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Biomedical subjects

C Williams

Publications and source records attributed to C Williams.

At least 19 recordsLinked to original sources

Impact of consuming a milk drink containing a probiotic on mood and cognition.

OBJECTIVE: The impact on mood and memory of consuming a probiotic containing milk drink, or a placebo, was examined as, previously, a poor mood has been found to correlate with the frequency of constipation. DESIGN: A double-blind placebo-controlled trial with random allocation of subjects. SETTING: Subjects went about their normal life in the community apart from three visits to the laboratory. SUBJECTS: One hundred and thirty-two healthy members of general population, mean age 61.8 years, volunteered in response to local media coverage. One hundred and twenty-four finished the trial. INTERVENTION: For a 3-week period, either a probiotic containing milk drink, or a placebo, were consumed daily. Mood and cognition were measured at baseline, and after 10 and 20 days of consumption. RESULTS: At baseline those who reported themselves to be less frequently constipated were more clearheaded, confident and elated. Although the taking of the probiotic did not generally change the mood, this appeared to be a reflection of the generally good mood in this sample. When those in the bottom third of the depressed/elated dimension at baseline were considered, they selectively responded by reporting themselves as happy rather than depressed after taking the probiotic. The intervention did not, however, influence the reported frequency of defaecation, probably a reflection of the initially low incidence of constipation. An unexpected and possibly chance finding was that the consumption of probiotics resulted in a slightly-poorer performance on two measures of memory. CONCLUSIONS: The consumption of a probiotic-containing yoghurt improved the mood of those whose mood was initially poor. This improvement in mood was not, however, associated with an increased frequency of defaecation.

Affect↗

Chemotherapy for advanced, recurrent or metastatic endometrial cancer: a systematic review of Cochrane collaboration.

BACKGROUND: Cytotoxic chemotherapy has a limited place in the management of advanced or recurrent endometrial cancer. Commonly used agents include cisplatin and doxorubicin, but the side-effect profile may be unacceptable for many patients. The feasibility of administration of combination chemotherapy is limited in many patients on account of significant co-morbidity. While early-stage endometrial adenocarcinoma is a common gynaecological cancer with a favourable prognosis, advanced or recurrent disease presents a difficult management problem. The platinum and anthracycline compounds have been widely used for many years, but their impact on progression-free survival (PFS) and overall survival (OS) is not clear. This systematic review aimed to evaluate both the benefits and adverse effects of cytotoxic chemotherapy in these women. PATIENTS AND METHODS: We carried out systematic searches for randomised controlled trials (RCTs) comparing chemotherapy with another intervention. Data were extracted from trial reports or supplied by investigators. Where possible, hazard ratios (HRs) were calculated for OS and PFS and odds ratios (ORs) were calculated for acute toxicity. The impact of more versus less intensive chemotherapy on OS, PFS and acute toxicity was assessed in a meta-analysis. RESULTS: Eleven eligible RCTs were identified that recruited 2288 patients. A meta-analysis of six of these trials found that PFS [HR = 0.80, 95% confidence interval (CI) 0.71-0.90; P = 0.004], but not OS (HR = 0.90, 95% CI 0.80-1.03; P = 0.12), was significantly improved when more intensive chemotherapy was compared with less intensive chemotherapy. OS was improved when doxorubicin, cisplatin and other drugs were compared with doxorubicin and cisplatin. Toxicity was generally higher with more chemotherapy. There was insufficient evidence to assess the effect of chemotherapy on symptom control or quality of life (QoL). Platinums, anthracyclines and taxanes were the most studied in phase II trials and combinations gave the best responses, but patient selection and pre-treatment was very variable. CONCLUSIONS: More intense combination chemotherapy significantly improves the disease-free survival and the data indicate a modest improvement in OS. The addition of anthracyclines (e.g. doxorubicin) or the taxanes [e.g. paclitaxel (Taxol)] to cisplatin increases the response rate. More intensive regimens are associated with the gain in survival. However, grade 3 and 4 myelosuppression and gastrointestinal toxicity are also increased. Future developments are likely to exploit specific molecular characteristics of endometrial cancers, including their hormone dependence, growth factor target overexpression and PTEN loss. While no one drug or regimen offers a clear benefit for women with advanced endometrial cancer, platinum drugs, anthracyclines and paclitaxel seem the most promising agents. Future trials should address the impact of such agents on QoL and symptom control in addition to survival. Chemotherapy and endocrine therapy need to be compared directly in an RCT.

