High-dose transdermal nicotine in Parkinson's disease patients: a randomized, open-label, blinded-endpoint evaluation phase 2 study.

BACKGROUND AND PURPOSE: Studies of the effects of nicotine on motor symptoms in Parkinson's disease (PD) brought out discordant results. The aim of the present study was to evaluate the efficacy and safety of high doses of transdermal nicotine on motor symptoms in PD. METHODS: Forty PD patients were randomly assigned to a treated and untreated arm in an open-label study. Treated patients received increasing doses of nicotine to reach 90 mg/day by 11 weeks. This dosage was maintained for 28 weeks (W39) and then reduced over 6 weeks. Final evaluation was performed 6 weeks after washout. The main outcome measure was the OFF-DOPA Unified Parkinson's Disease Rating Scale (UPDRS) motor score measured on video recordings by raters blinded to the medication status of the patients. RESULTS: There was no significant difference in OFF-DOPA UPDRS motor scores between the nicotine-treated and non-treated groups, neither at W39 (19.4 ± 9.3 vs. 21.5 ± 14.2) nor considering W39 differences from baseline (-1.5 ± 12.1 vs. +0.9 ± 12.1). The 39-item Parkinson's disease questionnaire scores decreased in nicotine-treated patients and increased in non-treated patients, but the difference was not significant. Overall tolerability was acceptable, and 12/20 treated patients reached the maximal dosage. CONCLUSIONS: High doses of transdermal nicotine were tolerated, but our study failed to demonstrate significant improvement in UPDRS motor scores. Improvement in unblinded secondary outcomes (UPDRS-II, UPDRS-IV, doses of l-DOPA equivalents) suggest a possible benefit for patients treated with nicotine, which should be confirmed in larger double blind, placebo-controlled studies.

Chronic high dose transdermal nicotine in Parkinson's disease: an open trial.

Whether nicotine has therapeutic effects on Parkinson's disease (PD) symptoms is controversial, but high doses and chronic treatment have never been tested. We report the results of a pilot, open-label trial to assess the safety and possible efficacy of chronic high doses of nicotine. Six patients with advanced idiopathic PD received increasing daily doses of transdermal nicotine up to 105 mg/day over 17 weeks. All patients but one accepted the target dose. Nausea and vomiting were frequent but moderate, and occurred in most of the patients (four of six) who received over 90 mg/day and 14 weeks of nicotine treatment. During the plateau phase, patients improved their motor scores and dopaminergic treatment was reduced. These results confirm the feasibility of chronic high dose nicotinic treatment in PD but warrant validation of the beneficial effects by a randomized controlled trial.

Long-term outcome of unilaterally transplanted parkinsonian patients. I. Clinical approach.

Five patients with Parkinson's disease, unilaterally transplanted with foetal mesencephalic cells into putamen (n=1) or putamen and caudate (n=4), were followed throughout a period of 15-36 months after surgery, according to the recommendations of the core assessment programme for intracerebral transplantations (CAPIT). All these patients exhibited an increase in the fluorodopa uptake in the grafted putamen, which was most significant in the first and last patient of the series. Long-term bilateral improvement of skilled hand movements was observed, starting between the third and sixth month after grafting, and confirmed by the statistical analysis of CAPIT timed tests. A mild to moderate effect on the amount of 'off' time and 'on-off' fluctuations was observed, whereas, apart from one case, no other clear effect on gait, walking and speech was found. One patient included in the study, already suffering slight cognitive impairment, clearly exhibited progression of a dementia process after surgery. Daily living activities were clearly improved in only one of the other four patients. At the end of the study period, all patients needed L-dopa therapy at a similar or higher dose than before grafting, but, in most of them, other dopaminergic drugs were reduced or stopped. All patients exhibited bilateral dyskinesias before grafting that were greatly decreased in intensity a few months after surgery. Delayed asymmetrical dyskinesias, occurring on the side displaying the better motor improvement, i.e. contralateral to the graft, were observed in three patients. These results suggest that neural transplants may influence two central mechanisms involved in motor function and the onset of dyskinesias. These effects are likely to occur through complex interactions with the post-synaptic dopaminergic receptors. The occurrence of dyskinesias might simply reflect increased presynaptic storage and release of dopamine. Alternatively, it might, in part, represent some other long-term deleterious effect of the graft. Since PET-scan data indicate that the reinnervation obtained is sub-optimal, it will be of interest to obtain a larger and denser reinnervation of the host striatum and to try, thereafter, to reduce the dose of L-dopa.

Immobilization of coypus (Myocastor coypus) with ketamine hydrochloride and xylazine hydrochloride.

A combination of 100 mg/ml of ketamine hydrochloride (Ket) and 20 mg/ml of xylazine hydrochloride (Xyl) was used to immobilize coypus (Myocastor coypus). Eight mature coypus (four males and four females) were injected intramuscularly with doses ranging from 2.33 to 6.25 mg/kg of KET and 0.25 to 0.86 mg/kg of Xyl. The mean (+/- SE) time for induction, arousal, and recovery were 7.3 +/- 2 min, 23.5 +/- 0.3 min and 46 +/- 2.5 min, respectively. The mean +/- SE doses injected were 4.07 +/- 0.52 mg/kg Ket (range, 2.33 to 6.25 mg/kg) and 0.5 +/- 0.08 mg/kg Xyl (range, 0.25 to 0.86 mg/kg). No adverse responses were observed in any of the animals treated.

Hantavirus infection in laboratory and wild rodents in Argentina.

