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1.
Neurobiol Aging ; 33(7): 1318-9, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21257235

RESUMO

A recent publication suggested that hypocretin (Hcrt, orexin) may mediate the neuropathological process leading to Alzheimer's disease (AD) and that antagonism of hypocretin receptors decreases this process. Narcoleptics have an approximately 90% loss of Hcrt neurons and commensurate reductions in the levels of Hcrt in their cerebrospinal fluid beginning at disease onset, usually before the age of 30. If Hcrt mediates the disease process, narcoleptics should be protected against AD. We examined the postmortem neuropathology and clinical records of 12 sequentially encountered cases of human narcolepsy. We found that AD was present in 4 of these narcoleptics, a prevalence that is similar to that of the general population.


Assuntos
Doença de Alzheimer/complicações , Doença de Alzheimer/diagnóstico , Narcolepsia/complicações , Narcolepsia/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Humanos , Masculino
2.
Neurology ; 57(10): 1896-9, 2001 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-11723285

RESUMO

The neuroexcitatory peptide hypocretin and its receptors are central to the pathophysiology of both human and animal models of the disease. In this study of American and Icelandic patients with narcolepsy, the authors found no significant association between narcolepsy and single-nucleotide polymorphisms in the genes for hypocretin or its two known receptors, hypocretin receptor-1 and hypocretin receptor-2.


Assuntos
Proteínas de Transporte/genética , Peptídeos e Proteínas de Sinalização Intracelular , Narcolepsia/genética , Neuropeptídeos/genética , Polimorfismo Genético , Precursores de Proteínas/genética , Adulto , Mapeamento Cromossômico , Comparação Transcultural , Éxons , Feminino , Predisposição Genética para Doença/genética , Testes Genéticos , Genótipo , Humanos , Islândia , Íntrons , Masculino , Pessoa de Meia-Idade , Narcolepsia/diagnóstico , Receptores de Orexina , Orexinas , Receptores Acoplados a Proteínas G , Receptores de Neuropeptídeos/genética , Estados Unidos
3.
Am J Respir Crit Care Med ; 164(9): 1675-81, 2001 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-11719309

RESUMO

Patients with obstructive sleep apnea/hypopnea syndrome can experience residual daytime sleepiness despite regular use of nasal continuous positive airway pressure therapy. This randomized, double-blind, placebo-controlled, parallel group study assessed the efficacy and safety of modafinil for the treatment of residual daytime sleepiness in such patients. Patients received modafinil (n = 77) (200 mg/d, Week 1; 400 mg/d, Weeks 2 to 4) or matching placebo (n = 80) once daily for 4 wk. Modafinil significantly improved daytime sleepiness, with significantly greater mean changes from baseline in Epworth Sleepiness Scale scores at Weeks 1 and 4 (p < 0.001) and in multiple sleep latency times (MSLT) at Week 4 (p < 0.05). The percentage of patients with normalized daytime sleepiness (Epworth score < 10) was significantly higher with modafinil (51%) than with placebo (27%) (p < 0.01), but not for MSLT (> 10 min; 29% versus 25%). Headache (modafinil, 23%; placebo, 11%; p = 0.044) and nervousness (modafinil, 12%; placebo, 3%; p = 0.024) were the most common adverse events. During modafinil or placebo treatment, the mean duration of nCPAP use was 6.2 h/night, with no significant change from baseline observed between groups. Modafinil may be a useful adjunct treatment for the management of residual daytime sleepiness in patients with obstructive sleep apnea/hypopnea syndrome who are regular users of nasal continuous positive airway pressure therapy.


Assuntos
Compostos Benzidrílicos/uso terapêutico , Estimulantes do Sistema Nervoso Central/uso terapêutico , Apneia Obstrutiva do Sono/tratamento farmacológico , Fases do Sono/efeitos dos fármacos , Adulto , Idoso , Análise de Variância , Compostos Benzidrílicos/efeitos adversos , Estimulantes do Sistema Nervoso Central/efeitos adversos , Terapia Combinada , Qualidade de Produtos para o Consumidor , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modafinila , Polissonografia , Respiração com Pressão Positiva , Índice de Gravidade de Doença , Estatísticas não Paramétricas
5.
Magn Reson Med ; 40(4): 614-21, 1998 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-9771578

RESUMO

A quiet magnetic resonance (MR) imaging technique for detecting changes in cerebral activity functions is presented. This single-shot method, functional Burst imaging (FBI), combines elements of Burst imaging with an offset technique known as asymmetric spin echo (ASE). The FBI sequence has the unique feature of being nearly silent, because of the low number of gradient switching steps involved. Furthermore, this approach has the key advantage that it can be implemented on conventional MR systems. Established auditory and visual paradigms were used to evaluate whether FBI can detect changes in cerebral activity using a 1.5 Tesla MR system. In a second set of experiments, the FBI technique was used to evaluate cerebral activity changes during different sleep stages in humans. The results obtained demonstrate that the FBI sequence provides an alternative approach for functional imaging of brain activity in primary and secondary sensory areas of the human brain. Furthermore, in using this quiet MR technique, it was possible to scan continuously during different stages of human sleep without acoustic noise perturbation.


