摘要:

The white matter of the brain is vulnerable to a wide variety of toxins. Leukoencephalopathy is being increasingly recognized in a number of different patient populations. The detection of early and subtle toxin effects has been facilitated by the advent of magnetic resonance imaging, which offers better resolution of white matter than other neuroimaging methods. Neuropathologic features of leukoencephalopathy arc also becoming more completely elucidated. Injury to white matter has been described from cranial irradiation and cancer chemotherapeutic drugs, and from a number of other therapeutic agents, drugs of abuse, and environmental toxins. Many patients have reversible leukoencephalopathy, whereas others experience a progressive and irreversible course. Leukoencephalopathy is associated with neurobehavioral manifestations that may be subtle or devastating, and the syndrome of white matter dementia may result. The pathogenesis of toxic leukoencephalopathy remains largely unknown, and treatment is limited in most cases to prevention by avoidance or minimization of the toxin exposure. However, the prognosis for this syndrome may be relatively favorable because of the frequent sparing of axons even when myelin is affected. Toxic leukoencephalopathy is an emerging clinical disorder that presents the opportunity for improving clinical outcomes in a number of patient groups and for achieving a deeper understanding of the role of white matter in cognitive and emotional function.

ISSN:0362-5664    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Generalized convulsive status epilepticus (GCSE) is a medical emergency requiring prompt resolution. Acute treatment is often delayed by difficulty in obtaining intravenous (IV) access. Refractory GCSE is often difficult to treat, and traditional therapy with barbiturates induces hypotension and respiratory depression and prolongs recovery. Midazolam is particularly useful for treating acute GCSE because it has an imidazole ring that is open at low pH, allowing it to be dissolved in aqueous solution for intramuscular injection, but closed at physiologic pH, increasing lipophilicity and rendering good intramuscular absorption, brain penetration, and fast onset of action. When given intramuscularly as a 0.2 mg/kg bolus, it has efficacy at least equal to that of IV diazepam, is well tolerated, induces little respiratory compromise, and has a shorter latency to onset of action. Therefore, it should be considered for the treatment of acute GCSE when IV access is problematic. For refractory GCSE, continuous IV midazolam infusion at 0.1–0.6 mg/kg/hr after a 0.2 mg/kg IV bolus is effective and has advantages over traditional therapies because it induces less hypotension and cardiorespiratory depression and can be easily titrated. Further prospective studies are needed to define the role of continuous IV midazolam compared to other contemporary therapies.

ISSN:0362-5664    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

A case of a patient who developed symptomatic phenytoin-induced folic acid deficiency is reported. Folate supplementation of 5 mg/d was followed by a decrease of serum phenytoin concentration to a subtherapeutic level with a breakthrough seizure. Estimation of phenytoin's Km-Vmax Michaelis-Menten pharmacokinetic parameters in this patient demonstrated that folate supplements indeed caused a significant decrease in the Km value. This decrease correlates with a greater affinity of the metabolizing hepatic enzymes for the drug, and hence, with the resultant increase in phenytoin's metabolism and decrease of its serum concentration and anticonvulsive effect. In an era of increasing knowledge of folate's pivotal role in various diseases, we call attention to this drug-vitamin interaction, and to the previously suggested recommendation that folate supplementation should be initiated whenever phenytoin therapy commences. Because folic acid dosages as low as 1 mg/d may perturbate phenytoin's metabolism, smaller deficiency preventive doses may be the advisable allowance for phenytoin-treated patients with normal pretreatment folate levels. This suggestion must be confirmed by a prospective study in a large cohort of patients.

ISSN:0362-5664    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Our aim was to evaluate the effect of Memantine (1-amino 3,5-dimethyl-adamantane hydrochloride) on cardinal symptoms of Parkinson's disease and on the latency, duration, and magnitude of the response to a single dose of L-Dopa and on drug-induced dyskinesias. Twelve Hoehn-Yahr II1-IV patients with idiopathic Parkinson's disease with motor fluctuations and drug-induced dyskinesias were randomized to the NMDA antagonist memantine or placebo in a cross-over design. A single-dose L-Dopa challenge was performed after each medication arm. A significant drug effect on the Unified Parkinson's Disease Rating Scale motor score was observed in “off” and “on” states (F( 1,11) = 13.5;p< 0.003). No significant effect on drug-induced dyskinesias was seen. The results suggest that memantine may improve parkinsonian symptoms independently of dopaminergic drugs and, in contrast to recent findings with amantadine, it has no effect on drug-induced dyskinesias.

