Search

Preoperative embolization for intracranial meningiomas can cause tumor necrosis, reduce intraoperative blood loss, and facilitate surgery. This study aimed to evaluate the efficacy of tumor embolization using Embosphere microspheres for skull base meningiomas and analyze postembolization plain computed tomography (CT) and magnetic resonance imaging (MRI) scans to identify findings that could potentially predict treatment response.Between April 2014 and April 2020, 80 patients with skull base meningiomas presenting at our medical center underwent embolization with Embosphere microspheres. The effects of tumor embolization were evaluated through a comparison of postembolization plain CT and contrast-enhanced MRI.A total of 143 vessels (102 of 108 external carotid artery branches and 41 of 65 internal carotid artery branches) from 80 skull base meningiomas were embolized with Embosphere microspheres. Microspheres 100-300 μm in size were used in 2 cases, microspheres 300-500 μm in size were used in 12 cases, and microspheres 500-700 μm in size were used in 66 cases. Postembolization contrast-enhanced MRI showed reductions in enhancing lesions within the tumor in 55 of 80 cases. Postembolization plain CT scans showed high-density lesions within the tumor in 41 of 55 cases. Thus, reductions in enhancing lesions on postembolization contrast-enhanced MRI were statistically significantly associated with the presence of high-density lesions on postembolization plain CT (P0.001). Embolization-related neurological complications occurred in 3 cases.Embosphere microspheres are user friendly and effective embolic materials for the embolization of skull base meningiomas. Postembolization contrast-enhanced MRI and plain CT findings may be useful for evaluating the effects of tumor embolization.

To investigate the patient demographics, survival after diagnosis, and prognostic factors among patients with multiple-territory cerebral infarctions due to cancer-associated ischemic stroke (multiple CAIS).We performed a retrospective review of the medical records from a 10-year period of consecutive patients with multiple CAIS, defined as (1) newly developed multiple cerebral infarctions involving two or more cerebrovascular territories, (2) association with active cancer diagnosed or treated6 months before or after stroke, and (3) exclusion of obvious etiologies other than cancer-associated coagulopathy in routine screening. We extracted demographic features, stroke severity and characteristics, cancer characteristics, comorbidities, and laboratory data. Univariable Cox proportional hazards regression was used to idenify the prognostic factors.The median age was 74 years (interquartile range, 68.3-80.5), and the median survival after diagnosis was 44.5 (27.3-76.8) days in 26 patients with complete follow-up. The median National Institutes of Health Stroke Scale was 5.5 (2.0-9.0). Twenty (76.9%) patients had received a cancer diagnosis prior to the diagnosis of multiple CAIS, and most patients (25 patients, 96.2%) had stage IV cancer. Univariate analysis showed that high serum albumin (hazard ratio, 0.31; 95% confidence interval, 0.11-0.88) was significantly associated with prolonged survival, whereas stroke severity and comorbidities were not associated with survival.Multiple CAIS predominantly occurred in elderly patients with advanced cancer, and their survival was short. Serum albumin levels were significantly associated with prognosis, indicating the poor general condition associated with cancers may affect prognosis.

In residential areas where liquefaction occurred during the 2011 Great East Japan Earthquake, houses, roads, water pipes, sewage pipes and gas pipes were damaged, interrupting daily life. Though settled and tilted houses were repaired by uplifting, the ground in the whole area, including around lifelines and roads, must be treated by special measures to prevent liquefaction-induced damage. A project to improve the liquefiable soil of an entire area by lowering the ground water table started in November 2011. Based on case studies at sites of damaged and undamaged houses, a water table of about GL-3m was judged to be appropriate to prevent damage due to liquefaction. In-situ tests clarified that the pore water pressure decreased due to dewatering only at shallow depths and that subsidence was small.

Objective We aim to clarify the clinico-radiological characteristics of cerebral amyloid angiopathy-related intracerebral hemorrhage and to investigate the efficacy of pathological diagnosis using biopsy specimens. Method We retrospectively reviewed 253 consecutive patients with cortico-subcortical hemorrhage who had been admitted to Aizawa Hospital between January 2006 and July 2013. We had performed craniotomy and hematoma evacuation in 48 patients, as well as biopsy of the evacuated hematoma, cerebral parenchyma adjacent to the hematoma, or both, and they were classified according to the histological results (positive or negative for vascular amyloid deposition) and to the Boston criteria. We compared the clinico-radiological characteristics of cerebral amyloid angiopathy-related intracerebral hemorrhage. We also investigated the detection rate of cerebral amyloid angiopathy with respect to the origins of the specimens. Results Pathological examination revealed that 22 subjects were positive for vascular amyloid. The number of the cerebral microbleeds located in the deep or infratentorial region was significantly larger in the negative group than in the positive group ( P .05). There was no significant difference in the distribution of lobar cerebral microbleeds and in the prevalence of hypertension. In the probable cerebral amyloid angiopathy-related intracerebral hemorrhage patients, the probability of having vascular amyloid detected by biopsy of both hematoma and parenchyma was 100%. Rebleeding in the postoperative periods was observed in 2 cases (9.1%) of the positive group. Conclusions Our results demonstrate the importance and safety of biopsy simultaneously performed with hematoma evacuation. Deep or infratentorial microbleeds are less correlated with cerebral amyloid angiopathy-related intracerebral hemorrhage than with noncerebral amyloid angiopathy-related intracerebral hemorrhage.

