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Biomedical subjects

J Mally

Publications and source records attributed to J Mally.

10 recordsLinked to original sources
PubMed1995

Efficacy of an adenosine antagonist, theophylline, in essential tremor: comparison with placebo and propranolol.

Propranolol, which has long been used as the standard treatment for essential tremor, has been compared with placebo and theophylline in ten newly diagnosed patients without other, prior drug treatments. Patients were treated for four weeks with one drug, followed by placebo for four weeks, and then the second drug for the same period, in a blind cross-over trial. Tremor was quantified using the volumetric method, and was decreased significantly after one week on propranolol, 80 mg/day. Theophylline 150 mg/day reduced tremor to the same extent, although the improvement was not significant until the second week. Three patients reported side effects on propranolol. It is suggested that theophylline may be a useful alternative agent in the treatment of essential tremor, probably due to a chronic up-regulation of adenosine receptors.

Adenosine↗
PubMed1995

Delayed development of symptomatic improvement by (--)-deprenyl in Parkinson's disease.

Twenty de novo patients with Parkinson's disease (Hoehn-Yahr stages I, II, III) were studied in a double blind trial after introducing (--)-deprenyl monotherapy. The parkinsonian symptoms were assessed by a novel graded clinical rating scale, by UPDRS and by the North Western self-rating scale. A significant change was observed in motor behaviour and daily activity (UPDRS) after 3 weeks of treatment with (--)-deprenyl at 10 mg/day. The total scores using UPDRS and the North Western ratings were changed significantly after 4 weeks. The greatest changes observed were in walking and in hypokinesia. Rigidity was not modified by (--)-deprenyl.

Aged↗
PubMed1994

The effect of theophylline on parkinsonian symptoms.

Adenosine is known to inhibit the release of dopamine from central synaptic terminals. The present open trial was therefore conducted to determine whether the adenosine receptor-antagonist theophylline would be of value in Parkinson's disease. Fifteen parkinsonian patients were treated for up to 12 weeks with a slow release oral theophylline preparation (150 mg day-1), yielding serum theophylline levels of 4.44 mg L-1 after one week. The patients exhibited significant improvements in mean objective disability scores and 11 reported moderate or marked subjective improvement. It is suggested that theophylline might be a useful adjunct to the routine therapy of parkinsonian patients.

Administration, Oral↗
PubMed1993

Assessing the impact of essential tremor on upper limb function.

We compared the impact of essential tremor on the performance of three manual tasks: drawing spirals, holding a cup full of water and a joystick-controlled tracking test. Tremor amplitude and frequency were measured by accelerometry during the tracking test, when holding the cup and whilst a standard posture was maintained. The inter-relationships between tremor amplitude, frequency and task impairment were then examined. The results showed that the amplitude and frequency of essential tremor (measured from the principal spectral peak) changed with different activities, with the mildest postural tremors changing most in frequency (by up to 4-5 Hz). The amplitude of tremor decreased in almost every case during the tasks, relative to posture, and this decrement was greatest for the most severe tremors. We also demonstrate that for practical purposes, such as routine clinical situations and therapeutic trails, the effect of essential tremor upon upper limb function can be usefully assessed by two simple complementary techniques: rating spirals and measuring the volume of water split from a cup. The impairments in carrying out these tasks and the tracking test were highly correlated with one another and also with the amplitude and frequency of postural tremor. The concept of tremor "suppressability" is introduced: the relative percentage decrease in the amplitude of a particular tremor during the performance of a specific task compared to that recorded whilst holding a standard posture.

Acceleration↗
PubMed1992

Theophylline concentrations in serum, saliva, and cerebrospinal fluid in patients with essential tremor.

Theophylline concentrations in saliva and serum were compared in 20 patients with essential tremor. There was a strong correlation between the concentrations in saliva and serum (r = 0.9, slope of 0.48). The ratio between unbound and bound theophylline as assessed by ultrafiltration was 0.30. This ratio was similar to that between theophylline concentrations in CSF and serum. The theophylline concentration in serum was not predictable from that obtained in saliva in individual cases. Moreover, the levels in saliva were about 20% higher than the unbound concentrations of theophylline in serum.

Adult↗
PubMed1991

The effect of theophylline on essential tremor: the possible role of GABA.