Antineoplastic Agents↗

Effects of the glycemic index of breakfast on metabolic responses to brisk walking in females.

OBJECTIVE: The aim of this study was to examine the metabolic responses during 1 h of brisk walking, 3 h after ingesting high glycemic index (HGI) and moderate glycemic index (MGI) breakfasts. DESIGN AND SUBJECTS: Six females completed three treadmill walking trials (approximately 50% VO2 max), separated by at least 1 month. Three hours before walking, they ingested either water or a HGI or MGI breakfast. The MGI breakfast consisted of a mixture of an HGI breakfast cereal and low GI carbohydrate (CHO) foods. The GI values of the HGI and MGI meals were 77 and 51, respectively. SETTING: The study took place in the School of Sport and Exercise Sciences at Loughborough University, Loughborough, UK. RESULTS: In the HGI and MGI trials, plasma glucose and serum insulin concentrations peaked 15 min into the postprandial period. At the onset of exercise, plasma insulin concentrations were twofold higher in the HGI (31.5+/-7.7 microl U l(-1)) than in the MGI trial (15.2+/-1.9 microl U l(-1)) (P<0.05). However, there were no differences in substrate utilization between the two CHO trials. CONCLUSION: These results suggest that although the addition of LGI CHO foods to an HGI breakfast cereal reduces the overall GI of the meal, the metabolic response to exercise is similar to that following a breakfast comprised entirely of HGI foods.

Adult↗

Self-help and guided self-help for eating disorders.

BACKGROUND: Anorexia nervosa (AN), bulimia nervosa (BN), binge eating disorder (BED) and eating disorder not otherwise specified (EDNOS) are common and disabling disorders. Many patients experience difficulties accessing specialist psychological treatments. Pure self-help (PSH: self-help material only) or guided self-help (GSH: self-help material with therapist guidance), may bridge this gap. OBJECTIVES MAIN OBJECTIVE: Evaluate evidence from randomised controlled trials (RCTs) / controlled clinical trials (CCTs) for the efficacy of PSH/GSH with respect to eating disorder symptoms, compared with waiting list or placebo/attention control, other psychological or pharmacological treatments (or combinations/augmentations) in people with eating disorders. SECONDARY OBJECTIVE: Evaluate evidence for the efficacy of PSH/GSH regarding comorbid symptomatology and costs. SEARCH STRATEGY: CCDANCTR-Studies and CCDANCTR-References were searched in November 2005, other electronic databases were searched, relevant journals and grey literature were checked, and personal approaches were made to authors. SELECTION CRITERIA: Published/unpublished RCTs/CCTs evaluating PSH/GSH for any eating disorder. DATA COLLECTION AND ANALYSIS: Data was extracted using a customized spreadsheet. Relative Risks (RR) were calculated from dichotomous data and weighted/standardized mean differences (WMD/SMD) from continuous data, using a random effects model. MAIN RESULTS: Twelve RCTs and three CCTs were identified, all focusing on BN, BED, EDNOS or combinations of these, in adults, using manual-based PSH/GSH across various settings. Primary comparisons:At end of treatment, PSH/GSH did not significantly differ from waiting list in abstinence from bingeing (RR 0.72, 95% CI 0.47 to 1.09), or purging (RR 0.86, 95% CI 0.68 to 1.08), although these treatments produced greater improvement on other eating disorder symptoms, psychiatric symptomatology and interpersonal functioning but not depression. Compared to other formal psychological therapies, PSH/GSH did not differ significantly at end of treatment or follow-up in improvement on bingeing and purging (RR 0.99, 95% CI 0.75 to 1.31), other eating disorder symptoms, level of interpersonal functioning or depression. There were no significant differences in treatment dropout. Secondary comparisons:One small study in BED found that cognitive-behavioural GSH compared to a non-specific control treatment produced significantly greater improvements in abstinence from bingeing and other eating disorder symptoms. Studies comparing PSH with GSH found no significant differences between treatment groups at end of treatment or follow-up. Comparison between different types of PSH/GSH found significant differences on eating disorder symptoms but not on bingeing/purging abstinence rates. AUTHORS' CONCLUSIONS: PSH/GSH may have some utility as a first step in treatment and may have potential as an alternative to formal therapist-delivered psychological therapy. Future research should focus on producing large well-conducted studies of self-help treatments in eating disorders including health economic evaluations, different types and modes of delivering self-help (e.g. computerised versus manual-based) and different populations and settings.