A large number of houses suffered from liquefaction-induced damages in recent large earthquakes due to lack of economical countermeasures. In this study, the shallow ground improvement, up to several meters deep, was proposed as an economical liquefaction countermeasure for houses. Based on the case studies, the design criteria of allowable tilt angles and penetration settlements of houses were proposed for the required level of serviceability against moderate and large earthquakes. The results of questionnaire survey, airborne LiDAR survey and centrifuge model tests demonstrated that even a few meters of non-liquefiable layers in shallow ground could greatly reduce settlements and tilting of houses. A series of numerical analyses indicated that non-liquefiable layer of three meters thick below ground water table improved by solidification methods can prevent significant damages of houses. Furthermore, cost analyses were carried out for different ground improvement methods for both new and existing houses.

Objectives To clarify clinical picture of transient myoclonic state in elderly patients. Methods The Aizawa Hospital database was searched to identify all patients with transient myoclonic state with or without asterixis between April 2006 and June 2013. Medical records, brain images and laboratory data including electroencephalograms and electromyograms were reviewed. Results We found 26 patients: 10 women and 16 men, and their ages ranged from 56 to 96 years (79.7 ± 9.9 years, mean ± standard deviation). The affected sites of the myoclonic jerks were predominantly the lower face, neck and upper extremities. The myoclonus appeared at conscious resting condition, slightly exaggerated by posturing or action. Asterixis was observed in eight patients. Single myoclonic bursts were 1.70 ± 0.94 s long. The interval of myoclonic bursts was 4.47 ± 2.44 s. Single myoclonic bursts were composed of 9.5 ± 2.5 Hz myoclonic contractions, and single myoclonic contractions were 44.4 ± 12.3 ms in duration. Most of the patients suffered from chronic diseases, but they were basically independent in activity of daily living. Oral administration of clonazepam was effective. Conclusions Transient myoclonic state has relatively stereotyped features. The pathophysiology may include some metabolic abnormality on a background of age-related arteriosclerotic changes. Its prognosis is benign, and prompt oral administration of clonazepam abolishes it. Further investigations will be needed to clarify its cause and pathophysiology.

A 52-year old male with a history of insulin treated T2DM complicated by end stage renal disease (ESRD requiring hemodialysis and prior gastric bypass surgery presented with severe recurrent hypoglycemia with seizures. A 72 hour fast demonstrated hyperinsulinemic hypoglycemia. Abdominal CT scan and endoscopic ultrasound guided biopsy demonstrated a pancreatic neuroendocrine tumor (pNET). Symptoms persisted despite pNET resection and on further testing he was found to have a highly specific insulin antibody resulting in insulin autoimmune syndrome. He responded well to prednisone therapy with resolution of hypoglycemia and decline in the insulin autoantibody titers. This study concludes that autoimmune forms of hypoglycemia are uncommon and interpretation of tests can be challenging. However, insulin autoimmune syndrome (IAS) should be considered in a patient with both fasting and postprandial hypoglycemia in setting of very high insulin levels with associated anti-insulin antibodies and elevated insulin to C peptide molar ratio.

SUMMARY Aging is associated with loss of tissue mass and a decline in adult stem cell function in many tissues. In contrast, aging in the prostate is associated with growth-related diseases including benign prostatic hyperplasia (BPH). Surprisingly, the effects of aging on prostate epithelial cells have not been established. Here we find that organoid-forming progenitor activity of mouse prostate basal and luminal cells is maintained with age. This is caused by an age-related expansion of progenitor-like luminal cells that share features with human prostate luminal progenitor cells. The increase in luminal progenitor cells may contribute to greater risk for growth-related disease in the aging prostate. Importantly, we demonstrate expansion of human luminal progenitor cells in BPH. In summary, we define a Trop2+ luminal progenitor subset and identify an age-related shift in the luminal compartment of the mouse and human prostate epithelium., In Brief Aging is a significant risk factor for BPH and prostate cancer, but how aging increases disease risk in the prostate remains poorly defined. Crowell et al. show that progenitor-enriched luminal cells are expanded with aging in the mouse and human prostate, and may contribute to BPH., Graphical Abstract

We report on a patient with sporadic Creutzfeldt–Jakob disease (CJD) who showed dystonia, periodic myoclonus, and periodic sharp wave complexes (PSWCs) on EEG. The EEG–EMG polygraphic study revealed that dystonia appeared without relation to periodic myoclonus and PSWCs and that dystonia EMGs were strongly suppressed after periodic myoclonus EMGs. These findings suggest that dystonia has a pathogenesis different from that of periodic myoclonus and PSWCs, but dystonia and periodic myoclonus may be generated through the sensorimotor cortex in CJD.

