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Biomedical subjects

D B Calne

Publications and source records attributed to D B Calne.

At least 145 records · Page 8Linked to original sources
PubMed1989

Transplantation of human sympathetic neurons and adrenal chromaffin cells into parkinsonian monkeys: no reversal of clinical symptoms.

Cultured human fetal sympathetic ganglion explants or adrenal chromaffin cell aggregates were implanted into the left striatum of monkeys whose left nigrostriatal pathway had been lesioned with the neurotoxin MPTP. There was no clinical reversal of parkinsonian symptoms and PET scans did not show increased striatal fluorodopa uptake from pre-implant levels. At sacrifice, left striatal contents of dopamine were not statistically different from MPTP-treated but non-implanted controls. Histological examinations revealed pockets of extrinsic cells which were found at the end of needle tracks. There was no evidence of immune rejection. The extrinsic cells did not stain for tyrosine hydroxylase or neurofilament, suggesting that they were not dopaminergic neurons. The failure to reverse clinical parkinsonian symptoms highlights the stage of infancy of neural implantation in Parkinson's disease.

Adrenal Medulla↗
PubMed1989

A retinopathy on Guam with high prevalence in Lytico-Bodig.

A pigmentary retinopathy resembling that sometimes seen in posterior ophthalmomyiasis interna was found in 26 (53.1%) of 49 Chamorro patients from Guam who have Lytico-Bodig (also known as amyotrophic lateral sclerosis-Parkinsonism-dementia complex of Guam). In nine cases, the retinopathy was bilateral. Similar changes were found in 6 (16.2%) of 37 clinically normal individuals from southern villages on Guam that have a high incidence of Lytico-Bodig, and in 1 (3.1%) of 32 individuals from Saipan, an island north of Guam that has a low incidence of the disease. These results indicate the possibility of an association-between Lytico-Bodig and a retinopathy on Guam that may be parasitic in origin. Occurrence of a similar association in other debilitating diseases on Guam and frequency of occurrence of retinopathy in Guamanians with Lytico-Bodig after leaving Guam have yet to be determined.

Adult↗
PubMed1989

Optimal indices for testing parkinsonian rigidity.

We assessed parkinsonian rigidity objectively at the wrist to determine the optimal angular velocity and displacement for detecting abnormality. The wrist was moved passively with a torque motor and the average work done for one complete cycle was computed. This objective rigidity score (ORS) was compared with a clinical rigidity score (CRS). ORS was more pronounced at faster movement velocities in parkinsonian patients, whereas in normal subjects there was only a modest increase in the score. Angular velocities of 140 to 190 degrees/second and displacements of +/- 25 to +/- 30 degrees were most sensitive for detecting parkinsonian rigidity and had good correlation with the CRS.

Adult↗
PubMed1989

PET studies of parkinsonian patients treated with autologous adrenal implants.

Transplantation of autologous adrenal medulla tissue into the striatum has recently been proposed as a treatment for Parkinson's disease. We report the use of positron emission tomography (PET) to evaluate patients who had adrenal implants placed into the right caudate. 6-[18F] fluoro-L-dopa (6-FD) scans were performed to study the integrity and activity of the implant, and the nigrostriatal dopamine system before and six weeks after transplantation surgery. [68Ga] Gallium-ethylenediaminetetraacetate (Ga) scans were also performed to assess the blood brain barrier. The Ga scans performed on two patients showed increased permeability of the blood brain barrier at the surgical site. 6-FD PET scans in five patients did not show a consistent change in striatal uptake following adrenal medullary implantation after six weeks. Further assessment of implant viability with 6-FD PET scans after longer follow up may provide useful information if the blood-brain barrier becomes re-established with the passage of time.

Adrenal Medulla↗
PubMed1989

The relationship between Alzheimer's disease, Parkinson's disease and motor neuron disease.

We argue against the dominant status assigned to conventional microscopy in the categorization of disorders such as Alzheimer's disease, Parkinson's disease and ALS. As an example we criticize the emphasis that has been placed on correlating the presence of Lewy bodies with the diagnosis of Parkinson's disease. In essence, we submit that Parkinson's disease can exist without Lewy bodies, and Lewy bodies can exist without Parkinson's disease. Nevertheless, we consider that the newer techniques available to histology have led to an important concept that constitutes a shared feature for Alzheimer's disease. Parkinson's disease and ALS; they are all characterized by the deposition of cytoskeletal debris in tissue, so they may perhaps be collectively termed the "Cytoskeletal Disorders".

Aged↗
PubMed1989

Is "Parkinson's disease" one disease?

Consideration is given to how and why categories of ill health are divided into diseases. Aetiology is a fundamental criterion for the delineation of individual diseases. The same clinical and pathological picture may have many different causes; for example meningococcal meningitis and pneumococcal meningitis are distinct diseases that may display the same symptoms and signs. On the other hand, a single aetiology may lead to quite separate clinical and pathological phenomena; for example, neurosyphilis is a disorder that can present with general paresis or tabes dorsalis (or any combination of the two). In attempting to find a nosological placement for Parkinson's disease, we must take into account the extensive overlap with idiopathic dementia (Alzheimer's disease). Present evidence raises the possibility of several causes for Parkinson's disease, some of which may also be responsible for idiopathic dementia. A classification in accord with its position is desirable, and as a first step it would be helpful to replace "Parkinson's disease" with a term that is not saddled with implications of a single causal mechanism. "Idiopathic Parkinsonism" is suitable nomenclature for what is really a syndrome of unknown origin.

