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Biomedical subjects

C Foster

Publications and source records attributed to C Foster.

At least 37 records · Page 2Linked to original sources
PubMed2004

Effect of competitive distance on energy expenditure during simulated competition.

Concepts of how athletes should expend their aerobic and anaerobic energetic reserves are generally based on results of tests where an "all out" strategy is imposed on/required from the athlete. We sought to determine how athletes spontaneously expend their energetic reserves when the only instruction was to finish the event in minimal time, as in competition. Well trained, and task habituated, road cyclists (N = 14) completed randomly ordered laboratory time trials of 500 m, 1000 m, 1500 m and 3000 m on a windload braked cycle ergometer. The pattern of aerobic and anaerobic energy use was calculated from total work accomplished and V.O (2) during the trials. The events were completed in 40.3 +/- 0.6 s, 87.4 +/- 4.1 s, 133.8 +/- 6.6 s and 296.0 +/- 7.2 s. The peak V.O (2) during the terminal 200 m of all events was similar (2.72 +/- 0.22, 3.01 +/- 0.34, 3.23 +/- 0.44 and 3.12 +/- 0.13 l x min (-1)). In all events, the initial power output and anaerobic energy use was high, and decreased to a more or less constant value over the remainder of the event. However, the subjects seemed to reserve some ability to expend energy anaerobically for a terminal acceleration which is contrary to predictions of an "all out" starting strategy. Although the total work accomplished increased with distance (23.14 +/- 4.24, 34.14 +/- 6.37, 43.54 +/- 6.12 and 78.22 +/- 8.28 kJ), the energy attributable to anaerobic sources was not significantly different between the rides (17.29 +/- 3.82, 18.68 +/- 8.51, 20.60 +/- 6.99 and 23.28 +/- 9.04 kJ). The results are consistent with the concept that athletes monitor their energetic resources and regulate their energetic output over time in a manner designed to optimize performance.

Adult↗
PubMed2004

Non-uptake of predictive genetic testing for BRCA1/2 among relatives of known carriers: attributes, cancer worry, and barriers to testing in a multicenter clinical cohort.

BRCA1/2 test decliners/deferrers have received almost no attention in the literature and this is the first study of this population in the United Kingdom. The aim of this multicenter study is to examine the attributes of a group of individuals offered predictive genetic testing for breast/ovarian cancer predisposition who did not wish to proceed with testing at the time of entry into this study. This forms part of a larger study involving 9 U.K. centers investigating the psychosocial impact of predictive genetic testing for BRCA1/2. Cancer worry and reasons for declining or deferring BRCA1/2 predictive genetic testing were evaluated by questionnaire following genetic counseling. A total of 34 individuals declined the offer of predictive genetic testing. Compared to the national cohort of test acceptors, test decliners are significantly younger. Female test decliners have lower levels of cancer worry than female test acceptors. Barriers to testing include apprehension about the result, traveling to the genetics clinic, and taking time away from work/family. Women are more likely than men to worry about receiving less screening if found not to be a carrier. The findings do not indicate that healthy BRCA1/2 test decliners are a more vulnerable group in terms of cancer worry. However, barriers to testing need to be discussed in genetic counseling.

Adult↗
PubMed2003

Balancing autonomy and responsibility: the ethics of generating and disclosing genetic information.

Using data obtained during a retrospective interview study of 30 women who had undergone genetic testing-BRCA1/2 mutation searching-this paper describes how women, previously diagnosed with breast/ovarian cancer, perceive their role in generating genetic information about themselves and their families. It observes that when describing their motivations for undergoing DNA testing and their experiences of disclosing genetic information within the family these women provide care based ethical justifications for their actions. Finally, it argues that generating genetic information and disclosing this information to kin raise different types of ethical issues. The implications of these findings for ethical debates about informed choice in the context of genetic testing are discussed.

Adult↗
PubMed2002

Predictive testing for BRCA1/2: attributes, risk perception and management in a multi-centre clinical cohort.

