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Biomedical subjects

A Davies

Publications and source records attributed to A Davies.

At least 19 recordsLinked to original sources
PubMed2006

A new method of transvaginal ultrasound-guided polypectomy: a feasibility study.

OBJECTIVES: A new device has been manufactured (Safe T Choice), which allows attachment of a transvaginal ultrasound probe to a specially adapted cervical tenaculum. This affords the capacity to monitor intrauterine surgical procedures without the need for hysteroscopy. The purpose of this study was to investigate the feasibility of endometrial polypectomy using this device combined with saline contrast sonohysterography (SCSH) to monitor the procedure. METHODS: Women diagnosed with an endometrial polyp on routine B-mode two-dimensional transvaginal ultrasound (TVS) were invited to join the study. Transvaginal ultrasound-guided polypectomies were carried out by a single operator. The procedure was timed from application until removal of the tenaculum. The ultrasound views were rated as satisfactory or poor. Success of the procedure was gauged by complete removal of the polyp without recourse to hysteroscopy. Women also attended for postoperative follow-up ultrasound scans to check for residual disease. RESULTS: Thirty-seven women were recruited to the study. The mean operating time was 8 min (95% CI, 5.9-10.4). The procedure was successful in 32/37 (86.5%) cases (95% CI, 75.5-97.5). In three cases (8.1%) the procedure failed because of an inability to obtain satisfactory images of the uterine cavity, and in two further cases (5.4%) the operator was unable to grasp and remove the polyp. Two patients (5.4%) bled from the tenaculum insertion site, necessitating suture for hemostasis. There were no other complications and none of the patients had evidence of residual polyp tissue at the follow-up visit. CONCLUSION: This study showed that transvaginal ultrasound-guided polypectomy is a feasible technique for the removal of endometrial polyps. Further work is required to compare outcomes and cost-effectiveness of this technique with hysteroscopic polypectomy.

Adult↗
PubMed2006

Reproducibility of the measurement of submucous fibroid protrusion into the uterine cavity using three-dimensional saline contrast sonohysterography.

OBJECTIVE: To determine the intraobserver and interobserver reproducibility of measurement of the percentage of protrusion of submucous fibroids into the uterine cavity using three-dimensional saline contrast sonohysterography (3D-SCSH). METHODS: Women diagnosed with submucous uterine fibroids on B-mode two-dimensional (2D) ultrasound scan were invited to join the study and 3D-SCSH was carried out. 3D volume datasets were stored digitally and were examined later using the technique of planar reformatted sections. The reproducibilities of the measurement of fibroid diameter and protrusion ratio into the uterine cavity (ratio of the size of the segment of the fibroid protruding into the cavity to the total diameter of the fibroid) were examined by two independent observers who were unaware of the initial 2D scan findings. Interobserver reproducibility was assessed by calculating the difference between measurements taken by the two operators (limits of agreement) and interclass correlation coefficient. Intraobserver repeatability was assessed by calculating the difference between two measurements for each variable (limits of agreement) and further expressed as an intraclass correlation coefficient. RESULTS: Thirty-three 3D ultrasound volumes were examined. There was a good agreement between the observers in classifying the fibroids as greater or less than 50% confined to the myometrium (Cohen's kappa 0.81). There was no bias in measurements for both variables either between observers or with repeated measurements by each observer. For fibroid diameter and protrusion ratio the inter- and intraclass correlation coefficients were high (0.984-0.995), with narrow limits of agreement. CONCLUSION: 3D-SCSH is a reproducible method for the quantification of the percentage of a submucous fibroid protruding into the uterine cavity.

Adult↗
PubMed2006

Do voltage-gated calcium channel alpha2delta subunits require proteolytic processing into alpha2 and delta to be functional?

