The change process and a clinical evaluation unit at University of Massachusetts Medical Center.

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.

Cross-linked elastin and collagen degradation products in the urine of patients with scleroderma.

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 [LP]) in systemic sclerosis (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 +/- SD levels of urinary DES and IDES were elevated in SSc patients by 2-3-fold, and urinary HP and LP by 3-4-fold, compared with controls (DES 21.0 +/- 9.4 versus 7.5 +/- 1.4 micrograms/gm creatinine; HP 109.0 +/- 72.9 versus 24.9 +/- 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 +/- SD 6.9 +/- 1.5 versus 5.5 +/- 1.3) indicated a soft tissue origin for much of the increased HP. 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.

Eosinophilia-myalgia syndrome associated with L-tryptophan ingestion. Analysis of four patients and implications for differential diagnosis and pathogenesis.

Four patients fulfilling the case definition for eosinophilia-myalgia syndrome are described, including one whose disease began in 1986. Each displayed a variety of symptoms: one suffered principally from myalgia and recovered spontaneously on discontinuation of L-tryptophan therapy; one exhibited progressive sclerodermiform skin changes, neuropathy, and myopathy; a third had prominent neuromuscular disease and sclerodermiform skin changes; and the fourth experienced profound weight loss, an axonal polyneuropathy, and perivascular lymphoid infiltrates simulating a lymphoma. Evidence of T-cell activation was present in peripheral blood and affected tissues during the clinically active progressive phase of disease. Among other manifestations pleural effusion, cutaneous vasculitis, joint contractures, and bloody diarrhea were observed. A history of L-tryptophan ingestion should be sought in patients with myalgia, fatigue, or the above outlined symptoms.

Neurologic manifestations of giant cell arteritis.

Giant cell arteritis (GCA) is a common vasculitic disease in the elderly, with a multitude of neurologic manifestations including, but not limited to, stroke and blindness. Many uncommon manifestations are often unrecognized and proper diagnosis and treatment delayed. This review focuses on the pathophysiology and neurologic symptoms of GCA, with special emphasis on the diversity of ocular involvement.

Control of hypertension and reversal of renal failure in undifferentiated connective tissue disease by enalapril.

Activation of the renin angiotensin system is important in the development of accelerated hypertension and progression to acute renal failure in scleroderma and undifferentiated connective tissue disease. Inhibition of angiotensin-converting enzyme activity may effectively control blood pressure and ameliorate renal insufficiency. To our knowledge, we describe the first reversal of dialysis-dependent renal insufficiency by enalapril maleate and recovery and maintenance of near-normal renal function in a patient suffering from undifferentiated connective tissue disease with sclerodermatous features. The pathophysiologic mechanisms and long-term treatment implications with angiotensin-converting enzyme inhibitors in this setting are discussed.

Idiopathic retroperitoneal and mediastinal fibrosis mimicking connective tissue disease.

Combined retroperitoneal and mediastinal fibrosis is a rare manifestation of an idiopathic systemic sclerosing disease. This report describes a multisystem illness that clinically could best be described as polyserositis and progressive renal failure. Pathologically, it was characterized by diffuse infiltration of retroperitoneal and mediastinal tissues with plaquelike fibrofatty connective tissue encasing the kidneys, ureters, adrenal glands, and parietal pericardium. These features are diagnostic of a systemic sclerosing disease. It is important to recognize this unusual disorder to avoid confusion with other systemic connective tissue diseases such as systemic lupus erythematosus.

MM subisoenzymes of creatine kinase as an index of disease activity in polymyositis.

Creatine kinase (CK; EC 2.7.3.2), although the most commonly measured enzyme for assessing disease activity in polymyositis, is not always a reliable indicator of the extent and severity of myositis. Recently, the CK-MM isoenzyme has been found to undergo post-synthetic modifications upon release into the serum, such that electrophoretically identifiable sub-bands or subisoenzymes--MM1, MM2, and MM3--are produced. To determine the diagnostic and discriminative value of these subisoenzymes in polymyositis, we analyzed CK and its MM subisoenzyme forms in serum samples from 22 patients with myositis and from 23 controls. In the presence of inflammatory myositis and increased total CK activity, MM-patterns correlated with the clinical trend, often more accurately than did measurements of total CK. MM1 proportions greater than 30% of total CK-MM or ratios of MM3 to MM1 less than 1 were associated with an improving or stable condition, whereas MM1 activity less than 30% or MM3/MM1 greater than 1 reflected a deteriorating course of disease. Patients whose disease was assessed to be clinically deteriorating were clearly distinguished from patients with improving disease by their subisoenzyme patterns (p less than 0.01). Thus these patterns add significantly to the information obtainable by routine blood analysis.

A murine model of polymyositis induced by coxsackievirus B1 (Tucson strain).

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 electromyographic 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.

Myocardial involvement in polymyositis.

Polymyositis (PM) is a myopathic syndrome that results in pathology believed to be primarily confined to skeletal muscle. Several recent reports, based on quantitative determinations of total serum creatine kinase (CK) and MB isoenzyme activity, accepted serologic correlates of active myocardial injury, suggest that cardiac involvement in PM may occur more frequently than has been clinically appreciated. We retrospectively studied 12 patients with PM; 83% (10) were found to have substantial elevations in CK-MB activity, often to levels exceeding those seen with myocardial infarctions, thus confirming a high probability of myocardial involvement in PM. Failure to detect this clinically may be indicative of the insensitivity of current technology. A review of the literature substantiates the importance of appreciating the spectrum, frequency and functional consequences (i.e., conduction disturbances, cardiomyopathy) of myocardial involvement in PM.