14-3-3 proteins are now recognized to have a wide range of potential functions and pathological relevance, such as regulating the intercellular signal processes of differentiation, the development and growth of cells, or preventing or mediating cell apoptosis and survival by controlling the localization of potential signaling molecules. We investigated the immunolocalization of 14-3-3 proteins in atherosclerotic lesions of human cerebral and carotid arteries using 14-3-3 isoform-specific antibodies to distinguish 7 isoforms, and confirmed the cell type localization using double immunofluorolabeling. 14-3-3 common (COM)-like immunoreactivity (IR) was intense, mainly in the foam cells and multinucleated giant cells of the carotid artery. The beta, gamma, epsilon, tau, eta, and zeta (6/7) isoform-specific antibodies showed similar results to those with anti-14-3-3 COM antibody. However, among these isoform-specific antibodies, the anti-eta isoform antibody most intensely immunolabeled multinucleated giant cells and foam cells, and the anti-zeta isoform antibody most intensely immunolabeled infiltrating vascular smooth muscle cells (VSMCs), in carotid plaques. Zeta IR was also observed in one part of the mural thrombus and in the nuclei of foam cells. Gamma isoform-like IR was relatively limited in cell components, but extracellular lesions were partly positive for this isoform. In the main cerebral arteries, the anti-epsilon isoform antibody most intensely immunolabeled infiltrating VSMCs in the intima of thickened fibrous cap plaques. Endothelial cells were also positive for the epsilon isoform. These findings may provide a basis for understanding the isoform-specific role associated with atherosclerotic lesions of the cerebral and carotid arteries.

Spontaneously hypertensive rats (SHR) and their substrains are a useful model for studying essential hypertension which is a complex, polygenic, and multifactorial disorder. Their genetic and metabolic features are of great interest because they may provide insights into the mechanism of blood pressure regulation. We have compared urinary metabolic profiles of young SHR with those of their age-matched normotensive controls, Wistar Kyoto rats, using (1)H NMR-based metabonomics. Principal components analysis was applied to the NMR spectral data after data-reduced and normalized by the total integral or the creatinine integral. Consequently, a clear separation of urine samples between the two strains was observed in the principal components scores plot. The loadings plot from the data normalized by the creatinine integral showed that many metabolites such as citrate, alpha-ketoglutarate, and hippurate contributed to the separation, and the urinary levels of most metabolites used in this study, including these three, were lower in SHR than in Wistar Kyoto rats. These metabolic changes may be concerned with blood pressure regulation in SHR, although a relation to other strain differences cannot be ruled out. The present study suggests the usefulness of a (1)H NMR-based metabonomic approach using SHR in the field of hypertension research.

An equation is theoretically derived which describes the relative standard deviation (RSD) of the amount ratios of analyte to its isotope-labeled variant in gas chromatography/mass spectrometry (GC/MS) using the stable isotope dilution method. The determination of methyltestosterone is taken as an example. The uncertainty equation proposed is justified by comparing the theoretical RSD values with the experimental RSD values obtained by replication over a wide range of analyte amount. The detection limit and quantitation limit are estimated from the continuous plot (precision profile) of the theoretical RSD against analyte amount.

Hot coke oven gas (COG) with a temperature of about 1050 K was produced from a test unit for coke production, the capacity of which was 80 kg of coal. The COG was introduced into an experimental unit with a tar converter where oxygen and steam were injected. Over 98% of the total carbon in the hot COG was partially oxidized, reformed with steam and converted to hydrogen and CO. About 1 Nm 3 /h of hydrogen was continuously produced for 5 h in this experiment. The experimental results suggest that three to five times the amount of hydrogen and CO that were present in the original COG could be recovered by this technology, utilizing the heat of the hot COG for the reaction. The feasibility study showed that hydrogen can be produced by this technology at a lower cost and higher efficiency than by the separation of cold COG.

A method for the stereoselective determination of D- and L-enantiomers of both methionine and [(2)H3]methionine in rat plasma was developed using gas chromatography-mass spectrometry with selected-ion monitoring (GC-MS-SIM). DL-[(2)H7]Methionine was used as analytical internal standard to account for losses associated with the extraction, derivatization and chromatography. The amino acids were purified by cation-exchange chromatography using BondElut SCX cartridge and derivatized with HCl in methanol to form methyl ester followed by subsequent N-acylation with optically active (+)-alpha-methoxy-alpha-trifluoromethylphenylacetyl chloride to form diastereomeric amide. Quantification was performed by SIM of the molecular-related ions of the diastereomers on the chemical ionization mode. Endogenous L-methionine concentrations in 50 microl of rat plasma were measured with relative intra- and inter-day precision of 4.0 and 6.3%, respectively. The intra- and inter-day reproducibility in the amounts of D- and L-[(2)H3]methionine determined were in good agreement with actual amount added.