The accessory alpha2delta subunits of voltage-gated calcium channels are type 1 transmembrane proteins that are highly glycosylated and possess multiple disulfide bonds. From studies of the topology and processing of skeletal-muscle alpha2delta-1, it has been shown to be post-translationally cleaved into an alpha2 and a delta subunit, which remain disulfide-bonded. In the present study, we have examined the processing of alpha2delta-2 subunits when stably or transiently expressed, in tsA (temperature-sensitive A)-201, Cos-7 and NG108-15 cells, and compared it with that observed in the cerebellum. Despite showing full functionality and being expressed on the plasma membrane, the vast majority of heterologously expressed alpha2delta-2 is not cleaved into alpha(2)-2 and delta-2, unlike endogenous alpha2delta-2 in the cerebellum. It remains an open question for future research whether alpha2delta-2 is functional in its calcium channel trafficking role in its proteolytically cleaved or non-cleaved state.

Animals↗
PubMed2006

Human immunodeficiency virus and hepatitis C co-infection in sub-Saharan West Africa.

Co-infection with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) is becoming a major global problem, leading to increased morbidity and mortality in developed countries. Co-existence in sub-Saharan West Africa of a high prevalence of HIV and HCV, which share similar behavioural risk factors and modes of transmission, must be seen in the broader context of an emerging third epidemic of HIV and HCV co-infection, as many factors that may affect the spread of HIV and HCV co-infection are endemic in the continent, including host factors such as sexual behaviour, presence of other sexually transmitted diseases, female and male circumcision status, percutaneous and perinatal exposure, and poverty. This review examines the epidemiology, risk factors and transmission of HIV and HCV co-infection and draws attention to the possible emergence of an epidemic of HIV and HCV co-infection in the region.

Adolescent↗
PubMed2005

The metal-ion-dependent adhesion site in the Von Willebrand factor-A domain of alpha2delta subunits is key to trafficking voltage-gated Ca2+ channels.

All auxiliary alpha2delta subunits of voltage-gated Ca2+ (Ca(V)) channels contain an extracellular Von Willebrand factor-A (VWA) domain that, in alpha2delta-1 and -2, has a perfect metal-ion-dependent adhesion site (MIDAS). Modeling of the alpha2delta-2 VWA domain shows it to be highly likely to bind a divalent cation. Mutating the three key MIDAS residues responsible for divalent cation binding resulted in a MIDAS mutant alpha2delta-2 subunit that was still processed and trafficked normally when it was expressed alone. However, unlike WT alpha2delta-2, the MIDAS mutant alpha2delta-2 subunit did not enhance and, in some cases, further diminished Ca(V)1.2, -2.1, and -2.2 currents coexpressed with beta1b by using either Ba2+ or Na+ as a permeant ion. Furthermore, expression of the MIDAS mutant alpha2delta-2 reduced surface expression and strongly increased the perinuclear retention of Ca(V)alpha1 subunits at the earliest time at which expression was observed in both Cos-7 and NG108-15 cells. Despite the presence of endogenous alpha2delta subunits, heterologous expression of alpha2delta-2 in differentiated NG108-15 cells further enhanced the endogenous high-threshold Ca2+ currents, whereas this enhancement was prevented by the MIDAS mutations. Our results indicate that alpha2delta subunits normally interact with the Ca(V)alpha1 subunit early in their maturation, before the appearance of functional plasma membrane channels, and an intact MIDAS motif in the alpha2delta subunit is required to promote trafficking of the alpha1 subunit to the plasma membrane by an integrin-like switch. This finding provides evidence for a primary role of a VWA domain in intracellular trafficking of a multimeric complex, in contrast to the more usual roles in binding extracellular ligands in other exofacial VWA domains.

Binding Sites↗
PubMed2005

Prediction of DXA-determined whole body fat from skinfolds: importance of including skinfolds from the thigh and calf in young, healthy men and women.

