecting skeletal muscle isoforms of the tropomyosin genes may cause nemaline myopathy, cap myopathy, core-rod myopathy, congenital fiber-type disproportion, distal arthrogryposes, and Escobar syndrome. We correlate the clinical picture of these diseases with novel (19) and previously reported (31) mutations of the TPM2 and TPM3 genes. Included are altogether 93 families: 53 with TPM2 mutations and 40 with TPM3 mutations. Thirty distinct pathogenic variants of TPM2 and 20 of TPM3 have been published or listed in the Leiden Open Variant Database (http://www.dmd.nl/). Most are heterozygous changes associated with autosomal-dominant disease. Patients with TPM2 mutations tended to present with milder symptoms than those with TPM3 mutations, DA being present only in the TPM2 group. Previous studies have shown that five of the mutations in TPM2 and one in TPM3 cause increased Ca2+ sensitivity resulting in a hypercontractile molecular phenotype. Patients with hypercontractile phenotype more often had contractures of the limb joints (18/19) and jaw (6/19) than those with nonhypercontractile ones (2/22 and 1/22), whereas patients with the non-hypercontractile molecular phenotype more often (19/22) had axial contractures than the hypercontractile group (7/19). Our in silico predictions show that most mutations affect tropomyosin–actin association or tropomyosin head-to-tail binding. PMID:24692096

Detection of hypoglycin A in the seeds of sycamore (Acer pseudoplatanus) and box elder (A. negundo) in New Zealand; the toxin associated with cases of equine atypical myopathy.

PubMed

McKenzie, R K; Hill, F I; Habyarimana, J A; Boemer, F; Votion, D M

2016-05-01

During April and May 2014 four horses aged between 5 months and 9 years, located in the Canterbury, Marlborough and Southland regions, presented with a variety of clinical signs including recumbency, stiffness, lethargy, dehydration, depression, and myoglobinuria suggestive of acute muscle damage. Two horses were subjected to euthanasia and two recovered. In all cases seeds of sycamore maple (Acer pseudoplatanus) or box elder (A. negundo) were present in the area where the horse had been grazing. The samaras (seeds) of some Acer spp. may contain hypoglycin A, that has been associated with cases of atypical myopathy in Europe and North America. To determine if hypoglycin A is present in the samaras of Acer spp. in New Zealand, samples were collected from trees throughout the country that were associated with historical and/or current cases of atypical myopathy, and analysed for hypoglycin A. Serum samples from the four cases and four unaffected horses were analysed for the presence of hypoglycin A, profiles of acylcarnitines (the definitive diagnosis for atypical myopathy) and activities of creatine kinase and aspartate aminotransferase.Markedly elevated serum activities of creatine kinase and aspartate aminotransferase, and increased concentrations of selected acylcarnitines were found in the case horses. Hypoglycin A was detected in the serum of those horses but not in the healthy controls. Hypoglycin A was detected in 10/15 samples of samaras from sycamore maple and box elder from throughout New Zealand. Cases of atypical myopathy were diagnosed on properties where samaras containing hypoglycin A were also found. Sycamore and box elder trees in New Zealand are a source of hypoglycin A associated with the development of atypical myopathy. If pastured horses present with clinical and biochemical signs of severe muscle damage then the environment should be checked for the presence of these trees. Horses should be prevented from grazing samaras from Acer spp. in the

BAG3 myofibrillar myopathy presenting with cardiomyopathy.

PubMed

Konersman, Chamindra G; Bordini, Brett J; Scharer, Gunter; Lawlor, Michael W; Zangwill, Steven; Southern, James F; Amos, Louella; Geddes, Gabrielle C; Kliegman, Robert; Collins, Michael P

2015-05-01

Myofibrillar myopathies (MFMs) are a heterogeneous group of neuromuscular disorders distinguished by the pathological hallmark of myofibrillar dissolution. Most patients present in adulthood, but mutations in several genes including BCL2-associated athanogene 3 (BAG3) cause predominantly childhood-onset disease. BAG3-related MFM is particularly severe, featuring weakness, cardiomyopathy, neuropathy, and early lethality. While prior cases reported either neuromuscular weakness or concurrent weakness and cardiomyopathy at onset, we describe the first case in which cardiomyopathy and cardiac transplantation (age eight) preceded neuromuscular weakness by several years (age 12). The phenotype comprised distal weakness and severe sensorimotor neuropathy. Nerve biopsy was primarily axonal with secondary demyelinating/remyelinating changes without "giant axons." Muscle biopsy showed extensive neuropathic changes that made myopathic changes difficult to interpret. Similar to previous cases, a p.Pro209Leu mutation in exon 3 of BAG3 was found. This case underlines the importance of evaluating for MFMs in patients with combined neuromuscular weakness and cardiomyopathy. Copyright © 2015 Elsevier B.V. All rights reserved.

Large copy-number variations in patients with statin-associated myopathy affecting statin myopathy-related loci.

PubMed

Stránecký, V; Neřoldová, M; Hodaňová, K; Hartmannová, H; Piherová, L; Zemánková, P; Přistoupilová, A; Vrablík, M; Adámková, V; Kmoch, S; Jirsa, M

2016-12-13

Some patients are susceptible to statin-associated myopathy (SAM) either because of genetic variations affecting statin uptake and metabolism, or because they predispose their carriers to muscular diseases. Among the frequent variants examined using the genome-wide association study approach, SLCO1B1 c.521T>C represents the only validated predictor of SAM in patients treated with high-dose simvastatin. Our aim was to ascertain the overall contribution of large copy-number variations (CNVs) to SAM diagnosed in 86 patients. CNVs were detected by whole genome genotyping using Illumina HumanOmni2.5 Exome BeadChips. Exome sequence data were used for validation of CNVs in SAM-related loci. In addition, we performed a specific search for CNVs in the SLCO1B region detected recently in Rotor syndrome subjects. Rare deletions possibly contributing to genetic predisposition to SAM were found in two patients: one removed EYS associated previously with SAM, the other was present in LARGE associated with congenital muscular dystrophy. Another two patients carried deletions in CYP2C19, which may predispose to clopidogrel-statin interactions. We found no common large CNVs potentially associated with SAM and no CNVs in the SLCO1B locus. Our findings suggest that large CNVs do not play a substantial role in the etiology of SAM.

Two-compartment modeling of tissue microcirculation revisited.

PubMed

Brix, Gunnar; Salehi Ravesh, Mona; Griebel, Jürgen

2017-05-01

Conventional two-compartment modeling of tissue microcirculation is used for tracer kinetic analysis of dynamic contrast-enhanced (DCE) computed tomography or magnetic resonance imaging studies although it is well-known that the underlying assumption of an instantaneous mixing of the administered contrast agent (CA) in capillaries is far from being realistic. It was thus the aim of the present study to provide theoretical and computational evidence in favor of a conceptually alternative modeling approach that makes it possible to characterize the bias inherent to compartment modeling and, moreover, to approximately correct for it. Starting from a two-region distributed-parameter model that accounts for spatial gradients in CA concentrations within blood-tissue exchange units, a modified lumped two-compartment exchange model was derived. It has the same analytical structure as the conventional two-compartment model, but indicates that the apparent blood flow identifiable from measured DCE data is substantially overestimated, whereas the three other model parameters (i.e., the permeability-surface area product as well as the volume fractions of the plasma and interstitial distribution space) are unbiased. Furthermore, a simple formula was derived to approximately compute a bias-corrected flow from the estimates of the apparent flow and permeability-surface area product obtained by model fitting. To evaluate the accuracy of the proposed modeling and bias correction method, representative noise-free DCE curves were analyzed. They were simulated for 36 microcirculation and four input scenarios by an axially distributed reference model. As analytically proven, the considered two-compartment exchange model is structurally identifiable from tissue residue data. The apparent flow values estimated for the 144 simulated tissue/input scenarios were considerably biased. After bias-correction, the deviations between estimated and actual parameter values were (11.2 ± 6

[External progressive ophthalmoplegia secondary to mitochondrial myopathy. Report of a case and review of the literature].

PubMed

Calderón-Garcidueñas, A L; Pérez-Loria, O; Alberto-Sagástegui, J; Farías-García, R

2000-01-01

Progressive limitation of occular motility, accompanied by ptosis but usually without diplopia, occurs in many pathologic states, including mitochondrial diseases. A case with chronic progressive external ophthalmoplegia with onset during childhood, associated with proximal myopathy and dysphasia is presented. The muscle biopsy showed a myopathic pattern and abnormal subsarcolemmal mitochondrial deposits. Muscle biopsy for important in the correct diagnosis of this entity.

Membrane order in the plasma membrane and endocytic recycling compartment.

PubMed

Iaea, David B; Maxfield, Frederick R

2017-01-01

The cholesterol content of membranes plays an important role in organizing membranes for signal transduction and protein trafficking as well as in modulating the biophysical properties of membranes. While the properties of model or isolated membranes have been extensively studied, there has been little evaluation of internal membranes in living cells. Here, we use a Nile Red based probe, NR12S, and ratiometric live cell imaging, to analyze the membrane order of the plasma membrane and endocytic recycling compartment. We find that after a brief incubation to allow endocytosis, NR12S is distributed between the plasma membrane and the endocytic recycling compartment. The NR12S reports that the endocytic recycling compartment is more highly ordered than the plasma membrane. We also find that the plasma membrane and the endocytic recycling compartment are differentially affected by altering cellular cholesterol levels. The membrane order of the plasma membrane, but not the endocytic recycling compartment, is altered significantly when cellular cholesterol content is increased or decreased by 20%. These results demonstrate that changes in cellular cholesterol differentially alter membrane order within different organelles.

Myopathy caused by mammalian target of rapamycin complex 1 (mTORC1) inactivation is not reversed by restoring mitochondrial function

PubMed Central

Romanino, Klaas; Mazelin, Laetitia; Albert, Verena; Conjard-Duplany, Agnès; Lin, Shuo; Bentzinger, C. Florian; Handschin, Christoph; Puigserver, Pere; Zorzato, Francesco; Schaeffer, Laurent; Gangloff, Yann-Gaël; Rüegg, Markus A.

2011-01-01

Mammalian target of rapamycin complex 1 (mTORC1) is central to the control of cell, organ, and body size. Skeletal muscle-specific inactivation of mTORC1 in mice results in smaller muscle fibers, fewer mitochondria, increased glycogen stores, and a progressive myopathy that causes premature death. In mTORC1-deficient muscles, peroxisome proliferator-activated receptor gamma coactivator 1-α (PGC-1α), which regulates mitochondrial biogenesis and glucose homeostasis, is strongly down-regulated. Here we tested whether induction of mitochondrial biogenesis pharmacologically or by the overexpression of PGC-1α is sufficient to reverse the phenotype of mice deficient for mTORC1. We show that both approaches normalize mitochondrial function, such as oxidative capacity and expression of mitochondrial genes. However, they do not prevent or delay the progressive myopathy. In addition, we find that mTORC1 has a much stronger effect than PGC-1α on the glycogen content in muscle. This effect is based on the strong activation of PKB/Akt in mTORC1-deficient mice. We also show that activation of PKB/Akt not only affects glycogen synthesis but also diminishes glycogen degradation. Thus, our work provides strong functional evidence that mitochondrial dysfunction in mice with inactivated mTORC1 signaling is caused by the down-regulation of PGC-1α. However, our data also show that the impairment of mitochondria does not lead directly to the lethal myopathy. PMID:22143799

Analysis of NCAM helps identify unusual phenotypes of hereditary inclusion-body myopathy.

PubMed

Broccolini, A; Gidaro, T; Tasca, G; Morosetti, R; Rodolico, C; Ricci, E; Mirabella, M

2010-07-20

Hereditary inclusion-body myopathy or distal myopathy with rimmed vacuoles (h-IBM/DMRV) is due to mutations of the UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE) gene, which codes for an enzyme of the sialic acid biosynthetic pathway. By Western blot (WB) analysis, we have previously shown that in h-IBM/DMRV muscle, the neural cell adhesion molecule (NCAM) has increased electrophoretic mobility that reflects reduced sialylation of the protein. To identify patients with h-IBM/DMRV with atypical clinical or pathologic phenotype using NCAM analysis and the possible cellular mechanism associated with the overall abnormal sialylation of NCAM observed in this disorder. WB analysis of NCAM was performed on muscle biopsies of 84 patients with an uncharacterized muscle disorder who were divided in the following 2 groups: 1) 46 patients with a proximal muscle weakness in whom the main limb-girdle muscular dystrophy syndromes had been ruled out; and 2) 38 patients with a distal distribution of weakness in whom a neurogenic affection had been excluded. Patients in whom a reduced sialylation of NCAM was suspected were studied for the presence of GNE mutations. In 3 patients, we found that NCAM had increased electrophoretic mobility, thus suggesting an abnormal sialylation of the protein. The genetic study demonstrated that they all carried pathogenic GNE mutations. Further studies demonstrated that hyposialylated NCAM, showing increased electrophoretic mobility on WB, is expressed by nonregenerating fibers in h-IBM/DMRV muscle. WB analysis of NCAM may be instrumental in the identification of h-IBM/DMRV with atypical clinical or pathologic features.

S-25OHD is Associated with Hand Grip Strength and Myopathy at Five Years in Girls: An Odense Child Cohort Study.

