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Biomedical subjects

G Butler

Publications and source records attributed to G Butler.

At least 19 recordsLinked to original sources
PubMed2006

Pleasure or pain? A profile of smokers in Northern England.

OBJECTIVE: To construct a profile of smokers using multiple indices of physical, mental and social health. STUDY DESIGN: Cross-sectional study. METHODS: The setting was Wigan and Bolton Health Authority, an urban district in the North West of England. A random sample of over 15000 adults from the Health Authority adult population completed a written questionnaire. Prevalence ratios were calculated for physical, mental and social health indicators for smokers compared with non-smokers, adjusted for borough, age and deprivation score of place of residence. RESULTS: Smokers were less likely to report their current health as good, and reported a significantly higher prevalence of arthritis, bronchitis, backache and respiratory symptoms. Smokers had more mobility problems and recent severe pain. Smokers had less healthy lifestyles across many behaviours (e.g. poorer diet, taking less regular exercise and more problem drinking). Depression and the proportion of people with a high psychiatric morbidity score were increased. More women smokers reported a lack of social support, and smokers more often reported financial difficulties. Differences were exaggerated by comparing heavy smokers with non-smokers. CONCLUSIONS: Independent of the level of deprivation of their area of residence, smokers have poorer physical, social and mental health, with a dose-response effect. Smoking creates considerable pain, but little evidence of pleasure.

Adult↗
PubMed2006

The effects of growth hormone treatment on health-related quality of life in children.

BACKGROUND/AIMS: The effects of growth hormone deficiency (GHD) on linear growth in children are well documented, but there is less convincing evidence regarding the impact on health-related quality of life (QOL). We examined QOL in children aged 8-16 years with acquired GHD following treatment for malignancy (AGHD) or idiopathic GHD (IGHD) on commencing growth hormone treatment (GHT) over 6 months. We adopted a longitudinal design involving consecutive patients and their families attending clinic over an 18-month period. Mothers and children were invited to complete questionnaires before GHT (T1) and 6 months later (T2). METHODS: Mothers of 22 children (AGHD n = 14; IGHD n = 8) completed standardized measures of child QOL and behaviour. Children completed parallel measures of QOL, short-term memory tasks and fitness either in clinic or at the family home. RESULTS: For children with AGHD, QOL was significantly below population norms at T1 and improved over time. For children diagnosed with IGHD, QOL at T1 was below, but comparable with population norms. QOL improved over time, though not significantly. CONCLUSION: GHT is potentially valuable for improving QOL in children, especially in cases of AGHD. We conclude that benefits of GHT for QOL need to be evaluated independent of different diagnostic groups.

Adolescent↗
PubMed2005

Growth hormone treatment and quality of life among survivors of childhood cancer.

BACKGROUND: We report the health-related quality of life (QOL) of survivors of childhood cancer (acute lymphoblastic leukaemia, ALL, or central nervous system, CNS, tumour), and whether or not they had growth hormone deficiency (GHD) requiring growth hormone treatment (GHT). METHOD: We assessed 77 survivors of childhood ALL (n = 51) or CNS tumours (n = 26), aged between 8-18 years, and free from disease for > or = 4 years. Survivors and their mothers independently rated survivors' QOL, and mothers completed semi-structured interviews to determine their views of the benefits and disadvantages of GHT. RESULTS: Survivors, especially those treated for a CNS tumour, reported poorer QOL compared with UK population norms. Although survivors of ALL reported better QOL than survivors of CNS tumours, there were no differences depending on whether or not they were prescribed GHT. However, mothers reported that those prescribed GHT had worse QOL than those not. All but 2 survivors were responsible for their own injections. A minority of mothers were disappointed with the child's rate of growth, and reported that children experienced pain with injections. CONCLUSION: We conclude that QOL in survivors of childhood cancer is compromised compared with the normal population, especially following CNS tumours. Longitudinal studies are vital to determine whether GHT can contribute to improved QOL for cancer survivors, especially those who experience more intensive initial therapy regimes.

Adolescent↗
PubMed2005

Population impact of stricter adherence to recommendations for pharmacological and lifestyle interventions over one year in patients with coronary heart disease.

