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System Diseases (system + disease)
Kinds of System Diseases Selected AbstractsComorbid conditions associated with Parkinson's disease: A population-based studyMOVEMENT DISORDERS, Issue 4 2006Cynthia L. Leibson PhD Abstract The burden of comorbidity in Parkinson's disease (PD) remains unclear. All Olmsted County, Minnesota, residents with incident PD in 1976,1995 (n = 197) plus one age- and sex-matched non-PD referent subject per case were followed for all clinical diagnoses from 5 years before through 15 years after index (i.e., year of PD onset for each case and same year for the referent subject). Both members of a case,referent pair were censored at death or emigration of either member to ensure equivalent follow-up. Cases and referent subjects were compared for summary comorbidity (Charlson index) and for the likelihood of having one or more diagnoses within each International Classification of Diseases chapter/subchapter. Before index, the groups were similar for all comparisons. After index, cases had a higher likelihood of diagnoses within the chapters "Mental Disorders" and "Diseases of the Genitourinary System," and within the subchapters "Organic Psychotic Conditions," "Other Psychoses," "Neurotic/Personality/Other Nonpsychotic Disorders," "Hereditary/Degenerative Diseases of Central Nervous System," "Symptoms," "Other Diseases of Digestive System," "Other Diseases of Urinary System," "Diseases of Veins/Lymphatics/Other Circulatory System Diseases," "Fractures of Lower Limb," "Other Diseases of Skin/Subcutaneous Tissue," "Osteopathies/Chrondropathies/Acquired Musculoskeletal Deformities," and "Pneumonia and Influenza." The excess morbidity and mortality observed for persons with PD are consistent with recognized PD sequelae. © 2005 Movement Disorder Society [source] Quantification by real-time PCR of the magnitude and duration of leucocyte-associated viraemia in horses infected with neuropathogenic vs. non-neuropathogenic strains of EHV- 1EQUINE VETERINARY JOURNAL, Issue 3 2006G. P. Allen Summary Reasons for performing study: Neurological disease in horses caused by infection with certain ,paralytic' strains of equine herpesvirus-1 (EHV-1) is a potentially devastating condition the pathogenesis of which is poorly understood. Preliminary observations in both experimentally induced and naturally occurring cases of the central nervous system disease have revealed a more robust cell-associated viraemia in horses infected with paralytic isolates of EHV-1, relative to horses infected with abortigenic isolates. To investigate further this pathogenesis - rdevant question, the present study was performed using a greater number of horses and a more precise method for quantification of EHV-1 DNA present in viraemic leucocytes. Objective: To compare the magnitude and duration of leucocyte-associated viraemia in seronegative, age-matched foals following infection with paralytic vs. abortigenic isolates of EHV-1. Methods: Peripheral blood mononuclear cells (PBMC) were collected from 20 weanling foals at 2, 4, 7, 9, 11, 14 and 21 days after intranasal inoculation with either paralytic or abortigenic isolates of EHV-1. The amount of EHV-1 DNA present in each PBMC sample was measured by real-time quantitative PCR. Results: Foals inoculated with paralytic strains of EHV-1 developed both a greater magnitude and longer duration of PBMC-associated viraemia than foals inoculated with abortigenic strains of the virus. Conclusions: Both the higher magnitude and longer duration of cell-associated viraemia contribute to the risk for development of neurological signs in horses infected with paralytic strains of EHV-1. Potential relevance: Our results provide empirically derived, scientific data that contributes to a better understanding of the pathogenetic basis for the differing abilities of paralytic and abortigenic strains of EHV-1 to cause post infection central nervous system disease in the horse. The findings identify the importance of minimising the quantitative burden of viraemic leucocytes that follows exposure to the virus, by the use of effective therapeutic antiviral drugs and efficacious prophylactic vaccines that stimulate cytotoxic immune responses against EHV-1 infected cells. [source] CXCL10-induced cell death in neurons: role of calcium dysregulationEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 4 2006Yongjun Sui Abstract Chemokines play a key role in the regulation of central nervous system disease. CXCL10 over-expression has been observed in several neurodegenerative diseases, including multiple sclerosis, Alzheimer's disease and HIV-associated dementia. More recent studies by others and us have shown that CXCL10 elicits apoptosis in fetal neurons. The mechanism of CXCL10-mediated neurotoxicity, however, remains unclear. In this study, we provide evidence for the direct role of Ca2+ dysregulation in CXCL10-mediated apoptosis. We demonstrate that treatment of fetal neuronal cultures with exogenous CXCL10 produced elevations in intracellular Ca2+ and that this effect was modulated via the binding of CXCL10 to its cognate receptor, CXCR3. We