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J I Sage

Publications and source records attributed to J I Sage.

At least 19 recordsLinked to original sources
PubMed2001

The tau A0 allele in Parkinson's disease.

Parkinson's disease (PD) is primarily an alpha-synucleinopathy, rather than a tauopathy, but there is evidence for an indirect association of tau with the pathogenetic process in PD. We therefore assessed the frequency in PD of the tau A0 allele, a dinucleotide repeat marker that has been associated with a sporadic tauopathy, progressive supranuclear palsy (PSP). We found the A0 allele to comprise 79.2% of 758 alleles from PD patients and 71.2% of 264 control alleles (P = 0.008). We also performed a meta-analysis of three previous reports, two of which failed to produce statistically significant results. Taken together, they also support a PD/A0 allelic association, even after correction for misdiagnosis of PSP as PD (P< 0.001). The A0/A0 genotype frequency in our patients (62.3%) did not differ significantly from that in controls (53.0%, P = 0.062), but the meta-analysis, even after correction for misdiagnosis, showed a significant result, with P = 0.002. The frequency of A0 allele and the A0/A0 genotype were compatible with Hardy-Weinberg equilibrium. The frequency of the A0 allele and the A0/A0 genotype in our patients with familial PD was not significantly greater than in those with sporadic PD. We conclude that the tau protein may play a small role in the pathogenesis of PD and that biochemical characterization of this role may suggest opportunities for PD prophylaxis.

Aged↗
PubMed1999

Depression and anxiety in Parkinson's disease: possible effect of genetic variation in the serotonin transporter.

Recently, a functional polymorphism in the promoter region of the serotonin transporter gene has been linked to anxiety. In cell culture, the short allele of this polymorphism synthesizes less serotonin transporter, resulting in a reduction of the removal of serotonin from the synaptic cleft. This pilot study examines depression and anxiety in Parkinson's disease patients as a function of the variation in this polymorphism. Thirty-two patients were genotyped and then blindly administered the Hamilton Depression and Anxiety Scales. Clinical data on the neurologic features of the disease were also gathered. Patients with the short allele of the serotonin transporter promotor scored significantly higher on both the depression and anxiety measures. There were no differences between groups for any neurologic variable. Patients with the short allele were more likely to have scores for anxiety and depression that indicated "caseness." This study suggests that the short allele of the serotonin transporter gene may represent a significant risk factor for the development of anxiety and depression in Parkinson's disease patients.

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PubMed1998

Ten years' experience with enteral levodopa infusions for motor fluctuations in Parkinson's disease.

We report our long-term experience using enteral levodopa infusions in 22 patients with Parkinson's disease and severe motor fluctuations. Amelioration of intractable dyskinesias was the most important factor that determined whether patients chose to continue using the infusion pump system. Mechanical and physical problems associated with enteral access were the most common reasons for which patients discontinued pump use. Nearly all patients continued to have dramatically increased on time for the duration of follow up, suggesting that technically less-cumbersome systems that provide continuous dopaminergic stimulation are worthwhile and should be developed.

Administration, Oral↗
PubMed1998

Association of a serotonin transporter gene promoter polymorphism with harm avoidance behaviour in an elderly population.

A polymorphic 44-nucleotide insertion/deletion in the promoter region of the serotonin transporter gene (5-HTTLPR) has been shown to affect the level of expression of the serotonin transporter protein. An association between anxiety-related behavioural traits and the short form of the 5-HTTLPR has been reported. We determined the 5-HTTLPR genotype in genomic DNA samples from 84 subjects (47 Parkinson's disease patients and 37 controls) with a mean age of 67.4 years. The TPQ of Cloninger was used to obtain values for harm avoidance (HA), reward dependence and novelty seeking for all subjects. Analysis of variance showed a significant influence of the s-allele of the 5-HTTLPR on HA in both subject groups, with no significant interaction between diagnosis and genotype. Subjects with the l/l-genotype had significantly lower mean HA scores than the l/s subjects (P < 0.04) and s/s subjects (P < 0.003). A linear change in HA with genotype was observed, indicating a gene dose effect of the 5-HTTLPR s-allele on this personality dimension. Based on these findings it is suggested that there may be increased influence of the 5-HTTLPR short allele on anxiety-related traits during aging.

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PubMed1998

Association of long variants of the dopamine D4 receptor exon 3 repeat polymorphism with Parkinson's disease.

The dopamine D4 receptor (D4DR) has a highly polymorphic region in the third exon which has been associated with novelty seeking (NS) behavior. Due to the central position of dopamine and the documented low NS in Parkinson's disease (PD), the frequency of the exon 3 variants of D4DR in 95 PD patients and 47 controls was investigated. A significantly higher frequency of exon 3 alleles with six or more repeat units was found in the PD group (p = 0.039). This provides evidence that some forms of the highly polymorphic D4DR may represent a genetic susceptibility factor for PD.

