RESUMO
Muscle disease symptoms and myopathies are not uncommon in the elderly. Inflammatory and noninflammatory myopathies lead to proximal extremity or axial weakness and are superimposed on the intrinsic changes that occur in muscle with aging (sarcopenia). This article surveys the more common myopathies in the elderly based on a review of the process of sarcopenia, and how these age-related changes in muscle structure and function affect the results of the standard assessments of muscle disease in the elderly.
Assuntos
Envelhecimento , Doenças Musculares , Idoso , Humanos , Doenças Musculares/diagnóstico , Doenças Musculares/etiologia , Doenças Musculares/imunologiaRESUMO
The arthroscope can play an important diagnostic role in the arthritis patient. The major utility of this procedure is in the patient with unexplained knee pain and swelling or in the patient with an established knee arthritis whose symptoms are disproportionate to radiographic findings or refractory to standard-course medical therapy. Technologic advances have led to the production of smaller instruments, making office-based diagnostic arthroscopy a practical, cost-effective alternative in the evaluation of these patients, and supporting the clinical argument for it as a procedure distinct from conventional arthroscopy. Separate clinical scenarios further subdivide the indications for diagnostic arthroscopy and define potential intra-articular abnormalities that, if found, can justify alterations in or additions to therapeutic plans, including arthroscopically directed tissue resection and modification or application of tissue-modifying agents. The research capabilities of needle arthroscopy are only just beginning to be realized; opportunities now exist for design of prospective clinical trials in which patients are randomized based on intra-articular abnormalities, and for the serial assessment of specific treatment effects on gross, microscopic, and molecular features of target tissue as identified by the arthroscope.
Assuntos
Artrite/diagnóstico , Artroscopia , Adulto , Artrite Reumatoide/diagnóstico , Artroscópios , Diagnóstico Diferencial , Feminino , Humanos , Articulação do Joelho/patologia , Masculino , Pessoa de Meia-IdadeRESUMO
STUDY DESIGN: Case report. OBJECTIVES: To report on the diagnosis and current treatment of a rare tumor about the cervical spine. SUMMARY OF BACKGROUND DATA: Extraskeletal Ewing's sarcoma (EES) is rare and has not been previously described about the cervical spine. We present a case of a 24-year-old man with a large mass in the posterior triangle of the neck extending through the vertebral foramens of the cervical vertebrae. This was identified as an extraskeletal Ewing's sarcoma. Traditional treatment paradigms have been associated with a poor prognosis. Since the recommendations of the Intergroup Rhabdomyosarcoma Study II study of multimodal chemotherapy and radiotherapy, this tumor has a significantly better prognosis. METHOD: Surgical debulking of the tumor was necessary to relieve cord compression. Histologic analysis was used to confirm both magnetic resonance imaging and computed tomography diagnosis. A chemoradiation therapy program was commenced in accordance with Intergroup Rhabdomyosarcoma Study II recommendations. RESULTS: Computed tomography and magnetic resonance imaging demonstrated a large lobulated mass extending through the exit foramens of C2/C3 and C3/C4. The mass was entirely extraskeletal and extradural. Histologic examination of the excised mass showed microscopy consistent with extraskeletal Ewing's sarcoma. After surgical debulking and chemoradiation, the patient made a complete recovery. CONCLUSION: A review of the literature confirms that extraskeletal Ewing's sarcoma is a rare tumor and particularly so in the region of the cervical spine. Early diagnosis and surgical debulking combined with current multimodality chemoradiation programs can produce a favorable outcome.
