Predictive performance of dual modality of computed tomography angiography and intravascular ultrasound for no-reflow phenomenon after percutaneous coronary stenting in stable coronary artery disease.

Attenuated plaque on intravascular ultrasound (IVUS) and low attenuation plaque on computed tomography angiography (CTA) are associated with no-reflow phenomenon during percutaneous coronary intervention (PCI). However, evaluation by a single modality has been unable to satisfactorily predict this phenomenon. We investigated whether the combination of IVUS and CTA findings can ameliorate the predictive potential for no-reflow phenomenon after stent implantation during PCI in stable coronary artery disease (CAD). A total of 988 lesions of 707 stable CAD patients who underwent coronary CTA before PCI were enrolled. PCI was performed with preprocedural IVUS and stent implantation. As for plaque characters, very low attenuation plaque (CTA v-LAP) whose minimum density was < 0 Hounsfield units on CTA and attenuated plaque (IVUS AP) on IVUS were evaluated. No-reflow phenomenon was observed in 22 lesions (2.2%) of 19 patients (2.7%). Both CTA v-LAP and IVUS AP were much more frequently observed in patients with no-reflow phenomenon. Positive (PPV) and negative predictive values (NPV) and accuracy for prediction of no-reflow were almost equivalent between CTA v-LAP (13.2, 99.6, and 87.0%) and IVUS AP (15.7, 99.8, and 89.0%). The combination of CTA v-LAP and IVUS AP markedly ameliorated PPV (31.7%) without deterioration of NPV (99.7%) and increased the diagnostic accuracy (95.5%). These findings showed that the combination of CTA v-LAP and IVUS AP improved the predictive power for no-reflow phenomenon after coronary stenting in stable CAD patients, suggesting the usefulness of combined estimation by using CTA and IVUS for predicting no-reflow phenomenon during PCI in clinical practice.

Effects of cilostazol on cerebral vasospasm after aneurysmal subarachnoid hemorrhage: a multicenter prospective, randomized, open-label blinded end point trial.

OBJECT: Cerebral vasospasm following aneurysmal subarachnoid hemorrhage (SAH) is a major cause of subsequent morbidity and mortality. Cilostazol, a selective inhibitor of phosphodiesterase 3, may attenuate cerebral vasospasm because of its antiplatelet and vasodilatory effects. A multicenter prospective randomized trial was conducted to investigate the effect of cilostazol on cerebral vasospasm. METHODS: Patients admitted with SAH caused by a ruptured anterior circulation aneurysm who were in Hunt and Kosnik Grades I to IV and were treated by clipping within 72 hours of SAH onset were enrolled at 7 neurosurgical sites in Japan. These patients were assigned to one of 2 groups: the usual therapy group (control group) or the add-on 100 mg cilostazol twice daily group (cilostazol group). The group assignments were done by a computer-generated randomization sequence. The primary study end point was the onset of symptomatic vasospasm. Secondary end points were the onset of angiographic vasospasm and new cerebral infarctions related to cerebral vasospasm, clinical outcome as assessed by the modified Rankin scale, and length of hospitalization. All end points were assessed for the intention-to-treat population. RESULTS: Between November 2009 and December 2010, 114 patients with SAH were treated by clipping within 72 hours from the onset of SAH and were screened. Five patients were excluded because no consent was given. Thus, 109 patients were randomly assigned to the cilostazol group (n = 54) or the control group (n = 55). Symptomatic vasospasm occurred in 13% (n = 7) of the cilostazol group and in 40% (n = 22) of the control group (p = 0.0021, Fisher exact test). The incidence of angiographic vasospasm was significantly lower in the cilostazol group than in the control group (50% vs 77%; p = 0.0055, Fisher exact test). Multiple logistic analyses demonstrated that nonuse of cilostazol is an independent factor for symptomatic and angiographic vasospasm. The incidence of new cerebral infarctions was also significantly lower in the cilostazol group than in the control group (11% vs 29%; p = 0.0304, Fisher exact test). Clinical outcomes at 1, 3, and 6 months after SAH in the cilostazol group were better than those in the control group, although a significant difference was not shown. There was also no significant difference in the length of hospitalization between the groups. No severe adverse event occurred during the study period. CONCLUSIONS: Oral administration of cilostazol is effective in preventing cerebral vasospasm with a low risk of severe adverse events. Clinical trial registration no. UMIN000004347, University Hospital Medical Information Network Clinical Trials Registry.