Serum samples from urban and laboratory rats, laboratory mice and wild and laboratory cricetids in Argentina were tested by immunofluorescence and plaque reduction neutralization tests to investigate prevalence of anti-Hantavirus antibodies. A total of 102 sera were obtained from laboratory rodents in 4 different animal-rooms, 31 from harbor rats and 30 from wild cricetids in 1985-1987. Anti-Hantavirus antibodies were detected in 22.5% of Rattus norvegicus in 3 of the animal-rooms but harbor rats were found to be free of Hantavirus infection. Previously, the presence of anti-Hantavirus antibodies had been demonstrated in the sera obtained from laboratory workers in these same 3 animal-rooms; it can be concluded that the laboratory rats were the source of this human infection. On the contrary, laboratory mice and cricetids failed to show Hantavirus infection while the wild vesper mouse Calomys musculinus (the main Junin virus reservoir) showed a prevalence of 23.5%. The presence of Hantavirus infection is hereby reported for the first time in wild C. musculinus and in laboratory R. norvegicus in Argentina.

Hantavirus infection in laboratory and wild rodents in Argentina

Se determinó la presencia de anticuerpos anti-Hantavirus en sueros provenientes de roedores salvajes (de zonas urbanas y de campo) y de laboratorio para estudiar la existencia o no de infección con Hantavirus en la Argentina. Se utilizaron las técnicas de inmunofluorescencia indirecta (IF) y de reducción de placas por neutralización (PRNT). Ciento dos sueros correspondían a roedores de laboratorio pertenecientes a 2 bioterios de Mendoza y a 2 de Buenos Aires; 31 sueros fueron rcogidos de ratas urbanas capturadas en el puerto de Buenos Aires y 30 sueros pertenecían a cricétidos salvajes capturados en campos de Buenos Aires y Mendoza (Tabla 1). Se detectaron anticuerpos anti-Hantavirus en colonias de Rattus norvegicus de 3 de los 4 bioterios estudiados (22,5%) en estos mismos lugares. Previamente se habían detectado anticuerpos en sueros humanos por lo que, descartando otros orígenes para la infección, se determinó que las ratas de laboratorio son los candidatos más probables de diseminación del virus en humanos en estos ambientes. En las ratas del puerto de la ciudad de Buenos Aires no se encontraron anticuerpos ni por IF ni por PRNT. En las colonias de ratones y cricéticos de laboratorio no se encontró infección con Hantavirus, mientras que en cricétidos salvajes se demostró la presencia de Hantavirus tanto en Buenos Aires como en Mendoza. En la naturaleza se encontraron anticuerpos séricos anti-Hantavirus en un cricétido reservorio del virus Junín (agente etiológico de la fiebre...

Hantavirus infection in laboratory and wild rodents in Argentina

Se determinó la presencia de anticuerpos anti-Hantavirus en sueros provenientes de roedores salvajes (de zonas urbanas y de campo) y de laboratorio para estudiar la existencia o no de infección con Hantavirus en la Argentina. Se utilizaron las técnicas de inmunofluorescencia indirecta (IF) y de reducción de placas por neutralización (PRNT). Ciento dos sueros correspondían a roedores de laboratorio pertenecientes a 2 bioterios de Mendoza y a 2 de Buenos Aires; 31 sueros fueron rcogidos de ratas urbanas capturadas en el puerto de Buenos Aires y 30 sueros pertenecían a cricétidos salvajes capturados en campos de Buenos Aires y Mendoza (Tabla 1). Se detectaron anticuerpos anti-Hantavirus en colonias de Rattus norvegicus de 3 de los 4 bioterios estudiados (22,5%) en estos mismos lugares. Previamente se habían detectado anticuerpos en sueros humanos por lo que, descartando otros orígenes para la infección, se determinó que las ratas de laboratorio son los candidatos más probables de diseminación del virus en humanos en estos ambientes. En las ratas del puerto de la ciudad de Buenos Aires no se encontraron anticuerpos ni por IF ni por PRNT. En las colonias de ratones y cricéticos de laboratorio no se encontró infección con Hantavirus, mientras que en cricétidos salvajes se demostró la presencia de Hantavirus tanto en Buenos Aires como en Mendoza. En la naturaleza se encontraron anticuerpos séricos anti-Hantavirus en un cricétido reservorio del virus Junín (agente etiológico de la fiebre... (AU)

Hantavirus infection in laboratory and wild rodents in Argentina.

Serum samples from urban and laboratory rats, laboratory mice and wild and laboratory cricetids in Argentina were tested by immunofluorescence and plaque reduction neutralization tests to investigate prevalence of anti-Hantavirus antibodies. A total of 102 sera were obtained from laboratory rodents in 4 different animal-rooms, 31 from harbor rats and 30 from wild cricetids in 1985-1987. Anti-Hantavirus antibodies were detected in 22.5

of Rattus norvegicus in 3 of the animal-rooms but harbor rats were found to be free of Hantavirus infection. Previously, the presence of anti-Hantavirus antibodies had been demonstrated in the sera obtained from laboratory workers in these same 3 animal-rooms; it can be concluded that the laboratory rats were the source of this human infection. On the contrary, laboratory mice and cricetids failed to show Hantavirus infection while the wild vesper mouse Calomys musculinus (the main Junin virus reservoir) showed a prevalence of 23.5

. The presence of Hantavirus infection is hereby reported for the first time in wild C. musculinus and in laboratory R. norvegicus in Argentina.