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Quick, easy, cheap, effective, rugged, and safe extraction strategies are becoming increasingly adopted in various analytical fields to determine drugs in biological specimens. In the present study, we developed two fully automated quick, easy, cheap, effective, rugged, and safe extraction methods based on acetonitrile salting-out assisted liquid-liquid extraction (method 1) and acetonitrile salting-out assisted liquid-liquid extraction followed by dispersive solid-phase extraction (method 2) using a commercially available automated liquid-liquid extraction system. We applied these methods to the extraction of 14 psychotropic drugs (11 benzodiazepines and carbamazepine, quetiapine, and zolpidem) from whole blood samples. Both methods prior to liquid chromatography-tandem mass spectrometry analysis exhibited high linearity of calibration curves (correlation coefficients, > 0.9997), ppt level detection sensitivities, and satisfactory precisions (< 8.6% relative standard deviation), accuracies (within ± 16% relative error), and matrix effects (81-111%). Method 1 provided higher recovery rates (80-91%) than method 2 (72-86%), whereas method 2 provided higher detection sensitivities (limits of detection, 0.003-0.094 ng/mL) than method 1 (0.025-0.47 ng/mL) owing to the effectiveness of its dispersive solid-phase extraction cleanup step. These fully automated extraction methods realize reliable, labor-saving, user-friendly, and hygienic extraction of target analytes from whole blood samples., (© 2022 Wiley-VCH GmbH.)

Positional isomers o -, m -, and p -chloromethcathinones (CMCs) and m - and p -bromomethcathinones (BMCs) were effectively differentiated using gas chromatography (GC) and energy-resolved mass spectrometry (ERMS) analyses. GC demonstrated that the free bases of CMC and BMC isomers were simultaneously baseline-separated at a slow column heating rate (5 °C/min) using a conventional low-polar capillary column. ERMS showed that the trifluoroacetyl derivatives of the positional isomers differed in mass spectral abundances of both halophenyl and halobenzoyl cations. Moreover, the logarithmic plots of the abundance ratio of the two cations as a function of the collision energy (CE) exhibited marked differences among the isomers at each CE, following the order of ortho < para < meta for CMCs and para < meta for BMCs. The performed theoretical calculations of dissociation energy agreed well with the ERMS measurements. The GC and ERMS methodologies enabled unambiguous and reliable differentiation of CMC and BMC isomers. The developed approach is expected to significantly contribute to the accurate structural identification of new psychoactive substances in forensic, toxicological, and clinical fields.

Positional isomer differentiation is crucial for the analysis of forensic drugs. Presently, it is difficult to distinguish among ortho, meta, and para positional isomers of ring-fluorinated synthetic cathinones, a major class of new psychoactive substances (NPSs), because they exhibit similar chromatographic properties and mass spectral patterns. We describe herein that the ring-fluorinated synthetic cathinone positional isomers, viz. o-, m-, and p-fluoro-α-pyrrolidinopropiophenones (o-, m-, and p-FPPPs), can be discriminated by their benzyltrimethylammonium hydroxide (Triton B)-mediated one-pot reaction with methanol at ambient temperature, followed by chromatographic and mass spectral analyses of the corresponding products. For p-FPPP, fluorine was nucleophilically substituted by the methoxy group to afford p-methoxy-α-pyrrolidinopropiophenone, while o- and m-FPPPs afforded the corresponding FPPP-enamine-pyrrolidine adducts, which allowed the above positional isomers to be unambiguously differentiated by comparing the reaction product chromatograms and mass spectra. The adopted approach, which does not require excess heating or use of metallic catalysts and features the advantages of simplicity and convenience, is expected to contribute toward practical NPS identification., (Copyright © 2019 Elsevier B.V. All rights reserved.)

A reliable method for structural analysis is crucial for the forensic investigation of new psychoactive substances (NPSs). Towards this end, mass spectrometry is one of the most efficient and facile methods for the identification of NPSs. However, the differentiation among 2-, 3-, and 4-fluoromethcathinones (o-, m-, and p-FMCs), which are ring-fluorinated positional isomers part of the major class of NPSs referred to as synthetic cathinones, remains a challenge. This is mostly due to their similar retention properties and nearly identical full scan mass spectra, which hinder their identification. In this study, we describe a novel and practical method for differentiating the fluorine substitution position on the phenyl ring of FMCs, based on energy-resolved mass spectrometry (ERMS) using an electron ionization-triple quadrupole mass spectrometer. ERMS measurements showed that the three FMC positional isomers exhibited differences in relative abundances of both the fluorophenyl cation (m/z 95) and the fluorobenzoyl cation (m/z 123). The logarithmic plots of the abundance ratio of these two cations (m/z 95 to m/z 123) as a function of the collision energy (CE) followed the order of o-FMC < p-FMC < m-FMC at each CE, which allowed the three isomers to be unambiguously and reliably differentiated. The theoretical dissociation energy calculations confirmed the relationship obtained by ERMS analyses, and additional ERMS measurements of methylmethcathinone positional isomers showed that the differences in abundance among the FMCs were attributed to the differences in their collision-induced dissociation reactivities arising from the halogen-induced resonance effects on the phenyl ring. Moreover, the method for differentiation described herein was successfully applied to the actual samples containing seized drugs. We expect that the described methodology will also contribute significantly to the reliable and accurate structural identification of NPSs in the fields of therapeutic, clinical, and forensic toxicology., (© 2018 John Wiley & Sons, Ltd.)