Adult↗
PubMed1998

Pharmacoeconomic analysis of using Sinemet CR over standard Sinemet in parkinsonian patients with motor fluctuations.

OBJECTIVE: To compare the costs of pharmacotherapy in patients with Parkinson's disease before and after converting from standard Sinemet to extended-release Sinemet CR. DESIGN: Investigators retrospectively reviewed records of patients converting from Sinemet to Sinemet CR for efficacy and total drug costs. Cost-effectiveness was evaluated retrospectively from data collected in prospective Sinemet CR efficacy trials. SETTING: Parkinson's disease clinic at a tertiary care university teaching hospital. PATIENTS: 100 patients with motor fluctuations who had undergone an initial 6-month course of Sinemet therapy, followed by a 6-month course of Sinemet CR. MAIN OUTCOME MEASURES: Total cost was measured as the cost of Sinemet formulations plus the costs of other antiparkinson medications. Differences in pre- and postconversion costs were compared by using the paired, two-tailed Student's t-test. A substudy of 39 patients on the cost-effectiveness of conversion measured the ratio of daily medication costs to the daily hours "on" without chorea. RESULTS: While total daily medication costs after conversion increased by 21%, patients experienced either a comparable or an improved degree of disease control with Sinemet CR. Patients who were also taking selegiline were able to decrease selegiline expense by 20%. The costs of other adjunctive medications did not differ significantly after conversion. The cost-effectiveness analysis revealed an increase in postconversion on time by 2.2 hours (p = 0.0001), accompanied by a $2.85 decrease in total cost per hour on without chorea (p = 0.11). CONCLUSIONS: Although Sinemet CR is more costly, it may be more cost-effective in patients with motor fluctuations. Some patients may be able to reduce adjunctive medications.

Adult↗
PubMed1996

"Subclinical" orthostatic hypotension is associated with dizziness in elderly patients with Parkinson disease.

OBJECTIVE: To investigate risk factors associated with subjective complaints of dizziness in 12 elderly patients with Parkinson disease (PD), in whom no obvious cause for this symptom could be found. DESIGN: A case-controlled study, with patients prospectively recruited in a nonblinded fashion. SETTING: Patients were seen by one physician at a neurology outpatient clinic between August 1993 and August 1994. SUBJECTS: Thirty-six patients, all over age 65 years and all with PD; 12 complained of dizziness; 24 did not. INTERVENTIONS: Patients and controls were screened for blood pressure changes, postural instability, motor severity, multiple sensory deficits, drug use, cardiovascular disease, and diabetes mellitus. MAIN OUTCOME MEASURES: An orthostatic decrease of systolic BP > 15 mmHg (odds ratio = 6.5; 95% confidence interval = 1.22 - 34.52; chi 2mh = 6.7; p < .01) and an orthostatic decrease of diastolic BP > 5mmHg (odds ratio = 11; 95% confidence interval = 3.15 - 38.39; chi 2mh = 7.14; p < .01) were significant risk factors for complaints of dizziness. RESULTS: The only significant risk factors linked with dizziness were orthostatic decreases in systolic (15 mmHg) and diastolic (5 mmHg) blood pressure. CONCLUSIONS: An orthostatic decrease in blood pressure is associated with unexplained feelings of dizziness in elderly PD patients.

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PubMed1996

Clozapine for the treatment of psychosis in Parkinson's disease: chart review of 49 patients.

The records of 49 patients with Parkinson's disease and psychosis who were treated with clozapine for up to 18 months were reviewed. Average starting dose of clozapine was 16 mg. Average maximum dose was 39 mg. The psychotic symptoms improved in 76% of the patients at 3 months, and response to clozapine within the first year ranged from 71% to 80%. This response allowed a maximization of levodopa dose. Improvements in scores on the Unified Parkinson's Disease Rating Scale and tremor subscale were seen in some patients but were not statistically significant. This study, the largest of its kind to date, suggests that clozapine is well tolerated and effective in treating psychosis in patients with Parkinson's disease.

Aged↗
PubMed1996

Follow-up study of risk factors in progressive supranuclear palsy.

The cause of progressive supranuclear palsy (PSP) is not known and has been little studied. The one previous controlled epidemiologic survey, performed at our center in 1986, found small-town experience and greater educational attainment as PSP risks, but, in retrospect, these results may have been produced by ascertainment bias. Since that time, several anecdotal reports have implicated heredity and various environmental exposures in the cause of some cases of PSP. To clarify the results of the previous study and to evaluate the more recently implicated candidate factors in a controlled fashion, we mailed a validated 69-item questionnaire to 91 personally examined patients with PSP and 104 unmatched controls with other neurologic conditions for which they had been referred to our tertiary neurologic center. We were able to match 75 subjects from each group by year of birth, sex, and race and subjected them to a separate matched-pair analysis. We allowed surrogates to supply any or all of the responses. Questions concerned hydrocarbon, pesticide, and herbicide exposure; urban/rural living; auto repair and other occupations; head trauma; educational attainment; maternal age; and family history of PSP, parkinsonism, dementia, and other neurologic conditions. A statistically significant finding was that patients with PSP were less likely to have completed at least 12 years of school (matched odds ratio = 0.35, 95% CI = 0.12-0.95, p = 0.022; unmatched odds ratio = 0.44, 95% CI = 0.21-0.89, p = 0.020). We hypothesize that this result may be a proxy for poor early-life nutrition or for occupational or residential exposure to an as-yet unsuspected toxin. Future studies should examine these potential risk factors in PSP.