The chronic administration of theophylline was studied in twenty patients with essential tremor in a double-blind cross-over trial. The tremor was improved significantly after four weeks of treatment. In mice the chronic administration of theophylline was compared with propranolol on the modulation by adenosine, 5-HT, (-)isoprenaline or GABA of NMDA-induced depolarisation of neocortical slices. Adenosine depolarisation was abolished by two-weeks treatment with theophylline but not propranolol. Potentiation by (-)isoprenaline of NMDA responses was reduced by theophylline (100 mg/kg/day) and propranolol treatment (25 mg/kg/day), but a lower dose of propranolol further increased it. The enhancement by 5-HT of NMDA-induced depolarisation was unaffected by the pretreatment with theophylline, while the higher dose of propranolol blocked it. GABA caused no significant change of NMDA depolarisation in control slices, but after theophylline treatment (100 mg/kg/day) and propranolol administration at both doses it significantly potentiated NMDA depolarisation. The enhancement of GABA sensitivity might be an important common factor in decreasing the essential tremor after propranolol and theophylline treatment.

Adenosine↗
PubMed1991

Changes in neurotransmitter sensitivity in the mouse neocortical slice following propranolol and theophylline administration.

1. The mouse neocortical slice has been used to examine the sensitivity of neurones to isoprenaline, 5-hydroxytryptamine (5-HT) and adenosine acutely and following chronic treatment of animals with propranolol or theophylline. 2. While having little effect alone, all three agonists enhanced the d.c. depolarizing potential produced by N-methyl-D-aspartate (NMDA). The effect of (-)-isoprenaline (0.2 microM) was shared by (+)-isoprenaline at the much higher concentration of 10 microM. 3. Superfusion of slices with theophylline or 8-phenyltheophylline blocked responses to adenosine with evidence of selectivity. A single injection of theophylline 24 h before slice preparation did not alter agonist sensitivity, but when administered daily at 100 mg kg-1 for 14 days, the xanthine caused a loss of sensitivity to adenosine and (-)-isoprenaline but not 5-HT. The lower dose of theophylline, 10 mg kg-1 daily, also led to a loss of adenosine responses but no change of sensitivity to the amines. 4. Following the 14 day treatment with theophylline at 100 mg kg-1 daily in two groups of mice, responses to adenosine recovered to control levels after 20 days. 5. Propranolol superfusion blocked responses to both isomers of isoprenaline and 5-HT but did not affect sensitivity to adenosine. 6. Chronic treatment with propranolol at 25 mg kg-1 daily for 14 days induced a loss of sensitivity to (-)-isoprenaline and 5-HT but not adenosine. A lower dose of 5 mg kg-1 daily caused no change in responses to adenosine or 5-HT, but yielded an increased sensitivity to (-)-isoprenaline. 7. The results are discussed with respect to reports of receptor up-regulation in binding studies; caution is clearly required in extrapolating from such work to receptor activity in a functional system, especially in the case of theophylline and adenosine.

Adenosine↗
PubMed1990

Chronic benzodiazepine treatment and cortical responses to adenosine and GABA.

The effects of chronic treatment of mice with clonazepam have been examined on the responses of neocortical slices to adenosine, 5-hydroxytryptamine (5-HT) and gamma-aminobutyric acid (GABA). Responses to these agonists were measured as changes in the depolarisation induced by N-methyl-D-aspartate (NMDA). Added to the superfusion medium diazepam blocked responses to adenosine but not 5-HT; this effect was not observed with 2-chloroadenosine or in the presence of 2-hydroxynitrobenzylthioguanosine. GABA was inactive in control slices but chronic treatment with clonazepam induced responses to GABA and enhanced responses to adenosine but not 5-HT. It is suggested that the induction of GABA responses may reflect the up-regulation of GABA receptors, but the increase of adenosine responses by clonazepam implies that there is no simple relationship between adenosine receptor binding and functional responses.

Adenosine↗
PubMed1990

Theophylline down-regulates adenosine receptor function.

Chronic treatment of animals with caffeine or theophylline has been reported to increase the number of adenosine receptors in the CNS detected by ligand binding, but few functional studies have been performed. In the present study adenosine enhanced depolarising responses to the excitatory amino acid N-methyl-D-aspartate (NMDA) in slices of mouse cerebral cortex. This effect was blocked acutely by theophylline but not by theophylline given 24 h previously. Twenty-four hours after 2 weeks of treatment with this antagonist, however (10 or 100 mg/kg/day) adenosine was no longer effective, sensitivity recovering subsequently. Theophylline treatment also reduced sensitivity to (-)-isoprenaline but not 5-hydroxytryptamine. It is concluded that changes of adenosine receptor number in the brain do not necessarily reflect the induced changes of receptor function.

Adenosine↗