An optimal diagnostic threshold for minimal stent area to predict target lesion revascularization following stent implantation in native coronary lesions.
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Biomedical subjects
Publications and source records attributed to A Oshima.
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In rats, the subcutaneous injection of a dopamine uptake inhibitor, nomifensine (40 mg/kg), induced a significant increase in the c-fos mRNA levels in the neocortex on postnatal days 23 and 49, in the striatum on days 8, 14, 23 and 49, and in the hippocampus on day 23, when compared with saline administration. The repeated injection with nomifensine (40 mg/kg once daily) from postnatal days 49 to 53 and from 23 to 27, but not from days 8 to 12 and 14 to 18, resulted in an enhanced stereotypy response elicited by a subsequent challenge of the drug (5 mg/kg) 21 days after the last injection (behavioral sensitization). The present results suggest that the neuronal circuits regulated by nomifensine might undergo regionally-different developmental changes, which could be implicated in the development of behavioral expressions including nomifensine-induced stereotypy sensitization.
OBJECTIVES: The study was done to elucidate the relationship between baseline arterial remodeling and clinical outcome following stenting. BACKGROUND: The impact of preintervention arterial remodeling on subsequent vessel response and clinical outcome has been reported following nonstent coronary interventions. However, in stented segments, the impact of preintervention remodeling on clinical outcome has not been clarified. METHODS: Preintervention remodeling was assessed in 108 native coronary lesions by using intravascular ultrasound (IVUS). Positive remodeling (PR) was defined as vessel area (VA) at the target lesion greater than that of average reference segments. Intermediate or negative remodeling (IR/NR) was defined as VA at the target lesion less than or equal to that of average reference segment. Remodeling index expressed as a continuous variable was defined as VA at the target lesion site divided by that of average reference segments. RESULTS: Positive remodeling was present in 59 (55%) and IR/NR in 49 (45%) lesions. Although final minimal stent areas were similar (7.76 +/- 1.80 vs. 8.09 +/- 1.90 mm2, p = 0.36), target vessel revascularization (TVR) rate at nine-month follow-up was significantly higher in the PR group (22.0% vs. 4.1%, p = 0.01). By multivariate logistic regression analysis, higher remodeling index was the only independent predictor of TVR (p = 0.02). CONCLUSIONS: Lesions with PR before intervention appear to have a worse clinical outcome following IVUS-guided stenting. Intravascular ultrasound imaging before stenting may be helpful to stratify lesions at high risk for accelerated intimal proliferation.
Ten low molecular compounds analogous to galactose were screened for inhibition of human beta-galactosidase activity. Among them, 1-deoxy-galactonojirimycin and N-(n-butyl)-deoxy-galactonojirimycin showed an inhibitory effect at high concentrations. However, they restored mutant enzyme activities expressed in enzyme-deficient knockout mouse fibroblasts and human beta-galactosidosis fibroblasts at lower intracellular concentrations. This effect was more remarkable on G(M1)-gangliosidosis mutations (R201C, I51T, R201H, R457Q) than Morquio B disease mutations (W273L, Y83H). These low molecular compounds pass though the blood-brain barrier in mice. We hope that this new therapeutic approach will become clinically applicable in the near future.
A deficiency of lysosomal acid beta-galactosidase leads to G(M1)-gangliosidosis in humans, which progressively and profoundly affects the brain and other organs mainly in the early infantile period. We report the pathology of mice with targeted disruption of the beta-galactosidase gene. In the central nervous system, vacuolated neurons appeared in the spinal cord 3 days after birth. The vacuolation extended to neurons in the brainstem, cerebral cortex, hippocampus and thalamus and ballooning neurons became prominent with age. The vacuolation also appeared in Purkinje cells without a marked ballooning change. Reactive astrogliosis in the entire brain was marked at the terminal stage of the disease. Immunohistochemical study using anti-ganglioside G(M1) and G(A1) antibodies revealed extensive accumulation of G(M1) and G(A1) in the cerebral neurons. In the liver, however, accumulation of G(M1) was localized in the cytoplasm of hepatocytes, whereas that of G(A1) was localized in foamy macrophages and Kupffer cells. There were no significant abnormalities in the bone, bone marrow, or cornea at any stage. Although there are some phenotypic and biochemical differences between this knockout mouse and human GM1 gangliosidosis, the mouse will be a useful model for therapeutic trials for the human disease.
