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Background: Permanent metallic flow diverter (FD) implantation for treatment of intracranial aneurysms requires antiplatelet therapy for an unclear duration and restricts postprocedural endovascular access. Bioresorbable FDs are being developed as a solution to these issues, but the biological reactions and phenomena induced by bioresorbable FDs have not been compared with those of metallic FDs. Methods: We have developed a bioresorbable poly (L-lactic acid) FD (PLLA-FD) and compared it with an FD composed of cobalt-chromium and platinum-tungsten (CoCr-FD). FD mechanical performance and in vitro degradation of the PLLA-FD were evaluated. For in vivo testing in a rabbit aneurysm model, FDs were implanted at the aneurysm site and the abdominal aorta in the PLLA-FD group (n=21) and CoCr-FD group (n=15). Aneurysm occlusion rate, branch patency, and thrombus formation within the FD were evaluated at 3, 6, and 12 months. Local inflammation and neointima structure were also evaluated. Results: Mean strut, porosity, and pore density for the PLLA-FD were 41.7 μm, 60%, and 20 pores per mm 2 , respectively. The proportion of aneurysms exhibiting a neck remnant or complete occlusion did not significantly differ between the groups; however, the complete occlusion rate was significantly higher in the PLLA-FD group (48% versus 13%; P =0.0399). Branch occlusion and thrombus formation within the FD were not observed in either group. In the PLLA-FD group, CD68 immunoreactivity was significantly higher, but neointimal thickness decreased over time and did not significantly differ from that of the CoCr-FD at 12 months. Collagen fibers significantly predominated over elastic fibers in the neointima in the PLLA-FD group. The opposite was observed in the CoCr-FD group. Conclusions: The PLLA-FD was as effective as the CoCr-FD in this study and is feasible for aneurysm treatment. No morphological or pathological problems were observed with PLLA-FD over a 1-year period.

As an emerging additive manufacturing (AM) technique, melt electrospinning writing (MEW) is used to fabricate three-dimensional (3D) submicron filament-based scaffolds with adjustable pore size and customized structure for bone regeneration. Poly(L-lactic acid) (PLLA) scaffold with excellent biodegradability and biocompatibility is first successfully manufactured using our self-assembled MEW device. However, the ultralow cell affinity and poor bioactivity severely hamper their practical applications in bone tissue engineering. These issues are caused by the severe inherent biologically inert, hydrophobicity as well as the smooth surface of the MEW PLLA filaments. In this study, a green and robust alkaline method is applied to modify the scaffold surface and to improve the bioactivity of the MEW PLLA scaffold. Without deterioration in mechanical property but robust surface hydrophilicity, the optimal MEW PLLA scaffold shows promoted surface roughness, enhanced filament tensile modulus (~ 2 folds of the as-prepared sample), and boosted crystallizability (ultrahigh WAXD intensity). Moreover, after being cultured with KUSA-A1 cells, the 0.5 M NaOH, 2 h treated MEW PLLA scaffold exhibits higher osteoinductive ability and increased immature bone tissue amounts (3 times of controlled scaffold). Thus, the flexible surface functionalization by the specific alkaline treatment was found to be an effective method for the preparation of bioactivated MEW PLLA scaffolds with promoted bone regeneration.

The thermally sensitive polymer, poly ( l -lactic acid) PLLA, is first printed to a high-resolution object using an advanced 3D printing technology, called melt electrowriting (MEW). The MEW processing conditions are systematically investigated to manufacture PLLA scaffolds with adjustable filament diameter and pore size for the application of bone tissue engineering. To this end, the relationships among the rheological behavior of the molten polymer, the electro-hydrodynamics of the jet, and the processing parameters (applied voltage, collection speed, and flow rate) are illuminated. The scaffold with relatively high deposition accuracy and crystallinity of PLLA is achieved when the printing speed was set slightly above the critical translation speed. The MEW PLLA scaffold with filament diameter of 40 μm and pore size of 200 μm is evaluated with KUSA-A1 cells to prove its in vitro potential. This is a milestone work for MEW since it supplies one of the best strategies to design and manufacture an essential biobased polymer for tissue engineering.