Impaired tight junction sealing and precocious involution in mammary glands of PKN1 transgenic mice.

The mammary gland undergoes a complex set of changes to establish copious milk secretion at parturition. To test the hypothesis that signaling through the Rho pathway plays a role in secretory activation, transgenic mice expressing a constitutively activated form of the Rho effector protein PKN1 in the mammary epithelium were generated. PKN1 activation had no effect in late pregnancy but inhibited milk secretion after parturition, diminishing the ability of transgenic dams to support a litter. Mammary gland morphology as well as increased apoptosis and expression of IFGBP5 and TGFbeta3 suggest precocious involution in these animals. Furthermore, tight junction sealing at parturition was impaired in transgenic mammary glands as demonstrated by intraductal injection of [14C]sucrose. Consistent with this finding, tight junction sealing in response to glucocorticoid stimulation was highly impaired in EpH4 mammary epithelial cells expressing constitutively activated PKN1, whereas expression of a dominant-negative PKN1 mutant resulted in accelerated tight junction sealing in vitro. Tight junction formation was not impaired as demonstrated by the correct localization of occludin and ZO1 at the apical cell borders. Our results provide evidence that PKN1 participates in the regulation of tight junction sealing in the mammary gland by interfering with glucocorticoid signaling.

[A case of symptomatic arachnoid cyst of the occipital convexity in an adult].

Symptomatic arachnoid cyst in an adult patient is rare. We present a case of a 51-year-old female with an arachnoid cyst of the right occipital convexity who developed homonymous hemianopsia. She had complained of numbness in the limbs at the age of 47 and based on MRI was diagnosed with a cystic space-occupying lesion in the right occipital convexity. After being under observation for four and a half years, she complained of headache and visual disturbance, at which time we diagnosed growth of the cyst. On ophthalmologic examination, homonymous hemianopsia was demonstrated. She underwent membranectomy, which resulted in the disappearance of visual disturbance. This case is comparatively rare among previously reported cases of symptomatic arachnoid cyst with regard to both location and symptom. Membranectomy is one of effective methods for treating symptomatic arachnoid cyst in the occipital convexity.

The Rho kinase inhibitor fasudil inhibits tumor progression in human and rat tumor models.

The ability of cancer cells to undergo invasion and migration is a prerequisite for tumor metastasis. Rho, a Ras-related small GTPase, and the Rho-associated coiled coil-containing protein kinases (Rho kinases, ROCK1 and ROCK2) are key regulators of focal adhesion, actomyosin contraction, and thus cell motility. Inhibitors of this pathway have been shown to inhibit tumor cell motility and metastasis. Here, we show that fasudil [1-(5-isoquinolinesulfonyl)-homopiperazine], an orally available inhibitor of Rho kinases, and its metabolite 1-(hydroxy-5-isoquinoline sulfonyl-homopiperazine) (fasudil-OH) modify tumor cell morphology and inhibit tumor cell migration and anchorage-independent growth. In addition, we show that fasudil inhibited tumor progression in three independent animal models. In the MM1 peritoneal dissemination model, tumor burden and ascites production were reduced by > 50% (P < 0.05). In the HT1080 experimental lung metastasis model, fasudil decreased lung nodules by approximately 40% (P < 0.05). In the orthotopic breast cancer model with MDA-MB-231, there were 3-fold more tumor-free mice in the fasudil-treated group versus saline control group (P < 0.01). Fasudil has been approved for the treatment of cerebral vasospasm and associated cerebral ischemic symptoms. In patients, fasudil is well tolerated without any serious adverse reactions. Therefore, the concept of Rho kinase inhibition as an antimetastatic therapy for cancer can now be clinically explored.

[A middle cerebral artery dissecting aneurysm manifesting solely with pain, following a vertebral artery dissecting aneurysm].

A 41-year-old male had presented with severe neck pain and was diagnosed as having a left vertebral artery (VA) dissecting aneurysm. During the observation period, he suddenly suffered from a pain on his left temple. MR imaging revealed neither SAH nor cerebral infarction. MR angiography, computed tomographic (CT) angiography and cerebral angiography showed fusiform dilatation of the M1 portion of the left middle cerebral artery (MCA) which had been normal in the former study. The abnormality of the left MCA normalized on both MR and CT angiography 6 months after the second onset. Because of the chronological change of radiological findings compatible with the symptom, we diagnosed the second episode as a MCA dissecting aneurysm manifesting with isolated pain. Among the previous forty-four MCA dissecting aneurysms, all but one case presented with hemorrhagic or ischemic event. In addition, this is the only case of multiple dissecting aneurysms of VA and MCA manifesting with isolated pain.

