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Biomedical subjects

W Thompson

Publications and source records attributed to W Thompson.

At least 19 recordsLinked to original sources

Adolescent males' experience of the counselling process.

This study examines 11 adolescent males' self-reports of their experiences of 23 counselling sessions to identify what they found helpful and unhelpful during key moments in the therapeutic process. The findings suggest that the experiences of the adolescent males in this study are similar in many ways to the to the reported experiences of adults in counselling. In particular, the experience of emotional support and relief appears to be highly significant for adolescent males, who give significantly lesser importance to cognitive task factors.

Adolescent↗

New carbamoylpiperidines as human platelet aggregation inhibitors.

A series of 3-carbamoylpiperidines (nipecotamides) are designed, synthesized and tested for their inhibitory action against adenosine diphosphate (ADP)-induced aggregation of human platelets. A structure-activity analysis of the bis(nipecotamido)aralkane type showed that a substituent on the piperidine ring should preferably be an amide and that the electronegativity of the carbonyl oxygen and the orientation of the amide group affected activities. Based on the knowledge of factors influencing platelet activation and aggregation, a nitric ester moiety which could release nitric oxide (NO) in situ, is incorporated into the nipecotamide structure. These compounds exhibit increased activity compared to those having no -ONO2 function. They also show stereoselectivity, with the meso isomer being approximately twice as potent as the synthetic diastereomeric mixture. Replacement of the -ONO2 function with hydroxyl, ester or alkyl groups considerably diminishes aggregation-inhibitory potential. Nipecotamides are shown here to inhibit the basal and collagen-induced rise in platelet inositol trisphosphate (IP3) levels, as well as phosphoinositide turnover. A comprehensive mechanism of action is proposed taking earlier results into consideration.

Adult↗

Human-mouse genome comparisons to locate regulatory sites.

Elucidating the human transcriptional regulatory network is a challenge of the post-genomic era. Technical progress so far is impressive, including detailed understanding of regulatory mechanisms for at least a few genes in multicellular organisms, rapid and precise localization of regulatory regions within extensive regions of DNA by means of cross-species comparison, and de novo determination of transcription-factor binding specificities from large-scale yeast expression data. Here we address two problems involved in extending these results to the human genome: first, it has been unclear how many model organism genomes will be needed to delineate most regulatory regions; and second, the discovery of transcription-factor binding sites (response elements) from expression data has not yet been generalized from single-celled organisms to multicellular organisms. We found that 98% (74/75) of experimentally defined sequence-specific binding sites of skeletal-muscle-specific transcription factors are confined to the 19% of human sequences that are most conserved in the orthologous rodent sequences. Also we found that in using this restriction, the binding specificities of all three major muscle-specific transcription factors (MYF, SRF and MEF2) can be computationally identified.

Algorithms↗

Acceptability and patterns of uterine bleeding in sequential trimegestone-based hormone replacement therapy: a dose-ranging study.

Trimegestone is a norpregnane progestogen which is being developed in combination with oral oestradiol as postmenopausal hormone replacement therapy (HRT). In this multicentre dose-ranging study using randomized parallel groups, four doses of trimegestone were used to compare data on the patterns of uterine bleeding, the endometrial histology, and the control of menopausal symptoms in 203 women who completed treatment for 6 months. The treatment consisted of micronized oestradiol (2 mg/day) and one of four doses of trimegestone, which was administered sequentially for days 15-28 of the treatment cycle. Higher doses of trimegestone were associated with later onset of bleeding, which was lighter and of shorter duration than that observed with lower doses. The variability of the day of onset of bleeding in individual women was greater when bleeding occurred before the end of the progestogen phase (early bleeders) than when it occurred afterwards (late bleeders). All women enrolled in the study experienced good control of menopausal symptoms, with minimal progestogenic adverse effects, there being no statistically significant difference between the four dose groups.

Aged↗

The Outpatient Developmental Services Project: integration of pediatric psychology with primary medical care for children infected with HIV.

OBJECTIVE: To present a model in which pediatric psychology services are programmatically integrated into the primary care of children seen in a special immunology program. The program centers around serial neurodevelopmental/neuropsychological evaluation of children infected with HIV. METHOD: We describe the population served and the particular services provided, with specific focus on how the program was developed. We include a discussion of the barriers to service provision that have been encountered and the strategies employed to overcome these challenges. CONCLUSIONS: This approach, while not ideal, serves as a good example of how pediatric psychology can merge with primary medical care to maximize the benefits of both specialties for a patient population that is underserved in many respects.