Intracranial artery stenosis (ICAS) is the most common cause of ischemic stroke worldwide. RNF213 single nucleotide variant c.14429G > A (p.Arg4810Lys, rs112735431) was recently reported to be associated with ICAS in East Asians. However, the disease susceptibility of other RNF213 variants has not been clarified. This study comprehensively investigated ICAS-associated RNF213 variants in a pool of 168 Japanese ICAS patients and 1,194 control subjects. We found 138 nonsynonymous germline variants by target resequencing of all coding exons in RNF213. Association study between ICAS patients and control subjects revealed that only p.Arg4810Lys had significant association with ICAS (P = 1.5 × 10–28, odds ratio = 29.3, 95% confidence interval 15.31–56.2 [dominant model]). Fourteen of 138 variants were rare variants detected in ICAS patients not harboring p.Arg4810Lys variant. Two of these rare variants (p.Cys118Arg and p.Leu2356Phe) consistent with variants previously reported in moyamoya disease patients characterized by stenosis of intracranial artery and association with RNF213, and three rare variants (p.Ser193Gly, p.Val1817Leu, and p.Asp3329Tyr) were found neither in control subjects and Single Nucleotide Polymorphism Database. The present findings may improve our understanding of the genetic background of intracranial artery stenosis.

Optically transparent fibroin nanofiber (FNF) paper was obtained without using binders by passing a fibroin suspension through a mechanical nanofibrillation process using a water-jet. The optical transmittance of the nanofiber paper increased with the number of passes through the water-jet and reached 79.3% and 80.3% of light at 600 nm after 15 and 30 passes, respectively. The fibroin of the transparent nanopaper remained fibrous with a native β-sheet secondary structure. Therefore, the transparent nanopaper showed a high elastic modulus, high thermal durability, and low thermal expansion. This novel protein material, which can be fabricated without toxic chemicals or organic solvents, is bio-friendly and shows promise for new applications in biocompatible photonic devices.

Background and Purpose— Recently, we reported a common genetic variant, ring finger protein 213 ( RNF213 ) c.14576G>A variant, a susceptibility gene for moyamoya disease (MMD), among patients with intracranial major artery stenosis/occlusion (ICASO) in a selected Japanese population. The aim of this 2-center–based case–control study was to confirm our previous finding in a larger population. Methods— Study participants were recruited from The University of Tokyo Hospital and Kanto Neurosurgical Hospital. The occurrence rate of c.14576G>A variant was investigated in 323 patients, 22 with definite MMD, 8 with unilateral MMD, 84 with ICASO in the absence of MMD (non-MMD ICASO), 34 with extracranial carotid atherosclerosis, 44 with cerebral aneurysm, 21 with intracerebral hemorrhage, and 110 control subjects. Results— RNF213 c.14576G>A variant was found in 1.8% (2/110) of the normal control group and had significant associations with definite MMD ( P P =0.0001; odds ratio, 54.0; 95% confidence interval, 7.5–386.8), and non-MMD ICASO ( P Conclusions— A particular subset of patients with various phenotypes of ICASO has a common genetic variant, RNF213 c.14576G>A, indicating that RNF213 c.14576G>A variant is a high-risk allele for ICASO.

Background Cerebral metabolism can be disrupted by venous congestion in patients with intracranial dural arteriovenous fistula (DAVF), which may lead to adverse neurological outcomes. However, there are no clear indicators to guide cerebral evaluation and treatment selection in cases of DAVF. We describe a patient with a DAVF whose proton magnetic resonance spectroscopy ( 1 H-MRS) findings were associated with improvements in clinical status. Case Description An elderly woman with a history of myocardial infarction presented with progressive dementia, aphasia, and a severe headache. We detected a transverse-sigmoid sinus DAVF, as well as abnormal levels of lactate and N -acetylaspartic acid (NAA) in the 1 H-MRS, and successfully treated the patient using surgical sinus skeletonization. However, follow-up 1 H-MRS revealed inconsistent reversals in the levels of lactate and NAA. In addition, we calculated the NAA/creatinine ratios from before and after surgery, which revealed postoperative increases in the ratios for the left temporal, right parietal, and left parietal regions. These increases occurred concurrently with improvements in the patient's cognitive function. Conclusions 1 H-MRS may be useful for pretreatment detection of increased lactate levels, decreased NAA levels, and/or decreased NAA/creatinine ratios. These findings may indicate poorer cerebral metabolism, and show a need for more aggressive treatment. Furthermore, 1 H-MRS may be useful for evaluating the effect of conservative treatment and for indicating conversion to a more aggressive treatment.