OBJECTIVE: To investigate the relationship of percent body fat (%fat), assessed by dual energy-X-ray absorptiometry (DXA) or a four-compartment model, with upper body and lower limb skinfolds. DESIGN: Cross-sectional design involving forward stepwise and hierarchical multiple regression analyses to assess the relationship of %fat with skinfolds and a combination of four commonly used upper body skinfolds (biceps, triceps, subscapular and iliac crest) with the calf and thigh skinfolds. SETTING: University research laboratory. SUBJECTS: In all, 31 females, mean age 20.9 (+/-2.0) y, and 21 males, mean age 22.3 (+/-5.5) y volunteered for this study, which was approved by the Ethics Committee of the School of Sport, Health and Exercise Sciences, University of Wales, Bangor. MEASUREMENTS: %fat from DXA in both groups, and %fat from a four-compartment (water, bone mineral mass, fat and residual) model (%fat4C) in females only. Skinfolds were measured at the abdomen, iliac crest, biceps, triceps, subscapular, calf and thigh. RESULTS: All skinfolds were positively associated with DXA estimates of %fat (P < 0.01). In males and females, the thigh skinfold had the highest correlation with %fat. This was also observed when %fat4C was used as the criterion in females. Stepwise multiple regression analysis using %fatDXA as the criterion selected the thigh (R(2) = 0.82), calf (R(2) change 0.04) and iliac crest (R(2) change = 0.03) for females, and the thigh (R(2) = 0.79), iliac crest (R(2) change = 0.11) and abdomen (R(2) change = 0.03) for males (all P < 0.01). When %fat4C was used as the criterion in the females, only the thigh was selected as a significant predictor (R(2) = 0.76). Independent prediction factors were created from the sum of biceps, triceps, subscapular and iliac crest (sigma4skf) and from the sum of the thigh and calf (sigmathigh + calf). These factors were then entered into a hierarchical multiple linear regression analysis to predict percent fat. Order of entry was varied to allow the assessment of unique variance accounted for by each predictor. The sum of the thigh and calf explained more variance in %fatDXA than that explained by the sigma4skf alone, irrespective of the order of entry in both males and females. This was also observed when %fat4C was used as the criterion in the females. CONCLUSIONS: The results of this study confirm that lower body skinfolds are highly related to percent body fat in fit and healthy young men and women, and uphold current recommendations by the British Olympic Association to include the thigh skinfold with sigma4skf. Conventional use of the sigma4skf to estimate percent body fat is significantly enhanced by the inclusion of the thigh and calf skinfolds, either independently or in combination. In this group of males and females, the sum of the thigh and calf skinfolds accounted for the most variance in percent fat.

Absorptiometry, Photon↗
PubMed2005

Cost effectiveness of drotrecogin alfa (activated) for the treatment of severe sepsis in the United Kingdom.

Drotrecogin alfa (activated) is licensed in Europe for the treatment of severe sepsis in patients with multiple organ failure. We constructed a model to assess the cost effectiveness of drotrecogin alfa (activated) from the perspective of the UK National Health Service when used in adult intensive care units. Patient outcomes from a 28-day international clinical trial (PROWESS) and a subsequent follow-up study (EVBI) were supplemented with UK data. Cost effectiveness was assessed as incremental cost per life year and per quality adjusted life year saved compared to placebo alongside best usual care. Applying the 28-day mortality outcomes of the PROWESS study, the model produced a cost per life year saved of 4608 UK pounds and cost per quality adjusted life year saved of 6679 UK pounds. Equivalent results using actual hospital outcomes were 7625 UK pounds per life year and 11,051 UK pounds per quality adjusted life year. Drotrecogin alfa (activated) appears cost effective in treating severe sepsis in UK intensive care units.

Adult↗
PubMed2005

Non-dilated obstructed pelvicalyceal system.

Renal insufficiency because of obstruction may not always be represented by dilated pelvicalyceal system. This may make diagnosis and thence the management very difficult with the present available investigative armamentarium. Experience and clinical acumen may help with a decision of empirical treatment in the form of stenting or nephrostomy in these cases. This may be diagnostic as well as curative of the renal failure. We present herewith three such challenging cases managed by us. We also have reviewed the literature as to the diagnosis and management of such cases.

Aged, 80 and over↗
PubMed2005

The relationship between the onset of electrographic seizure activity after birth and the time of cerebral injury in utero.

In the fetal lamb model of hypoxic-ischaemic injury, the insult is followed by EEG depression, after which seizures emerge at 7-13 hours. We explored the relationship between the emergence of electrographic seizures and our estimate of the time of the cerebral injury in nine babies who underwent continuous video-EEG monitoring from soon after birth. Babies with prelabour insults had their first seizures before 12 hours of age, whereas those whose insult was peripartum had seizure onset at 18-20 hours of age. EEG seizure onset time could have important clinical and medico-legal applications, and be related to the time or severity of the insult, or both.

