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3.
Crit Rev Oncol Hematol ; 145: 102839, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31877534

RESUMO

BACKGROUND: The evidence that body composition parameters influence multiple cancer outcomes is rapidly expanding. Excess adiposity deposits in muscle tissue, termed myosteatosis, can be detected in CT scans through variations in the density of muscle tissues (Hounsfield Units). Patients with similar muscle mass but different amounts of intramuscular adipose infiltration have increased chemotherapy toxicity, time to tumor progression and other adverse outcomes among different cancer types. Our review examines the impact of myosteatosis on overall survival (OS) in patients with cancer. METHODS: A systematic search of the literature was conducted on PubMed/ MEDLINE, Cochrane CENTRAL, and EMBASE. Meta-analysis was conducted using a random-effects model. Risk of bias was evaluated using the Newcastle-Ottawa Quality assessment for cohort studies, funnel plot (publication bias), and GRADE summary of findings tool from Cochrane. RESULTS: A total of 4880 articles were screened from which 40 articles selected, including 21,222 patients. The overall mean proportion of patients with myosteatosis was 48 % (range 11-85 %). Using skeletal muscle density (SMD), patients classified as having myosteatosis had 75 % greater mortality risk compared to non-myosteatosis patients (HR 1.75 95 % CI 1.60-1.92, 40 studies) (p < .00001) (i2 = 62 %). Specifically, myosteatosis was prognostic for worse OS in patients with gynecological, renal, periampullary/pancreatic, hepatocellular, gastroesophageal, and colorectal carcinoma, and lymphomas. CONCLUSION: Our analysis of the literature shows that cancer patients with myosteatosis have shorter survival. Our findings suggest that in oncological practice, muscle density assessment is valuable as a prognostic parameter.


Assuntos
Músculo Esquelético , Doenças Musculares , Neoplasias , Composição Corporal , Estudos de Coortes , Humanos , Músculo Esquelético/patologia , Doenças Musculares/diagnóstico , Doenças Musculares/patologia , Neoplasias/complicações , Neoplasias/patologia , Obesidade/patologia , Prognóstico , Tomografia Computadorizada por Raios X
4.
Muscle Nerve ; 61(1): 95-100, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31587306

RESUMO

INTRODUCTION: Although peripheral neuropathy and cardiomyopathy are well-recognized manifestations of transthyretin (ATTR) amyloidosis, myopathy has been rarely reported. METHODS: In this study we reviewed our muscle biopsy database (January 1998 to June 2018) to identify patients with ATTR amyloid myopathy confirmed by molecular or proteomic analysis. Clinical and laboratory findings were reviewed. RESULTS: We identified eight ATTR amyloid myopathy patients (5 hereditary ATTR [ATTRv] and 3 wild-type ATTR [ATTRwt]). Myopathy was the initial manifestation in all ATTRwt patients and followed peripheral neuropathy (4 patients) or cardiomyopathy (1 patient) in ATTRv patients. One ATTRv patient developed myopathy after liver transplant. Peripheral neuropathy and cardiac amyloidosis occurred in seven and six patients, respectively. Muscle biopsy showed interstitial amyloid deposition in all patients, rare necrotic/regenerating fibers in six, and vacuoles in four. DISCUSSION: Myopathy can be the initial manifestation of ATTRwt amyloidosis and can precede the peripheral neuropathy or occur after liver transplant in ATTRv amyloidosis.


Assuntos
Neuropatias Amiloides Familiares/patologia , Doenças Musculares/patologia , Pré-Albumina , Adulto , Idoso , Idoso de 80 Anos ou mais , Neuropatias Amiloides Familiares/complicações , Biópsia , Cardiomiopatias/patologia , Bases de Dados Factuais , Eletromiografia , Feminino , Humanos , Transplante de Fígado/efeitos adversos , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/patologia , Doenças Musculares/etiologia , Necrose , Condução Nervosa , Doenças do Sistema Nervoso Periférico/patologia , Proteômica
5.
Aust Vet J ; 97(12): 499-504, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31674019