Osaterone acetate (17 alpha-acetoxy-6-chloro-2-oxa-4,6-pregnadiene-3,20-dione; OA) is a steroidal antiandrogen. In order to clarify the species differences, metabolites of OA were examined in plasma, urine, and feces of dogs and humans after oral administration of OA. Eleven metabolites in plasma, urine, and feces were identified by their spectral properties and comparison to appropriate standards. The primary routes of OA metabolism involve 11 beta-, 15 beta- and 21-hydroxylation, 17 alpha-deacetylation, and dechlorination. Other metabolites arise from combinations of these pathways to form multiple oxidized metabolites. All metabolites observed in humans occurred in dogs. 11 beta-Hydroxylated metabolites (11 beta-OH OA and 11-oxo OA) were found in the plasma and urine of dogs, but there was no evidence of their presence in humans. 11 beta-Hydroxylation of exogenous steroids represents a distinctive biotransformation pathway.

Surface electromyogram (SEMG) is a useful tool to depict involuntary movements, but evaluation of the intensity of such movements with SEMG over multiple recording instances requires awareness of factors influencing quantified SEMG signals. We investigated the differences in the amplitude of SEMGs due to electrode displacement in isometric voluntary contraction in the upper arm, forearm and lower leg in 8 healthy men. The SEMGs of gross muscle activity simultaneously recorded with 4 electrode pairs from the agonist and antagonist sides in 3 displacement conditions with respect to parallel position, interelectrode distance, and rotation were compared. The amount of EMG integration (equivalent to the average SEMG amplitude) of each electrode pair was compared to the reference electrode pair with interelectrode distance of 40 mm placed on the center of the tested muscles. The average EMG difference ratios ranged 1.1–2.2%/mm in parallel shift, 1.0–1.9%/mm in distance shift, and 0.3–0.6%/degree in rotation shift. Displacement error of electrodes in separate recording instances should be reduced using anatomical landmarks, when SEMG is applied as a quantitative method to evaluate change in the states of involuntary movements.

Deep brain stimulation (DBS) has routinely been used as a treatment option in Parkinson's disease (PD), tremor disorders and, more recently, dystonia. Here, we describe a method of implantation of DBS leads in the monkey model of PD. By adapting procedures used in human patients, we have devised implantation techniques that can be readily applied to any animal model in which stimulation of subcortical structures is desired. The procedure for implantation consists of microelectrode mapping of the target structure, DBS lead preparation and implantation, and verification of lead placement. The stimulation system described in this paper allows for simultaneous recording of neuronal activity (during stimulation) and observation of animal behavior without restriction of the subject's head or body. In addition, we detail techniques for stimulation and recording from distant structures (utilizing either a one or two chamber system) to facilitate examination of the effects of DBS on neural activity. Thus, the correlation of changes in neuronal activity with behavior during stimulation of subcortical structures can be accomplished. In addition, the use of leads in primates which are analogous in size to human devices allows for close reproduction of the effects of stimulation as observed in humans.

We report two patients with idiopathic acute lumbosacral myelitis, a rare form of acute transverse myelitis. Both patients developed urinary retention, moderate motor and sensory paresis of the lower extremities, severe sensory deficit in the anogenital region and reduced deep tendon reflexes. Steroid pulse therapy was initiated within 2 days after onset, and progress of the symptoms stopped immediately after administration in both of our patients. The sequelae of the sensory deficits in the sacral dermatome distribution and urinary retention impaired daily functioning. Immediate immunosuppressive therapy, including high-dose steroid treatment, is important to improve the prognosis of acute lumbosacral transverse myelitis.

Hashimoto's encephalopathy (HE) is thought to be caused by disorders of immune mechanisms. Although immunologically mediated central nervous system vasculitis or unidentified anti-neuronal autoantibodies have been suspected of causing HE, its pathogenesis is still unclear. For the study presented here, two patients with typical clinical and laboratory/electrophysiological findings of HE were analyzed to clarify the role of anti-neuronal autoantibodies in the pathogenesis of HE. The autopsied brain of one of the patients was histopathologically examined. For Western blotting analysis and immunohistochemistry, serum and purified immunoglobulin G obtained from the other patient were used. Autopsy revealed no evidence of central nervous system vasculitis or other abnormal findings in the brain. The patient's serum contained an anti-neuronal autoantibody that immunohistochemically labeled neurons of mouse and human cerebral cortices and reacted with the 36-kDa antigenic protein present in a soluble fraction obtained from human cerebral cortex. Our results indicate that anti-neuronal autoantibodies may be associated with the pathogenesis of HE.

