Efficient Synthesis and Structural Analysis of Chiral 4,4'-Biazulene.

4,4'-Biazulene is a potentially attractive key component of an axially chiral biaryl compound, however, its structure and properties have not been clarified owing to the lack of its efficient synthesis. We report a breakthrough in the reliable synthesis of 4,4'-biazulene, which is achieved by the access to azulen-4-ylboronic acid pinacol ester and 4-iodoazulene as novel key synthetic intermediates for the Suzuki-Miyaura cross-coupling reaction. The X-ray crystallographic analysis of 4,4'-biazulene confirmed its axial chirality. The enantiomers of 4,4'-biazulene were successfully resolved by HPLC on the chiral stationary phase column. The kinetic experiments and DFT calculations indicate that the racemization energy barrier of 4,4'-biazulene is comparable to that of 1,1'-binaphthyl.

An Infected Aneurysm of the Vertebral Artery Treated with a Stent-graft: A Case Report.

In a 75-year-old man, a growing vertebral artery aneurysm at the C3/4 intervertebral level was found at postoperative evaluation of cervical abscess, which was diagnosed as a complication of sepsis subsequent to cholangitis. Even after a successful antibiotic treatment and a surgical drainage, the aneurysm grew enough to cause compression of esophagus and trachea. The aneurysm was judged to be infection-related, based on the clinical course and the anatomical vicinity to the abscess. Following a dual antiplatelet treatment (clopidogrel 75 mg and aspirin 100 mg per day) for a week, the patient underwent endovascular treatment of the aneurysm with a stent-graft. Postoperative angiography showed complete obliteration of the aneurysm with preserving patency of the vertebral artery. A dual antiplatelet treatment was continued for 6 months and was changed to a single antiplatelet treatment (clopidogrel 75 mg per day) thereafter. Neither recurrence of the aneurysm nor stent-graft infection was observed for 4 years of follow-up. This case illustrates the potential use of a stent-graft in the treatment of an infected aneurysm.

[The Efficacy of CT angiography using the IVR-CT/angio system for surgical treatment of spinal hemangioblastoma].

We performed 3D-CT angiography (3D-CTA) with contrast injection to a feeding artery through a selectively introduced catheter into the intercostal artery in a patient with spinal hemangioblastoma. It revealed a relative three-dimensional (3D) anatomy between a tumor body, feeding arteries, draining veins, and surrounding vertebrae with superior resolution to 3D-CTA with intravenous contrast injection. This observation was used for preoperative planning facilitating tumor removal, through reconstructed 3D fly-through animation providing intraoperative identification and obliteration of feeding arteries. This examination was carried out without difficulty by utilizing IVR-CT/angio system (IVR: interventional radiology) which combines angiographic and CT equipment with a single fluoroscopy table, because it does not require a room-to-room transfer of the patient with the catheter left cannulated. DSA detection for any spinal lesions, neoplastic or vascular ones, is always better assisted by 3D-CTA with the IVR-CT/angio system (IVR-CTA).

Preventive effect of aggressive blood pressure lowering on hematoma enlargement in patients with ultra-acute intracerebral hemorrhage.

The preventive effect of aggressive blood pressure lowering on hematoma enlargement was investigated in patients with ultra-acute spontaneous intracerebral hemorrhage (ICH). Retrospective review of 248 patients (145 males, 103 females) with spontaneous ICH treated in our hospital between 2005 and 2008 identified patients with ultra-acute ICH who were directly taken to our institute by ambulance within 3 hours after onset. Patients who could not be assessed twice by computed tomography (CT) within 24 hours after arrival were excluded. Systolic blood pressure (SBP) was aggressively controlled in all patients using intravenous nicardipine to below 140 mmHg as soon as possible after diagnosis of ICH with CT. Hematoma enlargement was defined as increase in volume of more than 33% or more than 12.5 ml in the first 24 hours. Hematoma enlargement was observed in 11 of the 73 patients (15.0%). The time course of SBP change was not significantly different in patients with and without hematoma enlargement. The incidence of hematoma enlargement in patients with ultra-acute ICH in this study was 15.0%, which was lower than that in other series in which blood pressure was not reduced aggressively. This finding suggests that aggressive SBP lowering to below 140 mmHg has a preventive effect on hematoma enlargement in patients with ultra-acute ICH.