RESUMO

BACKGROUND: Cervicothoracic vertebral subluxation in sheep presents as a postural and locomotor disorder, and has been described in several breeds in Australia and overseas. Cervical myopathy may also be present in these cases. CASE REPORT: A New South Wales sheep producer reported a postural and locomotor disorder with a low prevalence in his Poll Merino stud flock, affecting neonate, weaner and adult sheep. Animals with postural abnormalities, variable degrees of ataxia and proprioceptive deficits involving both fore and hind limbs were described. Abnormalities of the cervicothoracic vertebral column were identified grossly during necropsy, with misalignment and consequent narrowing of the posterior cervical spinal canal. Lesions ranging from pallor (cellular degeneration) to white streaky lesions with pinpoint haemorrhage (necrosis) were identified in the cervicothoracic paravertebral musculature of affected animals. Boney abnormalities were further characterised by imaging studies. Pedigree analysis of the very extensive breeding and disease incident records available for this flock suggested that the disease was inherited. A similar case recognised in a separate New South Wales Poll Merino flock is also described. CONCLUSION: This report describes an entity of cervicothoracic vertebral subluxation in two Poll Merino sheep flocks, with cervical myopathy also identified in one, with preliminary evidence in the primary case that there is likely to be a hereditary basis. The two cases outlined in this report resemble the findings of several historical investigations into ovine flock postural disorders in Australia and beyond.


Assuntos
Vértebras Cervicais/patologia , Doenças Musculares/veterinária , Doenças dos Ovinos/genética , Doenças dos Ovinos/patologia , Vértebras Torácicas/patologia , Animais , Autopsia/veterinária , Cruzamento , Eutanásia Animal , Doenças Musculares/genética , Doenças Musculares/patologia , New South Wales , Ovinos , Carneiro Doméstico
6.
Muscle Nerve ; 60(6): 687-692, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31478199

RESUMO

INTRODUCTION: Nerve imaging has a limited role in axonal and muscle fiber loss. In this study, we sought to explore the utility of standardized muscle ultrasound (US) assessment in these clinical scenarios. METHODS: We performed a prospective study from March to August 2018 of patients attending the neuromuscular clinic. All patients underwent clinical evaluation and standardized muscle thickness measurement by US in seven muscles. RESULTS: The study cohort consisted of 114 participants, including patients with polyneuropathy, motor neuron disease, and myopathy. The smallest distal muscle thickness was found in patients with polyneuropathy, while the smallest proximal muscle thickness was found in patients with myopathy. Muscle thickness was strongly correlated with muscle strength (r 2 = 0.62), electrophysiological findings (r 2 : 0.44-0.55), and disability score (r 2 = 0.53). DISCUSSION: Standardized muscle thickness measured by US shows diagnostic usefulness in a spectrum of neuromuscular disorders and correlates with clinical and electrophysiological findings.


Assuntos
Músculo Esquelético/diagnóstico por imagem , Doenças Neuromusculares/diagnóstico por imagem , Potenciais de Ação/fisiologia , Adulto , Idoso , Esclerose Amiotrófica Lateral/diagnóstico por imagem , Esclerose Amiotrófica Lateral/patologia , Esclerose Amiotrófica Lateral/fisiopatologia , Eletromiografia , Feminino , Humanos , Masculino , Sintomas Inexplicáveis , Pessoa de Meia-Idade , Força Muscular , Músculo Esquelético/patologia , Músculo Esquelético/fisiopatologia , Atrofia Muscular Espinal/diagnóstico por imagem , Atrofia Muscular Espinal/patologia , Atrofia Muscular Espinal/fisiopatologia , Doenças Musculares/diagnóstico por imagem , Doenças Musculares/patologia , Doenças Musculares/fisiopatologia , Condução Nervosa/fisiologia , Doenças Neuromusculares/patologia , Doenças Neuromusculares/fisiopatologia , Tamanho do Órgão , Polineuropatias/diagnóstico por imagem , Polineuropatias/patologia , Polineuropatias/fisiopatologia , Estudos Prospectivos , Radiculopatia/diagnóstico por imagem , Radiculopatia/patologia , Radiculopatia/fisiopatologia , Ultrassonografia
8.
Muscle Nerve ; 60(6): 648-657, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31449669

