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Cerebrospinal Fluid (cerebrospinal + fluid)
Kinds of Cerebrospinal Fluid Terms modified by Cerebrospinal Fluid Selected AbstractsCytologie Du Liquide Cephaloricachidien (Cytology of the Cerebrospinal Fluid)NEUROPATHOLOGY & APPLIED NEUROBIOLOGY, Issue 4 2005Roy O. Weller No abstract is available for this article. [source] Reissner's Fibre Proteins and p73 Variations in the Cerebrospinal Fluid and Subcommissural Organ of Hydrocephalic RatANATOMIA, HISTOLOGIA, EMBRYOLOGIA, Issue 4 2009E. M. Carmona-Calero Summary Reissner's fibre (RF) is formed by the polymerization of the glycoprotein secreted by the subcommissural organ (SCO). The SCO also secretes soluble glycoprotein into the cerebrospinal fluid (CSF); variations in RF and SCO have been reported in hydrocephalus. On the other hand, hydrocephalus and other brain alterations have been described in p73 mutant mice. The p73 belongs to the tumour suppressor p53 protein family and has two isoforms: the TAp73 with apoptotic activity and ,Np73 with anti-apoptotic function. Moreover, the TAp73 isoform is glycosylated and secreted into the CSF. In the present work, we analysed the variations in RF and p73 proteins in the CSF and SCO of spontaneously hydrocephalic rats. Brains from control rats and spontaneously hydrocephalic rats of 12 months of age were used. The SCO sections were immunohistochemically processed with anti-TAp73 and anti-Reissner fibre (AFRU). The spontaneous hydrocephalus presents a decrease in the AFRU immunoreactive material in the SCO and an absence of RF. The anti-TAp73 was also present, slightly decreased, in the hydrocephalic SCO. AFRU and p73 bands were also detected in the CSF by western blot and six AFRU and p73 protein bands of a similar molecular weight were found in the CSF of the control rats. The number of AFRU and p73 bands was lower in the hydrocephalic rats than in the control rats. In conclusion, hydrocephalus produces a decrease in the secretions of the SCO and an absence of RF and a decrease in p73 and RF proteins in the CSF. [source] Use of Quantitative Broad-based Polymerase Chain Reaction for Detection and Identification of Common Bacterial Pathogens in Cerebrospinal FluidACADEMIC EMERGENCY MEDICINE, Issue 7 2010Richard Rothman MD ACADEMIC EMERGENCY MEDICINE 2010; 17:741,747 © 2010 by the Society for Academic Emergency Medicine Abstract Background:, Conventional laboratory diagnosis of bacterial meningitis based on microscopy followed by culture is time-consuming and has only moderate sensitivity. Objectives:, The objective was to define the limit of detection (LOD), analytic specificity, and performance characteristics of a broad-based quantitative multiprobe polymerase chain reaction (PCR) assay for rapid bacterial detection and simultaneous pathogen-specific identification in patients with suspected meningitis. Methods:, A PCR algorithm consisting of initial broad-based detection of Eubacteriales by a universal probe, followed by pathogen identification using either pathogen-specific probes or Gram-typing probes, was employed to detect pathogens. The 16S rRNA gene, which contains both conserved and variable regions, was chosen as the target. Pathogen-specific probes were designed for Streptococcus pneumoniae, Neisseria meningitidis, Haemophilus influenzae, Staphylococcus epidermidis, Staphylococcus aureus, Escherichia coli, and Listeria monocytogenes. Gram-positive and -negative typing probes were designed based on conserved regions across all eubacteria. The LOD and time to detection were assessed by dilutional mocked-up samples. A total of 108 convenience cerebrospinal fluid (CSF) clinical samples obtained from the Johns Hopkins Hospital (JHH) microbiology laboratory were tested, and results were compared with hospital microbiologic culture reports. Results:, The LOD of the assay ranged from 101 to 102 colony-forming units (CFU)/mL. Pathogen-specific probes showed no cross-reactivity with other organisms. Time to detection was 3 hours. In clinical specimens, the universal probe correctly detected 16 of 22 culture-positive clinical specimens (sensitivity = 72.7%; 95% confidence interval [CI] = 49.8% to 89.3%), which were all correctly characterized by either pathogen-specific or Gram-typing probes. Adjusted sensitivity after removing probable microbiologic laboratory contaminants was 88.9% (95% CI = 65.3% to 98.6%). The universal probe was negative for 86 of 86 culture-negative specimens. Conclusions:, A broad-based multiprobe PCR assay demonstrated strong analytic performance characteristics. Findings from a pilot clinical study showed promise in translation to human subjects, supporting potential utility of the assay as an adjunct to traditional diagnostics for early identification of bacterial meningitis. [source] Cerebrospinal fluid and serum antibodies against neurofilaments in patients with amyotrophic lateral sclerosisEUROPEAN JOURNAL OF NEUROLOGY, Issue 4 2010L. Fialová Background:, The aim of the study was to assess autoimmune involvement in amyotrophic lateral sclerosis (ALS). Methods:, We measured IgG antibodies against light (NFL) and medium (NFM) subunits of neurofilaments using ELISA in paired cerebrospinal fluid (CSF) and serum samples from 38 ALS patients and 20 