Restenosis after successful percutaneous transluminal coronary angioplasty: serial angiographic follow-up of 229 patients

To further understand the temporal mode and mechanisms of coronary restenosis, 229 patients were studied by prospective angiographic follow-up on day 1 and at 1, 3 and 6 months and 1 year after successful percutaneous transluminal coronary angioplasty. Quantitative measurement of coronary stenosis was achieved by cinevideodensitometric analysis. Actuarial restenosis rate was 12.7% at 1 month, 43.0% at 3 months, 49.4% at 6 months and 52.5% at 1 year. In 219 patients followed up for greater than or equal to 3 months, mean stenosis diameter was 1.91 +/- 0.53 mm immediately after coronary angioplasty, 1.72 +/- 0.52 mm on day 1, 1.86 +/- 0.58 mm at 1 month and 1.43 +/- 0.67 mm at 3 months. In 149 patients followed up for greater than or equal to 6 months, mean stenosis diameter was 1.66 +/- 0.58 mm at 3 months and 1.66 +/- 0.62 mm at 6 months. In 73 patients followed up for 1 year, mean stenosis diameter was 1.65 +/- 0.56 mm at 6 months and 1.66 +/- 0.57 mm at 1 year. Thus, stenosis diameter decreased markedly between 1 month and 3 months after coronary angioplasty and reached a plateau thereafter. In conclusion, restenosis is most prevalent between 1 and 3 months and rarely occurs beyond 3 months after coronary angioplasty.     

Serum C-reactive protein levels predict survival in hepatocellular carcinoma.

BACKGROUND/AIMS: C-reactive protein (CRP) was recently identified as a prognostic factor for patients with hepatocellular carcinoma (HCC) after surgical resection. We investigated the relationship between the serum levels of high sensitivity CRP (H-CRP) and the prognosis of HCC patients. METHOD: We conducted a cohort study of 90 HCC patients enrolled from 1997 to 1998. All patients were treated and followed for a mean period of 3.2 years. Clinical variables were compared between patients positive for H-CRP (serum H-CRP levels >/=3.0 mg/L, n=47) and those negative for H-CRP (serum H-CRP levels <3.0 mg/L, n=43). We also determined the relationship between serum H-CRP and prognosis in HCC patients. RESULTS: The survival rate of patients of the H-CRP-positive group was lower than that of H-CRP-negative patients. Tumour stage (stages 3 or 4), total bilirubin >/=1.2 mg/dL, albumin (Alb) <3.5 g/dL, des-gamma-carboxy prothrombin >/=40 mAU/mL, positive H-CRP and initial treatment (transcatheter arterial chemoembolization, hepatic arterial infusion chemotherapy or best supportive care) were identified as significant poor prognostic factors by univariate analysis, while positive H-CRP [hazard ratio (HR), 1.58; P=0.048], Alb<3.5 g/dL (HR, 2.10; P=0.004), tumour stage (stages 3 or 4; HR, 3.05; P=0.001) and initial treatment (HR, 1.88; P=0.029) were considered to be significant determinants of poor prognosis by multivariate Cox proportional hazards analysis. CONCLUSIONS: The prognosis of H-CRP-positive patients was poorer compared with H-CRP-negative patients. This study confirmed that H-CRP, like CRP, is a marker of poor prognosis in HCC patients.     

Characteristics of syncopal falls in community-living older people transported to an emergency department

In older people, falls are major reasons for transporting to emergency departments (ED). Falls are etiologically classified into syncopal falls and non-syncopal ones. The aim of this study is to clarify the characteristics of syncopal falls in community-living older people transported to ED. The retrospective chart review was performed on patients older than 65 years, transported to the ED of Keio University Hospital in Tokyo because of falls during a 12-month period. Age, sex, blood pressure and pulse rate at the arrival to ED, episode of syncope, type of fall, sustained injury and medical problems were screened. We analyzed the differences between syncopal falls and non-syncopal ones. Patients with syncopal falls were given blood tests, electrocardiograms, and standing tests for orthostatic hypotension. The number of syncopal falls was 33 (29.5%), and that of non-syncopal ones was 79 (69.3%). Syncopal falls frequently occurred on same level compared with from one level to another (84.8% versus 9.1%). In patients with syncopal falls, the frequency of falling on the same level was significantly higher than that in patients with non-syncopal falls (84.8% vs 60.8%). Patients with syncopal falls significantly sustained fewer fractures (12.1% vs 34.2%), and used more antihypertensive agents (45.5% vs 18.9%) than those with non-syncopal ones, respectively. The 14 syncopal fall patients were given standing tests, and four patients presented orthostatic hypotension. In community-living older people transported to ED, syncopal falls frequently occurred on the same level, and the patients with syncopal falls were found to have sustained fewer fractures and use more antihypertensive agents.     

