Protein tyrosine phosphatase receptor type Q in cerebrospinal fluid reflects ependymal cell dysfunction and is a potential biomarker for adult chronic hydrocephalus.

BACKGROUND AND PURPOSE: Protein tyrosine phosphatase receptor type Q (PTPRQ) was extracted from the cerebrospinal fluid (CSF) of patients with probable idiopathic normal-pressure hydrocephalus (iNPH) by proteome analysis. We aimed to assess the feasibility of using CSF PTPRQ concentrations for the additional diagnostic criterion of iNPH in Japanese and Finnish populations. METHODS: We compared PTPRQ concentrations among patients with probable iNPH and neurologically healthy individuals (normal control [NC] group), patients with normal-pressure hydrocephalus (NPH) of acquired and congenital/developmental aetiologies, patients with Alzheimer's disease and patients with Parkinson's disease in a Japanese analysis cohort. A corresponding iNPH group and NC group in a Finnish cohort was used for validation. Patients in the Finnish cohort who underwent biopsy were classified into two groups based on amyloid and/or tau deposition. We measured PTPRQ expression levels in autopsied brain specimens of iNPH patients and the NC group. RESULTS: Cerebrospinal fluid PTPRQ concentrations in the patients with NPH of idiopathic, acquired and congenital/developmental aetiologies were significantly higher than those in the NC group and those with Parkinson's disease, but iNPH showed no significant differences when compared with those in the Alzheimer's disease group. For the patients with iNPH, the area under the receiver-operating characteristic curve was 0.860 in the Japanese iNPH and 0.849 in the Finnish iNPH cohorts. Immunostaining and in situ hybridization revealed PTPRQ expression in the ependymal cells and choroid plexus. It is highly possible that the elevated PTPRQ levels in the CSF are related to ependymal dysfunction from ventricular expansion. CONCLUSIONS: Cerebrospinal fluid PTPRQ levels indicated the validity of this assay for auxiliary diagnosis of adult chronic hydrocephalus.

Disease duration: the key to accurate CSF tap test in iNPH.

OBJECTIVES: The cerebrospinal fluid tap test for idiopathic normal pressure hydrocephalus (iNPH) is one of the good predictors of the shunt treatment, although this test has a low sensitivity. We aimed to identify key parameters that could be used to improve this sensitivity. MATERIALS & METHODS: During 2010-2011, we recruited and then followed 93 patients with possible iNPH for 12 months after shunt. Among them, 82 patients were finally enrolled in this study. The modified Rankin Scale, iNPH grading scale, and several quantitative measurements were evaluated at entry, after the tap test, before and after shunt. Area under the receiver-operating characteristic curves (AUCs), sensitivities, and specificities of the tap test for predicting shunt effectiveness were calculated for each measurement. They were additionally assessed after stratification by disease duration since the initial presentation of iNPH symptoms. RESULTS: The gait disturbance on the iNPH grading scale had the highest accurate scale at the tap test for predicting effectiveness 12 months after shunt: AUC 0.74, sensitivity 56.5%, specificity 91.7%. This AUC increased to 0.76, 0.91 and 0.94 in the subgroup of disease duration <24, <12, and <6 months, respectively. The sensitivity and specificity of the gait disturbance on the iNPH grading scale in the subgroup of <12 months' duration were 92.3% and 90.0%. CONCLUSIONS: The shorter period of clinical symptoms, for example, <12 months, made the tap test sufficiently accurate examination for predicting improvement 12 months after shunt surgery. The findings imply that the tap test should be applied to patients being considered for shunt surgery as soon as possible.

Cranial arachnoid protrusions and contiguous diploic veins in CSF drainage.

