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1.
Eur J Neurol ; 23(5): 891-7, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26822417

RESUMO

BACKGROUND AND PURPOSE: Apathy is the most commonly reported behavioural change in amyotrophic lateral sclerosis (ALS). However, the degree to which it affects prognosis and overlaps with depression in this population is unknown. The present study examined the relationship between level of apathy, mortality and survival time and whether apathy was linked to specific symptom clusters of depression. METHODS: A cohort of 76 consecutive ALS patients attending specialized multidisciplinary clinics were classified according to level of apathy. The effects of clinical factors and apathy on survival time were analysed using univariate and multivariate methods. RESULTS: The majority of patients with moderate to severe apathy died during the study (P = 0.003) and had a median survival time of 21.7 months, considerably shorter than patients with mild apathy (46.9 months) and no apathy (51.9 months) (P = 0.0001). Apathy remained a significant predictor of survival even after controlling for clinical factors and symptom duration at the time of study entry (hazard ratio 3.8, 95% confidence interval 1.9-7.5, P = 0.0001). Depression with demoralization was not associated with level of apathy (P = 0.172) whereas depression with anhedonia was more common in patients with apathy than in those without apathy (P = 0.006). CONCLUSIONS: The presence of severe apathy is an independent, negative prognostic factor in ALS.


Assuntos
Esclerose Lateral Amiotrófica/diagnóstico , Apatia/fisiologia , Depressão/complicações , Idoso , Esclerose Lateral Amiotrófica/complicações , Esclerose Lateral Amiotrófica/psicologia , Depressão/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico
2.
Mol Cell Neurosci ; 53: 34-41, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23110760

RESUMO

Neuroinflammation in now established as an important factor in the pathogenesis of many neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). At various time points, astrocytes and microglia are markedly activated, either producing neuroprotective or pro-inflammatory molecules, which can decrease or increase the rate of primary motor neuron degeneration respectively. Recent research has shown that this neuroinflammatory component is affected by the peripheral immune system; T lymphocytes in particular are able to cross into the brain and spinal cord parenchyma, where they interact with resident microglia, either inducing them to adopt an M1 (cytotoxic) or M2 (protective) phenotype, depending on the stage of disease. Clearly understanding the changes that occur to allow the interaction between peripheral and central immune responses will be essential in any attempt to manipulate the disease process via neuroinflammatory mechanisms. However, our understanding of the endothelial changes, which facilitate the infiltration of peripheral immune cells into the brain and spinal cord, is still in its infancy. There are suggestions, though, of up-regulation of cellular adhesion molecules, which are able to arrest circulating leukocytes and facilitate diapedesis into the brain parenchyma. In addition, tight junction proteins appear to be down-regulated, leading to an increase in vascular permeability, an effect that is amplified by vascular damage late in the disease process. This review summarises our current knowledge regarding neuroinflammation, peripheral immune involvement, and endothelial changes in ALS. This article is part of a Special Issue entitled 'Neuroinflammation in neurodegeneration and neurodysfunction'.


Assuntos
Esclerose Lateral Amiotrófica/imunologia , Endotélio Vascular/imunologia , Inflamação/imunologia , Esclerose Lateral Amiotrófica/patologia , Animais , Astrócitos/imunologia , Moléculas de Adesão Celular/imunologia , Moléculas de Adesão Celular/metabolismo , Citocinas/imunologia , Endotélio Vascular/patologia , Humanos , Inflamação/patologia , Leucócitos/imunologia , Microglia/imunologia , Neurônios Motores/imunologia , Linfócitos T/imunologia , Migração Transendotelial e Transepitelial
3.
J Neurol Neurosurg Psychiatry ; 82(8): 853-4, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20562391

