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Biomedical subjects

A McMahon

Publications and source records attributed to A McMahon.

At least 19 recordsLinked to original sources
PubMed2006

Dental health of 5-year-olds following community-based oral health promotion in Glasgow, UK.

AIM: A community development oral health promotion programme based on the principles of the Ottawa Charter was conducted in an attempt to improve the dental health of children under 5 years of age in two severely socioeconomically challenged pilot districts in Glasgow, UK. Later phased extension involved all of the area's most deprived communities. The aim of the present study was to assess dental health outcomes by secondary analysis of routine caries datasets for Glasgow 5-year-olds over the interval from 1997-1998 to 2003-2004. DESIGN: Wilcoxon tests assessed change in d3mft scores and logistic regression was used to analyse binomial scores (e.g. % d3mft = 0). RESULTS: After adjusting for age and deprivation (DepCat) in pilot districts 1 and 2, significant redistributions of the relative frequency of d3mft scores were observed (P = 0.012 and P < 0.001, respectively), mean d3mft decreased from 5.5 to 3.6 and from 6.0 to 3.6, respectively, and the proportions with d3mft = 0 increased from 11% to 29% and from 10% to 32%, respectively [P = 0.010, odds ratio (OR) = 0.25, and P = 0.006, OR = 0.30, respectively, for d3mft > 0]. Following extension of the programme into all of Glasgow's socioeconomically challenged areas, the mean d3mft values of 5-year-olds reduced in all DepCat 7 communities, and across Glasgow as a whole from 4.9 to 4.1 and from 3.5 to 3.1, respectively, while the proportion with d3mft = 0 increased from 20% to 32% (P < 0.001) and from 34% to 42% (P < 0.001), respectively. CONCLUSION: Dental health improvements were observed in pilot districts and across all DepCat 7 communities following the roll-out of the programme. This change was of sufficient magnitude to impact upon area-wide statistics for Glasgow.

Age Factors↗
PubMed2005

Investigation of factors affecting the adsorption of functional molecules onto gel silicas. 1. Flow microcalorimetry and infrared spectroscopy.

Flow microcalorimetry and infrared spectroscopy were used to study the surface structure and adsorptive properties of a series of calcined and uncalcined porous silicas. The adsorbates DL-menthol, (R)-(+)-limonene, (+/-)-citronellal and carvone were selected for their functionality, that included carbonyl, vinylic and hydroxyl groups. The amounts of probe retained by the silicas together with the energy exchange involved in the adsorption/desorption process were determined by flow microcalorimetry. The functional groups involved in these interactions were studied by means of infrared spectroscopy. It was observed that the strongest interactions with the silica surface took place through hydrogen bonding onto the surface silanol. The most retentive probes were found to be those with a carbonyl group in their structure. Adsorption onto calcined silicas was found to be less energetic than onto the equivalent calcined samples. The adsorption densities were compared with theoretical predictions based on molecular models. In all cases apart from citronellal monolayer coverage were not observed due to steric effects.

Journal Article↗
PubMed2005

Are atrial fibrillation guidelines altering management? A community based study.

BACKGROUND AND AIMS: We wanted to determine the prevalence of atrial fibrillation (AF) in a community based cross sectional study in greater Glasgow and how current anti-thrombotic management compares to published guidelines. METHODS: 1466 patients with AF were identified in General Practices in our community and 1008 consented to take part. Their demographic details and medical history were recorded. RESULTS: 1466 patients (mean age 73.4; 55% female) with AF were identified, in our community, giving a prevalence of 1%. 53% of patients were on warfarin therapy. Of those not receiving warfarin, only one third had a putative contra-indication. The proportion ofAF patients on warfarin increased with increasing stroke risk, and over the period of the study. CONCLUSIONS: Prevalence of AF was in keeping with previous estimates. The proportion of patients with AF receiving warfarin therapy appears to be increasing. In the moderate risk group, there was a tendency to use more warfarin in the younger age groups compared to the elderly. It was in the moderate and low risk groups that there was still evidence of deviation from published guidelines.

Aged↗
PubMed2005

Further evidence for biological effects resulting from ionizing radiation doses in the diagnostic X-ray range.

