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A murine model of polymyositis induced by coxsackievirus B1, Tucson strain (CVBT) is described. Intraperitoneal CVBT inoculation of CD 1 Swiss mice less than 48 hours old resulted in proximal hindquarter weakness that was first apparent 7 days after viral challenge and persisted for more than 10 weeks. Electromyographic and histologic evidence of a continuing myositis was present during this entire period of time. However, virus was not detectable later than 2 weeks post infection, despite clinical progression of disease. The finding of electromyographir and histologic abnormalities in CVBT-infected mice, long after virus had cleared and neutralizing antibody production evoked, suggests that persistent myositis may be immunologically mediated, triggered by the initial acute viral infection.Polymyositis (PM) is a treatable myopathic disease whose etiology is unknown. Prcvious investigations of this disorder have centered on examining the role of viral infection and autoimmune dysfunction in the pathogenesis of PM, but to date these studies have failed to provide an understanding of the pathogenetic mechanisms involved (1). Further progress in

In the late 1980s, the University of Massachusetts (UMass) began its evolution toward the creation of a clinical evaluation unit (CEU). This article presents an overview of the history leading up to the formation of our clinical evaluation program and some of the projects developed to measure and improve clinical outcomes and reduce costs. Our experience in establishing the UMass CEU reflects an attempt to change clinical practice through effecting organizational change.

Objective. To measure the urinary excretion of specific cross-link amino acid markers for mature elastin (desmosine [DES] and isodesmosine [IDES]) and fibrillar collagen (hydroxylysylpyridinoline [HP] and lysylpyridinoline [LPJ) in systemic sderosis (SSc) patients and healthy controls.Methods. Urine specimens from 20 patients with SSc and 22 controls were assessed for DES, IDES, HP, and LP using high performance liquid chromatography and ultraviolet absorption spectroscopy, in combination with an isotope dilution technique in which the urine specimen was spiked with isotopically labeled cross-link amino acids.Results. Mean f SD levels of urinary DES and IDES were elevated in SSc patients by 2-3-fold, and urinary HP and LP by --fold, compared with controls (DES 21.0 f 9.4 versus 7.5 f 1.4 pglgm creatinine; HP 109.0 f 72.9 versus 24.9 k 5.7 nmoles/mmole creatinine). Nineteen of the 20 SSc patients had urinary DES and HP values that were >3 SD above the control mean. A significant elevation in the HP:LP ratio in SSc patients as compared with controls (mean f SD 6.9 2 1.5 versus Conclusion. Patients with SSc have higher levels of urinary cross-link amino acids specific for the degradation of mature collagen and elastin. These markers distinguish most SSc patients from healthy controls.Systemic sclerosis (SSc; scleroderma) is a disease in which excessive connective tissue is found in the dermis, blood vessels, and internal organs (1). Excessive collagen deposition results from an imbalance between the amount of newly synthesized collagen incorporated into the extracellular matrix by the formation of collagen cross-links and the amount of both newly synthesized and mature collagens degraded. Studies of this imbalance in SSc have focused on excess collagen synthesis deriving from overproduction by fibroblasts. While elastin accumulation has been reported in other fibrotic conditions (2,3), abnormalities of elastin metabolism in SSc have not been reported. Similarly, little work has been done on the in vivo degradation of collagen or elastin in SSc, which might regulate the net amount of deposited protein.Degradation of mature (cross-linked) elastin can be quantified by measuring the amount of urinary desmosine (DES) and isodesmosine (IDES), cross-link amino acids derived exclusively from mature elastin (4). Degradation of mature fibrillar (types I, 11, 111, V, and XI) collagen can be quantified by measurement of hydroxylysylpyridinoline (HP) and lysylpyridinoline (LP) (5). The cross-link amino acids DES, IDES, HP, and LP are not appreciably metabolized, but are excreted intact in the urine, reflecting mature elastin and collagen solubilization in vivo (6,7).We measured urinary DES, IDES, HP, and LP in SSc patients and control subjects, with an assay that