BACKGROUND AND PURPOSE: Studies have suggested that arachnoid villi or granulations found in the walls of the cranial dural sinuses, olfactory mucosa, and cranial nerve sheaths function as outlets for intracranial CSF. However, their role as CSF outlets has not yet been verified. Here we show that arachnoid protrusions and contiguous diploic veins provide an alternative drainage route for intracranial CSF. MATERIALS AND METHODS: Four hundred patients with intact skull, dura mater, and dural sinuses underwent MR imaging to explore arachnoids protruding into the skull and diploic veins. Patients with symptoms of increased intracranial pressure or intracranial hypotension were excluded. For 15 patients undergoing craniotomy, both peripheral and diploic venous blood was collected. Albumin and the CSF-specific biomarkers were measured by enzyme-linked immunosorbent assay. RESULTS: With MR imaging, arachnoid protrusions into the skull and contiguous diploic veins were consistently identified throughout the cranium with their characteristic appearance depending on the cranial region. In addition, elevated amounts of prostaglandin D synthase and cystatin C were confirmed in diploic veins compared with peripheral venous blood. CONCLUSIONS: Diploic veins are distributed ubiquitously throughout the cranium. A portion of the intracranial CSF may be drained through arachnoid protrusions and contiguous diploic veins.

Soluble amyloid precursor protein α in the cerebrospinal fluid as a diagnostic and prognostic biomarker for idiopathic normal pressure hydrocephalus.

BACKGROUND: Cognitive impairment is difficult to improve after shunt operation in patients with idiopathic normal pressure hydrocephalus (iNPH). This study aims to identify cerebrospinal fluid (CSF) biomarkers predictive of improvement in cognitive function. METHODS: This study was conducted between January 2008 and December 2010 on consecutive, unselected admissions to our program for the treatment of patients with clinically suspected iNPH. Lumbar CSF concentrations of total tau (Tau), tau phosphorylated at threonine 181 (p-tau), soluble amyloid precursor protein (sAPP), sAPPα, sAPPß, and ß-amyloid(1-42) (Aß42) were analyzed by ELISA. RESULTS: Concentrations of p-tau, sAPP, sAPPα, and sAPPß were strong diagnostic biomarkers for distinguishing between iNPH and Alzheimer's disease (AD). sAPPα exhibited the highest accuracy in differentiating iNPH from patients with AD and normal controls, with an area under the curve value of 0.994. We examined the prognostic value of p-tau and sAPPα for cognition function after surgery. With a cutoff value of 198 ng/ml or less for sAPPα, sensitivity and specificity are 66.7% and 82.9%, respectively, whilst the Mini-Mental State Examination score at 6 months after surgery is expected to be 25 or more. CONCLUSION: Our results show that sAPPα is a suitable biomarker for the diagnosis and prognosis of iNPH.

Brain localization of leucine-rich α2-glycoprotein and its role.

OBJECTIVES: We have previously reported that the level of leucine-rich alpha-2-glycoprotein (LRG) expression is specifically increased in cerebrospinal fluid (CSF) of idiopathic normal pressure hydrocephalus (INPH). The objective of this study is to examine the localization of LRG - the cerebral areas where it is expressed. METHOD: The histological sections of autopsied brain specimens from ten subjects, five adult cases (mean age 43.6 years; range 34-50 years) and five senile cases (mean age 76.0 years; range 67-88 years) were prepared, multistained with antibodies against human LRG, glial fibrillary acidic protein (GFAP), CD31, and aquaporin-4 (AQP4), and reviewed for the expression sites of LRG. RESULTS: Immunostains of GFAP and LRG were compared in standard brain specimens from elderly patients. The results indicated that LRG is distributed throughout the entire brain, with especially high expression in the deep cerebral cortex. In addition, the cells that express LRG showed similar morphology to astrocytes. Double staining of CD31 and LRG revealed a significant expression of LRG in the pericapillary regions. The expression was observed in resident astrocytes, as well as in the capillary vessel to which astrocytic processes grow and adhere. When age-related comparisons were made between senile and adult specimens, LRG expression increased with age. CONCLUSION: LRG expression in resident astrocytes increased with age.

Antihypertensive effect of a fixed-dose combination of losartan/hydrochlorothiazide in patients with uncontrolled hypertension: a multicenter study.

