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Biomedical subjects

W Thompson

Publications and source records attributed to W Thompson.

At least 37 records · Page 2Linked to original sources
PubMed1998

Treatment-seeking women at menopause: a comparison between two university menopause clinics.

OBJECTIVE: We wished to determine the expectations of women about the benefits of hormone replacement therapy (HRT) and how these expectations may be influenced by cultural factors and previous experience of disease by the patient or in their families. DESIGN: The attitudes of patients seeking HRT in Belfast, United Kingdom (n = 218) and Portland, USA (n = 100) were compared at their first clinic attendance using a questionnaire. Physical and mental health issues, previous use of HRT and continuance on treatment were compared. RESULTS: Belfast women were less healthy than their Portland counterparts, with a higher prevalence of cardiovascular disease and psychiatric disorders (p < 0.05). Belfast patients showed a significantly lower continuance with treatment (p < 0.01). Collectively, the patients ranked relief of menopausal symptoms as their main expectation from HRT followed by osteoporosis protection, psychiatric relief and cardioprotection. The Belfast group had higher expectations for the relief of psychological/psychiatric problems (p < 0.01). All women with a family history of cardiac disease or fractures were more concerned for the protective effects of HRT than those women with no relevant family history (p < 0.05). There were cultural difference in expectations from HRT with Belfast women expecting more psychological/psychiatric relief and therefore trying a greater number of preparations. CONCLUSIONS: These findings suggest that menopausal women in both countries are well informed about the potential protective benefits of HRT, and now expect an improvement in the quality of their lives well beyond the relief of menopausal symptoms.

Attitude↗
PubMed1997

Two potential clinical applications of the alkaline single-cell gel electrophoresis assay: (1). Human bladder washings and transitional cell carcinoma of the bladder; and (2). Human sperm and male infertility.

Part 1: The alkaline single-cell gel electrophoresis (comet) assay was used to analyse the integrity and DNA content of exfoliated cells extracted from bladder washing specimens from 9 transitional cell carcinoma patients and 15 control patients. DNA damage, as expressed by % tail DNA and tail moment values, was observed to occur in cells from both control and bladder cancer samples. The extent of the damage was, however, found to be significantly greater in the cancer group than in the control group. Comet optical density values were also recorded for each cell analysed in the comet assay and although differences observed between tumour grades were not found to be statistically significant, the mean comet optical density value was observed to be greater in the cancer group than in the control population studied. These preliminary results suggest that the comet assay may have potential as a diagnostic tool and as a prognostic indicator in transitional cell carcinoma. Part 2: Baseline DNA damage in sperm cells from 13 normozoospermic fertile males, 17 normozoospermic infertile males and 11 asthenozoospermic infertile males were compared using a modified alkaline comet assay technique. No significant difference in the level of baseline DNA damage was observed between the 3 categories of sperm studied; however the untreated sperm cells were observed to display approximately 20% tail DNA. This is notably higher than the background DNA damage observed in somatic cells where the % tail DNA is normally less than 5%. Sperm from the 3 groups of men studied were also compared for sensitivity to DNA breakage, using the modified alkaline comet assay, following X-ray irradiations (5, 10 and 30 Gy) and hydrogen peroxide treatments (40, 100 and 200 microM). Significant levels of X-ray-induced damage were found relative to untreated control sperm in the two infertile groups following 30 Gy irradiation. Significant damage in hydrogen peroxide-treated sperm was observed in sperm from fertile samples, at 200 microM and in infertile samples at 100- and 200-microM doses relative to controls. These results therefore indicate that fertile sperm samples are more resistant to X-ray- and hydrogen peroxide-induced DNA breakage than infertile samples. Further studies involving greater numbers of individuals are currently in progress to confirm these findings.

Aged↗
PubMed1997

Reproducibility of human sperm DNA measurements using the alkaline single cell gel electrophoresis assay.