In forensic drug analysis, extractive pretreatment is required prior to instrumental analysis to ensure successful detection of the target compounds. However, conventional extraction methods such as hydrophilic polymer-based solid-phase extraction and liquid-liquid extraction are unsuitable for an emerging class of new psychoactive substances, namely, synthetic cathinones, because they exhibit a lack of class selectivity and increased risk of target analyte decomposition during extraction. To address these issues, we describe a highly class-selective sample clean-up method for the extraction of synthetic cathinones from urine and whole blood samples, exploiting a molecularly imprinted polymer solid-phase extraction cartridge. In terms of the influence of the synthetic cathinone molecular structure on the extraction recovery, we showed that while longer alkyl side chains slightly reduced the extraction efficiency, substituent variation on the aromatic ring exerted no effect. Molecularly imprinted polymer solid-phase extraction of 11 synthetic cathinones from urine samples yielded higher recoveries than the two conventional extraction methods, and smaller matrix effect was observed than that with hydrophilic polymer-based solid-phase extraction. Molecularly imprinted polymer solid-phase extraction from whole blood samples gave recoveries comparable to those of urine samples. Therefore, the proposed method is applicable for the extraction and quantitative determination of synthetic cathinones in biological samples., (© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Purpose: Positional isomer differentiation is crucial for forensic analysis. The aim of this study was to differentiate AB-FUBINACA positional isomers using liquid chromatography (LC)-electrospray ionization (ESI)-linear ion trap mass spectrometry (LIT-MS) and LC-ESI-triple quadrupole mass spectrometry (QqQ-MS)., Methods: AB-FUBINACA, its two fluorine positional isomers on the phenyl ring, and three methyl positional isomers in the carboxamide side chain were analyzed by LC-ESI-LIT-MS and LC-ESI-QqQ-MS., Results: Four of the positional isomers, excluding AB-FUBINACA and its 3-fluorobenzyl isomer, were chromatographically separated on an ODS column in isocratic mode. ESI-LIT-MS could discriminate only three isomers, i.e., the 2-fluorobenzyl isomer, the N -(1-amino-2-methyl-1-oxobutan-2-yl) isomer, and the N -(1-amino-1-oxobutan-2-yl)- N -methyl isomer, based on their characteristic product ions observed at the MS 3 stage in negative mode. ESI-QqQ-MS differentiated all six isomers in terms of the relative abundances of the product ions that contained the isomeric moieties involved in collision-induced dissociation reactions. The six isomers were more clearly and significantly differentiated upon comparison of the logarithmic values of the product ion abundance ratios as a function of collision energy., Conclusions: The present LC-MS methodologies were useful for the differentiation of a series of AB-FUBINACA positional isomers., Competing Interests: Compliance with ethical standardsThe authors declare that they have no conflict of interest.This article does not contain any studies involving human participants or animals performed by any of the authors.

To clarify the mechanism for the endothelin-1 (ET-1)-induced release of catecholamines from the adrenal gland, we examined the effects of removal of extracellular Ca2+, blockers of L-, N-, P- and Q-types of voltage-operated Ca2+ channels (VOCC) such as nifedipine (L-type), ω-conotoxin GVIA (N-type), ω-agatoxin IVA (P-type) and ω-conotoxin MVIIC (Q-type) and blockers of voltage-independent Ca2+ entry channel such as SK&F 96365 and LOE 908 on release of catecholamines, the cytosolic free Ca2+ concentration ([Ca2+]i), and 45Ca2+ uptake in cultured bovine adrenal chromaffin cells. ET-1 but not ET-3 induced increases in release of catecholamines, [Ca2+]i, and 45Ca2+ uptake. The responses to ET-1 were abolished by the antagonist for ETA receptors, BQ-123, but not by the antagonist for ETB receptors, BQ-788, and they were abolished by removal of extracellular Ca2+. The increases were only partially inhibited (to about 65% of control) by nifedipine but unaffected by any of the ω-toxins. The nifedipine-resistant increase was inhibited by SK&F 96365 (to about 40%) and abolished by LOE 908 alone. These results indicate that ET-1 augments the release of catecholamines from adrenal chromaffin cells through ETA receptors, by activating two types of Ca2+ entry channels in addition to L-type VOCC: one (nonselective cation channel-1; NSCC-1) is sensitive to LOE 908 but resistant to SK&F 96365, whereas the other (NSCC-2) is sensitive to both LOE 908 and SK&F 96365. [ABSTRACT FROM AUTHOR]

To clarify the pathogenesis of two different types of adult-onset normal-pressure hydrocephalus (NPH), we investigated cerebrospinal fluid distribution on the high-field three-dimensional MRI. The subarachnoid spaces in secondary NPH were smaller than those in the controls, whereas those in idiopathic NPH were of similar size to the controls. In idiopathic NPH, however, the basal cistern and Sylvian fissure were enlarged in concurrence with ventricular enlargement towards the z-direction, but the convexity subarachnoid space was severely diminished. In this article, we provide evidence that the key cause of the disproportionate cerebrospinal fluid distribution in idiopathic NPH is the compensatory direct CSF communication between the inferior horn of the lateral ventricles and the ambient cistern at the choroidal fissure. In contrast, all parts of the subarachnoid spaces were equally and severely decreased in secondary NPH. Blockage of CSF drainage from the subarachnoid spaces could cause the omnidirectional ventricular enlargement in secondary NPH.

