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Biomedical subjects

J D Gillies

Publications and source records attributed to J D Gillies.

At least 19 recordsLinked to original sources

Early use of inhaled nedocromil sodium in children following an acute episode of asthma.

BACKGROUND: Current guidelines on the treatment of childhood asthma recommend the introduction of an anti-inflammatory drug in children who have persistent symptoms and require regular treatment with a bronchodilator. The efficacy and safety of inhaled nedocromil sodium (Tilade Mint aerosol) administered using a Fisonair spacer at a dose of 4 mg three times daily was compared with placebo in the treatment of asthmatic children aged 6-12 years who are symptomatic and recovering from an acute exacerbation of asthma. METHODS: A group comparative, double blind, placebo controlled trial was performed in children who were recovering from an acute episode of asthma following treatment in the emergency department of the hospital or in children referred from their general practitioner following a wheezing episode and documented evidence of at least two previous episodes of wheezing. A two week baseline period on existing bronchodilator treatment was followed by a 12 week treatment period on either nedocromil sodium (2 mg/puff) or placebo. Both treatments were administered using a Fisonair spacer at a dose of two puffs three times daily. Changes from baseline values in daytime asthma and night time asthma symptom scores, usage of rescue bronchodilators, mean peak expiratory flow (PEF) recorded twice daily on diary cards, patients' opinion of treatment, and withdrawals due to treatment failure were measured during the primary treatment period (last six weeks of treatment). RESULTS: One hundred and forty two children aged 6-12 years entered the baseline period. Sixty three were withdrawn due to failure to meet the entry criteria (18) or the criteria for asthma symptom severity (15) or reversibility (9), because they developed uncontrolled asthma (2), because they took disallowed treatment (2), or for other non-trial related reasons (17). Seventy nine patients (46 boys) of mean age 8. 8 years entered the treatment period. There were significant differences in the changes from baseline values during the last six weeks of treatment in favour of nedocromil sodium compared with placebo in the primary variables of daytime asthma and night time asthma, morning and evening PEF, and the usage of rescue inhaled bronchodilators; 53% of patients reported nedocromil sodium to be very or moderately effective compared with 44% placebo. Improvement in asthma symptoms, PEF, and reduction in use of rescue bronchodilators did not reach statistical significance until after six weeks of treatment. Twenty two patients were withdrawn or dropped out during the treatment phase, 12 due to uncontrolled asthma or persistence of asthma symptoms, four due to suspected adverse drug reactions (nedocromil sodium 3 (headaches 2, angio-oedema/urticaria 1), placebo 1(persistent cough)), and six due to non-treatment related reasons. Seventy one adverse events were reported by 27 patients in the nedocromil group and 75 by 30 patients in the placebo group. CONCLUSIONS: Asthma symptoms, use of bronchodilators, and lung function can be improved significantly in children recovering from an acute exacerbation of asthma or wheeze and currently receiving treatment with bronchodilators alone by the addition of inhaled nedocromil sodium at a dose of 4 mg three times daily administered using a Fisonair holding chamber.

Acute Disease↗

Dose response of subcutaneous terbutaline and epinephrine in children with acute asthma.

In a double-blind dose response study in 26 children, 3, 6, or 12 microgram/kg of terbutaline sulfate was compared with 10 microgram/kg of epinephrine administered subcutaneously. In the first hour after injection, all doses of terbutaline and epinephrine resulted in improvement in mean clinical score, mean forced vital capacity, mean forced expiratory volume in the first second, and mean forced expiratory flow from 25% to 75% of vital capacity. Terbutaline epinephrine. However, while adverse effects following terbutaline were clinically imperceptible, epinephrine produced unpleasant headache and excitement in a few patients. Terbutaline did not change mean PaO2 or PaCO2 significantly in a subgroup of patients. The 12 microgram/kg dose of terbutaline was superior to 3 or 6 microgram/kg in relieving obstruction to airflow measured at the midportion of the vital capacity. This dose caused tremor in some children, but the tremor was not apparent to patients or their parents.

Adolescent↗

Vegetative state following coma in childhood: evolution and outcome.

The data have been analysed for 17 children who showed features of the vegetative state following an acute illness that resulted in coma. 15 were under three years of age. Diffuse anoxia/ischaemia (N=12) and meningitis (N=4) were the most common causes of the comatose state. Seven children died, and nine of the 10 survivors have remained severely neurodevelopmentally handicapped, with no cognitive function (follow-up two months to five years). One child became ambulant a year after the initial insult and is moderately retarded. The findings suggest that children who develop the vegetative state following an illness resulting in coma have a poor prognosis and that decorticate or decerebrate responses, roving eye-movements and spontaneous blinking may be early indicators of its emergence.

