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Biomedical subjects

C Foster

Publications and source records attributed to C Foster.

At least 19 recordsLinked to original sources

Effects of detraining on the functional capacity of previously trained breast cancer survivors.

The purpose of this study was to assess the effects of a relatively short (8-weeks) period of detraining on cardiorespiratory capacity, dynamic strength endurance, task specific functional muscle capacity and quality of life (QOL) of breast cancer survivors who had previously undergone a combined supervised (aerobic and resistance) training program. Eleven women survivors of stage I - II ductal breast carcinoma (47 +/- 7 yrs) entered the study and performed a battery of tests (including anthropometric evaluation, a graded cycle ergometer test, tests of strength endurance [leg and bench press] and the sit-stand test) and completed a specific QOL questionnaire (EORTC-C30) at three time points: i) before, ii) after an exercise program (including aerobic and resistance exercises) of 8-weeks duration, and iii) after a subsequent 8-weeks period of training cessation. Training-induced improvements in strength endurance, muscle functional capacity (sit-stand test) and QOL were not significantly changed after detraining (p > 0.05 for post-training vs. detraining comparisons). The lack of significant loss in muscle strength endurance occurred despite significant losses in estimated total muscle mass after detraining (27.3 +/- 2.4 kg) compared with post-training (28.5 +/- 2.9 kg). In contrast, cardiorespiratory capacity was significantly decreased during detraining (V.O (2peak) of 29.0 +/- 4.6 vs. 22.7 +/- 3.9 ml . kg ( -1) . min (-1) at post-training vs. detraining, p < 0.01). In conclusion, cancer survivors who have participated in a combined training program can retain some of the training gains (particularly improved QOL and muscle strength endurance/functional performance) after a relatively short duration detraining period.

Breast Neoplasms↗

The relationship between access and quality of urban green space with population physical activity.

OBJECTIVES: This study examined the association between access to quality urban green space and levels of physical activity. STUDY DESIGN: A cross-sectional examination of the relationship between access to quality urban green space and level of recreational physical activity in 4950 middle-aged (40-70 years) respondents from the European Prospective Investigation into Cancer and Nutrition (EPIC), who resided in Norwich, UK. METHODS: Using geographic information systems (GIS), three measures of access to open green space were calculated based on distance only, distance and size of green space and distance, size and quality of green space. Multiple regression models were used to determine the relationship between the three indicators of access to open green space and level of recreational physical activity. RESULTS: There was no evidence of clear relationships between recreational activity and access to green spaces. Non-significant associations were apparent for all variables, and there was no evidence of a clear trend in regression coefficients across quartiles of access for either the distance, size adjusted, and quality and size-adjusted models. Furthermore, the neighbourhood measures of access to green spaces showed non-significant associations with recreational physical activity. CONCLUSIONS: Access to urban green spaces does not appear to be associated with population levels of recreational physical activity in our sample of middle-aged adults.

Adult↗

Mobilisation of mesenchymal cells into blood in response to skeletal muscle injury.

Mesenchymal cells recruited to damaged tissues must circulate through the bloodstream. The absolute numbers of circulating mesenchymal stem cells (cMSCs) in two different models of acute and chronic skeletal muscle injury were determined. cMSCs were present in significantly higher numbers in both models than in healthy controls. These results support the hypothesis that MSCs are mobilised into the bloodstream after skeletal muscle tissue damage. These two models (acute and chronic) would be of value in the search for molecular mediators of mobilisation of MSCs into the circulation.

Adult↗

ACTN3 genotype in professional endurance cyclists.

The Z-disk protein alpha-actinin-3 is only expressed in type II muscle fibres, which are responsible for generating forceful contractions at high velocity. Despite the evolutionary conservation of alpha-actinin-3, approximately one in every five Caucasians of European ancestry is totally deficient in this protein, due to homozygosity for a R577X polymorphism in the ACTN3 gene. This, together with the results of recent research on elite athletes, suggests that the "null" XX polymorphism might confer some advantage to endurance performance events. To test this hypothesis, we studied the frequency distribution of R577X genotypes in a group of 50 top-level male professional cyclists (26.9 +/- 0.4 yrs [mean +/- SEM]; VO2max: 73.5 +/- 0.8 ml x kg (-1) x min (-1)). Their results were compared with those of a group of 52 Olympic-class male endurance runners (26.8 +/- 0.6 yrs; VO2max: 73.3 +/- 0.8 ml x kg (-1) x min (-1)) and 123 healthy, sedentary male controls. All subjects were Caucasian, and of European ancestry. No significant differences (p > 0.05) were found between groups: RR: 28.5 %; RX: 53.6 % and XX: 17.9 % in controls; RR: 28.0 %; RX: 46.0 % and XX: 26.0 % in cyclists; and RR: 25.0 %; RX: 57.7 %; XX: 17.3 % in runners). No differences were found in indices of endurance performance (VO2peak or ventilatory thresholds) between athlete carriers of each R577X genotype. In summary, although the alpha-actinin-3 deficient XX genotype may be detrimental for sprint performance in humans, the R577X polymorphism of the ACTN3 gene does not appear to confer an advantage on the ability of male athletes to sustain extreme endurance performance.

