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Biomedical subjects

J P Hubble

Publications and source records attributed to J P Hubble.

At least 37 records · Page 2Linked to original sources
PubMed1995

Apolipoprotein E genotypes in Parkinson's disease with and without dementia.

The apolipoprotein E gene (Apo E) type 4 allele is a genetic risk factor influencing the development and age of onset of Alzheimer's disease. Because Parkinson's disease shares many characteristics of Alzheimer's disease, we studied the frequencies of Apo E genotypes in a cohort of 52 Parkinson's disease patients with dementia and 61 patients without dementia. Dementia was determined per National Institute of Neurological and Communicative Disorders and Stroke criteria and Mattis Dementia Rating Scale (DRS) < 126. Normal cognition was defined as DRS > 132. Apo E genotype and allele frequencies did not differ between demented and nondemented parkinsonian patients. Neither group's genotype and allele frequencies differed from that of a nondemented population of 78 controls. We conclude that the Apo E epsilon 4 allele influences neither the development of Parkinson's disease nor the dementia associated with Parkinson's disease.

Age of Onset↗
PubMed1995

Pramipexole in patients with early Parkinson's disease.

We evaluated the efficacy, safety, tolerability, and pharmacokinetics of pramipexole, a novel dopamine D2 receptor agonist, in early Parkinson's disease (PD). The study design was a parallel, placebo-controlled trial using an ascending dose of 4.5 mg/day pramipexole maximum. All subjects received selegiline (10 mg/day) but were not treated with levodopa. Of the 55 subjects who received at least one dose of the study medication, all but one, in the placebo group, completed the trial, which was 9 weeks in duration. The primary efficacy endpoints were changes in scores from baseline to final measurement on the Unified Parkinson's Disease Rating Scale (UPDRS) Parts II and III. The pramipexole group had a significantly greater improvement (p = 0.002) than the placebo group on UPDRS Part II (Activities of Daily Living). The change in score from baseline to final measurement on UPDRS Part III (Motor Examination) was not significantly different (p = 0.10) between the pramipexole and placebo groups, although the trend favoured the pramipexole group. All subjects in both the pramipexole and the placebo groups experienced one or more episodes of asymptomatic orthostatic hypotension; there was no significant difference between the pramipexole and the placebo groups in the number of subjects experiencing symptomatic orthostatic hypotension. The adverse events profile of pramipexole was similar, in general, to that of other dopamine receptor agonists. Plasma pramipexole levels increased linearly with dose. Pramipexole appears to be promising agent in the treatment of early PD.

Adult↗
PubMed1995

Nocardia species as an etiologic agent in Parkinson's disease: serological testing in a case-control study.

To test the hypothesis that Nocardia spp. may be an etiologic factor in Parkinson's disease (PD), we used a serodiagnostic panel to determine if PD patients had antibodies specific for Nocardia spp. To validate the serological test panel, sera from healthy volunteers and from patients with culture-proven nocardiosis (n = 307) were compared in part 1 of the study. The sensitivity of the panel was 88% for detection of culture-proven nocardial infections, and specificity was 85% (excluding cross-reactive leprosy cases). In part 2, no difference in seropositivity was found when PD patients were compared with their age- and gender-matched controls (n = 140). We found a high exposure rate of humans to nocardial antigens, especially among men and older individuals. Our results offer no support to the hypothesis that Nocardia spp. are causative in PD; however, it is possible that serological testing may not be optimal for detection of nocardial central nervous system infection.

Antibodies, Bacterial↗
PubMed1995

Differentiation of the dementias of Alzheimer's and Parkinson's disease with the dementia rating scale.