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PubMed1996

Nonmotor fluctuations in patients with Parkinson's disease.

We studied the nature and frequency of nonmotor "off" phenomena in 130 consecutive patients with Parkinson's disease (PD) with motor fluctuations. Twenty-two patients (17%) experienced nonmotor fluctuations as an end-of-dose phenomenon. Previously unreported, or little appreciated, nonmotor "off" states include sensory dyspnea, nausea, facial flushing, cough, hunger, unilateral limb edema, proximal limb pain, and trigeminal neuralgia-like pain. We attempted treatment modification in 12 of 22 patients; nonmotor "off" symptoms improved in nine of these 12 patients (75%). Recognizing these phenomena will prevent unnecessary tests and treatments.

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PubMed1995

Drenching sweats as an off phenomenon in Parkinson's disease: treatment and relation to plasma levodopa profile.

We followed 4 patients with Parkinson's disease and severe, intermittent, drenching sweats. One patient was studied with serial plasma levodopa levels and simultaneous clinical examinations. She was observed during a severe sweating episode; this was associated with subtherapeutic plasma levodopa levels (low dopa state). All 4 patients' sweats responded favorably to the institution of agonist therapy. Drenching sweats should be considered part of the spectrum of off-period levodopa-related fluctuations in Parkinson's disease.

Aged↗
PubMed1995

Binswanger's disease presenting as levodopa-responsive parkinsonism: clinicopathologic study of three cases.

We report three cases of autopsy-proven Binswanger's disease (subcortical arteriosclerotic encephalopathy) with unusual clinical features. Two patients had supranuclear gaze disturbances, early gait dysfunction, and speech disorders suggestive of progressive supranuclear palsy. One of these patients was not demented at the time of death. The third patient had features typical of Parkinson's disease. All three patients were responsive to treatment with levodopa. The clinical spectrum of Binswanger's disease should be expanded to include levodopa-responsive parkinsonism.

Aged↗
PubMed1995

Apomorphine for motor fluctuations and freezing in Parkinson's disease.

OBJECTIVE: To review the pharmacokinetics and use of apomorphine in patients with Parkinson's disease; to report a case of beneficial outcome with apomorphine in a patient with Parkinson's disease with severe levodopa "on-off" fluctuations and freezing; and to outline the types of patients or situations where apomorphine may be useful. DATA SOURCES: Case reports, review articles, and relevant clinical studies identified by a MEDLINE search of the English-language literature published between 1975 and October 1994. STUDY SELECTION: Because all but 2 reports were of open-label design with small sample sizes, all studies identified were evaluated. DATA EXTRACTION: The following data were extracted from each study: apomorphine treatment duration, dosing, onset, duration, and adverse effects. The following efficacy variables were extracted: percent decrease in off periods, improvement in parkinsonian symptoms, and percent decrease in levodopa dosage. DATA SYNTHESIS: Efficacy of apomorphine following subcutaneous, rectal, sublingual, and intranasal dosage forms are evaluated. We also describe the use of apomorphine in a patient with Parkinson's disease who experienced on-off fluctuations and freezing. Based on these reports, recommendations for patient selection, product selection, and apomorphine dosing guidelines are presented. CONCLUSIONS: Apomorphine decreases off time, freezing, and levodopa requirements in patients with Parkinson's disease. It can be administered via a number of different nonoral routes; however, subcutaneous apomorphine is the most extensively studied. Rectal, sublingual, and intranasal routes also have been shown to provide benefit in motor fluctuations, but differ from the subcutaneous route in onset of action, duration of effect, and adverse effect profile.

Administration, Intranasal↗
PubMed1994

Severe evening dyskinesias in advanced Parkinson's disease: clinical description, relation to plasma levodopa, and treatment.

We report four patients with Parkinson's disease who had an unusual pattern of severe chorea and dystonia in the evenings only. The temporal pattern of abnormal movements and simultaneous monitoring of plasma levodopa and clinical state were consistent with dyskinesias associated with subtherapeutic (low dopa dyskinesias) rather than peak concentrations of levodopa (high dopa dyskinesias). In two patients, addition of a direct-acting dopamine receptor agonist was helpful in ameliorating this complication of antiparkinson therapy.

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