Persistent primitive hypoglossal artery (PPHA) is a persistent carotid-basilar anastomosis. It rarely remains at birth. It occasionally may be a risk for ischemia and embolic infarction to the posterior cerebral circulation, especially in patients with carotid stenosis proximal to the origin of persistent primitive arteries. We describe a case of a 60-year-old woman with asymptomatic internal carotid artery (ICA) stenosis and ipsilateral PPHA successfully treated by carotid artery stenting (CAS). A few cases of CAS for ICA stenosis with PPHA have been reported, but the strategy and methods in each case were different because of its unique anatomy and hemodynamics. It is essential to prevent distal embolisms and preserve blood flow at the territory of both the ICA and PPHA. The protection method should be selected carefully. We review the literature and discuss appropriate treatment strategies.

Poly(tetrafluoroethylene) (PTFE) fiber with a superior mechanical property was prepared directly from its emulsion by the novel manufacturing process. The PTFE emulsion turned into a paste when a high shear flow was applied and the paste was extruded through a nozzle into a strand consisting of fine PTFE particles. The diameter of the strand was reduced stepwise by applying the die-drawing process through a conical die at a low temperature. The strand was further die-drawn down at elevated temperatures into fine PTFE fibers with a highly oriented crystalline structure. The crystalline orientation factor of the PTFE fiber reached very close to unity. Although the fibers obtained have a very high tensile modulus, the tensile strength was not as high as that expected from the crystalline orientation, suggesting that the presence of some defects in the PTFE fiber formed in the instantaneous deformation.

For the purpose of nationwide surveillance of the antimicrobial susceptibility of bacterial respiratory pathogens collected from patients in Japan, the Japanese Society of Chemotherapy conducted a third year of nationwide surveillance during the period from January to April 2008. A total of 1,097 strains were collected from clinical specimens obtained from well-diagnosed adult patients with respiratory tract infections. Susceptibility testing was evaluable with 987 strains (189 Staphylococcus aureus, 211 Streptococcus pneumoniae, 6 Streptococcus pyogenes, 187 Haemophilus influenzae, 106 Moraxella catarrhalis, 126 Klebsiella pneumoniae, and 162 Pseudomonas aeruginosa). A total of 44 antibacterial agents, including 26 β-lactams (four penicillins, three penicillins in combination with β-lactamase inhibitors, four oral cephems, eight parenteral cephems, one monobactam, five carbapenems, and one penem), three aminoglycosides, four macrolides (including a ketolide), one lincosamide, one tetracycline, two glycopeptides, six fluoroquinolones, and one oxazolidinone were used for the study. Analysis was conducted at the central reference laboratory according to the method recommended by the Clinical and Laboratory Standard Institute (CLSI). The incidence of methicillin-resistant S. aureus (MRSA) was as high as 59.8%, and those of penicillin-intermediate and penicillin-resistant S. pneumoniae (PISP and PRSP) were 35.5 and 11.8%, respectively. Among H. influenzae, 13.9% of them were found to be β-lactamase-non-producing ampicillin (ABPC)-intermediately resistant (BLNAI), 26.7% to be β-lactamase-non-producing ABPC-resistant (BLNAR), and 5.3% to be β-lactamase-producing ABPC-resistant (BLPAR) strains. A high frequency (76.5%) of β-lactamase-producing strains was suspected in Moraxella catarrhalis isolates. Four (3.2%) extended-spectrum β-lactamase-producing K. pneumoniae were found among 126 strains. Four isolates (2.5%) of P.aeruginosa were found to be metallo β-lactamase-producing strains, including three (1.9%) suspected multidrug-resistant strains showing resistance to imipenem, amikacin, and ciprofloxacin. Continual national surveillance of the antimicrobial susceptibility of respiratory pathogens is crucial in order to monitor changing patterns of susceptibility and to be able to update treatment recommendations on a regular basis.