Birth Injuries↗
PubMed2005

One year results of the Middlesbrough early revascularisation to limit infarction (MERLIN) trial.

OBJECTIVE: To report one year results of the MERLIN (Middlesbrough early revascularisation to limit infarction) trial, a prospective randomised trial comparing the strategy of coronary angiography and urgent revascularisation with conservative treatment in patients with failed fibrinolysis complicating ST segment elevation myocardial infarction (STEMI). The 30 day results have recently been published. At the planning stage of the trial, it was determined that follow up of trial patients would continue annually to three years to determine whether late benefit occurred. SUBJECTS: 307 patients who received a fibrinolytic for STEMI but failed to reperfuse early according to previously described ECG criteria and did not develop cardiogenic shock. METHODS: Patients were randomly assigned to receive either emergency coronary angiography with a view to proceeding to urgent revascularisation (rescue percutaneous coronary intervention (rPCI) arm) or continued medical treatment (conservative arm). The primary end point was all cause mortality at 30 days. The secondary end points included the composite end point of death, reinfarction, stroke, unplanned revascularisation, or heart failure at 30 days. The same end points were evaluated at one year and these results are presented. RESULTS: All cause mortality at one year was similar in the conservative arm and the rPCI arm (13.0% v 14.4%, p = 0.7, risk difference (RD) -1.4%, 95% confidence interval (CI) -9.3 to 6.4). The incidence of the composite secondary end point of death, reinfarction, stroke, unplanned revascularisation, or heart failure was significantly higher in the conservative arm (57.8% v 43.1%, p = 0.01, RD 14.7%, 95% CI 3.5% to 25.5%). This was driven almost exclusively by a significantly higher incidence of subsequent unplanned revascularisation in the conservative arm (29.9% v 12.4%, p < 0.001, RD 17.5%, 95% CI 8.5% to 26.4%). Reinfarction and clinical heart failure were numerically, but not statistically, more common in the conservative arm (14.3% v 10.5%, p = 0.3, RD 3.8%, 95% CI -3.7 to 11.4, and 31.2% v 26.1%, p = 0.3, RD 5.0%, 95% CI -5.1 to 15.1). There was a strong trend towards fewer strokes in the conservative arm (1.3% v 5.2%, p = 0.06, RD -3.9%, 95% CI -8.9 to 0.06). CONCLUSION: At one year of follow up, there was no survival advantage in the rPCI arm compared with the conservative arm. The incidence of the composite secondary end point was significantly lower in the rPCI arm, but this was driven almost entirely by a highly significant reduction in the incidence of further revascularisation.

Adult↗
PubMed2005

mRNA expression of genes involved in lipid efflux and matrix degradation in occlusive and ectatic atherosclerotic disease.

BACKGROUND: Atherosclerotic plaque behaviour is influenced by intra-plaque inflammation, matrix turnover, and the lipid core volume. Peroxisome proliferator activated receptor gamma (PPARgamma) modulates atherosclerosis by its anti-inflammatory and anti-protease activity. PPARgamma promotes lipid efflux through the liver X receptor alpha (LXRalpha) and the ATP binding cassette transporter A1 (ABCA1). Matrix metalloproteinase 9 (MMP-9) and cyclooxygenase 2 (COX-2) are implicated in plaque instability. AIMS: To assess the expression of these genes in occlusive and ectatic atherosclerotic disease to determine the relation between genes involved in lipid efflux and matrix degradation. METHODS: Carotid endarterectomy specimens from 16 patients and aneurysm tissue from 16 patients undergoing abdominal aortic aneurysm repair were used. Inferior mesenteric arteries from colectomy specimens from 12 patients served as controls. Total RNA was extracted from pulverised tissue and reverse transcribed into cDNA. Quantitative real time polymerase chain reaction (PCR) was performed using fluorescently labelled probes for ABCA1, LXRalpha, PPARgamma, COX-2, and MMP-9. RESULTS: PPARgamma expression was significantly lower in both occlusive and ecstatic atherosclerotic disease (p<0.001), whereas LXRalpha and ABCA1 expression was significantly increased (p<0.01). MMP-9 expression was significantly increased in diseased tissues (p<0.0001), and values were highest in occlusive disease (p<0.01). The increases in ABCA1 and MMP-9 mRNA were significantly correlated in diseased tissues (p<0.01, r=0.71 and r=0.78). COX-2 expression was increased in ectatic but low in occlusive disease (p<0.01). CONCLUSION: This observational study suggests a role for therapeutic upregulation of PPARgamma, which could potentially upregulate lipid efflux through ABCA1 and inhibit matrix degradation through inhibition of MMP-9.