In this study we assessed cell response to ionizing radiation doses in the diagnostic X-ray range, using metabolic performance as the biological end point. HeLa cells were irradiated between 3.5 mGy (standard deviation (SD=2.5%) and 55.1 mGy (SD=0.9%) with 110 kV X-rays, and after 7 days metabolic capacity of cultures was measured spectrophotometrically with resazurin. Cells receiving 7.5 mGy or greater showed impaired proliferation. At 7.5 mGy this effect was prevented by nitric oxide synthase inhibitor N G-monomethyl-L-arginine but not by ascorbic acid or p38 MAPK inhibitor SB203580. We conclude that HeLa cell proliferation is adversely affected by doses within the range of some radiological examinations, through a mechanism involving nitric oxide.

Cell Proliferation↗
PubMed2001

Alcohol hypersensitivity, increased locomotion, and spontaneous myoclonus in mice lacking the potassium channels Kv3.1 and Kv3.3.

The Shaw-like potassium (K(+)) channels Kv3.1 and Kv3.3 are widely coexpressed in distinct neuronal populations in the CNS, possibly explaining the relatively "mild" phenotypes of the Kv3.1 and the Kv3.3 single mutant. Kv3.1-deficient mice show increased cortical gamma- and decreased delta-oscillations (Joho et al., 1997, 1999); otherwise, the Kv3.1-mutant phenotype is relatively subtle (Ho et al., 1997; Sánchez et al., 2000). Kv3.3-deficient mice display no overt phenotype (Chan, 1997). To investigate whether Kv3.1 and Kv3.3 K(+) channels are functionally redundant, we generated the Kv3.1/Kv3.3 double mutant. Kv3.1/Kv3.3-deficient mice were born at the expected Mendelian frequencies indicating that neither Kv3.1 nor Kv3.3 K(+) channels are essential for embryonic development. Although there are no obvious changes in gross brain anatomy, adult Kv3.1/Kv3.3-deficient mice display severe ataxia, tremulous movements, myoclonus, and hypersensitivity to ethanol. Mice appear unbalanced when moving, whereas at rest they exhibit whole-body jerks every few seconds. In spite of the severe motor impairment, Kv3.1/Kv3.3-deficient mice are hyperactive, show increased exploratory activity, and display no obvious learning or memory deficit. Myoclonus, tremor, and ethanol hypersensitivity are only seen in the double-homozygous Kv3.1/Kv3.3-deficient mice, whereas increased locomotor and exploratory activity are also present in double-heterozygous mice. The graded penetrance of mutant traits appears to depend on the number of null alleles, suggesting that some of the distinct phenotypic traits visible in the absence of Kv3.1 and Kv3.3 K(+) channels are unrelated and may be caused by localized dysfunction in different brain regions.

Animals↗
PubMed2001

Dynamic interaction of S5 and S6 during voltage-controlled gating in a potassium channel.

A gain-of-function mutation in the Caenorhabditis elegans exp-2 K(+)-channel gene is caused by a cysteine-to-tyrosine change (C480Y) in the sixth transmembrane segment of the channel (Davis, M.W., R. Fleischhauer, J.A. Dent, R.H. Joho, and L. Avery. 1999. Science. 286:2501-2504). In contrast to wild-type EXP-2 channels, homotetrameric C480Y mutant channels are open even at -160 mV, explaining the lethality of the homozygous mutant. We modeled the structure of EXP-2 on the 3-D scaffold of the K(+) channel KcsA. In the C480Y mutant, tyrosine 480 protrudes from S6 to near S5, suggesting that the bulky side chain may provide steric hindrance to the rotation of S6 that has been proposed to accompany the open-closed state transitions (Perozo, E., D.M. Cortes, and L.G. Cuello. 1999. Science. 285:73-78). We tested the hypothesis that only small side chains at position 480 allow the channel to close, but that bulky side chains trap the channel in the open state. Mutants with small side chain substitutions (Gly and Ser) behave like wild type; in contrast, bulky side chain substitutions (Trp, Phe, Leu, Ile, Val, and His) generate channels that conduct K(+) ions at potentials as negative as -120 mV. The side chain at position 480 in S6 in the pore model is close to and may interact with a conserved glycine (G421) in S5. Replacement of G421 with bulky side chains also leads to channels that are trapped in an active state, suggesting that S5 and S6 interact with each other during voltage-dependent open-closed state transitions, and that bulky side chains prevent the dynamic changes necessary for permanent channel closing. Single-channel recordings show that mutant channels open frequently at negative membrane potentials indicating that they fail to reach long-lasting, i.e., stable, closed states. Our data support a "two-gate model" with a pore gate responsible for the brief, voltage-independent openings and a separately located, voltage-activated gate (Liu, Y., and R.H. Joho. 1998. Pflügers Arch. 435:654-661).