Acquired Immunodeficiency Syndrome↗

Effect of physical training on total and visceral fat in obese children.

PURPOSE: Children with high levels of total body fat mass (TFM) and visceral adipose tissue (VAT) have elevated levels of certain risk factors for coronary artery disease and non-insulin-dependent diabetes mellitus. We tested the hypothesis that controlled physical training, without dietary intervention, would have a favorable impact on VAT and percent body fat (%BF) in obese children. METHODS: A volunteer sample of 74 obese children, 7-11 yr of age, accepted random assignment to physical training or control groups. Before and after 4 months of intervention, measurements were obtained for VAT, TFM, %BF, daily physical activity, and cardiovascular fitness. The intervention involved 4 months of controlled physical training 5 d x wk(-1), 40 min per session, at a mean heart rate (HR) of 157 beats x min(-1). The estimated energy expenditure (EE) per training session was 925+/-201 kJ. RESULTS: Compared with the control group, the physical training group declined significantly in %BF (delta = -2.2%) (P < 0.01), TFM (delta = -3.1%) (P < 0.01), and subcutaneous abdominal adipose tissue (delta = - 16.1%) (P < 0.05), and increased significantly in fat-free mass (delta = +6.1%) (P < 0.05) and moderate-to-very hard physical activity (delta = +14.1%) (P < 0.05). The increase in VAT was significantly less in the physical training group (delta = +0.5%) as compared with that in the control group (delta = +8.1%) (P < 0.05). CONCLUSIONS: This study showed that during physical training obese children: 1) were capable of participating in a substantial amount of high intensity physical training over a 4-month period: 2) accumulated significantly less VAT as compared with nonexercising controls; and 3) experienced other beneficial changes in total and regional body composition.

Abdomen↗

Multi-institutional melanoma lymphatic mapping experience: the prognostic value of sentinel lymph node status in 612 stage I or II melanoma patients.

PURPOSE: To compare the effect of pathologic sentinel lymph node (SLN) status with that of other known prognostic factors on recurrence and survival in patients with stage I or II cutaneous melanoma. PATIENTS AND METHODS: We reviewed the records of 612 patients with primary cutaneous melanoma who underwent lymphatic mapping and SLN biopsy between January 1991 and May 1995 to determine the effects of tumor thickness, ulceration, Clark level, location, sex, and SLN pathologic status on disease-free and disease-specific survival. RESULTS: In the 580 patients in whom lymphatic mapping and SLN biopsy were successful, the SLN was positive by conventional histology in 85 patients (15%) but negative in 495 patients (85%). SLN status was the most significant prognostic factor with respect to disease-free and disease-specific survival by univariate and multiple covariate analyses. Although tumor thickness and ulceration influenced survival in SLN-negative patients, they provided no additional prognostic information in SLN-positive patients. CONCLUSION: Lymphatic mapping and SLN biopsy is highly accurate in staging nodal basins at risk for regional metastases in primary melanoma patients and identifies those who may benefit from earlier lymphadenectomy. Furthermore, pathologic status of the SLN in these patients with clinically negative nodes is the most important prognostic factor for recurrence. The information from SLN biopsy is particularly helpful in establishing stratification criteria for future adjuvant trials.

Biopsy↗

Temporal stability of ambulatory blood pressure and heart rate in youths.

BACKGROUND: The use of ambulatory blood pressure monitoring for pediatric populations is increasing. OBJECTIVE: ; To determine the 2-year stability of ambulatory blood pressure in youths. METHODS: We evaluated 2-year stabilities of resting and ambulatory blood pressures in 197 youths (aged 13.9+/-2.3 years at initial evaluation). Readings were taken every 20 min during the daytime (0800-2200 h) and every 30 min at night (0000-0600 h). RESULTS: Daytime and night-time systolic blood pressure increased (P < 0.01 for both) as did resting systolic blood pressure (P < 0.05). Measures of diastolic blood pressure did not change. Changes in systolic blood pressure were related to changes in body size. Estimates of stability for resting and ambulatory measurements were similar, ranging from 0.65 to 0.75. In addition, correlation coefficients for relationships between first and second readings for resting and ambulatory measurements were similar ranging from 0.43 and for resting heart rate to 0.72 for 24h systolic blood pressure (P < 0. 001 for each). The only significant correlation between change scores for resting and ambulatory values was that between resting and night-time diastolic blood pressures (r = 0.33, P < 0.001). CONCLUSION: Measures of blood pressure derived from ambulatory blood pressure monitoring reflect changes in blood pressure in youths at least as well as do changes in resting blood pressure despite the high degree of variability in levels of physical activity and affective states of the children during the ambulatory recordings.