The single cell gel electrophoresis (SCGE) assay is a simple visual technique used to assess DNA integrity in individual cells by measuring damage reflected as strand breaks under alkaline conditions. Cells are embedded in agarose on glass slides followed by lysis of the cell membranes after which damaged DNA strands are electrophoresed away from the nucleus towards the anode and deposited to one side giving the appearance of a tail. DNA damage may be measured by assessing the relative amounts of DNA remaining in the head as opposed to those strands which have formed the tail. The assay has been used to determine DNA quality in human sperm (Hughes, C.M., S.E.M. Lewis, V.J. McKelvey-Martin, W. Thompson, A comparison of baseline and induced DNA damage in human sperm from fertile and infertile man, using a modified comet assay. Mol. Human Reprod., in press) by measuring fifty cells on one slide for each individual. Coefficients of variation between three control slides prepared for ten individuals were less than 4% and less than 9% for three slides prepared using irradiated sperm. Ten readings of fifty sperm each from a single slide showed a coefficient of variation of less than 6% for ten individuals studied. These results indicate that the measurement of fifty sperm from a single slide is sufficient to assess the DNA damage within a sperm population. Coefficients of variation of less than 5.4% for repeated analysis of individual cells were obtained which demonstrates the reproducibility of the image analysis software.

DNA↗
PubMed1997

Comparison of individual antioxidants of sperm and seminal plasma in fertile and infertile men.

OBJECTIVE: To measure individual antioxidants in sperm and seminal plasma from fertile and infertile men to determine if any particular antioxidant is reduced in infertile men. DESIGN: Semen samples were prepared by a discontinuous Percoll gradient to separate sperm and seminal plasma, and the antioxidant concentrations of each were assessed. Samples also were screened for phorbol ester-induced reactive oxygen species (ROS) activity. SETTING: Departments of Obstetrics and Gynaecology, and Clinical Biochemistry, The Queen's University of Belfast, Northern Ireland. PATIENT(S): Fifty-nine male patients attending our infertility center: 18 men whose wives had ongoing pregnancies from IVF with normozoospermic semen profiles, 20 infertile men with normozoospermic and 21 men with asthenozoospermic semen profiles. MAIN OUTCOME MEASURE(S): Ascorbate, urate, sulphydryl groups, tocopherol and carotenoid concentrations were measured in sperm and seminal plasma from fertile and infertile men. RESULT(S): In seminal plasma, ascorbate contributes almost twice as much as urate and thiol levels are about one third of ascorbate. Ascorbate levels in seminal plasma of asthenozoospermic individuals (+ROS) are significantly reduced. In sperm, thiols contributed most and ascorbate only a fraction of the total. CONCLUSION(S): In seminal plasma, ascorbate, urates, and thiols are the major antioxidants present. In contrast, within sperm, this group is the major contributor. In samples exhibiting ROS activity, ascorbate concentrations in the seminal plasma are significantly reduced.

Antioxidants↗
PubMed1997

The effect of hormone replacement therapy on the oxidation of low density lipoprotein in postmenopausal women.

The oxidative modification of low density lipoprotein (LDL) is important in the pathogenesis of atherosclerosis, and oestrogen has been shown to inhibit copper and cell mediated oxidation of LDL in vitro. We have investigated the effect of oral and transdermal oestrogens (oestradiol valerate 1 mg, conjugated equine oestrogens 0.625 mg and patches releasing 50 microg oestradiol daily), oestrogen implants (oestradiol 50 mg) and oral combined oestrogen and progestogen (oestradiol valerate 2 mg with medroxyprogesterone acetate 5 mg and oestradiol valerate 2 mg with norethisterone acetate 1 mg), on the susceptibility of LDL to oxidation in postmenopausal women (total n = 56). Oxidation of LDL was initiated by the addition of copper ions, and monitored by measurement of conjugated dienes. Changes in fasting serum levels of total cholesterol, LDL, HDL and triglycerides were also evaluated, as were changes in LDL composition. Total cholesterol decreased by 5.5% (P < 0.05) with CEE, 6.8% with oestradiol implants (P < 0.05), 9.3% with oestradiol + MPA (P < 0.01) and 10% with oestradiol + norethisterone (P < 0.05). There were reductions in LDL with oral oestradiol valerate (7.8%) (P < 0.05), CEE (13.8%) (P < 0.01) and oestradiol combined with MPA (12.7%) (P < 0.05). HDL increased by 7.1% (P < 0.01) and 6.3% (P < 0.05), with oestradiol valerate and CEE respectively, and decreased by 9% (P < 0.05) with implants and by 14.7% with oestradiol combined with norethisterone (P < 0.01). Triglycerides were significantly increased with CEE (14.9%) and reduced with oestradiol implants (15.2%) (both P < 0.05). While there was no change in the ratio of 'cholesterol ester' to 'free cholesterol' within LDL with any of the HRT preparations, a reduction in total cholesterol and cholesterol ester content of LDL occurred with transdermal oestradiol and a reduction in free cholesterol occurred with oestradiol plus MPA. Although we found a small but significant decrease in plasma hydroperoxide concentration four weeks after insertion of the oestradiol implant from 1.17 +/- 0.06 to 1.03 +/- 0.04 micromol/l (P < 0.05), we found no significant change in the lag time to oxidation, or in the maximum rate of propagation of the reaction, after treatment with any of the above forms of hormone replacement therapy. This study does not therefore support the role of oestrogens as antioxidants in vivo.