PubMed

Al-Jwadi, Rada Faris; Jespersen, Eva; Dalgård, Christine; Bilenberg, Niels; Christesen, Henrik Thybo

2018-05-16

Severe vitamin D deficiency may lead to myopathy in adults. Little is known about vitamin D and muscle strength in children. To test whether hand grip strength (HGS) in 5-year-old-children associates with serum 25-hydroxyvitamin D (s-25OHD) from pregnancy to five years. Observational study in the population-based Odense Child Cohort, Denmark. At five years, anthropometrics, body fat percentage by skin fold measurements and HGS were obtained (n=881). Myopathy was defined as HGS <10th percentile. S-25OHD2+3 was analyzed with liquid chromatography mass spectrometry (5-y; n=499). Mean (SD) HGS was higher for boys compared to girls, 8.76 (1.76) vs. 8.1 (1.64) kg, p<0.001. Mean (SD) 5-year s-25OHD was 70.7 (24.5) nmol/L. HGS was directly associated with height in girls, and with weight (directly) and body fat percentage (inversely) in both sexes (p<0.01 for all). In girls, 5-year s-25OHD was associated with HGS, adjusting for height, weight and body fat percentage, β=0.011 (95% CI 0.004;0.019), p=0.003. S-25OHD ≥75nmol/L associated with higher HGS compared to values <50nmol/L, adjusted β=0.783 (0.325;1.241), p=0.001. The odds of having myopathy were reduced by approximately 70% for s-25OHD ≥50 vs. <50 nmol/L, adjusted odds ratio 0.310 (95% CI 0.126;0.762), p=0.011. No associations were seen for boys. S-25OHD at other time points did not associate with 5-year HGS. Five-year s-25OHD was independently associated with HGS and myopathy in girls, but not in boys. Muscle strength may be dependent on vitamin D status even in the higher range in preschool girls. The sex difference remains unexplained.

14 CFR 23.853 - Passenger and crew compartment interiors.

Code of Federal Regulations, 2011 CFR

2011-01-01

... allowed— (1) There must be an adequate number of self-contained, removable ashtrays; and (2) Where the... the entry door and self-contained, removable ashtrays located conspicuously on or near the entry side... stowage compartments and compartments for stowing small items such as magazines and maps) must be self...

Dynamics of the Establishment of Multinucleate Compartments in Fusarium oxysporum

PubMed Central

Shahi, Shermineh; Beerens, Bas; Manders, Erik M. M.

2014-01-01

Nuclear dynamics can vary widely between fungal species and between stages of development of fungal colonies. Here we compared nuclear dynamics and mitotic patterns between germlings and mature hyphae in Fusarium oxysporum. Using fluorescently labeled nuclei and live-cell imaging, we show that F. oxysporum is subject to a developmental transition from a uninucleate to a multinucleate state after completion of colony initiation. We observed a special type of hypha that exhibits a higher growth rate, possibly acting as a nutrient scout. The higher growth rate is associated with a higher nuclear count and mitotic waves involving 2 to 6 nuclei in the apical compartment. Further, we found that dormant nuclei of intercalary compartments can reenter the mitotic cycle, resulting in multinucleate compartments with up to 18 nuclei in a single compartment. PMID:25398376

Metabolic profiles of exercise in patients with McArdle disease or mitochondrial myopathy

PubMed Central

Sharma, Rohit; Tadvalkar, Laura; Clish, Clary B.; Haller, Ronald G.; Mootha, Vamsi K.

2017-01-01

McArdle disease and mitochondrial myopathy impair muscle oxidative phosphorylation (OXPHOS) by distinct mechanisms: the former by restricting oxidative substrate availability caused by blocked glycogen breakdown, the latter because of intrinsic respiratory chain defects. We applied metabolic profiling to systematically interrogate these disorders at rest, when muscle symptoms are typically minimal, and with exercise, when symptoms of premature fatigue and potential muscle injury are unmasked. At rest, patients with mitochondrial disease exhibit elevated lactate and reduced uridine; in McArdle disease purine nucleotide metabolites, including xanthine, hypoxanthine, and inosine are elevated. During exercise, glycolytic intermediates, TCA cycle intermediates, and pantothenate expand dramatically in both mitochondrial disease and control subjects. In contrast, in McArdle disease, these metabolites remain unchanged from rest; but urea cycle intermediates are increased, likely attributable to increased ammonia production as a result of exaggerated purine degradation. Our results establish skeletal muscle glycogen as the source of TCA cycle expansion that normally accompanies exercise and imply that impaired TCA cycle flux is a central mechanism of restricted oxidative capacity in this disorder. Finally, we report that resting levels of long-chain triacylglycerols in mitochondrial myopathy correlate with the severity of OXPHOS dysfunction, as indicated by the level of impaired O2 extraction from arterial blood during peak exercise. Our integrated analysis of exercise and metabolism provides unique insights into the biochemical basis of these muscle oxidative defects, with potential implications for their clinical management. PMID:28716914

Hereditary inclusion-body myopathy with sparing of the quadriceps: the many tiles of an incomplete puzzle.

PubMed

Broccolini, A; Gidaro, T; Morosetti, R; Sancricca, C; Mirabella, M

2011-10-01

The hereditary inclusion-body myopathies encompass several syndromes with autosomal recessive or dominant inheritance. Despite a different clinical presentation they all have a progressive course leading to severe disability and share similar pathologic findings at the muscle biopsy. Quadriceps-sparing autosomal recessive hereditary inclusion-body myopathy (h-IBM) is the commonest form and is tied to mutations of the UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE) that codes for a rate-limiting enzyme in the sialic acid biosynthetic pathway. Despite the identification of the causative gene defect, it has not been clarified how mutations of the GNE gene impair muscle homeostasis. Although several lines of evidence argue in favor of an abnormal sialylation of muscle glycoproteins playing a key role in h-IBM pathogenesis, others studies have demonstrated new functions of the GNE gene, outside the sialic acid biosynthetic pathway, that may also be relevant. This review illustrates the clinical and pathologic characteristics of h-IBM and the main clues available to date concerning the possible pathogenic mechanisms of this disorder. Understanding the molecular mechanism underlying h-IBM pathology is a fundamental requisite to plan a future attempt to therapy.

Muscle Microvascular Blood Flow, Oxygenation, pH, and Perfusion Pressure Decrease in Simulated Acute Compartment Syndrome.

PubMed

Challa, Sravya T; Hargens, Alan R; Uzosike, Amarachi; Macias, Brandon R

2017-09-06

The current gold standard for diagnosing acute compartment syndrome (ACS) is an assessment of clinical signs, invasive measurement of intramuscular pressure (IMP), and measurement of local perfusion pressure. However, IMP measurements have several shortcomings, including pain, risk of infection, risk of technique error, plugging of the catheter tip, lack of consensus on the diagnostic pressure threshold, and lack of specificity and sensitivity. The objective of this study was to evaluate muscle hemodynamics, oxygenation, and pH as diagnostic parameters in a human model of ACS. We hypothesized that as IMP increases, muscle microvascular blood flow, oxygenation, and pH decrease in the anterior compartment of a leg at heart level and that they decrease significantly more when the leg is elevated further. An external pneumatic leg pressure chamber, combined with a venous stasis thigh cuff, was used to increase IMP and simulate ACS. Eight healthy subjects (5 males and 3 females; mean age, 26 years) had photoplethysmography and near-infrared spectroscopy-pH sensors placed over the middle aspect of the tibialis anterior muscle of the right (experimental) and left (control) legs. Leg chamber pressure conditions (40, 50, and 60 mm Hg) were applied in a randomized order after baseline measurements were taken. Data were collected continuously for each 11-minute pressure condition, with an 11-minute recovery period after each condition, and the average of the last 6 minutes was used for data analyses. The same protocol was repeated with each subject's legs elevated 12 cm above heart level. Data were analyzed using repeated-measures analysis of variance (ANOVA). As IMP increased, muscle microvascular blood flow (p = 0.01), oxygenation (p < 0.001), and pH (p < 0.001) all decreased significantly in the experimental leg compared with the control leg. At all IMP levels, leg elevation significantly decreased muscle oxygenation (p = 0.013) and perfusion pressure (p = 0.03) compared

Skeletal muscle biopsy analysis in reducing body myopathy and other FHL1-related disorders.

PubMed

Malfatti, Edoardo; Olivé, Montse; Taratuto, Ana Lía; Richard, Pascale; Brochier, Guy; Bitoun, Marc; Gueneau, Lucie; Laforêt, Pascal; Stojkovic, Tanya; Maisonobe, Thierry; Monges, Soledad; Lubieniecki, Fabiana; Vasquez, Gabriel; Streichenberger, Nathalie; Lacène, Emmanuelle; Saccoliti, Maria; Prudhon, Bernard; Alexianu, Marilena; Figarella-Branger, Dominique; Schessl, Joachim; Bonnemann, Carsten; Eymard, Bruno; Fardeau, Michel; Bonne, Gisèle; Romero, Norma Beatriz

2013-09-01

FHL1 mutations have been associated with various disorders that include reducing body myopathy (RBM), Emery-Dreifuss-like muscular dystrophy, isolated hypertrophic cardiomyopathy, and some overlapping conditions. We report a detailed histochemical, immunohistochemical, electron microscopic, and immunoelectron microscopic analyses of muscle biopsies from 18 patients carrying mutations in FHL1: 14 RBM patients (Group 1), 3 Emery-Dreifuss muscular dystrophy patients (Group 2), and 1 patient with hypertrophic cardiomyopathy and muscular hypertrophy (Group 2). Group 1 muscle biopsies consistently showed RBs associated with cytoplasmic bodies. The RBs showed prominent FHL1 immunoreactivity whereas desmin, αB-crystallin, and myotilin immunoreactivity surrounded RBs. By electron microscopy, RBs were composed of electron-dense tubulofilamentous material that seemed to spread progressively between the myofibrils and around myonuclei. By immunoelectron microscopy, FHL1 protein was found exclusively inside RBs. Group 2 biopsies showed mild dystrophic abnormalities without RBs; only minor nonspecific myofibrillar abnormalities were observed under electron microscopy. Molecular analysis revealed missense mutations in the second FHL1 LIM domain in Group 1 patients and ins/del or missense mutations within the fourth FHL1 LIM domain in Group 2 patients. Our findings expand the morphologic features of RBM, clearly demonstrate the localization of FHL1 in RBs, and further illustrate major morphologic differences among different FHL1-related myopathies.

The mechanism of muscle injury in the crush syndrome: ischemic versus pressure-stretch myopathy.

PubMed

Better, O S; Abassi, Z; Rubinstein, I; Marom, S; Winaver, Y; Silberman, M

1990-01-01

Crush injuries are ubiquitous, common sequelae in victims of seismic, industrial and military catastrophes, and were considered to be mainly due to ischemia of the affected limbs. Our clinical experience suggests that early in the crush syndrome, interference with the circulation may occur but is rare. The predominant earliest lesion in the crush syndrome is postulated to be pressure-stretch myopathy, rather than ischemic myopathy. It is proposed that at the membrane level, stretch increases sarcoplasmic influx of Na, Cl, H2O and Ca down their electrochemical gradient. Energy-requiring cationic extrusion pumps work at maximal capacity, but are unable to cope with the increased load. This results in cell swelling and increase in cytosolic and mitochondrial calcium with activation of autolytic destructive processes and interference with cellular respiration. Extensive muscle swelling may cause late muscle tamponade and myoneural ischemic damage (compartmental syndrome). Thus, whereas prevalent theory suggests that the sarcolemmal cationic pump activity is attenuated in the crush syndrome due to early ischemia, we propose that the cationic extrusion pump is maximally activated as in the amphotericin B model. Because the cationic pump is maximally activated in the stretched muscle and in cells exposed to amphotericin, these models rapidly deplete their scarce ATP stores and are susceptible to hypoxia in the face of initially normal circulation.

The Story of Equine Atypical Myopathy: A Review from the Beginning to a Possible End

PubMed Central

Votion, Dominique-Marie

2012-01-01

Atypical myopathy (AM) is a frequently fatal seasonal pasture myopathy that emerges in Europe. Outbreaks are of an acute and unexpected nature and practitioners should be prepared to handle these critically ill patients. This review retraces the history of AM and describes results of epidemiological investigations that were conducted to raise hypotheses concerning the etiology of this devastating disease as well as to be able to suggest potential preventive measures. Also, clinical studies have contributed to a better definition and recognition of the syndrome, whereas elucidation of the pathological process, identified as a multiple acyl-CoA dehydrogenase deficiency (MADD), was a great step forward improving medical management of AM and guiding the search for the etiological agent towards toxins that reproduce the identified defect. Treatment plans can be extrapolated from the described clinical signs and metabolic problems, but they remain limited to supportive care until the causative agent has been identified with certainty. Since treatment is still unsuccessful in the majority of cases, the main emphasis is currently still on prevention. This paper aims at being a practical support for equine clinicians dealing with AM and is based on discussion and comparison of the currently available scientific data. PMID:23762581

Defects of Vps15 in skeletal muscles lead to autophagic vacuolar myopathy and lysosomal disease

PubMed Central

Nemazanyy, Ivan; Blaauw, Bert; Paolini, Cecilia; Caillaud, Catherine; Protasi, Feliciano; Mueller, Amelie; Proikas-Cezanne, Tassula; Russell, Ryan C; Guan, Kun-Liang; Nishino, Ichizo; Sandri, Marco; Pende, Mario; Panasyuk, Ganna

2013-01-01

The complex of Vacuolar Protein Sorting 34 and 15 (Vps34 and Vps15) has Class III phosphatidylinositol 3-kinase activity and putative roles in nutrient sensing, mammalian Target Of Rapamycin (mTOR) activation by amino acids, cell growth, vesicular trafficking and autophagy. Contrary to expectations, here we show that Vps15-deficient mouse tissues are competent for LC3-positive autophagosome formation and maintain mTOR activation. However, an impaired lysosomal function in mutant cells is traced by accumulation of adaptor protein p62, LC3 and Lamp2 positive vesicles, which can be reverted to normal levels after ectopic overexpression of Vps15. Mice lacking Vps15 in skeletal muscles, develop a severe myopathy. Distinct from the autophagy deficient Atg7−/− mutants, pathognomonic morphological hallmarks of autophagic vacuolar myopathy (AVM) are observed in Vps15−/− mutants, including elevated creatine kinase plasma levels, accumulation of autophagosomes, glycogen and sarcolemmal features within the fibres. Importantly, Vps34/Vps15 overexpression in myoblasts of Danon AVM disease patients alleviates the glycogen accumulation. Thus, the activity of the Vps34/Vps15 complex is critical in disease conditions such as AVMs, and possibly a variety of other lysosomal storage diseases. PMID:23630012

Limited fiber type grouping in self-reinnervation cat tibialis anterior muscles.

