A randomized, controlled trial of remacemide for motor fluctuations in Parkinson's disease.

BACKGROUND: Preclinical studies suggest that glutamate antagonists help ameliorate motor fluctuations in patients with PD treated with levodopa. METHODS: In a multicenter, randomized, double-blind, placebo-controlled, parallel-group, dose-ranging study, the authors assessed the safety, tolerability, and efficacy of the glutamate receptor blocker remacemide hydrochloride in 279 patients with motor fluctuations treated with levodopa. The primary objective was to assess the short-term tolerability and safety of four dosage levels of remacemide during 7 weeks of treatment. Patients were also monitored with home diaries and the Unified PD Rating Scale (UPDRS) to collect preliminary data on treatment efficacy. RESULTS: Remacemide was well tolerated up to a dosage of 300 mg/d on a twice daily schedule and 600 mg/d on a four times daily schedule. The most common dosage-related adverse events were dizziness and nausea, as observed in previous studies of remacemide. The percent "on" time and motor UPDRS scores showed trends toward improvement in the patients treated with 150 and 300 mg/d remacemide compared with placebo-treated patients, although these improvements were not significant. CONCLUSION: Remacemide is a safe and tolerable adjunct to dopaminergic therapy for patients with PD and motor fluctuations. Although this study had limited power to detect therapeutic effects, the observed improvement is consistent with studies of non-human primates with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced parkinsonian signs and symptoms. Additional studies are warranted to confirm these results over an extended period of observation, and to explore the potential neuroprotective effects of remacemide in slowing the progression of PD.

Maternal mortality in Mississippi: 1987-1991.

OBJECTIVE: To characterize the maternal mortality in the state of Mississippi for 1987-1991 and compare the maternal mortality from 1977-1986 with that of the last 5 years. STUDY DESIGN: Factors associated with maternal mortality were obtained from death certificates, replies to questionnaires, medical records, and autopsy reports. RESULTS: The maternal mortality rate in Mississippi for 1987-1991 (14.1/100,000) was not significantly different than for 1977-1986 (11.8/1000,000; P = 0.45). Over the last 5 years there was an increased incidence of direct obstetric deaths (50% vs 73%). During 1987-1991, toxemia as a cause of death for parturients decreased, while hemorrhage as a cause of maternal death increased. There was a rise in the incidence of patient related factors which were avoidable and which led to several deaths during 1987-1991. CONCLUSION: The state's maternal mortality rate remains stable. Improved patient and health care provider's education are necessary to further decrease the incidence of maternal death in Mississippi.

Independent travel for developmentally disabled persons: a comprehensive model of instruction.

Independence and self-determination are long established goals for developmentally disabled persons. Some aspects of independence depend upon the ability to to gain access to resources in the local community. As a result, the acquisition of independent travel skills has received much attention over the years. However, most attempts to teach travel skills to this population have been limited in scope. This paper advocates a more comprehensive approach based upon the principles used to teach orientation and mobility to blind and visually impaired people.

Paradoxial response to dopaminergic agents in parkinsonism.

A patient with the classical stigmata of parkinsonism was treated on three separate occasions with levodopa, a combination of levodopa and carbidopa, and lergotrile mesylate, a direct-acting dopamine-receptor agonist. All three treatment regimens resulted in dose-related increases in parkinsonian features. To our knowledge, this response has not been previously described. Lergotrile did not alter CSF homovanillic acid concentration. It is suggested that this rare paradoxical motor response to dopaminergic agents may be associated with dysfunction of the postsynaptic dopamine receptor site.

Oral choline administration to patients with tardive dyskinesia.

We gave pharmacologic doses of choline to patients with tardive dyskinesia in an attempt to suppress involuntary facial movements. Choline is the physiologic precursor of acetylcholine, and its administration elevates brain acetylcholine levels in laboratory animals and, possibly, in human beings. Hence, we thought that its use could benefit patients with diseases like tardive dyskinesia, which is believed to result from deficient central cholinergic tone. Twenty patients with stable baccal-lingual-masticatory movements took oral doses of choline for two weeks according to a double-blind crossover protocol. Plasma choline levels rose from 12.4 +/- 1.0 to 33.5 +/- 2.5 nmol per milliliter (mean +/- S.E.M.; P less than 0.001) during this period. Choreic movements decreased in nine patients, worsened in one and were unchanged in 10. Thus, oral doses of choline can be useful in neurologic diseases in which an increase in acetylcholine release is desired.