Assuntos
Vértebras Cervicais/patologia , Sarcoma de Ewing/patologia , Neoplasias de Tecidos Moles/patologia , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Terapia Combinada , Dactinomicina/administração & dosagem , Doxorrubicina/administração & dosagem , Humanos , Ifosfamida/administração & dosagem , Laminectomia , Masculino , Radioterapia , Sarcoma de Ewing/diagnóstico por imagem , Sarcoma de Ewing/terapia , Neoplasias de Tecidos Moles/diagnóstico por imagem , Neoplasias de Tecidos Moles/terapia , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Vincristina/administração & dosagemRESUMO
OBJECTIVE: To determine whether physical examination maneuvers that focus on each knee compartment and assess crepitus at several distinct sites can specifically disclose articular cartilage abnormalities in the compartment being assessed. METHODS: Twenty patients with knee pain were examined before needle arthroscopy. Crepitus was sought from the patellofemoral compartment, medial tibiofemoral compartment, and lateral tibiofemoral compartment. Any crepitus felt in the distal tibia during a tibiofemoral stress maneuver was recorded as transmitted bony crepitus (TBC). Needle arthroscopy assessed articular cartilage (5 sites) and both menisci in each knee. RESULTS: Crepitus by conventional assessment revealed patellar cartilage disruption (69% sensitive, 50% specific) and abnormalities of tibiofemoral cartilage (67% sensitive, 40% specific) but could not indicate their location. Tibiofemoral crepitus found cartilage disruption in the compartment at a sensitivity of 22% and a specificity of 100%, and with added tibiofemoral stress, a sensitivity of 65% and a specificity of 94% (the one "false positive" had bare bone in the other compartment). TBC was detected in 7 compartments, all of which had focal bare bone on tibial and femoral surfaces; 6 other compartments had tibial bare bone without TBC. Thus, TBC was 54% sensitive and 100% specific for tibial bare bone, and 88% sensitive and 100% specific for bone-on-bone. CONCLUSION: Compartment-directed physical examination of the painful knee can locate and assess the severity of certain articular cartilage abnormalities that are not reliably found by conventional methods. Transmitted bony crepitus is a specific finding for bone-on-bone in the compartment being assessed.
Assuntos
Artroscopia/normas , Cartilagem Articular/anormalidades , Articulação do Joelho/patologia , Exame Físico/normas , Adulto , Idoso , Idoso de 80 Anos ou mais , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/patologia , Artroscopia/métodos , Cartilagem Articular/patologia , Feminino , Fêmur/anormalidades , Fêmur/patologia , Humanos , Articulação do Joelho/anormalidades , Masculino , Pessoa de Meia-Idade , Osteoartrite/diagnóstico , Osteoartrite/patologia , Dor/patologia , Valor Preditivo dos Testes , Índice de Gravidade de Doença , Tíbia/anormalidades , Tíbia/patologiaRESUMO
OBJECTIVE: To determine whether intraarticular abnormalities in osteoarthritis (OA) of the knee can be detected as well by needle arthroscopy as by standard arthroscopy. METHODS: Needle arthroscopy followed by standard arthroscopy was performed on 10 patients with knee OA (diagnosed according to American College of Rheumatology criteria) whose symptoms were not entirely attributable to the OA and were therefore an indication for further evaluation. Each knee was assessed for abnormalities of the menisci, articular cartilage (6 sites), and synovium (6 sites). RESULTS: Evaluation of the 18 menisci visualized with both techniques yielded the same results: 6 abnormal and 12 normal. Among the 54 articular cartilage sites evaluable with both procedures, 16 were judged normal by both needle arthroscopy and standard arthroscopy. Of the 38 cartilage sites judged abnormal by standard arthroscopy, 34 (89%) were abnormal by needle arthroscopy. Both techniques indicated cartilage changes were the same at 42 (78%) of the 54 sites; changes at the other 12 sites were 1 grade higher by standard arthroscopy than by needle arthroscopy. Both needle arthroscopy and standard arthroscopy revealed 51 evaluable sites in the synovium. Of 34 areas judged abnormal by standard arthroscopy, 24 (71%) were also judged abnormal by needle arthroscopy; 17 areas were judged normal by both techniques. The 2 techniques assigned the same macroscopic score in 27 (53%) of 51 areas of the synovium, with a higher grade by standard arthroscopy in all but 1 of the other 16 areas. CONCLUSION: These pilot data suggest that in knee OA, needle arthroscopy can 1) accurately detect meniscal abnormalities, 2) detect cartilage abnormalities, but may underestimate the severity, and 3) detect most synovial abnormalities, but often underestimates the severity. Needle arthroscopy is a potentially valuable rheumatologic tool for the assessment of OA of the knee.