The aim of this multi-centre UK study is to examine the attributes of a cohort offered predictive genetic testing for breast/ovarian cancer predisposition. Participants are adults unaffected with cancer from families with a known BRCA1/2 mutation. This is the first large multi-centre study of this population in the UK. The study evaluates mental health, perceived risk of developing cancer, preferred risk management options, and motivation for genetic testing. Participants were assessed when coming forward for genetic counselling prior to proceeding to genetic testing. Three hundred and twelve individuals, 76% of whom are female, from nine UK centres participated in the study. There are no gender differences in rates of psychiatric morbidity. Younger women (<50 years) are more worried about developing cancer than older women. Few women provide accurate figures for the population risk of breast (37%) or ovarian (6%) cancer but most think that they are at higher risk of developing breast (88%) and ovarian (69%) cancer than the average woman. Cancer related worry is not associated with perceived risk or uptake of risk management options except breast self-examination. The findings indicate that younger women may be particularly vulnerable at the time of the offer of a predictive genetic test.

Adult↗
PubMed2002

Genetic testing for women previously diagnosed with breast/ovarian cancer: examining the impact of BRCA1 and BRCA2 mutation searching.

This study sought to investigate the impact of BRCA1 and BRCA2 mutation searching on women previously diagnosed with breast or ovarian cancer. In-depth interviews were undertaken with 30 women who had undergone a BRCA1 and BRCA2 mutation search within the clinical setting. The main reasons reported for undergoing mutation searching were: to provide genetic information for other family members, general altruism, curiosity about the aetiology of cancer, and to provide information to facilitate risk management decisions. In the main, the process of undergoing genetic testing was not experienced as anxiety provoking. The benefit of receiving a result confirming the presence of a genetic mutation was seen as an end to uncertainty, whereas the costs included difficulties in disclosing information to kin and potentially increased anxiety about one's own or others' cancer risks. Women receiving an inconclusive test result reported a range of emotional reactions. There was evidence that some women misunderstood the meaning of this result, interpreting it as definitive confirmation that a cancer-predisposing mutation was not present within the family. It is concluded that women with cancer who participate in BRCA1 and BRCA2 testing need to receive clear information about the meaning and implications of the different types of test results. Some recommendations for clinical practice are discussed.

Adult↗
PubMed2001

Unique pathway of thrombin-induced platelet aggregation mediated by glycoprotein Ib.

Thrombin plays a central role in normal and abnormal hemostatic processes. It is assumed that alpha-thrombin activates platelets by hydrolyzing the protease-activated receptor (PAR)-1, thereby exposing a new N-terminal sequence, a tethered ligand, which initiates a cascade of molecular reactions leading to thrombus formation. This process involves cross-linking of adjacent platelets mediated by the interaction of activated glycoprotein (GP) IIb/IIIa with distinct amino acid sequences, LGGAKQAGDV and/or RGD, at each end of dimeric fibrinogen molecules. We demonstrate here the existence of a second alpha-thrombin-induced platelet-activating pathway, dependent on GP Ib, which does not require hydrolysis of a substrate receptor, utilizes polymerizing fibrin instead of fibrinogen, and can be inhibited by the Fab fragment of the monoclonal antibody LJIb-10 bound to the GP Ib thrombin-binding site or by the cobra venom metalloproteinase, mocarhagin, that hydrolyzes the extracellular portion of GP Ib. This alternative alpha-thrombin pathway is observed when PAR-1 or GP IIb/IIIa is inhibited. The recognition sites involved in the cross-linking of polymerizing fibrin and surface integrins via the GP Ib pathway are different from those associated with fibrinogen. This pathway is insensitive to RGDS and anti-GP IIb/IIIa antibodies but reactive with a mutant fibrinogen, gamma407, with a deletion of the gamma-chain sequence, AGDV. The reaction is not due to simple trapping of platelets by the fibrin clot, since ligand binding, signal transduction, and second messenger formation are required. The GP Ib pathway is accompanied by mobilization of internal calcium and the platelet release reaction. This latter aspect is not observed with ristocetin-induced GP Ib-von Willebrand factor agglutination nor with GP Ib-von Willebrand factor-polymerizing fibrin trapping of platelets. Human platelets also respond to gamma-thrombin, an autoproteolytic product of alpha-thrombin, through PAR-4. Co-activation of the GP Ib, PAR-1, and PAR-4 pathways elicit synergistic responses. The presence of the GP Ib pathway may explain why anti-alpha-thrombin/anti-platelet regimens fail to completely abrogate thrombosis/restenosis in the cardiac patient.

