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Background: Natalizumab is a highly effective monoclonal antibody for the treatment of multiple sclerosis (MS), which can diffuse in different anatomical compartments, including cerebrospinal fluid (CSF) and milk. Objectives: Starting from incidental detection of natalizumab in the CSF of MS patients, the objective of this study was to develope a flow-cytometry-based assay and apply it to quantify natalizumab in body fluids, including milk collected from nursing patients over 180 days and in patients with neutralizing antibodies against natalizumab. Methods: CSF, milk and sera samples from patients with multiple sclerosis were tested by flow-cytometry for binding to a VLA-4 expressing cell line or to a control cell line. A standard curve was prepared by incubating the same cells with natalizumab at 50 µg/ml and serially diluted to 0.005 ng/ml. Binding specificity was confirmed using an anti-natalizumab neutralizing antibody. Results: Our assay was sensitive enough to detect natalizumab in CSF, with a lower detection limit of 1.5 ng/ml. Neutralizing antibodies against natalizumab inhibited binding to the cell line. In breastmilk, the peak concentration was observed during the first 2 weeks after infusion and the average concentration over the observation time was 173.3 ng/ml, with a trend toward increased average milk concentration over subsequent administrations. Conclusion: Routine use of such an assay would enable a better understanding of the safety of therapeutic antibody administration during pregnancy and lactation.
RESUMO
PURPOSE: Psychological factors have shown to be associated with treatment outcomes in hand injury patients. This study aimed to investigate the role of health locus of control (HLOC) and its dimensions internal, social-external, and fatalistic-external HLOC in treatment outcomes of hand injury patients. METHOD: One hundred thirty-two consecutive patients of a tertiary center for hand surgery undergoing treatment for acute hand injury or degenerative hand problems were included in this study. Pretreatment levels of depression, anxiety, HLOC, and pain intensity were measured, along with pain intensity levels at 4-month follow-up. Hierarchical regression analyses were calculated to test for moderation effects of the HLOC dimensions on the relationship between pretreatment and follow-up pain intensity. RESULTS: Controlling for age, gender, treatment modality, source of hand pain, and depressive symptoms, a moderation effect emerged (ß = - 0.16, p < 0.05), such that among patients higher in initial pain intensity, those lower in social-external HLOC experienced higher pain intensity at follow-up compared to those with high social-external HLOC. Internal HLOC and fatalistic-external HLOC did not moderate the effect of initial pain intensity on pain intensity at follow-up. CONCLUSION: Hand injury patients suffering greater initial pain intensity who also had lower versus higher social-external HLOC experienced less favorable treatment outcome. This finding suggests that if patients with high initial pain succeed in transferring perceived health control to professionals and to gain confidence in treatment and clinicians, treatment outcome could be improved in hand surgery.
