Immunocamouflaged red blood cells (RBC) are produced by cell surface derivatization with methoxypolyethylene glycol (mPEG). These immunologically attenuated cells may reduce the risk of allosensitization in chronically transfused patients. To characterize the effects of differing linker chemistries and polymer lengths, RBC were modified with cyanuric chloride activated mPEG (C-mPEG 5 kDa), benzotriazole carbonate methoxyPEG (BTC-mPEG; 5 or 20 kDa) or N-hydroxysuccinimidyl ester of mPEG propionic acid (SPA-mPEG; 2, 5 or 20 kDa). Biophysical methods including particle electrophoresis and aqueous two-phase polymer partitioning were employed to compare the PEG derivatives. While C-mPEG was faster reacting, both BTC-mPEG and SPA-mPEG gave comparable findings after 1 h. Both PEG surface density and molecular mass had a large effect on RBC surface properties. Proportional changes in electrophoretic mobility and preferential phase partitioning were achieved by increasing either the quantity of surface PEG or the PEG molecular mass. In addition, two-phase partitioning may provide a means for efficiently removing unmodified or lightly modified (hence potentially immunogenic) RBC in the clinical setting. Furthermore, mPEG modification significantly inhibits cell-cell interaction as evidenced by loss of Rouleaux formation and, consequently, sedimentation rate. Importantly, BTC-mPEG 20 kDa RBC showed normal in vivo survival in mice at immunoprotective concentrations (up to 2 mM).
Using a structured interview method, we sought to address the following questions regarding cervical dystonia (CD) and employment: (1) what is the frequency and severity of job impairment in CD; (2) what are the clinical features that contribute to job impairment; (3) how does the effectiveness of botulinum toxin (BTx) compare to oral medications in restoring employment status. In our population of 155 CD patients, employment was affected by CD in 53.3% (31.2% reduced hours or responsibilities, 3.3% changed to different job, 18.9% loss of employment) and 68.9% of patients reported reduced overall productivity. The likelihood of altered employment (P < 0.0006), reduced productivity (P < 0.0001), and seeking disability benefits (P < 0.003) was significantly associated with the presence of neck pain, but not type of employment, spasmodic head motions, or duration of CD symptoms before treatment with BTx. Treatment with BTx was more likely to improve employment status than oral medications (66.1 vs. 18.5%) and much more likely to restore full employment with normal productivity (12.9 vs. 0.0%). These findings suggest that employment status is frequently affected by CD, particularly in patients withneck pain. BTx is significantly more effective than oral medications in restoring premorbid employment status.
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