The pathogenesis of on-off motor fluctuations in parkinsonism remains incompletely understood, but slowed or erratic gastric emptying of orally administered levodopa may be involved. In 3 patients with resistant on-off fluctuations, direct duodenal continuous infusion of levodopa via a nasoduodenal tube resulted in a heightened therapeutic effect, including a reduction in motor fluctuations. In 1 of these patients, continuous duodenal levodopa infusion produced greater benefit than did intermittent duodenal levodopa administration. Direct duodenal delivery of levodopa lessens the problems with gastric emptying and may be suitable for long-term therapy in selected patients with resistant on-off motor fluctuations.

To clarify the influence of gastric emptying on levodopa-related motor fluctuations in Parkinson's disease, we assessed mobility and plasma levodopa concentrations in 10 patients during five modes of levodopa administration: (1) standard intermittent oral (SIO), (2) intermittent duodenal (ID), (3) continuous duodenal infusion (CDI), (4) continuous gastric infusion (CGI), and (5) controlled-release Sinemet (CR-4). The rank order from greatest to least for both percentage of time "on" and average mobility score was CDI, CGI, ID, CR-4, and SIO. The rank order for variance of means, a measure of fluctuation, from least to greatest for mobility was CDI, CGI, CR-4, ID, SIO, and for plasma levodopa concentrations was CDI, CGI, ID, SIO, and CR-4. The results demonstrate that it is possible to produce very steady plasma concentrations of levodopa with a corresponding reduction in motor fluctuations by continuous intraduodenal administration of the drug. This mode of delivery is an ideal model for the development of optimal continuous-release preparations of levodopa. Other enteral routes have produced a more variable plasma levodopa concentration and clinical response.

We carried out a controlled clinical trial to examine the potential of baclofen to slow the functional decline of patients with early Huntington's disease (HD). The basis of the trial was: (1) the hypothesis that excitatory amino acid neurotransmission mediates the neuronal degeneration of HD, (2) preclinical evidence that baclofen retards corticostriatal release of glutamate and aspartate, and (3) reports that baclofen produces short-term clinical benefits in some HD patients. Sixty patients with early HD were randomized to chronic baclofen, 60 mg/day, or placebo treatments and followed systematically for up to 42 months. Total functional capacity was not favorably influenced by baclofen treatment. Factors that contributed, although nonsignificantly, to a more rapid rate of total functional capacity decline included younger age (less than 35 years), earlier stage (stage I) of illness, paternal inheritance of the HD gene, and baclofen treatment. Our patients declined at a pace slower than that observed in other prospective studies, a finding likely due to selection criteria, avoidance of neuroleptic therapy, and strong psychosocial support.

1. Sulkin SE, Pike RM: Viral infections contracted in the laboratory. N Engl J Med 1949; 241:205-213. 2. Sulkin SE, Pike RM: Survey of laboratory-acquired infections. Am J Public Health 1951; 41:769-781. 3. Pike RM, Sulkin SE, Schulze ML: Continuing importance of laboratory-acquired infections. Am J Public Health 1965; 55:190-199. 4. Pike RM: Laboratory-associated infections: A summary and analysis of 3921 cases. Health Lab Sci 1976; 13:106-114. 5. Pike RM: Past and present hazards ofworking with infectious agents. Arch Pathol Lab Med 1978; 102:333-336. 6. Pike RM: Laboratory-associated infections: Incidence, fatalities, causes and prevention. Annu Rev Microbiol 1979; 33:41-66. 7. Blaser MJ, Lofgren JP: Fatal salmonellosis originating in a clinical microbiology laboratory. J Clin Microbiol 1981; 13:855-858. 8. Olle-Goig JE, Canela-Siler J: An outbreak of Brucella melitensis infection by airborne transmission among laboratory workers. Am J Public Health 1987; 77:335-338. 9. DeBoy JM: Thirty months of personal injury accident reports in a state diagnostic laboratory. Abstract: This paper compares the results of analyses of 1984 fatalities as identified in the National Institute for Occupational Safety and Health (NIOSH) National Traumatic Occupational Fatality (NTOF) data base with those of the Bureau of Labor Statistics' Annual Survey of Occupational Injuries and Illnesses (AS) for 1984. The fatality rates for industries were similar in both analyses; however, differences in number of injuries suggest underrepresen-tation in the AS of fatal injuries in several, high-risk industries. Differences and similarities in methods and results between the two national surveillance systems are described and their application to research and injury prevention are discussed. (Am J Public Health

The National Animal Disease Center's experience with personnel exposure or infection with pathogenic agents is summarized. A total of 128 laboratory-associated exposures to infectious disease agents were reported. Of these exposures, 103 resulted from known accidents. The other 25 were identified only after the development of clinical or serological manifestations of infection. Thirty-four cases of laboratory-acquired infections were reviewed. Class 3 organisms--Chlamydia sp., Brucella sp. and Mycobacterium sp.--were responsible for 76% of the infections encountered, with Brucella sp. incriminated most frequently. The most commonly reported cause of exposure was associated with hypodermic syringe use. Unknown routes of exposure, presumed to be aerosol related, were the overwhelming explanation involved in the laboratory-associated infections.