Systemic Delivery of Synthetic MicroRNA-16 Inhibits the Growth of Metastatic Prostate Tumors via Downregulation of Multiple Cell-cycle Genes

Recent reports have linked the expression of specific microRNAs (miRNAs) with tumorigenesis and metastasis. Here, we show that microRNA (miR)-16, which is expressed at lower levels in prostate cancer cells, affects the proliferation of human prostate cancer cell lines both in vitro and in vivo. Transient transfection with synthetic miR-16 significantly reduced cell proliferation of 22Rv1, Du145, PPC-1, and PC-3M-luc cells. A prostate cancer xenograft model revealed that atelocollagen could efficiently deliver synthetic miR-16 to tumor cells on bone tissues in mice when injected into tail veins. In the therapeutic bone metastasis model, injection of miR-16 with atelocollagen via tail vein significantly inhibited the growth of prostate tumors in bone. Cell model studies indicate that miR-16 likely suppresses prostate tumor growth by regulating the expression of genes such as CDK1 and CDK2 associated with cell-cycle control and cellular proliferation. There is a trend toward lower miR-16 expression in human prostate tumors versus normal prostate tissues. Thus, this study indicates the therapeutic potential of miRNA in an animal model of cancer metastasis with systemic miRNA injection and suggest that systemic delivery of miR-16 could be used to treat patients with advanced prostate cancer.     

Effect of Toki-Shakuyaku-San (TJ-23) on the activity of choline acetyltransferase in the brain of menopausal rats

This study was designed to examine the effect of TJ-23 on the synthesis of acetylcholine menopausal rats. TJ-23 (500 mg/kg body weight) was administered daily through drinking water for either 1 or 3 months. Treatment with TJ-23 for 1 month resulted in an increase in the choline acetyltransferase (ChAT) activity in the ventral hippocampus, but there was no statistically significant change in the frontoparietal cerebral cortex. Treatment with TJ-23 for 3 months resulted in a decrease in the ChAT activity in the frontoparietal cortex, but there was no statistically significant change in the hippocampus. Furthermore, treatment with TJ-23 for 3 months resulted in a decrease in the ChAT activity in the amygdala-pyriform cortex complex. From these observations, it is inferred that TJ-23 treatment brings on the synthesis of acetylcholine in the frontoparietal cerebral cortex and hippocampus, and furthermore, treatment with the same regimen brings on different time sequences of acetylcholine synthesis in the frontoparietal cerebral cortex and hippocampus in menopausal rats.     

Increased Prevalence of HTLV-I Infection in Patients with Hepatocellular Carcinoma Associated with Hepatitis C Virus

The progression from chronic hepatitis C virus (HCV) infection to hepatocellular carcinoma (HCC) has been reported. We evaluated whether co-infection with the human T-lymphotropic virus type I (HTLV-I) might be associated with this transition in a cross-sectional analysis of 127 patients with HCV-chronic hepatitis (mean age=51.7) and 43 patients with HCV-associated HCC (mean age=62.4); the seroprevalence of anti-HTLV-I was 9.5% and 30.2%, respectively. For subjects 50 years or older, the seroprevalence of anti-HTLV-I in HCC patients was 13/41 (31.7%) which was significantly higher than that in chronic hepatitis patients (6/82, 7.3%) ( P =0.001). The relative risk (RR) of association was 12.8 ( P =0.0004) among the males, however, no association was evident among the females, RR=1.3 ( P =0.80). The increased prevalence of HTLV-I positivity among the HCC cases could not be attributed to a higher rate of prior transfusion. These data suggest that co-infection with HTLV-I may contribute to the development of HCC among patients with HCV-induced chronic liver diseases in a highly HTLV-I-endemic area.     

