RESUMO
In calcium pyrophosphate dihydrate (CPPD) crystal deposition disease, metabolic abnormalities favoring extracellular inorganic pyrophosphate (PPi) accumulation have been suspected. Elevations of intracellular PPi in cultured skin fibroblasts from a single French kindred with familial CPPD deposition (19) and elevated nucleoside triphosphate pyrophosphohydrolase activity (NTPPPH), which generates PPi in extracts of CPPD crystal-containing cartilages (14) favor this suspicion. To determine whether NTPPPH activity or PPi content of cells might be a disease marker expressed in extraarticular cells, human skin-derived fibroblasts were obtained from control donors and patients affected with the sporadic and familial varieties of CPPD (CPPD-S and CPPD-F) deposition. Intracellular PPi was elevated in both CPPD-S (P less than 0.05) and CPPD-F (P less than 0.01) fibroblasts compared with control fibroblasts. Ecto-NTPPPH activity was elevated in CPPD-S (P less than 0.01) but not CPPD-F. Intracellular PPi correlated with ecto-NTPPPH (P less than 0.01). Elevated PPi levels in skin fibroblasts may serve as a biochemical marker for patients with familial or sporadic CPPD crystal deposition disease; ecto-NTPPPH activity further separates the sporadic and familial disease types. Expression of these biochemical abnormalities in nonarticular cells implies a generalized metabolic abnormality.
Assuntos
Pirofosfato de Cálcio/metabolismo , Difosfatos/análise , Difosfatos/metabolismo , Distúrbios do Metabolismo do Fósforo/metabolismo , Pirofosfatases/metabolismo , Pele/metabolismo , Células Cultivadas , Cristalização , Fibroblastos/metabolismo , HumanosRESUMO
Sixty-four patients were evaluated prospectively for a reflex sympathetic dystrophy syndrome (RSDS), using quantitative clinical measurements, high-resolution roentgenography and scintigraphy. Five separate groups were identified by their clinical features, allowing us to distinguish patients with definite or incomplete forms of the RSDS as well as 16 patients with other disorders. Scintigraphy was found to be a useful diagnostic study that may also provide a method of predicting therapeutic response. Systemic corticosteroid therapy proved to be a highly effective mode of treatment for up to 90 percent of the patients with the RSDS.
Assuntos
Distrofia Simpática Reflexa/diagnóstico , Diagnóstico Diferencial , Extremidades/diagnóstico por imagem , Bloqueadores Ganglionares/uso terapêutico , Humanos , Prednisona/uso terapêutico , Radiografia , Cintilografia , Distrofia Simpática Reflexa/tratamento farmacológico , Gânglio EstreladoRESUMO
Despite an increase in the number of rheumatologists in clinical practice over the past 15 years, the outcome for patients with rheumatoid arthritis (RA) remains relatively poor. The poor prognosis for patients with this disease is due to a lack of effective therapies. Better therapies will be developed only after the cause and pathogenesis of RA are better understood. Although the precise cause is unknown, a variety of evidence indicates that RA results from the presentation of a relevant antigen to an immunogenetically susceptible host. This report reviews recognized potential antigens and known genetic variables affecting the immune response, as well as the various cellular and humoral immune responses that result from the antigen-host interaction. More successful therapy for RA will most certainly result from a better understanding of the pathobiology of the disease.
Assuntos
Artrite Reumatoide/etiologia , Formação de Anticorpos , Artrite Reumatoide/imunologia , Artrite Reumatoide/terapia , Citocinas/fisiologia , Suscetibilidade a Doenças , Previsões , Antígenos HLA/análise , Humanos , Imunogenética , Linfócitos/fisiologiaRESUMO
An in vitro model of ADA deficiency is selectively toxic to cartilage from immature rabbits with a greater effect on growth plate than articular cartilage. The selective toxicity observed appears to be the consequence of ATP depletion. These results support the hypothesis that the chondro-osseous dysplasia observed in patients with ADA deficiency is caused by the disordered metabolism that results from the enzyme deficiency.
