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Biomedical subjects

V McGovern

Publications and source records attributed to V McGovern.

13 recordsLinked to original sources

Monitoring growth in asthmatic children treated with high dose inhaled glucocorticoids does not predict adrenal suppression.

AIMS: To determine whether routine outpatient monitoring of growth predicts adrenal suppression in prepubertal children treated with high dose inhaled glucocorticoid. METHODS: Observational study of 35 prepubertal children (aged 4-10 years) treated with at least 1000 microg/day of inhaled budesonide or equivalent potency glucocorticoid for at least six months. Main outcome measures were: changes in HtSDS over 6 and 12 month periods preceding adrenal function testing, and increment and peak cortisol after stimulation by low dose tetracosactrin test. Adrenal suppression was defined as a peak cortisol < or =500 nmol/l. RESULTS: The areas under the receiver operator characteristic curves for a decrease in HtSDS as a predictor of adrenal insufficiency 6 and 12 months prior to adrenal testing were 0.50 (SE 0.10) and 0.59 (SE 0.10). Prediction values of an HtSDS change of -0.5 for adrenal insufficiency at 12 months prior to testing were: sensitivity 13%, specificity 95%, and positive likelihood ratio of 2.4. Peak cortisol reached correlated poorly with change in HtSDS (rho = 0.23, p = 0.19 at 6 months; rho = 0.33, p = 0.06 at 12 months). CONCLUSIONS: Monitoring growth does not enable prediction of which children treated with high dose inhaled glucocorticoids are at risk of potentially serious adrenal suppression. Both growth and adrenal function should be monitored in patients on high dose inhaled glucocorticoids. Further research is required to determine the optimal frequency of monitoring adrenal function.

Administration, Oral↗

Prescribing practice for intermittent oxygen therapy: a GP survey.

INTRODUCTION: UK figures show that the prescription of home oxygen cylinders for intermittent use is substantial. AIM: To examine GP assessment criteria and prescribing practice for intermittent oxygen therapy in patients with a diagnosis of chronic obstructive pulmonary disease (COPD) in Northern Ireland. METHODS: A postal questionnaire was sent to all GPs (n = 534) in two health boards who had prescribed cylinder oxygen in a six month period prior to the study. The questionnaire was piloted to establish reliability and validity. RESULTS: Completed questionnaires were returned by 52% (280/534) of GPs. GPs 'most frequently' used advice from hospital specialists [82% (230/280)] to determine the need for intermittent oxygen. Criteria such as breathlessness score on exercise (e.g., BORG), oximetry on exercise, local guidelines or national guidelines were used less frequently or never. CONCLUSIONS: Most patients are likely to have been prescribed intermittent oxygen without any objective assessment. Implementation of evidence-based guidelines and a formal oxygen assessment service, would rationalize the use of intermittent oxygen therapy and enable better targeting of this expensive resource.

Follow-Up Studies↗

Linear growth of very young asthmatic children treated with high-dose nebulized budesonide.

The aim of this open study was to observe linear growth in young children with asthma treated with nebulized budesonide. Infants and young children (< 3 years old) with severe uncontrolled asthma were studied. They were treated with nebulized budesonide (1-4 mg day-1) and treated for at least 6 months. Height standard deviation scores (HtSDS) were measured before ("pre-measurements") immediately prior to commencing nebulized budesonide therapy (baseline) and after at least 6 months of therapy ("post-measurements"). The mean HtSDS score at pretreatment was -0.21 and at baseline had fallen further to -0.46. The mean HtSDS increased to -0.17 when the post-measurements were made (p = 0.035) after at least 6 months of nebulized budesonide therapy. Treatment with nebulized budesonide for longer than 6 months in very young children with severe asthma was not associated with reduced linear growth.

Administration, Inhalation↗

H-NS over-expression induces an artificial stationary phase by silencing global transcription.