Administration, Cutaneous↗
PubMed1997

Relationships between children's cardiovascular stress responses and resting cardiovascular functioning 1 year later.

Resting cardiovascular parameters were predicted from anthropometric data, resting baseline cardiovascular data, and cardiovascular responses to three laboratory stressors completed 1 year earlier. Subjects were 106 male and female children (72 Whites, 34 Blacks) aged 6-7 years at the initial evaluation. During initial testing, blood pressure, heart rate, cardiac output, and total peripheral resistance were assessed at rest and also during a forehead cold pressor task, postural change, and treadmill exercise. The same cardiovascular parameters were then assessed at rest 1 year later. After controlling for significant anthropometric measures and the pertinent previous year's resting data, systolic and diastolic responses to the cold pressor were predictive of respective follow-up resting levels. Postural change heart rate responses were predictive of follow-up resting heart rate after controlling for initial resting levels. Exercise cardiac index reactivity predicted follow-up cardiac index after controlling for earlier resting levels and adiposity. Follow-up total peripheral resistance index was predicted by earlier resting levels.

Blood Pressure↗
PubMed1997

Sperm nitric oxide and motility: the effects of nitric oxide synthase stimulation and inhibition.

Nitric oxide (NO) is synthesized from L-arginine by a family of enzymes known as the nitric oxide synthases (NOS). We have recently shown a NOS similar to constitutive brain NOS (bNOS) and endothelial NOS (ecNOS) to be present in spermatozoa. The aim of this study is to investigate NO production by human spermatozoa and the effects of stimulation and inhibition of NOS. This was carried out using the Iso-NO, an isolated NO meter and sensor, which provides rapid, accurate and direct measurements of NO. Semen samples with normozoospermic and asthenozoospermic profiles were prepared using a direct swim-up technique. Basal concentrations of NO and stimulated NO production were measured after exposure to the calcium ionophore (A23187; 0.01-10 microM) a potent activator of constitutive NOS. NO production in human spermatozoa was significantly increased by the addition of A23187 30 seconds after stimulation. Furthermore, this response was greatly diminished by pre-incubating the samples with competitive inhibitors of L-arginine, the substrate for NOS, before treatment with calcium ionophore. In the presence of N(G)-nitro-L-arginine methyl ester (L-NAME), N(G)-nitro-L-arginine (L-NA) or N(G)-methyl-L-arginine (L-NMMA; all at 10 microM), NO production was inhibited with a rank order of potency L-NAME > L-NMMA > L-NA which is in accordance with the inhibition of an endothelial type of constitutive NOS.

Calcimycin↗
PubMed1997

A randomised controlled trial evaluating a novel cytotoxic drug delivery system for the treatment of cervical intraepithelial neoplasia.