further explored the association of intracellular Ca2+ elevations with the caspases that are involved in CXC10-induced neuronal apoptosis. Our data showed that increased Ca2+, which is available for uptake by the mitochondria, is associated with membrane permeabilization and cytochrome c release from this compartment. The released cytochrome c then activates the initiator active caspase-9. This initiator caspase sequentially activates the effector caspase-3, ultimately leading to apoptosis. This study identifies the temporal signaling cascade involved in CXCL10-mediated neuronal apoptosis and provides putative targets for pharmaceutical intervention of neurological disorders associated with CXCL10 up-regulation. [source] Retrospective study of fever in dogs: laboratory testing, diagnoses and influence of prior treatmentJOURNAL OF SMALL ANIMAL PRACTICE, Issue 7 2006I. A. Battersby Objectives: To analyse the demographic information of dogs referred for investigation of fever, to determine the usefulness of various diagnostic investigations and to assess the effect of treatment before referral on the presence of fever at referral, the duration of the investigation and the ability to reach a final diagnosis. Methods: The clinical records of 66 dogs, in which fever was part of the clinical signs documented by the referring veterinary surgeon, were reviewed. The effects of treatment 24 hours before referral on temperature at initial consultation and on time to diagnosis were evaluated. The effect of body temperature at initial consultation on cost and on time to diagnosis was also determined. The effect of insurance on costs incurred was assessed. The utility of different diagnostic investigations was recorded, and cases were classified according to the final diagnosis. Results: Only 34·8 per cent of dogs were diagnosed with immune-mediated disease, with most frequent diagnoses being steroid-responsive meningitis and polyarthritis. Treatment 24 hours before referral significantly increased the time to diagnosis (P=0·004) and affected the presence of fever at referral (P=0·006). Insurance status did not significantly affect cost incurred by the owner. Clinical Significance: This study documents a high incidence of immune-mediated disease in dogs referred for investigation of fever. It also documents a higher incidence of inflammatory central nervous system disease in febrile dogs than that reported previously. Of the diagnostic modalities employed in the majority of cases, radiography, cytology and bacteriological and fungal cultures (fluids/tissues) were the most useful. It is suggested that treatment is withdrawn or withheld before commencing diagnostic investigation of fever. [source] Small heat shock proteins, the cytoskeleton, and inclusion body formationNEUROPATHOLOGY & APPLIED NEUROBIOLOGY, Issue 4 2000M. W. Head Since first being implicated in central nervous system disease 10 years ago, much has been learned concerning the regulation and function of the small heat shock protein ,B-crystallin. Neuropathological, cellular and molecular studies all now point to a functional relationship between ,B-crystallin and intermediate filaments. ,B-crystallin accumulation marks reactive astrocytes in general in a wide variety of disorders and specifically intermediate filament-based glial inclusion bodies such as Rosenthal fibres found in astrocytes in Alexander's disease. In vitro, ,B-crystallin expression suppresses intermediate filament aggregation and can prevent or reverse experimentally induced glial inclusion body formation. Conversely, dysregulation of glial fibrillary acidic protein expression in vivo results in Rosenthal fibre formation and upregulation of endogenous ,B-crystallin expression. These data and those from studies recently carried out on other tissues strongly suggest that one function of this small heat shock protein is to modulate intermediate filament organization under conditions of physiological stress and neurodegenerative disease. [source] Motor evoked potentials from the pelvic floorNEUROUROLOGY AND URODYNAMICS, Issue 7 2003Sřren Brostrřm Proper function of the lower urinary tract depends on the integrity of the central and peripheral nervous pathways on multiple levels, and the complexity of this system leaves it susceptible to even minor lesions. While dysfunction of the lower urinary tract is prevalent amongst patients with nervous system disease, e.g., multiple sclerosis (MS), most women with lower urinary tract dysfunction (LUTD) have no overt neurological cause. Refined neuro-diagnostic approaches are needed to reveal neurogenicity in these patients. A potential method is transcranial magnetic stimulation (TMS), which is used routinely to test the motor innervation of limb muscles, but also can be applied to test pelvic floor efferents. To resolve the lack of methodological clarity and the need for normative values for the use of pelvic floor motor evoked potentials (MEPs), 30 healthy women and 16 women with MS were studied. Methods The healthy women underwent MEP studies with various stimulus and recording modalities, and, to test reproducibility, 18 of them were retested at a