Diagnosis of anterior inferior cerebellar artery occlusion on magnetic resonance angiography with reference to basiparallel anatomic scanning-magnetic resonance imaging.

A 67-year-old woman presented with symptomatic infarction in the territory of the anterior inferior cerebellar artery manifesting as vertigo, vomiting, and right facial weakness. Basiparallel anatomic scanning (BPAS) magnetic resonance (MR) imaging combined with MR angiography demonstrated the occluded anterior inferior cerebellar artery. Common anatomic variations and limited detection of the smaller branches on MR angiography sometimes hinder evaluation of the occluded artery. BPAS-MR imaging may have a supplementary role to MR angiography in the diagnosis of cerebellar artery occlusions.

Early detection of metachronous brain metastases by biannual brain MRI follow-up may provide patients with non-small cell lung cancer with more opportunities to have radiosurgery.

PURPOSE: Those who have brain metastases smaller than 30 mm in diameter and less than 5 in number can be treated less invasively with radiosurgery. This retrospective study evaluated the optimal brain magnetic resonance image (MRI) follow-up interval for non-small cell lung cancer (NSCLC) patients to detect radiosurgically manageable metachronous brain metastases (MBM). PATIENTS AND METHODS: The records of 551 patients with primary NSCLC, treated in our institute between 2002 and 2007, were reviewed. The initial brain MRI was performed within one month after diagnosis of NSCLC, and the follow-up brain MRI interval was at the discretion of physicians. The interval between the last MRI in which brain metastases were not found and the first MRI in which brain metastases were found was defined as the critical MRIs interval (CMI). The relationship between CMI and the maximum size or number of MBM was evaluated. RESULTS: Among reviewed patients, the initial MRI of 38 patients showed brain metastases and 29 patients were diagnosed as MBM. In these MBM patients, the median interval from diagnosis of NSCLC to diagnosis of brain metastases was 8.9 months. The median CMI was 4.7 (range: 1.6-18.9) months. All brain metastases smaller than 30 mm in maximum diameter were found when CMI was shorter than 6.0 months, although 5 or more brain metastases in number were detected even by shorter CMI than 3 months. CONCLUSION: Early detection of MBM by biannual MRI follow-up may provide NSCLC patients with more opportunities to have less invasive treatment.

Plasma level of platelet-derived microparticles is associated with coronary heart disease risk score in healthy men.

AIM: The aim of this study was to clarify the relationship between platelet-derived microparticles (PDMPs) and the Framingham 10-yr coronary heart disease (CHD) risk score. METHODS: A cross-sectional study of healthy volunteers free of medication, and cardiovascular or cerebrovascular disease was conducted. The subjects were 190 Japanese men (median age 41). An ELISA kit and monoclonal antibodies against CD42b and CD42a (glycoprotein Ib and IX) were used. RESULTS: PDMPs are correlated with platelet count, high sensitivity C-reactive protein (hsCRP), and diastolic blood pressure by multivariate analysis (R(2)=0.316, p <0.001). Quartile range of PDMPs is significantly associated with the 10-yr CHD risk score after adjusting for age, platelet count, hsCRP, and hypertension (p=0.033) and for age, platelet count, hsCRP, and presence of metabolic syndrome (MS) (p=0.020). In individuals with a predicted 10-yr risk for CHD >or=8% (corresponding with the highest quartile), compared to those with a predicted 10-yr risk <8%, the odds ratio (OR), adjusted for age, platelet count, hsCRP, and hypertension, was 3.3 (1.2-8.9) and adjusted for age, platelet count, hsCRP, and MS, was 4.5 (1.6-11.8). The age-, platelet count-, hsCRP- and hypertension-adjusted OR for a 10-yr CHD risk score >or=8% was 0.8 (0.5-1.3) for hsCRP and 3.9 (1.6-9.4) for hypertension. The age-, platelet count-, hsCRP- and MS -adjusted OR for a 10-yr CHD risk score >or=8% was 0.7 (0.4-1.2) for hsCRP and 7.9 (2.6-24.5) for MS. CONCLUSION: Elevated PDMPs are associated with the 10-yr CHD risk score in healthy men.