RESUMO

Although myopathies and neuromuscular junction disorders are typically distinct, their coexistence has been reported in several inherited and acquired conditions. Affected individuals have variable clinical phenotypes but typically display both a decrement on repetitive nerve stimulation and myopathic findings on muscle biopsy. Inherited causes include myopathies related to mutations in BIN1, DES, DNM2, GMPPB, MTM1, or PLEC and congenital myasthenic syndromes due to mutations in ALG2, ALG14, COL13A1, DOK7, DPAGT1, or GFPT1. Additionally, a decrement due to muscle fiber inexcitability is observed in certain myotonic disorders. The identification of a defect of neuromuscular transmission in an inherited myopathy may assist in establishing a molecular diagnosis and in selecting patients who would benefit from pharmacological correction of this defect. Acquired cases meanwhile stem from the co-occurrence of myasthenia gravis or Lambert-Eaton myasthenic syndrome with an immune-mediated myopathy, which may be due to paraneoplastic disorders or exposure to immune checkpoint inhibitors.


Assuntos
Músculo Esquelético/fisiopatologia , Doenças Musculares/fisiopatologia , Síndromes Miastênicas Congênitas/fisiopatologia , Junção Neuromuscular/fisiopatologia , Cardiomiopatias/complicações , Cardiomiopatias/patologia , Cardiomiopatias/fisiopatologia , Eletrodiagnóstico , Eletromiografia , Humanos , Músculo Esquelético/patologia , Doenças Musculares/complicações , Doenças Musculares/patologia , Distrofias Musculares/complicações , Distrofias Musculares/patologia , Distrofias Musculares/fisiopatologia , Miastenia Gravis/complicações , Miastenia Gravis/patologia , Miastenia Gravis/fisiopatologia , Síndromes Miastênicas Congênitas/complicações , Síndromes Miastênicas Congênitas/patologia , Miopatias Congênitas Estruturais/complicações , Miopatias Congênitas Estruturais/patologia , Miopatias Congênitas Estruturais/fisiopatologia , Transtornos Miotônicos/complicações , Transtornos Miotônicos/patologia , Transtornos Miotônicos/fisiopatologia , Condução Nervosa
9.
Medicina (Kaunas) ; 55(9)2019 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-31466356

RESUMO

Calcific myonecrosis is a rare disease that has been shown to be a late sequela of trauma. This article presents a 68-year-old man with calcific myonecrosis of the leg 40 years after a tibial fracture complicated with peroneal nerve palsy. The soft tissue mass increased in size after another injury to the leg that occurred two years before his presentation. Physical examination at presentation showed a palpable extra-osseous mass at the anterior aspect of the left leg; the mass was not adherent to adjacent soft-tissues and bone, and it was painless but tender to palpation. Radiographs of the left leg showed extensive calcification at the soft-tissue of the anterior and posterior leg. An ultrasonography-guided trocar biopsy was done; histological findings were indicative of calcific myonecrosis. Given the benign entity of the lesion and known high rate of complications, he was recommended for no further treatment except for clinical and imaging observation. Located at the site of the biopsy, he experienced infection with drainage that eventually healed after six months with antibiotics and wound dressing changes. During the last follow-up examination, two years after diagnosis, the patient was asymptomatic without progression of the mass.