RESUMO

BACKGROUND: Focality of onset of amyotrophic lateral sclerosis (ALS) is not understood. Attempts to implicate physical exercise in the aetiology of ALS have provided inconsistent results. If physical use of a limb were important in defining the site of onset, then handedness might be expected to influence the side of upper limb-onset disease and footedness likewise in lower limb-onset ALS. METHODS: ALS patients registered with an internet-based support site were invited to complete an online questionnaire concerning site of onset of symptoms and their dominant hand and foot. A binomial test of proportions was used to investigate the null hypothesis that handedness and footedness do not influence side of onset in upper and lower limb-onset ALS, respectively. RESULTS: 343 ALS patients with limb-onset disease were studied. For upper limb-onset patients, there was concordance for side of onset and handedness (64%; p<0.0006). For lower limb-onset patients, concordance for side of onset and footedness was absent. The frequency of left handedness was commensurate with that found in the general population. INTERPRETATION: These results are potentially consistent with the hypothesis that exercise influences pathogenesis in ALS since routine physical demands on the upper limb are heavily influenced by limb dominance, whereas in the lower limbs the commonest function is standing or locomotion, which uses both legs equally. However, there may also be an inherent cortical vulnerability underlying upper limb-onset laterality, possibly influenced by changes in neuronal connectivity and cortical excitability in relation to handedness and reflected by the "split hand" phenomenon consistently observed in ALS.


Assuntos
Esclerose Lateral Amiotrófica/fisiopatologia , Mãos/fisiopatologia , Perna (Membro)/fisiopatologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Lateralidade Funcional , Humanos , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Inquéritos e Questionários , Fatores de Tempo
4.
J Neurol Neurosurg Psychiatry ; 82(8): 843-9, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21515558

RESUMO

BACKGROUND: The homogeneous genotype and stereotyped phenotype of a unique familial form of amyotrophic lateral sclerosis (ALS) (patients homozygous for aspartate-to-alanine mutations in codon 90 (homD90A) superoxide dismutase 1) provides an ideal model for studying genotype/phenotype interactions and pathological features compared with heterogeneous apparently sporadic ALS. The authors aimed to use diffusion tensor tractography to quantify and compare changes in the intracerebral corticospinal tracts of patients with both forms of ALS, building on previous work using whole-brain voxelwise group analysis. METHOD: 21 sporadic ALS patients, seven homD90A patients and 20 healthy controls underwent 1.5 T diffusion tensor MRI. Patients were assessed using 'upper motor neuron burden,' El Escorial and ALSFR-R scales. The intracranial corticospinal tract was assessed using diffusion tensor tractography measures of fractional anisotropy (FA), mean diffusivity, and radial and axial diffusivity obtained from its entire length. RESULTS: Corticospinal tract FA was reduced in sporadic ALS patients compared with both homD90A ALS patients and controls. The diffusion measures in sporadic ALS patients were consistent with anterograde (Wallerian) degeneration of the corticospinal tracts. In sporadic ALS, corticospinal tract FA was related to clinical measures. Despite a similar degree of clinical upper motor neuron dysfunction and disability in homD90A ALS patients compared with sporadic ALS, there were no abnormalities in corticospinal tract diffusion measures compared with controls. CONCLUSIONS: Diffusion tensor tractography has shown axonal degeneration within the intracerebral portion of the corticospinal tract in sporadic ALS patients, but not those with a homogeneous form of familial ALS. This suggests significant genotypic influences on the phenotype of ALS and may provide clues to slower progression of disease in homD90A patients.


Assuntos
Esclerose Lateral Amiotrófica/genética , Esclerose Lateral Amiotrófica/patologia , Imagem de Tensor de Difusão , Degeneração Neural/patologia , Tratos Piramidais/patologia , Superóxido Dismutase/genética , Adulto , Idoso , Esclerose Lateral Amiotrófica/diagnóstico , Anisotropia , Códon , Feminino , Homozigoto , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Degeneração Neural/genética , Superóxido Dismutase-1
5.
Clin Med (Lond) ; 11(3): 292-3, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21902090

RESUMO

The depolarising neuromuscular blocking agent suxamethonium chloride, frequently used during endotracheal intubation, is contraindicated in patients with chronic denervation in whom it can cause a life-threatening hyperkalaemic reaction, thought to be mediated through upregulation of nicotinic alpha7 acetylcholine receptors. An underlying neuromuscular disorder should be considered in all patients with acute respiratory insufficiency, and an alternative neuromuscular blocking drug must be used if there is any possibility of widespread denervation.