Objectives : The objective of this study is to clarify the participation of cortical motor control abnormality in the motor dysfunction of Parkinson's disease (PD), especially at the onset of movement. Methods : Conditioning effects of transcranial magnetic simulation (TMS) on the soleus (SOL) H-reflex evoked with tibial nerve stimulation were examined in 19 patients with PD and 10 normal volunteers. Experiments were done at rest, during tonic plantarflexion (PF), and at PF onset. Stimulus intensity of TMS was maintained at less than 5% of the motor threshold in each situation. Seven patients underwent pallidotomy and were examined twice, once before and once after the operation. Results : Short latency subthreshold TMS stimulation did not facilitate the SOL H-reflex neither during tonic PF nor at PF onset in the patients with PD, though it was evident in normal subjects. In some patients, paradoxical inhibition appeared at PF onset. The facilitation increase at PF onset, as compared to that at rest, was negatively correlated with the motor part of the unified Parkinson's disease rating scale and with the rigidity grade. Pallidotomy improved both modulation and the clinical scores. Conclusions : Cortical activity for the proper execution of reciprocal control between the agonist and antagonist seems to be disturbed in PD.

Deep brain stimulation (DBS) is a neurosurgical technique that has been widely applied for the treatment of tremor or motor symptoms associated with advanced Parkinson's disease. Large stimulus artifacts, however, have hampered investigations of physiological mechanisms underlying DBS effects using extracellular recording techniques. We have developed an off-line procedure for removing stimulus artifacts from recorded neuronal signals (monopolar) and applied this method of artifact subtraction to DBS studies using extracellular recording techniques in a nonhuman primate. The procedure consists of developing a template of the artifact by averaging the artifact signals triggered by its onset. The template is then subtracted from the individual triggered signals. The experimental results indicate that this method is highly effective in removing the majority of the stimulus artifact, while leaving recorded neuronal activity intact. In fact, removal of stimulation artifact using this technique has revealed a short-latency neuronal response to stimulation that was previously obscured by the stimulus artifact. Thus, this technique may not only improve the quality of electrophysiological studies employing DBS techniques, but may also help to elucidate neuronal mechanisms underlying the effect of DBS.

The pharmacokinetics of methionine has been studied in rats by means of stable isotope methodology. After the i.v. bolus injection of [ 2 H 7 ]methionine (5 mg/kg body wt.), the plasma concentrations of [ 2 H 7 ]methionine, demethylated [ 2 H 4 ]homocysteine and remethylated [ 2 H 4 ]methionine were determined simultaneously with endogenous methionine and homocysteine by gas chromatography-mass spectrometry. The half-life for [ 2 H 7 ]methionine were 35.0 ± 6.9 min. The appearance of the metabolites, [ 2 H 4 ]homocysteine and [ 2 H 4 ]methionine, in the plasma was very rapid. The fraction of [ 2 H 7 ]methionine that remethylated to [ 2 H 4 ]methionine through [ 2 H 4 ]homocysteine were 0.185 ± 0.028. The administered [ 2 H 7 ]methionine did not influence the plasma levels of endogenous methionine and homocysteine. The present stable isotope methodology has made it possible to evaluate the pharmacokinetics of methionine, including the estimation of remethylation.

To study the effects of posteroventral pallidotomy on both the size of long-latency stretch reflex (LLR) and the muscle stiffness in the wrist flexor muscles.Eleven consecutive patients (right-handed, 6 men and 5 women) underwent left-side microelectrode-guided pallidotomy. The LLR of the contralesional forearm was studied at baseline and 2-3 months after surgery while patients continued to take their optimal medical regimens ('on' period). Patients were instructed not to respond to the perturbation (passive mode) or to oppose the mechanical extensor perturbation (active mode).The stretch reflex evoked by extension perturbations of the wrist consisted of a short-latency reflex (M1) and an LLR (M2). Pallidotomy had no effects on the size of M1 components in both passive and active mode and on that of M2 component in the passive mode, however, it significantly reduced M2 component in the active mode (P0.05). The inherent muscle stiffness over 60 ms period of mechanical stretch was not influenced by pallidotomy in any experimental condition (preoperative vs. postoperative or passive mode vs. active mode). The hand displacement following M2 component increased significantly after pallidotomy in both passive (P0.005) and active mode (P0.05). The inverted value of the displacement following M2 component correlated with the size of M2 component (r=0.60, P0.001).Pallidotomy decreased the transcortical reflex gain, probably at cortical level, and consequently reduced muscle stiffness.