BACKGROUND: Achieving adequate blood pressure (BP) control often requires more than one antihypertensive agent. The purpose of this study was to determine whether a fixed-dose formulation of losartan (LOS) plus hydrochlorothiazide (HCTZ) (LOS/HCTZ) is effective in achieving a greater BP lowering in patients with uncontrolled hypertension. METHODS: The study was a prospective, multicenter, observational trial exploring the antihypertensive effect of a single tablet of LOS 50 mg/HCTZ 12.5 mg. A total of 228 patients whose BP had previously been treated with more than one antihypertensive agents without having achieved BP goal below 130/80 mmHg enrolled in the study. RESULTS: A significant decrease in systolic and diastolic BP was observed in both clinic and home measurement after switching from the previous treatment to LOS/HCTZ. There was a significant decrease in both B-type natriuretic peptide (BNP) and urinary albumin creatinine (Cr) excretion ratio (ACR), especially in patients with elevated values. In contrast, there was a significant increase in serum Cr concentration in conjunction with a decrease in estimated glomerular filtration rate (eGFR). Overall serum uric acid (UA) concentration increased, whereas in patients with hyperuricemia there was a significant reduction in this value. CONCLUSION: Switching to LOS/HCTZ provides a greater reduction in clinic and home BP in patients with uncontrolled hypertension. This combination therapy may lead to cardio-, reno protection and improve UA metabolism.

New measurement of the K+-->pi+ nunu branching ratio.

Three events for the decay K+-->pi+ nunu have been observed in the pion momentum region below the K+-->pi+pi0 peak, 140 < Ppi < 199 MeV/c, with an estimated background of 0.93+/-0.17(stat.) -0.24+0.32(syst.) events. Combining this observation with previously reported results yields a branching ratio of B(K+-->pi+ nunu) = (1.73(-1.05)+1.15) x 10(-10) consistent with the standard model prediction.

[Thoracic surgery for the penetrating lung or tracheal trauma].

Seven cases suffered from a chest trauma (stab wound in 6 and impalement injury in 1) were emergently transferred to our hospital. Open thoracotomy was performed for the intolerable bleeding immediately after admission. Injured lung was treated by lobectomy in 1 patient, lingual segmentectomy in 2, lower basal segmentectomy in 2, partial resection in 4 and direct suture in 2. The penetrating trachea was carefully repaired by direct suture with additional midsternal thoracotomy. To accomplish appropriate partial resection of the injured lung, a metallic straight suction tube inserted into a pulmonary stab wound was retracted and a stapling instrument was applied underneath the suction tube. With the segmentectomy and the partial resection, the volume of the residual lung was maximally saved. As a result, all 7 patients were successfully alive.

Analysis of potential diagnostic biomarkers in cerebrospinal fluid of idiopathic normal pressure hydrocephalus by proteomics.

BACKGROUND: The pathogenesis of idiopathic normal pressure hydrocephalus (INPH) is unknown, and the syndrome of INPH remains a diagnostic and therapeutic challenge. The present study investigated the disease-specific proteins that aid in the diagnosis and treatment of INPH and thus to study their role in the disease process. METHODS: A comparative proteomic analysis was used for clinical screening of cerebrospinal fluid (CSF) proteins in 15 patients with INPH and compared with 12 normal subjects. Furthermore, enzyme linked immunosorbent assay (ELISA) was performed for comparison with CSF proteins between individual INPH patients and controls. RESULTS: Seven proteins and their isoforms, including leucine-rich alpha-2-glycoprotein (LRG), alpha1-antichymotrypsin, apolipoprotein D, apolipoprotein J, haptoglobin alpha1, serum albumin, and alpha-1-microglobulin/bikunin precursor showed significant changes in CSF of INPH patients compared with controls by proteomic analysis. And significant higher CSF levels of LRG in INPH patients compared with controls were found by ELISA. CONCLUSIONS: These results indicate that there are significant differences in the expression of certain proteins in the CSF of patients with INPH and normal subjects. In particular, the CSF level assay of LRG suggests that LRG is a specific biomarker for INPH and has potential use in the diagnosis and indication for CSF shunting.

Cranial reshaping employing distraction and contraction in the treatment of sagittal synostosis.

We treated four patients with scaphocephaly using a combination of distraction and contraction techniques and achieved satisfactory results. Radial osteotomies in the frontal and occipital bones flattened these abnormal bossing bones and accelerated the disappearance of bony bumps created by distraction. This technique facilitates the achievement of the desired shape of the skull through fine adjustments of the distraction and contraction devices.

