ABSTRACT
Purpose: To examine the reliability of a novel technique to measure the range of the dart-throwing motion. Methods: Two raters measured the range of the dart-throwing motion in 40 healthy subjects. For the measurement, subjects were asked to perform a simulated hammering motion using various experimental tools (a real hammer, a thick wooden rod, and a thin wooden rod). The inclination angle of the tool in the vertical plane was measured with a manual goniometer at the maximal position of radial extension and ulnar flexion. The sum of these angles was defined as the range of the dart-throwing motion. To evaluate relative interrater reliability, intraclass correlation coefficients were calculated. To account for absolute reliability, Bland-Altman analysis was performed. Results: Intraclass correlation coefficients ranged 0.72 to 0.86. Bland-Altman analysis revealed that some systematic errors existed when the measurement was carried out with the real hammer or the thin rod, but not the thick rod. The 95% confidence intervals of minimal detectable change for the thick rod were 36.0° and 35.8° for the dominant and nondominant sides, respectively. Measured values between the experimental tools were similar. Conclusions: Relative reliability was shown to be good or moderate for each set of measurements. Some refinements are required to reduce measurement error. Accuracy of measurement should also be confirmed. Clinical relevance: No standardized methods for measuring the range of the dart-throwing motion have yet been established. Our technique can be performed rapidly and with easily available materials, producing reliable measurements for the range of the dart-throwing motion.
ABSTRACT
[Purpose] To examine the reliability of using a manual goniometer for measuring the range of dart-throwing motion. [Participants and Methods] The range of dart-throwing motion in 24 healthy participants was measured by three raters on the same day, and one rater repeated the measurement on another day of the same week. The stationary arm of the goniometer was placed along the radius, and the moveable arm was placed along the shaft of the second metacarpal, approximately 45° supinated from Lister's tubercle. All of the participants performed the dart-throwing motion on a plane that passed through the anatomical neutral wrist position, inclined 45° to the orthogonal anatomical plane. [Results] The intra-rater reliability was moderate (0.5-0.75) only for some parameters of the radial extension, and the intraclass correlation coefficients (ICCs) of all other parameters were <0.5. For the inter-rater reliability, the ICCs of all parameters were <0.5. Brand-Altman analysis revealed some fixed biases between the raters, although no proportional bias was observed. [Conclusion] The goniometric measurement procedure examined in this study appeared to be unsuitable for clinical use because of its poor reliability.
ABSTRACT
Cholangiocarcinoma is markedly resistant to chemotherapy and has a dismal prognosis, but its mechanism of drug resistance is unknown. This study examines whether glutathione S-transferase-pi (GSTP1-1) is involved in resistance to anticancer drugs in cholangiocarcinoma and whether GSTP1-1-specific inhibitors can overcome this resistance. First, immunohistochemical examination disclosed strong staining of all our 17 cholangiocarcinoma specimens for GSTP1-1, irrespective of histological type. Transfection of the GSTP1-1 antisense expression vector into a human cholangiocarcinoma cell line (HuCCT1) apparently decreased its intracellular GSTP1-1 concentration, and the sensitivity of transfectants to adriamycin (ADR), cisplatin, and alkylating agents such as melphalan and 4-hydroxyperoxycyclophosphamide (4-HC) was increased significantly, compared with that of mock transfectants. We next synthesized GSTP1-1-specific inhibitors by elongating the carbon chain of the ethylester at the N-terminal of gamma-glutamyl-S-benzylcysteinyl-phenylglycyl diethylester and performed a pharmacokinetic study on them. Of six GSTP1-1 inhibitors tested, O1-hexadecyl-gamma-glutamyl-S-benzylcysteinyl-d-phenylglycine ethylester (C16C2) showed the smallest volume of central compartment and smallest volume of distribution at steady state and the second smallest clearance, being the most effective inhibitor in vivo. The IC50 value of ADR or 4-HC for HuCCT1 cells decreased greater by treatment with C16C2 in a dose-dependent manner, paralleling the decrease in GSTP1-1 activity, than that of ADR or 4-HC alone. The antitumor activity of ADR or cyclophosphamide was clearly enhanced by combination therapy with C16C2 in a xenograft model. In conclusion, our results demonstrated that GSTP1-1 is a resistance factor for anticancer drugs in cholangiocarcinoma and that C16C2, a GSTP1-1-specific inhibitor, is a potent agent against the resistance.
