Angioscopic evaluation of stabilizing effects of an antilipemic agent,bezafibrate, on coronary plaques in patients with coronary artery disease: a multicenter prospective study

To evaluate the stabilizing effects of an antilipemic agent, bezafibrate, on coronary plaques, we carried out a prospective angioscopic and angiographic open trial. From April 1997 to December 1998, 24 patients underwent coronary angioscopy of plaques in non-targeted vessels during coronary interventions and then again 6 months later. The patients were divided into control (10 patients, 14 plaques) and bezafibrate (14 patients, 21 plaques) groups. Oral administration of bezafibrate (400 mg/day) was started immediately after the intervention and was continued for 6 months. The vulnerability score was determined based on the angioscopic characteristics of plaques and compared before and 6 months later. Six months later, the vulnerability score was reduced (from 1.6 to 0.8; P<0.05) in the bezafibrate group and unchanged (from 1.4 to 1.3; NS) in the control group. In the bezafibrate group, the changes in the vulnerability score were not correlated with those in % stenosis or minimal lumen diameter. The plasma total cholesterol level (T-C) was unchanged, triglyceride level (TG) was decreased, and high density lipoprotein cholesterol level (HDL-C) was increased in the bezafibrate group, but were unchanged in the control group. In the bezafibrate group, T-C and TG were decreased and HDL-C was increased in patients with a reduced vulnerability score but were unchanged in those with an unchanged score. These results indicate that 6 month administration of bezafibrate stabilizes coronary plaques and that the stabilization is not correlated with angiographic changes.     

Biochemical markers for the detection of bone metastasis in patients with prostate cancer: diagnostic efficacy and the effect of hormonal therapy

In the present study, we investigated the diagnostic effectiveness of biochemical markers of bone turnover for the detection of bone metastasis from prostate cancer and changes in the levels of these markers caused by hormonal therapy. Ninety-five patients with prostate cancer were divided into one of three groups: 26 patients with bone metastasis (BM(+)), 35 patients without bone metastasis on nonhormonal therapy (BM(−)HT(−)) and 34 patients without bone metastasis on hormonal therapy (BM(−)HT(+)). All patients in the BM(+) group had received hormonal therapy. Serum or urinary levels of the following biochemical markers of bone turnover were examined: bone-specific alkaline phosphatase (B-ALP), osteocalcin (OC), type I procollagen C-propeptide (PICP), type I collagen cross-linked C-telopeptide (ICTP), C-telopeptide fragment (CTx), N-telopeptide fragment (NTx), total pyridinoline (T-Pyr), total deoxypyridinoline (T-D-Pyr) and free deoxypyridinoline (F-D-Pyr). The BM(+) group showed significantly higher values than the BM(-)HT(-) group for B-ALP, PICP, NTx, CTx, T-Pyr, T-D-Pyr, and F-D-Pyr. Compared with the BM(−)HT(+) group, the BM(+) group showed significantly higher values for B-ALP, ICTP, NTx, T-Pyr and T-D-Pyr. The levels of B-ALP, NTx, CTx, T-D-Pyr and F-D-Pyr were significantly different between the BM(−)HT(−) and BM(−)HT(+) groups. All markers, except OC and CTx, significantly were correlated with the extent of bone metastasis on bone scintigraphy. Of all markers, receiver operating characteristic (ROC) analyses revealed B-ALP and F-D-Pyr to be the most sensitive and specific for differentiation between the BM(+) and BM(−)HT(−) groups with regard to bone formation and resorption, respectively. In contrast, B-ALP and ICTP were most sensitive and specific for differentiation between the BM(+) and BM(−)HT(+) groups. The results suggest that hormonal therapy greatly affects the efficacy of PICP, CTx and F-D-Pyr in the diagnosis of bone metastasis, whereas its effects on ICTP are small. Although bone metabolic markers would be useful in the diagnosis of bone metastasis from prostate cancer, the effects of hormonal therapy on bone metabolism should be kept in mind in their evaluation. Received: November 18, 1999 / Accepted: June 12, 2000     

Assessment of ablative margin after radiofrequency ablation for hepatocellular carcinoma; comparison between magnetic resonance imaging with ferucarbotran and enhanced CT with iodized oil deposition

Background and purpose

Our aim was to investigate whether magnetic resonance imaging (MRI) with ferucarbotran administered prior to radiofrequency ablation could accurately assess ablative margin when compared with enhanced computed tomography (CT) with iodized oil marking.