controls. Results:, Serum levels of anti-NFL were higher in ALS patients than in controls (P < 0.005). Serum anti-NFL antibodies and intrathecal anti-NFM antibodies were related to patient disability (serum anti-NFL: P < 0.05; intrathecal anti-NFM: P < 0.05). Anti-NFL levels were significantly correlated with anti-NFM levels in ALS (P < 0.001) and the control group (P < 0.0001) in the CSF, but not in serum. Anti-NFL and anti-NFM antibodies significantly correlated between serum and CSF in the ALS group (anti-NFL: P < 0.0001; anti-NFM: P < 0.001) and in the control group (anti-NFL: P < 0.05; anti-NFM: P < 0.05). Conclusions:, Autoimmune humoral response to neurocytoskeletal proteins is associated with ALS. [source] Cerebrospinal fluid 14-3-3-, protein level in eight HIV-negative cryptococcal meningitis adultsEUROPEAN JOURNAL OF NEUROLOGY, Issue 4 2008W. N. Chang The clinical data and cerebrospinal fluid (CSF) 14-3-3-, protein detection of eight adult HIV-negative cryptococcal meningitis (CM) cases were examined. The eight cases included six males and two females aged 35,70 years (mean = 49.8 years). The duration between the onset of CM symptoms and the first CSF study ranged from 1 to 60 days. Initial neuroimaging study was abnormal in 87.5% (7/8) of the cases. All the eight had positive initial and subsequent follow-up CSF 14-3-3-, protein detection. The densitometric values of CSF 14-3-3-, protein were not correlated with either the CSF white blood cell counts or the therapeutic results. The therapeutic results showed that three cases died and five survived. Significant neurologic deficits were shown in 60% (3/5) of the survivors. This study revealed that HIV-negative CM patients have elevated CSF 14-3-3-, protein levels, and that this level is not changed with a short-term treatment. [source] The importance of cerebrospinal fluid on neural cell proliferation in developing chick cerebral cortexEUROPEAN JOURNAL OF NEUROLOGY, Issue 3 2006F. Mashayekhi Cerebrospinal fluid (CSF) is mainly produced by the choroid plexuses within the ventricles of the brain. The CSF circulates in a regular manner after the ventricular system and the choroids plexuses have developed, and the foramina in the fourth ventricle have opened to enable it to carry chemical information. CSF flows through the ventricular system passing over all regions of germinal activity. In this study, chick embryos were used to show the importance of CSF on neural cell proliferation in the developing cerebral cortex. The chick embryos were cannulated in situ with a fine capillary tube to drain CSF out of the ventricular system. At the same time, BrdU was administered to the embryos. After surgery the embryos were incubated for another 3 days. Quantitative measurements showed that the thicknesses of the germinal epithelium and cerebral cortex in CSF-drained embryos were less than those in the control group at the same age. The number of cells produced in the germinal epithelium of CSF-drained embryos was decreased when compared with the normal group. This study provides confirmatory evidence that CSF is important for neural cell proliferation and therefore normal development of the cerebral cortex. It is proposed that CSF is vital in controlling development of the cerebral cortex. [source] Expression of nerve growth factor in cerebrospinal fluid of congenital hydrocephalic and normal childrenEUROPEAN JOURNAL OF NEUROLOGY, Issue 8 2005F. Mashayekhi Cerebrospinal fluid (CSF) is secreted by the choroids plexuses and has the potential to act as a signaling pathway for physiological control as it has been demonstrated to contain molecules such as interleukins, leukoterins, neuropeptides, growth transforming factor-beta (TGF- ,) and nerve growth factor (NGF), which are present at specific times during development. In this study, CSF from hydrocephalic and normal children were analysed using SDS-PAGE followed by silver staining. In order to obtain semi-quantitative estimates of the relative amounts of 26 kDa protein, an image analyzer was used to determine the intensities of the band in the respective lanes in silver-stained gels. Quantification of the silver-stained gels from repeated experiments showed that the amount of 26 kDa protein was clearly increases in the hydrocephalic CSF when compared with the normal CSF. A Western blot analysis using anti-NGF antibody as a probe confirmed the presence of NGF. Using enzyme-linked immunosorbent assay (ELISA), it was shown that the level of NGF in the hydrocephalic CSF is higher than in normal CSF. It is concluded that NGF is not only a constant component of human CSF but could also be significantly involved in the pathophysiology of hydrocephalus. [source] Cerebral epidural hematoma following cerebrospinal fluid drainage during thoracoabdominal aortic repairACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 9 2009Y. B. JEONG Cerebrospinal fluid (CSF) drainage is a common adjunct to thoracoabdominal aortic aneurysm (TAAA) repair. CSF drainage may improve perioperative spinal cord perfusion and thereby decrease the incidence of paraplegia or paraparesis. Complications of CSF drainage may arise. We present a case of cerebral epidural hematoma (EDH), possibly arising from excessive CSF drainage, during thoracoabdominal aortic