Correlation and association of plasma interleukin-6 and plasma platelet-derived microparticles, markers of activated platelets, in healthy individuals.

INTRODUCTION: The aim of this study was to clarify the correlation and association of plasma IL-6 and PDMPs, both of which are associated with metabolic syndrome, in healthy individuals. MATERIALS AND METHODS: We conducted a cross-sectional study of 464 healthy Japanese volunteers (210 men and 254 women, median age 39 and 35years, respectively) who had no signs, symptoms or history of cardiovascular- or cerebrovascular disease and took no medications. We assayed their IL-6 levels with a conventional ELISA kit and their PDMP levels by ELISA and monoclonal antibodies against CD42b and CD42a (glycoprotein Ib and IX). RESULTS: By multivariate analysis, the plasma level of PDMP was correlated with diastolic blood pressure (p=0.015), platelet count (p<0.001), high sensitivity C-reactive protein, and the plasma level of IL-6 (p<0.001) in men (R(2)=0.454, p<0.001) and was correlated with platelet count (p<0.001) and the plasma level of IL-6 (p<0.001) in women (R(2)=0.159, p<0.001). Quartile range of plasma level of IL-6 was associated with plasma level of PDMP after adjustment for diastolic blood pressure, platelet count, and high sensitivity C-reactive protein in men (p<0.001) and associated with plasma level of PDMP after adjustment for platelet count in women (p<0.001). CONCLUSIONS: These results suggest the plasma IL-6 is correlated and associated with the plasma PDMPs, markers of activated platelets in healthy individuals.

Cerebral microbleeds predict first-ever symptomatic cerebrovascular events.

OBJECTIVE: Cerebral microbleeds (CMB) on gradient-echo T2*-weighted magnetic resonance image (MRI) are frequently seen in patients with cerebral diseases. In this observational study we assessed whether CMB are a predictive factor for first-ever cerebrovascular events. PATIENTS AND METHODS: This study consisted of 698 subjects without a history of symptomatic cerebrovascular events, who received gradient-echo T2*-weighted MRI for 3 months between November 2003 and January 2004 in Kishiwada City Hospital, Osaka, Japan. These subjects were then observed as outpatients for over 3.5 years. RESULTS: The prevalence of CMB at baseline was 17.0% (119/698) in this population, and the follow-up rate was 51%. A total of 36 first-ever symptomatic cerebrovascular events were observed during the 3 and a half-year follow-up period. First-ever symptomatic cerebrovascular events occurred significantly more frequently in subjects with CMB (15 cases) than those without CMB (21 cases) (p=0.001). Even after adjusting for age, sex and hypertension, it was revealed that the presence of CMB was an independent predictor for the first-ever symptomatic cerebrovascular event by using the Cox proportional hazards model (hazard ratio, 2.87; 95% CI, 1.27-6.48; p=0.01). CONCLUSION: The presence of CMB is an independent predictor of first-ever symptomatic cerebrovascular diseases.

Cerebral microbleeds in patients with intracerebral hemorrhage are associated with previous cerebrovascular diseases and white matter hyperintensity, but not with regular use of antiplatelet agents.