Assuntos
Calcinose , Músculo Esquelético/patologia , Doenças Musculares , Idoso , Calcinose/diagnóstico por imagem , Calcinose/etiologia , Calcinose/patologia , Humanos , Perna (Membro)/diagnóstico por imagem , Masculino , Músculo Esquelético/diagnóstico por imagem , Doenças Musculares/diagnóstico por imagem , Doenças Musculares/etiologia , Doenças Musculares/patologia , Necrose , Fraturas da Tíbia/complicações
10.
Intern Med ; 58(21): 3189-3194, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31292376

RESUMO

A 69-year-old Japanese woman was admitted to our hospital with progressive muscle weakness and dysphagia. She was taking pitavastatin for dyslipidemia. Her serum creatine kinase was 6,300 U/L. Pitavastatin was stopped, but her symptoms deteriorated, and cardiac congestion appeared. A muscle biopsy showed necrotizing myopathy (NM), and anti-signal recognition particle (SRP) antibody was positive. 18F-fluorodeoxyglucose-positron emission tomography showed an abnormal uptake, and magnetic resonance imaging showed abnormal gadolinium enhancement in the left ventricular wall. An endomyocardial biopsy revealed inflammatory cardiomyopathy. Steroid, tacrolimus, and intravenous immunoglobulins were effective against the symptoms. This is the first case of biopsy-proven secondary cardiomyopathy due to anti-SRP-positive NM.


Assuntos
Cardiomiopatias/etiologia , Imagem Multimodal , Músculo Esquelético/patologia , Doenças Musculares/patologia , Idoso , Autoanticorpos/sangue , Biópsia , Cardiomiopatias/diagnóstico por imagem , Meios de Contraste , Ecocardiografia , Feminino , Gadolínio , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Imunossupressores/uso terapêutico , Imagem por Ressonância Magnética , Debilidade Muscular/patologia , Doenças Musculares/complicações , Doenças Musculares/diagnóstico por imagem , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Partícula de Reconhecimento de Sinal/imunologia , Tacrolimo/uso terapêutico
11.
Poult Sci ; 98(11): 6170-6176, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31287889

RESUMO

Broiler breast meat with the woody breast (WB) myopathy exhibits abnormal tissue hardness and muscle rigidity in the raw state. The effectiveness of using instrumental shear measurements to characterize texture in WB fillets before and after cooking is not well understood. The objective of this study was to determine the influence of WB on razor shear force measurements in fresh never-frozen and frozen-thawed broiler breast fillets in both the raw and cooked state. Deboned breast fillets (n = 234) were collected from a commercial processing plant and categorized as normal (n = 78), moderate WB (n = 86), or severe WB (n = 70). At 24 h postmortem fillets were either used for texture analysis directly or frozen-thawed prior to analysis. Each fillet was measured before and after cooking using either the blunt blade (BMORS) or sharpened blade (MORS) versions of the Meullenet-Owens razor shear test. The ability of BMORS to distinguish between normal and WB fillets was different between raw and cooked fillets. In both fresh and frozen-thawed fillets, raw BMORS shear values (peak shear force and shear energy) increased (P < 0.0001) with WB severity. In fresh fillets, cooked BMORS values were similar between normal, moderate WB, and severe WB fillets. In frozen-thawed fillets, cooked BMORS values were greater (P < 0.001) in severe WB compared to normal fillets but were similar between normal and moderate WB fillets. Cooking had less impact on the ability of MORS to distinguish between normal and WB fillets. For both fresh and frozen-thawed fillets, MORS shear values (peak shear force and shear energy) were greater (P < 0.05) in WB fillets than normals in both the raw and cooked states. Data from this study demonstrate that the WB myopathy influences razor shear measurements in raw broiler breast fillets, but suggest that the ability to objectively detect texture differences in cooked WB meat is strongly dependent upon razor shear technique.


