UMLS:C0848771 - FACTA Search

Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Target Concepts:

Query: UMLS:C0848771 (neurological disability)
928 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An experimental model of meningeal carcinomatosis has been produced by intracisternal inoculation of Walker 256 carcinoma cell suspension into Wistar rats. The tumor grows rapidly and is fatal in about 15 days if 10(6) cells are injected. The histopathological pattern observed is similar to that seen in diffuse leptomeningeal involvement of systemic cancer in human beings. The model will be useful for investigating the pathophysiology of the neurological disability produced by meningeal carcinomatosis and the efficacy of chemotherapeutic agents.
...
PMID:Meningeal carcinomatosis: development of an experimental model. 83 39

Neurological involvement with systemic cancer is frequently a cause of major disability. Second to brain metastases, metastasis to the spinal cord and its nerve roots constitutes the most common neurological complication of cancer with an estimated 5 to 10% of patients developing spinal cord involvement that leads to serious impairment of function. With advances in cancer therapy and consequent extension of survival, the overall incidence of neurological complications of cancer is on the rise. Spinal cord dysfunction, while usually nonfatal, leaves the patient with a major neurological disability. The author discusses epidural metastases, highlighting the importance of early recognition and management.
...
PMID:Myelopathies in the cancer patient: incidence, presentation, diagnosis and management. Part 1. 183 42

Ataxia telangiectasia is a genetically determined multi-system disorder in which senile skin changes are at an early stage. The patients have progressive neurological disability, cellular and humoral immunodeficiencies and increased cancer incidence. Heterozygous carriers of the gene, estimated to comprise about 1% of the general population, have an increased risk of cancer. We have initiated an identification of a cohort of patients and their relatives in order to evaluate their cancer risk.
...
PMID:[Ataxia telangiectasia]. 765 49

Many patients who receive cardiopulmonary resuscitation (CPR) for cardiac arrest do not survive to leave hospital. Factors associated with adverse outcomes include unwitnessed cardiac arrest in general wards, particularly at night, prolonged resuscitation, asystole, associated disorders (e.g. sepsis, malignancy, renal failure, and left ventricular dysfunction), absent pupillary responses, hypoxaemia, low PetCO2 during resuscitation, and severe acid base imbalance. Outside hospitals, cardiac arrests result in more favourable outcomes if they occur at work, and bystander CPR and early defibrillation are initiated. On admission to ICU, likely predictors of death or severe neurological disability include prolonged coma, impaired brainstem reflexes, and persistent convulsions. Experience with cerebrospinal fluid enzymes and electrophysiological measurements is limited. Multivariate scoring systems are not sufficiently reliable. The importance of hyperglycaemia, the required level of CPR training, and the appropriateness of responding to some cases, remain debatable.
...
PMID:Factors affecting outcome following cardiopulmonary resuscitation. 789 67

In contrast to CHD and cancer, the burden of stroke lies with long term disability as opposed to death and it is the most common cause of neurological disability in the western world. Consequently such patients frequently require longer acute hospital stays followed by lengthy periods of rehabilitation where such services are available, long term nursing care or indefinite dependency on community care. Inevitably stroke is a major economic burden on healthcare systems. It has been estimated that approximately 6% of total healthcare resources are consumed in the management of this condition a figure which is expected to grow with an increasing elderly population. Due to the high level of disability caused by stroke, patients often require longer and therefore costly periods of acute hospital stay. The aim of this study is to determine the cost of treating an acute episode of ischaemic stroke in an Irish teaching hospital. The costing evaluation was from the hospital admission perspective and the strategy used was a microcosting detailed collection of resources used on patients admitted to St. James's hospital between January 1999 and March 2000. The average cost of a hospital admission for the treatment of an episode of acute ischaemic stroke was 6,722 euros. The average cost per day was calculated at 263 euros. Approximately 83% of hospital costs were associated with ward costs whereas medications accounted for just 1% of total costs. The projected cost for the treatment of stroke in euros using the consumer price index for October 2002 would be 7,686 euros. The availability of Irish cost data is essential for the assessment of the cost effectiveness of therapeutic interventions for the treatment of stroke in our healthcare system.
...
PMID:Cost of treating stroke in an Irish teaching hospital. 1513 76