Assuntos
Esclerose Lateral Amiotrófica , Hiperpotassemia/induzido quimicamente , Intubação Intratraqueal/métodos , Fármacos Neuromusculares Despolarizantes/efeitos adversos , Succinilcolina/efeitos adversos , Fasciculação/induzido quimicamente , Evolução Fatal , Feminino , Humanos , Hiperpotassemia/tratamento farmacológico , Intubação Intratraqueal/efeitos adversos , Pessoa de Meia-Idade , Taquicardia/induzido quimicamente
6.
Eur J Neurol ; 17(4): 526-e20, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20136647

RESUMO

BACKGROUND AND PURPOSE: These European Federation of Neurological Societies guidelines on neuroimaging of motor neuron diseases (MNDs) are designed to provide practical help for the neurologists to make appropriate use of neuroimaging techniques in patients with MNDs, which ranges from diagnostic and monitoring aspects to the in vivo study of the pathobiology of such conditions. METHODS: Literature searches were performed before expert members of the Task Force wrote proposal. Then, consensus was reached by circulating drafts of the manuscript to the Task Force members and by discussion of the classification of evidence and recommendations. RESULTS AND CONCLUSIONS: The use of conventional MRI in patients suspected of having a MND is yet restricted to exclude other causes of signs and symptoms of MN pathology [class IV, level good clinical practice point (GCPP)]. Although the detection of corticospinal tract hyperintensities on conventional MRI and a T2-hypointense rim in the pre-central gyrus can support a pre-existing suspicion of MND, the specific search of these abnormalities for the purpose of making a firm diagnosis of MND is not recommended (class IV, level GCPP). At present, advanced neuroimaging techniques, including diffusion tensor imaging and proton magnetic resonance spectroscopic imaging, do not have a role in the diagnosis or routine monitoring of MNDs yet (class IV, level GCPP). However, it is strongly advisable to incorporate measures derived from these techniques into new clinical trials as exploratory outcomes to gain additional insights into disease pathophysiology and into the value of these techniques in the (longitudinal) assessment of MNDs (class IV, level GCPP).


Assuntos
Imageamento por Ressonância Magnética/métodos , Doença dos Neurônios Motores/diagnóstico , Doença dos Neurônios Motores/patologia , Tomografia por Emissão de Pósitrons/métodos , Família , Humanos , Doença dos Neurônios Motores/metabolismo , Doença dos Neurônios Motores/terapia
7.
Artigo em Inglês | MEDLINE | ID: mdl-33602011

RESUMO

Primary lateral sclerosis (PLS) is a motor neuron disease characterized by spinobulbar spasticity, absence of progressive lower motor neuron (LMN) dysfunction and marked by a slow functional decline. Electromyography is essential to exclude significant LMN involvement, particularly in the context of distinguishing PLS from amyotrophic lateral sclerosis (ALS), given that the prognosis is substantially better, and respiratory complications are unusual, in PLS. Nevertheless, minor neurogenic changes and occasional fasciculation potentials can be observed in PLS. The most useful technique for the objective assessment of upper motor neuron (UMN) dysfunction is transcranial magnetic stimulation (TMS), which in PLS is characterized by a high cortical threshold and delayed central conduction times. TMS is sensitive to identify cortical dysfunction in PLS and might have potential for monitoring UMN function in longitudinal studies and in clinical trials. The findings of TMS need to be interpreted in the context of the clinical presentation and phenotype, particularly in the differentiation between PLS and ALS. While other neurophysiological techniques have been investigated, studies to date have tended to involve small patient cohorts and as such, their value in distinguishing PLS from ALS remains unclear.