Mass spectrometric differentiation of structural isomers is important for the analysis of forensic samples. Presently, there is no mass spectrometric method for differentiating halogen positional isomers of cannabimimetic compounds. We describe here a novel and practical method for differentiating one of these compounds, N-(1-amino-3-methyl-1-oxobutan-2-yl)-1-(4-fluorobenzyl)-1H-indazole-3-carboxamide (AB-FUBINACA (para)), and its fluoro positional (ortho and meta) isomers in the phenyl ring by electron ionization-triple quadrupole mass spectrometry. It was found that the three isomers differed in the relative abundance of the ion at m/z 109 and 253 in the product ion spectra, while the detected product ions were identical. The logarithmic values of the abundance ratio of the ions at m/z 109 to 253 (ln(A 109 /A 253 )) were in the order meta < ortho < para and increased linearly with collision energy. The differences in abundances were attributed to differences in the dissociation reactivity between the indazole moiety and the fluorobenzyl group because of the halogen-positional effect on the phenyl ring. Our methodology, which is based on the abundance of the product ions in mass spectra, should be applicable to determination of the structures of other newly encountered designer drugs. Copyright © 2016 John Wiley & Sons, Ltd., (Copyright © 2016 John Wiley & Sons, Ltd.)

Mycosporine-like amino acids (MAAs) are UV-absorbing pigments, and structurally unique glycosylated MAAs are found in the terrestrial cyanobacterium Nostoc commune. In this study, we examined two genotypes of N.commune colonies with different water extract UV-absorption spectra. We found structurally distinct MAAs in each genotype. The water extract from genotype A showed a UV-absorbing spectrum with an absorption maximum at 335nm. The extract contained the following compounds: 7-O-(β-arabinopyranosyl)-porphyra-334 (478Da), pentose-bound shinorine (464Da), hexose-bound porphyra-334 (508Da) and porphyra-334 (346Da). The water extract from genotype B showed a characteristic UV-absorbing spectrum with double absorption maxima at 312 and 340nm. The extract contained hybrid MAAs (1050Da and 880Da) with two distinct chromophores of 3-aminocyclohexen-1-one and 1,3-diaminocyclohexen linked to 2-O-(β-xylopyranosyl)-β-galactopyranoside. A novel 273-Da MAA with an absorption maximum at 310nm was also identified in genotype B. The MAA consisted of a 3-aminocyclohexen-1-one linked to a γ-aminobutyric acid chain. These MAAs had potent radical scavenging activities in vitro and the results confirmed that the MAAs have multiple roles as a UV protectant and an antioxidant relevant to anhydrobiosis in N. commune. The two genotypes of N. commune exclusively produced their own characteristic glycosylated MAAs, which supports that MAA composition could be a chemotaxonomic marker for the classification of N. commune., (Copyright © 2014 Elsevier B.V. All rights reserved.)

We describe a unique UV-visible absorption spectral property of 5,10,15,20-tetrakis(4-hydroxyphenyl)porphyrin (THPP) in the presence of organophosphorus (OP) pesticides. Upon titrating each 16 among total 40 different OP pesticides, the Soret band was significantly red-shifted, and a very intense Q band appeared. They were attributed to the diprotonation of THPP. A suitable solvent for this reaction was determined to be methanol. THPP would become a potential sensor molecule used to detect OP pesticides with high sensitivity in the concentration range of 10(-6) - 10(-4) M.

Due to the forensic aspects of drinking and exposure to toxic substances, more sophisticated quantitative technology is needed to quantify the concentration of ethyl alcohol and acetaldehyde in the blood. In this study, we developed a headspace gas chromatography tandem mass spectrometry method that could simultaneously detect ethyl alcohol and acetaldehyde in human plasma. Through a simple preparation process, ethyl alcohol and acetaldehyde were quickly detected within 4 min, and a lower limit of quantification (LLOQ) (20 and 0.2 µg/mL) was obtained; these results confirmed the suitability of the system. According to Food and Drug Administration guidelines, the linearity (correlation coefficient > 0.9996), intraday and intraday accuracy, precision, and both short- and long-term stability and freeze-thaw stability satisfied the evaluation criteria (within 100.0 ± 15.0% and 20.0% of the LLOQ). Carryover and batch size assessment for the evaluation of the sample influence during analysis also satisfied the evaluation criteria. A valid method was applied to the pharmacokinetics study, and the plasma from 43 subjects after oral administration of the placebo or HK-GCM-H01 was analyzed. The developed analysis method for ethyl alcohol and acetaldehyde in blood could be used in various fields, such as forensics and those requiring precise quantification. [ABSTRACT FROM AUTHOR]