Actinin↗

Exposure-efficacy relationships of a fingolimod-everolimus regimen in kidney transplant patients at risk for delayed graft function.

OBJECTIVE: We explored relationships between blood levels of fingolimod (FTY720) and everolimus versus treated biopsy-proven acute rejection (BPAR) in an open-label trial in de novo kidney transplant recipients. METHODS: Patients (n = 52) who fulfilled predefined criteria placing them at increased risk of delayed graft function received fingolimod 2.5 mg/d, everolimus 2 mg twice daily with trough blood levels (C0) adjusted to 4 to 8 ng/mL, and corticosteroids. Everolimus and fingolimod C0 were collected over 1 year; efficacy readout was at 3 months. RESULTS: Fingolimod C0 accumulated over the first 3 months with a time-averaged level (C0avg) of 5.7 +/- 3.5 ng/mL. At steady state in months 3 to 12, C0 was 7.0 +/- 4.4 ng/mL. Overall, 30 patients (58%) were free from BPAR to month 3. Patients were divided into four groups based on whether their fingolimod C0avg and everolimus C0avg were above or below the population medians. Freedom from BPAR was 53% and 57% for low fingolimod combined with low and high everolimus, whereas the percentages were improved to 83% and 85% for high fingolimod combined with low and high everolimus. CONCLUSIONS: This pilot study with an everolimus-fingolimod regimen demonstrated trends in freedom from rejection that were drug concentration-related and that underscored, in particular, a strong contribution to efficacy from fingolimod.

Drug Therapy, Combination↗

Combined aerobic and resistance training in breast cancer survivors: A randomized, controlled pilot trial.

The purpose of this pilot study was to examine the effects of a combined cardiorespiratory and resistance exercise training program of short duration on the cardiorespiratory fitness, strength endurance, task specific functional muscle capacity, body composition and quality of life (QOL) in women breast cancer survivors. Sixteen subjects were randomly assigned to either a training (n = 8; age: 50 +/- 5 yrs) or control non-exercising group (n = 8; age: 51 +/- 10 yrs). The training group followed an 8-week exercise program consisting of 3 weekly sessions of 90-min duration, supervised by an experienced investigator and divided into resistance exercises and aerobic training. Before and after the intervention period, all of the subjects performed a cardiorespiratory test to measure peak oxygen uptake (VO2peak), a dynamic strength endurance test (maximum number of repetitions for chest and leg press exercise at 30 - 35 % and 100 - 110 % of body mass, respectively) and a sit-stand test. Quality of life was assessed using the European Organization for Research and Treatment of Cancer QLQ-C30 (EORTC-C30) questionnaire. In response to training, QOL, VO2peak (mean 3.9 ml/kg/min; 95 % CI, 0.93, 6.90) performance in leg press (17.9 kg; 95 % CI, 12.8, 22.4) and sit-stand test (- 0.67 s; 95 % CI, - 0.52, - 1.2) improved (p < or = 0.05). We observed no significant changes in the control group. Combined cardiorespiratory and resistance training, even of very brief duration, improves the QOL and the overall physical fitness of women breast cancer survivors.

Adult↗

Exercise capacity in a 78 year old patient with McArdle's disease: it is never too late to start exercising.

The case is reported of a 78 year old man with McArdle's disease and a history of treated coronary heart disease. Despite the pre-exercise administration of sucrose allowing the patient to exercise with normal physiological responses, and without typical McArdle's symptoms or biochemical evidence of muscle damage, his exercise capacity was very low (V(O2)peak = 10.7 ml/min/kg), probably attributable to his lifetime of sedentary living. The data suggest that, with pre-exercise sucrose administration, such patients may be candidates for systematic reconditioning, which may improve functional capacity and quality of life.

