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Biomedical subjects

G M Stern

Publications and source records attributed to G M Stern.

At least 37 records · Page 2Linked to original sources
PubMed1992

The properties of cultured fetal human and rat brain tissue and its use as grafts for the relief of the parkinsonian syndrome.

Primary cultures were derived from human fetal ventral mesencephalon and cerebral cortex at 7-11 weeks gestation, and from fetal rat mesencephalon and cortex at embryonic day 14-15. Immunohistochemical analysis of the mesencephalic cultures using antibodies to tyrosine hydroxylase (TH) showed between 0.1-0.5% of human cells to be TH positive and 0.1-1% of rat cells to be TH positive. HPLC analysis of extracts from the cultures showed that they had the ability to synthesise and store dopamine. Implantation of the cultured human and rat mesencephalic tissue into a 6-hydroxydopamine rat model of Parkinson's disease produced marked recovery from amphetamine induced rotational asymmetry in the recipient rats, but no such recovery was observed following implantation of cortical cultures. Histological examination demonstrated the presence of surviving human mesencephalic and cortical grafts at least 6 months after implantation. Implants of cultured fetal rat tissue were less obviously but still significantly effective in these experiments. These rat tissue grafts were detectable for periods of at least 6-8 weeks by histological staining.

Animals↗
PubMed1991

The motor response to repeated apomorphine administration in Parkinson's disease.

Seven patients with Parkinson's disease and levodopa-induced motor fluctuations were studied with repeated injections of apomorphine over a 10-h period to explore possible changes in the latency, duration, and quality of motor response with recurrent dopaminergic stimulation. Doses were given when the motor effects induced by the previous dose had just worn off. No significant change in the motor response to repeated boluses of subcutaneous apomorphine was found. Our results do not support the suggestion that rapid changes in receptor sensitivity during repeated intermittent dopaminergic stimulation are a major factor in the pathogenesis of parkinsonian motor fluctuations.

Aged↗
PubMed1991

Sublingual apomorphine in the treatment of Parkinson's disease complicated by motor fluctuations.

Subcutaneous apomorphine is a useful treatment for refractory motor fluctuations in Parkinson's disease. We have now clinically evaluated a formulation of sublingual apomorphine (57 mg) and performed preliminary pharmacokinetic studies. In acute studies, all 10 patients switched "on" after a mean latency of 25 min with a mean duration of motor benefit of 118 min. In three patients followed for a mean of 4.7 months, we have shown that chronic sublingual use can be effective, safe, and convenient in controlling motor fluctuations. The pattern of clinical response followed closely the plasma profile of apomorphine with a mean Cmax of 76 pmol/ml (50-106 pmol/ml) and a mean Tmax of 60 min (45-80 min), with moderate interpatient variability in bioavailability. Sublingual apomorphine is a practical alternative to subcutaneous use in selected patients with severe motor fluctuations.

Administration, Sublingual↗
PubMed1991

The motor response to sequential apomorphine in parkinsonian fluctuations.

Fifteen patients with Parkinson's disease and levodopa-induced motor fluctuations, were studied with repeated injections of apomorphine using two protocols to explore possible changes in the duration of motor response. One involved different interdose intervals; in the other, doses were given when the motor effects induced by the previous dose had just worn off. No significant change in the duration of motor response to sequential subcutaneous apomorphine with either protocol was found. The results suggest that rapid changes in receptor sensitivity during repeated intermittent dopaminergic stimulation do not contribute to the pathogenesis of Parkinsonian motor fluctuations.

Adult↗
PubMed1991

Challenge tests to predict the dopaminergic response in untreated Parkinson's disease.

To clarify the predictive role of dopaminergic challenge tests, we compared the responses to subcutaneous apomorphine and oral levodopa with the therapeutic effect of ongoing levodopa treatment in 45 previously untreated patients with idiopathic Parkinson's disease. The response to long-term levodopa was accurately predicted by apomorphine in 67% (30) of patients and by levodopa in 80% (35) of patients. There were nine cases without a definite response to sustained levodopa, four in patients who developed atypical clinical features during the period of follow-up. These tests have a predictive value for subsequent dopaminergic responsiveness and may help in the early differential diagnosis of parkinsonian syndromes.

Administration, Oral↗
PubMed1990

Apomorphine test to predict dopaminergic responsiveness in parkinsonian syndromes.

To evaluate apomorphine as an indicator of dopaminergic responsiveness, responses to subcutaneous apomorphine, to a single levodopa challenge, and to prolonged levodopa therapy were studied in 100 patients with parkinsonian syndromes (65 with idiopathic Parkinson's disease, 35 with other parkinsonian syndromes). Excellent agreement was found between the initial challenges of apomorphine and levodopa. Apomorphine also accurately predicted the response to long-term levodopa in 90% of the patients. There were 8 false-negative results; 7 were in patients with mild deficits. The apomorphine test is a quick, safe, reliable indicator of dopaminergic responsiveness in parkinsonian syndromes. The test is especially helpful to reassess patients who seem to have become less responsive to levodopa and it also has some predictive value in the assessment of an untreated patient's likely response to dopaminergic therapy.