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BACKGROUND: Testicular cancer is one of those cancers for which the prognosis has improved remarkably since the introduction of effective chemotherapy. METHODS: Study subjects were 709 testicular cancer patients who were registered to the population-based Osaka Cancer Registry (OCR) as diagnosed between 1975 and 1992. The testicular cancer patients diagnosed/treated in the Osaka Medical Center for Cancer and Cardiovascular Diseases (OMCC) were also analyzed for comparison. RESULTS: The 5-year relative survival was 75.2% for the total of 709 patients and 77.9% for those diagnosed during 1990-92. These figures were much lower than those for patients in the USA and in Europe. In contrast, the 5-year survival of the 113 patients diagnosed in the OMCC during 1975-93 was 91.5% and similar to those in the USA and in Europe. CONCLUSIONS: The present study suggests that there are problems in the speed and extent of diffusion of effective chemotherapy for testicular cancer in Osaka.
To assess the risk of developing second primary cancers following breast cancer in Japanese females, we performed a retrospective cohort study of 2786 patients who were newly diagnosed with breast cancer at our hospital between 1970 - 1994, until the end of 1995 (average follow-up period, 8.6 years). The expected number of each second primary cancer was calculated by multiplying the number of appropriate person-years at risk by the corresponding age- and calendar period-specific cancer incidence rates for women obtained from the Osaka Cancer Registry. One hundred and seventeen patients developed a second primary cancer other than subsequent breast cancer, yielding an observed-to-expected ratio (O / E) of 1.3 [95% confidence interval (CI) = 1.1 - 1.6]. The risk for developing a second primary cancer was significantly elevated during the first year following the diagnosis of breast cancer, and decreased with the passage of time to unity. A significantly increased risk was noted for the development of ovarian cancer (O / E = 2.4, 95% CI = 1.0 - 4.6), thyroid cancer (O / E = 3.7, 95% CI = 1.5 - 7.6) and non-Hodgkin's lymphoma (NHL) (O / E = 3.5, 95% CI = 1.4 - 7.1) among the breast cancer patients compared with the general population. Patients who received hormonal therapy as the breast cancer treatment showed a significantly increased risk for ovarian cancer (O / E = 5.5, 95% CI = 1.8 - 12.9). Patients who received chemotherapy as the breast cancer treatment had an increased risk for NHL (O / E = 5.0, 95% CI = 1.6 - 11.6). These findings indicate that Japanese female patients with breast cancer had a 30% higher risk of developing a second primary cancer than the general population, the higher risk being manifested in the early period following the diagnosis of breast cancer. Medical surveillance of breast cancer patients for NHL, as well as for ovarian cancer and thyroid cancer, is required.
Male breast cancer is rare. The total number of incidence in Osaka for the period of 1966-95 was 182. Male-to-female ratio for breast cancer incidence was 1:164 in Osaka during this period. Mean age of the male breast cancer incidence was 63.3. The numbers of incidence and the crude incidence rates for male breast cancer have increased during the last 3 decades, while the age-standardized rates have remained constant. The age-specific incidence rates for males showed a gradual increase with age, while those for females showed a steep increase beginning at twenty years of age and a peak around 45-49 or 50-54 years old. The age-standardized incidence rates of male breast cancer were lower in Japan than in European countries and North America, as were those of female breast cancer. Distributions of the histological type and the extent of disease were not significantly different between males and females. Relative 5-year survival for the male breast cancer was, however, lower than that for the female, especially in the "regional" stage and "distant" stage. Further studies on the sex-difference in survival will be mandatory based on high-quality hospital cancer registries' data, which provide detailed information on the clinical stage and treatment.
We examined the effect of smoking cessation on natural killer (NK) activity of peripheral blood lymphocytes in terms of a prospective study of 27 Japanese subjects who participated in a smoking cessation intervention program. This program was delivered by means of group-counseling offering 7 sessions of about 2 hours over 6 months to help smokers to discontinue the habit. Thirteen subjects ceased smoking (quitters), while 14 continued to smoke (cigarette smokers). NK activity before the intervention was correlated positively with age (correlation coefficient=0.46, P<0.05). NK activity remained almost constant among quitters, comparing the activity before and after the intervention, while it decreased among cigarette smokers although it was not statistically significant. In the subgroup analysis, NK activity increased among those aged less than 65 years, or urine cotinine levels over 800 ng/ml before the intervention, especially among quitters, but there were no statistical significances. Multiple regression analysis showed changes in NK activity were correlated significantly only with age (standard regression coefficient=-0.44, P<0.05). These findings suggest that smoking cessation intervention programs might have been more effective for younger than elder subjects in consideration of NK activity.