PubMed

Unguez, G A; Roy, R R; Bodine-Fowler, S; Edgerton, V R

1996-10-01

The percent and distribution patterns of three immunohistochemically identified fiber types within the anterior compartment of the cat tibialis anterior were determined 6 months after denervation and self-reinnervation. After self-reinnervation, mean frequencies of slow (9%) and fast (91%) fibers were similar to those in control (12% and 88%, respectively) muscles. However, a lower proportion of fast-1 (26%) and a higher proportion of fast-2 (65%) fibers were observed in self-reinnervated than control (32% and 56%) muscles. Quantitation of adjacencies between fibers of similar myosin heavy chain (MHC) phenotype, a measure of type grouping, revealed that the frequencies of two slow or two fast-1 fibers being adjacent in self-reinnervated muscles were similar to control. In contrast, the frequency of fast-2/fast-2 fiber adjacencies found in self-reinnervated muscles (45%) was significantly higher than in control muscles (37%). In both groups, the frequency of adjacencies between slow, fast-1, or fast-2 fibers was largely attributable to the number of each fiber type present. These data show that the incidence of grouping within each fiber type present was not altered after 6 months of self-reinnervation. Minimal changes in the spatial distribution of fiber types following self-reinnervation in adults suggests a limited degree of conversion of muscle fibers to a MHC phenotype matching the motoneuron characteristics.

14 CFR 23.853 - Passenger and crew compartment interiors.

Code of Federal Regulations, 2010 CFR

2010-01-01

... constructed of at least fire resistant materials and must contain fires likely to occur in it under normal use... Design and Construction Fire Protection § 23.853 Passenger and crew compartment interiors. For each compartment to be used by the crew or passengers: (a) The materials must be at least flame-resistant; (b...

A novel Ile1455Thr variant in the skeletal muscle sodium channel alpha-subunit in a patient with a severe adult-onset proximal myopathy with electrical myotonia and a patient with mild paramyotonia phenotype.

PubMed

Bednarz, Marcin; Stunnenberg, Bas C; Kusters, Benno; Kamsteeg, Erik-Jan; Saris, Christiaan G; Groome, James; Winston, Vern; Meola, Giovanni; Jurkat-Rott, Karin; Voermans, Nicol C

2017-02-01

In sodium channelopathies, a severe fixed myopathy caused by a dominant mutation is rare. We describe two unrelated patients with a novel variant, p.Ile1455Thr, with phenotypes of paramyotonia in one case and fixed proximal myopathy with latent myotonia in another. In-vitro whole cell patch-clamp studies show that the mutation slows inactivation and accelerates recovery, in line with other paramyotonia variants with destabilized fast inactivation as pathomechanism. Additionally, p.IleI1455 causes a loss-of-function by reduced membrane insertion, right-shift of activation, and slowed kinetics. Molecular dynamics simulations comparing wild type and mutant Nav1.4 showed that threonine substitution hindered D4S4 mobility in response to membrane depolarization, consistent with effects of the mutation on channel inactivation. The fixed myopathy is likely to be associated to gain-of-function leading to sodium accumulation, regional edema, T-tubular swelling and mitochondrial stress. A possible contribution of the loss-of-function features towards myotonia and myopathy is discussed. Copyright © 2016. Published by Elsevier B.V.

The Presence of Multiple Cellular Defects Associated with a Novel G50E Iron-Sulfur Cluster Scaffold Protein (ISCU) Mutation Leads to Development of Mitochondrial Myopathy*

PubMed Central

Saha, Prasenjit Prasad; Kumar, S. K. Praveen; Srivastava, Shubhi; Sinha, Devanjan; Pareek, Gautam; D'Silva, Patrick

2014-01-01

Iron-sulfur (Fe-S) clusters are versatile cofactors involved in regulating multiple physiological activities, including energy generation through cellular respiration. Initially, the Fe-S clusters are assembled on a conserved scaffold protein, iron-sulfur cluster scaffold protein (ISCU), in coordination with iron and sulfur donor proteins in human mitochondria. Loss of ISCU function leads to myopathy, characterized by muscle wasting and cardiac hypertrophy. In addition to the homozygous ISCU mutation (g.7044G→C), compound heterozygous patients with severe myopathy have been identified to carry the c.149G→A missense mutation converting the glycine 50 residue to glutamate. However, the physiological defects and molecular mechanism associated with G50E mutation have not been elucidated. In this report, we uncover mechanistic insights concerning how the G50E ISCU mutation in humans leads to the development of severe ISCU myopathy, using a human cell line and yeast as the model systems. The biochemical results highlight that the G50E mutation results in compromised interaction with the sulfur donor NFS1 and the J-protein HSCB, thus impairing the rate of Fe-S cluster synthesis. As a result, electron transport chain complexes show significant reduction in their redox properties, leading to loss of cellular respiration. Furthermore, the G50E mutant mitochondria display enhancement in iron level and reactive oxygen species, thereby causing oxidative stress leading to impairment in the mitochondrial functions. Thus, our findings provide compelling evidence that the respiration defect due to impaired biogenesis of Fe-S clusters in myopathy patients leads to manifestation of complex clinical symptoms. PMID:24573684

Membrane order in the plasma membrane and endocytic recycling compartment

PubMed Central

Iaea, David B.; Maxfield, Frederick R.

2017-01-01

The cholesterol content of membranes plays an important role in organizing membranes for signal transduction and protein trafficking as well as in modulating the biophysical properties of membranes. While the properties of model or isolated membranes have been extensively studied, there has been little evaluation of internal membranes in living cells. Here, we use a Nile Red based probe, NR12S, and ratiometric live cell imaging, to analyze the membrane order of the plasma membrane and endocytic recycling compartment. We find that after a brief incubation to allow endocytosis, NR12S is distributed between the plasma membrane and the endocytic recycling compartment. The NR12S reports that the endocytic recycling compartment is more highly ordered than the plasma membrane. We also find that the plasma membrane and the endocytic recycling compartment are differentially affected by altering cellular cholesterol levels. The membrane order of the plasma membrane, but not the endocytic recycling compartment, is altered significantly when cellular cholesterol content is increased or decreased by 20%. These results demonstrate that changes in cellular cholesterol differentially alter membrane order within different organelles. PMID:29125865

9 CFR 354.241 - Cleaning of rooms and compartments.

Code of Federal Regulations, 2013 CFR

2013-01-01

... compartments. Rooms, compartments, or other parts of the official plant shall be kept clean and in sanitary... light fixtures in the official plant shall be kept clean. (c) All docks and rooms shall be kept clean... rooms should be kept clean at all times. (e) Floors in live rabbit holding rooms shall be cleaned with...

9 CFR 354.241 - Cleaning of rooms and compartments.

Code of Federal Regulations, 2014 CFR

2014-01-01

... compartments. Rooms, compartments, or other parts of the official plant shall be kept clean and in sanitary... light fixtures in the official plant shall be kept clean. (c) All docks and rooms shall be kept clean... rooms should be kept clean at all times. (e) Floors in live rabbit holding rooms shall be cleaned with...

Mutations in repeating structural motifs of tropomyosin cause gain of function in skeletal muscle myopathy patients

PubMed Central

Marston, Steven; Memo, Massimiliano; Messer, Andrew; Papadaki, Maria; Nowak, Kristen; McNamara, Elyshia; Ong, Royston; El-Mezgueldi, Mohammed; Li, Xiaochuan; Lehman, William

2013-01-01

The congenital myopathies include a wide spectrum of clinically, histologically and genetically variable neuromuscular disorders many of which are caused by mutations in genes for sarcomeric proteins. Some congenital myopathy patients have a hypercontractile phenotype. Recent functional studies demonstrated that ACTA1 K326N and TPM2 ΔK7 mutations were associated with hypercontractility that could be explained by increased myofibrillar Ca2+ sensitivity. A recent structure of the complex of actin and tropomyosin in the relaxed state showed that both these mutations are located in the actin–tropomyosin interface. Tropomyosin is an elongated molecule with a 7-fold repeated motif of around 40 amino acids corresponding to the 7 actin monomers it interacts with. Actin binds to tropomyosin electrostatically at two points, through Asp25 and through a cluster of amino acids that includes Lys326, mutated in the gain-of-function mutation. Asp25 interacts with tropomyosin K6, next to K7 that was mutated in the other gain-of-function mutation. We identified four tropomyosin motifs interacting with Asp25 (K6-K7, K48-K49, R90-R91 and R167-K168) and three E-E/D-K/R motifs interacting with Lys326 (E139, E181 and E218), and we predicted that the known skeletal myopathy mutations ΔK7, ΔK49, R91G, ΔE139, K168E and E181K would cause a gain of function. Tests by an in vitro motility assay confirmed that these mutations increased Ca2+ sensitivity, while mutations not in these motifs (R167H, R244G) decreased Ca2+ sensitivity. The work reported here explains the molecular mechanism for 6 out of 49 known disease-causing mutations in the TPM2 and TPM3 genes, derived from structural data of the actin–tropomyosin interface. PMID:23886664

49 CFR 38.127 - Sleeping compartments.

Code of Federal Regulations, 2012 CFR

2012-10-01

... SPECIFICATIONS FOR TRANSPORTATION VEHICLES Intercity Rail Cars and Systems § 38.127 Sleeping compartments. (a...., heating and air conditioning controls, lighting controls, call buttons, electrical outlets, etc.) shall be...

49 CFR 38.127 - Sleeping compartments.

Code of Federal Regulations, 2013 CFR

2013-10-01

... SPECIFICATIONS FOR TRANSPORTATION VEHICLES Intercity Rail Cars and Systems § 38.127 Sleeping compartments. (a...., heating and air conditioning controls, lighting controls, call buttons, electrical outlets, etc.) shall be...

49 CFR 38.127 - Sleeping compartments.

Code of Federal Regulations, 2014 CFR

2014-10-01

... SPECIFICATIONS FOR TRANSPORTATION VEHICLES Intercity Rail Cars and Systems § 38.127 Sleeping compartments. (a...., heating and air conditioning controls, lighting controls, call buttons, electrical outlets, etc.) shall be...

49 CFR 38.127 - Sleeping compartments.

Code of Federal Regulations, 2011 CFR

2011-10-01

... SPECIFICATIONS FOR TRANSPORTATION VEHICLES Intercity Rail Cars and Systems § 38.127 Sleeping compartments. (a...., heating and air conditioning controls, lighting controls, call buttons, electrical outlets, etc.) shall be...

49 CFR 38.127 - Sleeping compartments.

Code of Federal Regulations, 2010 CFR

2010-10-01

... SPECIFICATIONS FOR TRANSPORTATION VEHICLES Intercity Rail Cars and Systems § 38.127 Sleeping compartments. (a...., heating and air conditioning controls, lighting controls, call buttons, electrical outlets, etc.) shall be...

Compartment Syndrome of the Hand: A Rare Sequela of Transradial Cardiac Catheterization

PubMed Central

Jue, Jennifer; Karam, Joseph A.; Mejia, Alfonso

2017-01-01

A 64-year-old man who underwent percutaneous coronary intervention via right radial artery access reported right-hand pain and swelling 2 hours after the procedure. He had developed compartment syndrome of the hand, specifically with muscular compromise of the thenar compartment but with no involvement of the forearm. He underwent emergency right-hand compartment release and carpal tunnel release, followed by an uneventful postoperative course. In addition to our patient's case, we discuss compartment syndrome of the hand and related issues. PMID:28265219

[Orbital compartment syndrome. The most frequent cause of blindness following facial trauma].