Montmorillonites (MMT) treated with various organic amines were added to the acrylic rubber in the polymerization process. Effects of the kind of organic amines, the contents of added MMT, and the method of the addition of MMT to the acrylic rubber on the dispersion state of MMT in the matrix and on the mechanical property of the obtained rubber were studied. As a result, the remarkable improvement of the mechanical property was achieved when 5 wt% of MMT organically treated with the laurylamine was added, although the deterioration of the mechanical property was observed at higher MMT contents. On the other hand, the mechanical property of the sample, to which MMT was added in the solution state, was improved gradually with the MMT content without showing a significant deterioration. Although the addition of organically treated MMT having a hydrophobic surface was added in the aqueous emulsion polymerization system, an excellent dispersion state was achieved when 5 wt% of MMT treated with laurylamine was added. Moreover, comparing with the friction property, the heat resistance, and the water resistance of the acrylic rubber added with MMT to those of the acrylic rubber added with the white carbon, it was proved that the addition of MMT significantly improve various physical and practical properties of the acrylic rubber.

Summary Background Currently, there is no available test for monitoring the clinical effect of active tuberculosis (TB) disease treatment. Therefore, we studied the usefulness of two commercial IFN-γ assays (QuantiFERON TB-2G (QFT-2G) and T-SPOT.TB tests) for monitoring clinical efficacy. Methods The subjects were 40 patients with active TB disease. These two commercial IFN-γ assays were carried out every three months during active TB disease treatment. Results While the positive response rate of QFT-2G test significantly decreased from 83% at treatment initiation to 58% at treatment completion, that of T-SPOT.TB decreased from 90% at treatment initiation to 63% at treatment completion. Although there was a significant decrease in patients with TB infection showing positive responses for ESAT-6 only or CFP-10 only antigens on both IFN-γ assays, there was no significant decrease in patients showing positive responses for both ESAT-6 and CFP-10 antigens on both IFN-γ assays. On both QFT-2G test and T-SPOT.TB test, the mean values of the IFN-γ levels in the pre- and post-treatment responses showed significantly decreased responses to CFP-10. On the other hand, smear conversion results of clinical specimens were obtained in all patients at treatment completion. Conclusions Antituberculous treatment induced a significant decrease in T-cell responses to separate ESAT-6 and CFP-10 antigens as measured by both IFN-γ assays. Although IFN-γ assays might be later than smear conversion results of clinical specimens, the quantitative responses especially to CFP-10 may be one of the useful monitoring markers of clinical efficacy for active TB disease treatment.

Montmorillonites organically treated with various alkylamines were filled to the acrylic rubber and various properties including mechanical, oil resistance, and abrasion were investigated. Montmorillonite tended to exfoliate after the organic treatment and uniformly dispersed in the acrylic rubber. This uniform dispersion of the filler resulted in the improvement of the mechanical property. Number of carbon atoms in the alkylamine used for the organic treatment increased the swelling with oil at high temperature. Abrasion wear rate of the acrylic rubber was reduced when organically treated montmorillonite was well dispersed in the matrix.

A case of pulmonary cryptococcosis with focal endobronchial polypoid lesions is described. A 64-year-old woman consulted our hospital for further evaluation of an abnormal shadow on a chest radiograph. She had been prescribed corticosteroid for rheumatoid arthritis. Chest radiographs revealed an infiltrative shadow in the right lower and left middle and lower lung fields, and chest computed tomography (CT) revealed bilateral airspace consolidations and multiple nodules. A bronchoscopic finding revealed white polypoid lesions at the orifice of the posterior basal bronchus in the left lower lobe. Histopathological examination of transbronchial biopsy specimens demonstrated cryptococcal organisms. After fluconazole therapy for 4 months, the infiltrate had decreased in size and the bronchial polypoid lesions had disappeared.

Although patients with risk factors for tuberculosis have increased with the increased use of immunosuppressive therapy, there have been few reports about differences in clinical findings between immunocompromised patients and nonimmunocompromised patients with pulmonary tuberculosis. Therefore, we investigated differences between the clinical features of immunocompromised patients with pulmonary tuberculosis and those of nonimmunocompromised patients in the past decade. We analyzed findings in 840 patients (312 immunocompromised and 528 nonimmunocompromised) with pulmonary tuberculosis who were found to be culture-positive for Mycobacterium tuberculosis between January 1997 and December 2006. The characteristic clinical findings of the immunocompromised patients, compared with findings in the nonimmunocompromised group, were as follows: (1) an increase in the number of patients with respiratory symptoms during the period of follow-up of underlying diseases; (2) an increase in the number of patients in a hyponutritional state and with a negative response for the tuberculin skin test; (3) an increase in the number of microbiologically smear-positive sputum specimens; (4) an increase in the number of patients with atypical radiological findings, such as a few cavities or calcification, bilateral and expansive consolidation, miliary shadows, and mediastinal and/or hilar lymphadenopathy ; (5) an increase in the number of patients with misdiagnosed pneumonia at admission; and (6) an increase in the mortality rate. We concluded that, among the immunocompromised patients with pulmonary tuberculosis, there were many patients with atypical radiological findings and with smear-positive findings for acid-fast bacilli examination that was carried out to isolate M. tuberculosis (which had become infectious). We must perform the acid-fast bacilli examination for patients who have a fever and continuous cough, and antituberculous drugs should be administered as soon as possible when the results are positive.

