ISSN:0362-5664    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

Eleven parkinsonian patients participated in a pharmacokinetic/pharmacodynamic study in an attempt to model levodopa (L-DOPA) plasma concentrations to clinical effect. Carbidopa 25 mg/L-DOPA 100 mg (Sinemet 25/100) was given orally, and blood samples were obtained before and serially for 4 hours after the dose. Effect measurements were obtained with each blood sample and included tapping score, timed walking, and global assessment of motor function. Mean L-DOPA plasma concentrations were fitted to a one-compartment pharmacokinetic model. A time-wise plot of modeled plasma L-DOPA concentrations versus mean effect measurements revealed a counterclockwise hysteresis. Effect compartment concentrations were determined by a least squares approach, which determined elimination rate constants by minimizing hysteresis. Half-times for the equilibration between plasma and the effect compartment were 0.39 h for tapping, 0.36 h for walking, and 0.34 h for the global score. Pharmacodynamic data were fit best with an Emaxmodel with baseline effect for tapping (Emax= 53.2 taps/60 s, EC50= 0.58 μg/ml) and global score (Emaxset at 5.0 by limits of scale, EC50= 2.53 (μg/ml). A linear model best described the relationship between predicted effect site concentration and timed walking. L-DOPA plasma concentrations after oral Sinemet did not correlate well with clinical response because clinical response lags behind plasma concentrations. Half-times for equilibration between plasma and the effect site were similar for all of the effects measured.

ISSN:0362-5664    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

One hundred patients with Parkinson's disease (PD) and five patients with progressive supranuclear palsy were questioned about the frequency, circumstances, and consequences of falling. Parkinsonian symptoms were scored using the unified rating scale. Thirty-eight percent of parkinsonian patients fell, and 13% fell more than once a week. Broken bones (13%), hospitalization (18%), confinement to wheelchair (3%), and fear of walking occurred. Postural hypotension was uncommon and did not correlate to falling. Sensory loss, dementia, heart disease, and the use of antihypertensive medications were not related to falling. Falling did correlate with postural instability, bradykinesia, and rigidity but not with tremor. Falling was also related to age and duration of disease. The frequency of falling was correlated only to the severity of one parkinsonian symptom, postural instability. Progressive supra-nuclear palsy patients fell often and had marked postural instability. Factor analysis of parkinsonian characteristics yielded three groups, with tremor being an independent symptom. Frequent fallers and postural instability were not changed by dopaminergic therapy. Some fallers with gait difficulties and bradykinesia were improved with levodopa. Physical therapy was also of benefit to some patients. It is concluded that falling is a common problem in PD and may cause serious disability. Falling may be related to all the major motor signs except for tremor. Frequent falling is caused by postural instability, which is not reversible with dopaminergic therapy.

ISSN:0362-5664    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

Yohimbine hydrochloride was administered intravenously to nine normal volunteers to assess α2-adrenergic receptor function. Plasma catecholamines, cortisol, and psychophysiological parameters (blood pressure, pulse, somatic symptoms checklist, and visual analogue scales assessing mood) were used as dependent variables. Plasma norepinephrine and plasma cortisol increased significantly after yohimbine administration, while epinephrine remained unchanged. Systolic blood pressure and somatic symptoms were also significantly increased by yohimbine. These findings suggest that low-dose intravenous yohimbine is an effective probe for α2-adrenergic receptors and the hypothalamic-pituitary-adrenal axis.

ISSN:0362-5664    

出版商:OVID    

年代:1989

数据来源: OVID

ISSN:0362-5664    

出版商:OVID    

年代:1989

数据来源: OVID

ISSN:0362-5664    

出版商:OVID    

年代:1989

数据来源: OVID

ISSN:0362-5664    

出版商:OVID    

年代:1989

数据来源: OVID

ISSN:0362-5664    

出版商:OVID    

年代:1989

数据来源: OVID

ISSN:0362-5664    

出版商:OVID    

年代:1989

数据来源: OVID

ISSN:0362-5664    

出版商:OVID    

年代:1989

数据来源: OVID