PubMed

Klenk, Gusztáv; Katona, József; Kenderfi, Gábor; Lestyán, János; Gombos, Katalin; Hirschberg, Andor

2017-09-01

Although orbital compartment syndrome is a rare condition, it is still the most common cause of blindness following simple or complicated facial fractures. Its pathomechanism is similar to the compartment syndrome in the limb. Little extra fluid (blood, oedema, brain, foreign body) in a non-space yielding space results with increasingly higher pressures within a short period of time. Unless urgent surgical intervention is performed the blocked circulation of the central retinal artery will result irreversible ophthalmic nerve damage and blindness. Aim, material and method: A retrospective analysis of ten years, 2007-2017, in our hospital among those patients referred to us with facial-head trauma combined with blindness. 571 patients had fractures involving the orbit. 23 patients become blind from different reasons. The most common cause was orbital compartment syndrome in 17 patients; all had retrobulbar haematomas as well. 6 patients with retrobulbar haematoma did not develop compartment syndrome. Compartment syndrome was found among patient with extensive and minimal fractures such as with large and minimal haematomas. Early lateral canthotomy and decompression saved 7 patients from blindness. We can not predict and do not know why some patients develop orbital compartment syndrome. Compartment syndrome seems independent from fracture mechanism, comminution, dislocation, amount of orbital bleeding. All patients are in potential risk with midface fractures. We have a high suspicion that orbital compartment syndrome has been somehow missed out in the recommended textbooks of our medical universities and in the postgraduate trainings. Thus compartment syndrome is not recognized. Teaching, training and early surgical decompression is the only solution to save the blind eye. Orv Hetil. 2017; 158(36): 1410-1420.

Abdominal compartment syndrome: a rare complication of plication of the diaphragm.

PubMed

Phadnis, Joideep; Pilling, John E; Evans, Timothy W; Goldstraw, Peter

2006-07-01

Abdominal compartment syndrome is an increasingly recognized phenomenon. We report the case of an otherwise fit and healthy 42-year-old man who underwent plication of the right hemidiaphragm for idiopathic phrenic paresis. His postoperative recovery was complicated by abdominal compartment syndrome, which was managed conservatively. We believe this is the only report of this complication after diaphragmatic plication and one of very few reported thoracic causes of abdominal compartment syndrome.

Are certain fractures at increased risk for compartment syndrome after civilian ballistic injury?

PubMed

Meskey, Thomas; Hardcastle, John; O'Toole, Robert V

2011-11-01

Compartment syndrome after ballistic fracture is uncommon but potentially devastating. Few data are available to help guide clinicians regarding risk factors for developing compartment syndrome after ballistic fractures. Our primary hypothesis was that ballistic fractures of certain bones would be at higher risk for development of compartment syndrome. A retrospective review at a Level I trauma center from 2001 through 2007 yielded 650 patients with 938 fractures resulting from gunshots. We reviewed all operative notes, clinic notes, discharge summaries, and data from our prospective trauma database. Cases in which the attending orthopedic surgeon diagnosed compartment syndrome and performed fasciotomy were considered cases with compartment syndrome. We excluded all prophylactic fasciotomies. Univariate analyses were conducted to identify risk factors associated with development of compartment syndrome. Twenty-six (2.8%) of the 938 fractures were associated with compartment syndrome. Only fibular (11.6%) and tibial (11.4%) fractures had incidence significantly higher than baseline for all ballistic fractures (p < 0.001). Fractures of the proximal third of the fibula were more likely to result in compartment syndrome than fractures of the middle or distal third (p = 0.03), as were fractures of the proximal third of the tibia (p = 0.01). No other demographic or injury parameters were associated with compartment syndrome. Ballistic fractures of the fibula and tibia are at increased risk for development of compartment syndrome over other ballistic fractures. We recommend increased vigilance when treating these injuries, particularly if the fracture is in the proximal aspect of the bone or is associated with vascular injury.

Loss-of-function mutations in SCN4A cause severe foetal hypokinesia or 'classical' congenital myopathy.

PubMed

Zaharieva, Irina T; Thor, Michael G; Oates, Emily C; van Karnebeek, Clara; Hendson, Glenda; Blom, Eveline; Witting, Nanna; Rasmussen, Magnhild; Gabbett, Michael T; Ravenscroft, Gianina; Sframeli, Maria; Suetterlin, Karen; Sarkozy, Anna; D'Argenzio, Luigi; Hartley, Louise; Matthews, Emma; Pitt, Matthew; Vissing, John; Ballegaard, Martin; Krarup, Christian; Slørdahl, Andreas; Halvorsen, Hanne; Ye, Xin Cynthia; Zhang, Lin-Hua; Løkken, Nicoline; Werlauff, Ulla; Abdelsayed, Mena; Davis, Mark R; Feng, Lucy; Phadke, Rahul; Sewry, Caroline A; Morgan, Jennifer E; Laing, Nigel G; Vallance, Hilary; Ruben, Peter; Hanna, Michael G; Lewis, Suzanne; Kamsteeg, Erik-Jan; Männikkö, Roope; Muntoni, Francesco

2016-03-01

Congenital myopathies are a clinically and genetically heterogeneous group of muscle disorders characterized by congenital or early-onset hypotonia and muscle weakness, and specific pathological features on muscle biopsy. The phenotype ranges from foetal akinesia resulting in in utero or neonatal mortality, to milder disorders that are not life-limiting. Over the past decade, more than 20 new congenital myopathy genes have been identified. Most encode proteins involved in muscle contraction; however, mutations in ion channel-encoding genes are increasingly being recognized as a cause of this group of disorders. SCN4A encodes the α-subunit of the skeletal muscle voltage-gated sodium channel (Nav1.4). This channel is essential for the generation and propagation of the muscle action potential crucial to muscle contraction. Dominant SCN4A gain-of-function mutations are a well-established cause of myotonia and periodic paralysis. Using whole exome sequencing, we identified homozygous or compound heterozygous SCN4A mutations in a cohort of 11 individuals from six unrelated kindreds with congenital myopathy. Affected members developed in utero- or neonatal-onset muscle weakness of variable severity. In seven cases, severe muscle weakness resulted in death during the third trimester or shortly after birth. The remaining four cases had marked congenital or neonatal-onset hypotonia and weakness associated with mild-to-moderate facial and neck weakness, significant neonatal-onset respiratory and swallowing difficulties and childhood-onset spinal deformities. All four surviving cohort members experienced clinical improvement in the first decade of life. Muscle biopsies showed myopathic features including fibre size variability, presence of fibrofatty tissue of varying severity, without specific structural abnormalities. Electrophysiology suggested a myopathic process, without myotonia. In vitro functional assessment in HEK293 cells of the impact of the identified SCN4A

The longest telomeres: a general signature of adult stem cell compartments

PubMed Central

Flores, Ignacio; Canela, Andres; Vera, Elsa; Tejera, Agueda; Cotsarelis, George; Blasco, María A.

2008-01-01

Identification of adult stem cells and their location (niches) is of great relevance for regenerative medicine. However, stem cell niches are still poorly defined in most adult tissues. Here, we show that the longest telomeres are a general feature of adult stem cell compartments. Using confocal telomere quantitative fluorescence in situ hybridization (telomapping), we find gradients of telomere length within tissues, with the longest telomeres mapping to the known stem cell compartments. In mouse hair follicles, we show that cells with the longest telomeres map to the known stem cell compartments, colocalize with stem cell markers, and behave as stem cells upon treatment with mitogenic stimuli. Using K15-EGFP reporter mice, which mark hair follicle stem cells, we show that GFP-positive cells have the longest telomeres. The stem cell compartments in small intestine, testis, cornea, and brain of the mouse are also enriched in cells with the longest telomeres. This constitutes the description of a novel general property of adult stem cell compartments. Finally, we make the novel finding that telomeres shorten with age in different mouse stem cell compartments, which parallels a decline in stem cell functionality, suggesting that telomere loss may contribute to stem cell dysfunction with age. PMID:18283121

A mouse model offers novel insights into the myopathy and tendinopathy often associated with pseudoachondroplasia and multiple epiphyseal dysplasia

PubMed Central

Piróg, Katarzyna A.; Jaka, Oihane; Katakura, Yoshihisa; Meadows, Roger S.; Kadler, Karl E.; Boot-Handford, Raymond P.; Briggs, Michael D.

2010-01-01

Pseudoachondroplasia (PSACH) and multiple epiphyseal dysplasia (MED) are relatively common skeletal dysplasias belonging to the same bone dysplasia family. PSACH is characterized by generalized epi-metaphyseal dysplasia, short-limbed dwarfism, joint laxity and early onset osteoarthritis. MED is a milder disease with radiographic features often restricted to the epiphyses of the long bones. PSACH and some forms of MED result from mutations in cartilage oligomeric matrix protein (COMP), a pentameric glycoprotein found in cartilage, tendon, ligament and muscle. PSACH-MED patients often have a mild myopathy characterized by mildly increased plasma creatine kinase levels, a variation in myofibre size and/or small atrophic fibres. In some instances, patients are referred to neuromuscular clinics prior to the diagnosis of an underlying skeletal dysplasia; however, the myopathy associated with PSACH-MED has not previously been studied. In this study, we present a detailed study of skeletal muscle, tendon and ligament from a mouse model of mild PSACH harbouring a COMP mutation. Mutant mice exhibited a progressive muscle weakness associated with an increased number of muscle fibres with central nuclei at the perimysium and at the myotendinous junction. Furthermore, the distribution of collagen fibril diameters in the mutant tendons and ligaments was altered towards thicker collagen fibrils, and the tendons became more lax in cyclic strain tests. We hypothesize that the myopathy in PSACH-MED originates from an underlying tendon and ligament pathology that is a direct result of structural abnormalities to the collagen fibril architecture. This is the first comprehensive characterization of the musculoskeletal phenotype of PSACH-MED and is directly relevant to the clinical management of these patients. PMID:19808781

Measuring Compartment Size and Gas Solubility in Marine Mammals

DTIC Science & Technology

2015-09-30

bends? Effect of diving behaviour and physiology on modelled gas exchange for three species: Ziphius cavirostris, Mesoplodon densirostris and Hyperoodon...1 DISTRIBUTION STATEMENT A. Approved for public release; distribution is unlimited. Measuring Compartment Size and Gas Solubility in Marine...is to develop methods to estimate marine mamal tissue compartment sizes, and tissue gas solubility. We aim to improve the data available for the

The Spectrum of Mitochondrial Ultrastructural Defects in Mitochondrial Myopathy

PubMed Central

Vincent, Amy E.; Ng, Yi Shiau; White, Kathryn; Davey, Tracey; Mannella, Carmen; Falkous, Gavin; Feeney, Catherine; Schaefer, Andrew M.; McFarland, Robert; Gorman, Grainne S.; Taylor, Robert W.; Turnbull, Doug M.; Picard, Martin

2016-01-01

Mitochondrial functions are intrinsically linked to their morphology and membrane ultrastructure. Characterizing abnormal mitochondrial structural features may thus provide insight into the underlying pathogenesis of inherited and acquired mitochondrial diseases. Following a systematic literature review on ultrastructural defects in mitochondrial myopathy, we investigated skeletal muscle biopsies from seven subjects with genetically defined mtDNA mutations. Mitochondrial ultrastructure and morphology were characterized using two complimentary approaches: transmission electron microscopy (TEM) and serial block face scanning EM (SBF-SEM) with 3D reconstruction. Six ultrastructural abnormalities were identified including i) paracrystalline inclusions, ii) linearization of cristae and abnormal angular features, iii) concentric layering of cristae membranes, iv) matrix compartmentalization, v) nanotunelling, and vi) donut-shaped mitochondria. In light of recent molecular advances in mitochondrial biology, these findings reveal novel aspects of mitochondrial ultrastructure and morphology in human tissues with implications for understanding the mechanisms linking mitochondrial dysfunction to disease. PMID:27506553

Fire safety evaluation of aircraft lavatory and cargo compartments

NASA Technical Reports Server (NTRS)

Kourtides, D. A.; Parker, J. A.; Hilado, C. J.; Anderson, R. A.; Tustin, E.; Arnold, D. E.; Gaume, J. G.; Binding, A. T.; Mikeska, J. L.

1975-01-01

Large-scale aircraft lavatory and cargo compartment fire tests are described. Tests were conducted to evaluate the effectiveness of these compartments to contain fire and smoke. Two tests were conducted and are detailed. Test 1 involved a production Boeing 747 lavatory of the latest design installed in an enclosure outside the aircraft, to collect gases and expose animals to these gases. Results indicate that the interior of the lavatory was completely burned, evolving smoke and combustion products in the enclosure. Test 2 involved a simulated Douglas DC-10 cargo compartment retro-fitted with standard fiberglass liner. The fire caused excessive damage to the liner and burned through the ceiling in two areas. Test objectives, methods, materials, and results are presented and discussed.

Exercise Induced Rhabdomyolysis with Compartment Syndrome and Renal Failure

PubMed Central

Bhalla, Mary Colleen; Dick-Perez, Ryan

2014-01-01

Exertional rhabdomyolysis is sequela that is occasionally seen after strenuous exercise. The progression to compartment syndrome or renal failure is a rare complication that requires prompt recognition and treatment to prevent morbidity (Giannoglou et al. 2007). We present a case of a 22-year-old college football player who presented to the emergency department (ED) after a typical leg workout as part of his weight conditioning. He was found to have rhabdomyolysis with evidence of renal insufficiency. His condition progressed to bilateral compartment syndrome and renal failure requiring dialysis. After bilateral fasciotomies were performed he had resolution of his compartment syndrome. He continued to be dialysis dependent and had no return of his renal function at discharge 12 days after admission. PMID:25105034

Exercise induced rhabdomyolysis with compartment syndrome and renal failure.

