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Biomedical subjects

J G Gleeson

Publications and source records attributed to J G Gleeson.

30 records · Page 2Linked to original sources
PubMed1997

Linkage and physical mapping of X-linked lissencephaly/SBH (XLIS): a gene causing neuronal migration defects in human brain.

While disorders of neuronal migration are associated with as much as 25% of recurrent childhood seizures, few of the genes required to establish neuronal position in cerebral cortex are known. Subcortical band heterotopia (SBH) and lissencephaly (LIS), two distinct neuronal migration disorders producing epilepsy and variable cognitive impairment, can be inherited alone or together in a single pedigree. Here we report a new genetic locus, XLIS, mapped by linkage analysis of five families and physical mapping of a balanced X;2 translocation in a girl with LIS. Linkage places the critical region in Xq21-q24, containing the breakpoint that maps to Xq22.3-q23 by high-resolution chromosome analysis. Markers used for somatic cell hybrid and fluorescence in situ hybridization analyses place the XLIS region within a 1 cM interval. These data suggest that SBH and X-linked lissencephaly are caused by mutation of a single gene, XLIS, that the milder SBH phenotype in females results from random X-inactivation (Lyonization), and that cloning of genes from the breakpoint region on X will yield XLIS.

Cerebral Cortex↗
PubMed1991

The action of MPTP on synaptic transmission is affected by changes in Ca2+ concentrations.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) causes a disruption of nigrostriatal dopaminergic function which resembles parkinsonism. On the cellular level, the disruption involves a Ca2+ independent release of dopamine, depletion of nigral and striatal dopamine, and the death of dopaminergic neurons. We have previously reported that MPTP can cause a non-reversible inhibition of neostriatal synaptic transmission. In this study we investigated the effect of altering Ca2+ concentration on MPTP's actions in the mouse nigrostriatal brain slice. We report finding that the MPTP induced non-reversible decrease in N-2 amplitude did not occur if synaptic transmission had been blocked using a low Ca2(+)-high Mg2+ artificial cerebrospinal fluid (ACSF) during MPTP application. Low Ca2(+)-high Mg2+ ACSF did not however alter the decrease in slice dopamine content caused by MPTP. These data provide initial support for the hypothesis that MPTP's ability to alter functional synaptic transmission is Ca2+ dependent whereas its releasing action on dopamine is Ca2+ independent.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1990

Placebo controlled trial of systemic corticosteroids in acute childhood asthma.

In a randomised controlled trial 38 asthmatic children aged 2-11 yr who had not received regular oral or inhaled steroids during the previous year, were treated with a standard regime of nebulised salbutamol and intravenous aminophylline plus either hydrocortisone and oral prednisolone for 5 days, or placebo. The children were observed throughout their hospital stay and for 3 months afterwards. There was a greater fall in heart rates in the steroid treated group on the second day of treatment (mean diff. 16 beats/min) and at discharge (mean diff. 13 beats/min); p less than 0.025. Peak Expiratory Flow Rates recorded in 26 children, 13 in each group, showed more improvement on day 2 in those given steroids (mean diff 16% predicted); p less than 0.05. This difference was not apparent at discharge but 9 children treated with steroids were clinically wheeze-free when they left hospital compared with 3 in the placebo group, p less than 0.05. There were no differences in respiratory rate, pulsus paradoxus and arterial oxygen saturation. Trends in duration of hospital stay and relapse rate during the succeeding 3 months favoured active treatment. These findings support the use of systemic corticosteroids in addition to high dose bronchodilators to treat 'non steroid dependent' children hospitalised with acute severe asthma.

Acute Disease↗
PubMed1989

Aminophylline dosage in acute severe asthma.

In 27 cases of acute severe asthma, a loading dose of 5 mg/kg of aminophylline (omitted if already receiving oral theophylline) followed by a continuous infusion of 1 mg/kg per hour gave satisfactory theophylline levels at 4 h and 24 h. Theophylline clearance rates varied widely, vomiting was common, but unrelated to blood theophylline levels.

Aminophylline↗
PubMed1989

Persistent lung hyperinflation in apparently asymptomatic asthmatic children.

Serial measurements of functional residual capacity (FRC) by helium gas dilution were made in young asthmatic children over a 3 month period. Eight children were recruited during hospitalization for an acute asthma attack and eleven during routine outpatient attendances. Both groups of children had FRC's greater than 120% of that predicted for height at recruitment. Although the children denied symptoms throughout the three month follow-up period the majority remained hyperinflated. These results demonstrate a striking difference between objective and subjective assessment of respiratory function in young children. The significance of this persistent abnormality and its relationship to other lung function indices needs urgent investigation.

