Relationship between acetabular labrum evaluation by using radial magnetic resonance imaging and progressive joint space narrowing in mild hip dysplasia.

OBJECTIVE: The aim of this study was to investigate the relationship between abnormal acetabular labrum depicted by radial magnetic resonance and progressive joint space narrowing (JSN) of hip dysplasia. METHODS: Subjects were 23 joints [21 patients; mean age: 35.1 years (16-53 years)] that had acetabular dysplasia with lateral center-edge angle of Wiberg (CE angle) greater than 5 degrees and smaller than 25 degrees (mean, 16.4 degrees ), which did not show any arthrotic changes on plain radiograms and were followed up for 3 years or longer. Radial images of acetabular labrum were classified into three stages. RESULTS: Progression of JSN was not significantly related to CE angle but to progression of MRI stage (P=.006). In multivariate analysis, one rank progression of MRI stage was significantly associated with progression of JSN (adjusted OR=11.41, 95% CI: 1.51-86.24, P=.018). CONCLUSION: Our findings showed that in patients whose acetabular dysplasia has 5-25 degrees CE angle, MRI staging based on radial MRI is a better factor for prediction of progression of JSN than CE angle.

Age-related changes in the hemodynamics of the femoral head as evaluated by early phase of bone scintigraphy.

OBJECTIVE: The femoral head is reported to be in a markedly hypoemic state as compared with other tissues even under normal conditions, and it is therefore necessary to understand its hemodynamics to investigate the pathogenesis of hip disorders. It is known that aspects of intraosseous hemodynamics including blood flow and blood pool can be evaluated soon after radioisotope administration. In this study, hemodynamic changes in the femoral head according to gender and age were examined by investigating accumulation of radioisotope in the tissue during the early phase of bone scintigraphy. METHODS: The subjects of this study consisted of 58 joints of 31 men and 75 joints of 41 women, whose ages ranged from 15 to 87 years (average age: 67.9 years). Images of bone scintigraphy were obtained for 15 to 20 minutes at 5 minutes and at 3 hours after radioisotope administration. The ratio of accumulation in the femoral head to that in the diaphysis (head-to-diaphysis ratio, HD ratio) was calculated. RESULTS: HD ratios obtained 15-20 minutes later ranged from 0.01 to 7.35 (1.88 +/- 0.91, mean +/- SD). HD ratios decreased with age, and a significant inverse correlation was observed between age and HD ratio, demonstrating a correlation coefficient of -0.27 (p = 0.001). The HD ratio among men was 0.01-3.57 (1.66 +/- 0.71), while that among women was 0.53-7.35 (2.05 +/- 1.01), and a significant difference was observed in HD ratio between men and women (p = 0.02). There was a significant difference in HD ratios between men and women in their teens to forties (p = 0.03), while no significant differences was observed in the other age groups.. HD ratios obtained 3 hours later ranged from 0.44 to 6.32 (1.95 +/- 0.79, mean +/- SD), and no significant correlation was observed between age and HD ratio, demonstrating a correlation coefficient of -0.14. CONCLUSION: The present study demonstrated that blood flow and blood pool of the femoral head decrease with aging particularly in women. This hemodynamic deterioration of the femoral head caused by aging may have an effect on the onset and progression of hip disorders by influencing bone metabolism.

Reliability of one-point blood sampling method for calculating input function in Na18F PET.