An autopsy case of primary mixed choriocarcinoma and mature teratoma located in the thymic region associated with elevated human chorionic gonadotropin levels and characteristic testicular changes.

An autopsy case of a 19-year-old male Japanese student with a primary mixed choriocarcinoma and mature teratoma in the thymic region is reported. The patient died 7 days after he first noticed fever and dyspnea. On autopsy, an anterior mediastinal mass was found to be in contact with the thymic gland. The mass weighed 270 g and measured 12.5 cm x 10 cm x 5 cm. The left thoracic cavity contained 2200 ml bloody pleural effusion and 200 g coagula due to hemorrhage from the tumor. Metastasized choriocarcinoma was seen in both lungs and the liver. High serum levels of human chorionic gonadotropin (HCG, 1 634 000 mIU/ml) and a decreased weight of the testes (2.0 g each) with Leydig cell hyperplasia/hypertrophy and the seminiferous tubules with hyaline ghost tubules or Sertoli cell only tubules were seen; other male reproductive organs were histologically normal. Although the serum testosterone level was within the normal range (5.75 ng/ml), luteinizing hormone (LH, 0.1 mIU/ml) and follicle-stimulating hormone (FSH, 0.3 mIU/ml) levels were decreased. High serum levels of HCG and characteristic testicular changes are drscribed.

Were volatile organic compounds the inducing factors for subjective symptoms of employees working in newly constructed hospitals?

This study demonstrated possible relationships between environmental, personal, and occupational factors and changes in the subjective health symptoms of 214 employees after the relocation of a hospital in a region of Japan. Eight indoor volatile organic compounds (VOCs) were detected in at least one of the 19 rooms investigated, and total VOC (TVOC) concentrations in 8 rooms exceeded the advisable value (400 microg/m(3)) established by the Ministry of Health, Labour and Welfare of Japan. Formaldehyde was detected in all the investigated rooms, but none of the results exceeded the guideline value (100 microg/m(3)). Multiple logistic regression analysis was applied to select variables significantly associated with the subjective symptoms that can be induced by sick building syndrome. The results showed that subjective symptoms of deterioration in the skin, eye, ear, throat, chest, central nervous system, autonomic system, musculoskeletal system, and digestive system among employees were associated mainly with gender difference and high TVOC concentrations (>1200 microg/m(3)). Long work hours (>50 h per week) in females and smoking in males were to be blamed for the deterioration of their symptoms. The present findings suggest that to protect employees from indoor environment-related adverse health effects, it is necessary to reduce the concentration of indoor chemicals in new buildings, to decrease work hours, and to forbid smoking.

Size of cerebral aneurysms and related factors in patients with subarachnoid hemorrhage.

BACKGROUND: As the indication for surgical treatment of incidentally discovered small aneurysms remains controversial. METHODS: We retrospectively investigated the characteristics of small ruptured aneurysms and examined the relationship between the size and location of ruptured intracranial aneurysms and the sex, age, lifestyle, and medical history of 280 patients with ruptured aneurysm treated at our institute. RESULTS: The mean diameter of ruptured aneurysms in this series was 7.6 mm. In diameter, 135 (48.2%) ranged between 5 and 10 mm; 73 (26.1%) were smaller than 5 mm. The size of the ruptured aneurysms was significantly smaller (mean 6.5 mm) in patients with non- or poorly controlled hypertension than in normotensive patients (mean 8.3 mm) (p < 0.05). Ruptured aneurysms in the anterior communicating artery (AcomA) and anterior cerebral artery (ACA) were significantly smaller (p < 0.01) than those in the internal carotid artery or middle cerebral artery. Among 58 patients with multiple aneurysms, only 7 (12%) suffered rupture of aneurysms smaller than 5 mm (p < 0.01). Patients younger than 40 years and patients with a family history of subarachnoid hemorrhage appeared to predispose to the rupture of small-sized aneurysms, although those did not affect the statistical significance. CONCLUSIONS: This study shows that even aneurysms smaller than 10 mm may rupture. However, treatment decisions for unruptured aneurysm should not be based solely on the size of the unruptured aneurysms. Our data implies that even small aneurysms in the AcomA and ACA had an increased tendency for rupture, and that hypertensive patients were at higher risk for the rupture of small aneurysms.