repair. [source] Staphylococcal meningoencephalitis, nematodiasis, and typhlocolitis in a squirrel monkey (Saimiri sciureus)JOURNAL OF MEDICAL PRIMATOLOGY, Issue 5 2009A. García Abstract Background, Seizures were observed in a 16-year old male Guyanese squirrel monkey with a history of inappetence and weakness. Methods and results, Complete blood count, biochemical profile, and urinalysis indicated systemic disease. Nematode larvae were detected in the feces. Cerebrospinal fluid (CSF) analysis revealed leukocytes and gram-positive cocci. Staphylococcus aureus was isolated from the CSF. Histopathological evaluation revealed systemic lesions with inflammation and nematodes in the small and large intestine. Conclusion, This is the first report describing spontaneous staphylococcal CNS infection in a squirrel monkey. [source] Steroid-Responsive Meningitis-Arteritis in Dogs with Noninfectious, Nonerosive, Idiopathic, Immune-Mediated PolyarthritisJOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 3 2002Aubrey A. Webb Signs related to spinal pain are commonly reported in dogs with noninfectious, nonerosive, idiopathic immune-mediated polyarthritis (IMPA). This study examined the prevalence and etiology of spinal pain in these dogs through a retrospective review of 62 case records of dogs with IMPA. All dogs with IMPA and signs suggestive of spinal pain were described with regard to age, gender, breed, physical stature, location of vertebral pain, rectal temperature, and clinical laboratory findings. The prevalence of spinal pain in these dogs was 29% (18 of 62). Fourteen of the 18 dogs with spinal pain and IMPA were male. Cerebrospinal fluid (CSF) from 11 dogs with signs of spinal pain was analyzed. Five of these (46%) had concurrent steroid-responsive meningitis-arteritis (SRMA). We concluded that SRMA does occur concurrently in some dogs having IMPA. Meningeal involvement may explain the origin of spinal pain observed in some of these dogs. [source] Pharmacokinetics of 4-aminopyridine derivatives in dogsJOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 5 2009N. J. OLBY Blockade of potassium channels with 4-aminopryidine (4-AP) restores conduction to demyelinated axons and improves function. Unfortunately, 4-AP causes adverse effects and its clinical effects are unpredictable and limited. Derivatives of 4-AP have been tested in models of spinal cord injury in guinea pigs; three derivatives (methyl-, ethyl- and t -butyl carbamate derivatives) showed promise. This study investigates the safety and pharmacokinetics of these derivatives in dogs. Each derivative was administered orally to dogs starting at doses below effective doses in guinea pigs, and increasing the dose on sequential days. Routine blood work was performed prior to and 24 h after drug administration, blood samples were collected at intervals over 24 h after drug administration, and dogs were monitored for side effects. Derivative plasma levels were determined using high-pressure liquid chromatography. Cerebrospinal fluid (CSF) samples were taken to determine CSF levels. No adverse effects were seen even when using doses higher than those that improved conduction in spinal cord injured guinea pigs. Peak plasma levels occurred at 36.6 (ethyl), 87 (t -butyl) and 175 (methyl) min and plasma level was related to drug dose. Penetration of the central nervous system (CNS) was good, with CSF levels higher than plasma levels for the t -butyl derivative. [source] Further case of paroxysmal exercise-induced dystonia and some insights into pathogenesis,MOVEMENT DISORDERS, Issue 6 2002Michael H. Barnett MD Abstract Cerebrospinal fluid (CSF) analysis of pterin and monamine metabolites was performed before and after an attack in a patient with paroxysmal exercise-induced dystonia. A twofold increase in CSF homovanillic acid and 5-hydroxyindoleacetic acid after an attack was measured. This finding lends support to the hypothesis that increased dopaminergic transmission contributes to the clinical features of the hyperkinetic movement disorders. © 2002 Movement Disorder Society [source] CSF amyloid-, 1-38 and 1-42 in FTD and AD: Biomarker performance critically depends on the detergent accessible fractionPROTEOMICS - CLINICAL APPLICATIONS, Issue 10-11 2008Mirko Bibl Dr. Abstract Cerebrospinal fluid (CSF) A,1-38, A,1-40, and A,1-42 were comparatively analyzed by amyloid-beta SDS-PAGE with Western immunoblot (A,-SDS-PAGE/immunoblot), electrochemiluminescence detection and ELISA (MSD/ELISA) in patients with Alzheimer's disease (AD, n,=,40), frontotemporal dementia (FTD, n,=,30), and other dementias (n,=,50) and nondemented disease controls (n,=,30). CSF A,-peptide concentrations were higher and selective decreases of CSF A,1-38 in FTD and A,1-42 in AD were more evident as measured after SDS-denaturizing of samples by A,-SDS-PAGE/immunoblot. The SDS-accessible pool of CSF A,1-38 and A,1-42, represented by the individual gain of A,-peptide yield using A,-SDS-PAGE/immunoblot, was reduced in both FTD and AD. Accordingly, biomarker accuracies of A,1-38 and A,1-42 for detection of FTD and AD, respectively declined as determined by MSD/ELISA. We conclude that a pool of CSF A,1-38 and A,1-42, which shows disease-specific reductions in FTD and AD, may be bound to carriers and can