OBJECTIVE: Conventional methods of quantitative Na18F positron emission tomography require multiple arterial blood sampling in order to obtain the input function, and the procedures are invasive and complicated. This study aims to establish a simplified and reliable technique for obtaining the input function. METHODS: Multiple arterial blood sampling was performed on 12 persons. The time point for one-point sampling was determined as the time when (1) the plasma radioactivity obtained showed the highest correlation to the real integrated value, which was calculated from the input function, and (2) the coefficient of variation of the real integrated value divided by plasma radioactivity obtained at each time point became the minimum. Scaling factors were obtained in order to estimate the plasma radioactivity at each time point, and a reference table was produced in order to estimate the input function. RESULTS: The optimal timing for one-point sampling was 12 min after intravenous injection of Na18F. The estimated integrated value obtained from arterial blood sampling at 12 min and the reference table was highly correlated with the real integrated value (P<0.001). Levels of plasma radioactivity of arterial blood and venous blood were almost the same at 12 and 40 min after Na18F injection. Percentage errors in the estimation of the integrated value were 2.63% (n=12) for the arterial blood collected at 12 min and 4.14% (n=12) for the venous blood collected at 30 min. CONCLUSIONS: This simplified method is clinically applicable and would replace traditional methods that require multiple blood sampling.

Relationship between postrenal transplant osteonecrosis of the femoral head and gene polymorphisms related to the coagulation and fibrinolytic systems in Japanese subjects.

BACKGROUND: Nontraumatic osteonecrosis of the femoral head (ONFH) is one of the complications that may occur after renal transplantation. We investigated the relationship between the incidence of ONFH and polymorphisms in the genes for plasminogen activator inhibitor (PAI)-1, which is one of the major regulatory proteins of the fibrinolytic system, and 5,10-methylenetetrahydrofolate reductase (MTHFR), which is associated with the plasma levels of homocysteine in Japanese subjects. METHODS: Thirty-one patients with postrenal transplant ONFH and 106 patients without ONFH were selected. Genotypes of PAI-1 4G/5G and MTHFR C677T were determined by direct sequencing of genomic DNA. In addition, plasma PAI-1 antigen (Ag) levels and plasma total homocysteine (tHcy) levels at the steady state were measured. The relationships between the incidence of ONFH and these genotypes, as well as plasma levels of the gene products, were investigated. RESULTS: Plasma PAI-1 Ag levels were the highest in patients with the 4G/4G genotype, and plasma tHcy levels were the highest in patients with TT genotypes of MTHFR C677T. However, the relationship between the incidence of ONFHH and PAI-1 4G/5G or MTHFR C677T was not observed. The relationship between the incidence of ONFH and plasma levels of PAI-1 Ag or tHcy was not observed. CONCLUSIONS: Genotypes of PAI-1 4G/5G and MTHFR C677T or plasma concentrations of PAI-1 Ag and tHcy had no effect on the incidence of ONFH in Japanese subjects, unlike the results of studies performed in white subjects. The effect of genetic background on the pathologic conditions that developed in patients with postrenal transplant ONFH may differ according to race.

Combination analysis of three polymorphisms for predicting the risk for steroid-induced osteonecrosis of the femoral head.

BACKGROUND: Osteonecrosis of the femoral head (ONF) often develops following corticosteroid administration. We previously investigated the genetic background for the development of corticosteroid-induced ONF and found relations between ONF development and genetic polymorphisms in the ATP binding cassette B1 (ABCB1) gene (C3435T), apolipoprotein B (ApoB) gene (C7623T), and cAMP-response element binding protein-binding protein (CBP) gene (rs3751845). In the present study, we examined whether combined information regarding these three single nucleotide polymorphisms (SNPs) in the ABCB1, ApoB, and CBP genes is useful for predicting ONF development. METHODS: A case-control study was performed to study the development of corticosteroid-induced ONF. The cases were 34 patients who developed ONF, and the references were 123 patients who did not develop ONF. To evaluate the presence of interactions among the ABCB1, ApoB, and CBP genes, a synergistic index was calculated using an additive model. RESULTS: The synergistic index between the ABCB1 and CBP genes was >1.00 (1.99), revealing the presence of an interaction. CONCLUSIONS: Through analysis of multiple genes that may affect ONF development, we have shown a possible relation among genes encoding completely different proteins. We believe that analysis of the interactions among these genes can contribute to elucidating the mechanism of ONF development in addition to enabling identification of high-risk patients for ONF development.