Assuntos
Artroscopia/métodos , Articulação do Joelho/patologia , Agulhas , Osteoartrite/patologia , Adulto , Idoso , Artrografia , Artroscópios , Cartilagem Articular/diagnóstico por imagem , Cartilagem Articular/patologia , Estudos de Avaliação como Assunto , Feminino , Humanos , Articulação do Joelho/diagnóstico por imagem , Masculino , Meniscos Tibiais/diagnóstico por imagem , Meniscos Tibiais/patologia , Pessoa de Meia-Idade , Osteoartrite/diagnóstico por imagem , Projetos Piloto , Membrana Sinovial/diagnóstico por imagem , Membrana Sinovial/patologiaRESUMO
OBJECTIVE: To evaluate the utility of percutaneous needle muscle biopsy (NMB) as an alternative to open biopsy for the evaluation of patients with myopathy encountered in a university hospital based rheumatology setting. METHODS: Chart review of all patients (n = 30) who underwent NMB at our institution over a 4-year period. Patients were grouped according to clinical outcome. Records of 91 patients who underwent open biopsy during the same period were reviewed for comparison. RESULTS: NMB results either confirmed or added to the prebiopsy diagnostic suspicion in 11 patients and excluded a low prebiopsy suspicion in 13, thus yielding useful clinical information in 24 of 30 patients (80%). Biopsy left the suspected diagnosis unresolved more frequently in patients undergoing NMB compared to patients who had open biopsy during the same time period (6/30 vs 1/91). In the 6 cases unresolved by NMB, subsequent open biopsy added additional information in only 2 of 5 patients. Sensitivity of NMB for inflammatory myopathy was 83% in the 23 patients suspected of having this disease. NMB could be arranged twice as fast as open biopsy, and provided adequate tissue for evaluation in all cases. CONCLUSIONS: Our results suggest that NMB is an effective tool for obtaining useful diagnostic information, particularly pertaining to the presence of an inflammatory myopathy. The convenience, low morbidity, and sensitivity of NMB make it a procedure worthy of wider application by rheumatologists.
Assuntos
Biópsia por Agulha , Músculos/patologia , Doenças Musculares/diagnóstico , Reumatologia/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia/métodos , Biópsia por Agulha/instrumentação , Estudos de Avaliação como Assunto , Feminino , Hospitais Universitários , Humanos , Inflamação , Masculino , Pessoa de Meia-Idade , Doenças Musculares/patologia , Avaliação de Resultados em Cuidados de Saúde , Valor Preditivo dos Testes , Estudos Retrospectivos , Sensibilidade e EspecificidadeRESUMO
The biological mechanisms underlying decline in muscle power and fatigue with age are not completely understood. The contribution of alterations in the excitation-calcium release coupling in single muscle fibers was explored in this work. Single muscle fibers were voltage-clamped using the double Vaseline gap technique. The samples were obtained by needle biopsy of the vastus lateralis (quadriceps) from 9 young (25-35 years; 25.9 +/- 9.1; 5 female and 4 male) and 11 old subjects (65-75 years; 70.5 +/- 2.3; 6 f, 5 m). Data were obtained from 36 and 39 fibers from young and old subjects, respectively. Subjects included in this study had similar physical activity. Denervated and slow-twitch muscle fibers were excluded from this study. A significant reduction of maximum charge movement (Qmax) and DHP-sensitive Ca current were recorded in muscle fibers from the 65-75 group. Qmax values were 7.6 +/- 0.9 and 3.2 +/- 0.3 nC/muF for young and old muscle fibers, respectively (P < 0.01). No evidences of charge inactivation or interconversion (charge 1 to charge 2) were found. The peak Ca current was (-)4.7 +/- 0.08 and (-)2.15 +/- 0.11 muA/muF for young and old fibers, respectively (P < 0.01). The peak calcium transient studied with mag-fura-2 (400 microM) was 6.3 +/- 0.4 microM and 4.2 +/- 0.3 microM for young and old muscle fibers, respectively. Caffeine (0.5 mM) induced potentiation of the peak calcium transient in both groups. The decrease in the voltage-/Ca-dependent Ca release ratio in old fibers (0.18 +/- 0.02) compared to young fibers (0.47 +/- 0.03) (P < 0.01), was recorded in the absence of sarcoplasmic reticulum calcium depletion. These data support a significant reduction of the amount of Ca available for triggering mechanical responses in aged skeletal muscle and, the reduction of Ca release is due to DHPR-ryanodine receptor uncoupling in fast-twitch fibers. These alterations can account, at least partially for the skeletal muscle function impairment associated with aging.