Assuntos
Adenosina Desaminase/deficiência , Exostose Múltipla Hereditária/enzimologia , Nucleosídeo Desaminases/deficiência , Adenosina Desaminase/metabolismo , Envelhecimento , Animais , Cartilagem Articular/enzimologia , Cartilagem Articular/crescimento & desenvolvimento , Modelos Animais de Doenças , Lâmina de Crescimento/enzimologia , Lâmina de Crescimento/crescimento & desenvolvimento , CoelhosRESUMO
Articular cartilage contains any ectoenzyme activity, NTP-PPH, which is capable of generating PPi from NTP substrates. The PPi generated is from the cleavage of the alpha-beta pyrophosphate bond of NTP and does not result from the effects of NTP catabolites. NTP-PPH activity is expressed on human skin fibroblasts in culture and is significantly increased in subjects with CPPD deposition. In addition, cultured fibroblasts from subjects with CPPD disease have higher intracellular PPi concentrations compared to cells from normals and patients with OA. These results support the hypothesis that alterations in PPi metabolism provide the metabolic basis for CPPD deposition.
Assuntos
Pirofosfato de Cálcio/metabolismo , Cálculos/metabolismo , Cartilagem Articular/metabolismo , Difosfatos/metabolismo , Pirofosfatases/metabolismo , Nucleotídeos de Adenina/metabolismo , Animais , Cães , Técnicas de Cultura de Órgãos , Purinas/metabolismoRESUMO
These results indicate that measuring venous ammonia concentrations after forearm ischemic exercise is an effective means of screening for MADA deficiency but that submaximal exercise performance, whether due to weakness, pain or poor effort, can provide false positive results. Measurements of purine compounds released after exercise may increase the specificity of forearm ischemic exercise testing for MADA deficiency. The low level of purines released after exercise in MADA-deficient subjects supports the hypothesis that disordered purine metabolisms occurs when MADA activity is absent.
Assuntos
AMP Desaminase/deficiência , Nucleotídeo Desaminases/deficiência , Erros Inatos do Metabolismo da Purina-Pirimidina/diagnóstico , Adenosina/sangue , Adulto , Amônia/sangue , Humanos , Hipoxantina , Hipoxantinas/sangue , Inosina/sangue , Isquemia/sangue , Lactatos/sangue , Esforço Físico , Erros Inatos do Metabolismo da Purina-Pirimidina/sangueRESUMO
Ideally, primary care physicians can successfully manage cases of arthritis in a manner that obviates the need for reconstructive surgery. However, that is not always possible. When surgical intervention is believed to be of potential benefit, the primary care physician needs to enlist the help of a surgeon and other health professionals to determine the best approach. Primary care physicians should take an active role in preoperative planning, perioperative management, and rehabilitation. The unique characteristics of the patient's specific type of arthritis and use of medications must be carefully considered. This approach should optimize the chances for a successful outcome.
Assuntos
Artrite/cirurgia , Prótese Articular , Humanos , Prótese Articular/efeitos adversos , Educação de Pacientes como Assunto , Cuidados Pós-Operatórios , Complicações Pós-Operatórias , Cuidados Pré-Operatórios , Fatores de RiscoAssuntos
Supressores da Gota/uso terapêutico , Gota/tratamento farmacológico , Gota/metabolismo , Cooperação do Paciente , Educação de Pacientes como Assunto , Anti-Inflamatórios/uso terapêutico , Anti-Inflamatórios não Esteroides/uso terapêutico , Gota/prevenção & controle , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Esteroides , Fatores de Tempo , Uricosúricos/uso terapêuticoAssuntos
Adenosina Desaminase/deficiência , Osteocondrodisplasias/etiologia , Inibidores de Adenosina Desaminase , Animais , Cartilagem/efeitos dos fármacos , Cartilagem/enzimologia , Cartilagem/patologia , Sobrevivência Celular/efeitos dos fármacos , Desoxiadenosinas/farmacologia , Modelos Animais de Doenças , Técnicas In Vitro , Camundongos , Osteocondrodisplasias/enzimologia , Osteocondrodisplasias/patologia , Pentostatina/farmacologia , SuínosRESUMO