STUDY OBJECTIVE: To assess the potential number of lives saved associated with the full implementation of aspects of the National Service Framework (NSF) for coronary heart disease (CHD) in England using recently developed population impact measures. DESIGN: Modelling study. SETTING: Primary care. DATA SOURCES: Published data on prevalence of acute myocardial infarction and heart failure, baseline risk of mortality, the relative risk reduction associated with different interventions and the proportion treated, eligible for treatment and adhering to each intervention. MAIN RESULTS: Adopting the NSF recommendations for pharmacological interventions would prevent an extra 1027 (95% CI 418 to 1994) deaths in post-acute myocardial infarction (AMI) patients and an extra 37 899 (95% CI 25 690 to 52 503) deaths in heart failure patients in the first year after diagnosis. Lifestyle based interventions would prevent an extra 848 (95% CI 71 to 1 614) deaths in post-AMI patients and an extra 7249 (95% CI 995 to 16 696) deaths in heart failure patients. CONCLUSIONS: Moving from current to "best" practice as recommended in the NSF will have a much greater impact on one year mortality rates among heart failure patients compared with post-AMI patients. Meeting pharmacological based recommendations for heart failure patients will prevent more deaths than meeting lifestyle based recommendations. Population impact numbers can help communicate the impact on a population of the implementation of guidelines and, when created using local data, could help policy makers assess the local impact of implementing a range of health care targets.

Aged↗
PubMed2003

Congenital adrenal hypoplasia presenting as a chronic respiratory condition.

We describe two children with oxygen dependence, which resolved when congenital adrenal hypoplasia was diagnosed and treatment initiated. Chronic respiratory distress can be a symptom of adrenal hypoplasia and this should be taken into consideration when investigating a child with unexplained chronic respiratory difficulties. Respiratory symptoms resolve very quickly when the underlying condition is recognised and treated.

Adrenal Gland Diseases↗
PubMed2003

IGF-I and IGF-binding protein-3 measurements on filter paper blood spots in children and adolescents on GH treatment: use in monitoring and as markers of growth performance.

BACKGROUND/AIM: In childhood an appropriate response to GH treatment is achieved by titration of growth response against dose administered, with careful observation for side-effects. In order to evaluate the potential use of IGF monitoring in children treated with GH, a cross-sectional study has been carried in 215 children and adolescents (134 with GH deficiency (GHD), 54 with Turner syndrome (TS) and 27 with non-GHD growth disorders) treated with GH for 0.2-13.7 years. METHODS: IGF-I and IGF-binding protein-3 (IGFBP-3) were measured in ELISAs, using dried capillary blood collected onto filter papers. Results were expressed as the mean S.D. range (SDS). Values of either analyte < -2 or > +2 SDS were considered abnormal. RESULTS: IGF-I and IGFBP-3 SDS were higher in the TS and non-GHD groups (mean +0.01 and +0.1 respectively) than in those with GHD (mean value -0.6). Nineteen per cent of the IGF-I values (13% low, 6% high) and 12% of IGFBP-3 values were abnormal (10% low, 2% high). Abnormalities, either low or high, were most common in the GHD group. There was a weak but significant relationship between change in height SDS over the Year up to the time of sampling in the whole group and IGF-I SDS. Satisfactory growth performance (+0.5>change in height SDS> -0.5) was found in those with high (7.2%), normal (60%) and low (9.3%) IGF-I levels. Overall, it was estimated that 26% of the tests would indicate that an adjustment to GH dose (up in 18% and down in 8%) could be considered. CONCLUSIONS: From this cross-sectional study of IGF monitoring across a broad range of diagnoses and ages, it can be concluded that the majority of children on GH have normal levels of IGF-I and IGFBP-3, but 26% of tests could suggest that a change of GH dose should be considered. Regular monitoring of IGF-I and IGFBP-3 should be considered in any child on GH treatment.

Adolescent↗
PubMed2001

Overlapping and distinct roles of the duplicated yeast transcription factors Ace2p and Swi5p.