Assuntos
Encéfalo/anatomia & histologia , Imageamento por Ressonância Magnética/métodos , Estimulação Acústica , Encéfalo/fisiologia , Humanos , Processamento de Imagem Assistida por Computador , Estimulação Luminosa , Fases do Sono/fisiologia
7.
Clin Pharmacol Ther ; 57(5): 552-8, 1995 May.
Artigo em Inglês | MEDLINE | ID: mdl-7768078

RESUMO

We previously observed tht low oral doses of melatonin given at noon increase blood melatonin concentrations to those normally occurring nocturnally and facilitate sleep onset, as assessed using and involuntary muscle relaxation test. In this study we examined the induction of polysomnographically recorded sleep by similar doses given later in the evening, close to the times of endogenous melatonin release and habitual sleep onset. Volunteers received the hormone (oral doses of 0.3 or 1.0 mg) or placebo at 6, 8, or 9 PM. Latencies to sleep onset, to stage 2 sleep, and to rapid eye movement (REM) sleep were measured polysomnographically. Either dose given at any of the three time points decreased sleep onset latency and latency to stage 2 sleep. Melatonin did not suppress REM sleep or delay its onset. Most volunteers could clearly distinguish between the effects of melatonin and those of placebo when the hormone was tested at 6 or 8 PM. Neither melatonin dose induced "hangover" effects, as assessed with mood and performance tests administered on the morning after treatment. These data provide new evidence that nocturnal melatonin secretion may be involved in physiologic sleep onset and that exogenous melatonin may be useful in treating insomnia.


Assuntos
Melatonina/administração & dosagem , Sono/efeitos dos fármacos , Administração Oral , Adulto , Afeto/efeitos dos fármacos , Método Duplo-Cego , Esquema de Medicação , Humanos , Masculino , Melatonina/farmacologia , Polissonografia , Desempenho Psicomotor/efeitos dos fármacos , Fatores de Tempo
8.
Semin Arthritis Rheum ; 22(3): 151-61, 1992 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-1295088

RESUMO

A 27-year-old white man with no significant risk factors for coronary artery disease presented with a 9-month history of progressive impotence, gynecomastia, lower extremity paresthesias, and extensive myocardial infarction and subsequently developed ulcerative proctitis. A diagnosis of POEMS syndrome was made based on the clinical presentation; additional physical findings of papilledema, clubbing, and hyperpigmentation; and laboratory findings of an immunoglobulin G M component of the lambda subtype, elevated cerebrospinal fluid protein, and typical sclerotic bone lesions. Abnormal in vitro binding of the patient's serum immunoglobulin to testicular tissue was also seen. Cardiac catheterization showed evidence of diffuse coronary artery narrowing and left ventricular wall motion abnormalities. Diffuse coronary involvement and ulcerative proctitis have not been previously described in POEMS syndrome. It is hypothesized that an abnormal immunoglobin (or fragment) is responsible for both findings. Furthermore, the detection of antitesticular autoantibodies suggests the possibility of an interaction between the antibody and Leydig cells, leading to an alteration in the synthesis and release of sex steroids and thereby explaining the gonadal failure seen in this syndrome. Long-term glucocorticoid therapy for the past 5 years has resulted in marked subjective and objective improvement.


Assuntos
Infarto do Miocárdio/complicações , Infarto do Miocárdio/etiologia , Síndrome POEMS/complicações , Síndrome POEMS/etiologia , Adulto , Humanos , Masculino , Infarto do Miocárdio/fisiopatologia , Síndrome POEMS/fisiopatologia
9.
Arch Neurol ; 43(4): 338-40, 1986 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-3954617

RESUMO

Thirty-two patients with amyotrophic lateral sclerosis were studied with somatosensory evoked potentials (SEPs), visual evoked potentials, and brain-stem auditory evoked potentials. H-reflexes were used to screen for abnormalities of peripheral nerve conduction. Nineteen patients (59%) showed an abnormality of lower extremity SEPs. In 13 patients (40%) the delay was of central origin, while in six patients (19%) peripheral conduction delay was possible. Abnormality of upper limb SEPs was seen in 11 patients (34%), all but two of whom had abnormal lower limb SEPs as well. Four patients (12%) had abnormal brain-stem auditory evoked potentials, all of whom had abnormal SEPs from upper and lower limbs. Four patients had abnormal visual evoked potentials, which in three patients were of minor degree. These results give physiologic evidence to suggest that abnormalities in amyotrophic lateral sclerosis occur outside the motor system.


Assuntos
Esclerose Lateral Amiotrófica/fisiopatologia , Potenciais Evocados , Adulto , Idoso , Encéfalo/fisiopatologia , Tronco Encefálico/fisiopatologia , Potenciais Evocados Auditivos , Potenciais Somatossensoriais Evocados , Potenciais Evocados Visuais , Extremidades/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
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