An acute attack of gouty arthritis is one of the most painful experiences reported throughout medical history. Therefore it is paramount to initiate appropriate therapy quickly in order to terminate the acute phase. This goal can be achieved with non-steroidal anti-inflammatory agents, colchicine, or corticosteroid-based therapies. Rarely, because of contraindications to these agents, only symptomatic treatment can be given until the attack subsides. The next step is to lower the serum urate level below the limit of solubility (i.e., below 40.8 mmol/L, or 6.8mg/dL) which reduces recurrences and begins to return the total body urate pool to normal. This equally important goal can be achieved by uricosuric agents or xanthine oxidase inhibitors, although the latter is generally favored. Allopurinol is the agent most commonly preferred because of its safety profile and ease of use, but there are known serious allergic reactions and untoward side effects that occasionally require discontinuation. Febuxostat, a xanthine oxidase inhibitor, and pegylated uricase are new agents under development and may be beneficial in these situations or when other comorbid conditions prevent the use of conventional treatments. Alcohol and dietary consumption are also related to hyperuricemia and acute gout. Recently beer, wine, and liquor were studied and the risk of gout varied according to the alcohol ingested. Furthermore, recent data sheds light on important dietary modifications that may help in the treatment of gout, and dispels certain beliefs about protein ingestion and the occurrence of acute gout. As we learn more about the associated conditions of hypertriglyceridemia, hypertension, and the metabolic syndrome, it may allow the tailoring of medical regimens that directly prevent or reduce recurrent attacks of gouty arthritis. There are specific approved treatments for these common comorbidities that have parallel effects of lowering serum urate levels. These recent findings may be especially important for treating refractory cases. While patient education remains a cornerstone to ensure compliance, other quality indicators for the management of this disease have been reported and should guide the clinician in the treatment of gout and result in improved care.
Assuntos
Artrite Gotosa/tratamento farmacológico , Hiperuricemia/tratamento farmacológico , Corticosteroides/uso terapêutico , Hormônio Adrenocorticotrópico/uso terapêutico , Anti-Inflamatórios não Esteroides/uso terapêutico , Colchicina/uso terapêutico , Humanos , Hiperuricemia/diagnóstico , Transplante de Órgãos , Cooperação do Paciente , Fatores de Risco , Prevenção Secundária , Uricosúricos/uso terapêutico , Xantina Oxidase/antagonistas & inibidoresRESUMO
Metabolic myopathies are the result of genetic defects that cause disordered energy metabolism. These diseases can cause a variety of myopathic syndromes and can become clinically manifest at any age. Recent advances in the understanding of the molecular and metabolic bases for these diseases have resulted in expanded clinical descriptions, recognition of additional entities, and development of new therapeutic approaches.
Assuntos
Miopatias Mitocondriais/fisiopatologia , Humanos , Miopatias Mitocondriais/etiologia , Miopatias Mitocondriais/terapiaRESUMO
The term metabolic myopathy refers to a heterogeneous group of conditions that have in common abnormalities of muscle energy metabolism that result in skeletal muscle dysfunction. Most recognized metabolic myopathies are considered primary, represent inborn errors of metabolism, and are associated with known or postulated defects that affect the ability of muscle fibers to maintain adequate ATP concentrations. Traditionally, these diseases are grouped into abnormalities of glycogen, lipid, purine, and mitochondrial biochemistry. This discussion reviews the basic metabolic pathways that regulate normal muscle function; recent observations involving glycogen storage diseases, carnitine deficiency states, and myoadenylate deaminase deficiencies; and lastly, newer techniques available to assess patients with myopathic disorders.
Assuntos
Erros Inatos do Metabolismo/metabolismo , Doenças Musculares/metabolismo , HumanosRESUMO
The investigations used to diagnose an inflammatory muscle disease include history and physical examination, evaluation of serum levels of enzymes derived from skeletal muscle, electromyography, magnetic resonance imaging, and muscle histology. The evaluation of patients who may have noninflammatory myopathy includes, but is not limited to, these methods. Additional tools that may be useful include measurements of additional biochemistries, the forearm ischemic exercise test, magnetic resonance spectroscopy, and special tests on muscle tissue. Reports published in the past year have improved and expanded our understanding of the numerous noninflammatory myopathies and how these tools can be used more effectively.