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This study evaluated the utility of human blood micronucleated reticulocyte (MN CD71+ ) frequency measurement as a cytogenetic damage biomarker. The analytical methodology was flow cytometry in conjunction with a previously described three color fluorescence labeling technique that includes anti-CD71 to focus analyses on the most immature fraction of reticulocytes [Dertinger et al., Environ. Molec. Mutagen., 44:427-435 (2004)]. Blood specimens from fifty self-reported healthy adult volunteers were studied. In addition to MN CD71+ measurements, blood plasma folate and B 12 levels were assessed, since these variables tend to influence other indices of cytogenetic damage. Timecourse data are also provided for ten cancer patients undergoing treatment. For these subjects, frequency of MN CD71+ was measured immediately before therapy, and daily during the first week of chemotherapy and/or fractionated radiotherapy. For the group of healthy volunteers, the variables of age, and folate and B 12 levels demonstrated no significant effect on MN CD71+ frequency. In addition, no difference was observed between pre-treatment MN CD71+ values for cancer patients compared with healthy volunteers. Regarding chemotherapy and/or partial body radiotherapy, elevated frequencies were observed upon initiation of treatment for 9 of the 10 patients studied. Maximal effects were observed three to five days following initiation of therapy. The largest increases in frequency of MN CD71+ (up to 25.9-fold) were observed in those patients exposed to anti-neoplastic drugs, presumably due to the systemic red marrow exposure provided by these agents. Taken together, these data support the hypothesis that the MN CD71+ endpoint represents a valuable biomarker of cytogenetic damage that does not require cell culture or microscopy-based scoring.

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Objective Deficits in vestibular function increase the risk for falls while turning. However, the clinical assessment of turning in patients with vestibular dysfunction is lacking, and evidence is limited that identifies the effectiveness of vestibular physical therapy in improving turning performance. The purpose of this study was to quantify walking and turning performance during the instrumented Timed “Up and Go” (TUG) test using body-worn inertial measurement units (IMUs). Novel instrumented TUG parameters were investigated for ability to distinguish patients with unilateral vestibular deafferentation (UVD) from control groups and discriminate the differences in turning parameters of patients with UVD following vestibular physical therapy. Methods Thirty-eight patients were recruited following UVD surgery (26 age-matched veteran patient controls with reports of dizziness not from a peripheral vestibular origin, and 12 age-matched healthy controls). Participants were donned with IMUs and given verbal instructions to complete the TUG test as fast as safely possible. The IMU-instrumented and automated assessment of the TUG test provided component-based TUG parameters, including the novel walk:turn ratio. Among the patients with UVD, 19 completed an additional instrumented TUG testing after vestibular physical therapy. Results The walk:turn time ratio showed that turning performance in patients with UVD before rehabilitation is significantly more impaired than both the patients with nonperipheral conditions and healthy controls. Vestibular rehabilitation significantly improved turning performance and “normalized” their walk:turn time ratio compared with healthy controls. The duration of the straight walking component in patients with UVD before vestibular physical therapy, however, was not significantly different compared with that component in people after vestibular physical therapy and in healthy controls. Conclusion The IMU-instrumented TUG test can be used to distinguish patients with vestibular deafferentation and to objectively quantify the change in their turning performance after vestibular physical therapy. Impact The IMU-based instrumented TUG parameters have the potential to quantify the efficacy of vestibular physical therapy and be adopted in the clinic.

This classification system has enhanced our knowledge of this group of clients, provided a greater understanding of the varied outcomes of these children and clinical management required.