Characteristics of flexed knee gait and functional outcome of a patient who underwent knee reconstruction with a hingeless prosthesis for bone tumor resection: a case report with gait analysis and comparison with healthy subjects.

We report on a patient after knee reconstruction for osteosarcoma in the distal femur using a hingeless prosthesis K-MAX KNEE system K-5 who walked without ipsilateral knee extension in the latter half of the stance phase (flexed knee gait). We evaluated the patient using three-dimensional gait analysis and isokinetic knee strength measurement, and compared the patient with five healthy subjects. The Musculoskeletal Tumor Society (MSTS) score was also used for evaluation. The patient kept his operated knee flexed during mid stance. The maximal ankle plantarflexion internal moment was lower on the ipsilateral side than on the contralateral side, and lower than in the healthy subjects. The negative ankle power during the stance phase was generally stronger on the ipsilateral side than on the contralateral side, and also in the healthy subjects. Unusual contralateral hip flexion occurred after the initial contact, indicating increased joint load on the ipsilateral ankle and the contralateral hip. The ratios of the peak knee extension/flexion torque were 0.7 on the ipsilateral side, 1.9 on the contralateral side, and 1.7 in the healthy subjects. The MSTS score of the patient was 23/30 (76.6%). Flexed knee gait might account for the reduction of ipsilateral hip flexion and ankle plantarflexion moment during the late stance phase. These results suggest the importance of focusing more on the ipsilateral ankle joint and the contralateral hip joint to maintain the function of the entire limb joints of the patients with flexed knee gait.

Characteristics of flexed knee gait and functional outcome of a patient who underwent knee reconstruction with a hingeless prosthesis for bone tumor resection: a case report with gait analysis and comparison with healthy subjects.

We report on a patient after knee reconstruction for osteosarcoma in the distal femur using a hingeless prosthesis K-MAX KNEE system K-5 who walked without ipsilateral knee extension in the latter half of the stance phase (flexed knee gait). We evaluated the patient using three-dimensional gait analysis and isokinetic knee strength measurement, and compared the patient with five healthy subjects. The Musculoskeletal Tumor Society (MSTS) score was also used for evaluation. The patient kept his operated knee flexed during mid stance. The maximal ankle plantarflexion internal moment was lower on the ipsilateral side than on the contralateral side, and lower than in the healthy subjects. The negative ankle power during the stance phase was generally stronger on the ipsilateral side than on the contralateral side, and also in the healthy subjects. Unusual contralateral hip flexion occurred after the initial contact, indicating increased joint load on the ipsilateral ankle and the contralateral hip. The ratios of the peak knee extension/flexion torque were 0.7 on the ipsilateral side, 1.9 on the contralateral side, and 1.7 in the healthy subjects. The MSTS score of the patient was 23/30 (76.6%). Flexed knee gait might account for the reduction of ipsilateral hip flexion and ankle plantarflexion moment during the late stance phase. These results suggest the importance of focusing more on the ipsilateral ankle joint and the contralateral hip joint to maintain the function of the entire limb joints of the patients with flexed knee gait.

Pharmacokinetics of YK754, a novel If channel inhibitor in rats, dogs and humans.

The pharmacokinetics of YM758, a novel funny If current channel (If channel) inhibitor, was investigated after single intravenous (i.v.) and oral dosing to rats and dogs, and partially compared with the results in humans by using liver microsomes. After i.v. administration, the plasma YM758 concentrations decreased, with an elimination half-life (t(1/2)) of 1.14-1.16 h in rats and 1.10-1.30 h in dogs. Total body clearance (CL(tot)) was 5.71-7.27 and 1.75-1.90 L/h/kg in rats and dogs, respectively which was comparable to the hepatic blood flow rate. In dogs, the pharmacokinetic profiles for i.v. bolus administration and continuous infusion did not differ. After oral administration, the levels of YM758 in rat plasma increased more than dose-proportionally, whereas almost linear pharmacokinetics were observed in dogs. Absolute bioavailability was 7.5%-16.6% in rats and 16.1%-22.0% in dogs. The plasma protein binding saturation of YM758 was observed in dogs and humans; this finding is consistent with the result that the major binding protein of YM758 in plasma is alpha1-acid glycoprotein (AGP), in particular in humans. The blood-to-plasma partition coefficient values were 1.36-1.42 in rats, 0.95-1.15 in dogs and 0.71-0.85 in humans. The results of the metabolic study on liver microsomes indicated that the non-linear pharmacokinetics of YM758 observed in rats may be partially due to a first-pass effect in the gastrointestinal tract and the liver.

Pharmacokinetics of the antithyroid drug thiamazole in a chronic hemodialysis patient with hyperthyroidism.