The Mattis Dementia Rating Scale (DRS) was used to distinguish between 50 dementia of the Alzheimer's type (DAT) and 50 Parkinson's disease (PD) subjects matched for age, education, and DRS total score. Despite a similar level of overall cognitive impairment, the DAT group earned significantly lower scores than did the PD group on the Memory subscale, while the PD group displayed lower scores than did the DAT subjects on the Construction subscale. Ajackknifed, stepwise, linear discriminant function using the five DRS subscales revealed that the Memory, Construction, and Initiation subtests significantly distinguished the groups. These results suggest qualitative differences in the dementias of DAT and PD patients and reveal that such differences can emerge on brief mental status examinations.

Aged↗
PubMed1995

Erythrocyte thiolmethyltransferase: another failed marker for Alzheimer's and Parkinson's diseases.

There are reports that patients with Parkinson's disease (PD) and Alzheimer's disease (AD) have reduced levels of thiolmethyltransferase (TMT) in erythrocyte membranes. TMT methylates thiols and thiocarbamates, thereby reducing their toxicity. We examined TMT levels in erythrocytes from patients with PD and AD and from age-matched controls. Specific activities of TMT were 564 +/- 199 U/mg protein in PD (n = 32), 513 +/- 118 in AD (n = 13), and 565 +/- 183 in controls (n = 35). There was no difference between any of the groups (p = 0.64). We failed to confirm TMT as a marker for neurodegenerative diseases or for this metabolic defect predisposing to susceptibility to neurotoxins.

Aged↗
PubMed1995

The influence of depression on cognition in Parkinson's disease: a pattern of impairment distinguishable from Alzheimer's disease.

Conflicting reports about the effects of depression on cognition in Parkinson's disease (PD) are difficult to interpret because they are based on small sample sizes and confound depression with other variables. We found that a sample of 45 PD patients with current depression was cognitively more impaired than a sample of 45 PD patients without current depression matched for age, education, gender, age at disease onset, disease duration, and disease severity. The domains of cognition impaired in the two PD groups (compared with 45 age-, education-, and gender-matched controls) overlapped considerably, but only the depressed PD group had impaired memory relative to the control group. Our comparison of 22 depressed PD patients and 22 Alzheimer's disease (AD) patients matched for over-all severity of cognitive impairment, age, education, and gender indicated that the depressed PD group performed significantly worse on visuoconstructive tasks and marginally worse on conceptualization tasks. In contrast, the AD group performed significantly worse than the depressed PD group on memory tasks. Together, our results suggest that depression has a negative impact on cognition (and, in particular, memory) in PD, and that the pattern of this cognitive impairment is distinguishable from that associated with AD.

Aged↗
PubMed1995

Botulinum toxin treatment of essential head tremor.

We examined in a double-blind, placebo-controlled study the effects of botulinum toxin in 10 patients with essential head tremor. Each subject received two treatments approximately 3 months apart, one with botulinum toxin injections and another with normal saline injections into the sternocleidomastoid and splenius capitis muscles. The subjects were assessed before each treatment and at 2, 4, and 8 weeks after injections. There was moderate to marked improvement in clinical ratings in five subjects after botulinum toxin injections and in one subject after placebo. There was moderate to marked subjective improvement in five patients with botulinum toxin as compared with three subjects with placebo. Side effects were mild and transient. We conclude that botulinum toxin may be useful for patients with essential head tremor who have failed to benefit from oral medications.

Aged↗
PubMed1995

Influence of demographic variables on the Dementia Rating Scale.

Demographic characteristics influence many cognitive assessment tools. We evaluated the impact of age, education, and gender on the Dementia Rating Scale (DRS) in a sample of 212 normal people. Separate regression analyses revealed that age was the most potent demographic factor, whereas education and gender had little impact. However, the amount of variance accounted for by age was small (less than 20%). Clinical utility of age-adjusted DRS total score cut-offs was investigated in samples of Alzheimer's and Parkinson's disease patients. Hit rate analysis revealed greater sensitivity for a single cut-off value than age-corrected cut-off scores. Overall, these findings revealed the lack of a clinically meaningful relationship between demographic characteristics and DRS scores, suggesting that age, education, and gender can be ignored for interpretative purposes based on cut-off scores.