separate session. The women with MS underwent MEP testing as well as urodynamic studies. Results From the methodological studies of healthy women, the use of invasive concentric needle electrodes was found to be superior to surface electrodes. When applying magnetic stimuli over the sacral region, various methodological problems were encountered. In the healthy women, a large variability of responses was noted, the long-term reproducibility of pelvic floor MEP latencies was poor, and in some cases responses could not be obtained. In the study of women with MS, prolonged central conduction times were found, along with many cases of unevokable responses, and a poor correlation of MEPs to urodynamic findings. The problems of obtaining selective recordings from the inaccessible pelvic floor musculature are discussed, and possible sources of variability in MEPs from the pelvic floor are considered. By relating the findings in the present studies to those of others using different modalities, some reflections are presented on the nature of the neural pathways to the pelvic floor activated by magnetic stimulation. As unevokable responses from the pelvic floor were an occasional finding among the healthy women, it is argued that a pelvic floor non-response in a patient with suspected corticospinal lesion should be interpreted with care, and should not carry the same clinical significance as an absent limb response. Conclusions The inherent limitations of pelvic floor MEPs are discussed, and it is concluded that while there seems to be only limited clinical value of pelvic floor MEP testing, there might be some interesting scientific perspectives in studies that aim to control and explain the variability of responses. Neurourol. Urodynam. 22:620,637, 2003. © 2003 Wiley-Liss, Inc. [source] The open issue of central nervous system disease in pediatric acute myeloid leukemiaPEDIATRIC BLOOD & CANCER, Issue 3 2010Andrea Pession MD No abstract is available for this article. [source] Videofluoroscopic Swallow Studies in Unilateral Cricopharyngeal Dysfunction,THE LARYNGOSCOPE, Issue 6 2003Stacey L. Halum MD Abstract Objectives/Hypothesis Although the cricopharyngeus muscle is a ring-like structure, unilateral cricopharyngeal dysfunction can produce significant dysphagia. This entity has not been well described in the literature. The aims of the study were to identify the characteristic findings on videofluoroscopic swallow studies in patients with dysphagia secondary to unilateral cricopharyngeal dysfunction, to note the associated vagal nerve injury, and to evaluate patient outcomes following ipsilateral cricopharyngeal myotomy. Study Design Retrospective clinical investigation. Methods The clinic charts, electromyographic tests, videostroboscopic examinations, and videofluoroscopic swallow studies were reviewed from a series of patients who presented to our institution from 1993 to 2001 with dysphagia and findings on videofluoroscopic swallow studies suggestive of unilateral cricopharyngeal dysfunction on posterior,anterior view. In patients treated with ipsilateral cricopharyngeal myotomy, postoperative findings on swallow studies and patient outcomes were also reviewed. Results Eighteen patients demonstrated findings characteristic of unilateral cricopharyngeal muscle dysfunction on videofluoroscopic swallow study. The common feature was a unilateral shelf-like barrier at the cricopharyngeus on the posterior,anterior view with pooling of liquid bolus in the ipsilateral pyriform sinus and episodic shunting to the contralateral side. Eight patients did not have evidence of cricopharyngeal dysfunction (ie, cricopharyngeal bar) on lateral films. Of the 18 patients, 14 had histories consistent with vagal injury secondary to trauma (n = 2), neoplastic involvement (n = 7), iatrogenic injury (n = 2), or central nervous system disease (n = 3). Results of videostroboscopic examinations demonstrated vocal fold motion impairment in 14 patients, and electromyographic test results confirmed unilateral vagal injuries in those who underwent electromyographic testing (n = 6). In the remaining 4 of 18 patients, videostroboscopic examinations demonstrated normal vocal fold abduction but impaired lengthening with a posterior glottic gap, and electromyographic test results (n = 4) indicated unilateral superior laryngeal nerve involvement. Of the 15 patients treated with ipsilateral cricopharyngeal myotomy, 1 patient required postoperative esophageal dilations for an esophageal stricture distal to the cricopharyngeus, whereas the remaining 14 patients had functional resolution of their dysphagia. Conclusion In patients presenting with dysphagia and evidence of unilateral vagal injury, careful assessment of posterior,anterior view on videofluoroscopic swallow study should be included to evaluate for unilateral cricopharyngeal dysfunction. [source] Antibodies to native myelin oligodendrocyte glycoprotein in children with inflammatory demyelinating central nervous system disease,ANNALS OF NEUROLOGY, Issue 6 2009Fabienne Brilot PhD Objective Myelin oligodendrocyte glycoprotein (MOG) is a candidate target antigen in demyelinating diseases of the