Assuntos
Esclerose Lateral Amiotrófica , Doença dos Neurônios Motores , Esclerose Lateral Amiotrófica/diagnóstico , Eletromiografia , Humanos , Doença dos Neurônios Motores/diagnóstico , Prognóstico , Estimulação Magnética Transcraniana
9.
Br J Neurosurg ; 22(5): 705-8, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19016122

RESUMO

The case of a 39-year-old with intractable spontaneous intracranial hypotension (SIH) is presented. He developed bilateral and symptomatic subdural hygromas that were drained in response to clinical deterioration, but proved ineffective. An initial MRI of the lumbar region suggested a lumbosacral CSF leak, but he failed to respond to local blood patching. Subsequent CT myelography revealed a thoracic dural leak and a second directed blood patch proved effective. The aetiology, pitfalls and management of SIH are summarized.


Assuntos
Hipotensão Intracraniana/terapia , Adulto , Placa de Sangue Epidural/métodos , Marcha Atáxica/etiologia , Cefaleia/etiologia , Humanos , Hipotensão Intracraniana/etiologia , Linfangioma Cístico/etiologia , Linfangioma Cístico/cirurgia , Masculino , Derrame Subdural/etiologia , Derrame Subdural/terapia , Resultado do Tratamento , Vômito/etiologia
10.
Neuroimage Clin ; 17: 953-961, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29321969

RESUMO

MRI has emerged as one of several urgently needed candidate disease progression biomarkers for the neurodegenerative disorder amyotrophic lateral sclerosis (ALS), not least due to its unique ability to non-invasively assess structural and functional cerebral pathology. We sought to identify the extent of detectable change in cerebral MRI metrics over a more prolonged period. Analysis of multi-modal MRI data was performed in a cohort of sixteen patients (13 ALS and 3 with primary lateral sclerosis) in whom it was possible to acquire six-monthly images over two years. Structural brain changes were assessed using voxel-based morphometry of grey matter and shape analysis of sub-cortical grey matter structures, tract-based spatial statistics of diffusion tensor imaging (DTI) metrics optimized for longitudinal analysis in the white matter, as well as whole brain voxel-wise statistics of DTI metrics. Changes in resting state functional MRI (rs-fMRI) were investigated via independent component and dual regression analyses of functional connectivity (FC), controlled for confounding effects of grey matter decline. Both linear changes with time and brain changes correlated with revised ALS functional rating score (ALSFRS-R) decline were studied. Widespread and progressive reductions in grey matter were observed in the precentral gyri and posterior cingulate cortex, as well as progressive local atrophy of the thalamus, caudate, and pallidum bilaterally, and right putamen, hippocampus and amygdala. The most prominent DTI tract-based changes were in the superior longitudinal fasciculi and corpus callosum. More widespread areas of DTI changes included the thalami and caudate nuclei, hippocampi and parahippocampal gyri, insular cortices, anterior and posterior cingulate gyri, frontal operculum and cerebellum. FC decreases were noted between the sensorimotor resting state network and the frontal pole, between a network comprising both thalami and an area in the visual cortex, in relation to both time from baseline and ALSFRS-R decline. FC increases between the left primary motor cortex and left fronto-parietal network were seen for both statistical approaches. A longer period of follow-up, though necessarily involving more slowly-progressive cases, demonstrated widespread changes in both grey and white matter structural MRI measures. The mixed picture of regional decreases and increases in FC is compatible with compensatory change, in what should be viewed as a brain-based disease characterised by larger-scale disintegration of motor and frontal projection cerebral networks.