PubMed

Bhalla, Mary Colleen; Dick-Perez, Ryan

2014-01-01

Exertional rhabdomyolysis is sequela that is occasionally seen after strenuous exercise. The progression to compartment syndrome or renal failure is a rare complication that requires prompt recognition and treatment to prevent morbidity (Giannoglou et al. 2007). We present a case of a 22-year-old college football player who presented to the emergency department (ED) after a typical leg workout as part of his weight conditioning. He was found to have rhabdomyolysis with evidence of renal insufficiency. His condition progressed to bilateral compartment syndrome and renal failure requiring dialysis. After bilateral fasciotomies were performed he had resolution of his compartment syndrome. He continued to be dialysis dependent and had no return of his renal function at discharge 12 days after admission.

CscoreTool: fast Hi-C compartment analysis at high resolution.

PubMed

Zheng, Xiaobin; Zheng, Yixian

2018-05-01

The genome-wide chromosome conformation capture (Hi-C) has revealed that the eukaryotic genome can be partitioned into A and B compartments that have distinctive chromatin and transcription features. Current Principle Component Analyses (PCA)-based method for the A/B compartment prediction based on Hi-C data requires substantial CPU time and memory. We report the development of a method, CscoreTool, which enables fast and memory-efficient determination of A/B compartments at high resolution even in datasets with low sequencing depth. https://github.com/scoutzxb/CscoreTool. xzheng@carnegiescience.edu. Supplementary data are available at Bioinformatics online.

Current thinking about acute compartment syndrome of the lower extremity

PubMed Central

Shadgan, Babak; Menon, Matthew; Sanders, David; Berry, Gregg; Martin, Claude; Duffy, Paul; Stephen, David; O’Brien, Peter J.

2010-01-01

Acute compartment syndrome of the lower extremity is a clinical condition that, although uncommon, is seen fairly regularly in modern orthopedic practice. The pathophysiology of the disorder has been extensively described and is well known to physicians who care for patients with musculoskeletal injuries. The diagnosis, however, is often difficult to make. In this article, we review the clinical risk factors of acute compartment syndrome of the lower extremity, identify the current concepts of diagnosis and discuss appropriate treatment plans. We also describe the Canadian medicolegal environment in regard to compartment syndrome of the lower extremity. PMID:20858378

Hyperpigmentation and atrophy in folds as cutaneous manifestation in a case of mitochondrial myopathy.

PubMed

Campuzano-García, Andrés Eduardo; Rodríguez-Arámbula, Adriana; Torres-Alvarez, Bertha; Castanedo-Cázares, Juan Pablo

2015-05-18

Mitochondrial myopathies are inborn metabolism defect diseases manifested by symptoms reflecting failure of the final step in the mitochondrial respiratory chain. Clinical expression of these conditions can vary widely, but typically includes organ systems with a high energy demand, such as striated muscle, myocardium, and nervous and liver tissues. In contrast, cutaneous manifestations are rare and are non-specific, most commonly presenting as pigmentation disorders. In this case report, we present a case of Alpers syndrome accompanied by hyperpigmentation and atrophy in skin folds.

Myasthenic decrement and myasthenic myopathy. A study on the effects of thymectomy.

PubMed Central

Pinelli, P; Arrigo, A; Moglia, A

1975-01-01

Motor unit action potentials, M responses to repetitive nerve stimulation, and anticholinesterase tests were investigated in 12 myasthenic patients before and after thymectomy. In six of them the endarterial acetylcholine test was also carried out. Responsiveness to ACTH or to prednisone treatment was evaluated before and after thymectomy. The typical myasthenic presynaptic disorders were improved by thymectomy, while signs of myasthenic myopathy (according to Rowland's definition) were apparently increased. This process of 'functional myopathophanerosis' is discussed and explained in terms of a previous presynaptic disorder blocking the voluntary recruitment threshold of those motor units which are most affected at both presynaptic and postsynaptic level. Images PMID:168321

Mutations in the β-myosin rod cause myosin storage myopathy via multiple mechanisms

PubMed Central

Armel, Thomas Z.; Leinwand, Leslie A.

2009-01-01

Myosin storage myopathy (MSM) is a congenital myopathy characterized by the presence of subsarcolemmal inclusions of myosin in the majority of type I muscle fibers, and has been linked to 4 mutations in the slow/cardiac muscle myosin, β-MyHC (MYH7). Although the majority of the >230 disease causing mutations in MYH7 are located in the globular head region of the molecule, those responsible for MSM are part of a subset of MYH7 mutations that are located in the α-helical coiled-coil tail. Mutations in the myosin head are thought to affect the ATPase and actin-binding properties of the molecule. To date, however, there are no reports of the molecular mechanism of pathogenesis for mutations in the rod region of muscle myosins. Here, we present analysis of 4 mutations responsible for MSM: L1793P, R1845W, E1886K, and H1901L. We show that each MSM mutation has a different molecular phenotype, suggesting that there are multiple mechanisms by which MSM can be caused. These mechanisms range from thermodynamic and functional irregularities of individual proteins (L1793P), to varying defects in the assembly and stability of filaments formed from the proteins (R1845W, E1886K, and H1901L). In addition to furthering our understanding of MSM, these observations provide the first insight into how mutations affect the rod region of muscle myosins, and provide a framework for future studies of disease-causing mutations in this region of the molecule. PMID:19336582

Compartments in a marine food web associated with phylogeny, body mass, and habitat structure.

PubMed

Rezende, Enrico L; Albert, Eva M; Fortuna, Miguel A; Bascompte, Jordi

2009-08-01

A long-standing question in community ecology is whether food webs are organized in compartments, where species within the same compartment interact frequently among themselves, but show fewer interactions with species from other compartments. Finding evidence for this community organization is important since compartmentalization may strongly affect food web robustness to perturbation. However, few studies have found unequivocal evidence of compartments, and none has quantified the suite of mechanisms generating such a structure. Here, we combine computational tools from the physics of complex networks with phylogenetic statistical methods to show that a large marine food web is organized in compartments, and that body size, phylogeny, and spatial structure are jointly associated with such a compartmentalized structure. Sharks account for the majority of predatory interactions within their compartments. Phylogenetically closely related shark species tend to occupy different compartments and have divergent trophic levels, suggesting that competition may play an important role structuring some of these compartments. Current overfishing of sharks has the potential to change the structural properties, which might eventually affect the stability of the food web.

SChloro: directing Viridiplantae proteins to six chloroplastic sub-compartments.

PubMed

Savojardo, Castrense; Martelli, Pier Luigi; Fariselli, Piero; Casadio, Rita

2017-02-01

Chloroplasts are organelles found in plants and involved in several important cell processes. Similarly to other compartments in the cell, chloroplasts have an internal structure comprising several sub-compartments, where different proteins are targeted to perform their functions. Given the relation between protein function and localization, the availability of effective computational tools to predict protein sub-organelle localizations is crucial for large-scale functional studies. In this paper we present SChloro, a novel machine-learning approach to predict protein sub-chloroplastic localization, based on targeting signal detection and membrane protein information. The proposed approach performs multi-label predictions discriminating six chloroplastic sub-compartments that include inner membrane, outer membrane, stroma, thylakoid lumen, plastoglobule and thylakoid membrane. In comparative benchmarks, the proposed method outperforms current state-of-the-art methods in both single- and multi-compartment predictions, with an overall multi-label accuracy of 74%. The results demonstrate the relevance of the approach that is eligible as a good candidate for integration into more general large-scale annotation pipelines of protein subcellular localization. The method is available as web server at http://schloro.biocomp.unibo.it gigi@biocomp.unibo.it.

Gluteal Compartment Syndrome following an Iliac Bone Marrow Aspiration

PubMed Central

Vega-Najera, Carlos; Leal-Contreras, Carlos; Leal-Berumen, Irene

2013-01-01

The compartment syndrome is a condition characterized by a raised hydraulic pressure within a closed and non expandable anatomical space. It leads to a vascular insufficiency that becomes critical once the vascular flow cannot return the fluids back to the venous system. This causes a potential irreversible damage of the contents of the compartment, especially within the muscle tissues. Gluteal compartment syndrome (GCS) secondary to hematomas is seldom reported. Here we present a case of a 51-year-old patient with history of a non-Hodgkin lymphoma who underwent a bone marrow aspiration from the posterior iliac crest that had excessive bleeding at the puncture zone. The patient complained of increasing pain, tenderness, and buttock swelling. Intraoperative pressure validation of the gluteal compartment was performed, and a GCS was diagnosed. The patient was treated with a gluteal region fasciotomy. The patient recovered from pain and swelling and was discharged shortly after from the hospital. We believe clotting and hematologic disorders are a primary risk factor in patients who require bone marrow aspirations or biopsies. It is important to improve awareness of GCS in order to achieve early diagnosis, avoid complications, and have a better prognosis. PMID:24392235

Biomechanical comparison of anterior cervical plating and combined anterior/lateral mass plating.

PubMed

Adams, M S; Crawford, N R; Chamberlain, R H; Bse; Sonntag, V K; Dickman, C A

2001-01-01

Previous studies showed anterior plates of older design to be inadequate for stabilizing the cervical spine in all loading directions. No studies have investigated enhancement in stability obtained by combining anterior and posterior plates. To determine which modes of loading are stabilized by anterior plating after a cervical burst fracture and to determine whether adding posterior plating further significantly stabilizes the construct. A repeated-measures in vitro biomechanical flexibility experiment was performed to investigate how surgical destabilization and subsequent addition of hardware components alter spinal stability. Six human cadaveric specimens were studied. Angular range of motion (ROM) and neutral zone (NZ) were quantified during flexion, extension, lateral bending, and axial rotation. Nonconstraining, nondestructive torques were applied while recording three-dimensional motion optoelectronically. Specimens were tested intact, destabilized by simulated burst fracture with posterior distraction, plated anteriorly with a unicortical locking system, and plated with a combined anterior/posterior construct. The anterior plate significantly (p<.05) reduced the ROM relative to normal in all modes of loading and significantly reduced the NZ in flexion and extension. Addition of the posterior plates further significantly reduced the ROM in all modes of loading and reduced the NZ in lateral bending. Anterior plating systems are capable of substantially stabilizing the cervical spine in all modes of loading after a burst fracture. The combined approach adds significant stability over anterior plating alone in treating this injury but may be unnecessary clinically. Further study is needed to assess the added clinical benefits of the combined approach and associated risks.

Perforated peptic ulcer associated with abdominal compartment syndrome.

PubMed

Lynn, Jiun-Jen; Weng, Yi-Ming; Weng, Chia-Sui

2008-11-01

Abdominal compartment syndrome (ACS) is defined as an increased intra-abdominal pressure with adverse physiologic consequences. Abdominal compartment syndrome caused by perforated peptic ulcer is rare owing to early diagnosis and management. Delayed recognition of perforated peptic ulcer with pneumoperitoneum, bowel distension, and decreased abdominal wall compliance can make up a vicious circle and lead to ACS. We report a case of perforated peptic ulcer associated with ACS. A 74-year-old man with old stroke and dementia history was found to have distended abdomen, edema of bilateral legs, and cyanosis. Laboratory tests revealed deterioration of liver and kidney function. Abdominal compartment syndrome was suspected, and image study was arranged to find the cause. The study showed pneumoperitoneum, contrast stasis in heart with decreased caliber of vessels below the abdominal aortic level, and diffuse lymphedema at the abdominal walls. Emergent laparotomy was performed. Perforated peptic ulcer was noted and the gastrorrhaphy was done. The symptoms, and liver and kidney function improved right after emergent operation.

Numerical analysis of air-flow and temperature field in a passenger car compartment

NASA Astrophysics Data System (ADS)

Kamar, Haslinda Mohamed; Kamsah, Nazri; Mohammad Nor, Ahmad Miski

2012-06-01

This paper presents a numerical study on the temperature field inside a passenger's compartment of a Proton Wira saloon car using computational fluid dynamics (CFD) method. The main goal is to investigate the effects of different glazing types applied onto the front and rear windscreens of the car on the distribution of air-temperature inside the passenger compartment in the steady-state conditions. The air-flow condition in the passenger's compartment is also investigated. Fluent CFD software was used to develop a three-dimensional symmetrical model of the passenger's compartment. Simplified representations of the driver and one rear passenger were incorporated into the CFD model of the passenger's compartment. Two types of glazing were considered namely clear insulated laminated tint (CIL) with a shading coefficient of 0.78 and green insulated laminate tint (GIL) with a shading coefficient of 0.5. Results of the CFD analysis were compared with those obtained when the windscreens are made up of clear glass having a shading coefficient of 0.86. Results of the CFD analysis show that for a given glazing material, the temperature of the air around the driver is slightly lower than the air around the rear passenger. Also, the use of GIL glazing material on both the front and rear windscreens significantly reduces the air temperature inside the passenger's compartment of the car. This contributes to a better thermal comfort condition to the occupants. Swirling air flow condition occurs in the passenger compartment. The air-flow intensity and velocity are higher along the side wall of the passenger's compartment compared to that along the middle section of the compartment. It was also found that the use of glazing materials on both the front and rear windscreen has no significant effects on the air-flow condition inside the passenger's compartment of the car.

Abdominal compartment syndrome related to noninvasive ventilation.

PubMed

De Keulenaer, Bart L; De Backer, Adelard; Schepens, Dirk R; Daelemans, Ronny; Wilmer, Alexander; Malbrain, Manu L N G

2003-07-01

To study the effects of noninvasive positive pressure ventilation (NIPPV) on intra-abdominal pressure. Single case report from a tertiary teaching hospital. A 65-year-old man who experienced a sudden respiratory and cardiovascular collapse during NIPPV. This was caused by gastric overdistension due to aerophagia followed by raised intra-abdominal pressure leading to intra-abdominal hypertension and abdominal compartment syndrome. The respiratory and cardiovascular problems resolved immediately after the introduction of a nasogastric tube. This resulted in normalization of IAP. This is the first case reported of an abdominal compartment syndrome related to NIPPV. Clinicians should be aware of this possible complication while using NIPPV.