Mitoxantrone (Novantrone), a synthetic anthracenedione derivative, is an antineoplastic, immunomodulatory agent. Its presumed mechanism of action in patients with multiple sclerosis (MS) is via immunomodulatory mechanisms, although these remain to be fully elucidated. Intravenous mitoxantrone treatment improved neurological disability and delayed progression of MS in patients with worsening relapsing-remitting (RR) [also termed progressive-relapsing (PR) MS] or secondary-progressive (SP) disease. In a pivotal randomised, double-blind, multicentre trial, mitoxantrone 12 mg/m(2) administered once every 3 months for 2 years provided significant improvements in neurological disability ratings, including Kurtzke Expanded Disability Status Scale (EDSS), Ambulatory Index (AI) and Standardised Neurological Status (SNS) scores, compared with placebo. The drug also significantly reduced the mean number of corticosteroid-treated relapses and prolonged the time to the first treated relapse, with the beneficial effects on disease progression supported by magnetic resonance imaging. Post hoc analyses suggest that the benefits associated with mitoxantrone treatment may be sustained for at least 12 months after cessation of treatment, mean changes from baseline at 36 months in EDSS, AI and SNS scores of 0.10, 0.61 and 0.19, respectively, in the mitoxantrone group versus 0.46, 1.13 and 3.38 with placebo. Concomitant intravenous mitoxantrone 20mg plus intravenous methylprednisolone 1g once every month for 6 months was more effective than intravenous methylprednisolone monotherapy in preventing the development of new gadolinium-enhanced lesions in patients with very active RRMS or SPMS. The drug was generally well tolerated in patients with MS. Adverse events were generally mild to moderate in severity and usually resolved upon discontinuation of treatment or with appropriate pharmacotherapy. At the recommended dosage, mitoxantrone appears to have a low potential to cause cardiotoxicity. In conclusion, intravenous mitoxantrone reduces the relapse rate and slows progression of the disease in patients with worsening RRMS, PRMS or SPMS; thus providing a new option for the management of these patients. The drug was generally well tolerated at the recommended dosage, although potential cardiotoxicity limits the total cumulative dose to 140 mg/m(2). Further studies are warranted to determine which patients with worsening RRMS, PRMS or SPMS are most likely to benefit from mitoxantrone treatment and to more fully define the long-term safety and tolerability of mitoxantrone, including the use of concomitant cardioprotectants to extend the therapeutic lifespan of the drug. Pharmacodynamic Profile. Mitoxantrone, a synthetic anthracenedione derivative, is an established cytotoxic, antineoplastic agent. Its presumed mechanism of action in multiple sclerosis (MS) is immunosuppression. In antineoplastic studies, the drug showed several immunomodulatory effects, inducing macrophage-mediated suppression of B-cell, T-helper and T-cytotoxic lymphocyte function. Currently, the pharmacodynamic properties of mitoxantrone have not been investigated to any extent in patients with MS. In one study, 6 months' treatment with intravenous mitoxantrone generally had no effect on the distribution of cytokine-positive peripheral blood monocyte cells in patients with MS. In an animal model of the disease, mitoxantrone suppressed the development and progression of both actively and passively induced acute experimental allergic encephalomyelitis (EAE). It appeared to be 10-20 times more effective than cyclophosphamide in the suppression of EAE. Moreover, mitoxantrone approximately doubled the mean time to onset of EAE versus control animals (279 vs 148 days after immunisation; p < 0.00005). In vitro, mitoxantrone 10 and 100 micro g/L inhibited myelin degradation by leucocytes and peritoneal macrophages derived from mice with acute EAE by approximately 60% and 100%. Pharmacokinetic Profile. Currently, there are no published pharmacokinetic data for intravenous mitoxantrone in pitoxantrone in patients with MS, paediatric patients or in those with renal impairment. All studies, to date, have been in patients with cancer receiving a single, approximately 30-minute intravenous infusion of mitoxantrone 5-14 mg/m(2). The drug exhibits triexponential pharmacokinetics, with a rapid initial distribution (alpha) phase, an intermediate distribution (beta) phase and a much slower elimination (gamma) phase. The mean half-life of the alpha phase appears to be 6-12 minutes and that of the beta phase 1.1-3.1 hours. Mitoxantrone has a high affinity for tissue, with a volume of distribution of up to 2248 L/m(2). Mitoxantrone persists for prolonged periods in tissues and was detectable in autopsy tissue from patients who last received the drug up to 272 days before death. At concentrations of 10-10000 ng/mL, the drug was 70-80 % bound to plasma proteins in dogs. Elimination of mitoxantrone