Assuntos
Esclerose Lateral Amiotrófica/diagnóstico por imagem , Córtex Cerebral/diagnóstico por imagem , Córtex Cerebral/fisiopatologia , Imageamento por Ressonância Magnética , Idoso , Esclerose Lateral Amiotrófica/complicações , Transtornos Cognitivos/diagnóstico por imagem , Transtornos Cognitivos/etiologia , Imagem de Tensor de Difusão , Progressão da Doença , Feminino , Substância Cinzenta/diagnóstico por imagem , Humanos , Processamento de Imagem Assistida por Computador , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Descanso , Estudos Retrospectivos , Substância Branca/diagnóstico por imagem
11.
J Eng Math ; 106(1): 75-106, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-32009671

RESUMO

The coupled motion-between multiple inviscid, incompressible, immiscible fluid layers in a rectangular vessel with a rigid lid and the vessel dynamics-is considered. The fluid layers are assumed to be thin and the shallow-water assumption is applied. The governing form of the Lagrangian functional in the Lagrangian particle path (LPP) framework is derived for an arbitrary number of layers, while the corresponding Hamiltonian is explicitly derived in the case of two- and three-layer fluids. The Hamiltonian formulation has nice properties for numerical simulations, and a fast, effective and symplectic numerical scheme is presented in the two- and three-layer cases, based upon the implicit-midpoint rule. Results of the simulations are compared with linear solutions and with the existing results of Alemi Ardakani et al. (J Fluid Struct 59:432-460, 2015) which were obtained using a finite volume approach in the Eulerian representation. The latter results are extended to non-Boussinesq regimes. The advantages and limitations of the LPP formulation and variational discretization are highlighted.

12.
Brain ; 128(Pt 4): 896-905, 2005 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-15689356

RESUMO

The pathogenesis of amyotrophic lateral sclerosis (ALS) remains obscure, but it is now clear that neuronal loss is not confined to the motor cortex, even in cases without dementia. A reliable method of assessing cortical involvement in vivo remains elusive. WAY100635 binds selectively to the 5-hydroxytryptamine (5-HT1A) receptor, which is expressed on pyramidal neurones present throughout the cortex. [11C]-WAY100635 PET is, therefore, a potential marker of cerebral neuronal loss or dysfunction in ALS. Twenty-one ALS subjects and 19 healthy volunteers underwent [11C]-WAY100635 PET of the brain. A cortical template consisting of multiple volumes of interest (VOI) was applied to each individual's [11C]-WAY100635 binding potential (BP) image to determine the regional reduction in binding in ALS patients compared to controls. There was a marked reduction (21%) in both the global cortical and raphe BP of [11C]-WAY100635 in ALS patients (P < 0.001), with regional variations in the VOI analysis that ranged from 16% to 29% decrease compared with the control group, and trends to greater reductions in those with bulbar involvement. To clarify the significance of the global cortical reductions, statistical parametric mapping was used as an alternative method to identify the cortical regions with the most significant decreases in [11C]-WAY100635 binding. SPM analysis revealed the greatest differences between ALS cases and controls in frontotemporal regions, cingulate and lateral precentral gyri. The reductions in cortical [11C]-WAY100635 binding were not related to depression, riluzole or other drug use. We postulate that the reduction of 5-HT1A binding represents loss of, or damage to, neurones bearing these receptors although we cannot exclude the possibility that these reductions reflect alterations in receptor expression or function. Further investigation into the role of the 5-HT1A receptor and the potential of [11C]-WAY100635 PET as a marker of cortical dysfunction in ALS is warranted.


Assuntos
Esclerose Lateral Amiotrófica/diagnóstico por imagem , Esclerose Lateral Amiotrófica/metabolismo , Piperazinas , Piridinas , Receptor 5-HT1A de Serotonina/metabolismo , Antagonistas da Serotonina , Adulto , Idoso , Esclerose Lateral Amiotrófica/psicologia , Radioisótopos de Carbono , Córtex Cerebral/diagnóstico por imagem , Córtex Cerebral/metabolismo , Depressão/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons , Controle de Qualidade
13.
Brain ; 128(Pt 6): 1323-9, 2005 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-15843422

