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Biomedical subjects

A J Lees

Publications and source records attributed to A J Lees.

At least 19 recordsLinked to original sources
PubMed1979

Neurosyphilis today.

17 cases of recently diagnosed neurosyphilis are reviewed. The presenting features are diverse, and a clinical diagnosis may be difficult. Routine serological test are essential to confirm the clinical diagnosis.

Adult↗
PubMed1979

Niacin depletion in Parkinsonian patients treated with L-dopa, benserazide and carbidopa.

1. Benserazide and carbidopa, decarboxylase inhibitors used in the treatment of Parkinson's disease, have been shown to inhibit the enzyme kynurenine hydrolase in rat and mouse liver. This results in reduced synthesis of nicotinamide coenzymes from tryptophan, and hence an increased reliance on dietary niacin. 2. Pellagra might be expected as a result of this inhibition of endogenous synthesis of nicotinamide nucleotides, but has not been reported in patients treated with either drug. 3. The urinary excretion of N1-methyl-nicotinamide, a product of nicotinamide nucleotide metabolism, is considerably reduced in patients treated with dopa alone or in combination with an inhibitor of peripheral dopa decarboxylase, to as low as 40% of the control value. This means that many of these patients could be classified as 'at risk' of niacin deficiency, even if not frankly deficient. 4. Patients treated with dopa plus a decarboxylase inhibitor, but not those treated with dopa alone, also show a reduced excretion of xanthurenic acid, and an increased excretion of kynurenine, as would be expected after inhibition of the kynurenine pathway, and possibly indicative of marginal vitamin B6 deficiency.

Adolescent↗
PubMed1979

Backward walking and circling: behavioural responses induced by drug treatments which cause simultaneous release of catecholamines and 5-hydroxytryptamine.

1 The roles of catecholamine and 5-hydroxytryptamine (5-HT) release in mediating backward walking and circling were studied in rats. 2 These behaviours occurred in animals given 15 mg/kg intraperitoneally of (+)-amphetamine (which predominantly releases catecholamines) or either p-chloroamphetamine or fenfluramine (which predominantly release 5-HT). They also occurred when smaller doses of (+)-amphetamine (5 mg/kg) and either p-chloroamphetamine (2--5 mg/kg) or fenfluramine (5 mg/kg) were given together. 3 Characteristic dopamine-dependent behaviours (rearing, licking, gnawing) resulting from (+)-amphetamine injection were greatly reduced by p-chloroamphetamine or fenfluramine. 4 Characteristic 5-HT-dependent behaviours (wet dog shake, hind limb abduction) resulting from injection of either p-chloroamphetamine or fenfluramine were unaffected by (+)-amphetamine. 5 Fragmentary backward walking and circling resulting from levallorphan injection (50 mg/kg s.c.) were decreased by (+)-amphetamine at low dosage. 6 Results in general strengthen previous evidence that backward walking and circling are mediated by simultaneous dopamine and 5-HT release. 7 The possible relevance of the above findings to hallucinogenic activity, amphetamine psychosis, schizophrenia and abnormal movements due to L-DOPA treatment is discussed.

Amphetamines↗
PubMed1979

Tiapride in levodopa-induced involuntary movements.

Tiapride, a substituted benzamide derivative closely related to metoclopramide, reduced levodopa-induced peak dose involuntary movements in 16 patients with idiopathic Parkinson's disease. However, an unacceptable increase in disability from Parkinsonism with aggravation of end-of-dose akinesia led to its cessation in 14 patients. Tiapride had no effect on levodopa-induced early morning of "off-period" segmental dystonia. These results fail to support the notion that levodopa-induced dyskinesias are caused by overstimulation of a separate group of dopamine receptors.

Aged↗
PubMed1979

Spinal internuncial neurones in progressive encephalomyelitis with rigidity.

