ISSN:1040-8711    

出版商:OVID    

年代:1996

数据来源: OVID

ISSN:1040-8711    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Longitudinal studies of large cohorts of patients with Raynaud's phenomenon have addressed the predictors of developing a secondary disease. New insights have been reported into the pathogenesis of Raynaud's phenomenon and the consequences of ischemia. Studies have suggested that more than one defect may cause Raynaud's phenomenon, including increased α-2 sympathetic receptor activity on vessels, endothelial dysfunction, deficiency of calcitonin gene related peptide protein-containing nerves or some central thermoregulatory defect. The vasoconstricting and profibrotic cytokine endothelin-1 was found to be elevated in scleroderma but did not correlate with disease subset or with evidence of pulmonary hypertension. Oxidant stress is thought to be increased in scleroderma, causing tissue damage and provoking fibrosis. Treatment with infusion of prostacyclin for primary pulmonary hypertension was approved, paving the way for studies of secondary forms of pulmonary hypertension. Oral prostanoids are being tested for the treatment of Raynaud's phenomenon.

ISSN:1040-8711    

出版商:OVID    

年代:1996

数据来源: OVID

ISSN:1040-8711    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Validated, comprehensive measures for assessing disease activity and its irreversible sequelae, known as disease damage, have not been developed for the idiopathic inflammatory myopathies (IIM), thus limiting our capacity to assess individual patients and responses to therapies. This review summarizes current approaches for assessing disease activity and damage in the idiopathic inflammatory myopathies and speculates on possibly useful novel approaches for the future. Disease activity and damage indices that combine a number of these assessments are proposed for use in all therapeutic trials. Methods for assessing target organs of the idiopathic inflammatory myopathies will likely evolve as more sensitive and specific measures are developed that can distinguish active inflammation from the irreversible effects of disease.

ISSN:1040-8711    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Several infectious agents can cause chronic or acute myopathy. Most current investigations into possible infectious causes of the idiopathic inflammatory myopathies have focused on retroviruses, including HIV and human T-cell leukemia-lymphoma virus type I. In both cases, viruses likely do not directly infect muscle fibers but instead induce an immunologically mediated myositis. Other interest has focused on enteroviruses as potential etiologic agents of idiopathic inflammatory myopathy, but their relationship to human myositis is less clear. In addition to chronic muscle disease, several infectious agents can cause acute myositis, including pyomyositis, which is being recognized in temperate climates with increasing frequency, and rhabdomyolysis.

ISSN:1040-8711    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Genetic predisposition to development of the idiopathic inflammatory myopathies is probably multifactorial. Major histocompatibility complex associations with these diseases provide the strongest evidence for a genetic component. In Caucasoids, haplotypes marked by B8/DR3 are associated with each of the clinical subgroups, except mixed connective tissue disease (DR4). The strongest associations are with inclusion body myositis, polymyositis in the presence of anti-Jo-1, and with antibodies to PM-Scl in overlap syndromes. The underlying mechanisms of these associations are probably different. Unique major histocompatibility complex associations are seen with other myositis-associated autoantibodies. The association can vary between racial groups as can the type of autoantibody produced within a disease subgroup, perhaps reflecting different T cell receptor repertoires or different inducing agents. The mapping of a gene for one form of hereditary inclusion body myositis to chromosome 9p1-q1 provides a lead for the investigation of sporadic inclusion body myositis, as does the expanding knowledge of genetic factors in Alzheimer's disease. The demonstration of deletions of mitochondrial DNA in the muscle of patients with inclusion body myositis raises the question of their role in the pathogenesis of this disease.

ISSN:1040-8711    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Polymyositis and dermatomyositis are characterized by the production of a series of autoantibodies to various cellular constituents. Some of these autoantibodies are found specifically in patients with polymyositis or dermatomyositis or myositis overlap syndrome and predict clinical subgroups and prognosis. If we are to understand the etiology and pathogenic mechanisms of polymyositis and dermatomyositis, it will be particularly important to elucidate the structure and function of target autoantigens recognized by these myositis-specific autoantibodies. In recent years, many autoantigens and some epitopes have been identified using molecular biology approaches. During the 1-year period reviewed here, the nature and function of the Mi-2 and the Ku(p70/p80) antigens, which are recognized by autoantibodies in patients with dermatomyositis and with the myositis overlap syndrome, respectively, have been elucidated. Several new autoantibodies that are not specific for but that are associated with myositis have also been described.

ISSN:1040-8711    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Of the various muscular dystrophies, the dystrophinopathies are the most common, accounting for the majority of male muscle disease patients and for about 10% of female patients referred for the evaluation of muscular dystrophy or persistent high serum creatine kinase values (hyperCKemia). The approach to diagnosis and family genetic counseling for the dystrophinopathies is now well established, and implementation of carrier detection and prenatal diagnosis has dramatically decreased the incidence of familial cases. With the decreasing observation of a positive family history in newly ascertained cases, molecular genetic and protein studies become imperative for accurate diagnosis. Genetic counseling in families of isolated cases can still be problematic. There is a wide range of opinions regarding the management of Duchenne muscular dystrophy, with surgical interventions (eg, tendon lengthenings and spinal fusion), steroid use, and extent of respiratory support actively debated. There has been progress in defining the underlying cause of disease for some patients with muscular dystrophy who have normal dystrophin findings. Nearly all patients with proximal, hyperCKemic muscular dystrophy who have normal dystrophin show no family history of the disorder, consistent with autosomal recessive disease. Approximately 5% of both boys and girls with childhood-onset dystrophy and normal dystrophin have been found to have mutations in one of the four sarcoglycan proteins identified to date. Also, approximately half of the patients with congenital muscular dystrophy show deficiency of a component of the muscle extracellular matrix (merosin/laminin-α2). In this review, we give a short primer on relevant muscle structure and function, followed by a series of case reports on patients referred for molecular testing that illustrate the diagnostic protocols, range of clinical presentations, and genetic counseling options in the work-up of proximal muscular dystrophy and hyperCKemia.

ISSN:1040-8711    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

As the molecular defects that cause many muscle diseases have been identified, research has shifted to finding novel therapies. Gene therapy has been proposed both for correcting primary gene defects of muscle and as a way of using muscle for the production of proteins therapeutic in inflammatory or nonmuscle diseases. Several strategies have been developed to introduce foreign genes into diseased muscles, including myoblast transfer, direct injection of plasmids or DNA-liposome complexes, and infection with modified viruses. Related strategies, using antisense sequences or ribozymes, have been devised to modify gene expression in diseased cells. No method has yet proved itself in the clinic, although current work remains promising and some of the pitfalls that must be overcome have been identified.

ISSN:1040-8711    

出版商:OVID    

年代:1996

数据来源: OVID