RESUMO

Five to ten percent of amyotrophic lateral sclerosis (ALS) cases are associated with mutations of the superoxide dismutase-1 (SOD1) gene, and the 'D90A' mutation is associated with a unique phenotype and markedly slower disease progression (mean survival time 14 years). Relative sparing of inhibitory cortical neuronal circuits might be one mechanism contributing to the slower progression in patients homozygous for the D90A mutation (homD90A). The GABA(A) receptor PET ligand [11C]flumazenil has demonstrated motor and extra-motor cortical changes in sporadic ALS. In this study, we used [11C]flumazenil PET to explore differences in the pattern of cortical involvement between sporadic and genetically homogeneous ALS groups. Twenty-four sporadic ALS (sALS) and 10 homD90A patients underwent [11C]flumazenil PET of the brain. In addition, two subjects homozygous for the D90A mutation, but without symptoms or signs ('pre-symptomatic', psD90A), also underwent imaging. Results for each group were compared with those for 24 healthy controls of similar age. Decreases in the binding of [11C]flumazenil in the sALS group were found within premotor regions, motor cortex and posterior motor association areas. In the homD90A group of ALS patients, however, decreases were concentrated in the left fronto-temporal junction and anterior cingulate gyrus. In the two psD90A subjects, a small focus of reduced [11C]flumazenil binding at the left fronto-temporal junction was seen, similar to the pattern seen in the clinically affected patients. Within the sALS group, there was no statistically significant association between decreases in cortical [11C]flumazenil binding and revised ALS functional rating scale (ALSFRS-R score), whereas the upper motor neuron (UMN) score correlated with widespread and marked cortical decreases over the dominant hemisphere. In the homD90A group, there was a stronger statistical association between reduced cortical [11C]flumazenil binding and the ALSFRS-R, rather than the UMN, score, and also with disease duration. This study provides evidence for differences in the distribution of reduced cortical [11C]flumazenil binding in homD90A compared with sALS patients. We hypothesize that this might reflect differences in cortical neuronal vulnerability.


Assuntos
Esclerose Lateral Amiotrófica/genética , Mutação , Superóxido Dismutase/genética , Adulto , Idoso , Esclerose Lateral Amiotrófica/diagnóstico por imagem , Esclerose Lateral Amiotrófica/enzimologia , Radioisótopos de Carbono , Córtex Cerebral/diagnóstico por imagem , Progressão da Doença , Feminino , Flumazenil , Moduladores GABAérgicos , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons/métodos , Índice de Gravidade de Doença , Superóxido Dismutase-1
14.
Biochim Biophys Acta ; 1004(1): 49-52, 1989 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-2742873

RESUMO

In mammals, platelet activating factor (PAF, 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine) is a lipid mediator with biological activity at concentrations in the subnanomolar range. Although PAF is known to have many activities in mammals, little is known about its synthesis and importance in other vertebrate groups. We demonstrate here the synthesis of PAF from [3H]acetate by slices of trout gill, kidney, liver and spleen. PAF synthesis was stimulated by the calcium ionophore A23187 and was time-dependent. The radiolabeled PAF produced was characterized by TLC, HPLC, derivatization and by saponification and phospholipase A2 hydrolysis. These findings suggest that PAF may be an important mediator in fish.


Assuntos
Fator de Ativação de Plaquetas/biossíntese , Salmonidae/metabolismo , Truta/metabolismo , Animais , Cromatografia Líquida de Alta Pressão , Cromatografia em Camada Fina , Brânquias/metabolismo , Hidrólise , Técnicas In Vitro , Rim/metabolismo , Fígado/metabolismo , Fator de Ativação de Plaquetas/metabolismo , Baço/metabolismo , Trítio
15.
Thromb Haemost ; 39(2): 346-59, 1978 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-580986