ATP Binding Cassette Transporter 1↗
PubMed2004

A comparative study of three-dimensional saline infusion sonohysterography and diagnostic hysteroscopy for the classification of submucous fibroids.

BACKGROUND: The purpose of this study was to compare three-dimensional saline infusion sonohysterography (3D SIS) and diagnostic hysteroscopy for the diagnosis and classification of submucous uterine fibroids. METHODS: This was a prospective double-blind study of 49 women who presented with a history of menorrhagia, diagnosed on non-enhanced two-dimensional ultrasonography with submucous fibroids. Fibroids were classified on 3D SIS according to the proportion of fibroid contained within the endometrial cavity, using the European Society of Hysteroscopy Classification of Submucous Fibroids. These results were then compared with the findings at diagnostic hysteroscopy. RESULTS: A total of 61 submucous fibroids was identified in 49 symptomatic women. Diagnostic hysteroscopy confirmed these findings in all cases. There was agreement between the two methods in 11/12 cases of Type 0 fibroids (92%), 34/37 (92%) of Type I fibroids and 9/12 (75%) of Type II fibroids. The overall level of agreement was good with a kappa value of 0.80. CONCLUSIONS: There is a good overall agreement between 3D SIS and diagnostic hysteroscopy in classification of submucous fibroids. Agreement is better in cases where a greater proportion of the fibroid is contained within the uterine cavity.

Adult↗
PubMed2004

A soluble Nogo receptor differentially affects plasticity of spinally projecting axons.

In the central nervous system, regeneration of injured axons and sprouting of intact axons are suppressed by myelin-derived molecules that bind to the Nogo receptor (NgR). We used a soluble form of the NgR (sNgR), constructed as an IgG of the human NgR extracellular domain, to manipulate plasticity of uninjured primary afferent and descending monoaminergic projections to the rat spinal cord following dorsal rhizotomy. Rats with quadruple dorsal rhizotomies were treated with intrathecal sNgR or saline, or were left untreated for 2 weeks. Rhizotomy alone resulted in sprouting of serotonergic axons and to a lesser extent, tyrosine-hydroxylase (TH)-expressing axons, while axons expressing dopamine-beta-hydroxylase (DbetaH) were unaffected. Human IgG immunohistochemistry revealed that sNgR infused into the intrathecal space penetrated approximately 300 microm into spinal white and grey matter. Separate axonal populations differed in their responses to intrathecal sNgR: TH-expressing and DbetaH-expressing axons responded most and least vigorously, respectively. Serotonergic axons were identified by serotonin (5-HT) or serotonin transporter (SERT) immunohistochemistry. Interestingly, a large increase in 5-HT compared to SERT-positive axons density in both saline and sNgR-treated rats indicated that serotonergic axons both sprouted and increased their transmitter content in response to rhizotomy and sNgR treatment. Calcitonin gene-related peptide-positive axons were largely depleted ipsilaterally by rhizotomy, and sNgR increased axon density only in deeper contralateral laminae (III-V). GAP-43 immunohistochemistry revealed a small increase in axon density following dorsal rhizotomy that was further augmented by sNgR treatment. These results reveal a differential effect of myelin antagonism on distinct populations of spinally projecting axons.

Animals↗
PubMed2003

Determination of CD59 protein in normal human serum by enzyme immunoassay, using octyl-glucoside detergent to release glycosyl-phosphatidylinositol-CD59 from lipid complex.

