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John T Slevin

Publications and source records attributed to John T Slevin.

7 recordsLinked to original sources
PubMed2006

Asymmetric accumulation of hippocampal 7S SNARE complexes occurs regardless of kindling paradigm.

Modifications of neurotransmission may contribute to the synchronization of neuronal networks that are a hallmark of epileptic seizures. In this study we examine the synaptosomal proteins involved in neurotransmitter release to determine if alterations in their interactions correlate with the chronic epileptic state. Using quantitative western blotting, we measured the levels of 7S SNARE complexes and SNARE effectors in the effected hippocampi from animals that were electrically kindled through stimulation from one of three different foci. All three kindling paradigms, amygdalar, entorhinal, and septal, were associated with an accumulation of 7S SNARE complexes in the ipsilateral hippocampus, measured 1 month after completion of kindling. Of the eight SNARE effectors examined (alpha-SNAP, NSF, SV2A/B, Munc18a/nSec1, Munc13-1, Complexins 1 and 2, and synaptotagmin I), there was a statistically significant bihemispheric increase of hippocampal SV2 and decrease of NSF upon kindling; neither by itself would be expected to account for the asymmetry of SNARE complex distribution. These data suggest that an ipsilateral hippocampal accumulation of SNARE complexes is a permanent alteration of kindling-induced epilepsy, regardless of stimulation pathway. The significance of these findings toward a molecular understanding of epilepsy will be discussed.

Amygdala↗
PubMed2006

Restless legs syndrome.

PURPOSE: The signs and symptoms, epidemiology, etiology, pathophysiology, diagnosis, pharmacologic and nonpharmacologic treatments, and options and guidelines for the treatment of restless legs syndrome (RLS) are reviewed. SUMMARY: RLS was first described in the 17th century and further characterized in 1945. RLS is a common disorder, occurring in about 10% of the population. Patients with RLS often describe the urge to move, uncomfortable sensations, and pain, which begin or worsen during rest or inactivity such as lying or sitting. Symptoms of RLS make sleeping difficult for many patients, and significant daytime difficulties result from the condition. RLS can either be primary or arise from secondary causes that lead to iron deficiency. There is a familial component in primary RLS, but its underlying mechanisms remain unknown. Of individuals with conditions associated with iron-deficiency states, including pregnancy, renal failure, and anemia, 25-30% may develop RLS. The goals of RLS treatment include improving its symptoms and the patient's quality of life. There are limited data on the treatment of RLS. Pharmacologic therapies include iron replacement, dopaminergic agents (e.g., levodopa), dopamine agonists, anticonvulsants, opioids, and benzodiazepines. There have been no systematic trials of nonpharmacologic therapies for RLS, but good sleep hygiene and avoidance of alcohol, caffeine, and nicotine may improve symptoms. CONCLUSION: RLS is a common disorder thought to involve abnormal iron metabolism and dopaminergic systems. Nonpharmacologic therapy should be suggested for all patients with RLS, but pharmacologic therapy may be required, and evidence is strongest for levodopa and dopamine agonists.

Analgesics, Opioid↗
PubMed2006

Unilateral intraputaminal glial cell line-derived neurotrophic factor in patients with Parkinson disease: response to 1 year each of treatment and withdrawal.

OBJECT: Glial cell line-derived neurotrophic factor (GDNF) infused unilaterally into the putamen for 6 months was previously shown to improve motor functions and quality of life measures significantly in 10 patients with Parkinson disease (PD) in a Phase I trial. In this study the authors report the safety and efficacy of continuous treatment for 1 year or more. After the trial was halted by the sponsor, the patients were monitored for an additional year to evaluate the effects of drug withdrawal. METHODS: During the extended study, patients received unilateral intraputaminal infusion of 30 mg/day GDNF at a basal infusion rate supplemented with pulsed boluses every 6 hours at a convection-enhanced delivery rate to increase tissue penetration of the protein. When the study was stopped, the delivery system was reprogrammed to deliver sterile saline at the basal infusion rate of 2 ml/hour. The Unified PD Rating Scale (UPDRS) total scores after 1 year of therapy were improved by 42 and 38%, respectively, in the "off" and "on" states. Motor UPDRS scores were also improved: 45 and 39% in the off and on conditions, respectively. Benefits from treatment were lost by 9 to 12 months after GDNF infusion was halted. At that time, the patients had returned to their baseline UPDRS scores and required higher levels of conventional antiparkinsonian drugs to treat symptoms. After 11 months of treatment, the delivery system had to be removed in one patient because of the risk of infection. In seven patients antibodies to GDNF developed, with no evidence of clinical sequelae. There was also no evidence of GDNF-induced cerebellar toxicity, as evaluated using magnetic resonance imaging analysis and clinical testing. CONCLUSIONS: Unilateral administration of GDNF results in significant, sustained bilateral benefits. These improvements are lost within 9 months after drug withdrawal. Safety concerns with GDNF therapy can be closely monitored and managed.