Carotid artery stenting (CAS) has been covered by the health insurance system in Japan since 2008. There have been few studies concerning medical costs and charges for patients who received CEA or CAS in Japan. The aim of this study was to elucidate the difference in the costs between the patients who received CEA and those who received CAS in Japan. Between 2010 and 2011, 19 patients who received CEA and 20 patients who received CAS were retrospectively reviewed. Age, sex, symptomatic/asymptomatic, emergent/scheduled, length of stay, outcome, cost for the procedure (professional fee), supply for the operation, the total medical service fee, and copayment of the patients was compared between the two treatment groups. No significant difference was detected between the two groups except for the supply of the operation and the total medical service fee (CEA:mean 1,565,580 yen vs CAS 2,758,360 yen, p=0.0001). On the other hand, no significant difference was obtained in the copayment of the patients (CEA 71,895 yen, CAS 72,458 yen). Even when limited to the scheduled cases, similar results were obtained. There is a monthly copayment limit in the health insurance system in Japan, which results in a reasonable charge for patients who received CAS, despite the fact that the rest of the fee including high costs for the supplies was paid by the company and the nation. To reduce the medical costs, Japanese have to be aware of the high costs in CAS, most of which is due to the supplies.

Δ(9) -Tetrahydrocannabinol is the primary psychoactive component in cannabis, one of the most commonly used illicit drugs in the world. This paper describes a simple and rapid method for direct analysis of major metabolites of Δ(9) -tetrahydrocannabinol; 11-nor-Δ(9) -tetrahydrocannabinol-9-carboxylic acid and its glucuronide in urine by capillary electrophoresis/mass spectrometry. The only pretreatment needed for a urine sample was dilution with methanol containing an internal standard and centrifugation. Electrophoresis was carried out in an untreated fused-silica capillary (50 µm i.d. × 85 cm) filled with 40 m m ammonium formate (pH 6.4). An analysis could be completed within 10 min. For both compounds, the assay was linear over the range 0.1-10 µg/mL in urine with correlation coefficients (r(2) ) >0.99 and the limit of detection was 0.5 pg (10 nL injection). The detection yields and reproducibilities were determined at three different concentrations (0.1, 0.5 and 2 µg/mL in urine). The mean detection yields were 60-99%. The intra- and inter-day relative standard deviations of migration times were 0.063-0.19 and 0.18-0.36%, and those of peak areas were 4.2-18 and 5.9-25%, respectively. The proposed method successfully analyzed the urine samples of cannabis users., (Copyright © 2012 John Wiley & Sons, Ltd.)

We describe a new practical capillary electrophoresis/electrospray ionization-mass spectrometry (CE/ESI-MS) method for the forensic analysis of phosphorus-containing amino acid-type herbicides, glyphosate (GLYP), glufosinate (GLUF) and bialaphos (BIAL). A new sheathless interface, a high sensitivity porous sprayer (HSPS), was used in this study. The limits of detections of GLYP, GLUF and BIAL were 7.6, 0.61 and 0.57 pg, respectively. These values were 4-36 times lower than these obtained by conventional CE/ESI-MS using a sheath liquid. The developed method was successfully applied to the analysis of beverages spiked with the herbicides., (2011 © The Japan Society for Analytical Chemistry)

Objective: Endovascular stenting is an alternative treatment for brachiocephalic artery stenosis, replacing standard surgical approaches such as carotid endarterectomy. However, a percutaneous approach may be difficult because various conditions such as severe arteriosclerosis of iliac or femoral arteries and aortic disease. We report our experience with intraoperative stenting for these lesions, presenting indications, strategy, and results., Methods: Seven patients underwent intraoperative stent placement via an open cervical approach. The sites of lesions included 1 innominate artery, 1 common carotid artery, and 5 cervical carotid arteries. Stenting was performed with a sheath introducer placed through a surgically exposed common carotid artery via a small skin incision or common carotid artery exposed for simultaneously performed carotid endarterectomy. Distal protection was used in 6 patients with an endovascular protective balloon or external clamping with forceps., Results: Sufficient dilation of stenosis was obtained in all cases. No complications such as transient ischemic attack, cerebral infarction, and hyperperfusion were encountered. Wound hematoma was not experienced despite perioperative antiplatelet therapy and heparinization during the procedure. Angiographic follow-up over 1 year showed no restenosis in 5 available patients., Conclusion: Intraoperative stenting may be an excellent alternative for patients in whom both direct surgical approach and standard percutaneous endovascular approach are not possible.

Objectives: This study aimed to evaluate the relationship between the amount of aspirated debris during distal balloon-protected carotid artery stenting (CAS) and the pre-intervention plaque composition, as assessed by Virtual Histology (VH) intravascular ultrasound (IVUS)., Methods: The study subjects were 25 consecutive patients (mean age, 73.0 +/- 5.2 years; 20 males and 5 females) who underwent CAS under distal balloon protection. The average rate of carotid stenosis was 74.6 +/- 12.9% by North American Symptomatic Carotid Endarterectomy Trial criteria. We assessed culprit plaque components by VH-IVUS before CAS. Aspirated debris was filtered, stained with HE and mounted onto glass slides. The quantity of debris was evaluated by measuring its surface area. We evaluated the relationship between the quantity of aspirated debris and VH-IVUS measurements before CAS., Results: The amount of debris during CAS was positively correlated with the total plaque volume in grayscale IVUS (Rs = 0.480, p = 0.015) and fibro-fatty volumes over the entire lesion length in VH-IVUS (Rs = 0.561, p = 0.001)., Conclusions: Culprit lesions with large plaque volumes, especially larger fibro-fatty volumes, as imaged by VH-IVUS, are associated with large amounts of debris during balloon-protected CAS., (Copyright 2010 S. Karger AG, Basel.)

