Pitavastatin inhibits intimal hyperplasia in rabbit vein graft.

BACKGROUND: The autologous saphenous vein graft is currently the most suitable conduit for arterial bypass of the lower limbs. Various approaches have been attempted to control vein graft intimal hyperplasia, and several recent reports have suggested that statin use may be linked to improved patency of vein grafts. In this study, the efficacy of pitavastatin was evaluated on intimal hyperplasia and midkine expression of experimental normocholesterolemic rabbit autologous vein graft. MATERIALS AND METHODS: Rabbits were fed regular rabbit chow, and in half of them, pitavastatin (1 mg/kg/d) was administered. A week after starting the treatment, jugular vein was implanted into the carotid artery. At 2 and 4 wk after the operation, vein grafts were harvested, and intimal hyperplasia of vein grafts were assessed. Cell proliferation in neointima was determined by proliferative cell nuclear antigen and Ki-67 stain 2 wk after implantation. In addition, the effect of pitavastatin on midkine, a heparin-binding growth factor, expressed in vein grafts was analyzed by Western blotting. RESULTS: The intimal hyperplasia in the pitavastatin group was significantly suppressed compared with the control group. Both proliferative cell nuclear antigen and Ki-67 labeling index were significantly lower in the pitavastatin group, and pitavastatin significantly reduced midkine expression of vein graft. CONCLUSIONS: These results demonstrate the efficacy of pitavastatin in reducing the degree of intimal hyperplasia of rabbit autologous vein grafts under normocholesterolemic condition. The mechanism of inhibition of intimal hyperplasia might be associated with midkine suppression.

[A case of advanced breast cancer with multiple lung, bone and lymph node metastases successfully treated with 5'-DFUR alone].

A 78-year-old female patient with locally advanced breast cancer, bleeding from a deep ulcer, and with multiple bone, lung and distant lymph node metastases was successfully treated with 5'-DFUR alone. She was at first treated with docetaxel + 5'-deoxy-5-fluorouridine (5'-DFUR) + tamoxifen, but they were discontinued because of deep venous thrombosis. She underwent simple mastectomy due to periodically recurring bleeding and infection. After administration of 5'-DFUR alone, a decrease of abnormal accumulation on a bone scintigram was obtained in 10 months, the lung metastases were diagnosed as being in complete remission (CR) at 11 months and the lymph node metastases were diagnosed as being in CR at 14 months. These states have continued to the present. The administration of 5'-DFUR alone is suitable for tumor dormancy in some cases.

Hydrophilic statin suppresses vein graft intimal hyperplasia via endothelial cell-tropic Rho-kinase inhibition.

BACKGROUND: Recent studies suggest that statins can protect the vasculature in a manner that is independent of their lipid-lowering activity through inhibition of the small guanosine triphosphate-binding protein, Rho, and Rho-associated kinase. Little information is available on the inhibitory effect of statins on vein graft intimal hyperplasia, the main cause of late graft failure after bypass grafting. We therefore examined the effects of a hydrophilic statin on vein graft intimal hyperplasia in vivo and Rho-kinase activity in vitro. METHODS: In the first experiment, rabbits were randomized to a control group (n = 7) that was fed regular rabbit chow or to a pravastatin group (n = 7) that was fed regular rabbit chow supplemented with 10 mg/kg pravastatin sodium. The branches of the jugular vein were ligated and an approximately 3-cm segment of the jugular vein was taken for an autologous reversed-vein graft. The carotid artery was cut and replaced with the harvested autologous jugular vein. At 2 and 4 weeks after the operation, vein grafts in both groups were harvested, and intimal hyperplasia of the vein grafts was assessed. In the second experiment, human umbilical vein endothelial cells and vascular smooth muscle cells were cultured and then treated with 1 micromol/L and 30 micromol/L pravastatin for 24 hours and harvested. Immunoblotting was performed on the resulting precipitates. Quantitative evaluation of phosphorylated myosin binding subunit and endothelial nitric oxide synthase was performed by densitometric analysis. RESULTS: We demonstrated that oral administration of the hydrophilic statin pravastatin to normocholesterolemic rabbits inhibited intimal hyperplasia of carotid interposition-reversed jugular vein grafts 4 weeks after implantation (pravastatin group, 39.5 +/- 3.5 microm vs control group, 64.0 +/- 7.1 microm; n = 7; P < .05) and suppressed cell proliferation and apoptosis in the neointima 2 weeks after implantation. In addition, we found that pravastatin inhibited Rho-kinase activity and accelerated endothelial nitric oxide synthase expression in human umbilical vein endothelial cells but did not inhibit Rho-kinase activity in vascular smooth muscle cells. CONCLUSIONS: These novel findings clearly demonstrate that a hydrophilic statin can suppress intimal hyperplasia of the vein graft in vivo and also show endothelial cell-tropic inhibition of Rho-kinase in vitro. Furthermore, these results strongly support the clinical use of hydrophilic statins to prevent intimal hyperplasia of the vein graft after bypass grafting. CLINICAL RELEVANCE: Late graft failure caused by neointimal hyperplasia limits the efficacy of vein grafting. Various treatments were examined to reduce neointimal hyperplasia, but a standard clinical treatment has not yet been established. We report here the inhibitory effect of pravastatin on the development of vein graft intimal hyperplasia. In addition, we demonstrate that pravastatin showed endothelial cell-tropic benefits through both the inhibition of Rho-kinase activity and acceleration of eNOS expression in vitro. Because the clinical benefits and safety of pravastatin have been established to a certain extent through long-term clinical usage, pravastatin may soon become standard treatment after vein bypass grafting.

External iliac venous aneurysm in a pregnant woman: a case report.

We report an external iliac venous aneurysm in a young pregnant woman who was diagnosed incidentally by ultrasound scanning. The aneurysm was successfully treated by tangential aneurysmectomy and lateral venorrhaphy. Primary iliac venous aneurysm is a rare vascular abnormality. The clinical significance of the disease is unknown. However, embolism, rupture, and thrombosis might occur as they can occur with popliteal venous aneurysm. In fact, three of four reported patients with iliac venous aneurysms had a thromboembolic event. For those reasons, prophylactic treatment is indicated. This is the first patient with an iliac venous aneurysm to be diagnosed without complication.

A small, incidentally detected pancreatic somatostatinoma: report of a case.

We report an asymptomatic 72-year-old woman with a small, incidentally detected, pancreatic somatostatinoma. The tumor, measuring 1 cm in diameter, showed a hypervascular pattern of contrast enhancement on computed tomography, and was found angiographically to receive a blood supply from the posterior superior pancreaticoduodenal artery. The results of preoperative hormonal assays all were normal. No assay for somatostatin was performed. No abnormality in either the pituitary or parathyroid was found. We thus considered the tumor to be a sporadic, nonfunctioning endocrine cell tumor, and enucleation was carried out. As some tumor cells in the resected specimen showed immunoreactivity for somatostatin, a diagnosis of somatostatinoma was made. Therefore, the possibility of somatostatinoma should be kept in mind when making a differential diagnosis of pancreatic endocrine tumors in cases where even a small hypervascular tumor is detected on enhanced computed tomography.

Successful treatment of Fournier's gangrene with the assistance of preoperative computed tomography in an elderly man: report of a case.

An 87-year-old man presented with inguinal pain and swelling, and was later diagnosed as having Fournier's gangrene. The information gained from preoperative computed tomography (CT) proved very useful for defining the extent of necrosis, and emergency surgery saved his life. Thus, CT should be performed prior to treatment of Fournier's gangrene, even in an emergency situation.