The cancer incidence and mortality in Japan are described herein. The total number of deaths from all malignant neoplasms in 1998 was 284,000, corresponding to 30.3% of the total number of deaths among Japanese. Lung was the leading site of cancer deaths (17.9%), followed by the stomach (17.9%), large bowel (12.1%), liver (11.8%), pancreas (6.2%), gallbladder and extrahepatic biliary tract (5.2%), lymphatic tissue (3.7%), esophagus (3.4%), breast (3.1%), prostate (2.4%), leukemia (2.3%) and uterus (1.8%). The stomach was the leading site of cancer deaths until 1997, but was replaced by the lungs in 1998. The age-standardized mortality rates (1975-1998) have increased gradually for males, but decreased slightly for females. The rates have decreased remarkably for the stomach and uterus, while increasing for the lungs, large bowel, female breast, gallbladder and extrahepatic biliary tract, pancreas, and others. The total incidence for all cancers in Japan was estimated to be 454,000 in 1995. The stomach was the leading cancer site (22.2%), followed by the large bowel (17.7%), lung (11.6%), liver (7.8%), breast (6.6%), pancreas (3.7%), gallbladder and extrahepatic biliary tract (3.4%), lymphatic tissue (3.1%) and uterus (2.9%). The age-standardized incidence rates for all sites (1975-1995) have increased gradually for males, while remaining constant for females after a slight increase in the late 1970s. The incidence rates have decreased for the stomach and uterus, but increased for the large bowel, female breast, lung, liver, gallbladder and extrahepatic biliary tract, pancreas, prostate and others. The increase in the incidence rate was prominent for the large bowel, female breast and prostate.
In Japan, more than 90% of primary liver cancers consist of hepatocellular carcinoma (HCC), 80% of which is caused by chronic hepatitis C virus (HCV) infection, and the remaining 15% of which is caused by chronic hepatitis B virus (HBV) infection. The proportion of older patients among patients with HCC has been increasing in recent years because of the aging of the HCV-prevalent birth cohort born between 1925 and 1935. The cumulative risk of developing HCC among HCV carriers was estimated as 30% for males and 6% for females. Older age, being male, having a low platelet count, higher histological stage, genotype 1b, co-infection with HBV, heavy drinking and smoking increase the risk of developing HCC among patients with chronic HCV infection. Recent reports on the efficacy of interferon therapy on the incidence of HCC in Japanese patients with chronic hepatitis C demonstrate the importance of providing a screening system for chronic HCV infection and establishing a medical referral system so that patients undergo the appropriate therapy for the Japanese HCV carriers.
The effect of interferon on the long-term clinical outcome of patients with chronic hepatitis C remains unclear. This study included 594 patients with chronic hepatitis C who received interferon-alpha therapy (Interferon group) and 144 patients with chronic hepatitis C who did not receive interferon (Control group). The patients in the Interferon group were classified into the following three groups based on the response of the serum aminotransaminase level of the patient during and after completion of the therapy protocol: sustained responders (n = 175), transient responders (n = 165), and non-responders (n = 254). The age, sex, serum aminotransaminase level, platelet count, histological staging, hepatitis C virus (HCV) subtype, and HCV concentration at baseline were adjusted with the Cox proportional hazards model. The length of follow-up for assessment of the risk for developing hepatocellular carcinoma (HCC) was 57.2 +/- 13.9 months in the Interferon group and 67.7 +/- 28.7 months in the Control group. Multivariate analysis showed that interferon therapy decreased the risk for developing HCC by 48% compared with that in the Control group (P = 0.064). The older the age, being male, having a low platelet count, and higher histological stage were independent factors associated with the development of HCC. The hazard rate ratio for development of HCC in the sustained responders, transient responders, and non-responders was 0.16 (95% confidence interval [CI]: 0.04-0.62), 0.27 (95% CI: 0. 09-0.79), and 0.74 (95% CI: 0.37-1.48), respectively. During follow-up, 18 patients in the Interferon group died (10 from liver-related diseases) and 17 patients in the Control group died (10 from liver-related diseases). No sustained responder or transient responder in the Interferon group died of liver-related disease. The cumulative survival rates of the Interferon and Control groups were nearly identical during the first 5 years following diagnosis. Thereafter, the cumulative survival rate of the Control group declined, resulting in an 8-year survival rate in the Interferon and Control groups of 97% and 81%, respectively (P = 0. 061). Similar trends were seen in the survival analysis of those who had died of liver disease: the 8-year survival rates of the Interferon and Control groups were 98% and 88%, respectively (P = 0. 32). Our study demonstrated that interferon therapy significantly lowered the incidence of HCC among patients with chronic hepatitis C who showed sustained normalization and among patients who showed transient normalization of the serum aminotransferase level after completion of interferon therapy. The survival analyses and determination of cause of death suggested that interferon therapy improves the long-term survival of chronic hepatitis C patients who respond to this therapy, possibly by decreasing mortality from liver-related diseases.
