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Biomedical subjects

W Olanow

Publications and source records attributed to W Olanow.

8 recordsLinked to original sources
PubMed2000

Continuous dopamine-receptor stimulation in early Parkinson's disease.

Chronic L-dopa therapy is associated with the development of motor complications in the majority of Parkinson's disease (PD) patients. Although the precise mechanism responsible for these events is not known, increasing laboratory and clinical evidence points to a sequence of events that is initiated by abnormal pulsatile stimulation of dopamine receptors by the intermittent administration of agents with short half-lives such as L-dopa. Initiating therapy with a long-acting dopamine agonist has been shown to delay the onset and reduce the severity of motor complications in MPTP monkeys and PD patients. Administering L-dopa with a catechol-O-methyltransferase (COMT) inhibitor to block its peripheral metabolism increases its plasma half-life and might have a similar effect. Thus, a rational strategy for treating PD would be to initiate therapy with a long-acting dopamine-receptor agonist and supplement at the appropriate time with L-dopa combined with a COMT inhibitor.

Animals↗
PubMed1995

MRI and PET studies of manganese-intoxicated monkeys.

Using MRI and PET, we investigated the consequences of manganese intoxication in a primate model of parkinsonism and dystonia. Three rhesus monkeys were injected intravenously with doses of 10 to 14 mg/kg of MnCl2 on seven occasions, each a week apart. Two animals became hypoactive with abnormal extended posturing in the hind limbs. These motor disturbances did not improve with administration of levodopa. In all three monkeys, T1-weighted MRI demonstrated high signal intensities in the regions of the striatum, globus pallidus, and substantia nigra. No significant changes were found on [18F]6-fluoro-L-dopa, [11C]raclopride, or [18F]fluorodeoxyglucose PET. These results are consistent with the pathologic findings, which were primarily confined to the globus pallidus, and indicate that manganese intoxication is associated with preservation of the nigrostriatal dopaminergic pathway, despite clinical evidence of parkinsonian deficits. Chronic manganese intoxication may cause parkinsonism by damaging output pathways downstream to the nigrostriatal dopaminergic pathway. This is consistent with the demonstrated lack of therapeutic response to levodopa.

Animals↗
PubMed1994

Manganism and idiopathic parkinsonism: similarities and differences.

From the comparison we have made between PD and manganism, we draw the following conclusions: 1. There are similarities between PD and manganism, notably the presence of (a) generalized bradykinesia and (b) widespread rigidity. 2. There are also dissimilarities between PD and manganism, notably the following in manganism: (a) less-frequent resting tremor, (b) more frequent dystonia, (c) a particular propensity to fall backward, (d) failure to achieve a sustained therapeutic response to levodopa, and (e) failure to detect a reduction in fluorodopa uptake by PET. Further studies are likely to yield more discriminants between PD and manganism. For example, PET with raclopride may be useful in early cases of manganism, and MRI may be helpful in patients with advanced manganism.

Brain↗
PubMed1993

Progression after chronic manganese exposure.

We report a longitudinal follow-up study on six patients with chronic manganese-induced parkinsonism following cessation of manganese exposure. Compared with the 1987 study, their parkinsonian symptoms showed a slow progression, particularly in gait disturbances such as freezing during turning and walking backward with retropulsion. The mean disability scores on the King's College Hospital Rating Scale were 15.0 +/- 4.2 in 1987 and 28.3 +/- 6.7 in 1991 (p = 0.003, paired t test). Review of the video records also confirmed a worsening of parkinsonism, especially in difficulty turning. Three of six patients receiving levodopa treatment had an initial improvement. The response decreased after 2 to 3 years. During the therapy, they did not develop on-off fluctuation or dyskinesia. We conclude that patients with manganese-induced parkinsonism may develop increasing neurologic dysfunction long after cessation of exposure and that their responses to levodopa are different from those of patients with Parkinson's disease.

Adult↗
PubMed1986

Parkinson plus syndrome: diagnosis using high field MR imaging of brain iron.

The distribution of iron in the brain was analyzed using high field strength (1.5 T) magnetic resonance (MR) imaging in 14 healthy control individuals and six patients with Parkinson plus syndromes (multisystem atrophy and progressive supranuclear palsy) who were unresponsive to antiparkinsonian therapy. The normal topographic distribution of iron in the brain as indicated by high field MR images coincided precisely with the distribution of iron in the brain as determined by Perls staining for ferric iron. In Parkinson plus syndromes, there were abnormally increased concentrations of iron (decreased T2 relaxation times) in the putamen, and less prominent increases in the caudate nucleus and lateral pars compacta of the substantia nigra. In high field strength MR images of normal patients, the decreased signal intensity in the globus pallidus is more prominent than that of the putamen. In MR images of patients with Parkinson plus syndromes, the decreased signal intensity of the putamen is more prominent than that of the globus pallidus.

Adult↗
PubMed1983

Age-related changes in the thymus gland: CT-pathologic correlation.

Recent reports suggest that computed tomography (CT) is useful for thymoma detection in patients with myasthenia gravis. However, that usefulness may be conditioned by the state of the normal thymus. To examine this concept, the CT findings in 64 consecutive patients with histologic confirmation of thymic status after thymectomy or thymic biopsy during mediastinal exploration were reviewed. The normal thymus has a bilobed, arrowhead-shaped cross section at all ages, with gradual focal or diffuse fatty infiltration of the parenchyma usually occurring between 20 and 40 years of age. A thymoma is usually a spherical or oval mass, often producing a focal, distinct bulge in the adjacent pleural reflection. The differentiation of thymoma from normal thymus should be possible in most patients if age-related changes in the normal gland are appreciated.

Adolescent↗
PubMed1982

Thymoma detection by mediastinal CT: patient with myasthenia gravis.

The precise role of computed tomography (CT) in evaluating the mediastinum for thymomas in patients with myasthenia gravis is not defined. The only published CT accuracy assessment reports a false-positive rate of 90%. Mediastinal CT was performed in 23 consecutive unselected patients with myasthenia gravis who underwent thymectomy independent of their neurologic status or diagnostic imaging results. Four patients had discrete thymomas; all were detected by CT. Conventional chest radiography and tomography were positive in three and falsely negative in one. In the remaining 19 patients with a normal or atrophic thymus or microscopic hyperplasia, CT was falsely positive in two; conventional chest radiography and tomography were falsely positive in three. Mediastinal CT is an accurate technique for evaluation of thymoma in patients with myasthenia gravis.

Adolescent↗