Assuntos
Envelhecimento/fisiologia , Canais de Cálcio/fisiologia , Cálcio/fisiologia , Fibras Musculares de Contração Rápida/fisiologia , Músculo Esquelético/fisiopatologia , Adulto , Idoso , Animais , Transporte Biológico , Biópsia por Agulha , Canais de Cálcio Tipo L , Feminino , Humanos , Masculino , Contração Muscular/fisiologia , Denervação Muscular , Debilidade Muscular/fisiopatologia , Músculo Esquelético/patologia , Técnicas de Patch-Clamp , Ratos , Tetrodotoxina/farmacologiaRESUMO
Muscle biopsy remains a critical component in the evaluation of myopathies. Recent literature demonstrates that percutaneous biopsy instruments can effectively procure muscle tissue for analysis in clinical and research settings. We review issues of muscle biopsy technique and specimen processing in the context of available clinical methods for tissue analysis. A survey of recent literature illustrates contributions made by the histologic, histochemical, and ultrastructural aspects of muscle analysis to our understanding of the pathophysiologic mechanisms and clinical manifestations of selected inflammatory, mitochondrial, and infectious myopathies.
Assuntos
Biópsia/instrumentação , Doenças Musculares/diagnóstico , HumanosRESUMO
We have previously shown that administration of anti-C4 antibody to cells in culture can suppress the synthesis and secretion of C4. Lymphoid cells must be present along with the C4 secreting macrophages to achieve suppression of full magnitude and long duration. In this publication we have demonstrated that treatment of peritoneal macrophages with intact anti-C4 antibody results in reduction of intracellular and secreted C4. Intracellular levels of pro-C4 rapidly returned to normal after removal of the suppressing antibody and extracellular levels of C4 secreted into the media returned to normal within 24-48 h. This is in marked contrast to our previously published results with splenic fragments where intracellular pro-C4 remained markedly reduced long after removal of anti-C4. Using pulse-chase experiments we now demonstrate that, after recovery from suppression, intracellular pro-C4 levels remain low in splenic macrophages because nascent C4 is processed through the cell more rapidly. This results in a smaller intracellular pool of C4, even in the face of normal or high levels of C4 synthesis in the postsuppression phase. Finally, we demonstrate that suppression of full magnitude and duration could only be achieved with intact anti-C4 antibody. F(ab')2 fragments were not capable of inducing complete suppression.
Assuntos
Anticorpos Monoclonais/imunologia , Complemento C4/biossíntese , Macrófagos/metabolismo , Cavidade Peritoneal/citologia , Baço/citologia , Animais , Células Cultivadas , Complemento C3/biossíntese , Complemento C4/imunologia , Complemento C4/metabolismo , Fator B do Complemento/biossíntese , CobaiasRESUMO
Suppression of the synthesis of the fourth component of complement in vitro was originally accomplished by exposing cultured guinea pig peritoneal cells to anti-C4 alloantisera. When guinea pig splenic fragments were used instead of peritoneal cells, equivalent antibody treatment produced C4 suppression of significantly longer duration, lasting weeks instead of days after removal of antibody. As with peritoneal cell monolayers, antibody treatment induced specific suppression of C4 followed by nonspecific stimulation of C4 and other proteins such as C2. Although IgG2 is more readily sequestered by splenic tissue, both IgG1 and IgG2 antibodies were effective in inducing and maintaining suppression. Experiments with radiolabeled antibody demonstrated that a small amount (less than 5%) of the original dose of antibody was retained by the splenic fragments. Because there was no continuous slow release of that antibody, long-term suppression of C4 cannot be explained as a fluid-phase neutralization reaction. Because antibody treatment might induce production of aberrant C4 molecules with no functional activity, C4 antigens was also studied. Tissue culture supernatants were assayed by using an ELISA for C4. In none of these experiments was extracellular C4 antigen detectable immediately after antibody treatment. Extracellular and intracellular C4 were immunoprecipitated from biosynthetically labeled tissue cultures and analyzed by SDS-PAGE. Antibody treatment suppressed intracellular C4 as well as extracellular C4. Although extracellular C4 levels of antibody-treated cultures eventually returned to levels comparable to untreated cultures, intracellular C4 levels of treated fragments remained lower than controls for the full period of observation (22 days). Therefore, a short (4-day) exposure to anti-C4 antibody induced long-term effects that profoundly altered regulation of C4 synthesis and secretion by cultured splenic macrophages.