Adolescent↗

Epidemiology of contralateral breast cancer.

Two to 11% of women diagnosed with breast cancer will develop contralateral breast cancer in their lifetime. Women with a first primary are at a 2-6-fold increased risk of developing contralateral breast cancer compared with the risk in the general population of women developing a first primary cancer. The incidence rate of contralateral breast cancer varies from four to eight per 1000 person-years. To assess the risk factors associated with the development of contralateral breast cancer among women with a first primary breast cancer, the epidemiological literature concerning these factors was reviewed and summarized. Studies have shown that a family history of breast cancer, an early age at initial diagnosis, and a lobular histology of the first primary breast cancer increase the risk of developing contralateral breast cancer. Although chemotherapy and tamoxifen therapy may reduce this risk, there are inconsistent results regarding the effects of radiotherapy and the effects of reproductive, environmental and other factors. Additional analytical studies addressing all potential risk factors associated with the development of contralateral breast cancer are necessary in view of the increasing incidence and survival of women with a first primary.

Breast Neoplasms↗

In vitro fertilization and pregnancy rates: the influence of sperm motility and morphology on IVF outcome.

OBJECTIVE: To determine the relationship between sperm motility and sperm morphology parameters and IVF and pregnancy rates. DESIGN: Pre- and postpreparation analysis of semen samples from infertile couples undergoing IVF-ET. SETTING: Andrology Laboratory, Royal Maternity Hospital, Belfast, Northern Ireland. PATIENT(S): One hundred fifty couples undergoing IVF-ET treatment at the Regional Fertility Centre. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): The ability of human sperm to achieve IVF and pregnancy was investigated in relation to motility parameters (assessed with computer-aided sperm analysis [Integrated Visual Optical System] and percent normal morphology (determined with the strict criteria). RESULT(S): Significant differences were observed in motility parameters and percent normal morphology in samples that achieved > or =50% fertilization compared with < or =50% fertilization and between samples that achieved a pregnancy compared with those that did not. Significant positive correlations were observed between percent progressive motility, the velocity of sperm movement, and morphology parameters and both IVF and pregnancy. CONCLUSION(S): Both sperm motility parameters and percent normal morphology are significant factors in predicting fertilization and pregnancy rates in IVF.

Adult↗

The effects of antioxidant supplementation during Percoll preparation on human sperm DNA integrity.

The integrity of sperm DNA is crucial for the maintenance of genetic health. A major source of damage is reactive oxygen species (ROS) generation; therefore, antioxidants may afford protection to sperm DNA. The objectives of the study were, first, to measure the effects of antioxidant supplementation in vitro on endogenous DNA damage in spermatozoa using the single cell gel electrophoresis (comet) assay and, second, to assess the effect of antioxidant supplementation given prior to X-ray irradiation on induced DNA damage. Spermatozoa from 150 patients were prepared by Percoll centrifugation in the presence of ascorbic acid (300, 600 microM), alpha tocopherol (30, 60 microM), urate (200, 400 microM), or acetyl cysteine (5, 10 microM). DNA damage was induced by 30 Gy X-irradiation. DNA strand breakage was measured using the comet assay. Sperm DNA was protected from DNA damage by ascorbic acid (600 microM), alpha tocopherol (30 and 60 microM) and urate (400 microM). These antioxidants provided protection from subsequent DNA damage by X-ray irradiation. In contrast, acetyl cysteine or ascorbate and alpha tocopherol together induced further DNA damage. Supplementation in vitro with the antioxidants ascorbate, urate and alpha tocopherol separately has beneficial effects for sperm DNA integrity.

Acetylcysteine↗

Prediction of left ventricular mass in youth with family histories of essential hypertension.