Aged↗
PubMed2005

A multicenter, open-label, sequential study comparing preferences for carbidopa-levodopa orally disintegrating tablets and conventional tablets in subjects with Parkinson's disease.

BACKGROUND: Patients with Parkinson's disease (PD) may have difficulty taking their medications for various reasons. In these patients, orally disintegrating tablets (ODTs) can be given without water and may provide greater convenience and ease of use than conventional tablets. OBJECTIVE: This study compared preferences for ODTs with those of the conventional tablet formulation of the antiparkinsonism combination drug carbidopa-levodopa (C.-L.) in subjects with PD. METHODS: Subjects aged > or =18 years with PD controlled using a stable dosage of C-L were enrolled in this multicenter, open-label, sequential study. Subjects received their stable dose of conventional C-L for 7 +/- 3 days. They were then switched to the same dose of C-L in the ODT formulation for 14.+/- 3 days. During the last 3 days of each treatment period, subjects were to record in a diary their "on" and "off" times (asymptomatic and symptomatic parkinsonism, respectively) and medication use. On the final day of each treatment period, the Unified Parkinson's Disease Rating Scale (UPDRS) was administered to subjects before the first morning dose and then after dosing when they mentioned they were experiencing the "on" state. A Global Preference Questionnaire (GPQ) was completed by subjects at the end of the study. The primary variable was response to all GPQ items. Secondary variables were changes in UPDRS score and mean amount of "off" time per 24 hours. Adverse effects (AEs) also were monitored. RESULTS: Sixty-one subjects (31 men, 30 women; mean[SD] age, 71.8 [8.3] years; mean body weight, 76.2 kg) participated in the study and were included in the AE assessment; 60 completed the study and were included in the efficacy assessment. Twenty-seven subjects (45%) preferred ODTs compared with 12 (20%) who preferred the conventional tablets (P < 0.017). The remaining 21 subjects (35%) had no preference. The attributes of the ODTs that influenced subjects' preference for that formulation included accessibility to medication to treat "off" times (30 [50%]); ease of activities of daily living (28 [47%]); reduced concern about swallowing the medication (27 [45%]); and use for nighttime dosing, ease of compliance with dosing schedule, and feeling less self-conscious about others noticing medication use (each, 25 [42%]) (all, P < 0.001). No statistically significant differences in UPDRS scores in the "on" and "off" states were found between the 2 formulations. The incidence of AEs was statistically similar between the 2 formulations. CONCLUSIONS: In this small study of ODT C-L versus conventional C-L tablets in these adult subjects with PD, the results suggest that the ODTs may be of value in certain patients with PD, depending on their personal preferences, disease status, and willingness to alter an aspect of their medication use. For selected patients with PD, the ODT C-L formulation may provide increased convenience, ease of use, and rapid access to medication.

Aged↗
PubMed2005

Improvement of bilateral motor functions in patients with Parkinson disease through the unilateral intraputaminal infusion of glial cell line-derived neurotrophic factor.

OBJECT: Glial cell line-derived neurotrophic factor (GDNF) has demonstrated significant antiparkinsonian actions in several animal models and in a recent pilot study in England in which four of five patients received bilateral putaminal delivery. In the present study the authors report on a 6-month unilateral intraputaminal GDNF infusion in 10 patients with advanced Parkinson disease (PD). METHODS: Patients with PD in a functionally defined on and off state were evaluated 1 week before and 1 and 4 weeks after intraputaminal catheter implantation in the side contralateral to the most affected side. Each patient was placed on a dose-escalation regimen of GDNF: 3, 10, and 30 microg/day at successive 8-week intervals, followed by a 1-month wash-out period. The Unified Parkinson's Disease Rating Scale (UPDRS) total scores in the on and off states significantly improved 34 and 33%, respectively, at 24 weeks compared with baseline scores (95% confidence interval [CI] 18-47% for off scores and 16-51% for on scores). In addition, UPDRS motor scores in both the on and off states significantly improved by 30% at 24 weeks compared with baseline scores (95% CI 15-48% for off scores and 5-61% for on scores). Improvements occurred bilaterally, as measured by balance and gait and increased speed of hand movements. All significant improvements of motor function continued through the wash-out period. The only observed side effects were transient Lhermitte symptoms in two patients. CONCLUSIONS: Analysis of the data in this open-label study demonstrates the safety and potential efficacy of unilateral intraputaminal GDNF infusion. Unilateral administration of the protein resulted in significant, sustained bilateral effects.

Aged↗