The validity of regular use of antiplatelet agents was retrospectively assessed in 106 patients with intracerebral hemorrhage (ICH) (supratentorial hemorrhage 92, lobar 22 and deep 70; and infratentorial hemorrhage 14) who underwent T(2)*-weighted gradient-echo magnetic resonance (MR) imaging between January 2005 and December 2006 in Kishiwada City Hospital. The prevalence of cerebral microbleeds was 54.7% (58/106), and the presence was significantly associated with higher age (odds ratio 3.09, p = 0.007), presence of white matter hyperintensity on T(2)-weighted MR imaging (odds ratio 2.36, p = 0.032), and previous ICH and/or cerebral infarction (odds ratio 4.77, p = 0.020). Previous ICH and/or cerebral infarction was independently associated with the presence of cerebral microbleeds after adjustment for age, white matter hyperintensity, and hypertension (odds ratio 4.07, p = 0.043). Regular use of antiplatelet agents was not associated with the presence of cerebral microbleeds, whether the patients had cerebrovascular diseases or not. Our findings suggest that antiplatelet medication can be justified for patients with cerebral microbleeds.

Bilateral acute subdural hematomas with intracerebral hemorrhage without subarachnoid hemorrhage, caused by rupture of an internal carotid artery dorsal wall aneurysm. Case report.

A 45-year-old man presented with bilateral acute subdural hematomas (ASDHs) without subarachnoid hemorrhage (SAH). He was found comatose in a parked car. Computed tomography showed left frontal intracerebral hemorrhage (ICH) and bilateral ASDHs but no signs of SAH. Magnetic resonance angiography demonstrated an internal carotid artery dorsal wall aneurysm. Emergent surgical intervention was performed. However, he died of cerebral herniation 6 days later. We inferred that massive intracranial bleeding might have ruptured through the cortex and lacerated the arachnoid membrane. Aneurysm rupture generally results in unilateral SDH, whereas trauma is the usual cause of bilateral ASDHs with ICH. Our case suggests that ruptured aneurysm should be considered in patients with non-traumatic bilateral ASDHs without SAH.

A priority treatment of the intraventricular hemorrhage (IVH) should be performed in the patients suffering intracerebral hemorrhage with large IVH.

BACKGROUND: In patients suffering from intracerebral hemorrhage (ICH) with ventricular hemorrhage (IVH), the IVH severity is thought to be associated with prognosis. Therefore, treating IVH may be a beneficial therapeutic target. In this study, by examining the associations among IVH severity, hydrocephalus, initial level of consciousness and prognosis, we attempted to identify which grade of IVH severity should be considered for surgical treatment. METHODS: One hundred twenty-nine patients with spontaneous supratentorial ICH treated in our hospital between 2005 and 2006 were screened in this study. Of these patients, 100 with an ICH volume less than 60 ml were categorized into either the ICH patients without IVH (no-IVH) group (n=65) or the ICH patients with IVH (IVH) group (n=35). The Karnofsky Performance Status (KPS) scale assessed at the time of discharge was employed as an outcome index, and a KPS score of or=6) than in patients with low to moderate IVH volume (Graeb score

Normal pressure hydrocephalus after radiosurgery for sphenoid ridge meningioma.

Normal pressure hydrocephalus after radiosurgery for meningioma has rarely been reported. We report such a case and discuss the role of radiosurgery in the development of hydrocephalus. A 75-year-old man with a growing tumor underwent linac-based radiosurgery. The tumor received 16 Gy to the 80% isodose line. He exhibited the triad of symptoms of normal pressure hydrocephalus and became bedridden three months after radiosurgery. Dilated ventricles were demonstrated with MRI. Examination of the cerebrospinal fluid revealed a high level of protein. The patient underwent a ventriculoperitoneal shunt and recovered well.

Circulating oxidized LDL, measured with FOH1a/DLH3 antibody, is associated with metabolic syndrome and the coronary heart disease risk score in healthy Japanese.