Asthma↗
PubMed1988

Controlled trial of budesonide given by the nebuhaler in preschool children with asthma.

OBJECTIVE: To determine whether the inhaled corticosteroid budesonide, given by a Nebuhaler spacing device, was effective in prophylaxis of asthma in preschool children. DESIGN: Double blind, placebo controlled, random order crossover trial with two week practice run in period. SETTING: Outpatient clinic referrals in secondary referral centre. PATIENTS: 39 children aged 2-6 years selected for the following: able to use Nebuhaler; parents able to complete record card; poorly controlled asthma (defined); not already on systemic or inhaled steroids. Eleven withdrew for various reasons not connected with intolerance to budesonide. Age, sex, other atopies, and symptoms during run in period were similar in the 28 children who completed the trial and in the 11 who withdrew. INTERVENTIONS: Budesonide 200 micrograms or placebo (both one puff) given twice daily during 6-week treatment or control periods, using Nebuhaler after prior training. Three week "washout" at crossover. Compliance monitored by weighing canisters. Patients withdrawn if their acute attacks required treatment with systemic steroids. END POINT: Control of asthma. MEASUREMENTS AND MAIN RESULTS: Peak expiratory flow rate measured twice daily where cooperation allowed. Diary of symptoms and concomitant drug use kept daily. Results showed mean peak flow significantly higher (12% in mornings, 14% in evenings) in second three weeks of intervention compared with control period (95% confidence intervals 6.3-17.3% and 7.2-21.0%). Supplementary bronchodilator drugs reduced by 50% during intervention periods. CONCLUSIONS: Budesonide given by Nebuhaler is effective prophylaxis for preschool children with frequent asthma.

Asthma↗
PubMed1988

Nebuhaler technique.

Two Nebuhaler techniques were compared by measuring the response to terbutaline 0.25 mg in 13 asthmatic children. Five breaths each sufficient to operate the Nebuhaler valve resulted in greater bronchodilatation after 10 minutes (P less than 0.05) than two deep inspirations from residual volume each held for 5 seconds. The peak responses were similar and both methods produced significant bronchodilatation compared with placebo. Either method is satisfactory in children but the former is easier to perform.

Adolescent↗
PubMed1988

Inhaled bronchodilator treatment via the nebuhaler in young asthmatic patients.

Changes in functional residual capacity and peak flow rate were measured to assess bronchodilator response to terbutaline inhaled via a nebuhaler. In 10 children with asthma, aged 5-7 years, five breaths sufficient to operate the nebuhaler valve resulted in clinically important improvement in both the functional residual capacity and the peak flow rate. In 18 of 22 children, aged 2-5 years, who were too young to have their peak flow rate measured reliably, terbutaline administered via this modified nebuhaler technique was also associated with a clinically important change in functional residual capacity. The results suggest that effective bronchodilation using a nebuhaler can be achieved even in very young children.

Aerosols↗
PubMed1988

Air or oxygen as driving gas for nebulised salbutamol.

The effects of nebulised salbutamol driven by compressed air or oxygen were compared in a randomised crossover study during 27 attacks of acute asthma. Arterial oxygen saturation fell by 2-6% during or after treatment in 10 cases: seven with compressed air, two with oxygen, and one with both driving gases. Hypoxaemia occurred in younger children and in those who fell asleep, but was not related to the level of arterial oxygen saturation before treatment or the size of the response to bronchodilator therapy. More children fell asleep with compressed air nebulisation. Arterial oxygen saturation improved and heart rates remained stable during treatment when oxygen was the driving gas. After treatment, however, arterial oxygen saturation fell and heart rates rose to values that were similar to those after treatment with compressed air. The falls in arterial oxygen saturation we observed, though comparatively small, would be clinically important on the steep part of the oxygen dissociation curve, and our results emphasise that families with home nebulisers should seek medical advice early when their children develop severe asthma. The benefits of using oxygen as the driving gas during nebulisation were transient, and in severe asthma treatment with oxygen needs to be continued after the nebulised salbutamol has been given.

Acute Disease↗
PubMed1988

Effect of budesonide on pulmonary hyperinflation in young asthmatic children.

In 19 asthmatic children, aged 2-6 years, the effect of six weeks' treatment with inhaled budesonide or placebo on functional residual capacity (FRC--helium dilution) and bronchodilator responsiveness was assessed in a double blind, randomised crossover trial. FRC was increased in most children at the start of treatment. Treatment with budesonide was associated with a reduction in FRC by comparison with placebo (median change 9% v 0%; p less than 0.05). There was a trend towards a greater response to a bronchodilator after budesonide. The results suggest that inhaled corticosteroids reduce hyperinflation in young asthmatic children.

Airway Resistance↗