be released by SDS. Assessing this SDS-accessible A,-peptide pool may crucially enhance the accuracy of CSF biomarker tests. Identifying disease-specific binding properties of affected A, carriers may elucidate pathogenic aspects and open up a novel field for therapeutic approaches. [source] Cerebrospinal fluid of brain trauma patients inhibits in vitro neuronal network function via NMDA receptors,ANNALS OF NEUROLOGY, Issue 4 2009Frauke Otto MD Neurological diseases frequently induce pathological changes of cerebrospinal fluid (CSF) that might secondarily influence brain activity, as the CSF,brain barrier is partially permeable. However, functional effects of CSF on neuronal network activity have not been specified to date. Here, we report that CSF specimens from patients with reduced Glasgow Coma Scale values caused by severe traumatic brain injury suppress synchronous activity of in vitro-generated neuronal networks in comparison with controls. We present evidence that underlying mechanisms include increased N -methyl- D- aspartate receptor activity mediated by a CSF fraction containing elevated amino acid concentrations. These proof-of-principle data suggest that determining effects of CSF specimens on neuronal network activity might be of diagnostic value. Ann Neurol 2009;66:546,555 [source] West Nile virus neuroinvasive diseaseANNALS OF NEUROLOGY, Issue 3 2006Larry E. Davis MD Since 1999, there have been nearly 20,000 cases of confirmed symptomatic West Nile virus (WNV) infection in the United States, and it is likely that more than 1 million people have been infected by the virus. WNV is now the most common cause of epidemic viral encephalitis in the United States, and it will likely remain an important cause of neurological disease for the foreseeable future. Clinical syndromes produced by WNV infection include asymptomatic infection, West Nile Fever, and West Nile neuroinvasive disease (WNND). WNND includes syndromes of meningitis, encephalitis, and acute flaccid paralysis/poliomyelitis. The clinical, laboratory, and diagnostic features of these syndromes are reviewed here. Many patients with WNND have normal neuroimaging studies, but abnormalities may be present in areas including the basal ganglia, thalamus, cerebellum, and brainstem. Cerebrospinal fluid invariably shows a pleocytosis, with a predominance of neutrophils in up to half the patients. Diagnosis of WNND depends predominantly on demonstration of WNV-specific IgM antibodies in cerebrospinal fluid. Recent studies suggest that some WNV-infected patients have persistent WNV IgM serum and/or cerebrospinal fluid antibody responses, and this may require revision of current serodiagnostic criteria. Although there is no proven therapy for WNND, several vaccines and antiviral therapy with antibodies, antisense oligonucleotides, and interferon preparations are currently undergoing human clinical trials. Recovery from neurological sequelae of WNV infection including cognitive deficits and weakness may be prolonged and incomplete. Ann Neurol 2006;60:286,300 [source] Cerebrospinal fluid, serum and plasma protein oxidation in Alzheimer's diseaseACTA NEUROLOGICA SCANDINAVICA, Issue 1 2009M. A. Korolainen Objectives,,, Many studies have shown differences in carbonylation and nitration of individual proteins in brain and body fluids of Alzheimer's disease (AD) patients. Therefore, we wanted to examine whether total levels of these oxidative stress markers of proteins were altered in AD. Patients and methods,,, Total levels of carbonyls and nitrotyrosine in cerebrospinal fluid, serum and plasma were measured in 22 AD patients and 18 age-matched controls using commercially available enzyme immunoassay kits. Results,,, Protein carbonylation in cerebrospinal fluid did not differ between AD patients and controls but was decreased in APOE ,4 carriers as compared with non-carriers. Serum but not plasma levels of carbonyls tended to be decreased in AD patients as compared with aged controls. Nitrotyrosine concentrations did not differ between the groups. Surrogate cerebrospinal fluid markers for AD, beta-amyloid (1,42) and tau, correlated with blood carbonyl and nitrotyrosine levels. Conclusions,,, According to these preliminary data, changes in oxidative metabolism related to the pathogenesis of AD cannot be detected as increased cerebrospinal fluid, serum or plasma protein carbonylation or nitration. [source] Detection of bacterial DNA by PCR and reverse hybridization in the 16S rRNA gene with particular reference to neonatal septicemiaACTA PAEDIATRICA, Issue 2 2001S Shang Aim: The clinical diagnosis of sepsis is difficult, particularly in neonates. It is necessary to develop a rapid and reliable method for detecting bacteria in blood and cerebrospinal fluid (CSF) Polymerase chain reaction (PCR) and reverse hybridization of the 16S rRNA gene would permit fast and sensitive determination of the presence of bacteria and differentiate gram-positive bacteria from gram-negative ones in clinical specimens. Methods: We developed a pair of primers according to the gene encoding 16SrRNA found in all bacteria. DNA fragments from different bacterial species and from clinical samples were detected with PCR, and with reverse hybridization using a universal bacterial probe, a