Aneurysms in the supra-aortic extracranial arteries are rare in neurovascular pathology. Conventional surgery is effective but technically demanding and successful endovascular repair is reported. We treated 5 patients with supra-aortic extracranial artery aneurysms at our hospital (mean age 53.8 years). There were 2 aneurysms of the common carotid artery, 1 of the extracranial internal carotid artery, 1 of the subclavian artery, and 1 located at the innominate artery. Four patients were symptomatic. The lesion was the result of trauma in 3 patients. The procedure was conducted using bare stent placement and coil embolization of the aneurysm in 2 patients, covered stent in 2 patients, and bare stent only in 1 patient. No periprocedural complications occurred. Follow-up angiography revealed asymptomatic stent thrombosis in a patient treated using a covered stent, but the remaining 4 patients showed successful treatment of the aneurysms with the parent arteries remaining patent. Follow-up clinical assessment ranged between 30 and 81 months. The patient with stent thrombosis died of unrelated pathology; the remaining patients did not experience aneurysm recurrence, hemorrhage, or distal thromboembolism.

Purpose: To evaluate the effect of maxillary sinus anatomy on sinus floor elevation (SFE) operations performed with the lateral window approach. Materials and Methods: CBCT and digital panoramic radiographs were evaluated before and at least 6 months after maxillary sinus floor elevation (SFE) operations performed in 33 maxillary sinus regions in 26 patients. Maxillary sinus volume, grafted volume (GV), sinus width (SW), residual bone height (RBH), and vertical graft resorption (VGR) were calculated. The effects of RBH and SW on GV and VGR were evaluated statistically. Results: The mean GV values in the maxillary sinuses classified as narrow, average, and wide were 2.60 ± 0.57, 3.44 ± 0.65, and 3.70 ± 0.64 cm3, respectively. The mean VGR was 2.12 ± 1.67 mm, and in the sites classified as narrow, average, and wide, the mean VGR values were 1.50 ± 0.79, 1.58 ± 1.28, and 3.46 ± 2.06 mm, respectively. A statistically significant difference in GV and VGR was found between the SW groups. The mean posterior maxillary RBH was 2.30 ± 1.05 mm, and 17 and 16 sinuses were classified as = 2 and > 2 mm, respectively. There was no statistically significant difference in the effect of RBH on GV or VGR. Conclusion: Although posterior maxillary RBH did not affect new bone formation in the sinuses grafted only with hydroxyapatite-derived inorganic bovine bone, with increasing SW, the GV decreased and the VGR increased. [ABSTRACT FROM AUTHOR]

We report on the successful treatment of acute sinus thrombosis associated with endovascular treatment of intracranial dural arteriovenous fistulae (DAVF) by sinus angioplasty with stent deployment. A 76-year-old man presented with intracerebral hemorrhage, Cognard type IIa+b DAVF of the left sigmoid sinus, and type IIa DAVF of the torcular herophili. During transvenous sinus embolization, acute thrombosis of the stenotic lesion in the left transverse sinus occurred. The thrombosis caused isolated sinus and cortical venous reflux (CVR). The patient was treated by stent-supported sinus angioplasty, which led to an immediate improvement of the sinus thrombosis and associated CVR.

We report a rare case of spontaneous intracranial carotid artery dissection presenting with multiple infarctions. A 65-year-old man became aware of transient visual disturbance in the right eye and headache. Magnetic resonance imaging (MRI) at a local neurosurgical clinic depicted fresh multiple infarctions of the right cerebral hemisphere along with severe right carotid artery stenosis and delayed cerebral blood flow on the right side. The patient was transferred to our hospital. Three-dimensional computed tomography (3D-CT) showed an intimal flap in the righ petrous internal carotid artery and we diagnosed spontaneous intracranial carotid artery dissection of the petrous portion. We started conservative therapy including anti-coagulant and antiplatelet drug and blood pressure control. Two weeks after admission, angiography, 3D-CT, MR angiography demonstrated that the dissection had improved and the patient was discharged without neurological deficit. In this case, 3D-CT was effective for the diagnosis of intracranial carotid artery dissection. We report this rare case along with a literature review of the clinical profile and related neuroimaging findings.

A novel potent NMDA-NR2B selective antagonist without the reactive metabolites formation issue was identified. Through this study, a close correlation between reactive metabolites formation and calculated HOMO energies of parent compounds was found.