RESUMO

A major limitation to single-cell protein (SCP) as a human food is its high nucleic acid content, the purine moiety of which is metabolised to uric acid. Rats given a Fusarium mould as a source of SCP in diets containing oxonate, a uricase inhibitor, showed elevated plasma and kidney uric acid concentrations after 21 d, which were related to the level of dietary mould. ADP-induced and thrombin-induced platelet aggregation was greater in the hyperuricaemic rats than in controls and a progressive increase in aggregation with increasing levels of dietary mould was observed. Furthermore a time-lag, exceeding the life-span of rat platelets, was observed between the development of hyperuricaemia and the increase in aggregation. A similar time-lag was observed between the lowering of the hyperuricaemia and the reduction of platelet aggregation when oxonate was removed from the diet. If human platelets react to uric acid in the same manner as rat platelets this might explain the link that has been suggested between hyperuricaemia and ischaemic heart disease. In that event diets high in nucleic acids might be contra-indicated in people at risk from ischaemic heart disease. In rats given a low protein diet (50 g casein/kg) for 21 d ADP-induced and thrombin-induced platelet aggregation and whole blood platelet count were reduced compared with control animals receiving 200 g casein/kg diet but not in rats given 90 or 130 g casein/kg diet. A study of the time course on this effect indicated that the reduction both in aggregation tendency and in whole blood platelet count occurred after 4 d of feeding the low protein diet. These values were further reduced with time.


Assuntos
Agregação Plaquetária , Ácido Úrico/sangue , Animais , Proteínas Alimentares , Feminino , Ácido Oxônico , Deficiência de Proteína , Ratos
16.
J Psychopharmacol ; 15(1): 61-3, 2001 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-11277611

RESUMO

We present the case of a 36-year-old man who presented with a clinically neuroleptic malignant-like syndrome involving disorientation, signs of autonomic dysfunction, rigidity and raised total creatine kinase level, but in the absence of any neuroleptic medication. He had, however, abruptly stopped taking his long-term baclofen in the days prior to presentation. He improved markedly after the reintroduction of baclofen, and we postulate that his clinical syndrome resulted from the sudden withdrawal of this drug. We concur with the concept that neuroleptic malignant syndrome represents a spectrum of disorders, and add it to the list of possible sequelae after abrupt withdrawal of baclofen.


Assuntos
Baclofeno/efeitos adversos , Relaxantes Musculares Centrais/efeitos adversos , Síndrome Maligna Neuroléptica/psicologia , Síndrome de Abstinência a Substâncias/psicologia , Adulto , Baclofeno/uso terapêutico , Creatina Quinase/sangue , Eletrocardiografia/efeitos dos fármacos , Humanos , Masculino , Relaxantes Musculares Centrais/uso terapêutico , Rigidez Muscular/induzido quimicamente , Paraplegia/complicações
17.
Lipids ; 26(7): 517-20, 1991 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-1943495

RESUMO

In mammalian systems, platelet-activating factor, 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine, (PAF) is rapidly inactivated by a deacetylation/reacylation system that produces 1-O-alkyl-2-acyl-sn-glycero-3-phosphocholine which is highly enriched in arachidonic acid. There is some evidence that n-3 fatty acids may have an impact on this system in humans but the nature of this impact is unclear. In rainbow trout, n-3 fatty acids are known to be essential dietary components which are derived through the food chain. Substantial quantities of n-3 fatty acids are found in trout membrane phospholipids. We show here that in sharp contrast to mammalian cells, trout cells acylate lyso platelet-activating factor, alkyl-GPC, 1-O-alkyl-2-lyso-sn-glycero-3-phosphocholine, (lyso-PAF) with a high degree of specificity for n-3 fatty acids. When [3H]lysoPAF was incubated with these cells, only three molecular species of alkylacylglycerophosphocholine were produced, and 92% contained n-3 fatty acids. Since isolated membranes yielded similar results, it appears that the acylation proceeds via a coenzyme A-independent transacylase as found in mammalian systems.