gram-positive probe and a gram-negative probe. Results: A 371 bp DNA fragment was amplified from 20 different bacterial species. No signal was observed when human DNA and viruses were used as templates. The sensitivity could be improved to 10T -12 g. All 26 culture-positive clinical samples (22 blood samples and 4 CSF samples) were positive with PCR. The gram-negative and gram-positive probes hybridized to clinical samples and to known bacterial controls, as predicted by Gram's stain characteristics. Conclusions: Our results suggest that the method of PCR and reverse hybridization is rapid, sensitive and specific in detecting bacterial infections. This finding may be significant in the clinical diagnosis of sepsis in neonates. [source] Etiologic spectrum and pattern of antimicrobial drug susceptibility in bacterial meningitis in Sokoto, NigeriaACTA PAEDIATRICA, Issue 8 2000FE EmeleArticle first published online: 2 JAN 200 Etiologic agents of meningitis were prospectively investigated among patients admitted to Usman Danfodio University Teaching Hospital, Sokoto. Of 1097 cerebrospinal fluid (CSF) samples submitted to the microbiology laboratory from various wards of the hospital, 289 (26%) were microscopically, culturally and/or serologically proven to be bacterial meningitis. The etiologic spectrum was as follows: Neisseria meningitidis (61%), Streptococcus pneumoniae (18%), Haemophilus influenzae (10%), Staphylococcus aureus (6%), Coliform bacilli (3%), Escherichia coli (0.7%), Mycobacterium tuberculosis (0.7%), Listeria monocytogenes (0.4%), Flavobacterium meningosepticum (0.4%) and Pseudomonas putrifasciens (0.4%). Bacterial meningitis was most prevalent (195 or 68%) among children aged 1-9 y, while adults and neonates were least affected. Coliform bacilli caused five of eight neonatal cases. Males were more frequently affected than females (x2=12.50;p < 0.05). Culture and microscopy were comparatively less efficient than the search for bacterial antigens, especially in the diagnosis of Haemophilus meningitis. Antimicrobial susceptibility of N. meningitidis to ampicillin and benzyl penicillin reduced progressively over the years (F = 406.98;p < 0.001). Nineteen (11%) of the isolates (5 Meningococci, 7 Staph. aureus, 1 Haem. influenza and 6 others) showed simultaneous resistance to chloramphenicol, ampicillin and benzyl penicillin. [source] Hypocretin/orexin and narcolepsy: new basic and clinical insightsACTA PHYSIOLOGICA, Issue 3 2010S. Nishino Abstract Narcolepsy is a chronic sleep disorder, characterized by excessive daytime sleepiness (EDS), cataplexy, sleep paralysis and hypnagogic hallucinations. Both sporadic (95%) and familial (5%) forms of narcolepsy exist in humans. The major pathophysiology of human narcolepsy has been recently discovered based on the discovery of narcolepsy genes in animals; the genes involved in the pathology of the hypocretin/orexin ligand and its receptor. Mutations in hypocretin-related genes are rare in humans, but hypocretin ligand deficiency is found in a large majority of narcolepsy with cataplexy. Hypocretin ligand deficiency in human narcolepsy is probably due to the post-natal cell death of hypocretin neurones. Although a close association between human leucocyte antigen (HLA) and human narcolepsy with cataplexy suggests an involvement of autoimmune mechanisms, this has not yet been proved. Hypocretin deficiency is also found in symptomatic cases of narcolepsy and EDS with various neurological conditions, including immune-mediated neurological disorders, such as Guillain,Barre syndrome, MA2-positive paraneoplastic syndrome and neuromyelitis optica (NMO)-related disorder. The findings in symptomatic narcoleptic cases may have significant clinical relevance to the understanding of the mechanisms of hypocretin cell death and choice of treatment option. The discoveries in human cases lead to the establishment of the new diagnostic test of narcolepsy (i.e. low cerebrospinal fluid hypocretin-1 levels for ,narcolepsy with cataplexy' and ,narcolepsy due to medical condition'). As a large majority of human narcolepsy patients are ligand deficient, hypocretin replacement therapy may be a promising new therapeutic option, and animal experiments using gene therapy and cell transplantations are in progress. [source] The BSCC Code of Practice , exfoliative cytopathology (excluding gynaecological cytopathology)CYTOPATHOLOGY, Issue 4 2009A. Chandra Exfoliative cytopathology (often referred to as non-gynaecological cytology) is an important part of the workload of all diagnostic pathology departments. It clearly has a role in the diagnosis of neoplastic disease but its role in establishing non-neoplastic diagnoses should also be recognised. Ancillary tests may be required to establish a definitive diagnosis. Clinical and scientific teamwork is essential to establish an effective cytology service and staffing levels should be sufficient to support preparation, prescreening, on-site adequacy assessment and reporting of samples as appropriate. Routine clinical audit and histology/cytology correlation should be in place as quality control of a cytology service. Cytology staff should be involved in multidisciplinary meetings and appropriate professional networks. Laboratories should have an effective