OBJECTIVE: To investigate the efficacy of a novel method for the treatment of cervical intraepithelial neoplasia. A cytotoxic drug delivery system using a bilaminar bioadhesive polymeric film was applied directly to the cervix. This cytotoxic drug delivery system allowed the dose, the site and the duration of application of the cytotoxic drug (5-fluorouracil) to be controlled. DESIGN: A prospective, double-blind randomised controlled trial. SETTING: The Departments of Obstetrics and Gynaecology and Pathology of Belfast City Hospital and The Queen's University of Belfast, and the Department of Pharmacy of The Queen's University of Belfast. PARTICIPANTS: One hundred and four patients who had been referred to the colposcopy outpatient clinic because of abnormal cervical cytology were recruited into the trial. They were assessed colposcopically and biopsies for histopathology were obtained. Only patients with cervical intraepithelial neoplasia lesions Grades 1 and 2 were recruited. INTERVENTIONS: All patients were re-assessed one, three, and six months after application of the cytotoxic drug delivery system by colposcopy. Clinical endpoints were noted. MAIN OUTCOME MEASURES: Pre-treatment histopathological biopsy results were compared with those obtained after treatment. RESULTS: The cytotoxic drug delivery system fulfilled the requirements for treatment of cervical intraepithelial neoplasia without causing any architechtural damage, but the chemotherapeutic agent, 5-fluorouracil, did not provide effective treatment of disease. CONCLUSIONS: This study showed that the delivery system was effective, and further studies using this mechanism are now possible.

Administration, Topical↗
PubMed1996

Functional imaging of human right hemispheric activation for exploratory movements.

We employed positron emission tomography to examine the functional anatomy of the exploratory-motor aspect of spatial attention. Subjects moved their right hand under nonexploratory (control) versus exploratory (active) conditions. Movement architecture and eye movements were matched across conditions. Statistical parametric maps of the exploratory (active) minus nonexploratory (control) tasks in subjects using their right hand in the right hemispace demonstrated activation in right cingulate, premotor and posterior parietal areas. The net activation of multiple right hemisphere cortical areas ipsilateral to the active limb and hemispace strongly supports the predicted, distributed network anatomy and is consistent with possible right hemispheric dominance for exploratory attentional movements.

Adult↗
PubMed1996

The effect of various oestrogens and progestogens on the susceptibility of low density lipoproteins to oxidation in vitro.

OBJECTIVE: To investigate the effect of different oestrogens and progestogens, at various concentrations, on the oxidation of low density lipoproteins (LDL) in vitro. METHODS: Oestradiol, oestrone, oestriol and equilin, as well as medroxyprogesterone acetate, norgestrel and norethisterone, were added to isolated male LDL, before it was oxidised in the presence of copper ions at 37 degrees C. The oxidation process was monitored spectrophotometrically by the production of conjugated dienes. The lag time to oxidation and the maximum rate of propagation of the reaction were used as measures of the resistance and susceptibility of the LDL to oxidation respectively. RESULTS: The lag time was increased from 43.7 +/- 1.5 min (mean +/- SEM) for LDL without any added hormone, to 81.2 +/- 1.0 min by 1 microM oestradiol (P < 0.01), 77.9 +/- 4.6 min by 1 microM oestrone (P < 0.01), 67.6 +/- 6.2 min by 1 microM equilin (P < 0.01), and 51.8 +/- 2.8 min by 1 microM oestriol (P < 0.05). The maximum rate of propagation of the reaction was decreased from 0.23 +/- 0.01 nmol conjugated dienes/mg LDL-protein/min (mean +/- SEM) (control LDL) to 0.14 +/- 0.006 nmol/mg/min by oestradiol (P < 0.01), 0.15 +/- 0.009nmol/mg/min by oestrone (P < 0.01), 0.17 +/- 0.012 nmol/mg/min by equilin (P < 0.01) and 0.19 +/- 0.014 nmol/mg/min (P < 0.05) by oestriol. The progestogens alone had no antioxidant effect, nor did their addition to the oestrogens influence their antioxidant activity. CONCLUSIONS: These results demonstrate that all oestrogens investigated have an inhibitory effect on LDL oxidation in vitro. The magnitude of this effect varied, being of the order oestradiol > oestrone > equilin > oestriol.

Dose-Response Relationship, Drug↗
PubMed1996

Molecular analysis of HLA-DQB1 alleles in childhood common acute lymphoblastic leukaemia.