Aged↗

Submissions from non-existent claimants: the non-identity problem and the law.

Some medical interventions (or indeed omissions) determine the identity of a person. Those interventions or omissions may themselves cause harm, for which a child subsequently sues. Even if they do not themselves cause harm they may result in the birth of a child who subsequently brings a claim for being allowed to exist in the state caused by the intervention. The obvious objection to a claim of either class is that in the absence of the medical intervention or omission of which the claimant complains, the claimant would never have existed at all. This objection arises from what philosophers have called the "non-identity problem". This article examines the attitude that the English courts would be likely to have to such a claim. It concludes that the English law has so far failed to appreciate the significance of the non-identity problem, but will have to grapple with it soon.

Humans↗

Expression analysis onto microarrays of randomly selected cDNA clones highlights HOXB13 as a marker of human prostate cancer.

In a strategy aimed at identifying novel markers of human prostate cancer, we performed expression analysis using microarrays of clones randomly selected from a cDNA library prepared from the LNCaP prostate cancer cell line. Comparisons of expression profiles in primary human prostate cancer, adjacent normal prostate tissue, and a selection of other (nonprostate) normal human tissues, led to the identification of a set of clones that were judged as the best candidate markers of normal and/or malignant prostate tissue. DNA sequencing of the selected clones revealed that they included 10 genes that had previously been established as prostate markers: NKX3.1, KLK2, KLK3 (PSA), FOLH1 (PSMA), STEAP2, PSGR, PRAC, RDH11, Prostein and FASN. Following analysis of the expression patterns of all selected and sequenced genes through interrogation of SAGE databases, a further three genes from our clone set, HOXB13, SPON2 and NCAM2, emerged as additional candidate markers of human prostate cancer. Quantitative RT-PCR demonstrated the specificity of expression of HOXB13 in prostate tissue and revealed its ubiquitous expression in a series of 37 primary prostate cancers and 20 normal prostates. These results demonstrate the utility of this expression-microarray approach in hunting for new markers of individual human cancer types.

Biomarkers, Tumor↗

Interventions for promoting physical activity.

BACKGROUND: Little is known about the effectiveness of strategies to enable people to achieve an increase in their physical activity. OBJECTIVES: To assess the effects of interventions for promoting physical activity in adults aged 16 years and older, not living in an institution. SEARCH STRATEGY: We searched CENTRAL (Issue 4, 2001), MEDLINE, EMBASE, CINAHL, PsychLIT, BIDS ISI, SPORTDISCUS, SIGLE, SCISEARCH (from earliest date available to December 2001) and reference lists of articles. SELECTION CRITERIA: Randomised, controlled, trials comparing different interventions to encourage sedentary adults not living in an institution to become physically active. Studies required a minimum of six months follow up from the start of the intervention to the collection of final data and either used an intention to treat analysis or, failing that, had no more than 20% loss to follow up. DATA COLLECTION AND ANALYSIS: At least two reviewers independently assessed each study quality and extracted data. Study authors were contacted for additional information where necessary. Standardised mean differences and 95% confidence intervals were calculated for continuous measures of self reported physical activity and cardio-respiratory fitness. For studies with dichotomous outcomes, odds ratios and 95% confidence intervals were calculated. MAIN RESULTS: The effect of interventions on self reported physical activity (11 studies; 3940 participants) was positive and moderate, with a pooled standardised mean difference of 0.31 (95% CI 0.12 to 0.50), as was the effect on cardio-respiratory fitness (7 studies; 1406 participants) pooled SMD 0.4 (95% CI 0.09 to 0.70). The effect of interventions in achieving a predetermined threshold of physical activity (6 studies; 2313 participants) was not significant with an odds ratio of 1.30 (95% CI 0.87 to 1.95). There was significant heterogeneity in the reported effects as well as heterogeneity in characteristics of the interventions. The heterogeneity in reported effects was reduced in higher quality studies, when physical activity was self-directed with some professional guidance and when there was on-going professional support. AUTHORS' CONCLUSIONS: Our review suggests that physical activity interventions have a moderate effect on self reported physical activity and cardio-respiratory fitness, but not on achieving a predetermined level of physical activity. Due to the clinical and statistical heterogeneity of the studies, only limited conclusions can be drawn about the effectiveness of individual components of the interventions. Future studies should provide greater detail of the components of interventions.