The yeast transcription factors Ace2p and Swi5p regulate the expression of several target genes involved in mating type switching, exit from mitosis and cell wall function. We describe the analysis of 12 novel targets, some regulated by Ace2p or Swi5p alone and some by both. We show that Ace2p is the major regulator of four genes (CTS1, YHR143W, SCW11 and YER124C). Expression of all four is inhibited by Swi5p. Like Cts1p and Scw11p, the two new Ace2p targets are associated with cell wall metabolism. Yhr143p is localized to the cell wall, and deletion affects cell separation and enhances pseudohyphal growth. Deleting YER124C also affects cell separation and sensitivity to drugs targeted against the cell wall. Expression of PIR1, YPL158C and YNL046W is dependent on Swi5p alone. In contrast, expression of YBR158W, YNL078W and YOR264W is minimized when both ace2 and swi5 are disrupted. We propose that, although Ace2p and Swi5p co-operate to induce the expression of a subset of genes, some functional divergence has occurred. This results in a delay in the expression of those genes predominantly regulated by Ace2p, compared with those predominantly regulated by Swi5p.

Cell Cycle Proteins↗
PubMed2001

Temporal effects on the composition of a population of Sinorhizobium meliloti associated with Medicago sativa and Melilotus alba.

An assessment was made of the impact of temporal separation on the composition of a population of Sinorhizobium meliloti associated with Medicago sativa (alfalfa) and Melilotus alba (sweet clover) grown at a single site that had no known history of alfalfa cultivation. Root nodules were sampled on six occasions over two seasons, and a total of 1620 isolates of S. meliloti were characterized on the basis of phage sensitivity using 16 typing phages. Plant infection tests indicated that symbiotic S. meliloti were deficient in the soil at the time of planting and that these bacteria were present at low density during the first season (<10(2)/g of soil); in the second season numbers increased markedly to about 10(5)/g of soil. Overall, 37 and 51 phage types, respectively, were encountered among the nodule isolates from M. sativa and M. alba. The data indicate significant temporal shifts in the frequency and diversity of types associated with the two legume species. Apparent temporal variation with respect to the frequency of types appeared largely unpredictable and was not attributable to any one sampling time. The results indicate an apparent reduction in phenotypic diversity over the course of the experiment. Differential host plant selection of specific types with respect to nodule occupancy was indicated by significant interactions between legume species and either the frequency or diversity of phage types. Isolates from M. sativa that were resistant to lysis by all typing phages (type 14) were unusual in that they were predominant on this host at all sampling times (between 53% and 82% nodule occupancy) and were relatively homogeneous on the basis of DNA hybridization with 98% of the isolates analysed sharing the same nod EFG hybridization profile. In contrast, those isolates from M. alba comprising type 14 were encountered at low total frequency (2%) and were genetically heterogeneous on the basis of Southern hybridization. The implications of the observed temporal and host plant variation for ecological studies are discussed.

Bacteriophage Typing↗
PubMed2001

An open-label acceptability study of Norditropin SimpleXx--a new liquid growth hormone formulation.

A new liquid formulation of hGH (Norditropin SimpleXx) has been developed to avoid the need for reconstitution before administration. In addition, the liquid GH formulation has been combined with an advanced pen delivery system, either with or without a needle auto-insertion mechanism. This study was designed to assess the acceptability of the new system compared with the patient's previous system. A total of 103 children with GH deficiency received a daily injection of Norditropin liquid GH for 12 weeks with a choice of a pen/auto-insertion system. Acceptability was determined by nurse-supervised questionnaires administered to the patients and parents. Following treatment, 94% of patients preferred the Norditropin liquid GH system. This preference was irrespective of the previous system in use, patient age or length of GH therapy. More patients found it the less painful system (50% vs 13%), 92% of patients found it more convenient, and the formulation was well tolerated. In conclusion, Norditropin liquid GH was very well accepted and preferred by the majority of patients. It avoided reconstitution which had been a major cause of dissatisfaction with the patients' previous systems, and resulted in greater convenience and reduced levels of pain associated with injection.

Adolescent↗
PubMed2000

Magnetic field exposure of commercial airline pilots.