central nervous system (CNS). Although MOG is encephalitogenic in different animal models, the relevance of this antigen in human autoimmune diseases of the CNS is still controversial. Methods We investigated the occurrence and biological activity of antibodies to native MOG (nMOG) in 47 children during a first episode of CNS demyelination (acute disseminated encephalomyelitis [ADEM], n = 19 and clinical isolated syndrome [CIS], n = 28) by a cell-based bioassay. Results High serum immunoglobulin G (IgG) titers to nMOG were detected in 40% of children with CIS/ADEM but 0% of the control children affected by other neurological diseases, healthy children, or adults with inflammatory demyelinating diseases, respectively. By contrast, IgM antibodies to nMOG occurred in only 3 children affected by ADEM. Children with high anti-nMOG IgG titer were significantly younger than those with low IgG titer. Anti-nMOG IgG titers did not differ between the ADEM and CIS group, and did not predict conversion from CIS to MS during a mean 2-year follow-up. However, intrathecal IgG anti-MOG antibody synthesis was only seen in CIS children. IgG antibodies to nMOG not only bound to the extracellular domain of nMOG, but also induced natural killer cell-mediated killing of nMOG-expressing cells in vitro. Interpretation Overall, these findings suggest nMOG as a major target of the humoral immune response in a subgroup of children affected by inflammatory demyelinating diseases of the CNS. Children may provide valuable insight into the earliest immune mechanisms of CNS demyelination. Ann Neurol 2009;66:833,842 [source] Long-term neurological and functional outcome in Nipah virus infectionANNALS OF NEUROLOGY, Issue 3 2007James J. Sejvar MD Objective Nipah virus (NiV) is an emerging zoonosis. Central nervous system disease frequently results in high case-fatality. Long-term neurological assessments of survivors are limited. We assessed long-term neurologic and functional outcomes of 22 patients surviving NiV illness in Bangladesh. Methods During August 2005 and May 2006, we administered a questionnaire on persistent symptoms and functional difficulties to 22 previously identified NiV infection survivors. We performed neurologic evaluations and brain magnetic resonance imaging (MRI). Results Twelve (55%) subjects were male; median age was 14.5 years (range 6,50). Seventeen (77%) survived encephalitis, and 5 survived febrile illness. All but 1 subject had disabling fatigue, with a median duration of 5 months (range, 8 days,8 months). Seven encephalitis patients (32% overall), but none with febrile illness had persistent neurologic dysfunction, including static encephalopathy (n = 4), ocular motor palsies (2), cervical dystonia (2), focal weakness (2), and facial paralysis (1). Four cases had delayed-onset neurologic abnormalities months after acute illness. Behavioral abnormalities were reported by caregivers of over 50% of subjects under age 16. MRI abnormalities were present in 15, and included multifocal hyperintensities, cerebral atrophy, and confluent cortical and subcortical signal changes. Interpretation Although delayed progression to neurologic illness following Nipah fever was not observed, persistent fatigue and functional impairment was frequent. Neurologic sequelae were frequent following Nipah encephalitis. Neurologic dysfunction may persist for years after acute infection, and new neurologic dysfunction may develop after acute illness. Survivors of NiV infection may experience substantial long-term neurologic and functional morbidity. Ann Neurol 2007 [source] Shortened intensified multi-agent chemotherapy and non-cross resistant maintenance therapy for advanced lymphoblastic lymphoma in children and adolescents: report from the Children's Oncology GroupBRITISH JOURNAL OF HAEMATOLOGY, Issue 2 2008Minnie Abromowitch Summary Pediatric lymphoblastic lymphoma (LL) has utilized treatment strategies similar to childhood acute lymphoblastic leukaemia (ALL) with prolonged maintenance chemotherapy. We report the results of a pilot study to estimate the feasibility, toxicity and efficacy of a 12-month aggressive multi-agent chemotherapy regimen in children and adolescents with advanced LL. Between July 1994 and June 1997, 85 eligible children and adolescents with advanced LL (Stage III/IV) were enrolled on this pilot study. Patients achieving a complete response following induction and consolidation received six cycles of maintenance chemotherapy for a total duration of 12 months. Grade III/IV toxicities included: hematological (80%), infections (20%), stomatitis and elevated transaminases, (29%). There were a total of 19 events, 13 relapses, two secondary acute myeloid leukaemia and four toxic deaths (5%). The 5-year event-free survival (EFS) and overall survival (OS) was 78 ± 4·5% and 85 ± 3·9%, respectively. Relapsed patients had a 5-year OS of only 33 ± 14%. Multivariate analysis failed to demonstrate age, gender, lactate dehydrogenase level, presence of marrow and/or central nervous system disease to have independent prognostic value. These results suggest that this experimental approach is safe and results in similar outcomes