Bacteria organize their chromosomes in a complex interwound supercoiled structure called the nucleoid through the action of topoisomerases and a set of small (10-20 kDa) proteins. The two most abundant nucleoid-associated proteins are HU and H-NS. H-NS increases in abundance during stationary phase. Over-expression of HU is well tolerated and compatible with transcription and cell growth. Increasing the concentration of H-NS leads to a rapid silencing of global transcription and produces a growth-arrested state reminiscent of stationary phase. H-NS over-expression also induces a substantial loss of supercoiling in plasmid DNA during the time that transcription is arrested. Comparing the effects of over-expression of these two proteins gives some insight into the differential roles of these proteins in the activity of the chromosome. These observations are interpreted in a model of nucleoid organization.

Bacterial Outer Membrane Proteins↗

Mutations altering chromosomal protein H-NS induce mini-Mu transposition.

Bacteriophage Mu is one of the most efficient transposons known, capable of moving a hundred viral copies to new positions in the bacterial chromosome in an hour. Mu also forms stable lysogens. In bacteria lysogenic for the defective protein fusion-forming phage MudII1681, which can transpose and replicate but does not encode genes for DNA packaging and cell lysis, the frequency of transposition changes as colonies age. To find host genes that alter the spontaneous Mu transposition frequency, we used a genetic screen with mini-MudlacZ fusion formation as an assay. H-NS (also called H1a and B1) is an abundant nonspecific DNA-binding protein localized to the bacterial chromosome. H-NS has an unusual structure of interspersed patches of acidic and basic residues reminiscent of eukaryotic HMG proteins. Mutations in hns caused an increase in Mu-specific transcription and a dramatic increase in MudII1681 transposition rates when cells were put under certain growth conditions. Purified H-NS stabilized Mu repressor-DNA complexes in vitro, suggesting that H-NS contributes to the organization of transcriptionally inactive DNA in vivo.

Amino Acid Sequence↗

Concentration dependent alterations of DNA replication initiation and elongation by benzo[a]pyrene diol epoxide.

Vero cells treated with various concentrations of (+/-)7 beta, 8 alpha-dihydroxy-9 alpha, 10 alpha-epoxy, 7,8,9,10-dihydrobenzo[a]pyrene (BP-diol epoxide I) exhibited dose-dependent inhibition in both the rate of DNA synthesis and in the size of nascent DNA. The maximum inhibition was seen 2--3 h after addition of BP-diol epoxide I. A recovery in both the rate of synthesis and size of nascent DNA was observed 5--10 h after treatment. The pH step alkaline elution assay which separates different nascent DNA replication intermediates was used to investigate whether the inhibition and recovery noted above could be accounted for by alterations in DNA replication initiation (DNA synthesis within a replicon) or elongation (rejoining of replicons). At lowest dose studied (0.166 muM BP-diol epoxide I) a reversible inhibition in DNA initiation was observed. At the higher dose levels (0.66 muM and 1.66 muM BP-diol epoxide I) inhibition of both DNA initiation and elongation were observed and inhibition of elongation predominated. The inhibition in elongation was detected by an increase in the relative amount of low molecular weight nascent DNA associated with DNA synthesis within a replicon and a relative decrease in the higher molecular weight elongated DNA. A reversal in the inhibition of both initiation and elongation was noted.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗

Quantification of interventions and outcomes in an outpatient telemanagement and care management congestive heart failure program.

The congestive heart failure continuum was developed in collaboration with the medical management committee of our hospital in response to a need to decrease readmissions for this chronic and progressive disease. This is accomplished via a multidisciplinary team that provides education and long-term telemanagement, as well as care management to assist these patients in maintaining an optimum level of functioning and the ability to remain in their homes for as long as possible. Since October 1996 there have been 375 patients referred with a decrease in the 31-day readmission rate from 21% to an average of 5%. Costs are presently $55.00 per month per patient. Evaluation of the congestive heart failure phone management tool revealed a strong 77% positive correlation between the patient's score and the number of interventions needed to stabilize the patient. Care management visits, when necessary, help reduce the need for hospitalization. (c)2000 by CHF, Inc.

Journal Article↗