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Biomedical subjects

C W Olanow

Publications and source records attributed to C W Olanow.

At least 127 records · Page 7Linked to original sources
PubMed1991

Dopamine sulfate in ventricular cerebrospinal fluid and motor function in Parkinson's disease.

We measured sequential plasma and CSF levodopa and CSF dopamine sulfate levels following a single dose of levodopa/carbidopa in two patients with advanced Parkinson's disease (PD). We obtained CSF from an Ommaya reservoir implanted in the lateral ventricle several months earlier at the time of transplantation of adrenal medulla to caudate nucleus and could detect dopamine only in its sulfconjugated form. Peak CSF levodopa and dopamine sulfate levels occurred 1 to 1.5 hours after peak plasma concentration of levodopa. The time course of clinical improvement and worsening correlated precisely with the appearance and disappearance of both levodopa and dopamine sulfate in the CSF. The precise correlation between CSF dopamine sulfate and levodopa indicates that in patients with advanced PD the brain retains some capacity to convert levodopa to dopamine. The transient nature of the correlation between motor fluctuations, CSF levodopa, and CSF dopamine sulfate is consistent with suggestions that in patients with advanced PD there is a diminished capacity to store dopamine synthesized from exogenous levodopa. Dopamine sulfate appears to be a useful index of the availability of dopamine in the parkinsonian brain.

Carbidopa↗
PubMed1990

Autologous transplantation of adrenal medulla in Parkinson's disease. 18-month results.

Eighteen of 19 patients who underwent autologous adrenal medullary transplantation to the right caudate nucleus have been followed up for 18 months. During the course of this study, a statistically significant improvement was noted in percent "on" time, percent "on" time without dyskinesia, activity of daily living (ADL) scores during the "on" stages, and ADL, motor, and Schwab-England scores during the "off" stages. Benefits tended to be maximal at 6 months and to gradually lessen thereafter, although statistically significant improvement in comparison with baseline was still present at 18 months for ADL, motor, and Hoehn-Yahr scores during the "off" stages. Almost all parameters had deteriorated by 18 months compared with 12 months, including those remaining significantly improved in comparison with baseline. These patterns were similar for each of the three participating centers. Complications were largely restricted to the perioperative period.

Adrenal Medulla↗
PubMed1990

Oxidation reactions in Parkinson's disease.

Free radicals generated from oxidation reactions may contribute to the pathogenesis of Parkinson's disease (PD). Free radicals are capable of reacting almost instantaneously with membrane lipids and causing lipid peroxidation, membrane injury, and cell death. Dopamine is metabolized by oxidation reactions capable of generating free radicals. Recent evidence indicates that the substantia nigra of patients with PD contains increased iron, which enhances oxidation, and decreased glutathione, which protects against the formation of free radicals. Further, the end products of lipid peroxidation are increased in the substantia nigra of patients with PD, supporting the notions that free radicals are being generated and may contribute to dopamine neuronal death. This hypothesis suggests that antioxidant therapies may slow the rate of progression of PD and raises concern that metabolites of levodopa therapy may accelerate the rate of neuronal degeneration.

Free Radicals↗
PubMed1989

Multicenter study of autologous adrenal medullary transplantation to the corpus striatum in patients with advanced Parkinson's disease.

In 19 patients with severe Parkinson's disease, we replicated the surgical procedures developed by Madrazo et al. for transplantation of the adrenal medulla to the striatum, and followed them for six months after operation. We monitored their motor function with the use of standardized scales and determined the amount and quality of "on" and "off" time (the hours of the waking day when the antiparkinsonian medications were effective and ineffective, respectively). We found significant improvement in focal areas of motor function. The mean percentage of on time during the day increased from 47.6 percent to 75.0 percent (P = 0.012); the mean percentage of on time without chorea increased from 26.6 percent to 59.2 percent (P = 0.006); the mean severity of off time decreased as assessed by both the Activities of Daily Living subscale of the Unified Parkinson's Disease Scale (P = 0.002) and the Schwab and England scale (P = 0.037). In contrast to the finding of Madrazo et al., however, the dosages of antiparkinsonian medications could not be decreased and postoperative morbidity was substantial. Despite cautious optimism, we conclude that the widespread use of this procedure outside of research centers is premature, since the improvement we found was slighter than in the previous cases.

Activities of Daily Living↗
PubMed1989

Parkinsonism and amiodarone therapy.

We report a case of reversible, dose-related parkinsonian tremor in a patient taking amiodarone. In previous writings by others, basal ganglia dysfunction associated with amiodarone was dose related and reversibility was inversely related to duration of therapy. Patients receiving amiodarone are at risk for the development of basal ganglia dysfunction which may persist if the drug is not discontinued or the dosage reduced.