Administration, Oral↗
PubMed1990

Apomorphine in the diagnosis and treatment of parkinsonian tremor.

The response of rest tremor to single doses of subcutaneous apomorphine and oral levodopa was compared in 20 patients with tremor-dominant Parkinson's disease. In eight of these patients, who were experiencing refractory levodopa-induced fluctuations characterised by disabling tremor, we studied the efficacy of sustained subcutaneous apomorphine. Nineteen patients responded favourably to acute challenges of both apomorphine and levodopa, with abolition of tremor in 10. In three, the response was helpful in confirming the clinical diagnosis. Chronic apomorphine use led to a more than 50% reduction in tremor-filled hours per day. After a mean duration of follow-up of 7.5 months, there was no tachyphylaxis to its therapeutic action. Subcutaneous apomorphine is an effective adjunct in treating patients with resistant, tremor-dominant fluctuations, and may also be helpful in the diagnosis of parkinsonian tremor.

Administration, Oral↗
PubMed1990

The effect of benserazide on the peripheral and central distribution and metabolism of levodopa after acute and chronic administration in the rat.

1. The effects of levodopa alone (50 mg kg-1) and levodopa (10 mg kg-1) plus benserazide (50 mg kg-1) were tested on the levels of dopa, dopamine, 3-methoxytyrosine (3-MT), 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), measured by h.p.l.c. with electrochemical detection, in samples of plasma, CSF, urine, striatum and hypothalamus of rats taken 30 min after injection. Levodopa plus benserazide produced significantly higher levels of dopa in plasma and brain than levodopa alone and reduced the peripheral synthesis and metabolism of dopamine. 2. When given chronically over 6 weeks the advantages of adding benserazide (50 mg kg-1 day-1) to levodopa (40 mg kg-1 day-1) were less marked and although more dopamine was present in the striatum than with levodopa given alone (200 mg kg-1 day-1) there was no evidence of any increase in its metabolites (HVA and DOPAC) and therefore of its turnover and utilisation. 3. The most striking effect of chronic treatment with levodopa plus benserazide was the appearance of large quantities of 3-MT in plasma, CSF and brain. 4. When levodopa alone, or levodopa plus benserazide, was given as an acute challenge to animals receiving the same treatment chronically, it was found that levodopa alone still produced increases in striatal dopamine, DOPAC and HVA in those animals dosed chronically on levodopa, but it was less effective in this respect when given with benserazide to the animals dosed with levodopa plus benserazide. 5. It is concluded that this difference in levodopa distribution may depend on the persistence in benserazide-treated animals of 3-MT, which has a long half-life and may compete with dopa for transport into the blood and brain. 6. The implication of these findings to the treatment of Parkinsonism is discussed.

Animals↗
PubMed1990

Comparison of motor response to apomorphine and levodopa in Parkinson's disease.

The magnitude and pattern of motor responses to single doses of subcutaneous apomorphine and oral levodopa were compared in 14 patients with Parkinson's disease. Although apomorphine produced much shorter motor responses than levodopa, the quality of response to the two drugs was virtually indistinguishable. These clinical observations support the notion that integrity of striatal post-synaptic dopamine receptors is a key determinant of responsiveness to dopaminergic treatment in Parkinson's disease.

Administration, Oral↗
PubMed1990

Diurnal differences in response to oral levodopa.

Diurnal differences in duration and quality of motor response to levodopa are frequently described by patients. The quality and duration of motor responses were objectively assessed to morning and afternoon oral levodopa doses in five patients with Parkinsonian motor fluctuations who complained of diurnal variation in response to their normal levodopa medication. Results suggest that under controlled conditions which eliminated the effects of diet and overlapping levodopa effects the response to levodopa remained unchanged throughout the day, and that the duration of response could be predicted by plasma levodopa levels.

Administration, Oral↗
PubMed1990

Subcutaneous apomorphine in the treatment of Parkinson's disease.

Apomorphine a dopamine receptor agonist was given subcutaneously to 57 levodopa treated parkinsonian patients with refractory off-period disabilities for a median period of 16 months. In 30 given intermittent suprathreshold injections the mean number of hours spent in a disabling off state fell from 6.9 to 2.9. Similar benefit was observed in 21 patients receiving continuous infusions with additional boluses on demand by mini-pump (mean reduction of hours off from 9.9 to 4.5). Twelve patients have been treated for over two years without tachyphylaxis or loss of response. The incidence of neuropsychiatric side-effects has been low (7%). Six patients failed to show a sustained worthwhile response; severe disabilities during "on" periods being the major problem. Subcutaneous apomorphine is proposed as an effective treatment for patients with incapacitating "off" period disabilities refractory to oral medication and should be considered before experimental implantation procedures.

Adult↗