Anorexia Nervosa↗

Review article: proton pump inhibitors and bacterial overgrowth.

Proton pump inhibitors are potent drugs producing profound suppression of gastric acid secretion. Consequently, they are highly effective at treating acid-related disorders. There have been concerns that the suppression of gastric acid will alter the bacterial flora of the upper gastrointestinal tract and lead to complications such as cancer, enteric or other infections and malabsorption. Studies have confirmed that proton pump inhibitors do alter the bacterial population but present evidence indicates that this only rarely leads to clinical disease. As with all drugs, proton pump inhibitors should only be used for disorders shown clearly to benefit from the therapy and where the benefits will outweigh the small risks associated with them. Further research to more fully quantify the risk associated with PPI therapy is required.

Achlorhydria↗

Cost-effectiveness of using prognostic information to select women with breast cancer for adjuvant systemic therapy.

OBJECTIVES: To investigate the cost-effectiveness of using prognostic information to identify patients with breast cancer who should receive adjuvant therapy. DATA SOURCES: Electronic databases from 1980 through to February 2002. A survey of clinical practice in UK cancer centres and units. Large retrospective dataset containing data on prognostic factors, treatments and outcomes for women with early breast cancer treated in Oxford. REVIEW METHODS: Between six and nine databases were searched by an information expert. Evidence-based methods were used to review and select those studies and the quality of each included paper was assessed using standard assessment tools reported in the literature or piloted and developed for this study. A survey of clinical practice in UK cancer centres and units was carried out to ensure that conclusions drawn from the report could be implemented. These data, along with the information gathered in the systematic reviews, informed the methodological approach adopted for the health economic modelling. An illustrative framework was developed for incorporating patient-level prediction within a health economic decision model. This framework was applied to a large retrospective dataset containing data on prognostic factors, treatments and outcomes for women with early breast cancer treated in Oxford. The data were used to estimate directly a parametric regression-based risk equation, from which a prognostic index was developed, and prognosis-specific estimates of the baseline breast cancer hazard could be observed. Published estimates of treatment effects, health service treatment costs and utilities were used to construct a decision analytic framework around this risk equation, thus enabling simulation of the effectiveness and cost-effectiveness of adjuvant therapy for all possible combinations of prognostic factors included in the model. RESULTS: The lack of good-quality systematic reviews and well-conducted studies of prognostic factors in breast cancer is a striking finding. There are no registers of studies of prognostic factors or of reviews of prognostic studies. Many of the reviews used weak methods, primary studies are similar with poor methodology and reporting of results. In addition, there is much variation in patient populations, assay methods, analysis of results, definitions used and reporting of results. Most studies appear to be retrospective and some use inappropriate methods likely to inflate outcomes such as optimising cut points and failing to test the results in an independent population. Very few reviews used meta-analysis to conduct a pooled analysis and to provide an estimate of the average size of any association. Instead, most reviews relied on vote counting. Although many prognostic models for breast cancer have been published, remarkably few have been re-examined by independent groups in independent settings. The few validation studies have been carried out on ill-defined samples, sometimes of smaller size and short follow-up, and sometimes using different patient outcomes when validating a model. The evidence from the validation studies shows support for the prognostic value of the Nottingham Prognostic Index (NPI). No new prognostic factors have been shown to add substantially to those identified in the 1980s. Improvement of this index depends on finding factors that are as important as, but independent of, lymph node, stage and pathological grade. The NPI remains a useful clinical tool, although additional factors may enhance its use. We accepted that hormone receptor status (ER) for hormonal therapy such as tamoxifen and prediction of response to trastuzumab by HER2 did not require systematic review, as the mechanism of action of these drugs requires intact receptors. There was no clear evidence that other factors were useful predictors of response and survival. The survey confirmed pathological nodal status, tumour grade, tumour size and ER status as the most clinically important factors for consideration when selecting women with early breast cancer for adjuvant systemic therapy in the UK. The protocols revealed that although UK cancer centres appear to be using the same prognostic and predictive factors when selecting women to receive adjuvant therapy, much variation in clinical practice exists. Some centres use protocols based upon the NPI whereas others do not use a single index score. Within NPI and non-NPI users, between-centre variability exists in guidelines for women for whom the benefits are uncertain. Consensus amongst units appears to be greatest when selecting women for adjuvant hormone therapy with the decision based primarily upon ER or progesterone receptor status rather than combinations of a number of factors. Guidelines as to who should receive adjuvant chemotherapy, however, were found to be much less uniform. Searches of the literature revealed only five published papers that had previously examined the cost-effectiveness of using prognostic information for clinical decision-making. These studies were of varying quality and highlight the fact that economic evaluation in this area appears still to be in its infancy. By combining methodologies used in determining prognosis with those used in health economic evaluation, it was possible to illustrate an approach for simulating the effectiveness (survival and quality-adjusted survival) and the cost-effectiveness associated with the decision to treat individual women or groups of women with different prognostic characteristics. The model showed that effectiveness and cost-effectiveness of adjuvant systemic therapy have the potential to vary substantially depending upon prognosis. For some women therapy may prove very effective and cost-effective, whereas for others it may actually prove detrimental (i.e. the reductions in health-related quality of life outweigh any survival benefit). CONCLUSIONS: Outputs from the framework constructed using the methods described here have the potential to be useful for clinicians, attempting to determine whether net benefits can be obtained from administering adjuvant therapy for any presenting woman; and also for policy makers, who must be able to determine the total costs and outcomes associated with different prognosis based treatment protocols as compared with more conventional treat all or treat none policies. A risk table format enabling clinicians to look up a patient's prognostic factors to determine the likely benefits (survival and quality-adjusted survival) from administering therapy may be helpful. For policy makers, it was demonstrated that the model's output could be used to evaluate the cost-effectiveness of different treatment protocols based upon prognostic information. The framework should also be valuable in evaluating the likely impact and cost-effectiveness of new potential prognostic factors and adjuvant therapies.