Intracranial peripheral primitive neuroectodermal tumor manifesting as abducens nerve palsy.

INTRODUCTION: Peripheral primitive neuroectodermal tumor (PNET) occurring as an extra-axial lesion within the intracranial space and extending to the subarachnoid space is extremely rare. CASE REPORT: An 18-month-old girl presented with an intracranial peripheral PNET manifesting as abducens nerve palsy. Magnetic resonance imaging on admission revealed a lesion affecting the trigeminal and abducens nerves. The tumor was partially removed via the subtemporal approach. Histological examination showed a high-grade, undifferentiated neoplasm of small cell type with positive immunostaining for MIC2. The histological diagnosis was peripheral PNET. OUTCOME: Craniospinal radiotherapy reduced the tumor size, but adjuvant chemotherapy designed for Ewing's sarcomas and PNETs was not effective. She died 1 month after the last chemotherapy, despite whole craniospinal irradiation (total dose 53.2 Gy) and chemotherapy.

Improved measurement of the K+-->pi+nunu; branching ratio.

An additional event near the upper kinematic limit for K+-->pi(+)nunu; has been observed by experiment E949 at Brookhaven National Laboratory. Combining previously reported and new data, the branching ratio is B(K+-->pi(+)nunu;)=(1.47(+1.30)(-0.89))x10(-10) based on three events observed in the pion momentum region 211

Characterization of urease-positive thermophilic Campylobacter subspecies by multilocus enzyme electrophoresis typing.

Thirty-one urease-positive thermophilic Campylobacter (UPTC) isolates, including three reference strains (NCTC12892, NCTC12895 and NCTC12896), and three Campylobacter lari isolates, which were isolated from several countries and sources, were compared genotypically by using multilocus enzyme electrophoresis (MLEE). We examined allelic variation around seven enzyme loci, including the adenylate kinase, alkaline phosphatase, catalase, fumarase, malic enzyme, malate dehydrogenase, and L-phenylalanyl-L-leucine peptidase loci. MLEE typing revealed the presence of 23 different electrophoretic types (ETs) among the 31 UPTC isolates, and 14 isolates shared six electrophoretic profiles. Three different ETs were identified for the three C. lari isolates examined, and no ETs were shared by UPTC and C. lari isolates. Quantitative analyses were subsequently performed by using allelic variation data, and the results demonstrated that the mean genetic diversity was 0.655. In conclusion, MLEE demonstrated that the UPTC isolates examined are genetically hypervariable and form a cluster separate from the C. lari cluster.

Cloning and sequencing of 16S rDNA and 16S-23S rDNA internal spacer region (ISR) from urease-positive thermophilic Campylobacter (UPTC).

AIMS: To clone and sequence the 16S rDNA and 16S-23S rDNA internal spacer region (ISR) from urease-positive thermophilic Campylobacter (UPTC). METHODS AND RESULTS: The primer sets for 16S rDNA and 16S-23S rDNA ISR amplified almost the full length of 16S rDNA and 16S-23S rDNA ISR. About 1500 bp for 16S rDNA and about 720 bp for 16S-23S rDNA ISR of the rrn operon of four strains of UPTC were identified after molecular cloning and sequencing. CONCLUSIONS: The four strains and CCUG18267 of UPTC showed approximately 99% sequence homology of 16S rDNA to each other, 96-97% to Camp. coli, 97-98% to Camp. jejuni and 97-98% to Camp. lari. SIGNIFICANCE AND IMPACT OF THE STUDY: For the first time, the nucleotide sequence of 16S-23S rDNA ISR of UPTC has been analysed. The sequence of ISR was almost identical among the four strains of UPTC. It is interesting that the UPTC intercistronic tRNAs demonstrated an order of tRNA of 5'-16S-tRNAAla-tRNAIle-23S-3' in the organisms.

Further evidence for the decay K+ -->pi+nu(nu).

Additional evidence for the rare kaon decay K+-->pi+nu(nu) has been found in a new data set with comparable sensitivity to the previously reported result. One new event was observed in the pion momentum region examined, 211pi+nu(nu)) = 1.57(+1.75)(-0.82)x10(-10).

