Faiblesse et douleurs musculaires generalisees chez une patiente de 88 ans: avez-vous pense aux medicaments [88 years old woman with acute muscular weakness and diffuse muscular pain: have you thought about the drugs?].

An 88 years old woman was admitted for muscular pain and weakness. She was under a treatment of simvastatin and was recently prescribed clarithromycin for a lung infection. The diagnosis of statin induced rhabdomyolysis by drug interaction was made. The evolution is good with eviction of the statin and aggressive hydratation. This case shows how important it is to know the risks factors and drug interactions predisposing to statin-induced myopathy.

Um olhar paradigmático sobre a Assistência de Enfermagem: um caminhar para o cuidado complexo

O texto aborda os paradigmas cartesiano (moderno) e o da complexidade (pós-moderno de Edgar Morin) objetivando aprofundar a reflexão sobre o tema e a compreensão do modo de assistir predominante na enfermagem. Para tanto, as autoras põem em discussão o modelo de assistência de enfermagem pautado no paradigma cartesiano definindo-o como produtor de uma assistência autoritária, fragmentada e linear. Apontam a necessidade de repensar esse modelo pelo fato de restringir a autonomia das pessoas/pacientes, caminhando na direção de um assistir pautado na complexidade, que proporciona condições de participação dos clientes/atores no planejamento dos cuidados à sua saúde.

Respiratory surveillance of patients with Duchenne and Becker muscular dystrophy.

Duchenne muscular dystrophy is is the most common form of the childhood muscular dystrophies. It follows a predictable clinical course marked by progressive skeletal muscle weakness, lost of ambulation before teen-age and death in early adulthood secondary to respiratory or cardiac failure. Becker muscular dystrophy is less common and has a milder clinical course but also results in respiratory and cardiac failure.Altough recent advances in respiratory care and new technologies have improved the outlook many patients already received only a traditional non-interventional approach. The aims of this work are: to analyse the pathophysiology and natural history of respiratory function in these diseases, to descript their clinical manifestations, to present the diagnostics tools and to provide recommendations for an adequated respiratory care in this particular population based on the updated literature referenced.

Co-morbidade fadiga e depressão em pacientes com câncer colo-retal

O estudo teve como objetivos caracterizar e identificar a comorbidade entre fadiga e depressão em pacientes com câncer colorretal. A amostra não-probabilística foi de 154 pacientes ambulatoriais (53% homens; idade média 49,6±11,7 anos; escolaridade média 8,9±5,4 anos). A fadiga foi avaliada pela Escala de Fadiga de Piper Revisada e o humor pelo Inventário de Depressão de Beck. A Fadiga foi relatada por 76 (49,4%) pacientes e foi intensa (escore total > 6) para 19,7% deles. Escores que sugerem depressão (IDB>20) foram encontrados em 11 (7,1%) pacientes. Fadiga e depressão estavam correlacionadas (r=0,395; p 0,001). A co-morbidade fadiga moderada/intensa e disforia/depressão ocorreu em 12,3%. A Fadiga estava presente na totalidade dos doentes deprimidos (100%), e a depressão ocorreu em 18% dos doentes fatigados. Fadiga e depressão são fenômenos relacionados, a sua comorbidade pode ser muito deletéria ao doente; a depressão foi mais importante para a ocorrência de fadiga do que a fadiga para a depressão.

Pictograma de Fadiga: uma alternativa para avaliação da intensidade e impacto da fadiga

O objetivo foi validar o Fatigue Pictogram para uso no Brasil. Os dados foram coletados em quatro ambulatórios de oncologia de São Paulo (SP) e na Escola de Enfermagem da USP. A amostra de conveniência envolveu 584 pacientes com câncer, 184 acompanhantes e 189 estudantes de graduação enfermagem, que responderam ao Pictograma de Fadiga, ao Inventário de Depressão de Beck (IDB) e Escala de Karnofsky (KPS). Foram feitos testes de validade e confiabilidade. O Teste-reteste mostrou que o instrumento tem boa estabilidade. O primeiro item do Pictograma de Fadiga discriminou estudantes de cuidadores de pacientes, mas não pacientes de cuidadores. O segundo item discriminou todos os grupos. Observou-se adequada validade convergente (fadiga e depressão) e divergente (fadiga e Karnofsky). O Pictograma de Fadiga é válido, confiável e fácil de usar para avaliar fadiga em câncer, mas necessita ajustes para uso em pessoas saudáveis.