as more prolonged childhood ALL regimens. [source] Smoking and Risk of Premature Death among Middle-aged Japanese: Ten-year Follow-up of the Japan Public Health Center-based Prospective Study on Cancer and Cardiovascular Diseases (JPHC Study) Cohort ICANCER SCIENCE, Issue 1 2002Megumi Hara To update the evidence on the association between smoking and mortality, we analyzed data from a population-based prospective study in Japan. In total, 19 950 men and 21 534 women aged 40,59 who reported their smoking history and had no serious disease at baseline survey were followed. During 1990,1999, 1014 men and 500 women died. Smokers were associated with an unhealthy life-style. Relative risks (RRs) for selected cause of death due to smoking were slightly attenuated by adjusting for possible confounding factors. Age- and area-adjusted RRs of male current smokers compared with never smokers were 1.66 (95% confidence intervals (CI): 1.40, 1.95) for all causes, 1.69 (1.31, 2.18) for all cancers, 1.67 (1.20, 2.34) for all circulatory system disease, and 1.63 (1.24, 2.15) for other causes, while those of females were 2.03 (1.52, 2.73), 2.06 (1.35, 3.15), 2.99 (1.75, 5.11), 1.31 (0.69, 2.51), respectively. After adjusting for multivariate variables, the corresponding RRs of male smokers were 1.55 (1.29, 1.86), 1.61 (1.20, 2.15), 1.41 (0.97, 2.03), and 1.61 (1.17, 2.19), against 1.89 (1.36, 2.62), 1.83 (1.14, 2.95), 2.72 (1.45, 5.07), and 1.39 (0.71, 2.73) for females. Twenty-two percent of death from all causes, 25% of all cancer, and 17% of all circulatory system disease deaths, could be attributed to cigarette smoking in males, and 5%, 4%, and 11% in females, respectively. Cumulative dose as indicated by pack-years was clearly associated with cancer death. These findings provided information as to the quantitative risk for premature death due to smoking among middle-aged Japanese men and women, and showed that the elevated risk was not explained by the unhealthy lifestyle of smokers. [source] Causes of death among HIV-infected patients in the era of highly active antiretroviral therapy, Bordeaux, France, 1998,1999HIV MEDICINE, Issue 3 2002F Bonnet Objectives To describe the causes of death in HIV-infected patients in the era of highly active antiretroviral therapy (HAART). Method A retrospective survey conducted in Bordeaux, France. Medical records of all deaths that had occurred in 1998 and 1999 amongst patients followed within the Aquitaine cohort were reviewed by the same physician. Immediate and underlying causes of death were described, taking into account the morbidity at the time of death. Results Sixty-six deaths occurred in 1998, and 41 in 1999. Sixty-seven per cent of deceased patients were male. Median age at time of death was 43 years (range 25,71), median CD4 was 162 cells/µL (0,957); 28% of patients had a CD4 count > 200 cells/µL and 7% plasma viral load < 500 HIV-RNA copies/mL. Amongst morbidity present at the time of death, there were 23 bacterial infections, 16 non-Hodgkin's lymphomas, 16 cirrhoses, 15 non HIV-related malignancies, 13 central nervous system diseases and 10 myocardiopathies. The main immediate causes of death were: multiple organ failure (21%), coma (18%), septic shock (15%) and acute respiratory failure (14%). Underlying causes of death were AIDS-defining events (48%), non AIDS HIV-related infection (3%), hepatitis B- or C-associated cirrhosis (14%), non HIV-related malignancies (11%), cardiovascular events (10%), suicide and overdose (6%), treatment-related fatalities (4%), injury (2%) and unknown (2%). Patients dying from AIDS-related events were more often female, had a lower CD4 count, a higher level of HIV-RNA, a shorter history of HIV infection and were less often coinfected with hepatitis B and C viruses than those dying from other underlying causes. Conclusions AIDS-related events are no longer the major causes of death of HIV-infected patients in the era of HAART. This evolving mortality pattern justifies an adaptation of both the epidemiological surveillance and the clinical monitoring of HIV-infected patients. [source] Central nervous system diseases: innovative animal models from lab to clinicHUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 4 2001B. E. Leonard No abstract is available for this article. [source] Beliefs of chronically ill Japanese patients that lead to intentional non-adherence to medicationJOURNAL OF CLINICAL PHARMACY & THERAPEUTICS, Issue 5 2004N. Iihara BS Summary Objective:, To identify factors, associated with personal beliefs, involved in intentional non-adherence to prescribed medication of Japanese patients with chronic diseases. Methods:, A cross-sectional study of Japanese subjects with chronic, primarily liver, gastrointestinal, or nervous system diseases who had been prescribed oral medicines for regular use, was performed. The subjects were admitted to a university hospital and were interviewed face-to-face on admission. Intentional non-adherence was defined as experience of deliberate adjustment of self-managed prescription medicines during the few months prior to hospital admission. Patients' beliefs about taking medicines were assessed