BACKGROUND: Intravascular ultrasound (IVUS) can assess stent geometry more accurately than angiography. Several studies have demonstrated that the degree of stent expansion as measured by IVUS directly correlated to clinical outcome. However, it is unclear if routine ultrasound guidance of stent implantation improves clinical outcome as compared with angiographic guidance alone. METHODS AND RESULTS: The CRUISE (Can Routine Ultrasound Influence Stent Expansion) study, a multicenter study IVUS substudy of the Stent Anti-thrombotic Regimen Study, was designed to assess the impact of IVUS on stent deployment in the high-pressure era. Nine centers were prospectively assigned to stent deployment with the use of ultrasound guidance and 7 centers to angiographic guidance alone with documentary (blinded) IVUS at the conclusion of the procedure. A total of 525 patients were enrolled with completed quantitative coronary angiography, quantitative coronary ultrasound, and clinical events adjudicated at 9 months for 499 patients. The IVUS-guided group had a larger minimal lumen diameter (2.9+/-0.4 versus 2.7+/-0. 5 mm, P<0.001) by quantitative coronary angiography and a larger minimal stent area (7.78+/-1.72 versus 7.06+/-2.13 mm(2), P<0.001) by quantitative coronary ultrasound. Target vessel revascularization, defined as clinically driven repeat interventional or surgical therapy of the index vessel at 9 month-follow-up, occurred significantly less frequently in the IVUS-guided group (8.5% versus 15.3%, P<0.05; relative reduction of 44%). CONCLUSIONS: These data suggest that ultrasound guidance of stent implantation may result in more effective stent expansion compared with angiographic guidance alone.
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Automated 3-dimensional intravascular ultrasound (IVUS) analysis was used to assess status of the treated coronary artery immediately and 6 months after placement of a self-expanding Radius stent in 15 patients. Serial 3-dimensional IVUS analysis demonstrated gradual stent expansion that countered neointimal proliferation and preserved the lumen.
BACKGROUND: Conventional gray-scale images of intravascular ultrasound (IVUS) cannot accurately differentiate histologic subtypes of sonolucent coronary plaques with or without a lipid core. METHODS: We analyzed radiofrequency signals obtained in vitro from 24 regions of interest (ROI) of noncalcified (sonolucent) plaques in 10 atherosclerotic coronary artery specimens pressure-fixed by formalin. Radiofrequency signals were sampled with a 30-MHz IVUS catheter and digitized at 500 MHz in 8-bit resolution. The ROIs were histologically categorized into 12 plaques with a lipid core and 12 plaques without it. Integrated backscatter and statistical parameters of the radiofrequency envelope (mean/SD ratio [MSR], skewness, and kurtosis) within the ROI were calculated offline, and their ability to detect a lipid core was compared with visual analysis of the IVUS video images. In the group with lipid cores, percent area of a lipid core in each ROI was measured in a digitized histologic image by a computerized planimeter. RESULTS: Sensitivity and specificity of MSR, skewness, and kurtosis for lipid core detection were substantially greater than visual video image analysis (83.3% and 91.7%, 100% and 91.7%, 100% and 91.7% vs 53.3% and 71.7%). Furthermore, the parameters of integrated backscatter, MSR, skewness, and kurtosis were significantly correlated to percent of core area (r = -0.64, -0.73, 0.78, and 0.63, respectively; P<.05). CONCLUSIONS: Compared with IVUS video images, the parameters of radiofrequency signal analysis may be used to aid in more accurate detection and quantitative evaluation of a lipid core, which is one of the major factors of a vulnerable coronary plaque.
The histologic types of lung cancer cases diagnosed in 1979-1980 (n=799) and 1987 (n=587) were independently reviewed by two pathologists in order to investigate the reproducibility of the diagnosis of the histologic type when the WHO classification (1981) was used. The specimens from 354 surgical cases and biopsy or cytology specimens from 1032 non-surgical cases were reviewed. The inter-observer agreement was 87.9% (kappa=0.79) for surgical cases and 81.4% (kappa=0.72) for non-surgical cases. When compared to the original diagnosis, the agreement was 86.8% (kappa=0.78) for surgical and 86.4% (kappa=0.79) for non-surgical cases in 1979-1980 and the agreement was 92.8% (kappa=0.87) for surgical and 89.1% (kappa=0.83) for non-surgical cases in 1987. By histologic type, no difference in the agreement was observed except for large cell carcinoma. The distribution of histologic types after the review differed only slightly (less than 6%) from the original distribution. This suggests that in Osaka, Japan, the diagnosis based on the WHO classification (1981) had only a limited influence on the distribution of histologic types, and is not a major reason for the changing trends in lung cancer incidence by histologic type.