Fadiga entre estudantes de graduação em enfermagem

A fadiga entre os estudantes pode prejudicar a aprendizagem. Avaliou-se a fadiga de graduandos de enfermagem e as relações com o ano de graduação, a participação em atividades extracurriculares, com quem o aluno reside, com a depressão e o índice de massa corporal (IMC). Participaram 189 (60,2%) estudantes da EEUSP, sendo 96,2% de mulheres com idade média de 21,6 anos, 80,9% residiam com os pais, 43,9% realizavam atividades extracurriculares, 24,8% tinham IMC alterado e 22,2% apresentaram disforia ou depressão (Inventário de Depressão de Beck). A fadiga foi moderada/ intensa para 83,5% dos estudantes (Escala de Fadiga de Piper Revisada e Pictograma de Fadiga) e 59,8% relataram prejuízo moderado/intenso nas atividades habituais. A fadiga apresentou correlação positiva com ano de graduação, com o IMC e a depressão (p<0,001). A atividade acadêmica foi a principal causa de fadiga, enquanto o sono e o lazer foram as estratégias mais utilizadas para seu manejo. A fadiga foi significativa e intensa, todavia observou-se descompasso entre freqüência, magnitude e impacto da fadiga nas atividades da vida diária.

Prevalência e comorbidade de dor e fadiga em mulheres com câncer de mama

O estudo analisou a prevalência e a comorbidade de dor e fadiga em mulheres com câncer de mama. Trata-se de estudo transversal, com amostra, não probabilística de 182 mulheres em tratamento ambulatorial para câncer de mama, entrevistadas no período de julho 2006 a março de 2007. Fadiga, avaliada pela Escala de Fadiga de Piper, foi dividida em duas categorias (escore 0,1-4,9 e >5-10). Dor, avaliada pela escala de 0-10, foi categorizada do mesmo modo que fadiga. Fadiga ocorreu em 94 mulheres (51,6%), sendo >5 em 44 (46,8%) delas. Dor ocorreu em 86 mulheres (47,2%), sendo >5 em 50 (58,1%). Fadiga e dor correlacionaram-se (r=0,38, p=0,003) e a comorbidade fadiga e dor foi de 38,3%. Dor intensa acentuou a fadiga (p=0,089) e fadiga intensa acentuou a dor (p=0,016). Tais dados são inéditos em nosso meio, confirmam a existência de um cluster de sintoma e dos prejuízos decorrentes dessa comorbidade.

Diagnosis of muscular dystrophies at the nanometer scale

The diagnosis of muscular dystrophies or the assessment of the functional benefit of gene or cell therapies can be difficult, especially for poorly accessible muscles, and it often lacks a singlefiber resolution. In the present study, we evaluated whether muscle diseases can be diagnosed from small biopsies using atomic force microscopy (AFM). AFM was shown to provide a sensitive and quantitative description of the resistance of normal and dystrophic myofibers within live muscle tissues explanted from Duchenne mdx mice. The rescue of dystrophin expression by gene therapy approaches led to the functional recovery of treated dystrophic muscle fibers, as probed using AFM and by in situ wholemuscle strength measurements. Comparison of muscles treated with viral or non-viral vectors indicated that the efficacy of the gene transfer approaches could be distinguished with a single myofiber resolution. This indicated full correction of the resistance to deformation in nearly all of the muscle fibers treated with an adeno-associated viral vector that mediates exon-skipping on the dystrophin mRNA. Having shown that AFM can provide a quantitative assessment of the expression of muscle proteins and of the muscular function in animal models, we assessed myofiber resistance in the context of human muscular dystrophies and myopathies. Thus, various forms of human Becker syndrome can also be detected using AFM in blind studies of small frozen biopsies from human patients. Interestingly, it also allowed the detection of anomalies in a fraction of the muscle fibers from patients showing a muscle weakness that could not be attributed to a known molecular or genetic defect. Overall, we conclude that AFM may provide a useful method to complement current diagnosis tools of known and unknown muscular diseases, in research and in a clinical context.

A dystroglycan mutation associated with limb-girdle muscular dystrophy.

Dystroglycan, which serves as a major extracellular matrix receptor in muscle and the central nervous system, requires extensive O-glycosylation to function. We identified a dystroglycan missense mutation (Thr192→Met) in a woman with limb-girdle muscular dystrophy and cognitive impairment. A mouse model harboring this mutation recapitulates the immunohistochemical and neuromuscular abnormalities observed in the patient. In vitro and in vivo studies showed that the mutation impairs the receptor function of dystroglycan in skeletal muscle and brain by inhibiting the post-translational modification, mediated by the glycosyltransferase LARGE, of the phosphorylated O-mannosyl glycans on α-dystroglycan that is required for high-affinity binding to laminin.

Orofacial dysfunction in Duchenne muscular dystrophy.

Duchenne muscular dystrophy (DMD) affects orofacial function. Our aim was to evaluate certain characteristics of orofacial function in DMD and relate possible deteriorations to the age of the patients and to the diminished internal structure quality of the masseter muscle. Bite force and finger force were measured in 16 DMD patients (6-20 years old) and 16 age matched controls. The thickness and internal structure quality of the masseter muscle were evaluated ultrasonographically. We found reduced mouth opening but no signs of masticatory muscle tenderness. Bite force values were lower for DMD patients. Masseter thickness showed no significant differences between the two groups, but poorer internal muscle structure quality characterised the elder, non-walking DMD patients explaining their low bite force values. In conclusion, the masseter muscle follows the general progress of the disease. Orofacial function in DMD patients is becoming ever more important as their life expectancy increases.