Assuntos
Fator de Ativação de Plaquetas/análogos & derivados , Truta/metabolismo , Acilação , Animais , Coenzima A/metabolismo , Ácidos Graxos Ômega-3/biossíntese , Técnicas In Vitro , Fator de Ativação de Plaquetas/metabolismo , Baço/metabolismo
18.
J Hum Lact ; 12(1): 50-3, 1996 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-8715240

RESUMO

A simple post-service consumer survey is presented with which the lactation consultant can gather and analyze data to determine the extent to which services are meeting the needs of clients. The brief survey can be used to gather data from all clients or from a sample of clients. The survey can be administered by telephone or by postal return form. After analyzing the data obtained, the lactation consultant can identify where improvement in practice is needed. An additional " self assessment questionnaire" enables the lactation consultant to identify areas where personal growth is needed.


Assuntos
Aleitamento Materno , Consultores , Mães , Satisfação do Paciente , Garantia da Qualidade dos Cuidados de Saúde , Inquéritos e Questionários , Feminino , Necessidades e Demandas de Serviços de Saúde , Humanos , Recém-Nascido , Mães/educação , Mães/psicologia
19.
Hosp Med ; 62(10): 627-30, 2001 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11688126

RESUMO

Starting a research post after ward-based work can be a leap of faith and, as rewarding as it ultimately is, the initial transition can be a difficult one. This article addresses some of the questions which someone considering research should ask.


Assuntos
Educação de Pós-Graduação em Medicina/organização & administração , Corpo Clínico Hospitalar/educação , Pesquisa/educação , Humanos , Apoio à Pesquisa como Assunto , Reino Unido
20.
Lancet Neurol ; 12(4): 339-45, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23453347

RESUMO

BACKGROUND: Lithium has neuroprotective effects in cell and animal models of amyotrophic lateral sclerosis (ALS), and a small pilot study in patients with ALS showed a significant effect of lithium on survival. We aimed to assess whether lithium improves survival in patients with ALS. METHODS: The lithium carbonate in amyotrophic lateral sclerosis (LiCALS) trial is a randomised, double-blind, placebo-controlled trial of oral lithium taken daily for 18 months in patients with ALS. Patients aged at least 18 years who had ALS according to the revised El Escorial criteria, had disease duration between 6 and 36 months, and were taking riluzole were recruited from ten centres in the UK. Patients were randomly assigned (1:1) to receive either lithium or matched placebo tablets. Randomisation was via an online system done at the level of the individual by block randomisation with randomly varying block sizes, stratified by study centre and site of disease onset (limb or bulbar). All patients and assessing study personnel were masked to treatment assignment. The primary endpoint was the rate of survival at 18 months and was analysed by intention to treat. This study is registered with Eudract, number 2008-006891-31. FINDINGS: Between May 26, 2009, and Nov 10, 2011, 243 patients were screened, 214 of whom were randomly assigned to receive lithium (107 patients) or placebo (107 patients). Two patients discontinued treatment and one died before the target therapeutic lithium concentration could be achieved. 63 (59%) of 107 patients in the placebo group and 54 (50%) of 107 patients in the lithium group were alive at 18 months. The survival functions did not differ significantly between groups (Mantel-Cox log-rank χ(2) on 1 df=1·64; p=0·20). After adjusting for study centre and site of onset using logistic regression, the relative odds of survival at 18 months (lithium vs placebo) was 0·71 (95% CI 0·40-1·24). 56 patients in the placebo group and 61 in the lithium group had at least one serious adverse event. INTERPRETATION: We found no evidence of benefit of lithium on survival in patients with ALS, but nor were there safety concerns, which had been identified in previous studies with less conventional designs. This finding emphasises the importance of pursuing adequately powered trials with clear endpoints when testing new treatments. FUNDING: The Motor Neurone Disease Association of Great Britain and Northern Ireland.


Assuntos
Esclerose Lateral Amiotrófica/tratamento farmacológico , Esclerose Lateral Amiotrófica/mortalidade , Idoso , Método Duplo-Cego , Feminino , Humanos , Carbonato de Lítio/uso terapêutico , Masculino , Pessoa de Meia-Idade , Fármacos Neuroprotetores/uso terapêutico , Taxa de Sobrevida/tendências , Resultado do Tratamento
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