Assuntos
Criação de Animais Domésticos/métodos , Carne/análise , Doenças Musculares/veterinária , Músculos Peitorais/fisiologia , Doenças das Aves Domésticas/patologia , Perus/fisiologia , Animais , Culinária , Manipulação de Alimentos/métodos , Masculino , Doenças Musculares/patologia , Resistência ao Cisalhamento
12.
Redox Biol ; 26: 101232, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31181458

RESUMO

There is more skeletal muscle tissue in the body than any other tissue and, as it is the organ of the majority of metabolic activity, muscle defect can affect the health of the entire body. Endoplasmic reticulum (ER) stress due to defects in protein folding/degradation balance, altered calcium and lipid levels and alterations in ER-mitochondria contacts has recently been recognised as the pathogenic cause of many different myopathies. In addition, a maladaptive ER stress response triggered by ER stress and mediated by three ER stress sensors (PERK, IRE1 and ATF6) is involved in a failure to relieve muscle tissue from this stress. Targeting ER stress and the ER stress response pathway offers a broad range of opportunities for treating myopathies but, as the inhibition of the three ER stress sensors may not be safe because it could lead to unexpected effects; it therefore calls for careful analysis of the changes in downstream signal transduction in the different myopathies so these sub-pathways can be pharmacologically targeted. This review summarises the known inhibitors of the ER stress response and the successful results obtained using some of them in mouse models of muscle diseases caused by ER stress/ER stress response.


Assuntos
Retículo Endoplasmático/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Músculo Esquelético/efeitos dos fármacos , Doenças Musculares/tratamento farmacológico , Fenilbutiratos/farmacologia , Sulfonamidas/farmacologia , Tiofenos/farmacologia , Fator 6 Ativador da Transcrição/antagonistas & inibidores , Fator 6 Ativador da Transcrição/genética , Fator 6 Ativador da Transcrição/metabolismo , Adenina/análogos & derivados , Adenina/farmacologia , Aldeídos/farmacologia , Animais , Retículo Endoplasmático/metabolismo , Retículo Endoplasmático/patologia , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Endorribonucleases/antagonistas & inibidores , Endorribonucleases/genética , Endorribonucleases/metabolismo , Humanos , Indóis/farmacologia , Camundongos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Terapia de Alvo Molecular/métodos , Fibras Musculares Esqueléticas/efeitos dos fármacos , Fibras Musculares Esqueléticas/metabolismo , Fibras Musculares Esqueléticas/patologia , Músculo Esquelético/metabolismo , Músculo Esquelético/patologia , Doenças Musculares/genética , Doenças Musculares/metabolismo , Doenças Musculares/patologia , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , Transdução de Sinais , eIF-2 Quinase/antagonistas & inibidores , eIF-2 Quinase/genética , eIF-2 Quinase/metabolismo
13.
Cell Physiol Biochem ; 53(1): 62-75, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31184447

RESUMO

BACKGROUND/AIMS: Skeletal muscle injuries are the most common type of injury occurring in sports, and investigating skeletal muscle regeneration as well as understanding the related processes is an important aspect of the sports medicine field. The process of regeneration appears to be complex and precisely orchestrated, involving fibro-adipogenic progenitors (FAPs) which are a muscle-resident stem cell population that appears to play a major role in abnormal development of fibrotic tissue or intermuscular adipose tissue (IMAT). Our present study aims to investigate whether muscle resting or endurance exercise following muscle injury may change the behavior of FAPs and subsequently impact the development of fatty infiltrations and fibrosis, two hallmarks of regeneration failure. METHODS: We used the validated glycerol muscle injury model to mimic abnormal muscle regenerative conditions in mice. We challenged this specific regeneration model with hindlimb unloading or endurance exercise and, in a second set of experiments, we treated mice with decorin, a TGF-ß inhibitor. RESULTS: In this study, we demonstrated that: i) muscle resting just after injury leads to inhibition of IMAT development, ii) TNF-α mediated FAP apoptosis might be perturbed in this specific glycerol model of muscle injury, leading to IMAT development, and iii) treatment with the TGF-ß inhibitor decorin decreases IMAT development and might restores FAP apoptosis. CONCLUSION: In addition to the potential clinical relevance of decorin treatment in situations involving muscle plasticity and regeneration, this study also demonstrates that a period of muscle resting is necessary following muscle injury to achieve efficient muscle regeneration which is associated with a reduction in fatty infiltration. Unreasonably early resumption of exercise brings no gain to regeneration, further highlighting that this resting period is necessary.