To achieve appropriate efficacy of paclitaxel (PTX) used in drug eluting stents, uniform PTX coating on the stent and increased initial release of PTX leading to immediate therapeutic level of the drug are required. The present study investigated whether either restriction of crystal growth though sonication and subsequent liquid nitrogen cooling, or formation of anhydrous PTX crystals through heating microcrystals after seeding and crystal growth could increase PTX initial release coated on a fully-bioabsorbable poly(L-lactic acid) stent. The sonication and subsequent liquid nitrogen cooling of the growing PTX crystals could prevent stable attachment of the crystals onto the stent surface. In addition, the initial PTX release from the stent applied sonication during the crystal growth process followed by heating showed five times as high as the stent without heating, which indicated the heating improved the PTX release from the stent at early phase. These results suggested that PTX was changed into an anhydrous soluble form.

A first clinically-used, fully-bioabsorbable poly(L-lactic acid) (PLLA) stent was coated with microcrystals of paclitaxel (PTX), antiproliferative agent through seeding and/or crystal growing technique to investigate the drug properties on the stent surface and drug release behavior from the stent. PTX particles subject to only seeding process was peeled off after stent compression, while less PTX was coated on the stent subject to only crystal growth without seeding. PLLA stent with both processes could stably maintain an increased amount of PTX on its surface. The maximum amount of initial release (10 μg/cm2) was found in the sample only with seeding, which decreased to 3 μg/cm2 or below after one week. Also in the PLLA stent only with crystal growth, release amount decreased after one week. In the PLLA stent with seeding and crystal growth, formation of needle-like PTX crystals on the surface resulted in decreased initial release and lower solubility after hydration in phosphate buffered solution compared to other types of stent with different procedures. It is suggested that both seeding and crystal growth are required for stable application of PTX on fully-bioabsorbable PLLA stent and needle-like crystals containing water have lower aqueous solubility resulting in decreased PTX release.

Object. To evaluate a newly developed enzyme-linked immunosorbent assay (ELISA) (Hitazyme C. pneumoniae) detecting Chlamydophila pneumoniae-specific immunoglobulin M (IgM) antibody, we compared the assay with culturing, immunoblotting and the microimmunofluorescence (MIF) test. Patients and Methods. Two hundred five patients with stable chronic lung diseases without acute respiratory tract infections (ARTIs) and 116 healthy volunteers without ARTIs were enrolled in this study. Nasopharyngeal swab specimens and sera were obtained from all subjects for isolation and serological testing of C. pneumoniae. Results. C. pneumoniae IgM-positive results were observed in 16.5% of patients with stable chronic lung diseases and in 8.6% of asymptomatic healthy subjects. However, there were no positive cases with cell culture, immunoblot or MIF test. In addition, no cases with a significant increase in IgA or IgG antibody titer for the ELISA kit and MIF test between paired sera were observed in the followed-up groups. IgM-positive cases were more frequent among patients with chronic obstructive pulmonary disease (p=0.1566), collagen disease-associated interstitial lung disease (p

Two research groups have reported the effect of genetic polymorphisms of CYP2C9 and CYP2C19 on the pharmacokinetic parameters of phenytoin in Japanese epileptic patients. We measured the plasma phenytoin concentrations at steady-state in 20 routinely treated Japanese patients, and evaluated the usefulness of genotyping the CYP2C subfamily in predicting plasma concentrations and determining the dosage regimens of phenytoin. The plasma phenytoin concentrations predicted by genotypes of the CYP2C subfamily were well correlated with the observed concentrations in some patients, but not in some patients. The pharmacokinetic parameters (Vmax and Km) in individual patients, which were obtained from population estimates according to Bayes' theorem, showed considerable interindividual variability even among patients with the same genotype. In addition, we assessed the effect of plasma protein binding on the residual interindividual variability in the clearance of phenytoin; however, there was no significant correlation between the unbound fraction and the intrinsic metabolic activity (Vmax/Km). These findings suggested that the mechanism responsible for the large variability in the clearance of phenytoin is not completely resolved, and that we should not overestimate the usefulness of genotyping the CYP2C subfamily in determining the dosage regimens of the drug.