Amino Acid Sequence↗
PubMed2001

Impact evaluation of a folate education campaign with and without the use of a health claim.

OBJECTIVE: To measure the impact of a Kellogg/Northcott Society multimedia folate education campaign, run nationally from July 1998 to June 1999, with and without the use of health claims. METHOD: Three national telephone surveys of more than 500 Australian women aged 18-44 in July and November 1998 and May 1999. RESULTS: Awareness of the role of folate in the prevention of birth defects rose from 21% at baseline to 29% in November 1998 and 44% in May 1999. Awareness of the recommendation to take folate before pregnancy rose by 8% in the first six months of the campaign (without health claims) and by 22% in the second half (when health claims were incorporated). At the end of the campaign, the foods most commonly cited as sources of folate were leafy green vegetables (72%), breakfast cereals (70%), fruit (41%) and bread (40%). CONCLUSION: Inclusion of a specific health claim explaining the role of folate in preventing birth defects appeared to increase the impact of the folate education campaign. IMPLICATIONS: Changing food regulations to permit health claims may increase the impact of health promotion campaigns involving industry partnerships. Future folate programs should target young women (aged 18-24), those in rural areas and those on lower incomes.

Adolescent↗
PubMed2000

Does blastocyst culture eliminate paternal chromosomal defects and select good embryos?: inheritance of an abnormal paternal genome following ICSI.

Following intracytoplasmic sperm injection (ICSI), approximately 60-70% of oocytes are fertilized and of these embryos, approximately 45% withstand in-vitro culture conditions to produce healthy blastocysts. The efficiency of implantation of 2-4-cell embryos selected at the pronuclear stage and that of blastocysts are comparable. However, prolonged selection of embryos in vitro (4-5 days), has been proposed to eliminate chromosomal abnormalities, more specifically those inherited by defective spermatozoa. This hypothesis is based upon the assumption that the paternal genetic contribution is indispensable for blastocyst development. Here we examine this hypothesis and suggest that phenotypic manifestation of paternal genomic abnormalities might not occur prior to implantation. In addition to the parent-of-origin effect during embryogenesis, blastocyst transfer may not prevent the inheritance of genetic defects involving 'male factor' loci.

Animals↗
PubMed2000

An acute stroke service: potential to improve patient outcome without increasing length of stay.

Acute stroke is associated with a high morbidity and mortality: up to 24% of patients may not survive their hospital admission. Stroke unit care has been shown in a meta-analysis to reduce this morbidity and mortality. We present a three-year audit of the first acute stroke service in an Irish teaching hospital. The audit was carried out prospectively on 193 patients admitted to the acute stroke service, from July 1996 to end of June 1999. Details regarding patients, type and severity of stroke, length of stay and outcome were collected prospectively on a standard pro-forma. We observed a reduction in mortality from 19% to 15% to 9%, and an increasing percentage of patients discharged home from 55% to 64% to 68%, in year 1, year 2 and year 3 respectively. A trend towards a greater number of patients, younger age and improved outcome with lower mortality was observed from year to year, without significant change in length of stay. This study confirms the value to patients of organised stroke care in terms of reduction in mortality and morbidity without increasing length of stay or disability. We suggest that every acute hospital should have organised stroke care.

Acute Disease↗
PubMed1999

Dishevelled proteins lead to two signaling pathways. Regulation of LEF-1 and c-Jun N-terminal kinase in mammalian cells.

Dishevelled (Dsh/Dvl) proteins are known to mediate Wnt signaling by up-regulating beta-catenin levels and stimulating T cell factor (TCF)/LEF-1-dependent transcription. We have identified a new Dvl-mediated signaling pathway in that mouse Dvl proteins, when expressed in COS-7 cells, stimulate c-Jun-dependent transcription activity and the kinase activity of the c-Jun N-terminal kinase (JNK). The DEP domain of Dvl1 is essential for JNK activation. By contrast, all three conserved domains of Dvl, including DIX, PDZ, and DEP, are required for up-regulation of beta-catenin and for stimulation of LEF-1-mediated transcription in mammalian cells. Thus, Dvl can lead to two different signaling pathways. Furthermore, the small G proteins of Cdc42 or Rac1, which are involved in JNK activation by many stimuli, do not appear to play a major role in Dvl-mediated JNK activation, because the dominant negative mutants of Cdc42 and Rac1 could not inhibit Dvl-induced JNK activation. This suggests that Dvl may activate JNK via novel pathways.