quality management system conforming to the requirements of a recognised accreditation scheme such as Clinical Pathology Accreditation (UK) Ltd. Consultant pathologists should sign out the majority of exfoliative cytology cases. Where specimens are reported by experienced biomedical scientists (BMS), referred to as cytotechnologists outside the UK, this must only be when adequate training has been given and be defined in agreed written local protocols. An educational basis for formalising the role of the BMS in exfoliative cytopathology is provided by the Diploma of Expert Practice in Non-gynaecological Cytology offered by the Institute of Biomedical Science (IBMS). The reliability of cytological diagnoses is dependent on the quality of the specimen provided and the quality of the preparations produced. The laboratory should provide feedback and written guidance on specimen procurement. Specimen processing should be by appropriately trained, competent staff with appropriate quality control. Microscopic examination of preparations by BMS should be encouraged wherever possible. Specific guidance is provided on the clinical role, specimen procurement, preparation and suitable staining techniques for urine, sputum, semen, serous cavity effusion, cerebrospinal fluid, synovial fluid, cyst aspirates, endoscopic specimens, and skin and mucosal scrapes. [source] Audit can reduce inappropriate requests for cytological examination of cerebrospinal fluidCYTOPATHOLOGY, Issue 2 2004M. W. Weatherall No abstract is available for this article. [source] The clinical presentation of mitochondrial diseases in children with progressive intellectual and neurological deterioration: a national, prospective, population-based studyDEVELOPMENTAL MEDICINE & CHILD NEUROLOGY, Issue 5 2010CHRISTOPHER M VERITY Aim, Our aim was to study the clinical presentation, mode of diagnosis, and epidemiology of mitochondrial disorders in children from the UK who have progressive intellectual and neurological deterioration (PIND). Method, Since April 1997, we have identified patients aged 16 years or younger with suspected PIND through the monthly notification card sent to all UK consultant paediatricians by the British Paediatric Surveillance Unit. Clinical details obtained from reporting paediatricians are classified by an Expert Group. Results, By July 2008, 2493 cases of PIND had been reported, among which there were 112 children (69 males, 43 females) with mitochondrial diseases presenting between birth and 14 years 7 months (median 12mo), divided into 13 subgroups. In some instances, clinical features were characteristic of mitochondrial disease, but many children presented non-specifically with combinations of developmental delay, hypotonia, failure to thrive, and seizures; 16 children had multisystem disease at presentation. Mortality was high: 40 children had died. Blood and/or cerebrospinal fluid lactate measurements were abnormal in 87 children, and 47 of 78 brain magnetic resonance images showed increased basal ganglia signal. Definite diagnoses were usually made by muscle enzyme or genetic studies. Interpretation, This is a unique population-based study of the mitochondrial disorders that cause childhood neurodegenerative disease. It provides detailed information about the clinical presentation and investigation of these complex cases. [source] Infantile spasms and cytomegalovirus infection: antiviral and antiepileptic treatmentDEVELOPMENTAL MEDICINE & CHILD NEUROLOGY, Issue 9 2007Dorota Dunin-Wasowicz MD PhD From 1 January 1995 to 31 December 2004, 22 patients (13 males, nine females; age range 2-12mo) with infantile spasms and cytomegalovirus (CMV) infection were treated with intravenous ganciclovir (GCV) and antiepileptic drugs. GCV was given for 3 to 12 weeks with a 1-month interval (one, two, or three courses). Epileptic spasms occurred before (group A: eight patients), simultaneously (group B: eight patients), and after (group C: six patients) a diagnosis of human CMV (HCMV) infection and antiviral treatment. In 11 patients, DNA HCMV was found in cerebrospinal fluid by nested-polymerase chain reaction method (neuroinfection). All infants excreted CMV in urine. DNA HCMV and specific immunoglobulin M and immunoglobulin G antibodies were present in blood. Ten patients, including four with neuroinfection, have been seizure-free for at least the past 18 months. In two patients with neuroinfection, vigabatrin monotherapy was withdrawn after a 2 year 6 month seizure-free period. Eighteen patients required antiepileptic drugs polytherapy, four of whom required additional adrenocorticotropic hormone (ACTH). Six patients on polytherapy were seizure-free on follow-up, two of whom were treated with ACTH, but no patient with hypsarrhythmia who required ACTH treatment was seizure-free on follow-up. In five patients, psychomotor development was normal, 16 had tetraplegia (Gross Motor Function Classification System [GMFCS] Level V), and one had diplegia (GMFCS Level III). Early antiviral and antiepileptic therapy could result in the long-term cessation of seizures. [source] Cerebrospinal fluid insulin-like growth factors IGF-1 and IGF-2 in infantile autismDEVELOPMENTAL MEDICINE & CHILD NEUROLOGY, Issue 9 2006Raili Riikonen MD PhD There has been little exploration