Clinical features of vertebral artery dissections presenting with isolated headache or neck pain were investigated, and management was clarified. Forty cases that had only pain at the time of onset, showed neither subarachnoid hemorrhage nor cerebral infarction, and were diagnosed as having vertebral artery dissection by angiography were targeted. In the cases accompanied with aneurysmal dilatation, application of surgical treatment was examined. In other cases, the course was observed by MRA. In the first 18 months, 17 cases were examined. Among them, aneurysmal dilatation was found in 4 cases, and they underwent direct surgery. The other 13 cases were observed: 2 cases showed complete occlusion (at 1.5 months and 5 months, respectively), 3 cases showed no change, and 8 cases showed spontaneous improvement. In the course, neither subarachnoid hemorrhage nor cerebral infarction developed. Therefore, in the last 18 months, observation of the course was attempted as much as possible for the cases, including those of aneurysmal dilatation. In the period, 23 cases were examined, and aneurysmal dilatation expanded in 2 cases (at 2.5 months and 4 months, respectively). The lesion was obstructed by direct surgery in 1 case and by intravascular treatment in the other. Of the remaining 21 cases, 2 showed no changes in the course by MRA and 19 exhibited spontaneous improvement. In the course, neither subarachnoid hemorrhage nor cerebral infarction developed in any case. For the treatment of vertebral artery dissection presenting with only pain, observation of the course by MRA was effective. Changes occurred in the lesions within several months after onset, and spontaneous improvement occurred in many cases. Therefore, observation of the course is basically sufficient for management. When aneurysmal dilatation is expanded in the course, direct surgery or intravascular treatment is recommended.

Background Quasi-moyamoya disease (MMD) and MMD (definite MMD) have similar cerebral angiographic features, but whether these related diseases have similar etiology or genetic background remains unclear. Recently, we have reported that the recently identified MMD susceptibility gene variant RNF213 c.14576G>A (rs112735431) was associated with atherosclerotic intracranial major artery stenosis/occlusion. The present study investigated the occurrence of RNF 213 c.14576G>A in patients with nonatherosclerotic quasi-MMD. Methods This study was a 2-hospital–based case–control study conducted at the Department of Neurosurgery, The University of Tokyo Hospital and Kanto Neurosurgical Hospital. A total of 87 Japanese patients who agreed to participate in this study were enrolled among both new and revisiting outpatients from October 2011 to December 2013 as follows: 78 patients with definite MMD and 9 patients with nonatherosclerotic quasi-MMD. Results The 9 patients with nonatherosclerotic quasi-MMD included 3 patients with previous irradiation, 2 with hyperthyroidism, 1 with Turner syndrome, 1 with meningitis, 1 with Behcet disease, and 1 with idiopathic pachymeningitis. The 78 patients with definite MMD included 66 patients (84.6%) with the c.14576G>A variant (64 heterozygotes and 2 homozygous). In contrast, no patients with nonatherosclerotic quasi-MMD had the variant. Conclusions Nonatherosclerotic quasi-MMD did not have RNF213 c.14576G>A variant. Moyamoya disease and related diseases might be classified by genetic analysis of the RNF213 c.14576G>A genotype. Further larger studies are required to confirm the present findings.

Escherichia coli pneumonia was clinically reviewed. Twenty-two patients with E. coli pneumonia were admitted for treatment to Kawasaki Medical School Kawasaki Hospital, between January 2006 and December 2008. Clinical features were retrospectively reviewed. Results showed that: (1) hospital-acquired pneumonia occurred in elderly patients with underlying diseases, such as cerebrovascular disease, diabetes mellitus, or chronic obstructive pulmonary disease; (2) more patients had complications of urinary-tract infection or alimentary infection due to E. coli; (3) previous administration of antibacterial agents did not become a risk factor; (4) resistance to ampicillin (ABPC) and levofloxacin (LVFX) was observed; and (5) mortality was 22.7%.