3T3 Cells↗
PubMed1999

Costs associated with symptomatic systolic heart failure.

OBJECTIVE: To investigate whether the extent of systolic dysfunction is a useful predictor of the costs of healthcare and social support for patients with heart failure. DESIGN: Cross-sectional study with collection of cost data attributed to management of heart failure in the previous year. SETTING: Four primary-care practices in Scotland. PATIENTS: Patients receiving long term therapy with loop diuretics for suspected heart failure. INTERVENTIONS: Two-dimensional and Doppler echocardiography. MAIN OUTCOME MEASURES AND RESULTS: Two hypotheses were tested: (i) the proportion of patients incurring costs is higher in patients with abnormal left ventricular (LV) function; and (ii) the median cost per patient that incurs costs is higher in patients with abnormal LV function. Of the 226 patients in the study, 67 (30%) had abnormal systolic function. In comparison with the remaining 159 patients, they had higher healthcare costs [560 Pounds vs 440 Pounds per patient year (1994/1995 values)], were more likely to incur hospital inpatient or outpatient costs [Odds ratio (OR): 2.02; 95% confidence interval (CI): 1.06 to 3.84] and had significantly higher primary-care costs (mean 292 Pounds vs 231 Pounds per patient year; p = 0.02, Mann Whitney test). In contrast, they were no more likely to incur social support costs (OR: 1.22; 95% CI: 0.52 to 2.86) and the mean cost of social support per patient year was lower (234 Pounds vs 373 Pounds). CONCLUSIONS: Patients with objectively measured systolic dysfunction incurred significantly higher healthcare costs in the year before diagnosis. This suggests that treatment that improves systolic function will reduce healthcare costs, even in a primary-care population with relatively mild congestive heart failure.

Cross-Sectional Studies↗
PubMed1998

FGF is an essential regulator of the fifth cell division in preimplantation mouse embryos.

Fibroblast growth factor (FGF) signaling is required prior to gastrulation in the mouse embryo. To test for the spatial and temporal requirements of FGF signaling, a dominant negative FGF receptor (dnFGFR) was used to make transgenic mouse embryos. In mosaic embryos, cell division ceased at the fifth cell division in all cells that expressed the mutant receptor, but cell death did not increase. After the fifth cell division, the progeny of unaltered cells and cells expressing lacZ continued to accumulate at the same rate, suggesting that the FGF requirement is cell autonomous. In mosaic embryos, lacZ, but not dnFGFR expression was detected in mitotic trophoblasts adjacent to the ICM. Conversely, dnFGFR-expressing extraembryonic ectoderm cells were detected at the abembryonic pole in postmitotic cells. In blastocysts expressing the dnFGFR in all cells, the morphology appeared normal and inner cell masses (ICMs) formed, but resultant embryos had only one-third the number of cells as control embryos. In these blastocysts, cell division had also ceased at the fifth cell division, but cavitation, a concurrent morphogenetic event, initiated and progressed normally. To test for the continuing requirement of FGF, FGFR-3 was overexpressed in all cells and resulted in an increase in cell numbers after the fifth cell cycle. In a model for postimplantation development, addition of FGF-4 to blastocyst outgrowths increased the number of extraembryonic ectoderm cells, suggesting a continuing role for FGF. Thus, FGF signaling induces the cell division of embryonic and extraembryonic cells in the preimplantation mouse embryo starting at the fifth cell division. The signal requirement for FGF is cell autonomous, but is not required to prevent cell death. This provides the first evidence for the necessity of a growth factor before implantation.

Animals↗
PubMed1998

Inhibitory action of BMPs on Pax1 expression and on shoulder girdle formation during limb development.

