Burden of illness and costs in patients with myasthenia gravis currently receiving treatment in the United States.

INTRODUCTION/AIMS: If myasthenia gravis (MG) symptoms are inadequately controlled, patients may experience exacerbations or life-threatening myasthenic crises. Patients with inadequately controlled MG symptoms tend to be treated with chronic intravenous immunoglobulin (IVIg) therapy and/or multiple immunosuppressant therapies (ISTs). This study aimed to examine disease burden, healthcare resource utilization, and associated costs in these patients. METHODS: This was a retrospective observational study using a claims database. Patients with MG were classified into three cohorts based on treatment over a 1-y follow-up period: (a) treated with four or more IVIg episodes (chronic IVIg cohort); (b) received two or more non-steroidal ISTs (NSISTs) sequentially (multiple NSIST cohort); (c) received neither chronic IVIg nor multiple NSISTs (reference cohort). Incidences of crises and exacerbations and annual healthcare costs in each cohort were estimated. RESULTS: In total, 3516 patients with MG were included in the analysis. Compared with the reference cohort (n = 2992), the MG crisis rate was approximately twice as high in both the chronic IVIg (n = 324) and multiple NSIST (n = 291) cohorts (p < 0.001); and the MG exacerbation rate was approximately four-fold higher in the chronic IVIg cohort (p < 0.001) and three-fold higher in the multiple NSIST cohort (p < 0.001). Median annual MG-related inflation-adjusted total healthcare costs were higher in the chronic IVIg ($81,900) and multiple NSIST ($30,300) cohorts than in the reference cohort ($2540). DISCUSSION: The burden of crises/exacerbations was substantially higher and healthcare costs were considerably greater in patients with MG treated with chronic IVIg or multiple NSISTs than in patients not receiving these treatments.

Chronic relapsing experimental allergic encephalomyelitis (CREAE) in plasminogen activator inhibitor-1 knockout mice: the effect of fibrinolysis during neuroinflammation.

UNLABELLED: During neuroinflammation in multiple sclerosis (MS) fibrinogen, not normally present in the brain or spinal cord, enters the central nervous system through a compromised blood-brain barrier. Fibrin deposited on axons is ineffectively removed by tissue plasminogen activator (tPA), a key contributory factor being the upregulation of plasminogen activator inhibitor-1 (PAI-1). AIMS: This study investigated the role of PAI-1 during experimental neuroinflammatory disease. METHODS: Chronic relapsing experimental allergic encephalomyelitis (CREAE), a model of MS, was induced with spinal cord homogenate in PAI-1 knockout (PAI-1(-/-)) and wild type (WT) mice, backcrossed onto the Biozzi background. RESULTS: Disease incidence and clinical severity were reduced in PAI-1(-/-) mice, with animals developing clinical signs significantly later than WTs. Clinical relapses were absent in PAI-1(-/-) mice and the subsequent reduction in neuroinflammation was coupled with a higher capacity for fibrinolysis in spinal cord samples from PAI-1(-/-) mice, in association with increased tPA activity. Axonal damage was less apparent in PAI-1(-/-) mice than in WTs, implicating fibrin in both inflammatory and degenerative events during CREAE. CONCLUSIONS: PAI-1 is a potential target for therapy in neuroinflammatory degenerative diseases, allowing effective fibrin removal and potentially reducing relapse rate and axonal damage.

Laser Raman spectroscopic studies of ocular lens and its isolated protein fractions.

The water-soluble proteins of the bovine lens were separated on a column of Sephadex G-200 into five fractions designated as alpha-, beta1-, beta2-, and gamma-crystallin. Laser Raman scattering studies on these isolated proteins (both in the lyophilized state and in solution) and insoluble albuminoid reveal that they contain predominantly antiparallel pleated sheet structure in the main chains and that sulfhydryl groups are highly localized in gamma-crystallin. This light-scattering technique was also applied to probe the homogeneity of protein structure in the intact lens. The analysis of the scattered light selectively collected from various parts of the lens indicated that these proteins also exist in an antiparallel beta structure throughout the entire lens. However, the central (nucleus) and outer (cortex) portions have somewhat different amino acid composition. Based on the relative intensities of the lines at 624 (phenylalanine) and 644 cm-1 (tyrosine), it is concluded that the nuclear part has the highest concentration of gamma-crystallin and that the content of alpha-crystallin increases significantly from the nucleus to the cortex. By examining the Raman spectra in the 2582 cm-1 and the amide I and III regions, we have demonstrated that the sulfhydryl groups and the beta conformation of the lens proteins are unaffected in the conversion of transparent to totally opaque lens by heat denaturation at 100 degrees. This means that the opacification of a lens does not necessarily involve the oxidation of sulfhydrul groups or conformation changes.