Epidemiological studies suggest that childhood common acute lymphoblastic leukaemia (c-ALL) may be the rare outcome of early post-natal infection with a common infectious agent. One of the factors that may determine whether a child succumbs to c-ALL is how it responds to the candidate infection. Since immune responses to infection are under the partial control of (human leucocyte antigen) HLA genes, an association between an HLA allele and c-ALL could provide support for an infectious aetiology. To define the limit of c-ALL susceptibility within the HLA region, we have compared HLA-DQB1 allele frequencies in a cohort of 62 children with c-ALL with 76 newborn controls, using group-specific polymerase chain reaction (PCR) amplification, and single-strand conformation polymorphism (SSCP) analysis. We find that a significant excess of children with c-ALL type for DQB1*05 [relative risk (RR): 2.54, uncorrected P=0.038], and a marginal excess with DQB1*0501 (RR: 2.18; P=0.095). Only 3 of the 62 children with c-ALL have the other susceptibility allele, DPB1*0201 as well as DQB1*0501, whereas 15 had one or the other allele. This suggests that HLA-associated susceptibility may be determined independently by at least two loci, and is not due to linkage disequilibrium. The combined relative risk of the two groups of children with DPB1*0201 and/or DQB1*0501 is 2.76 (P=0.0076). Analysis of amino acids encoded by exon 2 of DQB1 reveal additional complexity, with significant (P<0.05) or borderline-significant increases in Gly26, His30, Val57, Glu66-Val67 encoding motifs in c-ALL compared with controls. Since these amino acids are not restricted to DQB1*0501, our results suggest that, as with DPB1, the increased risk of c-ALL associated with DQB1 is determined by specific amino acid encoding motifs rather than by an individual allele. These results also suggest that HLA-associated susceptibility to c-ALL may not be restricted to the region bounded by DPB1 and DQB1.

Alleles↗
PubMed1996

Nitric oxide synthase and nitrite production in human spermatozoa: evidence that endogenous nitric oxide is beneficial to sperm motility.

The aim of this study was to investigate the presence of nitric oxide synthase (NOS) and the production of nitric oxide (NO) by human spermatozoa. Immunoreactivity was examined using a polyclonal antibody raised against porcine cerebellar nitric oxide synthase and monoclonal endothelial (eNOS) and brain (bNOS) antibodies. Using each antibody, NOS was observed localized in the head and midpiece regions of the spermatozoon. Immunofluorescence observed for eNOS and bNOS was more intense in normozoospermic samples. Sperm motility was assessed by computer-assisted semen analysis (CASA) in the presence and absence of NG-nitro-L-arginine methyl ester (L-NAME; 10(-5)M), and NO synthesis inhibitor or tumour necrosis factor (TNF)-alpha (20 IU/ml), a superoxide inducer. In the presence of L-NAME, percentage progressive motility, average path velocity (VAP), straight line velocity (VSL) and curvilinear velocity (VCL) were significantly reduced after 30 min. Sperm viability was not decreased by TNF alpha or L-NAME. The accumulation of nitrite (the stable end-product of the NOS/NO pathway) by spermatozoa was measured using the Griess reaction. After 8 h, nitrite concentrations were lower in asthenozoospermic compared to normozoospermic samples. In the presence of TNF alpha, nitrite accumulation was significantly reduced in normozoospermic samples. We conclude that NOS is present in human spermatozoa and that eNOS and bNOS are abundant in normozoospermic samples. Nitric oxide (at endogenous concentrations) appears to be necessary for adequate sperm motility.

Animals↗
PubMed1996

A comparison of baseline and induced DNA damage in human spermatozoa from fertile and infertile men, using a modified comet assay.