Pax1 expression in vertebrate limb buds is confined to cells in a discrete anterior proximal domain (Timmons et al. [1994] Development 120:2773-2785; Ebensperger et al. [1995] Anat. Embryol. 191:297-310). In dorsoventral patterning of Drosophila, expression of pox meso, an insect gene with high sequence similarity to Pax1, is repressed by decapentaplegic (dpp) in dorsal mesoderm and, thus, is restricted to a discrete ventral domain (Staehling-Hampton et al. [1994] Nature 372:783-786). In the chick wing, cells expressing a vertebrate homolog of dpp, bone morphogenetic protein 4 (Bmp4), abut the Pax1 domain, suggesting a similar relationship between homologous genes in both vertebrates and invertebrates. Here, we show that two BMPs (BMP4, and BMP2, also highly related to dpp) can repress Pax1 in the developing chick wing. Chick wing bud cells expressing Pax1 give rise to the shoulder girdle. Cells in an equivalent position in the mouse forelimb also express Pax1, and Pax1 mutant mice display shoulder girdle defects. Similarly in chick embryos, girdle defects are produced by treatments with signalling molecules that lead to expression of BMPs, which subsequently reduce Pax1 expression in the limb bud. Recently, BMP4 has been shown to inhibit Pax1 expression in the developing trunk (Monsoro-Burq et al. [1996] Development 122:3607-3616) and Pax9 expression in developing teeth (Neubüser et al. [1997] Cell 90:247-255). Thus, a property of BMPs appears to be to regulate pox meso homologs negatively and, thus, limit their expression domains.

Animals↗
PubMed1998

Calbindin-D28k buffers intracellular calcium and promotes resistance to degeneration in PC12 cells.

The calcium-binding protein calbindin-D28k (CB) has been hypothesized to function, in part, as a neuroprotective protein. CB is localized within nerve cells that are often less vulnerable to degeneration in patients with Alzheimer's disease and Parkinson's disease, and cells containing CB can buffer intracellular calcium concentrations ([Ca2+]i). The present study was designed to directly test the hypothesis that CB can protect cells from degeneration by reducing [Ca2+]i. PC12 cells, transfected to express different levels of CB, were found to be significantly less vulnerable to degeneration caused by serum withdrawal, glutamate, and the neurotoxin 1-methyl-4-phenylpyridinium (MPP+). However, CB did not protect cells from degeneration caused by the calcium ionophore A23187. CB-transfected cells exhibited reduced elevations in [Ca2+]i following treatment with bradykinin, or ATP compared to non-CB-containing cells. These data indicate that CB can protect cells from degeneration caused by certain conditions, and it reduces elevations in [Ca2+]i caused by influx from extracellular sources.

1-Methyl-4-phenylpyridinium↗
PubMed1998

Long-term intravenous prostaglandin (epoprostenol or iloprost) for treatment of severe pulmonary hypertension.

OBJECTIVE: To investigate the relation between the severity of pulmonary hypertension and the outcome of medical treatment. METHODS: 98 patients with primary pulmonary hypertension--nine (6%) with systemic disease and pulmonary hypertension and 39 (27%) with thromboembolic pulmonary hypertension--received medical treatment and were followed between 1982 and 1995. They were given long term intravenous prostaglandin treatment (either epoprostenol (n = 61) or iloprost (n = 13)) or conventional treatment with oral anticoagulants (n = 24) with or without calcium channel blockers. Event-free survival was measured to death or transplant surgery, or pulmonary thromboendarterectomy. RESULTS: Prognosis (hazard ratio) was affected by: New York Heart Association grade, 1.52 (95% confidence interval 1.11 to 2.09); mixed venous oxygen saturation (SvO2%), 0.97 (0.95 to 0.98); cardiac index, 0.72 (0.49 to 1.06); mean right atrial pressure, 1.04 (1.01 to 1.07); and pulmonary vascular resistance, 1.02 (1.00 to 1.04). The median event-free survival time of patients with SvO2 < 60% was 239 days (0 to 502) on conventional treatment (n = 22) and 585 days (300 to 870) on prostaglandin treatment (n = 42). No difference was seen in patients with SvO2 > or = 60% between conventional treatment and prostaglandin treatment, survival being 1275 days (732 to 1818; (n = 48)) and 986 days (541 to 1431; n = 30)), respectively. Capacity for pulmonary vasodilatation did not predict outcome of treatment. CONCLUSIONS: Continuous intravenous prostaglandins were more effective than anticoagulants, with or without calcium channel blockers, in prolonging survival in patients with right heart failure. In these patients a capacity to vasodilate did not predict outcome from medical treatment.

Adult↗