Inhibition of Pulmonary Metastases and Tumor Cell Invasion in Experimental Tumors by Sodium d-Glucaro-δ-lactam (ND2001)

Sodium d -glucaro-δ-lactam (ND2001) inhibited spontaneous pulmonary metastases of the highly metastatic B16 melanoma variant with a maximal inhibition rate of 99.5%, and 6 of 7 animals remained metastasis-free. Likewise, ND2001 inhibited the spontaneous pulmonary metastases of both Lewis lung carcinoma (3LL) with a rate of 98.0% (3 of 5 animals remaining metastasis-free) and rat KDH-8 liver carcinoma with a rate of 82.5% (3 of 7 animals remaining metastasis-free), although it was unable to inhibit the metastases of mouse BMT-11 fibrosarcoma and rat SST-2 breast carcinoma. Pretreatment with ND2001 in vitro inhibited the pulmonary metastases of the B16 variant and 3LL cells, which indicates direct action upon the cancer cells. When the invasive activity of cancer cells was measured by the Boyden chamber method, the number of invading B16 variant or 3LL cells was reduced with maximal inhibition rates of 93.0% or 89.9%, respectively, but pretreatment with ND2001 failed to reduce the invasive activity of BMT-11 or SST-2 cells. ND2001 showed neither cytocidal nor antitumor activity. These results suggest that ND2001 inhibited pulmonary metastases at the invasive step into the basement membrane by directly changing some property of the tumor cells.     

Renal protective effect of YM598, a selective endothelin ET(A) receptor antagonist,against diabetic nephropathy in OLETF rats

We have investigated the effect of potassium (E)-N-[6-methoxy-5-(2-methoxyphenoxy)-2-(pyrimidin-2-yl) pyrimidin-4-yl]-2-phenylenthenesulfonamidate (YM598), a selective endothelin ET(A) receptor antagonist, on renal function in Otsuka Long-Evans Tokushima Fatty (OLETF) rats, an animal model of type II diabetes. YM598 (0.1 or 1 mg kg(-1)), enalapril (5 mg kg(-1)), an angiotensin-converting enzyme inhibitor, or vehicle was administered once daily by gastric gavage to 22-week-old male Otsuka Long-Evans Tokushima Fatty rats for 32 weeks. Enalapril but not YM598 mildly lowered blood pressure in the diabetic rats. YM598 blunted the development of albuminuria in a dose-dependent manner. High dose of YM598 reduced albuminuria comparable to enalapril. Urinary endothelin-1 excretion was greater in the diabetic than in the control rats, and was not substantially influenced by the agents. These data suggest that endothelin is involved in the progression of diabetic nephropathy in Otsuka Long-Evans Tokushima Fatty rats, and an endothelin ET(A) receptor antagonist may be useful for the treatment of diabetic nephropathy.     

Cytoskeleton disruption causes apoptotic degeneration of dentate granule cells in hippocampal slice cultures

Colchicine, a potent microtubule-depolymerizing agent, is well known to selectively kill dentate granule cells in the hippocampal formation in vivo. Using organotypic cultures of rat entorhino-hippocampal slices, we confirmed that in vitro exposure to 1 μM and 10 μM of colchicine reproduced a specific degeneration of the granule cells after 24 h. Similar results were obtained with other types of microtubule-disrupting agents, i.e., nocodazole, vinblastine, and Taxol. Interestingly, the actin-depolymerizing agents cytochalasin D and latrunculin A also elicited selective neurotoxicity in the dentate gyrus without affecting survival of hippocampal pyramidal cells. The selective pattern of degeneration was observable 24 h after a brief treatment with the toxins as short as 5 min, but this delayed neuronal death was unlikely to be a result of excitotoxicity because it was virtually unaffected by glutamate receptor antagonists, tetrodotoxin, or extracellular Ca²⁺-free conditions. The damaged tissues contained a large number of TUNEL-positive neurons and exhibited an increased level in caspase-3-like activity, suggesting that cytoskeleton disruption triggers an apoptosis-like process in dentate granule cells. Thus, this study may provide a basis for understanding the distinctive mechanism that supports granule cell survival.