[The perichromatin compartment of the cell nucleus].

PubMed

Bogoliubov, D S

2014-01-01

In this review, the data on the structure and composition of the perichromatin compartment, a special border area between the condensed chromatin and the interchromatin space of the cell nucleus, are discussed in the light of the concept of nuclear functions in complex nuclear architectonics. Morphological features, molecular composition and functions of main extrachromosomal structures of the perichromatin compartment, perichromatin fibrils (PFs) and perichromatin granules (PGs) including nuclear stress-bodies (nSBs) that are derivates of the PGs under heat shock, are presented. A special attention was paid to the features of the molecular compositions of PFs and PGs in different cell types and at different physiological conditions.

Measuring Compartment Size and Gas Solubility in Marine Mammals

DTIC Science & Technology

2014-09-30

analyzed by gas chromatography . Injection of the sample into the gas chromatograph is done using a sample loop to minimize volume injection error. We...1 DISTRIBUTION STATEMENT A. Approved for public release; distribution is unlimited. Measuring Compartment Size and Gas Solubility in Marine...study is to develop methods to estimate marine mammal tissue compartment sizes, and tissue gas solubility. We aim to improve the data available for

Treatment options for mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome.

PubMed

Santa, Kristin M

2010-11-01

Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome is a rare neurodegenerative disease caused by the decreased ability of cells to produce sufficient energy in the form of adenosine 5'-triphosphate. Although it is one of the most common maternally inherited mitochondrial disorders, its exact incidence is unknown. Caused most frequently by an A-to-G point mutation at the 3243 position in the mitochondrial DNA, MELAS syndrome has a broad range of clinical manifestations and a highly variable course. The classic neurologic characteristics include encephalopathy, seizures, and stroke-like episodes. In addition to its neurologic manifestations, MELAS syndrome exhibits multisystem effects including cardiac conduction defects, diabetes mellitus, short stature, myopathy, and gastrointestinal disturbances. Unfortunately, no consensus guidelines outlining standard drug regimens exist for this syndrome. Many of the accepted therapies used in treating MELAS syndrome have been identified through a small number of clinical trials or isolated case reports. Currently, the drugs most often used include antioxidants and various vitamins aimed at minimizing the demands on the mitochondria and supporting and maximizing their function. Some of the most frequently prescribed agents include coenzyme Q(10), l-arginine, B vitamins, and levocarnitine. Although articles describing MELAS syndrome are available, few specifically target education for clinical pharmacists. This article will provide pharmacists with a practical resource to enhance their understanding of MELAS syndrome in order to provide safe and effective pharmaceutical care.

Hereditary internal anal sphincter myopathy causing proctalgia fugax and constipation. A newly identified condition.

PubMed

Kamm, M A; Hoyle, C H; Burleigh, D E; Law, P J; Swash, M; Martin, J E; Nicholls, R J; Northover, J M

1991-03-01

A newly identified myopathy of the internal anal sphincter is described. In the affected family, at least one member from each of five generations had severe proctalgia fugax; onset was usually in the third to fifth decades of life. Three members of the family have been studied in detail. Each had severe pain intermittently during the day and hourly during the night. Constipation was an associated symptom, in particular difficulty with rectal evacuation. Clinically the internal anal sphincter was thickened and of decreased compliance. The maximum anal canal pressure was usually increased with marked ultraslow wave activity. Anal endosonography confirmed a grossly thickened internal anal sphincter. Two patients were treated by internal anal sphincter strip myectomy; one showed marked improvement and one was relieved of the constipation but had only slight improvement of the pain. The hypertrophied muscle in two of the patients showed unique myopathic changes, consisting of vacuolar changes with periodic acid-Schiff-positive polyglycosan bodies in the smooth muscle fibers and increased endomysial fibrosis. In vitro organ-bath studies showed insensitivity of the muscle to noradrenaline, isoprenaline, carbachol, dimethylpiperazinium, and electrical-field stimulation. Immunohistochemical studies for substance P, calcitonin gene-related peptide, galanin, neuropeptide Y, and vasoactive intestinal peptide showed staining in a similar distribution to that in control tissue. A specific autosomal-dominant inherited myopathy of the internal anal sphincter that causes anal pain and constipation has been identified and characterized.

Inflammatory myopathies in childhood: correlation between nailfold capillaroscopy findings and clinical and laboratory data.

PubMed

Nascif, Ana K S; Terreri, Maria T R A; Len, Cláudio A; Andrade, Luis E C; Hilário, Maria O E

2006-01-01

Nailfold capillaroscopy is an important tool for the diagnosis and follow-up of patients with rheumatic diseases, in particular dermatomyositis and scleroderma. A relationship has been observed in adults between improved capillaroscopic findings and reduced disease activity. Our aim was to correlate disease activity (clinical and laboratory data) and nailfold capillaroscopy findings in 18 patients with inflammatory myopathies. This prospective study included 13 juvenile dermatomyositis patients (Bohan and Peter criteria) (mean age of 8.8 years) and five patients with overlap syndrome (mean age of 15.7 years). We evaluated disease activity (skin abnormalities and muscle weakness, muscle enzymes and acute phase reactants) and its correlation with nailfold capillaroscopy findings (dilatation of isolated loops, dropout of surrounding vessels and giant capillary loops). We used a microscope with special light and magnification of 10 to 16X. Eighteen patients underwent a total of 26 capillaroscopic examinations, seven of them on two or more occasions (13 were performed during the active disease phase and 13 during remission). Twelve of the 13 examinations performed during the active phase exhibited scleroderma pattern and 8 of the 13 examinations performed during remission were normal. Therefore, in 20 of the 26 examinations clinical and laboratory data and nailfold capillaroscopy findings correlated (p = 0.01). Nailfold capillaroscopy is a non-invasive examination that offers satisfactory correlation with disease activity and could be a useful tool for the diagnosis and follow-up of inflammatory myopathies.

Targeted Expression of Catalase to Mitochondria Protects Against Ischemic Myopathy in High-Fat Diet–Fed Mice

PubMed Central

Ryan, Terence E.; Schmidt, Cameron A.; Green, Thomas D.; Spangenburg, Espen E.; Neufer, P. Darrell

2016-01-01

Patients with type 2 diabetes respond poorly to treatments for peripheral arterial disease (PAD) and are more likely to present with the most severe manifestation of the disease, critical limb ischemia. The underlying mechanisms linking type 2 diabetes and the severity of PAD manifestation are not well understood. We sought to test whether diet-induced mitochondrial dysfunction and oxidative stress would increase the susceptibility of the peripheral limb to hindlimb ischemia (HLI). Six weeks of high-fat diet (HFD) in C57BL/6 mice was insufficient to alter skeletal muscle mitochondrial content and respiratory function or the size of ischemic lesion after HLI, despite reducing blood flow. However, 16 weeks of HFD similarly decreased ischemic limb blood flow, but also exacerbated limb tissue necrosis, increased the myopathic lesion size, reduced muscle regeneration, attenuated muscle function, and exacerbated ischemic mitochondrial dysfunction. Mechanistically, mitochondrial-targeted overexpression of catalase prevented the HFD-induced ischemic limb necrosis, myopathy, and mitochondrial dysfunction, despite no improvement in limb blood flow. These findings demonstrate that skeletal muscle mitochondria are a critical pathological link between type 2 diabetes and PAD. Furthermore, therapeutically targeting mitochondria and oxidant burden is an effective strategy to alleviate tissue loss and ischemic myopathy during PAD. PMID:27284110

Monoamine oxidase inhibition prevents mitochondrial dysfunction and apoptosis in myoblasts from patients with collagen VI myopathies.

PubMed

Sorato, E; Menazza, S; Zulian, A; Sabatelli, P; Gualandi, F; Merlini, L; Bonaldo, P; Canton, M; Bernardi, P; Di Lisa, F

2014-10-01

Although mitochondrial dysfunction and oxidative stress have been proposed to play a crucial role in several types of muscular dystrophy (MD), whether a causal link between these two alterations exists remains an open question. We have documented that mitochondrial dysfunction through opening of the permeability transition pore plays a key role in myoblasts from patients as well as in mouse models of MD, and that oxidative stress caused by monoamine oxidases (MAO) is involved in myofiber damage. In the present study we have tested whether MAO-dependent oxidative stress is a causal determinant of mitochondrial dysfunction and apoptosis in myoblasts from patients affected by collagen VI myopathies. We find that upon incubation with hydrogen peroxide or the MAO substrate tyramine myoblasts from patients upregulate MAO-B expression and display a significant rise in reactive oxygen species (ROS) levels, with concomitant mitochondrial depolarization. MAO inhibition by pargyline significantly reduced both ROS accumulation and mitochondrial dysfunction, and normalized the increased incidence of apoptosis in myoblasts from patients. Thus, MAO-dependent oxidative stress is causally related to mitochondrial dysfunction and cell death in myoblasts from patients affected by collagen VI myopathies, and inhibition of MAO should be explored as a potential treatment for these diseases. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

[Hot spot mutation screening of RYR1 gene in diagnosis of congenital myopathies].

PubMed

Chang, Xing-zhi; Jin, Yi-wen; Wang, Jing-min; Yuan, Yun; Xiong, Hui; Wang, Shuang; Qin, Jiong

2014-10-18

To detect hot spot mutation of RYR1 gene in 15 cases of congenital myopathy with different subtypes, and to discuss the value of RYR1 gene hot spot mutation detection in the diagnosis of the disease. Clinical data were collected in all the patients, including clinical manifestations and signs, serum creatine kinase, electromyography. Fourteen of the patients accepted the muscle biopsy. Hot spot mutation in the C-terminal of RYR1 gene (extron 96-106) had been detected in all the 15 patients. All the patients presented with motor development delay, and they could walk at the age of 1 to 3.5 years,but were always easy to fall and could not run or jump. There were no progressive deteriorations. Physical examination showed different degrees of muscle weakness and hypotonia.High arched palates were noted in 3 patients. The serum levels of creatine kinase were mildly elevated in 3 cases, and normal in 12 cases. Electromyography showed "myogenic" features in 11 patients, being normal in the other 4 patients. Muscle biopsy pathologic diagnosis was the central core disease in 3 patients, the central nuclei in 2 patients, the congenital fiber type disproportion in 2 patients, the nameline myopathy in 3 patient, the multiminicore disease in 1 patient, and nonspecific minimal changes in the other 3 patients; one patient was diagnosed with central core disease according to positive family history and gene mutation. In the family case (Patient 2) of central core disease, the c.14678G>A (p.Arg4893Gln) mutation in 102 extron of RYR1 was identified in three members of the family, which had been reported to be a pathogenic mutation. The c.14596A>G(p.Lys4866Gln) mutation in 101 extron was found in one patient with central core disease(Patient 1), and the c.14719G>A(p.Gly4907Ser) mutation in 102 extron was found in another case of the central core disease(Patient 3).The same novel mutation was verified in one of the patients' (Patient 3) asymptomatic father. Congenital myopathies in

The muscle protein dysferlin accumulates in the Alzheimer brain

PubMed Central

Palamand, Divya; Strider, Jeff; Milone, Margherita; Pestronk, Alan

2006-01-01

Dysferlin is a transmembrane protein that is highly expressed in muscle. Dysferlin mutations cause limb-girdle dystrophy type 2B, Miyoshi myopathy and distal anterior compartment myopathy. Dysferlin has also been described in neural tissue. We studied dysferlin distribution in the brains of patients with Alzheimer disease (AD) and controls. Twelve brains, staged using the Clinical Dementia Rating were examined: 9 AD cases (mean age: 85.9 years and mean disease duration: 8.9 years), and 3 age-matched controls (mean age: 87.5 years). Dysferlin is a cytoplasmic protein in the pyramidal neurons of normal and AD brains. In addition, there were dysferlin-positive dystrophic neurites within Aβ plaques in the AD brain, distinct from tau-positive neurites. Western blots of total brain protein (RIPA) and sequential extraction buffers (high salt, high salt/Triton X-100, SDS and formic acid) of increasing protein extraction strength were performed to examine solubility state. In RIPA fractions, dysferlin was seen as 230–272 kDa bands in normal and AD brains. In serial extractions, there was a shift of dysferlin from soluble phase in high salt/Triton X-100 to the more insoluble SDS fraction in AD. Dysferlin is a new protein described in the AD brain that accumulates in association with neuritic plaques. In muscle, dysferlin plays a role in the repair of muscle membrane damage. The accumulation of dysferlin in the AD brain may be related to the inability of neurons to repair damage due to Aβ deposits accumulating in the AD brain. PMID:17024495

Congenital myopathy associated with the triadin knockout syndrome

PubMed Central

Redhage, Keeley R.; Tester, David J.; Ackerman, Michael J.; Selcen, Duygu

2017-01-01

Objective: Triadin is a component of the calcium release complex of cardiac and skeletal muscle. Our objective was to analyze the skeletal muscle phenotype of the triadin knockout syndrome. Methods: We performed clinical evaluation, analyzed morphologic features by light and electron microscopy, and immunolocalized triadin in skeletal muscle. Results: A 6-year-old boy with lifelong muscle weakness had a triadin knockout syndrome caused by compound heterozygous null mutations in triadin. Light microscopy of a deltoid muscle specimen shows multiple small abnormal spaces in all muscle fibers. Triadin immunoreactivity is absent from type 1 fibers and barely detectable in type 2 fibers. Electron microscopy reveals focally distributed dilation and degeneration of the lateral cisterns of the sarcoplasmic reticulum and loss of the triadin anchors from the preserved lateral cisterns. Conclusions: Absence of triadin in humans can result in a congenital myopathy associated with profound pathologic alterations in components of the sarcoplasmic reticulum. Why only some triadin-deficient patients develop a skeletal muscle phenotype remains an unsolved question. PMID:28202702

Risk Factors and Predictors of Significant Chondral Surface Change From Primary to Revision Anterior Cruciate Ligament Reconstruction: A MOON and MARS Cohort Study.