Aged↗
PubMed1989

CV 205-502: safety, tolerance to, and efficacy of increasing doses in patients with Parkinson's disease in a double-blind, placebo crossover study.

CV 205-502 (CV) is a long-acting dopamine agonist with potent D2 and weak D1 activity, which has not as yet been tested in patients with Parkinson's disease. We performed a dosage ranging and placebo crossover study in six patients to evaluate the efficacy and tolerance of CV when used as an adjunct to Sinemet in patients with Parkinson's disease. All patients had striking improvement. This effect was lost with placebo substitution and regained with reintroduction of CV. Benefits were sustained throughout the 6 month study. Single daily dosing could sustain the response in all but one patient. Adverse effects were mild and transient and resolved with dosage manipulation or a divided dosage regimen. CV is a promising drug for use in Parkinson's disease and further studies are indicated to test its long-term safety and efficacy.

Adult↗
PubMed1984

Dyskinesias associated with lithium therapy in parkinsonism.

Five patients with the "on-off" phenomenon of parkinsonism who developed dyskinesias associated with a reduction in akinesia during treatment with lithium carbonate are described. The data show that lithium-induced dyskinesias may occur in the absence of lithium neurotoxicity and at normal serum lithium concentrations. These observations are interpreted in the context of recent evidence that indicates that lithium may "stabilize" dopaminergic and cholinergic receptor sensitivity.

Adult↗
PubMed1984

Myoadenylate deaminase deficiency. Functional and metabolic abnormalities associated with disruption of the purine nucleotide cycle.

To assess the role of the purine nucleotide cycle in human skeletal muscle function, we evaluated 10 patients with AMP deaminase deficiency (myoadenylate deaminase deficiency; MDD). 4 MDD and 19 non-MDD controls participated in an exercise protocol. The latter group was composed of a patient cohort (n = 8) exhibiting a constellation of symptoms similar to those of the MDD patients, i.e., postexertional aches, cramps, and pains; as well as a cohort of normal, unconditioned volunteers (n = 11). The individuals with MDD fatigued after performing only 28% as much work as their non-MDD counterparts. Muscle biopsies were obtained from the four MDD patients and the eight non-MDD patients at rest and following exercise to the point of fatigue. Creatine phosphate content fell to a comparable extent in the MDD (69%) and non-MDD (52%) patients at the onset of fatigue. Following exercise the 34% decrease in ATP content of muscle from the non-MDD subjects was significantly greater than the 6% decrease in ATP noted in muscle from the MDD patients (P = 0.048). Only one of four MDD patients had a measurable drop in ATP compared with seven of eight non-MDD patients. At end-exercise the muscle content of inosine 5'-monophosphate (IMP), a product of AMP deaminase, was 13-fold greater in the non-MDD patients than that observed in the MDD group (P = 0.008). Adenosine content of muscle from the MDD patients increased 16-fold following exercise, while there was only a twofold increase in adenosine content of muscle from the non-MDD patients (P = 0.028). Those non-MDD patients in whom the decrease in ATP content following exercise was measurable exhibited a stoichiometric increase in IMP, and total purine content of the muscle did not change significantly. The one MDD patient in whom the decrease in ATP was measurable, did not exhibit a stoichiometric increase in IMP. Although the adenosine content increased 13-fold in this patient, only 48% of the ATP catabolized could be accounted for by the combined increases of adenosine, inosine, hypoxanthine, and IMP. Studies performed in vitro with muscle samples from seven MDD and seven non-MDD subjects demonstrated that ATP catabolism was associated with a fivefold greater increase in IMP in non-MDD muscle. There were significant increases in AMP and ADP content of the muscle from MDD patients following ATP catabolism in vitro, while there was no detectable increase in AMP or ADP in non-MDD muscle. Adenosine content of MDD muscle increased following ATP catabolism, but there was no detectable increase in adenosine content of non-MDD muscle following ATP catabolism in vitro. These studies demonstrate that AMP deaminase deficiency leads to reduced entry of adenine nucleotides into the purine nucleotide cycle during exercise. We postulate that the resultant disruption of the purine nucleotide cycle accounts for the muscle dysfunction observed in these patients.

AMP Deaminase↗
PubMed1984

Autologous mixed lymphocyte reaction in patients with myasthenia gravis: correlation with disease activity.