of major biologic regulators of cerebral development in autism. We measured insulin-like growth factors (IGF) -1 and -2 from cerebrospinal fluid (CSF) by radio immunoassay in 25 children with autism (median age 5y 5mo; range 1y 11mo-15y 10mo; 20 males, 5 females), and in 16 age-matched comparison children without disability (median age 7y 4mo; range 1y 1mo-15y 2mo; eight males, eight females). IGF-1 and -2 concentrations were further correlated with age of patients and head size. CSF IGF-1 concentration was significantly lower in patients with autism than in the comparison group. The CSF concentrations of children with autism under 5 years of age were significantly lower than their age-matched comparisons. The head circumferences correlated with CSF IGF-1 in children with autism but no such correlation was found in the comparison group. There was no difference between the two groups in CSF IGF-2 concentrations. No patients with autism had macrocephaly. We conclude that low concentrations of CSF IGF-1 at an early age might be linked with the pathogenesis in autism because IGF-1 is important for the survival of Purkinje cells of the cerebellum. The head growth might be explained by the actions of IGF-1 and -2 reflected in CSF concentrations. [source] Childhood encephalopathy: viruses, immune response, and outcomeDEVELOPMENTAL MEDICINE & CHILD NEUROLOGY, Issue 4 2006Michael Clarke BSc MB ChB FRCPCH This study examined children with an acute encephalopathy illness for evidence of viral infection, disordered blood-brain barrier function, intrathecal immunoglobulin synthesis, and interferon (IFN) production, and related their temporal occurrence to outcome. A prospective study of 22 children (13 males, 9 females; age range 1mo to 13y, median 2y 4mo), recorded clinical details, with serum and cerebrospinal fluid (CSF) analysis near presentation and then on convalescent specimens taken up to day 39 of the neurological illness. Outcome was assessed with standard scales between 18 months and 3 years after presentation. A history consistent with viral infection was given in 17 children but laboratory evidence of viral infection was found in only 7 (7/17). In 18 out of 21 children, an elevated CSF: serum albumin ratio indicative of impairment of the blood,CSF and blood,brain barriers was detected at some stage of the illness. In 14 of the 15 children with a raised immunoglobulin G index, and in 12 of the 14 children where the CSF was positive for oligoclonal bands, this was preceded by, or was observed at the same time as, an abnormal albumin ratio. Sixteen children (16/18) had elevated IFN-, levels in serum, or CSF, or in both. We conclude that these findings indicate an initial disruption of the blood-brain barrier followed by intrathecal antibody production by activated lymphocytes, clonally restricted to a few antigens. This is the first in vivo study to show this as an important pathogenetic mechanism of encephalitis in children. Poor outcome was associated with young age, a deteriorating electroencephalogram pattern from grade 1 to grade 2, and the degree of blood-brain barrier impairment, particularly when prolonged, but not with Glasgow Coma Scale score. The persistence of IFN-, was associated with a good prognosis. [source] Decreased activities of mitochondrial respiratory chain complexes in non-mitochondrial respiratory chain diseasesDEVELOPMENTAL MEDICINE & CHILD NEUROLOGY, Issue 2 2006Joannie Hui MBBS The aim of this study was to illustrate the difficulties in establishing a diagnosis of mitochondrial respiratory chain (MRC) disorders based on clinical grounds in combination with intermediate activities of the MRC enzyme complexes. We reviewed retrospectively all medical and laboratory records of patients initially considered likely to have MRC disorders on clinical grounds, and subsequently diagnosed with other disorders (n=20; 11 males, 9 females). Data were retrieved from hospital records, referral letters, and results of enzymatic analysis at a reference laboratory. Clinical symptoms included developmental delay, epilepsy, hypotonia, movement disorder, spastic quadriplegia, tetany, microcephaly, visual problems, carpopedal spasms, dysmorphism, hearing loss, muscle weakness and rhabdomyolysis, and fulminant hepatitis. Blood and cerebrospinal fluid lactate levels were elevated in 13/20 and 9/20 respectively. One or more MRC complex activities (expressed as ratios relative to citrate synthase and/or complex II activity) were less than 50% of control mean activity in 11/20 patients (including patients with deficiencies of pyruvate dehydrogenase complex, pantothenate kinase, holocarboxylase synthetase, long-chain hydroxy acyl-CoA dehydrogenase, molybdenum co-factor, and neonatal haemochromatosis). One patient had a pattern suggestive of mitochondrial proliferation. We conclude that intermediate results of MRC enzymes should be interpreted with caution and clinicians should be actively looking for other underlying diagnoses. [source] Pyruvate dehydrogenase deficiency presenting as dystonia in childhoodDEVELOPMENTAL MEDICINE & CHILD NEUROLOGY, Issue 10 2004R A Head MA Two individuals with pyruvate dehydrogenase (PDH) deficiency due to missense mutations in the gene for the E1, subunit (PDHA1) presented during childhood