The clinical and pathological features of a fourth patient with progressive encephalomyelitis with rigidity are reported and compared with those previously described. It is suggested that the muscular rigidity, abnormal postures, painful muscular spasms, and myoclonus are a product of excessive and abnormal discharges of alpha motor neurones caused by their release from control by spinal internuncial neurones. A count of neuronal perikarya in the ventral horns confirmed that the disease selectively destroyed small and medium sized neurones, most of which were spinal internuncial neurones. Experimental, clinical, and pathological evidence concerning spinal internuncial neurones is reviewed and found to conform to this theory. The pathogenesis of opsoclonus may be similar.

Astrocytes↗
PubMed1978

Deprenyl administration in man: a selective monoamine oxidase B inhibitor without the 'cheese effect'.

After pretreatment with the selective monoamine oxidase B inhibitor, (-)-deprenyl, in doses sufficient for complete inhibition of the platelet enzyme, 4 normal and 6 parkinsoniam volunteers (2 receiving levodopa and 2 levodopa plus carbidopa) suffered no adverse pressor reaction ('cheese effect') after challenge with oral tyramine in amounts considerably greater than those likely to be encountered in a normal diet. Nor did the levodopa-deprenyl combination itself result in a pressor response. Normal human intestinal mucosa was shown predominantly to contain the deprenyl-insensitive A form of the enzyme, which presumably degraded administered tyramine in the deprenyl-treated volunteers; even those receiving the drug for prolonged periods manifested no 'cheese effect', suggesting that the A form remained uninhibited. Intestinal monoamine oxidase A was able to oxidise dopamine, whereas in human platelet or striatum the amine is a monoamine oxidase B substrate. Like tyramine, oral phenylethylamine challenge with amounts greater than those known to be present in a normal diet similarly gave rise to no adverse reaction in (-)-deprenyl-treated subjects; the reasons for this remain to be determined.

Adult↗
PubMed1978

Endocrine aspects of bromocriptine therapy in Parkinsonism.

Plasma growth hormone (GH) concentrations in Parkinsonian patients following 3 months optimum therapy with bromocriptine showed no significant change from pretreatment values, whilst plasma prolactin concentrations were uniformly suppressed. Pretreatment GH and prolactin levels were unrelated to clinical disability, and no correlation between hormonal changes and therapeutic response was found. These results suggest the presence of different dopaminergic receptor mechanisms for GH and prolactin release as well as between the extrapyramidal and neuroendocrine systems.

Bromocriptine↗
PubMed1978

Baclofen in Parkinson's disease.

In a controlled trial, baclofen (mean dose 45 mg daily) signficantly increased disability from Parkinsonism in 12 patients with the long-term levodopa syndrome. Peak dose choreoathetosis was not improved but benefit was observed in all four patients with "off period dystonia." Adverse side effects were common and severe, and included visual hallucinations, vomiting, and dizziness.

Aged↗
PubMed1977

Deprenyl in Parkinson's disease.

In a double-blind crossover trial, (-)-deprenyl, a fast-acting selective monoamine-oxidase-B inhibitor without a "cheese effect", was given to 41 patients with idiopathic Parkinson's disease who were receiving maximum tolerated doses of levodopa either alone or combined with carbidopa ("Sinemet"). In a dose of 10 mg, daily or on alternate days, (-)-deprenyl prolonged the therapeutic effect of levodopa and was effective in mild "on-off" disabilities with end-of-dose akinesia; the majority of patients with nocturnal and early-morning akinesia also improved. No statistically significant improvement occurred in diurnal akinesia, and there was no improvement in patients with severe on-off disabilities with freezing and rapid oscillations ("yo-yo" effect). Levodopa-induced dyskinesias were aggravated in 14 patients. In 5 previously untreated patients, (-)-deprenyl alone gave no benefit, but when it was used with levodopa and carbidopa a mean dosage reduction of 200 mg levodopa daily was possible. Depression, present in 15 patients, was unchanged. (-)-Deprenyl in combination with smaller total daily doses of levodopa and a peripheral decarboxylase inhibitor may prove useful in reducing the frequency and severity of some types of on-off effect with overall benefit comparable to that obtained with larger doses of levodopa.

Adult↗