from the perspective of what the patient valued in order to take medicines without anxiety; whether the patient valued information about the medication such as its function and side-effects and/or mutual reliance on doctors. Using logistic multivariate regression analyses, factors associated with intentional non-adherence were identified. Results:, Among 154 subjects, 51 showed intentional non-adherence. Intentional non-adherence was associated with the following three factors: (a) the patients' beliefs with respect to taking medicines without anxiety, especially putting no value on mutual reliance on the patient,doctor relationship (P < 0·001) and putting great value on knowing the drug's side-effects (P < 0·001), (b) poor comprehension of general aspects of medication (P for trend <0·001), and (c) being in the prime of life (40,59 years) (P = 0·011). Comprehension of the function of each medicine, experience of side-effects, anxiety about taking medicines, and the number of types of medicines taken, were not associated with non-adherence. Conclusions:, Beliefs on which individual Japanese patients with chronic diseases attach value in order to take medicines without anxiety were potential factors for intentional non-adherence. This emphasizes the necessity of a patient-oriented approach to take account of patients' personal beliefs about medicines to increase adherence rate in Japan. [source] Cause-specific mortality and death certificate reporting in adults with moderate to profound intellectual disabilityJOURNAL OF INTELLECTUAL DISABILITY RESEARCH, Issue 11 2009F. Tyrer Abstract Background The study of premature deaths in people with intellectual disability (ID) has become the focus of recent policy initiatives in England. This is the first UK population-based study to explore cause-specific mortality in adults with ID compared with the general population. Methods Cause-specific standardised mortality ratios (SMRs) and exact 95% confidence intervals were calculated by age and sex for adults with moderate to profound ID living in the unitary authorities of Leicester, Leicestershire and Rutland, UK, between 1993 and 2006. Causes of death were also studied to determine how often ID and associated conditions, such as Down syndrome, were mentioned. Results A total of 503 (17% of population) adults with ID died during the 14-year study period (30 144 person-years). Relatively high cause-specific mortality was seen for deaths caused by congenital abnormalities (SMR = 8560), diseases of the nervous system and sense organs (SMR = 1630), mental disorders (other than dementia) (SMR = 1141) and bronchopneumonia (SMR = 647). Excess deaths were also seen for diseases of the genitourinary system or digestive system, cerebrovascular disease, other respiratory infections, dementia (in men only), other circulatory system diseases (in women only) and accidental deaths (in women only). Two-fifths (n = 204; 41%) of deaths recorded in adults with ID mentioned ID or an associated condition as a contributing cause of death. Conclusions Strategies to reduce inequalities in people with ID need to focus on decreasing mortality from potentially preventable causes, such as respiratory infections, circulatory system diseases and accidental deaths. The lack of mention of ID on death certificates highlights the importance of effective record linkage and ID reporting in health and social care settings to facilitate the government's confidential inquiry into causes of death in this population. [source] Biomimetic affinity purification of cardiotoxin and its pharmacological effects on the nervous system,JOURNAL OF MOLECULAR RECOGNITION, Issue 3 2008Dexian Dong Abstract Cobra venom is a very precious natural resource. The traditional method for purification of cardiotoxin from cobra venom is a multi-step, high cost, and low recovery procedure. By molecular modeling and docking with SYBYL software, we designed and synthesized an affinity ligand, m-aminobenzoic acid, for high efficiency purification of this therapeutically useful Chinese cobra venom cardiotoxin. The one-step recovery of cardiotoxin reached 64% and the purity reached 92% upon purification. The binding capacity of this synthetic ligand was 9.1,mg cardiotoxin/g moist weight gel and the affinity constant for cardiotoxin was 5.5,×,103,M,1. Unlike a natural affinity ligand, this synthetic ligand is highly stable, and has great potential for industrial scale production of cardiotoxin. In addition, we examined the effects of cardiotoxin on the nervous system in a mouse model. Results showed that cardiotoxin could maintain analgesic effects for 120,min with a dose of less than 0.06,mg/kg (2.8% of the LD50). Administration of 0.12,mg/kg cardiotoxin could improve scopolamine impairments of memory in mice. These results suggest that cardiotoxin may be a potential drug for nervous system diseases. Copyright © 2008 John Wiley & Sons, Ltd. [source] Neuropharmacological and pharmacokinetic properties of berberine: a review of recent researchJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 7 2009Minzhong Ye Abstract Objectives This review summarizes recent research on the