Aged↗
PubMed1994

Enhanced MPTP neurotoxicity after treatment with isoflurophate or cholinergic agonists.

Administration of the irreversible cholinesterase inhibitor isoflurophate (diisopropylfluorophosphate, DFP) before 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) enhanced the loss in tyrosine hydroxylase activity and dopamine and 3,4-dihydroxy-phenylacetic acid content in the striatum of mice in a dose-dependent manner. The effect of DFP on the MPTP-induced changes of dopaminergic markers was evident 30 days after initiating treatment, suggesting augmented neurotoxicity. Neurotoxicity was also enhanced by prior treatment with nicotine, carbachol or oxotremorine. We conclude that activation of either muscarinic or nicotinic receptors enhances the neurotoxicity of MPTP.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1993

Interactive video conferencing: a means of providing interim care to Parkinson's disease patients.

Inequity in health care delivery is attributable to a variety of factors including geographic isolation. Patients living far from major urban centers have limited access to medical specialists. In the instance of Parkinson's disease (PD), optimal assessment and care may depend upon availability of specialty health care providers. In order to broaden health care access, interactive video conference (IVC) units are being developed for medical use. IVC allows a patient at a distant site to be "seen and heard" by a hospital-based physician; simultaneously, the patient can "see and hear" the doctor. To establish the validity of this technology in the evaluation of PD, nine patients were independently examined and scored (UPDRS) by two movement disorder specialists. One examination was performed in-person by the usual physician. The other examination was performed on the same day via IVC over a distance of 350 miles by an examiner previously unfamiliar with the patients. Individual patient scores did not differ based on examiner (Spearman Rho Correlation Coefficients: UPDRS total scores r = 0.933, p < 0.0002; Hoehn and Yahr Scale r = 0.883, p < 0.001). A standardized exit interview was conducted to assess patients' perceptions of this application of video technology. Responses were favorable and virtually all patients viewed this as a means of accessing better health care. We conclude that valid motor assessments of PD patients can be made via IVC.

Aged↗
PubMed1993

Effects of selegiline dosing on motor fluctuations in Parkinson's disease.

To examine selegiline's dosing effects, we studied 16 Parkinson disease patients with motor fluctuations in a double-blind, crossover trial of selegiline at 0, 5, and 10 mg daily. Patients' motor diaries, disability scores, and walking speed were marginally improved, with no advantage of 10 mg over 5 mg found. We conclude that in patients with motor fluctuations, selegiline provides modest symptomatic effects, with daily dosing of 5 mg being indistinguishable from 10 mg.

Aged↗
PubMed1993

Personality and depression in Parkinson's disease.

The Parkinson's disease (PD) patient has been characterized as having a distinctive personality with introverted features. These personality traits are said to predate motor symptoms and are theorized to serve as a subtle clue to latent PD. To examine this hypothesis, we compared remote and current personality features in 35 PD subjects and 35 controls. Subjects' spouses completed a personality inventory (PI) characterizing patients' premorbid and current status. The premorbid PI of PD subjects differed from that of controls in being more "quiet," "generous," "cautious," and "even-tempered," and less "flexible." The characterization of the PD subjects' current personality differed greatly from reported premorbid personality features, i.e., significant change in 13 of 24 PI items. Personality inventory responses regarding both the PD subjects' premorbid and current personality correlated to symptoms of depression and disease severity. Cognition, tobacco use, alcohol consumption, and rural versus urban residency did not correlate with PI responses. We conclude that PD patients are apt to be viewed as introverts premorbidly, and, with disease onset, more striking personality changes are recognized. These perceptions appear to be closely linked to depressed affect and correlate with motor impairment to a lesser extent.

Alcohol Drinking↗
PubMed1993

Aromatic L-amino acid decarboxylase activity of mouse striatum is modulated via dopamine receptors.