Adenosine Triphosphate↗
PubMed2001

Discovery of 4-[3-(trans-3-dimethylaminocyclobutyl)-1H-indol-5-ylmethyl]-(4S)-oxazolidin-2-one (4991W93), a 5HT(1B/1D) receptor partial agonist and a potent inhibitor of electrically induced plasma extravasation.

Utilizing a pharmacophoric model of binding of 3-(2-aminoethyl)indoles to 5HT(1B/1D) receptors, we identified the 3-aminocyclobutyl group as a potential ethylamine isostere. A novel multidimensional chemometric approach was used to predict the intrinsic activity (degree of agonism) at the receptor. A qualitative model for pharmacokinetic properties was then used to guide the synthesis toward molecules likely to have oral bioavailability in humans. A novel synthetic route to 3-(3-dimethylaminocyclobutyl)indoles was developed. Analogues showed generally lower intrinsic activity at 5HT(1B/1D) receptors than their ethylamine counterparts. 4-[3-(trans-3-Dimethylaminocyclobutyl)-1H-indol-5-ylmethyl]-(4S)-oxazolidin-2-one (4991W93, 1) was identified as a partial agonist against 5HT(1B/1D) receptors, with low intrinsic activity. This molecule also has significant activity against 5HT(1F) receptors but is selective over other 5HT receptors. In addition this compound was found to be an exceptionally potent inhibitor of electrically induced plasma extravasation. Compound 1 may have utility in the treatment and prophylaxis of migraine.

Administration, Oral↗
PubMed2001

Physical activity and exercise training prescriptions for patients.

The dominant outcome from exercise prescription is an increase in various markers of exercise capacity. A very large group of studies have demonstrated that the VO2max is increased in response to exercise performed according to well-accepted principles of exercise prescription. Other markers of exercise capacity, such as the VT, also improve substantially following exercise training. Finally, improvement in exercise capacity is generally related to improved quality of life, particularly in patients with exercise capacity limited by various disease processes. Beyond the specific physiologic gains from training, exercise contributes to a better overall clinical outcome. Although there are few data conclusively demonstrating that exercise independently causes favorable changes in other risk factors, it should be recognized that exercise can contribute indirectly to modulation of other risk factors. Exercise represents positive health advice. Since most of our other recommendations to patients are in the nature of negative advice (e.g., don't smoke, don't eat high-fat foods), and since people are infamous for ignoring negative advice, the value of using a positive recommendation that may indirectly lead the patient to discontinue bad behaviors can hardly be overstated.

Cardiac Rehabilitation↗
PubMed2001

Treatment demands and differential treatment of patients with cystic fibrosis and their siblings: patient, parent and sibling accounts.

Cystic fibrosis (CF) is a progressive disease with no known cure. Advances in diagnosis and treatment have resulted in patients living longer and thus families live with the illness for longer. Treatments are becoming increasingly demanding and are largely performed in the family home. Mothers are often reported to experience greater stress and poorer adjustment than mothers of well children or population norms. Patients and siblings are also reported to display adjustment difficulties. Siblings have rarely been included in research designs. This qualitative study investigates the impact of CF and treatment on eight patients, eight mothers, one father and eight siblings. A family systems perspective was adopted. Each individual was interviewed independently using semistructured interviews. Patients and siblings were aged between 9 and 21 years. Qualitative analyses revealed high levels of non-adherence (intentional and unintentional) and parental involvement in treatment, minimal involvement of siblings, and preferential treatment towards patients. Demanding treatment, coupled with the progressive nature of CF, promote high levels of parental involvement for younger children as well as older teenagers, often due to attempted or actual non-adherence. Siblings may receive less attention while patients' needs take priority. Future development of a measure of adherence suitable for children and adolescents should take into account different motivations for non-adherence, particularly regarding the level of personal control over adherence to treatment. In addition, the potential impact of having a brother or sister with CF should not be underestimated and the needs of siblings should not go unnoticed.

Adaptation, Psychological↗
PubMed2001

Last but not least.

When a simple rectangular grid is drawn toward one's face there is the striking illusion that a spherical bulge is protruding from the grid. This illusion may be helpful in studying the interaction of spatial and motion processing.

Humans↗
PubMed2001

Comparison of incremental treadmill exercise and free range running.