PURPOSE: Airline pilots are exposed to magnetic fields generated by the aircraft's electrical and electronic systems. The purpose of this study was to directly measure the flight deck magnetic fields to which commercial airline pilots are exposed when flying on different aircraft types over a 75-hour flight-duty month.METHODS: Magentic field measurements were taken using personal dosimeters capable of measuring magnetic fields in the 40-800 Hz frequency range. Dosimeters were carried by either the Captain or the First Officer on Boeing 737/200, Boeing 747/400, Boeing 767/300ER, and Airbus 320 aircraft. The data were analyzed by aircraft type, with statistics based on block hours. Block hours begin when the aircraft departs the gate prior to take off and end when the aircraft returns to the gate after landing.RESULTS: Approximately 1008 block hours were recorded at a sampling rate of 3 seconds. Total block time exposure to the pilots ranged from a harmonic geometric mean of 6.7 milliGauss (mG) for the Boeing 767/300ER to 12.7 mG for the Boeing 737/200.CONCLUSIONS: Measured flight deck magnetic field levels were substantially above the 0.8 to 1 mG level typically found in the home or office and suggest the need for further study to evaluate potential health effects of long-term exposure.

Journal Article↗
PubMed2000

Dimerization of bovine F1-ATPase by binding the inhibitor protein, IF1.

In mitochondria, the hydrolytic activity of ATP synthase is regulated by a natural inhibitor protein, IF(1). The binding of IF(1) to ATP synthase depends on pH values, and below neutrality, IF(1) forms a stable complex with the enzyme. Bovine IF(1) has two oligomeric states, dimer and tetramer, depending on pH values. At pH 6.5, where it is active, IF(1) dimerizes by formation of an antiparallel alpha-helical coiled-coil in its C-terminal region. This arrangement places the inhibitory N-terminal regions in opposition, implying that active dimeric IF(1) can bind two F(1) domains simultaneously. Evidence of dimerization of F(1)-ATPase by binding to IF(1) is provided by gel filtration chromatography, analytical ultracentrifugation, and electron microscopy. At present, it is not known whether IF(1) can bring about the dimerization of the F(1)F(0)-ATPase complex.

Animals↗
PubMed2000

Cloning, sequencing and expression of the gene for flavodoxin from Megasphaera elsdenii and the effects of removing the protein negative charge that is closest to N(1) of the bound FMN.

The gene for the electron-transfer protein flavodoxin has been cloned from Megasphaera elsdenii using the polymerase chain reaction. The recombinant gene was sequenced, expressed in an Escherichia coli expression system, and the recombinant protein purified and characterized. With the exception of an additional methionine residue at the N-terminus, the physico-chemical properties of the protein, including its optical spectrum and oxidation-reduction properties, are very similar to those of native flavodoxin. A site-directed mutant, E60Q, was made to investigate the effects of removing the negatively charged group that is nearest to N(1) of the bound FMN. The absorbance maximum in the visible region of the bound flavin moves from 446 to 453 nm. The midpoint oxidation-reduction potential at pH 7 for reduction of oxidized flavodoxin to the semiquinone E2 becomes more negative, decreasing from -114 to -242 mV; E1, the potential for reduction of semiquinone to the hydroquinone, becomes less negative, increasing from -373 mV to -271 mV. A redox-linked pKa associated with the hydroquinone is decreased from 5.8 to < or = 4.3. The spectra of the hydroquinones of wild-type and mutant proteins depend on pH (apparent pKa values of 5.8 and < or = 5.2, respectively). The complexes of apoprotein and all three redox forms of FMN are much weaker for the mutant, with the greatest effect occurring when the flavin is in the semiquinone form. These results suggest that glutamate 60 plays a major role in control of the redox properties of M. elsdenii flavodoxin, and they provide experimental support to an earlier proposal that the carboxylate on its side-chain is associated with the redox-linked pKa of 5.8 in the hydroquinone.

Amino Acid Sequence↗
PubMed2000

Dominant and recessive inheritance of morbid obesity associated with melanocortin 4 receptor deficiency.

Over 20 severely obese subjects in 11 independent kindreds have been reported to have pathogenic heterozygous mutations in the gene encoding the melanocortin 4 receptor (MC4R), making this the most common known monogenic cause of human obesity. To date, the detailed clinical phenotype of this dominantly inherited disorder has not been defined, and no homozygous subjects have been described. We determined the nucleotide sequence of the entire coding region of the MC4R gene in 243 subjects with severe, early-onset obesity. A novel two-base pair GT insertion in codon 279 was found in two unrelated subjects, and four novel missense mutations, N62S, R165Q, V253I, C271Y, and one mutation (T112M) reported previously were found in five subjects. N62S was found in homozygous form in five children with severe obesity from a consanguineous pedigree. All four heterozygous carriers were nonobese. Several features of the phenotype, e.g. hyperphagia, tendency toward tall stature, hyperinsulinemia, and preserved reproductive function, closely resemble those reported previously in Mc4r knock-out mice. In addition, a marked increase in bone mineral density was seen in all affected subjects. In transient transfection assays, the N62S mutant receptor showed a responsiveness to alphaMSH that was intermediate between the wild-type receptor and mutant receptors carrying nonsense and missense mutations associated with dominantly inherited obesity. Thus MC4R mutations result in a syndrome of hyperphagic obesity in humans that can present with either dominant or recessive patterns of inheritance.