Aromatic L-amino acid decarboxylase (AAAD) activity is enhanced in the striatum of control and MPTP-treated mice after administration of a single dose of the dopamine receptor antagonists haloperidol, sulpiride, and SCH 23390. MPTP-treated mice appear more sensitive to the antagonists, i.e., respond earlier and to lower doses of antagonists than control mice. The rise of AAAD activity induced by the antagonists is prevented by pretreatment with cycloheximide. The apparent Km values for L-3,4-dihydroxyphenylalanine (L-DOPA) and pyridoxal 5-phosphate appear unchanged after treatment with the antagonists. Increased AAAD activity was observed also after subchronic administration of dopamine receptor antagonists or treatment with reserpine. A single dose of a selective dopamine receptor agonists had no effect on AAAD activity. In contrast, administration of L-DOPA, quinpirole, or SKF 23390 for 7 days lowers AAAD activity in the striatum. We conclude that AAAD is modulated in striatum via dopaminergic receptors.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1993

Clinical experience with controlled-release carbidopa/levodopa in Parkinson's disease.

We converted 158 Parkinson's disease (PD) patients on stable doses of standard carbidopa/levodopa (Std-L) to controlled-release carbidopa/levodopa (L-CR). Of the 141 patients who completed the study, 103 (73%) preferred L-CR, 26 (18.5%) preferred Std-L, and 12 (8.5%) had no preference. One hundred fourteen patients elected to continue L-CR, and we performed the primary data analysis on this group. Following conversion to L-CR, patients reported an increase in length of benefit from each dose and an increased "kick-in" time. There was a decrease in the total number of doses, "off" periods, sleep interruptions per night, dose failures, and sleep disturbances. Conversion to L-CR resulted in a significant increase in total levodopa dose. There was no significant change in the dyskinesias. However, early-morning dystonia resolved in eight of 14 patients. Our findings suggest that L-CR is particularly effective in decreasing motor fluctuations, reducing nocturnal problems, and minimizing levodopa dose failures in PD.

Adult↗
PubMed1993

Risk factors for Parkinson's disease.

Parkinson's disease (PD) has been associated with rural living, well-water consumption, and pesticide exposure; however, the individual risk contribution of these variables has not been established. We examined social and medical histories of predominantly rural populations to determine relative risk factors for PD. Patients and controls were surveyed regarding residency, occupation, medical history, and social and dietary habits. An initial multiple logistic regression model was confounded by excessive variable colinearity. Principal factor analysis yielded three factors: rural living (including years of rural residency and ground-water use), pesticide use, and male lifestyle (male gender, head trauma, male-dominated occupations). Other variables did not load in factor analysis and were entered separately, with the three factor scores, in a second multiple logistic regression model. Significant predictors of PD emerged (in order of strength): pesticide use, family history of neurologic disease, and history of depression. The predicted probability of PD was 92.3% (odds ratio = 12.0) with all three predictors positive. Pesticide use (distinguishable from rural living) can be considered a risk factor for the development of PD, with family history of neurologic disease and history of depression serving as weaker predictors of PD.

Adult↗
PubMed1992

Osteomyelitis of the skull base.

Three cases of osteomyelitis of the skull base with associated problems in diagnosis and therapy are discussed. Patients with atypical skull base osteomyelitis are difficult to diagnose as they have no ear abnormalities, but they often develop multiple cranial nerve deficits mimicking symptoms of a posterior fossa mass. We conclude that computed tomographic scans, magnetic resonance imaging studies, bone scans indium-labeled white blood cell scans, and gallium scans are useful in making the diagnosis. A biopsy of the bony lesion often is needed to identify the causative organism and to rule out a tumor. Intravenously administered antibiotics are the mainstay of therapy and should be continued until 1 week after the gallium scan shows no abnormalities. Follow-up gallium scans then are done at 1 week and 3 months after the cessation of antibiotic therapy to search for a recurrence.

Adult↗