Objectives : To study the deficit of inhibition of excessive motor drive generated in the central nervous system in chorea. Methods : Identical associated movements in the contralateral limb elicited by rapid hand squeezing were measured in 6 patients with Huntington's disease, 7 patients with peak-dose dyskinesia, 10 patients with Parkinson's disease, 8 patients with spinocerebellar degeneration and in 8 normal subjects. The intensity of associated movements was assessed by the EMG amplitude ratio of associated contractions to active contractions. Results : The associated movement ratios were larger in Huntington's disease and peak-dose dyskinesia as compared to other groups. The ratios in akinetic ‘off' phase were smaller than those in dyskinetic ‘on' phase in all peak-dose dyskinesia patients. Conclusions : Enhanced associated movements support a possible common mechanism that chorea may result from failure in inhibition of phasic neural activity pathologically generated in the brain.

PURPOSE: We report an abnormal electroretinogram with a negative configuration in a child who presented with moderate myopia, nystagmus, and visual developmental delay. We investigated the electroretinogram and explored the possibility of a metabotropic glutamate receptor subtype 6 mutation in six family members spanning four generations. METHODS: Case report and family study: Complete eye examinations and Ganzfeld electroretinograms were recorded from the maternal great-grandmother, maternal grandmother, mother, uncle, and sibling of the 7-month-old female proband. The electroretinogram was repeated in the proband at 17 months of age. Dark adaptometry was performed in all adult subjects. Fundus photographs and visual field examinations were administered to the grandmother and mother. The metabotropic glutamate receptor subtype 6 gene was amplified and sequenced in all affected subjects. RESULTS: The proband had a negative electroretinogram and a normal fundus. The maternal grandmother, uncle, and mother had an abnormal electroretinogram identical to the proband yet had no visual complaints. The ophthalmology examinations in the adult subjects were normal, and subsequent examination of the proband at 17 months, 5 years, and 6.5 years of age showed no changes in the fundus or refractive error. Her nystagmus resolved by 5 years of age. Rod threshold and visual fields were normal in the affected adult subjects. No mutation in the metabotropic glutamate receptor subtype 6 gene was found. CONCLUSIONS: In this family, a negative electroretinogram was not associated with decreased rod threshold, visual acuity loss, visual field loss, muscle disease, or metabotropic glutamate receptor subtype 6 mutation. Additional study will be required to understand the nature of the negative electroretinogram phenotype in this family.

A method for determination of alpha-ketoisocaproic acid (KIC) and [4,5,5,5,6,6,6-2H7]alpha-ketoisocaproic acid ([2H7]KIC) in rat plasma was developed using gas chromatography-mass spectrometry-selected ion monitoring (GC-MS-SIM). [5,5,5-2H3]alpha-Ketoisocaproic acid ([2H3]KIC) was used as an analytical internal standard to account for losses associated with the extraction, derivatization and chromatography. The keto acids were extracted by cation-exchange chromatography using BondElut SCX cartridge and derivatized with N-phenyl-1,2-phenylenediamine to form N-phenylquinoxalinone derivatives. Quantitation was performed by SIM of the respective molecular ions at m/z 278, 281 and 285 for the derivatives of KIC, [2H3]KIC and [2H7]KIC on the electron impact method. The limit of detection was found to be 70 fmol per injection (S/N=3) and the limit of quantitation for [2H7]KIC was around 50 nM in rat plasma. Endogenous KIC concentrations in 50 microl of rat plasma were measured with relative intra- and inter-day precision of 4.0% and 3.3%, respectively. The intra- and inter-day precision for [2H7]KIC spiked to rat plasma in the range of 0.1 to 10 microM gave good reproducibility with relative standard deviation (RSD) of 6.5% and 5.4%, respectively. The intra- and inter-day relative errors (RE) for [2H7]KIC were less than 6.4% and 3.8%, respectively. The method was applied to determine the plasma concentration of [2H7]KIC after an intravenous administration of [2H7]KIC in rat.

A method based on gas chromatography-mass spectrometry-selected-ion monitoring was developed to measure the main metabolites of 17alpha-methyltestosterone, 17alpha-methyl-5alpha-androstan-3alpha,17beta-di ol and 17alpha-methyl-5beta-androstan-3alpha,17beta-dio l, in human urine. 17alpha-Methyl-[(2)H3]-5alpha-androstan-3alpha,1 7beta-diol and 17alpha-methyl-[(2)H3]-5beta-androstan-3alpha,17 beta-diol were used as internal standards. The methods involved purification using a Sep-Pak C(18) cartridge, hydrolysis by beta-glucuronidase from Ampullaria and derivatization with N-methyl-N-trimethylsilyl-trifluoroacetamide/dithioerythriol/ammon ium iodide. Quantitation was achieved by selected-ion monitoring of the characteristic fragment ions ([(M+H)-2xTMSOH]+) of the di-TMS derivatives on the chemical ionization mode. The method provides a specific, sensitive and reliable technique to determine the urine levels of 17alpha-methyl-5alpha-androstan-3alpha,17beta-di ol and 17alpha-methyl-5beta-androstan-3alpha,17beta-dio l, and can be applied to pharmacokinetic studies of 17alpha-methyltestosterone.