The principles of cerebrospinal fluid (CSF) production, circulation and outflow and regulation of fluid volumes and pressures in the normal brain are summarised. Abnormalities in these aspects in intracranial hypertension, ventriculomegaly and hydrocephalus are discussed. The brain parenchyma has a cellular framework with interstitial fluid (ISF) in the intervening spaces. Framework stress and interstitial fluid pressure (ISFP) combined provide the total stress which, after allowing for gravity, normally equals intracerebral pressure (ICP) with gradients of total stress too small to measure. Fluid pressure may differ from ICP in the parenchyma and collapsed subarachnoid spaces when the parenchyma presses against the meninges. Fluid pressure gradients determine fluid movements. In adults, restricting CSF outflow from subarachnoid spaces produces intracranial hypertension which, when CSF volumes change very little, is called idiopathic intracranial hypertension (iIH). Raised ICP in iIH is accompanied by increased venous sinus pressure, though which is cause and which effect is unclear. In infants with growing skulls, restriction in outflow leads to increased head and CSF volumes. In adults, ventriculomegaly can arise due to cerebral atrophy or, in hydrocephalus, to obstructions to intracranial CSF flow. In non-communicating hydrocephalus, flow through or out of the ventricles is somehow obstructed, whereas in communicating hydrocephalus, the obstruction is somewhere between the cisterna magna and cranial sites of outflow. When normal outflow routes are obstructed, continued CSF production in the ventricles may be partially balanced by outflow through the parenchyma via an oedematous periventricular layer and perivascular spaces. In adults, secondary hydrocephalus with raised ICP results from obvious obstructions to flow. By contrast, with the more subtly obstructed flow seen in normal pressure hydrocephalus (NPH), fluid pressure must be reduced elsewhere, e.g. in some subarachnoid spaces. In idiopathic NPH, where ventriculomegaly is accompanied by gait disturbance, dementia and/or urinary incontinence, the functional deficits can sometimes be reversed by shunting or third ventriculostomy. Parenchymal shrinkage is irreversible in late stage hydrocephalus with cellular framework loss but may not occur in early stages, whether by exclusion of fluid or otherwise. Further studies that are needed to explain the development of hydrocephalus are outlined. [ABSTRACT FROM AUTHOR]

Forensic pathologists often encounter cases of acute subdural hematoma (SDH) due to trauma, whereas those attributable to endogenous causes are rare. Here, we report a case of the latter type in a 42-year-old man who was found dead at home after several months of fever and malaise. Postmortem computed tomography (PMCT) and autopsy were undertaken to clarify the cause of death. PMCT images revealed a fatal SDH and a localized hyper-density area in the right parietal lobe; macroscopic and microscopic examinations revealed SDH due to rupture of a mycotic aneurysm (MA) associated with meningitis. The PMCT images also indicated thickening and calcification of the mitral valve, while autopsy demonstrated infective endocarditis (IE). In addition, PMCT demonstrated a low-density area in the spleen, which was shown to be a splenic abscess at autopsy. PMCT also demonstrated tooth cavities. Based on the findings of autopsy, the cause of death was considered to be SDH due to rupture of the MA resulting from meningitis with IE and splenic abscess. Although PMCT was unable to clarify the significance of any individual feature, a retrospective review of the PMCT images might have suggested IE, bacteremia, or ruptured MA leading to SDH. This case suggests that, instead of interpreting individual features demonstrated on PMCT images, integrated interpretation of overall PMCT findings might provide clues for identifying causes of death, despite the fact that PMCT lacks diagnostic accuracy for infectious diseases such as IE and meningitis. [ABSTRACT FROM AUTHOR]

Background: Intracranial mycotic aneurysms, although rare neurovascular pathology, represented a neurosurgical challenge that required careful stepwise decision making. Different approaches for their management were used. We present our experience with 4 patients treated in terms of indications and efficacy of different treatment modalities., Methods: Four patients with infective endocarditis and 5 intracranial mycotic aneurysms were treated during the last 5 years. All of the patients were men; their ages ranged between 29 and 62 years (mean, 47.3 years). Distal MCA was the commonest site (3 patients) of aneurysm, 1 was located at the distal PCA, whereas the remaining aneurysm was at the distal ACA. Angiographic studies were done in 2 patients because of neurologic signs and for screening in 2 patients with documented endocarditis., Results: One patient was treated conservatively because of his moribund general condition; 1 patient was treated with direct surgical clipping; 1 patient was treated with surgical trapping and resection of the aneurysm without revascularization; and the remaining patient, harboring 2 distal mycotic aneurysms, was treated with selective embolization for his PCA aneurysm and endovascular trapping for the distal ACA aneurysm. Follow-up angiographic results showed stable occlusion of the aneurysms. No periprocedural technical complications were reported, and none of the patients, including the patient with medical treatment only, has ever experienced new neurologic events after definitive treatment., Conclusions: Prolonged courses of antibiotics are recommended for all patients with mycotic aneurysms. Selective endovascular embolization or trapping with soft and ultrasoft electrolytically detachable coils seems to be an effective technique that should be considered for treatment of dynamic unruptured mycotic aneurysms, with conventional surgical repair restricted for ruptured aneurysms with associated hematoma and high intracranial pressure.