Adolescent↗
PubMed2000

Evaluation of role of concentration and molecular weight of oat beta-glucan in determining effect of viscosity on plasma glucose and insulin following an oral glucose load.

Data from clinical studies established that there was an inverse linear relationship between measures of postprandial blood glucose and insulin responses to an oral glucose load, consumed in a drink, and the logarithm of viscosity of the drink. These data have been re-analysed using concentration and molecular weight as the dependent variables. Molecular weight (M) of the beta-glucans used was determined using high-performance size exclusion chromatography equipped with a triple detector system of right angle light scattering, viscometry and refractive index. A significant relationship between changes in peak blood glucose and a combination of logarithm of the concentration and logarithm of M was found.

Administration, Oral↗
PubMed2000

New strategies in the management of acute coronary syndromes.

Advances in the understanding of acute coronary syndromes have occurred rapidly in the last 5 years and have dramatically changed the way patients are evaluated, diagnosed, and managed. Medical advances, such as antiplatelet and antithrombin agents and growing databases on interventional outcomes have created a new world of therapeutic options for the spectrum of ischemic heart disease. As more options become available, nurses are under increasing pressure to stay abreast of what these options have to offer patients, and which patients benefit most from each therapeutic approach. The purpose of this article is to review the newest therapies for acute coronary syndromes, including GP IIb/IIIa inhibitors, low molecular weight heparins, and direct thrombin inhibitors, and discuss indications and contraindications for each of these therapies. Changes in diagnostic approach using troponin T and I are also presented.

Acute Disease↗
PubMed1999

Evaluation of some newer matrix metalloproteinases.

Recombinant protein expression techniques have been utilized to facilitate the biochemical and cell biological characterization of human matrix metalloproteinases (MMPs). The importance of the membrane type 1 MMP (MMP 14) in the regulation of pericellular proteolysis, either directly or through the activation of MMP-2, MMP-9, and MMP-13 has been identified. Studies on an in vitro chondrocyte-like cell and an in vivo cartilage repair model indicated that such MT1 MMP-regulated activation cascades are physiologically feasible. MMP19 shows a limited sequence identity with other MMPs and may represent a novel subclass. However, analysis of the recombinant protein identified a number of biochemical properties typical of the MMP family.

Animals↗
PubMed1999

Regulated nuclear localisation of the yeast transcription factor Ace2p controls expression of chitinase (CTS1) in Saccharomyces cerevisiae.

The yeast transcription factor Ace2p regulates expression of the chitinase gene CTS1 in a cell cycle-dependent manner. Nuclear localisation of Ace2p is restricted to late M and early G phases of the mitotic cell cycle. We show here that this nuclear localisation is directly associated with regulation of CTS1 expression. Using a version of Ace2p tagged with a c-myc epitope, we show that the protein is excluded from the nucleus of cells during most phases of the mitotic cell cycle. A mutant derivative in which one threonine and two serine residues, which are candidate phosphorylation sites, were replaced by alanine (to mimic constitutive dephosphorylation) is localised in the nucleus throughout the cell cycle. The mechanism of localisation of Ace2p therefore involves regulation of its phosphorylation state, and closely resembles that used by the homologous transcription factor Swi5p. The wild-type Ace2 protein associates with Cdc28p in vivo, suggesting this may be the kinase that mediates the phosphorylation event. The stability of the protein is greatly reduced in a mutant that is constitutively localised to the nucleus, but is restored in a deletion derivative which remains in the cytoplasm. Ace2p is therefore controlled throughout the cell cycle at three levels: transcription, nuclear localisation, and proteolysis.

Amino Acid Sequence↗