Alzheimer Disease↗
PubMed1989

The effect of dietary protein on the efficacy of L-dopa: a double-blind study.

We randomly placed 10 parkinsonian patients on high- and low-protein diets that tasted and looked alike, each for 1 week. All patients were taking L-dopa and carbidopa with or without other antiparkinson medications; medications remained unchanged. A "blind" physician recorded the modified Columbia scores, objective measurements of rigidity, movement velocity, and pegboard tests three times a day for 5 days during each week. The patients recorded fluctuations hour to hour. We measured serial blood L-dopa levels on day 4 of each week. Performance was significantly better while the patients were on low-protein diets. These results did not correlate with blood L-dopa levels, which had higher peaks in three patients while they were on high-protein diets despite inferior performance and increased number of "off" hours. Thus, high dietary protein probably affects the efficacy of L-dopa at a central level.

Antiparkinson Agents↗
PubMed1989

A double-blind, placebo-controlled, dose-ranging study to investigate the safety and efficacy of CY 208-243 in patients with Parkinson's disease.

We carried out a double-blind rising dose study of a D-1 dopamine agonist, CY 208-243, in 6 parkinsonian patients. Deficits monitored by Columbia scores were significantly improved at single doses ranging from 5 to 40 mg, though efficacy was low. Used alone, CY 208-243 was not a satisfactory therapeutic agent, and toxicity data precluded further increases in dosage.

Dose-Response Relationship, Drug↗
PubMed1988

A new device for the quantitative assessment of dopaminergic drug effects in unilateral MPTP-lesioned monkeys.

Non-human primates exposed to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) have been employed to study the clinical features of parkinsonism. Monkeys lesioned by unilateral intracarotid administration of MPTP display spontaneous and drug responsive turning behavior. However this seems to correlate poorly with their clinical deficits. We describe an objective measurement of arm movement velocity, applied in 4 cynomolgus monkeys before and after unilateral administration of MPTP. Reduced movement velocities correlated with clinical signs of unilateral flexed arm posture, rigidity, tremor and bradykinesia and could be reversed with L-DOPA therapy. This measurement technique has advantages for the quantitative assessment of parkinsonian deficits and will permit the evaluation of dopaminergic therapy and transplantation in non-human primates.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1988

Asymptomatic striatal dopamine depletion: PET scans in unilateral MPTP monkeys.

In cynomolgus monkeys, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) produces irreversible clinical, chemical, and pathological alterations that are similar to those found in Parkinson's disease. Unilateral carotid injections of this toxin produce ipsilateral nigrostriatal dopamine depletion while sparing the contralateral dopaminergic pathways. In order to study the damage to the nigrostriatal dopamine system in asymptomatic animals after unilateral MPTP administration, positron emission tomography (PET) scans were performed with [18F]fluoro-L-dopa (6-FD). This study demonstrates that clinically asymptomatic MPTP lesions may be assessed in vivo using 6-FD and PET.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1988

Normality and disease.

There have been trends to equate normal with an ideal state of health, and disease with disturbances that are determined solely by subclinical abnormalities. While in any living language there is a conflict between established definition and the need for change, modification in the use of words that are of such central importance to medical writing requires cogent justification that has not been forthcoming in these instances. To avoid further obscuration of the literature, the term normal should be limited to its traditional connotation of average, and the term disease should be reserved for disturbances of health that are clinically manifest.

Disease↗
PubMed1988

Late progression of post-encephalitic Parkinson's syndrome.

We have studied 11 patients with neurological deficits due to the pandemic of encephalitis lethargica, all of whom had remained in hospital for more than forty years. Retrospective information obtained from physicians and nurses dating back as far as 1931, our own Webster and Northwestern University Disability Rating Scales available from 1976, photographic records, published narrative and hospital charts all indicate that neurological disabilities attributable to basal ganglia damage frequently increase in late life. Deterioration was most marked in motor function and largely spared the intellect, special senses and somatosensory system. The findings are discussed in relation to current hypotheses concerning the aetiology of Parkinson's disease.

Aged↗
PubMed1988

Supranuclear disturbances of ocular motility in Lytico-Bodig.

We found abnormal supranuclear ocular or lid motility in all of 37 patients with Lytico-Bodig (amyotrophic lateral sclerosis/parkinsonism-dementia complex). Twenty-one patients had pursuit paresis, 18 abnormal vestibulo-ocular reflex (VOR) cancellation, 15 abnormal convergence, 13 abnormal optokinetic nystagmus (OKN), 12 conjugate gaze limitation, nine nystagmus, nine saccadic paresis, and six abnormal fixation. Lid abnormalities included glabellar hyperreflexia in 21, involuntary levator inhibition in three, and blepharospasm in two. Earlier reports have indicated infrequent ocular disturbances in Lytico-Bodig, but we now find supranuclear eye and lid deficits are universal and sometimes very prominent.

Aged↗