with dystonia. The first patient, a male, presented at age 4 years with dystonia affecting the lower limbs, which responded to treatment with combined carbidopa and levodopa. The second patient, a female, was first investigated at age 6 years because of a dystonic gait disorder. In both patients, the main clue to the biochemical diagnosis was a raised concentration of lactate in the cerebrospinal fluid. PDH activity was significantly reduced in cultured fibroblasts in both cases. Dystonia is a previously unrecognized major manifestation of PDH deficiency and is of particular interest as the mutations in the PDHA1 gene in these patients have both been identified previously in individuals with typical presentations of the condition. [source] Cytology of primary central nervous system neoplasms in cerebrospinal fluid specimensDIAGNOSTIC CYTOPATHOLOGY, Issue 4 2002David C. Chhieng M.D. Abstract Although two-thirds of tumors occurring in the central nervous system (CNS) are primary neoplasms, only 10% of positive cerebrospinal fluid (CSF) specimens are from primary CNS tumors. In this study, we reviewed the cytologic findings of 21 positive CSF specimens from primary CNS tumors. A computer search identified 21 cases of positive CSF specimens from patients with primary CNS tumors from the archives. Follow-up included review of medical charts and histologic correlation. The specimens were from 20 patients (9 females and 11 males). Their ages ranged from 6,83 yr, old with a mean of 30 yr. The cases included 9 medulloblastomas, 7 gliomas (3 glioblastoma multiformes, 2 anaplastic astrocytomas, and 2 ependymomas), 2 germinomas, 2 non-Hodgkin's large B-cell lymphomas, and 1 ganglioneurocytoma. Two cases were classified as suspicious and the remaining as positive for malignancy. Immunocytochemistry was employed in 3 cases to support the cytologic diagnosis. These cases included one large-cell lymphoma (leukocyte-common antigen-positive), one germinoma (placental alkaline phosphatase-positive), and the ganglioneurocytoma (neuron-specific enolase- and synaptophysin-positive). There were no false-positive cases. Our results suggest that positive CSF cytology in patients with a primary CNS tumor is a reliable indicator of malignancy and reflects leptomeningeal involvement. The use of immunocytochemistry is helpful in confirming the cytologic impression in some cases. Diagn. Cytopathol. 2002;26:209,212. © 2002 Wiley-Liss, Inc. [source] Translational medicine perspective in development of disease modifying therapies for Alzheimer's disease: biomarkers to buy down the riskDRUG DEVELOPMENT RESEARCH, Issue 2 2009Hong I. Wan Abstract Alzheimer's disease (AD) is a progressive neurodegenerative disease and the most common cause of age-related dementia. Currently available pharmacologic therapies, including acetylcholinesterase (AChE) inhibitors and N-methyl-D-aspartate (NMDA) receptor antagonists, only treat symptoms and do not address the underlying neurodegeneration. In addition to potentially improve the accuracy of diagnosis, biomarkers serve important roles for the development of putative disease-modifying drugs for AD. In this article, we review the existing and emerging areas of biomarker research and development for AD. Biochemical biomarkers in cerebrospinal fluid have been used to provide a link to disease pathology and may provide important proof of concept data for several classes of emerging therapeutics. Imaging biomarkers including volumetric magnetic resonance imaging and positron emission tomography assessing either glucose utilization or radioligands binding to amyloid plaque are discussed. Appropriate uses of these biomarkers in the context of the development of disease-modifying therapies are discussed. Drug Dev Res 70, 2009. © 2009 Wiley-Liss, Inc. [source] Effects of a new 1,3,4-thiadiazolium mesoionic compound, MI-D, on the acute inflammatory responseDRUG DEVELOPMENT RESEARCH, Issue 4 2004Júlio C. Cardoso Abstract A new mesoionic compound, 4-phenyl-5-(4-nitro-cinnamoyl)-1,3,4-thiadiazolium-2-phenylamine (MI-D), is described along with some of its biological properties. Its effects on hepatic metabolism, on O and nitric oxide (NO) production, and in in vivo models for potential antinociceptive, antipyretic, and antiinflammatory activities were determined. In perfused rat liver, MI-D (25 µM) stimulated glycogenolysis (95%), and inhibited oxygen uptake (37%) with affecting glycolysis. In phorbol 12-myristate 13-acetate-stimulated macrophages, O generation was reduced (95%) by MI-D (15 µM), whereas the production of NO was unaffected. MI-D (2 mg/kg) inhibited (55%) the number of abdominal writhings induced by acetic acid. At 1 mg/kg, MI-D inhibited the febrile response (5 h) induced by lipopolysaccharide (LPS) and was also effective against a preexisting febrile response. Treatment with MI-D (1 mg/kg) reduced by 67% prostaglandin (PGE2) levels in the cerebrospinal fluid of LPS-exposed mice, and at a higher dose (8 mg/kg) MI-D inhibited paw edema formation (2 h) induced by carrageenan. MI-D has a spectrum of activities similar to other nonsteroidal antiinflammatory drugs, qualifying it as a potential anti-inflammatory drug. Drug Dev. Res. 61:207,217, 2004. © 2004 Wiley-Liss, Inc. [source] | ||||||||||||||||||||||||||||||||||