BACKGROUND AND PURPOSE: The objective of this study was to clarify the relationship between circulating oxidized LDL (oxLDL) and metabolic syndrome (MS) and the coronary heart disease (CHD) risk score. METHODS: We conducted a cross-sectional study of healthy volunteers who had no signs, symptoms or history of cardiovascular or cerebrovascular disease and took no medications. We studied 382 Japanese volunteers, 190 men and 192 women (median age 41 and 38 years, respectively). We used an ELISA kit and a monoclonal oxLDL antibody, FOH1a/DLH3, to measure circulating oxLDL. RESULTS: The odds ratio (OR) for elevated oxLDL in individuals with MS compared to those without MS, adjusted for age and sex, was 1.94 (range 1.00-3.78). In individuals with a predicted Framingham 10-year risk for CHD>5% (corresponding with the highest quartile), compared to those with a predicted 10-year risk<5%, the OR, adjusted for age, sex, smoking, and LDL cholesterol, was 2.51 (1.17-5.36). The age-, sex-, smoking- and LDL cholesterol-adjusted OR for a 10-year CHD risk score >5% was 1.03 (1.01-1.04) for LDL cholesterol and 11.7 (4.69-29.0) for smoking. CONCLUSIONS: Elevated oxLDL is associated with the presence of MS and the CHD risk score in healthy people.

Level, distribution and correlates of platelet-derived microparticles in healthy individuals with special reference to the metabolic syndrome.

Platelet-derived microparticles (PDMPs), a procoagulant factor, are reportedly elevated in type 2 diabetes mellitus and acute coronary syndrome. The metabolic syndrome (MS) is strongly associated with cardio- and cerebrovascular disease-related atherothrombotic events. To clarify the level, distribution and correlates of PDMPs with special reference to MS, we conducted a cross-sectional study of 467 healthy Japanese volunteers without signs, symptoms, or a history of cardio- or cerebrovascular disease. They were 211 men and 256 women (median age 39 and 35 years, respectively). Using an ELISA kit and monoclonal antibodies against CD42b and CD42a (glycoprotein Ib and IX) we assayed the PDMP levels. Total cholesterol, low-density and high-density lipoprotein cholesterol, remnant cholesterol, triglycerides, C-reactive protein, and traditional cardiovascular risk factors were also recorded. There was a significant difference in the level of PDMPs between men and women. The median value and the interquartile range of PDMPs was 8.3 IU/ml and 6.2-10.5 IU/ml and 6.8 IU/ml and 5.2-8.6 IU/ml, respectively, in men and women. PDMPs were significantly associated with MS criteria in men (p < 0.001) and women (p = 0.040). Logistic regression analysis revealed a significant odds ratio of 3.9 [95% confidence interval (CI): 1.4-10.5] in men and of 4.2 [95% CI: 1.6-10.7] in the entire study population. Our results suggest that PDMPs identified by glycoprotein CD42b and CD42a are positively associated with MS.

Traumatic vertebro-vertebral arteriovenous fistula manifesting as radiculopathy. Case report.

A 58-year-old man presented with a traumatic vertebro-vertebral arteriovenous fistula (VVAVF) after attempting suicide by thrusting scissors into his right anterior cervical region. Two months later he noticed weakness and numbness of the right upper extremity. Examination revealed bruit in the right neck, no cranial nerve palsy, and weakness of the right deltoid and biceps muscles. Hypalgesia and hypesthesia were noted in the right C5 and C6 dermatomes. Magnetic resonance imaging demonstrated a mass lesion on the right ventral aspect of the spinal canal from C2 to C7. Right vertebral artery angiography showed a pseudoaneurysm of the right vertebral artery and a high-flow arteriovenous fistula between the right vertebral artery and vein. The right vertebral artery was occluded with detachable coils because the fistula showed high blood flow and the right posterior inferior cerebellar artery was well opacified from the left vertebral artery. This procedure resulted in complete obliteration of the arteriovenous fistula. The preoperative motor and sensory symptoms improved. Endovascular treatment by coil embolization was effective in our patient with traumatic VVAVF.

MATH-1 production by an adult medulloblastoma suggestive of a cerebellar external granule cell precursor origin.