Exercise↗

Men's decision-making about predictive BRCA1/2 testing: the role of family.

Men who have a family history of breast and/or ovarian cancer may be offered a predictive genetic test to determine whether or not they carry the family specific BRCA1/2 mutation. Male carriers may be at increased risk of breast and prostate cancers. Relatively little is known about at-risk men's decision-making about BRCA1/2 testing. This qualitative study explores the influences on male patients' genetic test decisions. Twenty-nine in-depth interviews were undertaken with both carrier and noncarrier men and immediate family members (17 male patients, 8 female partners, and 4 adult children). These explored family members' experiences of cancer and genetic testing, decision-making about testing, family support, communication of test results within the family, risk perception and risk management. Implicit influences on men's testing decisions such as familial obligations are examined. The extent to which other family members--partners and adult children--were involved in testing decisions is also described. It is demonstrated that mothers of potential mutation carriers not only perceive themselves as having a right to be involved in making this decision, but also were perceived by their male partners as having a legitimate role to play in decision-making. There was evidence that (adult) children were excluded from the decision-making, and some expressed resentment about this. The implications of these findings for the practice of genetic counseling are discussed.

Attitude↗

Communication about genetic testing in families of male BRCA1/2 carriers and non-carriers: patterns, priorities and problems.

This qualitative interview study explored the way in which information about predictive BRCA1/2 testing and its implications for children is disseminated within the families of at-risk men who undergo genetic testing. Twenty-nine in-depth interviews were carried out with family members [male patients (n = 17), their partners (n = 8) and adult children (n = 4)]. These explored the following themes: experiences of cancer and genetic testing, decision-making about testing and the communication of test results and genetic information within the immediate family. The interviews revealed that both male patients and their partners perceive themselves, rather than health professionals, as responsible for disclosing information about genetic testing and genetic risks to their children. Parents described three different communication strategies for the disclosure of genetic information to their children: complete openness, limited disclosure and total secrecy. The adoption of a particular communication strategy was justified in terms of children's rights to information vs their parental duties to protect their children from anxiety-provoking information. Some of the problems arising from the adoption of different disclosure patterns are identified and the implications for clinical practice are discussed.

Adult↗

Ventricular septal defect in a world class runner.

We report the case of an elite male, East African endurance runner (18 years old) who ranked in the top 15 in the World Cross Country Championships (sub 21 year old category) despite having a ventricular septal defect (VSD; width: 0.22 cm) that was diagnosed 2 weeks after this event with echocardiographic evaluation. This athlete was a moderate altitude native ( approximately 3000 m). Cardiac dimensions were within normal limits and no significant pathological signs were observed. His Vo(2max) was relatively low given his performance level (67.9 ml kg(-1) min(-1)). Despite his limited training background (only 1 year), his running economy was, however, better than the values reported in our laboratory for Caucasian runners of the same age. Further cardiological follow up might confirm that the VSD causes no pathological effects or any performance detriment in future years.

Adolescent↗

Psychosocial impact of breast/ovarian (BRCA1/2) cancer-predictive genetic testing in a UK multi-centre clinical cohort.

This multi-centre UK study assesses the impact of predictive testing for breast and ovarian cancer predisposition genes (BRCA1/2) in the clinical context. In the year following predictive testing, 261 adults (59 male) from nine UK genetics centres participated; 91 gene mutation carriers and 170 noncarriers. Self-report questionnaires were completed at baseline (pre-genetic testing) and 1, 4 and 12 months following the genetic test result. Men were assessed for general mental health (by general health questionnaire (GHQ)) and women for general mental health, cancer-related worry, intrusive and avoidant thoughts, perception of risk and risk management behaviour. Main comparisons were between female carriers and noncarriers on all measures and men and women for general mental health. Female noncarriers benefited psychologically, with significant reductions in cancer-related worry following testing (P<0.001). However, younger female carriers (<50 years) showed a rise in cancer-related worry 1 month post-testing (P<0.05). This returned to pre-testing baseline levels 12 months later, but worry remained significantly higher than noncarriers throughout (P<0.01). There were no significant differences in GHQ scores between males and females (both carriers and noncarriers) at any time point. Female carriers engaged in significantly more risk management strategies than noncarriers in the year following testing (e.g. mammograms; 92% carriers vs 30% noncarriers). In the 12 months post-testing, 28% carriers had bilateral risk-reducing mastectomy and 31% oophorectomy. Oophorectomy was confined to older (mean 41 yrs) women who already had children. However, worry about cancer was not assuaged by surgery following genetic testing, and this requires further investigation. In all, 20% of female carriers reported insurance problems. The data show persistent worry in younger female gene carriers and confirm changes in risk management consistent with carrier status. Men were not adversely affected by genetic testing in terms of their general mental health.