To determine predictors of left ventricular mass (LVM) and hypertrophy (LVH), 56 black and 30 white normotensive healthy youths (mean age 12.6 +/- 2.3 years at initial visit) were studied twice, 2.5 years apart. During the initial visit, anthropometric variables and hemodynamics were measured at rest and before, during, and after 4 physical and behavioral stressors. 2-D directed M-mode echocardiography was performed to derive LVM. Hierarchical multiple regression analyses indicated that follow-up LVM was predicted by initial LVM, weight, height (ht), and gender (males > females; total model R2 = 0.77, P < 0.0001). Predictors of LVM/ht2.7 were initial LVM/ht2.7, weight, ethnicity (blacks > whites), and the aggregate index of blood pressure reactivity (total model R2 = 0.66, P < 0.0001). Youth with LVH at follow-up were taller, heavier, and exhibited greater blood pressure reactivity at initial evaluation. These findings are important since interventional strategies can be developed that target obesity and exaggerated reactivity to stress.

Adolescent↗

Patient doses in abdominal aortogram and aorta femoral runoff examinations.

Radiation doses to adult male patients from abdominal aortogram and aorta femoral runoff examinations in a medical center were determined with the help of a dose-area product meter. The abdominal aortogram and aorta femoral runoff examination consisted of scout radiographs, fluoroscopy (to position a catheter near the area of interest), and serial films (to record the flow of contrast media). Measurements were converted to effective doses with the help of published results from Monte Carlo simulation calculations. Data from 19 male adult patients weighing 53 to 86 kg were analyzed. The resulting total effective dose had a value of 14.0 +/- 4A mSv (mean and standard deviation). The percent contribution by fluoroscopy was 18.5 +/- 9.9%. The fluoroscopy effective dose had a stronger correlation with the dose-area product (correlation coefficient of 0.97) than with duration of exposure (correlation coefficient of 0.84). Most of the radiation exposure in the observed abdominal aortogram and aorta femoral runoff examination was attributed to radiography.

Adult↗

A practical guide to prescribing hormone replacement therapy.

Over the past 20 years there has been increasing interest in the menopause and hormone replacement therapy (HRT). More recently, postmenopausal HRT has been seen as a specific treatment for symptoms in the short term and preventative therapy in the long term. Women must be counselled regarding the risks and benefits of HRT according to the best available evidence. The patient should also be actively involved in the decision regarding HRT therapy, which should then improve patient compliance. Generally, an appropriate regimen of HRT can be formulated for the majority of patients. Progestogen should be added to therapy in women with an intact uterus in a cyclical or continuous regimen. The management of common estrogenic and progestogenic adverse effects is important in improving compliance. At present, new drugs are being developed for the management of the menopause (selective estrogen receptor modulators and phytoestrogens). Obviously, further research will be necessary to determine whether these drugs have advantages over regular HRT. By offering postmenopausal women HRT an attempt is made to optimise their physical and psychological well-being. However, HRT is not without adverse effects, the most worrying of which is the possible increase in breast cancer risk with long term use. However, with patient education efforts, treatment regimens acceptable to both patient and practitioner can be initiated; in this regard, the aim of the practitioner should be to help the menopausal woman make the decision which is the most appropriate for her.

Contraindications↗

Improved sentinel lymph node localization in patients with primary melanoma with the use of radiolabeled colloid.

BACKGROUND: The purpose of this study was to determine whether the sentinel lymph node (SLN) localization technique, which uses blue dye and 99mTc-labeled sulfur colloid, provides advantages over blue dye alone in the management of patients with stages I and II cutaneous melanoma. METHODS: The records of 626 consecutive patients with melanoma who underwent lymphatic mapping and SLN biopsy between 1991 and 1997 at the M.D. Anderson Cancer Center were reviewed. Lymphatic mapping was performed with isosulfan blue dye alone (n = 252) or in combination with 99mTc-labeled sulfur colloid accompanied by a hand-held gamma probe (n = 374). SLNs were defined as those that stained blue or demonstrated increased focal radiotracer uptake. RESULTS: SLN identification rates improved from 87% (dye alone) to 99% (dye and colloid) (P < .0001) with the combined technique in all anatomic sites examined. The mean number of SLNs harvested from each basin was significantly greater in the patients mapped with dye and colloid (1.74 vs 1.31; P < .0001). Occult metastatic disease was identified in 17.5% of all patients and did not significantly differ between groups. In 92% of patients who had at least one positive SLN and were mapped with both agents, lymphatic metastases were identified in the SLN that contained the greatest radiotracer uptake. CONCLUSIONS: SLN identification is enhanced by the addition of radiolabeled sulfur colloid and intraoperative use of the hand-held gamma probe and may identify SLNs missed by the blue dye alone. These data support the combined use of radiolabeled sulfur colloid and blue dye in lymphatic mapping procedures to improve the nodal staging of stages I and II melanoma.

Adolescent↗

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↗

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↗

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↗