Adjuvants, Pharmaceutic↗

Chemotherapy for advanced, recurrent or metastatic endometrial carcinoma.

BACKGROUND: Endometrial adenocarcinoma is a common gynaecological cancer, but a comparatively small proportion of patients present with or develop recurrent or advanced disease. Progestogens are widely used, with little evidence of their efficacy. Co-morbidity including obesity and cardiac disease and concerns over toxicity have prevented more extensive studies of cytotoxic chemotherapy, although there are a number of active agents. OBJECTIVES: To assess any benefits or adverse effects of cytotoxic chemotherapy in women with advanced, recurrent or metastatic endometrial adenocarcinoma. SEARCH STRATEGY: The major medical literature databases were searched for all known randomised controlled trials (RCTs), as were trials registers and reference lists of relevant publications. SELECTION CRITERIA: RCTs comparing chemotherapy versus another intervention (including different chemotherapy) in advanced disease were considered. Trials of adjuvant treatment or for sarcomatous tumours were excluded. DATA COLLECTION AND ANALYSIS: Data were extracted from the papers by reviewers and authors of included studies contacted for further information. MAIN RESULTS: Eleven eligible trials were identified which entered 2288 patients between 1974 and 2000. A meta-analysis of the 6 trials comparing more with less chemotherapy with combination was possible and included 1135 patients. Progression-free survival (PFS) was significantly improved (Hazard Ratio (HR) = 0.80, 95% Confidence Interval (CI) 0.71 to 0.90, p = 0.004), but there was only a trend toward improved survival (HR = 0.90, 95% CI 0.80 to 1.03). Toxicity was in general higher with the combination chemotherapy regimens. Only one trial showed a significant survival benefit from the addition of paclitaxel to combination chemotherapy, but this was at the expense of increased toxicity. There was insufficient evidence to assess whether there was any benefit from cytotoxic chemotherapy in terms of symptom control or QOL compared with best supportive care. There were no comparative trials of chemotherapy with endocrine therapy. AUTHORS' CONCLUSIONS: The optimum cytotoxic drug regimen for advanced endometrial adenocarcinoma has still to be defined although our review suggests that it may contain paclitaxel or platinum. These mainly North American and European trial populations represent a highly selected subgroup of the 10,000 women dying annually from this disease. Future trials should include measures of QOL and symptom control in addition to PFS and overall survival (OS). They should also consider comparison of endocrine therapy and cytotoxic chemotherapy in patients with no prior drug therapy. Stratification of patients should take into account other prognostic factors including co-morbidity and prior radiation treatment.