Assuntos
Ativação do Complemento , Complemento C4/biossíntese , Tolerância Imunológica , Isoanticorpos/fisiologia , Baço/imunologia , Animais , Complemento C4/imunologia , Complemento C4/metabolismo , Técnicas de Cultura , Cobaias , Testes de Neutralização , Peritônio/citologia , Peritônio/metabolismo , Processamento de Proteína Pós-Traducional , Baço/metabolismo , Fatores de TempoRESUMO
Previous work in our laboratory established that individual complement components can be regulated in vivo by administration of specific antibody or immunocompetent cells to newborns and in vitro by administration of specific antibody to cultured peritoneal macrophages or splenic fragments. Antibody-induced suppression of C4 was much longer lasting in cultured guinea pig splenic fragments than in cultured guinea pig peritoneal macrophages, suggesting that splenic fragments contained elements necessary for long-term suppression that were not present in the macrophage monolayers. This publication presents data in support of this concept. Antibody-treated splenic fragments from normal guinea pigs--but not from C4-deficient guinea pigs--elaborated a soluble factor (FsC4) that suppressed C4 production in previously untreated splenic fragments. FsC4 activity was most potent in splenic fragment culture supernatants at those times when intracellular and secreted C4 hemolytic activity and C4 antigen were at their lowest. C4 itself or a fragment of C4 was therefore unlikely to mediate suppression in this system. Residual anti-C4 antibody was ruled out as a mediator of FsC4 activity since it was shown by two independent methods that the amount of anti-C4 antibody carried over with the supernatant was orders of magnitude less than the amount necessary to cause suppression or to neutralize fluid phase C4 in fresh splenic fragment cultures. Preliminary data revealed that FsC4 activity may be mediated by two or more distinct molecular species or may be mediated by a single molecule that exhibits secondary size and charge heterogeneity. The identification of factors that are capable of regulating C4 suggests that, as with immunoglobulins, complement components may be regulated by complex networks of immunocompetent cells and their soluble products.
Assuntos
Complemento C4/biossíntese , Fatores Supressores Imunológicos/fisiologia , Animais , Sistema Livre de Células , Complemento C4/deficiência , Complemento C4/imunologia , Cobaias , Soros Imunes/farmacologia , Imunização Passiva , Peso Molecular , Baço/imunologia , Baço/transplante , Fatores Supressores Imunológicos/biossíntese , Fatores Supressores Imunológicos/isolamento & purificação , Fatores de TempoRESUMO
A patient with Wegener's granulomatosis developed a systemic cytomegalovirus infection that mimicked an exacerbation of her vasculitis including pulmonary infiltrates, renal insufficiency, and cutaneous necrotizing ulcers. All of her symptoms resolved with ganciclovir. Physicians should maintain a high index of suspicion for similar presentations in other patients with vasculitis with or without immunosuppressive therapy.
Assuntos
Infecções por Citomegalovirus/diagnóstico , Granulomatose com Poliangiite/diagnóstico , Idoso , Ciclofosfamida/uso terapêutico , Infecções por Citomegalovirus/tratamento farmacológico , Diagnóstico Diferencial , Feminino , Ganciclovir/uso terapêutico , Granulomatose com Poliangiite/tratamento farmacológico , Humanos , Pulmão/diagnóstico por imagem , Pulmão/patologia , Prednisona/uso terapêutico , Radiografia TorácicaRESUMO
Our laboratory has shown that short-term treatment in vivo or in vitro with monospecific antibody to individual complement components can have long-term effects on the production of those components. In vitro studies have focused on the fourth component of complement (C4) in a guinea pig model. Uniform splenic fragments have been used to mimic the in vivo microenvironment of the C4-producing macrophages. A 4-day exposure to anti-C4 antibody led to a reduction of secreted C4 for 1 to 2 wk and a reduction of intracellular C4 that persisted even longer. In an attempt to understand how short-term exposure to antibody can specifically and permanently disrupt the C4-producing cell, we have determined whether C4 suppression could be enhanced by components that modulate cellular functions through their role as secondary intracellular messengers. We found that compounds which elevated cellular levels of cAMP by any of three mechanisms all enhanced antibody-induced suppression of C4.