PubMed

Magnussen, Robert A; Borchers, James R; Pedroza, Angela D; Huston, Laura J; Haas, Amanda K; Spindler, Kurt P; Wright, Rick W; Kaeding, Christopher C; Allen, Christina R; Anderson, Allen F; Cooper, Daniel E; DeBerardino, Thomas M; Dunn, Warren R; Lantz, Brett A; Mann, Barton; Stuart, Michael J; Albright, John P; Amendola, Annunziato; Andrish, Jack T; Annunziata, Christopher C; Arciero, Robert A; Bach, Bernard R; Baker, Champ L; Bartolozzi, Arthur R; Baumgarten, Keith M; Bechler, Jeffery R; Berg, Jeffrey H; Bernas, Geoffrey A; Brockmeier, Stephen F; Brophy, Robert H; Bush-Joseph, Charles A; Butler, J Brad; Campbell, John D; Carey, James L; Carpenter, James E; Cole, Brian J; Cooper, Jonathan M; Cox, Charles L; Creighton, R Alexander; Dahm, Diane L; David, Tal S; Flanigan, David C; Frederick, Robert W; Ganley, Theodore J; Garofoli, Elizabeth A; Gatt, Charles J; Gecha, Steven R; Giffin, James Robert; Hame, Sharon L; Hannafin, Jo A; Harner, Christopher D; Harris, Norman Lindsay; Hechtman, Keith S; Hershman, Elliott B; Hoellrich, Rudolf G; Hosea, Timothy M; Johnson, David C; Johnson, Timothy S; Jones, Morgan H; Kamath, Ganesh V; Klootwyk, Thomas E; Levy, Bruce A; Ma, C Benjamin; Maiers, G Peter; Marx, Robert G; Matava, Matthew J; Mathien, Gregory M; McAllister, David R; McCarty, Eric C; McCormack, Robert G; Miller, Bruce S; Nissen, Carl W; O'Neill, Daniel F; Owens, Brett D; Parker, Richard D; Purnell, Mark L; Ramappa, Arun J; Rauh, Michael A; Rettig, Arthur C; Sekiya, Jon K; Shea, Kevin G; Sherman, Orrin H; Slauterbeck, James R; Smith, Matthew V; Spang, Jeffrey T; Svoboda, Steven J; Taft, Timothy N; Tenuta, Joachim J; Tingstad, Edwin M; Vidal, Armando F; Viskontas, Darius G; White, Richard A; Williams, James S; Wolcott, Michelle L; Wolf, Brian R; York, James J

2018-03-01

Articular cartilage health is an important issue following anterior cruciate ligament (ACL) injury and primary ACL reconstruction. Factors present at the time of primary ACL reconstruction may influence the subsequent progression of articular cartilage damage. Larger meniscus resection at primary ACL reconstruction, increased patient age, and increased body mass index (BMI) are associated with increased odds of worsened articular cartilage damage at the time of revision ACL reconstruction. Case-control study; Level of evidence, 3. Subjects who had primary and revision data in the databases of the Multicenter Orthopaedics Outcomes Network (MOON) and Multicenter ACL Revision Study (MARS) were included. Reviewed data included chondral surface status at the time of primary and revision surgery, meniscus status at the time of primary reconstruction, primary reconstruction graft type, time from primary to revision ACL surgery, as well as demographics and Marx activity score at the time of revision. Significant progression of articular cartilage damage was defined in each compartment according to progression on the modified Outerbridge scale (increase ≥1 grade) or >25% enlargement in any area of damage. Logistic regression identified predictors of significant chondral surface change in each compartment from primary to revision surgery. A total of 134 patients were included, with a median age of 19.5 years at revision surgery. Progression of articular cartilage damage was noted in 34 patients (25.4%) in the lateral compartment, 32 (23.9%) in the medial compartment, and 31 (23.1%) in the patellofemoral compartment. For the lateral compartment, patients who had >33% of the lateral meniscus excised at primary reconstruction had 16.9-times greater odds of progression of articular cartilage injury than those with an intact lateral meniscus ( P < .001). For the medial compartment, patients who had <33% of the medial meniscus excised at the time of the primary reconstruction

Loss-of-function mutations in SCN4A cause severe foetal hypokinesia or ‘classical’ congenital myopathy

PubMed Central

Zaharieva, Irina T.; Thor, Michael G.; Oates, Emily C.; van Karnebeek, Clara; Hendson, Glenda; Blom, Eveline; Witting, Nanna; Rasmussen, Magnhild; Gabbett, Michael T.; Ravenscroft, Gianina; Sframeli, Maria; Suetterlin, Karen; Sarkozy, Anna; D’Argenzio, Luigi; Hartley, Louise; Matthews, Emma; Pitt, Matthew; Vissing, John; Ballegaard, Martin; Krarup, Christian; Slørdahl, Andreas; Halvorsen, Hanne; Ye, Xin Cynthia; Zhang, Lin-Hua; Løkken, Nicoline; Werlauff, Ulla; Abdelsayed, Mena; Davis, Mark R.; Feng, Lucy; Phadke, Rahul; Sewry, Caroline A.; Morgan, Jennifer E.; Laing, Nigel G.; Vallance, Hilary; Ruben, Peter; Hanna, Michael G.; Lewis, Suzanne; Kamsteeg, Erik-Jan; Männikkö, Roope

2016-01-01

Abstract See Cannon (doi: 10.1093/brain/awv400 ) for a scientific commentary on this article. Congenital myopathies are a clinically and genetically heterogeneous group of muscle disorders characterized by congenital or early-onset hypotonia and muscle weakness, and specific pathological features on muscle biopsy. The phenotype ranges from foetal akinesia resulting in in utero or neonatal mortality, to milder disorders that are not life-limiting. Over the past decade, more than 20 new congenital myopathy genes have been identified. Most encode proteins involved in muscle contraction; however, mutations in ion channel-encoding genes are increasingly being recognized as a cause of this group of disorders. SCN4A encodes the α-subunit of the skeletal muscle voltage-gated sodium channel (Na v 1.4). This channel is essential for the generation and propagation of the muscle action potential crucial to muscle contraction. Dominant SCN4A gain-of-function mutations are a well-established cause of myotonia and periodic paralysis. Using whole exome sequencing, we identified homozygous or compound heterozygous SCN4A mutations in a cohort of 11 individuals from six unrelated kindreds with congenital myopathy. Affected members developed in utero - or neonatal-onset muscle weakness of variable severity. In seven cases, severe muscle weakness resulted in death during the third trimester or shortly after birth. The remaining four cases had marked congenital or neonatal-onset hypotonia and weakness associated with mild-to-moderate facial and neck weakness, significant neonatal-onset respiratory and swallowing difficulties and childhood-onset spinal deformities. All four surviving cohort members experienced clinical improvement in the first decade of life. Muscle biopsies showed myopathic features including fibre size variability, presence of fibrofatty tissue of varying severity, without specific structural abnormalities. Electrophysiology suggested a myopathic process, without

Exome sequencing identifies titin mutations causing hereditary myopathy with early respiratory failure (HMERF) in families of diverse ethnic origins.

PubMed

Toro, Camilo; Olivé, Montse; Dalakas, Marinos C; Sivakumar, Kumaraswami; Bilbao, Juan M; Tyndel, Felix; Vidal, Noemí; Farrero, Eva; Sambuughin, Nyamkhishig; Goldfarb, Lev G

2013-03-20

Hereditary myopathy with early respiratory failure (HMERF) was described in several North European families and recently linked to a titin gene (TTN) mutation. We independently studied HMERF-like diseases with the purpose to identify the cause, refine diagnostic criteria, and estimate the frequency of this disease among myopathy patients of various ethnic origins. Whole exome sequencing analysis was carried out in a large U.S. family that included seven members suffering from skeletal muscle weakness and respiratory failure. Subsequent mutation screening was performed in further 45 unrelated probands with similar phenotypes. Studies included muscle strength evaluation, nerve conduction studies and concentric needle EMG, respiratory function test, cardiologic examination, and muscle biopsy. A novel TTN p.Gly30150Asp mutation was identified in the highly conserved A-band of titin that co-segregated with the disease in the U.S. family. Screening of 45 probands initially diagnosed as myofibrillar myopathy (MFM) but excluded based on molecular screening for the known MFM genes led to the identification of a previously reported TTN p.Cys30071Arg mutation in one patient. This same mutation was also identified in a patient with suspected HMERF. The p.Gly30150Asp and p.Cys30071Arg mutations are localized to a side chain of fibronectin type III element A150 of the 10th C-zone super-repeat of titin. Missense mutations in TTN are the cause of HMERF in families of diverse origins. A comparison of phenotypic features of HMERF caused by the three known TTN mutations in various populations allowed to emphasize distinct clinical/pathological features that can serve as the basis for diagnosis. The newly identified p.Gly30150Asp and the p.Cys30071Arg mutation are localized to a side chain of fibronectin type III element A150 of the 10th C-zone super-repeat of titin.

Spontaneous Compartment Syndrome of the Thigh in the Absence of Trauma.

PubMed

Javedani, Parisa P; Ratnabalasuriar, Radhika; Grall, Kristi J H

2016-07-01

Compartment syndrome occurs when an increase in pressure results in vascular and functional impairment of the underlying nerve and muscles. Thigh compartment syndrome (TCS) is uncommon, but clinical suspicion warrants emergent surgical consultation and fasciotomy. We present a 42-year-old man evaluated for right lateral thigh pain, without a history of trauma, deep venous thrombosis (DVT), previous surgery, or intravenous drug use. He was febrile, tachycardic, with a mild leukocytosis, an elevated C-reactive protein level, and an elevated creatinine kinase level. Radiographs showed no abnormality and right lower extremity duplex ultrasound showed no DVT. A computed tomography scan of the right lower extremity was concerning for compartment syndrome. Surgical consultation was obtained, and the patient was taken to the operating room for fasciotomy. He was diagnosed with compartment syndrome intraoperatively. The patient was discharged on hospital day 10. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: TCS is exceedingly rare, especially in the absence of underlying traumatic and nontraumatic etiologies. The diagnosis is challenging because more elastic fascia with larger space in the thigh allows for accommodation of acute increases in pressure. Consequently, there may not be the expected acute rise in compartment pressures; increased compartment pressure may only be a late sign, when underlying neurovascular damage has already occurred. TCS is complicated by high morbidity and mortality. Emergent surgical consultation should be obtained when there is a high clinical suspicion for TCS, and limb-saving fasciotomy should not be delayed. This case shows the importance of a high level of suspicion for TCS in patients with no identifiable etiology and no historical risk factors for development of compartment syndrome, because TCS may not present with classic symptoms. Copyright © 2016 Elsevier Inc. All rights reserved.

14 CFR 25.858 - Cargo or baggage compartment smoke or fire detection systems.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 14 Aeronautics and Space 1 2012-01-01 2012-01-01 false Cargo or baggage compartment smoke or fire... Construction Fire Protection § 25.858 Cargo or baggage compartment smoke or fire detection systems. If certification with cargo or baggage compartment smoke or fire detection provisions is requested, the following...

14 CFR 25.858 - Cargo or baggage compartment smoke or fire detection systems.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 14 Aeronautics and Space 1 2011-01-01 2011-01-01 false Cargo or baggage compartment smoke or fire... Construction Fire Protection § 25.858 Cargo or baggage compartment smoke or fire detection systems. If certification with cargo or baggage compartment smoke or fire detection provisions is requested, the following...

14 CFR 25.858 - Cargo or baggage compartment smoke or fire detection systems.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 14 Aeronautics and Space 1 2014-01-01 2014-01-01 false Cargo or baggage compartment smoke or fire... Construction Fire Protection § 25.858 Cargo or baggage compartment smoke or fire detection systems. If certification with cargo or baggage compartment smoke or fire detection provisions is requested, the following...

14 CFR 25.858 - Cargo or baggage compartment smoke or fire detection systems.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 14 Aeronautics and Space 1 2013-01-01 2013-01-01 false Cargo or baggage compartment smoke or fire... Construction Fire Protection § 25.858 Cargo or baggage compartment smoke or fire detection systems. If certification with cargo or baggage compartment smoke or fire detection provisions is requested, the following...

Anterior tibial stress fractures treated with anterior tension band plating in high-performance athletes.