PURPOSE: The aim of this study was to compare physiological responses during incremental treadmill exercise and free range running. METHODS: Fifteen competitive cross-country runners performed an incremental treadmill test and an unpaced 1-mile run on an indoor 200-m track. Physiological variables (VO(2peak), HR(peak), VO(2) x HR(-1)(peak), V(Epeak)) were measured using a portable metabolic analyzer. Blood lactate was measured post exercise. Outcome variables were analyzed with repeated measures ANOVA. RESULTS: Although directionally similar to previous studies with cycle ergometry, the observed peak values (track vs treadmill) for VO(2) (63.0 +/- 7.4 vs 61.9 +/- 7.2 mL x kg(-1) x min(-1)), V(E) (147 +/- 37 vs 144 +/- 30 L x min(-1)), HR (188 +/- 5 vs 189 +/- 7 beats.min-1), and VO(2) x HR(-1) (22.1 +/- 4.4 vs 21.5 +/- 4.5) were not significantly different. The observed peak values for blood lactate (14.4 +/- 3.3 vs 11.7 +/- 3.0 mmol x L(-1)) were significantly (P < 0.05) different. CONCLUSIONS: The results are not in full agreement with previous findings from cycling studies with the exception of post exercise blood lactate. Whether this represents a fundamental lack of effect of free range exercise or is related to mode specificity remains to be determined.

Adult↗
PubMed2001

Delayed puberty.

Explore the source record for details and available documents.

Adaptation, Psychological↗
PubMed2001

The Listening Skills Test--a new instrument to assess children's pragmatic ability.

Research has established that the development of autonomous (as opposed to collaborative) communication skills, using referential communication speaker and listener tasks, develops only slowly during the primary school years. Such a finding has implications for the classroom which puts a premium on independent language processing. Although the importance of oral language is recognised in the National Curriculum, there has been little attempt to assess the ability formally. The Listening Skills Test is a standardised pragmatic instrument focusing on the 3 1/2-7 years age group. The test is in four parts and assesses the ability to make judgements about the efficacy of verbal messages or instructions. Tasks include relating messages to arrays of pictorial items, making judgements about statements that refer to one complex picture, marking routes on a street plan in response to an extended set of instructions, and the ability to evaluate purely verbal utterances. The overall aim of the test is to assess children's ability to make sense on their own of verbal information in a decontextualised situation thought to represent the nature of much transactional communication in the classroom. Suggestions for remediation that have arisen from research conducted by the authors are also discussed.

Child↗
PubMed2001

Antimetastasis gene expression and numerical chromosomal abnormalities of chromosomes 1 & 17 in serous tumours of the ovary.

OBJECTIVE(S): The aim of this study was to examine the expression of the antimetastasis gene nm23 and numerical changes on chromosome 1 and 17 in ovarian tumours. METHODS: In this study 20 serous cystadenocarcinomas, ten borderline and five benign tumours were analysed for expression of the nm23 antimetastasis gene by immunohistochemistry and for numerical chromosomal abnormalities of chromosomes 1 and 17 by interphase cytogenetics. RESULTS: Strong intracytoplasmic immunoreactivity with the antimetastasis gene was observed in late stage carcinomas but not in benign or borderline tumours or in lymph node metastases. Numerical abnormalities were only observed in carcinomas. CONCLUSION(S): These sets of data are consistent with the majority of benign and borderline tumours lacking invasive potential. Odds Ratio (OR) assessment indicates that the presence of numerical aberrations correlates with immunopositivity.

Analysis of Variance↗
PubMed2001

A new approach to monitoring exercise training.

The ability to monitor training is critical to the process of quantitating training periodization plans. To date, no method has proven successful in monitoring training during multiple types of exercise. High-intensity exercise training is particularly difficult to quantitate. In this study we evaluate the ability of the session rating of perceived exertion (RPE) method to quantitate training during non-steady state and prolonged exercise compared with an objective standard based on heart rate (HR). In a 2-part design, subjects performed steady state and interval cycle exercise or practiced basketball. Exercise bouts were quantitated using both the session RPE method and an objective HR method. During cycle exercise, the relationship between the exercise score derived using the session RPE method and the HR method was highly consistent, although the absolute score was significantly greater with the session RPE method. During basketball, there was a consistent relationship between the 2 methods of monitoring exercise, although the absolute score was also significantly greater with the session RPE method. Despite using different subjects in the 2 parts of the study, the regression relationships between the session RPE method and the HR method were nearly overlapping, suggesting the broad applicability of this method. We conclude that the session RPE method is a valid method of quantitating exercise training during a wide variety of types of exercise. As such, this technique may hold promise as a mode and intensity-independent method of quantitating exercise training and may provide a tool to allow the quantitative evaluation of training periodization plans.