Echocardiographic features in a patient with primary oxalosis.

Primary oxalosis is a rare congenital disorder of oxalate metabolism characterized by deposits of calcium oxalate in several organs, including the heart. We present the case of a 38-year-old man with primary oxalosis who had unique echocardiographic findings. Two-dimensional echocardiography revealed the sparkling high intensity echocardiographic pattern and concentric thickening of myocardial walls. Microscopic examinations showed the extensive deposits of calcium oxalate crystals in the myocardium. Therefore, we suggest that primary oxalosis should be given important consideration in the differential diagnosis of a hypertrophied myocardium with high intensity echocardiograms.

Surgical experience of 120 patients with lumbosacral lipomas.

The surgical experience of 120 patients with lumbosacral lipomas is described. 47 of 120 patients were preoperatively found to be neurologically intact, the remaining 73 patients presented with various neurological signs including reflex changes, sensory disturbances, muscle weakness and sphincter problems. Neuro-imagings allowed a classification of lumbosacral lipomas into five types: (1) dorsal type; (2) caudal type; (3) combined type; (4) filar type; and (5) lipomyelomeningocele. Although all 120 patients underwent untethering of the spinal cord, the nerve roots passing through the lipoma itself and the neural tissues protruding externally to the spinal canal, respectively, tended to prevent satisfactory surgical removal of the lipoma in combined type lipomas and lipomyelomeningoceles. During 8.96 years of a mean postoperative follow-up period, there was no significant deterioration in most of the patients and some patients even improved in function. However, two patients with combined type lipomas developed neurological deterioration just after surgery, and five (two dorsal, two caudal and one combined type lipomas) did in the fashion of a late-onset. There are two different patient groups of lumbosacral lipomas; one group (caudal and filar type lipomas, and most of dorsal type lipomas) in whom the surgical anatomy is simple and satisfactory untethering surgery could be done without risk, and another (combined type lipomas and lipomyelomeningocele) in whom surgery would be accompanied with some risk and sometimes complete untethering could not be achieved because of the complicated anatomy of the lesion. Surgical difficulty of the latter group can be correlated with the increased frequency of neurological deterioration occurring just after the operation, but not of delayed one. Concerning prophylactic surgery for asymptomatic patients, the former group of patients are obviously good candidates, but the latter group is not.

Successful transarterial glue embolisation by wedged technique for a tentorial dural arteriovenous fistula presenting with a conjunctival injection.

Many tentorial dural arteriovenous fistulae (TDAVF) present with intracranial haemorrhage. We report a patient who presented with conjunctival injection. Transarterial embolisation of the TDAVF was undertaken with a wedged injection of a low concentration of N-butyl cyanoacrylate, arresting the flow next to the proximal segment of the venous outlet. After three sessions, a complete cure was achieved. We present a useful method which has not been reported previously.

Release behavior of ketoprofen from poly(acryloyl-L-proline methyl ester) gels having different crosslinked networks.

In order to clarify the relationship between the crosslinked structure of thermo-responsive polymer and drug release profile, polymer gels based on acryloyl-L-proline methyl ester (A-ProOMe) were synthesized in a mixture of water and acetone by the following two methods: a simultaneously occurring process of radiation-induced polymerization and crosslinking without a crosslinker (self-bridging method), and radiation-induced polymerization in the presence of the crosslinker tetradecaethylene glycol dimethacrylate (crosslinker method). The pronounced gap in thermo-response between two A-ProOMe gels, with an apparent degree of crosslinking of 11 for 1-propanol, shows a different shrinking pattern in the initial stage of time. The gels, which were obtained with the self-bridging method and the crosslinker method, were kept constant at a swelling ratio of 17 in water at 0 degree C for all systems. However, those values fell to 0.5 and 4, respectively, at 10 min after the temperature was increased to 37 degrees C. The release mechanism of ketoprofen from two gel devices showed an anomalous (non-Fickian) transport, in which the release of ketoprofen with a low water-solubility could be directly related to the rapid release of water accompanying a gel shrinkage.