A method for the stereoselective assay of d - and l -enantiomers of both leucine and [2H7]leucine in rat plasma was developed using gas chromatography–mass spectrometry–selected-ion monitoring. dl -[2H3]leucine was used as an internal standard. The method involved purification by cation-exchange chromatography using BondElut SCX cartridge and derivatization with hydrochloric acid in methanol to form methyl ester followed by subsequent chiral derivatization with (+)-α-methoxy-α-trifluoromethylphenylacetyl chloride to form diastereomeric amide. The derivatization made the separation of the leucine enantiomers possible with good gas chromatographic behavior. Quantitation was performed by selected-ion monitoring of the quasi-molecular ions of the diastereomers on the chemical ionization method. The sensitivity, specificity, accuracy and reproducibility of the method were demonstrated to be satisfactory for application to pharmacokinetic studies of leucine enantiomers.

beta, gamma-Methylene ATP (betagamma-mATP) significantly facilitated the electrically (4 Hz) evoked release of noradrenaline (NA) from the rabbit ear artery by activation of prejunctional purinoceptors on the sympathetic nerve terminals. In the present study, we investigated whether intracellular cAMP is involved in the purinoceptor mediated facilitatory mechanisms. Forskolin, an adenylate cyclase activator, and 8-bromo cAMP, a cAMP analogue, significantly enhanced the NA-release. The enhancement of NA-release by betagamma-mATP was significantly potentiated by Ro20-1724, a phosphodiesterase inhibitor, but abolished by SQ22536, an adenylate cyclase inhibitor. Both drugs alone had no effect on the NA-release. N-ethylmaleimide and pertussis toxin, inhibitors of Gi-proteins, did not affect the NA-release, or the enhancement of NA-release by betagamma-mATP. Alone Cholera toxin (CTX), an activator of Gs-proteins, significantly increased the NA-release, but in the presence of CTX, betagamma-mATP could not produce further enhancement of the NA-release. These results suggest that cAMP is closely associated with the facilitatory action of betagamma-mATP on NA-release in the rabbit ear artery.

Purpose: To evaluate the histopathological characteristics of choroidal neovascular membranes excised from eyes of patients with age-related macular degeneration (AMD) and to correlate their characteristics with the clinical features of AMD. Methods: Choroidal neovascular tissues were excised from 3 patients with AMD and examined by light and confocal scanning laser microscopy. The clinical features were obtained by fundus photography, fluorescein angiography (FA), and indocyanine green angiography (IA) and compared with the histopathological findings. Results: Light microscopy showed the presence around the vascular structures of cells containing pigment. Confocal scanning laser microscopy revealed lipofuscin signals of the retinal pigment epithelium cells around the vascular tissue that was also confirmed by three-dimensional reconstructed views from serial optical sections. Clinical observations of the fundus by IA showed that all 3 cases had areas with hyperfluorescence in early phase on IA. A dark rim was observed around the area of hyperfluorescence in 2 cases, and the dark rim was located within the neovascular membrane. The patterns of fluorescence were heterogeneous in some phases on IA, which reflected the histological heterogeneity of the neovascular membrane. Conclusions: The retinal pigment epithelium cells appear to play a special role in the induction and regression of the choroidal neovascular membrane associated with age-related macular degeneration.

We report on a patient with Amanita pantherina poisoning who showed a burst suppression pattern on electroencephalography during a comatose state. The patient recovered without sequelae a week after ingestion. Burst suppression pattern is defined as alternating bursts and periods of electrical silence, and it is associated with comatose states of various causes. The major toxins contained in A. pantherina are ibotenic acid, an excitatory amino acid at the glutamate receptors, and muscimol, an agonist of the gamma-aminobutyric acid receptors. Alteration of the synaptic transmission in the central nervous system by these toxins may lead to a burst suppression pattern.

We report the case of a 46-year-old male with myotonic dystrophy who developed daytime hypersomnia and dyspnoea. After a therapeutic tracheostomy, overnight polysomnographic studies were performed under three different ventilatory conditions. When the patient breathed spontaneously through a tracheal cannula, abnormal cyclical sleep increased and rapid eye movement (REM) sleep decreased markedly. The apnoea and hypopnoea index (AH index) was 35.1. When breathing spontaneously through his normal airway, there were many instances of cyclical sleep, but few instances of deep sleep and no episodes of REM sleep. The AH index was 58. Under assisted ventilation the patient's sleep pattern was normal. Our conclusion, therefore, is that these studies demonstrate the patient had sleep apnoea of central origin.