Assuntos
Anticorpos/fisiologia , Complemento C4/biossíntese , AMP Cíclico/fisiologia , Tolerância Imunológica , 1-Metil-3-Isobutilxantina/farmacologia , Adenilil Ciclases/metabolismo , Animais , Bucladesina/farmacologia , Toxina da Cólera/farmacologia , Complemento C4/imunologia , Fator B do Complemento/biossíntese , AMP Cíclico/metabolismo , Cobaias , Tolerância Imunológica/efeitos dos fármacos , Inibidores de Fosfodiesterase/farmacologia , Baço/citologia , Baço/metabolismoRESUMO
OBJECTIVE: Antigen-specific CD4+ T cells treated with DNA methylation inhibitors become autoreactive, suggesting a novel mechanism for autoimmunity. To test whether this mechanism might be involved in systemic lupus erythematosus (SLE), phenotypic markers for the autoreactive cells were sought. METHODS: Cloned normal T cells were treated with the DNA methylation inhibitor 5-azacytidine (5-azaC) and studied for altered gene expression. T cells from patients with active SLE were then studied for a similar change in gene expression, and cells expressing the marker were tested for autoreactivity. RESULTS: 5-azaC-treated normal T cells had increased CD11a (leukocyte function-associated antigen 1 alpha) expression relative to other membrane molecules. A T cell subset with similar CD11a expression was found in patients with active SLE. This subset contained cells that spontaneously lysed autologous macrophages, with a specificity similar to that of 5-azaC-treated cells.
Assuntos
Azacitidina/farmacologia , Lúpus Eritematoso Sistêmico/patologia , Linfócitos T/efeitos dos fármacos , Antígenos CD/imunologia , Autoimunidade/fisiologia , Antígenos CD11 , Eletroforese em Gel Bidimensional , Citometria de Fluxo , Humanos , Lúpus Eritematoso Sistêmico/genética , Lúpus Eritematoso Sistêmico/imunologia , Ativação Linfocitária/imunologia , Antígeno-1 Associado à Função Linfocitária/genética , Fenótipo , RNA Mensageiro/análise , Receptores de Antígenos de Linfócitos T/efeitos dos fármacos , Subpopulações de Linfócitos T/fisiologia , Linfócitos T/imunologiaRESUMO
BACKGROUND: Several scoring systems have been proposed in order to quantify the degree of cartilage damage observed by arthroscopy of the knee in patients with osteoarthritis. OBJECTIVE: To evaluate the inter-observer reliability of five different scoring systems of arthroscopic evaluation for chondropathy in osteoarthritis of the knee and to evaluate the utility of a training session between different observations on these scoring systems. METHODS: Videotapes of knee arthroscopies on five patients with osteoarthritis demonstrating different levels of severity of cartilage damage of the medial tibiofemoral compartment were analyzed by nine observers prior to (pre-training evaluation) and 2 months after a 6 h training session (post-training evaluation) by the following scoring systems: (1) cartilage deterioration by a 100 mm visual analogue scale (VAS), (2) overall assessment of degeneration in the entire medial compartment (cartilage, meniscus, osteophyte) using a 100 mm VAS, (3) French Society of Arthroscopy (SFA) Scoring System, (4) SFA Grading System, (5) American College of Rheumatology (ACR) Scoring System. RESULTS: At the pre-training evaluation, the SFA grading system produced the highest coefficient of reliability (r = 0.94), the other systems recording levels of < or = 0.80. At the post-training evaluation, the coefficient of reliability was r > 0.80 for four of the five scoring systems, with lack of improvement in the ACR Scoring System. CONCLUSION: There was an improved and acceptable inter-observer reliability for at least 2 months follow-up in four of five evaluated scoring systems of arthroscopically graded osteoarthritis of the knee following a training session. A scoring system using a 100 mm VAS may produce the best inter-observer reliability. These results show that scoring chondropathy is possible and demonstrate the importance of training in the analysis of articular cartilage breakdown.