Background: Endovascular embolization of cerebral aneurysms has evolved rapidly worldwide within the last years, and has gained more popularity at the expense of surgical clipping; however, both regimens have inherent risks. This study was undertaken to asses the cerebral complications associated with both modalities of cerebral aneurysm treatment., Methods: We retrospectively reviewed the charts, operative and embolization reports, and imaging of patients who underwent surgical clipping or embolization for cerebral aneurysms at our institution between October 2001 and October 2004. Patients were divided into 2 groups: group A, patients who had confirmed subarachnoid hemorrhage; group B, patients with unruptured cerebral aneurysms. Patients belonging to group A were evaluated according to the Hunt and Hess scale with their computed tomography scan evaluated according to Fisher scale. Short-term outcome was measured with Glasgow Outcome Scale for both groups., Results: One hundred thirty-three patients with 168 aneurysms were treated; 95 (71.4%) were women and 38 (28.6%) men; mean age was 60.28 years. Hypertension (29.6%) was the most commonly encountered risk factor; average size of aneurysms treated was 7.21 mm; 53 patients belonged to group A. Seven patients were Hunt and Hess grade I, 23 grade II, 11 grade III, 7 grade IV, and 5 grade V. Eighty patients belonged to group B; for both groups, the periprocedural technical complication rate associated with coiling was 8.4% vs 19.35% with clipping. Follow-up angiographic results were better with clipping, as total aneurysm occlusion was 81.4% vs 57.5% with coiling. In group A, the incidence of angiographic vasospasm was 17.4% vs 45.4% with coiling vs clipping, whereas the incidence of shunt-dependant hydrocephalus was comparable with embolization and clipping. In group A, excellent outcome was achieved in 62% vs 44% (endovascular vs surgical) of subgroups, whereas in group B, it was 93% vs 81%, respectively., Conclusion: With rapidly evolving technology of endovascular embolization, accumulated experience, and good selection of patients with optimum angioanatomical criteria and endovascular accessibility, our results of morbidity and mortality associated with both modalities of cerebral aneurysm treatment with short-term outcome show that endovascular embolization of cerebral aneurysms is a safe alternative to surgical clipping in the treatment of both ruptured and unruptured cerebral aneurysms; however, long-term outcome needs to be evaluated.

Background: Tentorial dural arteriovenous fistula (AVF) presented symptoms due to mass effect on the dilated draining vein. We report a patient presenting left hemisensory disturbance because of compression of the midbrain by a dilated draining vein of the AVF. The AVF has disappeared completely by drainer clipping after feeder embolization., Case Description: A 66-year-old woman presented with left hemisensory disturbance due to compression of the midbrain by a dilated draining vein with tentorial dural AVF. On admission, she complained of left hemisensory disturbance. Enhanced computed tomography (CT), magnetic resonance imaging, and magnetic resonance angiogram revealed the midbrain compressed by a mass lesion, which was a draining vein with AVF fed by numerous feeding arteries neighboring the right tentorial edge. The single-photon emission CT (SPECT) did not depict any laterality., Conclusion: This is a rare case of a tentorial dural AVF which caused left hemisensory disturbance not by venous congestion, but by a compression of the midbrain by the dilated draining vein, because SPECT showed no laterality. In this case, magnetic resonance angiogram, 3-dimensional CT angiography, and SPECT were useful in the diagnosis and planning the strategy for treatment.

A 34-year-old man presented with occlusion of the left vertebral artery (VA) secondary to dissection of the left subclavian artery manifesting as vertigo, nausea, vomiting, and neck pain. On admission, he was alert with left limb and truncal ataxia. Magnetic resonance (MR) imaging and MR angiography showed left cerebellar infarction and occlusion of the left VA. Conventional angiography and three-dimensional computed tomography (3D-CT) angiography showed stenosis with thrombosed pseudo-lumen of the left subclavian artery, and occlusion of the left VA. Presumably the idiopathic dissection of the left subclavian artery had reached the orifice of the left VA, and an embolism from the dissection had caused occlusion of the VA, leading to cerebellar infarction. After one month, he was discharged without severe neurological deficits. Idiopathic dissection of the subclavian artery is very rare. 3D-CT angiography is very useful for the diagnosis of arterial dissection.

We present an unusual case of multiple intracranial aneurysms, persistent primitive trigeminal artery (PPTA), and fenestration of the middle cerebral artery (MCA), associated with type 1 neurofibromatosis (NF 1). The patient was a 55-year-old woman in a state of semicoma. We observed widespread neurofibromas and café au lait spots on her trunk and limbs. Computed tomography (CT) scan revealed diffuse subarachnoid hemorrhage and right frontal intracerebral hemorrhage (WFNS grade IV, Fisher's classification group 4). Cerebral angiography showed two intracranial aneurysms at the anterior communicating artery, an aneurysm at the cavernous portion of the right carotid artery, a PPTA, and MCA fenestration. The patient remained in an apallic state, even after successful clipping of the anterior communicating artery aneurysms.

We performed stenting for the subclavian artery (SA) and innominate artery occlusive disease in 14 patients between April, 2000 and March, 2003. In 13 of 14 patients, good dilatation was obtained with stenting. In one patient with left SA occlusion, true lumen could not be detained from either proximal or distal sides of the occluded lesion, so stent deployment was not performed. From June, 2002, we performed stenting using combined femoral and brachial approaches in 6 of 8 patients. In patients in whom occlusive lesion existed in the proximal portion of the SA, it was useful strategy to create a "pull-through" system to stabilize the guiding catheter position in the aorta or the proximal portion of the SA, and to protect the vertebral artery (VA) with a balloon catheter. Post-operative morbidity was 0%. Restenosis was manifested in one patient (8%) two years after stent placement, and in-stent PTA was carried out. In stenting for the subclavian and innominate arteries, the pull-through system is considered useful for stabilization of the guiding catheter, and protection of the VA for prevention of distal embolism to the VA.