Baseline DNA damage in spermatozoa from fertile and infertile men was compared using a modified alkali single cell gel electrophoresis (comet) assay. Semen from normozoospermic fertile, normozoospermic infertile and asthenozoospermic infertile (World Health Organization criteria, 1992) samples were studied. No significant difference was observed in levels of baseline damage between the three groups. A median value for baseline damage of approximately 20% (80% head DNA) was obtained in all samples. Irradiation with X-rays (5-30 Gy) produced no additional damage in fertile samples when median values were examined. However, irradiation with 30 Gy X-rays produced significant damage in both infertile groups. Hydrogen peroxide (40 microM) treatment induced significant damage in the asthenozoospermic group, whereas 100 microM H2O2 was required to cause significant damage in the normozoospermic fertile and infertile samples. Within the fertile population a subgroup in which percentage head DNA was greater than 80% was observed in both treated and untreated specimens. This subgroup significantly decreased with treatment in both infertile groups. We conclude that the asthenozoospermic infertile group is more susceptible to damage than the normozoospermic infertile group, which in turn is more susceptible than the fertile group. The fertile group contains a resistant subpopulation of spermatozoa with relatively intact DNA.

DNA↗
PubMed1996

The passing score in the objective structured clinical examination.

The objective structured clinical examination (OSCE) now has an established place in the assessment of the medical undergraduate. While much has been written about the reliability of the OSCE, empirical work on the determination of the passing score which represents competence on the OSCE is rarely encountered. If the OSCE is to play its role in the 'high stakes' testing of clinical competence, it is important that this passing score be set reliably and defensibly. This article illustrates how a two-session modified Angoff standard-setting procedure is used to set the passing score on a 14 station Obstetrics and Gynaecology OSCE used to assess final year students at The Queen's University of Belfast. The Angoff methodology harnesses the professional judgement of expert judges to establish defensible standards. Four university teachers, five non-academic consultants and six junior clinical staff took part in a two-session Angoff standard-setting procedure. In the first session, the judges (individually and in silence) used their professional judgement to estimate the score which a minimally competent final year obstetrics and gynaecology student should achieve on each tested element of the OSCE. In the second session they revised their session 1 judgements in the light of the OSCE scores of real students and the opportunity for structured discussion. The passing score for the OSCE is reported together with the statistical measures which assure its reliability.

Clinical Competence↗
PubMed1996

Young children's cardiovascular stress responses predict resting cardiovascular functioning 2 1/2 years later.

BACKGROUND: Since the pathogenesis of coronary heart disease (CHD) has its origins in childhood, researchers have increasingly evaluated CHD risk factors in youth. In this study we examined the hypothesized behavioral risk factor of cardiovascular responsivity as a predictor of very young children's resting cardiovascular functioning 2 1/2 years later. SUBJECTS AND METHODS: During an initial visit to the laboratory, 97 children (30 blacks and 67 whites, 45 boys and 52 girls) aged 6-7 years completed three laboratory stressor tests (forehead cold pressor, postural change, and treadmill exercise). A comprehensive cardiovascular assessment was conducted during the tests. Resting cardiovascular activity (baseline values) was also assessed. Follow-up resting cardiovascular parameters were measured in the laboratory 2 1/2 years later. RESULTS: Cardiovascular stress responses were predictive of cardiovascular follow-up resting levels 2 1/2 years later. Multiple regression was used to evaluate the independent predictive power of stress responses after controlling for traditional risk factors. Follow-up resting systolic blood pressure (SBP) was predicted by the SBP response to postural change and treadmill exercise. Follow-up resting diastolic blood pressure (DBP) was predicted by the DBP response during treadmill exercise, particularly for blacks. The follow-up resting heart rate was predicted by the heart rate response to the forehead cold pressor and treadmill exercise. CONCLUSION: These results show that in very young children, stress responses are predictive of resting cardiovascular functioning 2 1/2 years later. Further developmental and longitudinal investigations will determine whether such responses are predictive of later preclinical manifestations of cardiovascular disease. If so, incorporation of stress testing in a standardized risk identification protocol might aid the design and practice of cardiovascular preventive medicine.

Analysis of Variance↗
PubMed1995

Estrogen replacement therapy in practice: trends and issues.

Since their availability in 1926, estrogens and their use in postmenopausal women have met with both acceptance and alarm by the medical profession and potential estrogen users. It was not until the 1980s that long-term research began to demonstrate the beneficial effects of estrogen, thus contributing to a significant increase in use during the past decade. This article provides information on current use of estrogen replacement therapy and describes factors influencing continuance. Poor continuance remains a barrier to the full potential of estrogen replacement therapy for postmenopausal women. The role of the physician in improving continuance is discussed.

Aged↗