Materials and methods

We enrolled 27 patients with 32 hepatocellular carcinomas in which iodized oil deposits were visible throughout the nodule after transcatheter arterial chemoembolization. For these nodules, radiofrequency ablation was performed after ferucarbotran administration. We then performed T2-weighted MRI after 1 week and enhanced CT after 1 month. T2-weighted MRI demonstrated the ablative margin as a low-intensity rim. We classified the margin into three grades; margin (+): high-intensity area with a continuous low-intensity rim; margin zero: high-intensity area with a discontinuous low-intensity rim; and margin (−): high-intensity area extending beyond the low-intensity rim.

Results

In 28 (86%) of 32 nodules, there was agreement between MRI and CT. The overall agreement between for the two modalities in the assessment of ablative margin was good (κ = 0.759, 95% confidence interval: 0.480–1.000, p < 0.001). In four nodules, ablative margins on MRI were underestimated by one grade compared with CT.

Conclusion

MRI using ferucarbotran is less invasive and allows earlier assessment than CT. The MRI technique performed similarly to enhanced CT with iodized oil marking in evaluating the ablative margin after radiofrequency ablation.     

Effects of genetic and nutritional factors on bone mineral density in young adults

To estimate the genetic and dietary factors influencing bone mineral density (BMD) in young adults, a total of 53 healthy volunteers (HV) (age 20.89+/-1.34), from whom informed consent was obtained, answered a questionnaire on dietary factors and had DNA from peripheral blood mononuclear cells analyzed for single nucleotide polymorphisms (SNPs) for vitamin (Vit) D receptor (VDR), estrogen receptor alpha (ERalpha), interleukin 1 receptor antagonist (IL1RA), and apolipoprotein E (ApoE) genes. Daily intakes of Vit C, fiber, soybean and related foods, and green and yellow vegetables showed a correlation with % BMD. In addition, Vit B2 as well as Vit C, and vegetables were identified as important factors for BMD by Stepwise regression analysis. Among the SNPs analyzed, the B+ type of the VDR gene tended to be associated with a lower BMD, and pp type of the ER gene digested by the PvuII enzyme in females indicated a significantly lower BMD than that in males. In addition, these SNPs were also identified by factor analysis to be associated with BMD. These results suggested that a complex array of genetic factors, such as two or more SNPs or SNPs and gender, may be important to BMD.     

Spontaneous closure of a large left ventricular pseudoaneurysm after mitral valve replacement

Left ventricular pseudoaneurysm is a rare, but potentially fatal, condition that generally occurs as a complication of myocardial infarction, infective endocarditis, or cardiac surgery. Surgical repair is the treatment of first choice because of the marked risk of rupture, but deteriorated hemodynamics and complicated procedures to treat the pseudoaneurysm may lead to a high mortality rate. We report a 62-year-old woman with a large left ventricular pseudoaneurysm after mitral valve replacement for rheumatic mitral valve stenosis. Surgical repair was not performed due to the patient’s refusal, but her pseudoaneurysm resolved spontaneously by 2 years after mitral valve replacement. Spontaneous obliteration of a large left ventricular pseudoaneurysm is very rare in a patient on warfarin therapy. This case suggests that a left ventricular pseudoaneurysm with a narrow neck may resolve spontaneously in rare settings.     

Competitive repopulation assay of two gene-marked cord blood units in NOD/SCID/gammac(null) mice.

In multiunit cord blood transplantation, hematopoietic stem cells from each unrelated cord blood (UCB) unit competitively reconstitute the hematopoietic system in a recipient. To evaluate the fate of the progeny of each UCB unit and to determine the effects of graft-versus-graft reaction, we established a novel competitive repopulation assay using NOD/SCID/gammac(null) mice in which human T lymphocytes develop from CD34+ cells. CD34+ cells from each UCB unit were labeled with recombinant lentivirus vectors carrying genes encoding either enhanced green fluorescent protein (EGFP) or enhanced yellow fluorescent protein (EYFP). Hematopoietic chimerism composed of both EGFP+ and EYFP+ cells was stably maintained up to 6 months after transplantation with purified CD34+ cells; the ratio of EGFP+ to EYFP+ cells in peripheral blood and bone marrow posttransplantation was equivalent to the ratio of these cells at transplantation. However, when mononuclear cells from two UCB units were cotransplanted with CD34+ cells, engraftment was highly competitive, with cells from only one or the other of the two UCB units surviving. Further subfractionations of mononuclear cells indicate that the skewed chimerism that is often observed in clinical multiunit cord blood transplantation may be mediated by the cooperation of both CD4+ and CD8+ T cells. The assay established here will be a useful tool for analyzing hematopoietic reconstitution in clinical multiunit cord blood transplantation.