We compared the findings of multislice computed tomography (MSCT) with angiography after stenting for supraaortic arteries. Twelve cases that underwent both MSCT and angiography were evaluated. In 4 cases, stenotic findings were shown by neither MSCT nor angiography. Lumen diameters measured by MSCT tended to be shorter than those measured by angiography. In-stent stenosis evaluated by MSCT was found in 6 cases, and all of them revealed low density areas in the inner stent lumen. In 4 of them, intimal hyperplasia was indicated by angiography, but in 2 of them, unexpectedly, no stenotic findings were found by angiography. In one case, using MSCT the part two stents partially lying over one another revealed severe artifact in the inner stent lumen, but no stenosis was found by angiography. In 2 cases, unevenly spread extra-stent space was found, but that was not revealed by angiography. We conclude that MSCT is useful to evaluate lumen diameter, in-stent intimal hyperplasia, in-stent thrombus, and extra-stent space.

Endothelin-1 (ET-1) has been shown to activate three types of Ca2+ channel, namely two Ca2+-permeable nonselective cation channels (designated NSCC-1 and NSCC-2) and a store-operated Ca2+ channel (SOCC), and that these channels can be discriminated by Ca2+ channel blockers such as LOE 908 (a blocker of NSCC-1 and NSCC-2) and SK&F 96365 (a blocker of NSCC-2 and SOCC). This study pharmacologically compared Ca2+ entry channels involved in contractions of rat thoracic aorta without endothelium induced by ET-1, noradrenaline (NA), or arginine-vasopressin (AVP). These agonists-induced contractions of aortic rings without endothelium and increases in the intracellular free Ca2+ concentration ([Ca2+]i) of cultured aortic smooth muscle cells were abolished by removal of extracellular Ca2+. A blocker of L-type voltage-operated Ca2+ channel (VOCC), nifedipine had no effect on the responses to ET-1, but it suppressed the responses to NA and AVP to 70% and 65% of control responses, respectively. LOE 908 partially suppressed the nifedipine-resistant responses to ET-1 and AVP, but not those to NA. SK&F 96365 also partially suppressed the nifedipine-resistant responses to ET-1 and AVP, whereas it abolished the responses to NA. LOE 908 in combination with SK&F 96365 abolished the nifedipine-resistant responses to either of the agonists. These results show that the contraction of rat aorta involves different Ca2+ entry channel depending on agonists: (a) NSCC-1, NSCC-2, and SOCC for ET-1; (b) VOCC and SOCC for NA; and (c) VOCC, NSCC-1, NSCC-2, and SOCC for AVP.

We report a case of a 7-month-old female with a dermoid cyst on the anterior fontanelle. She was born with a vacuum extractor. Two weeks later, her scalp on the anterior fontanelle bulged. A doctor was consulted when she was 3 months old, because the tumor was enlarging. Magnetic resonance image (MRI) showed a cystic mass on the anterior fontanelle. She was brought to our institute. At the first medical examination, she was alert and had no neurological deficit. The tumor was suspected to be a sinus pericranii or a pseudo meningocele. She was observed as an out patient, but the tumoral size become more enlarged. When she was seven months old, we punctured the cystic tumor and the tumor collapsed. But, two weeks later, it enlarged again. The cystic fluid was watery clear and the composition differed from cerebrospinal fluid (CSF). The tumor was resected totally. The histological examination revealed a dermoid cyst which involved ducts of the eccrine glands and folliculi pili. The cystic fluid was thought to be secreted from the eccrine glands.

In 1980, a 10-year-old boy was admitted to the authors' hospital with consciousness disturbance and vomiting. Computerized tomography (CT) scans revealed a pineal mass lesion and hydrocephalus. The tumor was totally removed and a ventriculoperitoneal (VP) shunt was inserted. Histological investigation of a surgical specimen revealed that it was a teratoma. Five years later, the patient was readmitted to the same institution with polyuria. Magnetic resonance (MR) imaging revealed a mass lesion in the suprasellar region. The patient received systemic chemotherapy, and the tumor disappeared; however, 2 years after the chemotherapy, MR imaging demonstrated a right lateral ventricular mass. The tumor was totally resected, and histopathological investigation revealed a teratocarcinoma. Three years after the chemotherapy, CT scanning revealed suprasellar and right lateral ventricular tumor recurrences, for which the patient received irradiation and chemotherapy. The tumors disappeared and the patient achieved complete remission that lasted longer than 10 years. On January 25, 2000, however, he noticed hip pain. Lumbar MR imaging demonstrated a spinal tumor below L-4 and also an abdominal tumor. The abdominal tumor was totally removed, and the histological findings identified it as a germinoma. The patient received systemic chemotherapy and the tumor disappeared completely. The authors believe that the suprasellar tumor was a metachronous germinoma and that it had metastasized through the intrathecal route and the VP shunt.

A 57-year-old man presented with a transient ischemic attack due to dissection of the middle cerebral artery. He suffered total aphasia and clouding of consciousness for several minutes. On admission, he was alert without neurological deficit. Magnetic resonance (MR) angiography and conventional angiography depicted irregularity and double lumen of the left middle cerebral artery. The diagnosis was dissection of the middle cerebral artery. After 1 month, he left our institute with no neurological deficit. Transient ischemic attack associated with dissection of an intracranial artery is unusual. The source images of MR angiography are useful for the essential follow up of dissection.