neuropharmacological and pharmacokinetic properties of berberine, an isoquinoline alkaloid extracted from Coptidis rhizoma. Key findings Berberine has multiple neuropharmacological properties, such as neuroprection, anti-neuronal apoptosis, improvement of cerebral microcirculation and anti-Alzheimer's disease, and so on. The pharmacokinetic characteristics of berberine are that it is not easily absorbed and it is not stable in the gastrointestinal tract of animals or humans. Summary Further studies need to be carried out to develop berberine as a drug for nervous system diseases, such as brain ischaemia and Alzheimer's disease, that has favorable pharmacokinetic properties. [source] 14-3-3 protein in the CSF of inflammatory peripheral neuropathiesJOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, Issue 2 2004A Bersano 14-3-3 proteins are a highly conserved protein family of unknown function, although some authors suggested a role in cellular proliferation and differentiation, neurotransmitters biosynthesis and apoptosis. The expression of these proteins increases during development, in particular, in large projection neurons such as spinal motor neurons. Recently the protein was described in cerebrospinal fluid (CSF) of patients with spongiform encephalopathies, in particular Creutzfeld-Jacob disease, where the protein is considered a highly sensitive and specific marker. 14-3-3 protein has been also detected in CSF of other prion-unrelated dementias and other neurodegenerative (Parkinson disease, stroke and paraneoplastic syndromes) and inflammatory diseases like Multiple Sclerosis. The aim of our study was to evaluate whether the 14-3-3 protein is also present in the CSF of peripheral nervous system diseases. We studied by Western Blot the CSF of 120 patients including 38 with Guillain-Barré syndrome (GBS), 23 with chronic inflammatory demyelinating polyneuropathy (CIDP), 12 with multifocal motor neuropathies (MMN), 20 motor neuron disease (MND), 8 paraneoplastic syndrome, 14 other neuropathies or radiculopathies (OPN), and 5 normal subjects (NC). We found the 14-3-3 protein in the CSF of 21 (55%) patients with GBS, 13 (56%) with CIDP, 1 (5%) with MND, 3 (21%) with OPN and none with paraneoplastic syndrome, MMN or NC. Our results reveal that 14-3-3 protein can be detected not only in central but also in peripheral nervous system diseases where it is significantly associated (p < 0.0001) with GBS and CIDP. [source] Neurochemical biomarkers in the differential diagnosis of movement disorders,MOVEMENT DISORDERS, Issue 10 2009Brit Mollenhauer MD Abstract In recent years, the neurochemical analysis of neuronal proteins in cerebrospinal fluid (CSF) has become increasingly accepted for the diagnosis of neurodegenerative dementia diseases such as Alzheimer's disease and Creutzfeldt,Jakob disease. CSF surrounds the central nervous system, and in the composition of CSF proteins one finds brain-specific proteins that are prioritized from blood-derived proteins. Levels of specific CSF proteins could be very promising biomarkers for central nervous system diseases. We need the development of more easily accessible biomarkers, in the blood. In neurodegenerative diseases with and without dementia, studies on CSF and blood proteins have investigated the usefulness of biomarkers in differential diagnosis. The clinical diagnoses of Parkinson's disease, dementia with Lewy bodies, multiple system atrophy, progressive supranuclear palsy, and corticobasal degeneration still rely mainly on clinical symptoms as defined by international classification criteria. In this article, we review CSF biomarkers in these movement disorders and discuss recent published reports on the neurochemical intra vitam diagnosis of neurodegenerative disorders (including recent CSF ,-synuclein findings). © 2009 Movement Disorder Society [source] Neurophatic Pain Treatment: The ChallengePAIN PRACTICE, Issue 1 2003Jose De Andrés Abstract: Neuropathic pain covers a heterogeneous group of pain conditions characterized by a primary lesion or dysfunction of the sensory nervous system. Its pathophysiology is not yet clear, but neuronal hyperexcitability in those neurons that have lost their normal patterned input seems to be a common denominator for neuropathic pain. A mechanism-based approach is being developed, but still the clinical workup is being based on the anatomical location and the determination of an underlying cause. In addition, clinicians are presented with a challenge because neuropathic pain does not respond well to traditional pain therapies and there are greater individual variations in pain responsiveness. A number of drug classes have been evaluated in the treatment of neuropathic pain syndromes; these are mainly drugs developed for other nervous system diseases, although their precise action and whether their action is central or peripheral remains unknown for the majority of them. First-line agents used in the treatment of neuropathic pain conditions are tricyclic antidepressants and anticonvulsants, especially carbamazepine and gabapentin. Novel therapies are currently being developed for neuropathic pain that are based in experimental