Adult↗
PubMed2000

Inhibition of cellular action of thrombin by N3-cyclopropyl-7-[[4-(1-methylethyl)phenyl]methyl]-7H-pyrrolo[3, 2-f]quinazoline-1,3-diamine (SCH 79797), a nonpeptide thrombin receptor antagonist.

A growing body of evidence suggests an important contribution of the cellular actions of thrombin to thrombosis and restenosis following angioplasty. Recently we reported on SCH 79797 (N3-cyclopropyl-7-¿[4-(1-methylethyl)phenyl]methyl¿-7H-pyrrolo[3, 2-f]quinazoline-1,3-diamine) and its analogs as new potent, nonpeptide thrombin receptor antagonists. This study further characterizes the biochemical and pharmacological actions of pyrroloquinazoline inhibitors of protease activated receptor-1 (PAR-1) in human platelets and coronary artery smooth muscle cells (hCASMC). SCH 79797 and its N-methyl analog (SCH 203099) inhibited binding of a high-affinity thrombin receptor-activating peptide ([(3)H]haTRAP, Ala-Phe(p-F)-Arg-ChA-HArg-[(3)H]Tyr-NH(2)) to PAR-1 with IC(50) values of 70 and 45 nM, respectively. SCH 79797 inhibited [(3)H]haTRAP binding in a competitive manner. SCH 79797 and SCH 203099 inhibited alpha-thrombin- and haTRAP-induced aggregation of human platelets, but did not inhibit human platelet aggregation induced by the tethered ligand agonist for protease-activated receptor-4 (PAR-4), gamma-thrombin, ADP, or collagen. SCH 203099 inhibited surface expression of P-selectin induced by haTRAP and thrombin, and it did not increase P-selectin expression or prevent thrombin cleavage of the receptor. Thrombin and TFLLRNPNDK-NH(2) (TK), a PAR-1-selective agonist, produced transient increases in cytosolic free Ca(2+) concentration ([Ca(2+)](i)) in hCASMC. This increase in [Ca(2+)](i) was inhibited effectively by SCH 79797. However, the Ca(2+) transients induced by SLIGKV-NH(2,) a PAR-2-selective agonist, were not inhibited by SCH 79797. Thrombin- and TK-stimulated [(3)H]thymidine incorporation also was inhibited completely by SCH 79797. The results of this study demonstrate that SCH 79797 and SCH 203099 are potent, selective antagonists of PAR-1 in human platelets and hCASMC. These data also suggest that the thrombin stimulation of Ca(2+) transients and mitogenesis in hCASMC is mediated primarily through activation of PAR-1.

Apoptosis Regulatory Proteins↗
PubMed2000

Decreased HLA-A expression in prostate cancer is associated with normal allele dosage in the majority of cases.

A comparison has been made of the phenotypic expression of MHC class I antigens with the corresponding HLA-A genotype in 15 cases of benign prostatic hyperplasia (BPH) and 34 cases of primary locally invasive prostatic carcinoma. Expression of class 1 protein, detected by immunocytochemistry, was partially or completely lost in approximately 90% of the tumours examined. Comparative genomic analysis of the beta2 microglobulin (beta2m) gene and 15 individual HLA-A haplotypes using a polymerase chain reaction (PCR)-based method demonstrated abnormal gene dosage in the minority of cases: homozygous deletion of the beta2m locus was detected in one case and HLA-A allele in two cases (HLA-A1 and HLA-A2, respectively), representing approximately 8% of the population studied. This first comparative study of gene dosage and expression of class 1 protein reported for prostate cancer reveals that deletion is not the cause of the partial or complete loss seen in the majority of cases. This raises the possibility, in the future, for novel selective immunomodulatory therapeutic strategies which stimulate a clinically significant re-expression of class 1 protein and associated cytotoxic T-cell response.

Alleles↗