We report a patient with Isaacs' syndrome associated with myasthenia gravis and pleural recurrence of thymoma, who showed severe limb pain attributed to hyperexcitability of sensory nerves. Myokymia and severe pain were successfully treated with cytoreductive surgery and intraoperative hyperthermic intrathoracic perfusion chemotherapy, but neither pharmacotherapy nor plasma exchange showed obvious clinical effects. Pleural thymoma in our patient may have caused Isaacs' syndrome, probably by unconfirmed humoral immune mechanisms. Cytoreductive treatment for recurrent thymoma should be actively considered as a potent therapeutic option in refractory patients with disabling neuromyotonia symptoms.

The releases of endogenous ATP from ear, femoral, renal and pulmonary arteries of rabbit were compared. Adenyl purines, such as ATP, ADP, AMP and adenosine, and norepinephrine (NE) were quantified by HPLC-fluorescence detection and HPLC-electrochemical detection, respectively. In all four blood vessels, electrical stimulation (ES) at 16 Hz significantly increased overflow of adenyl purine and NE. ATP was the main largest among adenyl purine released; release of adenosine was very small. The rank order of amounts of total purine released by ES was ear artery > renal artery = femoral artery ⪢ pulmonary artery. There was no significant difference among the amounts of NE release induced by ES from these four arteries. ES-induced purine release was notably reduced by denudation of endothelium and prazosin at 1 μM. Methoxamine, α1-adrenoceptor agonist, also produced release of adenyl purines in the four arteries. The rank order of amount of total purine released was ear artery > renal artery = femoral artery ⪢ pulmonary artery. These suggest that the sources of ATP released by sympathetic nerve stimulation, which seems to be α1-adrenoceptors on endothelial cells, not distributed homogeneously in the vasculature.

1. 1. High potassium 30 mM and noradrenaline at 10 μM significantly evoked the release of ATP and produced remarkable vasoconstriction in the rabbit pulmonary artery. 2. 2. Phentolamine and prazosin at 0.1 μM inhibited ATP release but not vasoconstriction by 30 mM potassium. 3. 3. 30 mM potassium significantly evoked the release of noradrenaline. 4. 4. There was a significant positive correlation between the amounts of release of total purines, sum of ATP, ADP, AMP and adenosine, and noradrenaline evoked by 30 mM potassium. 5. 5. 30 mM potassium-evoked ATP release was significantly reduced by denudation of endothelium.

We report 3 diabetic patients who developed hemiballism without involvement of the subthalamic nucleus. Each patient exhibited vigorous, flinging, ballistic involuntary movements in the extremities and slight facial grimacing involving one side of the body. Although diabetes was poorly controlled in all 3, each patient was nonketotic at the onset of hemiballism. Magnetic resonance imaging (MRI), in these patients showed abnormalities in the striatum contralateral to the hemiballism that were characterized by an increase in intensity on T1-weighted images and a slight decrease in intensity on T2-weighted images, and these changes persisted for more than 2 months. The striatal lesions are presumed to have developed following mild ischemia in the territory of the lateral striate branches of the middle cerebral artery. This combination of hemiballism and striatal lesions in diabetic patients may constitute a unique syndrome.

Methoxamine, an alpha 1-adrenoceptor agonist, significantly increased the overflow of ATP, ADP and AMP, but not adenosine, by a prazosin-sensitive mechanism in the rabbit pulmonary artery. Among the adenine nucleotides released, the amount of ATP was larger than those of the other two. Such release of adenine nucleotides was not induced by clonidine, an alpha 2-adrenoceptor agonist, and isoproterenol, a beta-adrenoceptor agonist. Methoxamine-induced release was observed in the absence of extracellular calcium, but was not observed at a low temperature, 27 degrees C. This suggests an extracellular calcium-independent and temperature-dependent ATP-releasing mechanism coupled with alpha 1-adrenoceptors in rabbit pulmonary artery.

Summary In order to elucidate the effect of serum on passive K permeability of vascular smooth muscle cells (VSMC) membrane, outward passive K permeability yielded as washout rate constant ( K e ) of 86 Rb washout, was measured in the presence and in the absence of cation transport modulators using VSMC in culture. The overall K e of 86 Rb washout subjected to 1% serum was significantly larger than that in controls. This stimulated K e was substantially blunted in the presence of 10 −4 m amiloride and was partially inhibited with 5 × 10 −4 m bumetanide. Angiotensin II of 10 −5 m exerted to a lesser extent, a similar significant stimulatory effect on K e of 86 Rb washout, which effect was inhibited with application of amiloride. Additionally, Ca-antagonist, 10 −5 m nifedipine reduced serum-stimulated K e to the basal level. It is concluded that both serum and angiotensin II increase K permeability in cultured VSMC. A part of this effect of serum may be attributable to angiotensin II in the serum. Furthermore, it is suggested that the stimulatory effect of serum on membrane permeability may be exerted, at least in part, via activation of both Na-H antiport and Na-K co-transport, possibly through mechanisms in conjunction with intracellular Ca.