Amelioration of Duchenne muscular dystrophy in mdx mice by elimination of matrix-associated fibrin-driven inflammation coupled to the αMβ2 leukocyte integrin receptor

In Duchenne muscular dystrophy (DMD), a persistently altered and reorganizing extracellular matrix (ECM) within inflamed muscle promotes damage and dysfunction. However, the molecular determinants of the ECM that mediate inflammatory changes and faulty tissue reorganization remain poorly defined. Here, we show that fibrin deposition is a conspicuous consequence of muscle-vascular damage in dystrophic muscles of DMD patients and mdx mice and that elimination of fibrin(ogen) attenuated dystrophy progression in mdx mice. These benefits appear to be tied to: (i) a decrease in leukocyte integrin α(M)β(2)-mediated proinflammatory programs, thereby attenuating counterproductive inflammation and muscle degeneration; and (ii) a release of satellite cells from persistent inhibitory signals, thereby promoting regeneration. Remarkably, Fib-gamma(390-396A) (Fibγ(390-396A)) mice expressing a mutant form of fibrinogen with normal clotting function, but lacking the α(M)β(2) binding motif, ameliorated dystrophic pathology. Delivery of a fibrinogen/α(M)β(2) blocking peptide was similarly beneficial. Conversely, intramuscular fibrinogen delivery sufficed to induce inflammation and degeneration in fibrinogen-null mice. Thus, local fibrin(ogen) deposition drives dystrophic muscle inflammation and dysfunction, and disruption of fibrin(ogen)-α(M)β(2) interactions may provide a novel strategy for DMD treatment.

Maintenance of neuronal expression of calbindin by a muscular extract in cultures of chick dorsal root ganglion cells.

Calbindin D-28K is a calcium-binding protein which is expressed by subpopulations of dorsal root ganglion cells cultured from 10-day-old (E10) chick embryos. After 7 or 10 days of culture, more than 20% of the ganglion cells are immunostained by an anticalbindin-antiserum; however, after 14 days of culture, the proportion drops to 10%. This fall can be prevented by addition of muscle extract to cultures at 10 days. Thus the transitory expression of calbindin-immunoreactivity by responsive sensory neurons would be not only induced but also maintained by a differentiation factor of muscular origin.

Human muscular fetal cells: a potential cell source for muscular therapies.

Myoblast transfer therapy has been extensively studied for a wide range of clinical applications, such as tissue engineering for muscular loss, cardiac surgery or Duchenne Muscular Dystrophy treatment. However, this approach has been hindered by numerous limitations, including early myoblast death after injection and specific immune response after transplantation with allogenic cells. Different cell sources have been analyzed to overcome some of these limitations. The object of our study was to investigate the growth potential, characterization and integration in vivo of human primary fetal skeletal muscle cells. These data together show the potential for the creation of a cell bank to be used as a cell source for muscle cell therapy and tissue engineering. For this purpose, we developed primary muscular cell cultures from biopsies of human male thigh muscle from a 16-week-old fetus and from donors of 13 and 30 years old. We show that fetal myogenic cells can be successfully isolated and expanded in vitro from human fetal muscle biopsies, and that fetal cells have higher growth capacities when compared to young and adult cells. We confirm lineage specificity by comparing fetal muscle cells to fetal skin and bone cells in vitro by immunohistochemistry with desmin and 5.1 H11 antibodies. For the feasibility of the cell bank, we ensured that fetal muscle cells retained intrinsic characteristics after 5 years cryopreservation. Finally, human fetal muscle cells marked with PKH26 were injected in normal C57BL/6 mice and were found to be present up to 4 days. In conclusion we estimate that a human fetal skeletal muscle cell bank can be created for potential muscle cell therapy and tissue engineering.

Essais thérapeutiques dans la dystrophie musculaire de Duchenne: entre espoirs et désespoirs [Therapeutic trials for Duchenne muscular dystrophy: between hopes and disappointments].

Duchenne muscular dystrophy is an X-linked progressive muscle disease. Since the discovery of the dystrophin gene responsible for the condition, various therapeutic strategies have been elaborated. In this paper we introduce three of them, which are well into clinical trials. The first is based on the ability to read through premature stop codons, the second is based on the technique of exon skipping. Both strategies are examples of "personalized medicines", tailored for specific mutation types. The third approach is a pharmacological one, potentially useful for all Duchenne patients, regardless of their mutation type. These first clinical trials raise many questions for researchers as well as for patients and their families, some of which are discussed.