occurs predominantly through biliary excretion and may be impaired in patients with hepatic dysfunction or third space abnormalities (e.g. ascites). The mean terminal elimination half-life of mitoxantrone ranged from 23 hours to 215 hours. Renal clearance accounts for 10 % of the total clearance of the drug. Total clearance of mitoxantrone ranged from 13 to 34.2 L/h/m(2) and renal clearance from 0.9 to 2.7 L/h/m(2). The drug appears to have a low potential for interaction with other concomitantly administered agents. Therapeutic Efficacy. Intravenous mitoxantrone (infusion of > or = 5 minutes), either as monotherapy or in combination with intravenous methylprednisolone, delayed the progression of the disease in patients with secondary-progressive (SP) or worsening relapsing-remitting (RR) MS (the latter is also termed progressive-relapsing MS) in comparative, randomised, multicentre trials. In a double-blind, monotherapy trial (Mitoxantrone In Multiple Sclerosis [MIMS] trial), mitoxantrone 12 mg/m(2) (n = 60) once every 3 months for 2 years significantly improved neurological disability relative to placebo (n = 64), as assessed by changes in mean Kurtzke Expanded Disability Status Scale (EDSS) score, mean Ambulatory Index (AI) score and mean Standardised Neurological Status (SNS) score. The drug also significantly reduced the mean number of corticosteroid-treated relapses per patient and prolonged the time to the first treated relapse. A Wei-Lachin multivariate analysis of these five efficacy variables indicated that the global difference between the two treatment groups was 0.30 (p < 0.0001). Mitroxantrone was also more effective than placebo according to secondary endpoints in this study, with fewer mitoxantrone recipients experiencing a relapse, a deterioration of > or =1 EDSS point or a confirmed deterioration in EDSS score over a 3-month period. Mitoxantrone recipients also showed less deterioration in quality-of-life ratings and had fewer hospital admissions, whereas more placebo recipients had new gadolinium-enhanced lesions at study end (the latter parameter was assessed using magnetic resonance imaging [MRI] in a subgroup of 110 patients, including 40 patients who received an exploratory 5 mg/m(2) dose). Furthermore, post hoc analyses indicated that the beneficial effects of mitoxantrone treatment on EDSS, SNS and AI scores were sustained for at least 12 months after cessation of treatment, with mean changes from baseline at 36 months in EDSS, AI and SNS scores of 0.10, 0.61 and 0.19, respectively, in the mitoxantrone group versus 0.46, 1.13 and 3.38 with placebo. Preliminary data from a cost-minimisation analysis based on results from the MIMS trial indicated that approximately half of the cost of mitoxantrone was offset by cost savings in other areas associated with the treatment of MS (direct and indirect major costs), with a total annual incremental cost for mitoxantrone of dollar 1661 per patient. Combination therapy once-monthly with intravenous mitoxantrone 20mg plus intravenous methylprednisolone 1g was more effective than intravenous methylprednisolone 1g once every month in preventing the development of gadolinium-enhanced lesions in patients with very active RRMS or SPMS (double-blind assessment using MRI scans). After 6 months, significantly more combination therapy recipients had no new gadolinium-enhanced lesions (90.5% vs 31.3% with monotherapy; p < 0.001) [primary endpoint]. There were also significant reductions in both the mean number of new enhancing lesions and the total number of gadolinium-enhanced lesions in patients receiving combination therapy versus methylprednisolone monotherapy.Tolerability. Mitoxantrone was generally well tolerated in patients with MS. Treatment-emergent adverse events occurring significantly more frequently with mitoxantrone (12 mg/m(2) once every 3 months for 2 years) than placebo were nausea, alopecia, menstrual disorders, urinary tract infection, amenorrhoea, leucopenia and elevated gamma-glutamyltranspeptidase levels. Adverse events were usually mild to moderate in severity and generally resolved with discontinuation of treatment or when treated with appropriate pharmacotherapy. Eight percent of patients discontinued treatment in the mitoxantrone 12 mg/m(2) group due to an adverse event versus 3% of placebo recipients. The incidence of drug-related acute myelogenous leukaemia was very low (0.12%) in a cohort of 802 patients with MS receiving mitoxantrone. Evidence suggests that the risk of cardiotoxicity is low in patients with MS. After 1 year of monotherapy, 3.4% of mitoxantrone recipients had a reduction in left ventricular ejection fraction (LVEF) to < or =50% compared with 0% of placebo recipients; at the end of the second year, respective incidences were 1.9% and 2.9% (total cumulative dose of mitoxantrone per patient was 96 mg/m(2) after 2 years' treatment). (ABSTRACT TRUNCATED)
...
PMID:Mitoxantrone: a review of its use in multiple sclerosis. 1508 10