models and theoretical frameworks on the pathosphysiological events that initiate this type of pain. [source] Cohort mortality study of Philadelphia firefightersAMERICAN JOURNAL OF INDUSTRIAL MEDICINE, Issue 5 2001Dalsu Baris MD Abstract Background Fire fighters are exposed to a wide variety of toxic chemicals. Previous studies have reported excess risk of some cancers but have been limited by small numbers or little information on employment characteristics. Methods We conducted a retrospective cohort mortality study among 7,789 Philadelphia firefighters employed between 1925 and 1986. For each cause of death, the standardized mortality ratios (SMRs) and 95% confidence intervals were estimated. We also compared mortality among groups of firefighters defined by the estimated number of career runs and potential for diesel exposure. Results In comparison with U.S. white men, the firefighters had similar mortality from all causes of death combined (SMR,=,0.96) and all cancers (SMR,=,1.10). There were statistically significant deficits of deaths from nervous system diseases (SMR,=,0.47), cerebrovascular diseases (SMR,=,0.83), respiratory diseases (SMR,=,0.67), genitourinary diseases (SMR,=,0.54), all accidents (SMR,=,0.72), and suicide (SMR,=,0.66). Statistically significant excess risks were observed for colon cancer (SMR,=,1.51) and ischemic heart disease (SMR,=,1.09). The risks of mortality from colon cancer (SMR,=,1.68), kidney cancer (SMR,=,2.20), non-Hodgkin's lymphoma (SMR,=,1.72), multiple myeloma (SMR,=,2.31), and benign neoplasms (SMR,=,2.54) were increased among firefighters with at least 20 years of service. Conclusions Our study found no significant increase in overall mortality among Philadelphia firefighters. However, we observed increased mortality for cancers of the colon and kidney, non-Hodgkin's lymphoma and multiple myeloma. There was insufficient follow-up since the introduction of diesel equipment to adequately assess risk. Am. J. Ind. Med. 39:463,476, 2001. Published 2001 Wiley-Liss, Inc. [source] Delivery of an Adenoviral Vector to the Crushed Recurrent Laryngeal Nerve,THE LARYNGOSCOPE, Issue 6 2003Adam Rubin MD Abstract Objectives Objectives were to create a model of recurrent laryngeal nerve injury for testing the efficacy of potential therapeutic viral gene therapy vectors and to demonstrate that remote injection of a viral vector does not cause significant additional neuronal injury. Study Design Animal model. Methods Rats were randomly assigned to three groups of 10 animals each. In group I, the recurrent laryngeal nerve was crushed. In group II, the nerve was crushed and then injected with an adenoviral vector containing no transgene. In group III, the nerve was identified but was not crushed. Rats were killed at 1 week, and their larynges and brainstems were cryosectioned in 15-,m sections. Laryngeal cryosections were processed for acetylcholine histochemical analysis (motor endplates) followed by neurofilament immunoperoxidase (nerve fibers). Percentage of nerve,endplate contact was determined and compared between groups. Fluorescent in situ hybridization was performed on brainstem sections from rats in group II to confirm the presence of virus. Results No significant difference in percentage of nerve,endplate contact exists between the two crushed-nerve groups (groups I and II) (P = .88). The difference between both crushed-nerve groups and the group with noncrushed nerves (group III) was highly significant (P <.0001). The presence of virus was confirmed in group II rats. Conclusions Crush provides a significant measurable injury to the recurrent laryngeal nerve and may be used as a model to explore therapeutic interventions for nerve injury. The remote injection of viral vector did not cause significant additional neuronal injury. Remote delivery of viral vectors to the central nervous system holds promise in the treatment of recurrent laryngeal nerve injury and central nervous system diseases. [source] An unstructured protein with destructive potential: TPPP/p25 in neurodegenerationBIOESSAYS, Issue 6 2009Judit Ovádi Abstract TPPP/p25 is a recently discovered, unstructured protein involved in brain function. It is found predominantly in oligodendrocytes in normal brain but is enriched in neuronal and glial inclusions of Parkinson's disease and other synucleinopathies. Its physiological function seems to be the dynamic stabilization of microtubular ultrastructures, as well as the projections of mature oligodendrocytes and ciliary structures. We reappraise the earlier belief that TPPP/p25 is a brain-specific protein. We have identified and cloned two shorter (N-terminal-free) homologs of TPPP/p25 that behave differently from each other and from TPPP/p25. Two unique cell models have been established and used to study the effect of the unstructured protein on the energy metabolism and the formation of pathological aggregates. Our data suggest that the intracellular level of TPPP/p25 influences the cell differentiation, proliferation and the formation of protein aggregates, and consequently, the etiology of central nervous system diseases. [source] | ||||||||||||||||||||||||||||