Assuntos
Decorina/uso terapêutico , Músculo Esquelético/lesões , Doenças Musculares/tratamento farmacológico , Fator de Crescimento Transformador beta/antagonistas & inibidores , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/metabolismo , Animais , Apoptose/efeitos dos fármacos , Decorina/farmacologia , Feminino , Glicerol/toxicidade , Camundongos , Camundongos Endogâmicos C57BL , Músculo Esquelético/patologia , Doenças Musculares/induzido quimicamente , Doenças Musculares/patologia , Condicionamento Físico Animal , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/metabolismo , Células-Tronco/citologia , Células-Tronco/efeitos dos fármacos , Células-Tronco/metabolismo , Fator de Crescimento Transformador beta/metabolismo
14.
Rinsho Shinkeigaku ; 59(7): 431-435, 2019 Jul 31.
Artigo em Japonês | MEDLINE | ID: mdl-31243249

RESUMO

A 53-year-old man suffering from squamous cell lung cancer presented with bilateral ptosis and bulbar palsy a month after initial treatment with the immune checkpoint inhibitor nivolumab. The symptoms showed worsening from midday, suggesting myasthenia gravis (MG), although anti-AChR antibody was negative. Although no muscle weakness was detected, the CK level was elevated to 5,255 IU/l, and MRI of the thigh revealed inflammation of the bilateral rectus femoris muscle. A muscle biopsy showed signs of necrotizing myopathy with expression of sarcolemmal HLA class I and accumulation of macrophages, CD4, CD8, and CD20-positive lymphocytes. Positivity for anti-titin antibody, one of the anti-striated muscle antibodies, was evident. The patient was diagnosed as having nivolumab-related necrotizing myopathy with myasthenia gravis, an immune-related adverse event (irAE). Treatment with prednisolone rapidly ameliorated the symptoms, and the serum CK level normalized. There have been several reports of nivolumab-related myositis with MG. On the basis of the muscle pathology and antibody data, we were able to clarify that necrotizing myopathy was related to the pathogenesis of this case.


Assuntos
Conectina/imunologia , Doenças Musculares/induzido quimicamente , Miastenia Gravis/induzido quimicamente , Nivolumabe/efeitos adversos , Autoanticorpos/sangue , Biomarcadores/sangue , Carcinoma de Células Escamosas/tratamento farmacológico , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Doenças Musculares/diagnóstico , Doenças Musculares/tratamento farmacológico , Doenças Musculares/patologia , Miastenia Gravis/diagnóstico , Miastenia Gravis/tratamento farmacológico , Necrose , Nivolumabe/uso terapêutico , Prednisolona/administração & dosagem , Músculo Quadríceps/patologia , Resultado do Tratamento
15.
Pediatr Dermatol ; 36(5): 743-744, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31231862

RESUMO

Muscular hernias, focal protrusions of muscle through fascial weaknesses, are uncommon in pediatric patients. When diagnosed, they are usually found on the legs from protrusions of tibialis anterior muscle in young male athletes. Here, we present a case of a healthy 16-year-old boy who developed asymptomatic nodules on the bilateral feet and lateral lower legs, which were confirmed by ultrasound to be focal muscle herniations. Our case highlights a rare example of bilateral muscle herniation in a pediatric patient and the utility of ultrasound as a diagnostic modality for this uncommon condition.


Assuntos
Hérnia/diagnóstico por imagem , Hérnia/patologia , Extremidade Inferior , Músculo Esquelético , Doenças Musculares/diagnóstico por imagem , Doenças Musculares/patologia , Adolescente , Humanos , Masculino , Ultrassonografia
18.
Am J Vet Res ; 80(6): 595-600, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31140851