To develop a stable immuno-assay system for quantification of human hemoglobin (Hb), the interaction between various antibodies and Hb was studied using a surface plasmon resonance (SPR) biosensor in the BIAcore equipment (Amersham Pharmacia Biotech) with an immobilized anti-Hb antibody sensor chip. When polyclonal antibodies were used, the immuno-reactivity of purified and commercially available Hb decreased drastically with incubation times up to 14 h. This instability of immuno-reactivity of Hb is attributable to the conformational changes in Hb induced by oxidation. On the other hand, of the sixteen monoclonal antibodies tested, four antibodies (MSU-102, -103, -106 and -115) were found to maintain their immuno-reactivities at least up to 24 h. During long-term storage, however, the immuno-reactivity of Hb with these monoclonal antibodies decreased significantly. The chemical betabeta-cross-linking of Hb was effectively able to stabilize the structure of Hb and immuno-reactivity with monoclonal antibodies such as MSU-103 for periods at least up to 70 days. Therefore, the combination of specific monoclonal antibodies such as MSU-103 and a betabeta-cross-linked Hb standard could be used for the quantification of Hb.

✓ This 47-year-old man was admitted to the hospital with disturbance of consciousness due to subarachnoid hemorrhage caused by a ruptured dissecting aneurysm of the left anterior cerebral artery (ACA). Conservative treatment resulted in improvement in the patient's consciousness; however, repeated rupture occurred during the chronic stage. Endovascular coil embolization of the parent artery was successful. Serial angiography demonstrated all stages in the development of the aneurysm. Follow-up angiography demonstrated an incidental dissecting aneurysm of the right vertebral artery. This aneurysm was also treated by endovascular embolization. No new neurological deficit appeared during or after the treatment.Multiple dissecting aneurysms are rare, especially those involving both supra- and infratentorial regions. A ruptured dissecting aneurysm of the ACA is also an uncommon vascular disorder. This case shows that rebleeding may occur, even during the chronic stage, and thus appropriate treatment for the prevention of subsequent bleeding is essential. Incidental dissecting aneurysms can be treated using the endovascular technique, but further study is necessary.

Intradural paraclinoidal aneurysm still presents conceptual confusion and technical surgical problems. The clinical features of 68 consecutive patients with paraclinoidal aneurysms were analyzed. The pterional approach was used in all patients. Subarachnoid hemorrhage (SAH) occurred in 37 patients from the paraclinoidal aneurysm and in 10 patients from another associated aneurysm. Thirty-four of the 37 ruptured paraclinoidal aneurysms were clipped, two blister-like aneurysms required trapping, and one blister-like aneurysm was coated. Thirteen of the 31 unruptured paraclinoidal aneurysms, consisting of 10 with ruptured associated aneurysm, four symptomatic, and 17 incidental, were clipped and 18 were coated. Favorable outcomes were obtained in 38 of 47 patients with SAH and 17 of 21 patients without SAH. Nine unfavorable outcomes in SAH patients were caused by primary brain damage (5), vasospasm (2), cerebral infarction after trapping (1), and pneumonia (1). All four unfavorable outcomes in non-SAH patients were due to surgical procedures for giant aneurysms or associated basilar artery aneurysm. Removal of the anterior clinoid process was performed to secure the proximal neck in 15 patients with large or giant aneurysms. Multiple clips with or without fenestrated clips were required in all giant aneurysms, and exposure of the cervical internal carotid artery (ICA) in 17 giant or large aneurysms. Fenestrated clips were also useful for one small aneurysm projecting posteriorly. A favorable outcome was achieved in 17 of 19 patients undergoing coating. Coating without clipping might be better for some blister-like ICA aneurysms, even if ruptured. Paraclinoidal aneurysms can be clipped with favorable results using these techniques except for giant aneurysms and associated basilar artery aneurysm.