Low molecular weight phenotype of Apo(a) is a risk factor of corticosteroid-induced osteonecrosis of the femoral head after renal transplant.

OBJECTIVE: Osteonecrosis of the femoral head (ONF) is a necrosis due to disruption of the blood flow. The disease often occurs in association with corticosteroid treatment. The pathology of corticosteroid-induced ONF is unclear, although abnormalities in the coagulation and fibrinolytic systems or in the lipid metabolism have been reported to be involved. We examined the relationships between development of ONF and genetic variations and plasma level of lipoprotein(a) (Lp(a)), which is closely involved in the coagulation and fibrinolytic systems and lipid metabolism. METHODS: The study population consisted of 112 renal transplant patients undergoing corticosteroid treatment. Their apolipoprotein (a) [apo(a)] isoform was determined by Western blotting, and patients were classified into low molecular weight (LMW) or high molecular weight (HMW) groups. The plasma Lp(a) level was measured. Patients were also examined for 3 single-nucleotide polymorphisms (SNP), -773 (G/A), +93 (C/T), and +121 (G/A). Relationships between these 3 genetic factors of Lp(a) and ONF development were examined using statistical methods including multivariate analysis. RESULTS: A strong relationship was observed between the apo(a) molecular weight phenotype and ONF development, with an increased risk of ONF development for the LMW group (adjusted odds ratio 5.75, 95% CI 1.76-18.74, p = 0.0038). No significant relationships were observed between ONF and plasma Lp(a) level and SNP. CONCLUSION: Apo(a) molecular weight phenotype would be a useful predictor of ONF that develops after corticosteroid treatment.

ApoB C7623T polymorphism predicts risk for steroid-induced osteonecrosis of the femoral head after renal transplantation.

BACKGROUND: Nontraumatic osteonecrosis of the femoral head (ONFH) is caused by disruption of blood flow. This disease often occurs in association with steroid treatment. The pathology of steroid-induced ONFH remains unclear, although abnormalities in lipid metabolism have been reported to be involved. In this study, we examined the differences of gene polymorphism frequencies of apolipoprotein B (ApoB) and apolipoprotein A1 (ApoA1), which are important proteins for lipid transport, as well as of lipid parameters, between ONFH cases and referent patients among those who were subjected to renal transplantation. METHODS: Subjects were 158 cases who had undergone renal transplant, including 34 cases that were diagnosed as ONFH after renal transplantation and 124 cases that were not. Four single nucleotide polymorphisms including C7623T and G12619A for the ApoB gene and G75A and C83T for the ApoA1 gene were analyzed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and Taqman real-time PCR chemistry. Also, serum levels of low-density lipoprotein (LDL), high-density lipoprotein (HDL), ApoB, and ApoA1 were measured. Their relationship to ONFH was statistically evaluated. RESULTS: A higher frequency of 7623TT or CT of the ApoB gene was observed in ONFH cases than in referent patients (P = 0.033), resulting in an elevated odds ratio that was statistically significant (adjusted odds ratio = 6.37, 95% CI = 1.53-26.5, P = 0.011). No significant relationship was observed between other genes and ONFH. Regarding lipid parameters, a higher value of ApoB/ApoA1 ratio was observed in cases (P = 0.045). CONCLUSION: For the prediction of ONFH, it is useful to analyze ApoB C7623T and plasma ApoB/ApoA1 ratio before the administration of steroids.

Chemical constituents of Millettia taiwaniana: structure elucidation of five new isoflavonoids and their cancer chemopreventive activity.

We describe the isolation and identification of five new isoflavonoids, millewanins A (1), B (2), C (3), D (4), and E (5), together with six known isoflavonoids and three rotenoids, from the stems of Millettia taiwaniana collected in Japan. The major component, auriculasin (6), exhibited significant inhibitory effect on mouse skin tumor promotion in an in vivo two-stage carcinogenesis test. The results of the present investigation indicate that 6 might be a valuable antitumor promoter.