Adult↗

Vascular endothelial cadherin and beta-catenin in human fetoplacental vessels of pregnancies complicated by Type 1 diabetes: associations with angiogenesis and perturbed barrier function.

AIMS/HYPOTHESIS: Increased angiogenesis of fetoplacental vessels is a feature of pregnancies complicated by Type 1 diabetes mellitus, but the underlying molecular mechanisms are unknown. This investigation tests whether the diabetic maternal environment alters the phenotypic expression of placental vascular endothelial cadherin and beta-catenin, which have been implicated as key molecules in barrier formation and angiogenesis in the endothelium. METHODS: Term placental microvessels from normal pregnancies (n=8) and from those complicated by Type 1 diabetes (n=8) were perfused with 76-Mr dextran tracers (1 mg/ml) and subjected to immunocytochemistry, immunoblotting and microscopy. Junctional integrity, localisation and phosphorylation were investigated along with total protein levels of vascular endothelial cadherin, beta-catenin and vascular endothelial growth factor. Stereological sampling and estimation tools were used to quantify aspects of angiogenesis and endothelial proliferation. RESULTS: In the Type 1 diabetic placentae, junctional localisations of vascular endothelial cadherin and beta-catenin altered significantly, with more than 50% of microvessels showing complete loss of immunoreactivity and with no overall loss of total protein. Tracer leakage was associated with these vessels. There was a two- to three-fold increase in vessels showing junctional phospho-tyrosine immunoreactivity and hyperphosphorylated beta-catenin. Vascular endothelial growth factor levels were higher in these placentae. A four-fold increase in endothelial proliferation was observed, along with an increase in total length of capillaries without any change in luminal diameter. CONCLUSIONS/INTERPRETATION: Molecular perturbations of vascular endothelial cadherin and beta-catenin occur in fetoplacental vessels of pregnancies complicated by Type 1 diabetes. Phosphorylation and loss of these molecules from the adherens junctional domains may be influenced in part by the elevated levels of vascular endothelial growth factor in the placenta. Perturbations of the junctional proteins may explain the observed breach in barrier integrity and may contribute to the mechanisms that drive proliferation and increases in capillary length.

Adult↗

Accommodating risk: responses to BRCA1/2 genetic testing of women who have had cancer.

The relationship between risk awareness and anxiety has been the subject of extensive theoretical debate and empirical research. Previous studies of women with a family history of hereditary breast and ovarian cancer suggest that both healthy at-risk women and former cancer patients report increased anxiety upon learning about their increased risks of developing these diseases. Indeed, anxiety about genetic risks has been reported as influencing decisions about DNA-testing and risk-reducing surgery on healthy breasts and ovaries. This qualitative study of women who had been treated for breast/ovarian cancer investigated their perceptions of, and reactions to, their genetic risks of developing further cancers following genetic testing (BRCA1/2 mutation searching). In-depth interviews were undertaken with 30 women (10 mutation carriers, 8 awaiting a result and 12 who received an inconclusive test result). Whilst the majority of women in all three groups adopted a fatalistic approach with regard to their future health and did not regard their genetic risks as a threat to self, a few reported heightened anxiety on learning they were at increased risk of developing a second primary cancer. The data suggest that affected women understand their genetic risks of cancer within the context of their previous disease experiences. It is observed that women's responses to their genetic risk are influenced by the degree to which they have accommodated their risk status in their biography following their diagnosis and treatment of cancer.

Adaptation, Psychological↗

Histological findings in "incidental" intraoperative pancreas allograft biopsies.

Thirty intraoperative needle core biopsies of well-functioning pancreas allografts were performed from 2 days to 7 years posttransplantation (mean 15.4 months). Most samples (83.3%) lacked significant inflammation or fibrosis. The five patients who showed features of ongoing low-grade acute rejection experienced premature graft losses due to chronic rejection. There were no complications related to the intraoperative biopsy itself.

Adult↗