Recently, ultra-thin bronchoscopy has made it possible to observe smaller bronchi not visualized using standard techniques. We describe a case of pulmonary mucormycosis with cavitation, diagnosed using an ultra-thin bronchoscope. A 15-year-old girl with acute myeloid leukaemia had taken oral prednisolone, 60 mg/day, for graft versus host disease after haematopoietic stem cell transplantation. She was admitted to our hospital with fever and a large cavitary lesion in the right hilum. Using an ultra-thin bronchoscope, the interior of the cavity in the superior segment of the right lower lobe was observed. The bronchoscopic findings revealed debris adhering to the cavity wall with a small volume of effusion. Cunninghamella bertholletiae was isolated from the effusion specimen obtained using the bronchoscope. Pulmonary mucormycosis (C. bertholletiae) complicating an immunocompromised state was diagnosed. Ultra-thin bronchoscopy is useful to diagnose complex pulmonary infections and more research is needed to verify its clinical indications and utility.

A 2-year-old-boy had rotavirus gastroenteritis and demonstrated afebrile partial seizures with secondary generalization. The presence of rotavirus genome and anti-rotavirus IgG was detected in the cerebrospinal fluid. The genotype of VP4 was P8 and that of VP7 was G4. The imaging analysis by computed tomography and single photon emission computed tomography implied encephalitis. The seizures were well controlled by standard antiepileptic therapy, and the child experienced normal development with neither physical nor neurologic sequelae, which appeared to mimic benign infantile partial epilepsy.

Serial evaluation of cerebral vasospasm following subarachnoid hemorrhage was attempted in 11 patients using magnetic resonance (MR) angiography. MR angiography demonstrated vasospasm with angiographic confirmation in three patients as a segmental narrowing or loss of flow signal, usually accompanied by decreased distal flow signal. MR angiography also showed decreased flow signal suggestive of vasospasm in another patient with clinical evidence of vasospasm but no angiographic confirmation was possible because of poor condition. MR angiography showed no vasospasm in five patients without clinical evidence of vasospasm, except in one patient with disappearance of the unilateral anterior cerebral artery signal, shown to be involvement of the clipped artery. MR angiography is a potential method for detection of vasospasm with further improvement of the technique.

Add-on therapy with flunitrazepam (FNZ) was performed in 5 children with marked sleep disturbance and intractable seizures. Correction of the sleep disturbance was attained immediately after the start of FNZ administration in all patients. Furthermore, a significant decrease in the seizure frequency (3 patients) and improved quality of life (4 patients) were concomitantly observed. There was no adverse effect or interaction with conventional AEDs on long-term use.

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.

The age changes of epileptic foci on EEG were evaluated in 208 patients with childhood partial epilepsies, who were followed for more than 3 years. 1) The incidence of EEG foci in each region apparently differed with age. Frontal and central foci were frequent before school age and after adolescence. Temporal foci showed a peak around adolescence, and occipital foci a peak from 3 to 7 years, respectively. Parietal foci were rare at all ages. 2) The migration of EEG foci was recognized 171 times in 81 of the 208 patients (38.9%) during the clinical course. The migration was frequently seen at early school age and preadolescence, and the direction of migration was predominantly anterior to posterior at early school age, and posterior to anterior at preadolescence. These results suggest that EEG foci show characteristic changes with age during the clinical course, which may be related to maturation of the central nervous system.

Neuronal differentiation of oligodendroglioma has been demonstrated by immunohistochemical and ultrastructural examinations in recent studies. However, oligodendrogliomas displaying a complete neurocytic morphology or even gangliocytic differentiation are rare. We describe a case of anaplastic oligodendroglioma that was characterized by the presence of ganglion cells in a 40-year-old-male. Histologically, the tumor was mainly composed of classical oligodendroglioma cells. The most exceptional finding of this tumor was the presence of ganglion cells and intermediate-sized ganglioid cells. Immunohistochemical analysis revealed that these cells were positive for Olig2 and negative for glial fibrillary acid protein (GFAP). Synaptophysin and microtubule-associated protein 2 (MAP2) were mainly detected in the ganglion cells. Fluorescence in situ hybridization analysis (FISH) revealed the deletion of the 1p and 19q chromosome arms in both the oligodendroglioma cells and ganglion cells. The R132H mutated isocitrate dehydrogenase 1 (IDH1) protein was detected by immunohistochemistry and direct DNA sequencing. The morphological, immunohistochemical, and genetic features of the tumor suggested a diagnosis of anaplastic oligodendroglioma, and this tumor was considered to be a rare form of oligodendroglioma displaying ganglioglioma-like maturation. FISH and mutant IDH1 examinations are useful diagnostic tools for the differential diagnosis of this tumor, i.e., ganglioglioma with anaplastic oligodendroglial features.