We performed a retrospective review of all patients admitted to a neurological rehabilitation unit over a 5-year period to identify the benefits and problems associated with inpatient rehabilitation of patients with a life-limiting illness. Twenty-one patients (14 men; mean age 54 years) with primary or nonprimary neurological malignancy resulting in disability were studied. For each patient the following data was extracted: gender, age, diagnosis, source of referral, mechanism of disability, prognosis at time of referral, length of inpatient stay, disability on admission and discharge, and the place of discharge. All patients made functional gains, and all but 2 were discharged home. One patient died and 4 required readmission to an acute unit because of worsening discomfort or debility within a month of discharge. Patients with life-limiting illness resulting in neurological disability can benefit from inpatient rehabilitation. Optimal management of such patients demands careful liaison with palliative care teams.
...
PMID:Rehabilitation of the cancer patient: experience in a neurological unit. 1522 2

Reversible posterior leukoencephalopathy syndrome (RPLS) is an uncommon but distinctive clinicoradiological entity comprising of headache, seizures, visual disturbance, and altered mental function, in association with posterior cerebral white matter edema. With appropriate management, RPLS is reversible in the majority of cases. Previous reported associations of RPLS include hypertension, eclampsia, renal failure, and use of immunosuppressive drugs; reports in the adult hematology setting are rare. We report two cases of adults undergoing treatment for hematological malignancies who developed RPLS, and we emphasize the importance of early recognition and institution of appropriate management in reducing the risk of development of permanent neurological disability.
...
PMID:Reversible posterior leukoencephalopathy syndrome complicating cytotoxic chemotherapy for hematologic malignancies. 1530 10

Congenital and neonatal viral infections usually display their acute manifestations in highly recognisable ways, for example, congenital rubella, cytomegalovirus (CMV), varicella, human immunodeficiency (HIV) and herpes simplex virus (HSV) infection. By contrast, congenital hepatitis B virus (HBV) infection may go undetected for years. Some of these are preventable, but what is not immediately apparent is that the long-term consequences are being prevented as well. The long-term consequences of congenital and neonatal infections include endocrine, immunological and cardiovascular disease, deafness, visual problems, intellectual handicap and cerebral palsy. With the survival of HIV-infected infants into adulthood the long-term consequences will soon be described. Maternally and neonatally transmitted HBV infection predisposes to carriage, liver cirrhosis and hepatocellular carcinoma in young adults. Neonatal HBV vaccination prevents adult cancer. Acquired viral infections may predispose to subsequent lung disease, malabsorption, fertility problems or neurological disability. In the prevention of acquired rubella, varicella, HBV, influenza, poliovirus, measles and hepatitis A, one should mention the added bonus of preventing secondary cases by preventing transmission from infants and children to other children and adults. Preventing paediatric HSV, HBV and HIV infection in females may even be preventing subsequent transmission to future generations. Turning to paediatric bacterial infections, vaccinating infants and young children against pertussis could not only prevent transmission to older children and adults but also break the cycle, which then transmits from adults back to infants and young children. There is evidence that disease in older age groups, including adults, has been prevented by virtue of herd immunity from paediatric vaccination, e.g. Neisseria meningitidis Group C and Streptococcus pneumoniae. The add-on benefits for other generations, including for adults, arising from the prevention of paediatric infections are considerable.
...
PMID:Paediatric infections: prevention of transmission and disease--implications for adults. 1575 76

Paraneoplastic disorders may affect any part of the central or peripheral nervous systems. Although relatively uncommon, these disorders are a significant cause of severe neurological disability among cancer patients. Most, if not all, neurological paraneoplastic disorders are believed to be autoimmune diseases in which an antitumour immune response also attacks neurons that express shared neuronal tumour antigens. Affected patients often have one or more circulating antineuronal antibodies, which serve as a diagnostic marker for the paraneoplastic condition, and in some cases are the direct mediators of neuronal injury. The exact immunopathogenesis and relative contributions of humoral or cellular immune effectors for most paraneoplastic syndromes are not well understood. Some patients have a gratifying neurological response to tumour treatment and/or immunotherapy, especially if the diagnosis is made early and treatment is initiated promptly. Unfortunately, many patients are left with severe and permanent neurological deficits despite aggressive treatment. This review summarises the current understanding of the clinical immunology of paraneoplastic disorders, and outlines immunotherapy options and outcomes.
...
PMID:Immunotherapy for paraneoplastic neurological disorders. 1619 39

1 2 3 Next >>