ISSN:0362-5664    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

It is well known that chronic administration of pergolide and other dopamine agonists may induce a downregulation of dopamine D2 receptors in the rat model of Parkinson's disease (PD). To our knowledge, this effect has not been demonstratedin vivoin patients with PD. At present, the status of striatal dopamine D2 receptors can be studied with use of positron emission tomographic (PET) technology. Five patients with PD chronically treated with levodopa were studied with use of PET and [ 11 C]-raclopride before and after 6 months of pergolide treatment (dose range = 4.5–7.5 mg/d). We found a slight reduction in the specific striatal [1 lC]-raclopride uptake index (mean reduction 14% in putamen and 9% in caudate) after pergolide treatment. This reduction appears to be related to downregulation of the receptor, although competitive binding of pergolide at the D2 receptor cannot be excluded.

ISSN:0362-5664    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

We assessed the antiparkinsonian response in MPTP-treated monkeys after acute or repeated treatment with oral L-Dopa, subcutaneous administration of L-Dopa methyl ester (LDME) or apomorphine, alone and in combination with D1antagonists SCH 23390 (SCH) or NNC 01–0112 (NNC). When given alone, the L-Dopa effect occurred within the first hour after treatment. Coadministration of SCH or NNC with L-Dopa significantly delayed the onset of action. The response duration remained unchanged, as did the extent of the antiparkinsonian effect, after SCH, whereas the former became shorter at the higher doses of NNC tested. Bypass of the gastrointestinal tract using parenteral injections of LDME and apomorphine allowed the rapid turning “on” of the animals. Both D1antagonists administered with LDME delayed the onset and shortened the duration of the therapeutic effect as the dose increased. Pretreatment with SCH failed to block the antiparkinsonian effect induced by apomorphine, but reduced the response duration markedly in a dose-related fashion. Repeated treatment of one monkey with SCH combined with the same dopaminergic drugs produced results similar to those obtained after acute treatment in four animals. The results obtained with parenteral administration of LDME and apomorphine most probably involve pharmacodynamic actions resulting in increased threshold of response. The delay observed with L-Dopa suggests pharmacokinetic interference possibly mediated via dopamine receptors located at the level of the gut.

ISSN:0362-5664    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Sargramostim (GM-C'SF) therapy was instituted in a 49-year-old woman with hepatitis C on chronic intcrferon alpha-2b therapy. Within two weeks, she developed progressive confusion, lethargy, and gait disturbance. At autopsy 4 months later, diffuse perivascular nonmonoclonal lymphoid infiltrates were demonstrated throughout the central nervous system (CNS). As the use of hematopoictic growth factors in clinical practice increases, potential adverse effects, such as the fulminant CNS lymphocytic proliferation in this patient, arc more likely to be encountered.

ISSN:0362-5664    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

We report a female patient in whom so-called apraxia of eyelid opening (AEO) developed after the onset of possible progressive supranuclear palsy (National Institute of Neurologieal Disorders and Stroke criteria) and the introduction of antipar-kinsonian medications including levodopa. Although parkinsonian symptoms responded poorly to levodopa, AEO worsened after increasing levodopa dosage and disappeared when levodopa was discontinued. Later, a dose of apomorphine widely accepted for acute tests had no significant effect on limb motor activity but induced AEO. Overall, these observations arc grounds for thinking that AEO developing in the course of parkinsonism may be either disease- or drug-related. The possibility of manipulating dopaminergic treatment should always be considered when dealing with AEO associated with parkinsonism.

ISSN:0362-5664    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Rhabdomyolysis is described as an adverse event of simvastatin therapy either by itself or in combination with other medications. It is unclear whether this phenomenon is specific to simvastatin or to all cholesterol-lowering agents as single-dose therapy or caused by the association of special coadministered medications. We describe two cases in which rhabodomyolysis developed after coadministration of simvastatin (20 mg/d) and the antifungal ketoconazole. The clinical features, blood examination results, and positive outcome were very similar in both cases. We concluded that ketoconazole, an antifungal sterol synthetic inhibitor of the azol group, may induce rhabdo-myolysis in patients undergoing treatment with simvastatin, a lipid lowering agent, and increase the possibility of muscle-damaging adverse events of the agents.

ISSN:0362-5664    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Standard mood stabilizers, such as lithium and haloperidol, and anticonvul-sants show effectiveness in a maximum of 60%–70% of acutely manic patients. Obviously, there is a clinical need to evaluate other treatment options. Current pathophysiologic concepts suggest that substances with an ameliorating effect on dopaminergic hyperfunction, serotonergic hypofunction, or GABAergic hypofunction might be useful, as may be substances with calcium-antagonistic effects.In vitro, the antidepressant trimipramine exerts dopamine- and calcium-antagonistic properties. Therefore, we conducted an open trial to screen it for antimanic action. We found no clinical benefit in four acutely manic patients receiving up to 400 mg/d of trimipramine. It is concluded that, at least in the case of trimipramine, the pharmacologic profile is not helpful in predicting potential effectiveness in mania.

ISSN:0362-5664    

出版商:OVID    

年代:1999

数据来源: OVID