There has been little information regarding the pharmacokinetics of antithyroid drugs in patients with endstage renal disease (ESRD). We report here the pharmacokinetics and dialyzability of the antithyroid drug thiamazole in a chronic hemodialysis patient with hyperthyroidism. The patient was a 46-year-old woman who complained of palpitations 3 years after starting chronic hemodialysis therapy, followed by several episodes of pulmonary edema. A diagnosis of hyperthyroidism due to Graves' disease was confirmed by a laboratory test for thyroid function and anti-thyroid-stimulating hormone (TSH) receptor antibodies. The plasma concentration of thiamazole was measured before and at 1, 3, 4, 5, 6, and 24 h after administration of the drug. The dialyzability of the drug was investigated during hemodialysis therapy. On the non-dialysis day, the serum half-life of thiamazole (6.4 h) was similar to that in healthy subjects (4-6 h). Further, thiamazole was removed via the dialyzer during dialysis therapy. The initial dose of thiamazole was set at 15 mg/day for the patient. Free thyroid hormone levels began to decrease 2 weeks after the initiation of thiamazole, followed by the normalization of the values after 1 month. The patient's symptoms also subsided. Several confirmations of the concentration of thiamazole in the plasma in the morning on the first dialysis day of the week did not disclose a trend of accumulation in the blood. Although this is a single case report, it is suggested that thiamazole can be used for patients with ESRD. Careful monitoring of thyroid function, however, is recommended, because the intrathyroid action of thiamazole in uremia is unknown.

Translin binds to the sequences adjacent to the breakpoints of the TLS and CHOP genes in liposarcomas with translocation t(12;6).

Myxoid and round-cell liposarcomas share the translocation t(12;16)(q13;p11) creating the TLS-CHOP fusion gene as a common genetic alteration. We previously reported several unique characteristics of genomic sequences around the breakpoints in the TLS and CHOP loci, and among them was the presence of consensus recognition motifs of Translin, a protein that associates with chromosomal translocations of lymphoid neoplasms. We further extended our search for Translin binding motifs in sequences adjacent to breakpoints and investigated whether Translin binds to these sequences in vitro by mobility-shift assay. Computer-assisted search found sequences highly homologous (>70%) with Translin binding motifs adjacent to the breakpoints in 10 out of 11 liposarcomas with the TLS-CHOP fusion genes. All of 13 oligonucleotides corresponding to the putative binding sequences in these cases bind to Hela cell extract and also recombinant Translin protein, although the binding affinity of each motif showed considerable differences. The DNA-protein complex formation was inhibited by non-labeled competitor or anti-Translin antibody, suggesting the specificity of the complex formation. Considering the high incidence and specific binding property, the presence of Translin binding motif may be one of the important determinants for the location of breakpoints in the TLS and CHOP genes in liposarcomas.

High incidence of SV40-like sequences detection in tumour and peripheral blood cells of Japanese osteosarcoma patients.

Recent studies have revealed the evidence for the significance of SV40 genome in human malignancies. In this paper, the presence of SV40-like sequences was investigated in 54 Japanese osteosarcomas in which mutations of the retinoblastoma (Rb), p53, MDM2, and CDK4 genes had been already analysed. Using polymerase chain reaction and Southern hybridization, SV40-like sequences were detected in 25 cases (46.3%). In most cases, only a part of SV40 genome was detected, and the regulatory region containing enhancer sequences was most frequently found (21/54, 38.9%). There was no apparent relationship between the presence of SV40-like sequences and tumour suppressor genes mutations in each tumour. The SV40-like sequences were also detected in peripheral blood cells of substantial proportion of the patients (43.3%), whereas the incidence was much lower (4.7%) in normal healthy controls. This difference is statistically highly significant (P < 0.0001), suggesting that the presence of SV40-like sequences, even if only a part, may play some roles to predispose individuals to osteosarcoma.

Situation of monomethoxypolyethylene glycol covalently attached to lysozyme.

We selectively introduced monomethoxypolyethylene glycol (mPEG) 5000, 2000, and 550 into Asp119 in lysozyme. To examine how the mPEGs were present on the surface of the modified lysozyme, the activities, binding abilities to the Fab fragment of anti-lysozyme monoclonal antibody, net charges and nuclear magnetic resonance (NMR) spectra of mPEG lysozymes were examined. With the increase in molecular weight of mPEG, the activities and binding abilities to the Fab of mPEG lysozyme decreased. However, introduced mPEG5000 did not cause complete inhibition of the activities and binding abilities to the Fab, while the maximum length of mPEG5000 was so great that it largely covered the surface of the lysozyme molecule. Analyses of the net charges and NMR suggested that the introduced mPEG preferentially assumed a folded conformation on the surface rather than spread all over the surface. Based on the structure of mPEG lysozyme, the mechanism of the reduced immunogenicity of mPEG lysozyme was discussed.