Enriched subpopulations of peripheral blood mononuclear cells from patients with myasthenia gravis and from normal control individuals were tested for proliferative ability in the autologous mixed lymphocyte reactions. Myasthenia gravis patients were studied at various phases of therapy. Longitudinal patient populations were studied. Purified T cells from untreated patients with active myasthenia gravis demonstrated enhanced proliferative responses when co-cultured with nonmodified autologous non-T cells. Furthermore, treatment by thymectomy with or without prior plasmapheresis was associated with a consequent normalization of the autologous reaction. The enhanced autologous mixed lymphocyte reaction in the pre-treatment group of myasthenia gravis patients was significantly different from the post-treatment and normal control groups (Stimulation Index, p less than 0.01 and p less than 0.02, respectively). This difference in activity was also confirmed in a longitudinal study of 10 patients followed pre- and post-treatment (Stimulation Index, p less than 0.02). There was no difference between the responses of post-treatment patients and normal control individuals. There was no evidence of altered T cell responsiveness or non-T cell stimulation, as measured by the allogeneic mixed lymphocyte reaction or by mitogen-induced lymphocyte proliferation, between pretreatment and post-treatment patients as compared to controls. The responses were not affected by serum substitution experiments whereby myasthenic responder T cells were co-cultured with pooled normal human sera. Other parameters studied included clinical status, anti-acetylcholine receptor antibody levels, and thymic pathology. An intriguing connection between abnormalities in the thymic cell populations and the autoaggressive state in myasthenia may be reflected by the in vitro autologous mixed lymphocyte reaction.

Adolescent↗
PubMed1983

Thymoma following transcervical thymectomy for myasthenia gravis.

A superior mediastinal thymoma was found in a patient two years following a transcervical thymectomy for myasthenia gravis. This case report illustrates another potential complication of incomplete thymectomy that may occur with the transcervical approach.

Female↗
PubMed1983

Effect of thymectomy on peripheral lymphocyte subsets in myasthenia gravis: selective effect on T-cells in patients with thymic atrophy.

Myasthenia gravis (MG) is an autoimmune disease affecting nicotinic acetylcholine receptors. The clinical improvement that follows thymectomy in some myasthenic patients implicates thymic factors as well in the pathogenesis of MG. We have studied circulating immunoregulatory T cell subsets before and after thymectomy in 11 adult patients with MG. Six patients had thymic hyperplasia and five patients had atrophic thymus at the time of thymectomy. Before thymectomy, patients who subsequently were shown to have an atrophic thymus, had lower lymphocyte counts than either patients later shown to have a hyperplastic thymus (1315 +/- 143 lymphocytes/mm3 vs. 2434 +/- 350 lymphocytes/mm3, p less than 0.01), or age-matched controls (1315 +/- 143 lymphocytes/mm3 vs. 2636 +/- 589 lymphocytes/mm3, p less than 0.02). Moreover, after thymectomy, in MG patients with an atrophic thymus, there was a significant rise in lymphocyte count (from 1315 +/- 143 lymphocytes/mm3 to 2279 +/- 292 lymphocytes/mm3, p less than 0.02) beginning 3 days postthymectomy and persisting for at least 6 weeks thereafter. In comparison, patients with a hyperplastic thymus showed no change in circulating lymphocyte counts (p greater than 0.1). Enumeration of lymphocyte subsets in MG patients with an atrophic thymus demonstrated normal B cell numbers before and after thymectomy (p greater than 0.1), whereas, T cells were significantly decreased before thymectomy compared with age-matched normal subjects (859 +/- 82 T cells/mm3 vs. 2215 +/- 545 T cells/mm3, p less than 0.05), and rose to near normal levels after thymectomy (1796 +/- 294 T cells/mm3, p less than 0.02 compared with prethymectomy levels). Using monoclonal anti-T cell antibodies 3A1, OKT4, and OKT8, we found that, before thymectomy in the atrophic thymus group, 3A 1+ T cells were significantly depressed compared with postthymectomy levels (620 +/- 173 cells/mm3 vs. 1627 +/- 331 cells/mm3, p less than 0.02) as were OKT4+ cells 436 +/- 88 cells/mm3 vs. 1112 +/- 63 cells/mm3, p less than 0.001), In contrast, no significant change was seen after thymectomy in the OKT8+ cell subset (p greater than 0.1). MG patients with an atrophic thymus had decreased plasma cortisol levels postthymectomy compared with prethymectomy levels, whereas thymectomy in MG patients with a hyperplastic thymus effected no change in plasma cortisol levels. These data demonstrate in MG patients with an atrophic thymus that thymectomy has an effect on the number of circulating T cells, and in particular, on those T cells expressing antigens 3A1 and OKT4. This effect may in part be mediated by changes in plasma adrenal corticosteroid levels after thymectomy or may be due to a factor produced by atrophic thymuses in MG.

Antigens, Differentiation, T-Lymphocyte↗