Radiological, histological and molecular findings in an uncommon adult case of cerebellar medulloblastoma suggested an external granular cell precursor origin. This 19-year-old woman had a 1-month history of progressively worsening headache. Neuroimaging studies demonstrated a homogeneously enhanced well-circumscribed mass lesion in the right cerebellar hemisphere and she underwent surgery. Postoperative neuronal imaging studies showed that the tumor located in the cerebellar folia had been removed totally. Pathological examination identified it as a desmoplastic medulloblastoma with subpial and subarachnoid infiltration and some infiltration into the molecular and granular layer via the perivascular space. Polymerase chain reaction and immunohistochemical findings revealed the presence of MATH-1, expressed in cerebellar external granule cell precursors during fetal development, in the tumor cells. These findings suggest that the tumor arose from external granule cell precursors of the cerebellum and that it was therefore of neuronal lineage.

Factors relating to terminally ill cancer patients' willingness to continue living at home during the early phase of home care after discharge from clinical cancer centers in Japan.

OBJECTIVE: To assess the willingness of Japanese terminally ill cancer patients to continue living at home during the early phase of home care after discharge from a Clinical Cancer Center (CCC) in Japan, and to identify factors relating to their willingness to continue living at home. METHODS: A cross-sectional questionnaire survey of a convenient sample of both Japanese terminally ill cancer patients and their caregivers (PFCs) was conducted (n = 294, effective response rate 25.0%). Questionnaires were mailed and medical records were accessed for 73 pairs of respondents, comprising one terminally ill cancer patient and one PFC. RESULTS: At about 10 days after discharge, 64 patients (88%) wished to continue living at home. A hierarchical logistic regression analysis was performed on the data. It was found that the fewer the medical treatments undergone (OR = 0.20, 95% CI: 0.05-0.72), the higher the patients' perception that their condition was consistent with care at home (OR = 2.77, 95% CI: 1.08-8.62) and with their functional well-being (OR = 1.45, 95% CI: 1.08-2.17). In addition, the higher the caregivers' satisfaction with life (OR = 2.37, 95% CI: 1.15-5.77), the more willing patients tended to be to continue living at home. SIGNIFICANT OF RESULTS: The willingness of Japanese terminally ill cancer patients to continue living at home appears to be affected by caregiver status. This indicates a need for discharging facilities to monitor the state of home assistance and to investigate the nature of assistance required for continuing home care.

Bright pituitary stalk on MR T1-weighted image: damming up phenomenon of the neurosecretory granules.

Characteristic findings of the pituitary stalk on magnetic resonance (MR) imaging, which suggest a damming-up phenomenon of neurosecretory granules, were reported. Neurosecretory granules containing vasopressin influence the signal intensity on MR T1-weighted image (T1WI). The normal posterior lobe of the pituitary gland appears as a bright signal on T1WI. The bright signal of the posterior lobe represents the normal content of neurosecretory granules and disappears in patients with central diabetes insipidus. The normal pituitary stalk appears as a low-intermediate intensity signal on sagittal and coronal T1WIs with 3 mm-slice thickness. The pituitary stalk appeared as a bright signal in 20 patients; 13 with pituitary adenoma, 4 with an intrasellar cystic lesion, one with cavernous sinus mass, and 2 with no abnormal MR findings. The pituitary stalk was not severed in any of the cases. The normal bright signal of the posterior lobe disappeared in 17 patients. No patients suffered from symptoms of central diabetes insipidus when the bright pituitary stalk appeared. It is suggested that the origin of the bright signal in the pituitary stalk is the damming up and accumulation of neurosecretory granules in the nerve fibers of the hypothalamohypophyseal tract obstructed by adenoma, postoperative scarring, cystic mass and so on. Probably, the damming-up phenomenon on MR imaging represents the functional integrity of the hypothalamo-neurohypophyseal system, and should be distinguished from an ectopic posterior lobe formation which is caused by stalk transection.