RESUMO

OBJECTIVE: To evaluate repeatability and reproducibility of muscle condition score (MCS) in dogs with various degrees of muscle loss; to compare MCS, muscle ultrasonographic measurements, and quantitative magnetic resonance (QMR) measurements; and to identify cutoff values for ultrasonographic measurements of muscle that can be used to identify dogs with cachexia and sarcopenia. ANIMALS: 40 dogs of various age, body condition score (BCS), and MCS. PROCEDURES: A prospective cross-sectional study was conducted. Body weight, BCS, QMR measurements, thoracic radiographic measurements, and muscle ultrasonographic measurements were assessed once in each dog. The MCS for each dog was assessed 3 separate times by 4 separate raters. RESULTS: For the MCS, overall κ for interrater agreement was 0.50 and overall κ for intrarater agreement ranged from 0.59 to 0.77. For both interrater and intrarater agreement, κ coefficients were higher for dogs with normal muscle mass and severe muscle loss and lower for dogs with mild and moderate muscle loss. The MCS was significantly correlated with age (r = -0.62), vertebral epaxial muscle score (VEMS; r = 0.71), forelimb epaxial muscle score (FLEMS; r = 0.58), and BCS (r = 0.73), and VEMS was significantly correlated (r = 0.84) with FLEMS. Cutoff values for identification of mild muscle loss determined by use of VEMS and FLEMS were 1.124 and 1.666, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: MCS had substantial repeatability and moderate reproducibility for assessment of muscle mass in dogs. Prospective studies of MCS, VEMS, and FLEMS for assessment of muscle mass in dogs are warranted.


Assuntos
Doenças do Cão/patologia , Doenças Musculares/veterinária , Animais , Peso Corporal , Estudos Transversais , Doenças do Cão/diagnóstico por imagem , Cães , Feminino , Imagem por Ressonância Magnética/veterinária , Masculino , Doenças Musculares/diagnóstico por imagem , Doenças Musculares/patologia , Estudos Prospectivos , Radiografia Torácica/veterinária , Reprodutibilidade dos Testes , Ultrassonografia/veterinária
19.
Am J Hum Genet ; 104(5): 847-860, 2019 05 02.
Artigo em Inglês | MEDLINE | ID: mdl-31051113

RESUMO

Collagen type IV alpha 1 and alpha 2 chains form heterotrimers ([α1(IV)]2α2(IV)) that represent a fundamental basement membrane constituent. Dominant COL4A1 and COL4A2 mutations cause a multisystem disorder that is marked by clinical heterogeneity and variable expressivity and that is generally characterized by the presence of cerebrovascular disease with ocular, renal, and muscular involvement. Despite the fact that muscle pathology is reported in up to one-third of individuals with COL4A1 and COL4A2 mutations and in animal models with mutations in COL4A1 and COL4A2 orthologs, the pathophysiological mechanisms underlying COL4A1-related myopathy are unknown. In general, mutations are thought to impair [α1(IV)]2α2(IV) secretion. Whether pathogenesis results from intracellular retention, extracellular deficiency, or the presence of mutant proteins in basement membranes represents an important gap in knowledge and a major obstacle for developing targeted interventions. We report that Col4a1 mutant mice develop progressive neuromuscular pathology that models human disease. We demonstrate that independent muscular, neural, and vascular insults contribute to neuromyopathy and that there is mechanistic heterogeneity among tissues. Importantly, we provide evidence of a COL4A1 functional subdomain with disproportionate significance for tissue-specific pathology and demonstrate that a potential therapeutic strategy aimed at promoting [α1(IV)]2α2(IV) secretion can ameliorate or exacerbate myopathy in a mutation-dependent manner. These data have important translational implications for prediction of clinical outcomes based on genotype, development of mechanism-based interventions, and genetic stratification for clinical trials. Collectively, our data underscore the importance of the [α1(IV)]2α2(IV) network as a multifunctional signaling platform and show that allelic and tissue-specific mechanistic heterogeneities contribute to the variable expressivity of COL4A1 and COL4A2 mutations.


Assuntos
Colágeno Tipo IV/genética , Doenças Musculares/etiologia , Mutação , Doenças Neuromusculares/etiologia , Animais , Feminino , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Doenças Musculares/patologia , Doenças Neuromusculares/patologia , Especificidade de Órgãos , Fenótipo
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