Brain↗

Radiologic assessment of severity of acute asthma in children.

In this prospective study, chest radiographs were obtained in 23 children during 33 acute asthmatic episodes. The degree of hyperinflation was assessed radiologically by three methods and compared to the clinical findings. There was no correlation between the radiologic impression of hyperinflation and the clinical severity of the asthmatic episode.

Adolescent↗

Sural nerve effects on medial gastrocnemius motoneurones in the cat.

1. Excitability cycles for medial gastrocnemius motoneurones were recorded following sural nerve stimuli with amplitudes of 1.5, 3, 5, 10 and 40 times the nerve threshold. The monosynaptic reflex was time-integrated to quantify the motoneuronal output and some implications of this technique are discussed. In particular it is calculated that this method specifically examines the 15-25% most excitable motoneurones of the medial gastrocnemius pool.2. In most cases high amplitude stimulation of the sural nerve caused a triphasic (excitatory-inhibitory-excitatory) change in excitability. Arguments are given to support the conclusion that this represents a corresponding post-synaptic alteration in medial gastrocnemius motoneurone potential. It is concluded that this pattern illustrates the nature of the sural nerve projections to this portion of the medial gastrocnemius pool.3. The first period of excitation began after a latency, corrected to be compatible with intracellular recordings, of 2.8 ms and had a mean duration of 4.0 ms. The minimum stimulus level necessary for this effect lay between 1.5 and 3 times the nerve threshold. The maximum amplitude of this facilitation occurred with stimuli of 3-5 times threshold and was 60-90% of the amplitude of the monosynaptic facilitation which followed stimulation of the lateral gastrocnemius-soleus nerve.4. A period of inhibition followed immediately after the period of excitation and had a mean duration of 16 ms. The minimum stimulus level necessary for this effect lay between 1.5 and 3 times the nerve threshold and the degree of inhibition increased with stimuli up to 40 times threshold.5. The second period of excitation lasted a mean period of 50 ms and was due to activity in high threshold fibres. On average its amplitude was 50% that of the initial excitation.6. Exceptions to this triphasic variation of excitability were found. This result is interpreted as indicating the presence of projections with opposing actions which were simultaneously activated by sural stimuli.

Animals↗

Radiologic findings in acute childhood asthma.

One hundred and seventy-eight admissions of 142 children with acute asthma were reviewed and graded for clinical severity. Abnormalities including consolidation (21%), atelectasis (3%) and pneumomediastinum (2%) were found on chest radiographs, most commonly in patients with clinically moderate or severe acute asthma. Hyperinflation proved difficult to assess, but was present in only 67% of admissions using the criteria described. The frequency of complications detected justifies the use of chest radiographs in assessing children admitted to hospital for acute asthma.

Adolescent↗

Effects of neostigmine and pyridostigmine at the neuromuscular junction.

The effect of subcutaneous administration of pyridostigmine or neostigmine for 7 to 15 days on neuromuscular transmission has been studied in the rat phrenic nerve-hemidiaphragm preparation. The quantal contents of end-plate potentials at different stimulus rates and the amplitude and frequency of miniature end-plate potentials were compared with those of untreated controls. The rate of release of acetylcholine quanta at high stimulus rates, and the frequency of miniature end-plate potentials, were reduced by pretreatment with both pyridostigmine and neostigmine. Presynaptic effects differed in that the number of quanta released by each nerve impulse at a stimulus rate of 1/sec was not altered by pyridostigmine, but was reduced to 52% of normal by neostigmine. The amplitude of miniature end-plate potentials was reduced to 81% by pretreatment with neostigmine and to 54% by pretreatment with pyridostigmine. The cause appears to be a reduction in the number of acetylcholine receptor sites as a result of disorganisation of the postsynaptic muscle membrane, which may contribute to the muscular weakness associated with the long term use of anticholinesterase agents.

Animals↗

The continual administration of neostigmine and the neuromuscular junction.

The effect of continual administration of neostigmine on the neuromuscular junction of the rat diaphragm was examined by determining the number of quanta of acetylcholine released by each nerve impulse, the effect of differing repetition rats on quantal release and the amplitude and frequency of miniature end-plate potentials. The number of quanta of acetylcholine released at a nerve impulse repetition rate of 1/sec was reduced to 51% of normal in treated animals. The reduction was greater at faster repetition rates. The amplitude of miniature end-plate potentials was reduced to 75% of normal. This reduction appears to be due to blocking of receptor sites rather than the reduction in the amount of acetylcholine in each quantum. The frequency of spontaneous miniature end-plate potentials was reduced in treated animals.

Acetylcholine↗