PubMed

Cruz, Alexandre Santa; de Hollanda, João Paris Buarque; Duarte, Aires; Hungria Neto, José Soares

2013-06-01

The non-surgical treatment of anterior tibial cortex stress fractures requires long periods of abstention from sports activities and often results in non-union. Many different surgical techniques have already been previously described to treat these fractures, but there is no consensus on the best treatment. We describe the outcome of treatment using anterior tibial tension band plating in three high-performance athletes (4 legs) with anterior tibial cortex stress fractures. Tibial osteosynthesis with a 3.5-mm locking compression plate in the anterolateral aspect of the tibia was performed in all patients diagnosed with anterior tibial stress fracture after September 2010 at Santa Casa Hospital. All of the fractures were consolidated within a period of 3 months after surgery, allowing for an early return to pre-injury levels of competitive sports activity. There were no infection, non-union, malunion or anterior knee pain complications. Anterior tibial tension band plating leads to prompt fracture consolidation and is a good alternative for the treatment of anterior tibial cortex stress fractures. Bone grafts were shown to be unnecessary.

Isolation of the Lateral Border Recycling Compartment using a diaminobenzidine-induced density shift

PubMed Central

Sullivan, David P.; Rüffer, Claas; Muller, William A.

2014-01-01

The migration of leukocytes across the endothelium and into tissue is critical to mounting an inflammatory response. The Lateral Border Recycling Compartment (LBRC), a complex vesicular-tubule invagination of the plasma membrane found at endothelial cell borders, plays an important role in the this process. Although a few proteins have been shown to be present in the LBRC, no unique marker is known. Here we detail methods that can be used to characterize a subcellular compartment that lacks an identifying marker. Initial characterization of the LBRC was performed using standard subcellular fractionation with sucrose gradients and took advantage of the observation that the compartment migrated at a lower density than other membrane compartments. To isolate larger quantities of the compartment, we modified a classic technique known as a diaminobenzidine (DAB)-induced density shift. The DAB-induced density shift allowed for specific isolation of membranes labeled with HRP conjugated antibody. Because the LBRC could be differentially labeled at 4°C and 37°C, we were able to identify proteins that are enriched in the compartment, despite lacking a unique marker. These methods serve as a model to others studying poorly characterized compartments and organelles and are applicable to a wide variety of biological systems. PMID:24915828

Greater magnitude tibiofemoral contact forces are associated with reduced prevalence of osteochondral pathologies 2-3 years following anterior cruciate ligament reconstruction.

PubMed

Saxby, David John; Bryant, Adam L; Van Ginckel, Ans; Wang, Yuanyuan; Wang, Xinyang; Modenese, Luca; Gerus, Pauline; Konrath, Jason M; Fortin, Karine; Wrigley, Tim V; Bennell, Kim L; Cicuttini, Flavia M; Vertullo, Christopher; Feller, Julian A; Whitehead, Tim; Gallie, Price; Lloyd, David G

2018-06-07

External loading of osteoarthritic and healthy knees correlates with current and future osteochondral tissue state. These relationships have not been examined following anterior cruciate ligament reconstruction. We hypothesised greater magnitude tibiofemoral contact forces were related to increased prevalence of osteochondral pathologies, and these relationships were exacerbated by concomitant meniscal injury. This was a cross-sectional study of 100 individuals (29.7 ± 6.5 years, 78.1 ± 14.4 kg) examined 2-3 years following hamstring tendon anterior cruciate ligament reconstruction. Thirty-eight participants had concurrent meniscal pathology (30.6 ± 6.6 years, 83.3 ± 14.3 kg), which included treated and untreated meniscal injury, and 62 participants (29.8 ± 6.4 years, 74.9 ± 13.3 kg) were free of meniscal pathology. Magnetic resonance imaging of reconstructed knees was used to assess prevalence of tibiofemoral osteochondral pathologies (i.e., cartilage defects and bone marrow lesions). A calibrated electromyogram-driven neuromusculoskeletal model was used to predict medial and lateral tibiofemoral compartment contact forces from gait analysis data. Relationships between contact forces and osteochondral pathology prevalence were assessed using logistic regression models. In patients with reconstructed knees free from meniscal pathology, greater medial contact forces were related to reduced prevalence of medial cartilage defects (odds ratio (OR) = 0.7, Wald χ 2 (2) = 7.9, 95% confidence interval (CI) = 0.50-95, p = 0.02) and medial bone marrow lesions (OR = 0.8, Wald χ 2 (2) = 4.2, 95% CI = 0.7-0.99, p = 0.04). No significant relationships were found in lateral compartments. In reconstructed knees with concurrent meniscal pathology, no relationships were found between contact forces and osteochondral pathologies. In patients with reconstructed knees free from meniscal pathology, increased

Anterior ankle arthroscopy, distraction or dorsiflexion?

PubMed

de Leeuw, Peter A J; Golanó, Pau; Clavero, Joan A; van Dijk, C Niek

2010-05-01

Anterior ankle arthroscopy can basically be performed by two different methods; the dorsiflexion- or distraction method. The objective of this study was to determine the size of the anterior working area for both the dorsiflexion and distraction method. The anterior working area is anteriorly limited by the overlying anatomy which includes the neurovascular bundle. We hypothesize that in ankle dorsiflexion the anterior neurovascular bundle will move away anteriorly from the ankle joint, whereas in ankle distraction the anterior neurovascular bundle is pulled tight towards the joint, thereby decreasing the safe anterior working area. Six fresh frozen ankle specimens, amputated above the knee, were scanned with computed tomography. Prior to scanning the anterior tibial artery was injected with contrast fluid and subsequently each ankle was scanned both in ankle dorsiflexion and in distraction. A special device was developed to reproducibly obtain ankle dorsiflexion and distraction in the computed tomography scanner. The distance between the anterior border of the inferior tibial articular facet and the posterior border of the anterior tibial artery was measured. The median distance from the anterior border of the inferior tibial articular facet to the posterior border of the anterior tibial artery in ankle dorsiflexion and distraction was 0.9 cm (range 0.7-1.5) and 0.7 cm (range 0.5-0.8), respectively. The distance in ankle dorsiflexion significantly exceeded the distance in ankle distraction (P = 0.03). The current study shows a significantly increased distance between the anterior distal tibia and the overlying anterior neurovascular bundle with the ankle in a slightly dorsiflexed position as compared to the distracted ankle position. We thereby conclude that the distracted ankle position puts the neurovascular structures more at risk for iatrogenic damage when performing anterior ankle arthroscopy.

Anterior ankle arthroscopy, distraction or dorsiflexion?

PubMed Central

Golanó, Pau; Clavero, Joan A.; van Dijk, C. Niek

2010-01-01

Anterior ankle arthroscopy can basically be performed by two different methods; the dorsiflexion- or distraction method. The objective of this study was to determine the size of the anterior working area for both the dorsiflexion and distraction method. The anterior working area is anteriorly limited by the overlying anatomy which includes the neurovascular bundle. We hypothesize that in ankle dorsiflexion the anterior neurovascular bundle will move away anteriorly from the ankle joint, whereas in ankle distraction the anterior neurovascular bundle is pulled tight towards the joint, thereby decreasing the safe anterior working area. Six fresh frozen ankle specimens, amputated above the knee, were scanned with computed tomography. Prior to scanning the anterior tibial artery was injected with contrast fluid and subsequently each ankle was scanned both in ankle dorsiflexion and in distraction. A special device was developed to reproducibly obtain ankle dorsiflexion and distraction in the computed tomography scanner. The distance between the anterior border of the inferior tibial articular facet and the posterior border of the anterior tibial artery was measured. The median distance from the anterior border of the inferior tibial articular facet to the posterior border of the anterior tibial artery in ankle dorsiflexion and distraction was 0.9 cm (range 0.7–1.5) and 0.7 cm (range 0.5–0.8), respectively. The distance in ankle dorsiflexion significantly exceeded the distance in ankle distraction (P = 0.03). The current study shows a significantly increased distance between the anterior distal tibia and the overlying anterior neurovascular bundle with the ankle in a slightly dorsiflexed position as compared to the distracted ankle position. We thereby conclude that the distracted ankle position puts the neurovascular structures more at risk for iatrogenic damage when performing anterior ankle arthroscopy. PMID:20217392

Clinical practice guidelines for the management of acute limb compartment syndrome following trauma.

PubMed

Wall, Christopher J; Lynch, Joan; Harris, Ian A; Richardson, Martin D; Brand, Caroline; Lowe, Adrian J; Sugrue, Michael

2010-03-01

Acute compartment syndrome is a serious and not uncommon complication of limb trauma. The condition is a surgical emergency, and is associated with significant morbidity if not managed appropriately. There is variation in management of acute limb compartment syndrome in Australia. Clinical practice guidelines for the management of acute limb compartment syndrome following trauma were developed in accordance with Australian National Health and Medical Research Council recommendations. The guidelines were based on critically appraised literature evidence and the consensus opinion of a multidisciplinary team involved in trauma management who met in a nominal panel process. Recommendations were developed for key decision nodes in the patient care pathway, including methods of diagnosis in alert and unconscious patients, appropriate assessment of compartment pressure, timing and technique of fasciotomy, fasciotomy wound management, and prevention of compartment syndrome in patients with limb injuries. The recommendations were largely consensus based in the absence of well-designed clinical trial evidence. Clinical practice guidelines for the management of acute limb compartment syndrome following trauma have been developed that will support consistency in management and optimize patient health outcomes.

Association of narrow angles with anterior chamber area and volume measured with anterior-segment optical coherence tomography.

PubMed

Wu, Ren-Yi; Nongpiur, Monisha E; He, Ming-Guang; Sakata, Lisandro M; Friedman, David S; Chan, Yiong-Huak; Lavanya, Raghavan; Wong, Tien-Yin; Aung, Tin

2011-05-01

To describe the measurement of anterior chamber area and anterior chamber volume by anterior-segment optical coherence tomography and to investigate the association of these parameters with the presence of narrow angles. This was a cross-sectional study of subjects aged at least 50 years without ophthalmic symptoms recruited from a community clinic. All participants underwent standardized ocular examination and anterior-segment optical coherence tomography. Customized software was used to measure anterior chamber area (cross-sectional area bounded by the corneal endothelium, anterior surface of iris, and lens within the pupil) and anterior chamber volume (calculated by rotating the anterior chamber area 360° around a vertical axis through the midpoint of the anterior chamber area). An eye was considered to have narrow angles if the posterior pigmented trabecular meshwork was not visible for at least 180° on gonioscopy with the eye in the primary position. A total of 1922 subjects were included in the final analyses, 317 (16.5%) of whom had narrow angles. Mean anterior chamber area (15.6 vs 21.1 mm(2); P < .001) and anterior chamber volume (97.6 vs 142.1 mm(3); P < .001) were smaller in eyes with narrow angles compared with those in eyes without narrow angles. After adjusting for age, sex, anterior chamber depth, axial length, and pupil size, smaller anterior chamber area (odds ratio, 53.2; 95% confidence interval, 27.1-104.5) and anterior chamber volume (odds ratio, 40.2; 95% confidence interval, 21.5-75.2) were significantly associated with the presence of narrow angles. Smaller anterior chamber area and anterior chamber volume were independently associated with narrow angles in Singaporeans, even after controlling for other known ocular risk factors.

A novel syndrome of Klippel-Feil anomaly, myopathy, and characteristic facies is linked to a null mutation in MYO18B.

PubMed

Alazami, Anas M; Kentab, Amal Y; Faqeih, Eissa; Mohamed, Jawahir Y; Alkhalidi, Hisham; Hijazi, Hadia; Alkuraya, Fowzan S

2015-06-01

Klippel-Feil anomaly (KFA) can be seen in a number of syndromes. We describe an apparently novel syndromic association with KFA. Clinical phenotyping of two consanguineous families followed by combined autozygome/exome analysis. Two patients from two apparently unrelated families shared a strikingly similar phenotype characterised by KFA, myopathy, mild short stature, microcephaly, and distinctive facies. They shared a single founder autozygous interval in which whole exome sequencing revealed a truncating mutation in MYO18B. There was virtually complete loss of the transcript in peripheral blood, indicative of nonsense-mediated decay. Electron microscopy of muscle confirms abnormal myosin filaments with accompanying myopathic changes. Deficiency of MYO18B is linked to a novel developmental disorder which combines KFA with myopathy. This suggests a widespread developmental role for this gene in humans, as observed for its murine ortholog. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Clinical review: Critical illness polyneuropathy and myopathy

PubMed Central

Hermans, Greet; De Jonghe, Bernard; Bruyninckx, Frans; Berghe, Greet Van den

2008-01-01

Critical illness polyneuropathy (CIP) and myopathy (CIM) are major complications of severe critical illness and its management. CIP/CIM prolongs weaning from mechanical ventilation and physical rehabilitation since both limb and respiratory muscles can be affected. Among many risk factors implicated, sepsis, systemic inflammatory response syndrome, and multiple organ failure appear to play a crucial role in CIP/CIM. This review focuses on epidemiology, diagnostic challenges, the current understanding of pathophysiology, risk factors, important clinical consequences, and potential interventions to reduce the incidence of CIP/CIM. CIP/CIM is associated with increased hospital and intensive care unit (ICU) stays and increased mortality rates. Recently, it was shown in a single centre that intensive insulin therapy significantly reduced the electrophysiological incidence of CIP/CIM and the need for prolonged mechanical ventilation in patients in a medical or surgical ICU for at least 1 week. The electrophysiological diagnosis was limited by the fact that muscle membrane inexcitability was not detected. These results have yet to be confirmed in a larger patient population. One of the main risks of this therapy is hypoglycemia. Also, conflicting evidence concerning the neuromuscular effects of corticosteroids exists. A systematic review of the available literature on the optimal approach for preventing CIP/CIM seems warranted. PMID:19040777