In this study we have optimised the enzyme immunoassay (ELISA) to quantify CD59 antigen in human serum or plasma. The glycosyl-phosphatidylinositol (GPI)-linked form of CD59 is known to complex with serum high-density lipoprotein. For ELISA optimisation, therefore, we investigated the effect of detergents, added to the sample diluent, on the determined values of CD59. Values obtained in the presence of octyl-glucoside (OG) for 20 adults aged 18-35 years and 17 children 1-5 years old were, respectively, 33-119 ng/ml (mean +/- S.D.: 66+/-22 ng/ml) and 37-143 ng/ml (76+/-33 ng/ml). These results were higher than those measured without OG and were in contrast with published results showing absence, or eight to nine times lower levels, of the protein in serum. A known range for serum concentrations of CD59 in healthy individuals will establish an important reference point for clinical work and for the investigation of diseases involving the complement membrane attack complex (MAC) and its regulation.

Adolescent↗
PubMed2003

Microrheology, stress fluctuations, and active behavior of living cells.

We report the first measurements of the intrinsic strain fluctuations of living cells using a recently developed tracer correlation technique along with a theoretical framework for interpreting such data in heterogeneous media with nonthermal driving. The fluctuations' spatial and temporal correlations indicate that the cytoskeleton can be treated as a course-grained continuum with power-law rheology, driven by a spatially random stress tensor field. Combined with recent cell rheology results, our data imply that intracellular stress fluctuations have a nearly 1/omega2 power spectrum, as expected for a continuum with a slowly evolving internal prestress.

Cell Physiological Phenomena↗
PubMed2003

Changes in the quality of life in severely disabled people following provision of powered indoor/outdoor chairs.

PURPOSE: To determine the benefits for patients who received an electric powered inoor/outdoor chair (EPIOC) and to quantify their perceived changes to their quality of life. METHOD: Community-based cohort study of all patients provided with an EPIOC over 4 months; and followed up about 3 months later in a community served by a regional wheelchair service in North West London (population about 3.1 million) using the EuroQol EQ-5D with visual analogue scales for each of the five dimensions of the EQ-5D. RESULTS: Sixty-four wheelchair users were assessed initially and 51 completed follow up. Chair users showed no significant improvement in health state as measured by the EQ-5D after EPIOC provision. The visual analogue scales (VASs) indicated that, although perceived overall health state, independence and social life did not appear to improve, the dimensions of mobility, quality of life and pain/discomfort improved significantly on provision of an EPIOC. CONCLUSION: EPIOC users reported significant improvements in several important aspects of their lives; not just in mobility (as expected) but also in reduction of pain and discomfort. The use of VASs provided a more holistic set of outcome measures that demonstrate quality of life benefits beyond that of health state alone.

Activities of Daily Living↗
PubMed2003

Early and late reactions following the use of iopamidol 340, iomeprol 350 and iodixanol 320 in cardiac catheterization.

GOAL: To investigate the incidence of early (< 24 hours) and late (> 24 hours to 7 days) reactions to 3 contrast agents commonly used in cardiac catheterization. METHODS AND RESULTS: A total of 2,108 patients undergoing cardiac catheterization in a Regional Cardiothoracic Unit were randomly assigned to receive 1 of 3 commonly used contrast agents in a prospective, double-blind study. The contrast agents were iopamidol 340 (Niopam ), a nonionic monomer; iomeprol 350 (Iomeron ), a nonionic dimer; and iodixanol 320 (Visipaque ), a nonionic dimer. The main outcome measures were the incidence of early (< 24 hours) reactions following catheterization and the incidence of late (24 hours to 7 days) reactions. Early reactions, excluding patients with heat on left ventriculography as the sole symptom, were relatively common (7.4%), but there was no significant difference between the 3 agents (p = 0.35). Late skin reactions, excluding reactions solely at the site of the arterial puncture and continuations of early urticarial reactions, were also relatively common (5.4%), but the incidence differed between the 3 agents. Such reactions occurred in 2.7% of those receiving iopamidol 340 (Niopam ), 3.5% of those receiving iomeprol 350 (Iomeron ) and 10.4% of those receiving iodixanol 320 (Visipaque ) (p < 0.01). CONCLUSION: The incidence of early adverse reactions is similar with these 3 contrast agents. However, late skin reactions are significantly more common with iodixanol 320 (Visipaque ) than with the other 2 agents. Although such reactions were rarely troublesome, patients should be advised accordingly.

Adolescent↗