Antineoplastic Agents↗

Concomitant chemotherapy and radiation therapy for cancer of the uterine cervix.

BACKGROUND: The National Cancer Institute (USA) alert in February 1999 stated that concomitant chemoradiotherapy should be considered for all patients with cervical cancer, based on evidence from five randomised controlled trials (RCTs). OBJECTIVES: To review all known RCTs comparing concomitant chemotherapy and radiation therapy with radiotherapy for locally advanced cervical cancer. SEARCH STRATEGY: We searched electronic databases, trials registers and reference lists of published trial reports and review articles were also searched. SELECTION CRITERIA: This review includes RCTs in cervical cancer comparing concomitant chemoradiation with radiotherapy in the experimental arm. Trials allowing further adjuvant chemotherapy or hydroxyurea were included. Trials using radiosensitisers or radioprotectors in the experimental arm were excluded. DATA COLLECTION AND ANALYSIS: Two authors reviewed trials for inclusion and extracted data. For meta-analyses of time-to-event outcomes (survival, progression-free survival), a hazard ratio (HR) was extracted or estimated from trial reports, where possible. Only overall rates of local and distant recurrence were presented in many reports so only odds ratios (OR) of recurrence rates could be calculated, which takes no account of time to recurrence or censoring. Few trials reported acute toxicity adequately, but where possible ORs were calculated for the main types and severities of acute toxicity. The HRs and ORs for individual trials were combined across all trials, using the fixed effect model. Late toxicity was rarely described in sufficient detail so could only be reviewed qualitatively. MAIN RESULTS: The original review was based on nineteen trials (17 published and two unpublished) including 4580 patients. This update includes twenty four trials (21 published, 3 unpublished) and 4921 patients, although due to patient exclusion and differential reporting 61% to 75% were available for the analyses. The review strongly suggests chemoradiation improves overall survival and progression free survival, whether or not platinum was used with absolute benefits of 10% and 13% respectively. There was, however, statistical heterogeneity for these outcomes. There was some evidence that the effect was greater in trials including a high proportion of stage I and II patients. Chemoradiation also showed significant benefit for local recurrence and a suggestion of a benefit for distant recurrence. Acute haematological and gastrointestinal toxicity was significantly greater in the concomitant chemoradiation group. Late effects of treatment were not well reported and so the impact of chemoradiation on these effects could not be determined adequately. Treatment-related deaths were rare. AUTHORS' CONCLUSIONS: Concomitant chemoradiation appears to improve overall survival and progression-free survival in locally advanced cervical cancer. It also appears to reduce local and distant recurrence suggesting concomitant chemotherapy may afford radiosensitisation and systemic cytotoxic effects. Some acute toxicity is increased, but the long-term side effects are still not clear.

Combined Modality Therapy↗

Chemotherapy for advanced, recurrent or metastatic endometrial carcinoma.

BACKGROUND: Endometrial adenocarcinoma is a common gynaecological cancer, but a comparatively small proportion of patients present with or develop recurrent or advanced disease. Progestogens are widely used, with little evidence of their efficacy. Co-morbidity including obesity and cardiac disease and concerns over toxicity have prevented more extensive studies of cytotoxic chemotherapy, although there are a number of active agents. OBJECTIVES: To assess any benefits or adverse effects of cytotoxic chemotherapy in women with advanced, recurrent or metastatic endometrial adenocarcinoma. SEARCH STRATEGY: The major medical literature databases were searched for all known randomised controlled trials (RCTs), as were trials registers and reference lists of relevant publications. SELECTION CRITERIA: RCTs comparing chemotherapy versus another intervention (including different chemotherapy) in advanced disease were considered. Trials of adjuvant treatment or for sarcomatous tumours were excluded. DATA COLLECTION AND ANALYSIS: Data were extracted from the papers by reviewers and authors of included studies contacted for further information. MAIN RESULTS: Eleven eligible trials were identified which entered 2288 patients between 1974 and 2000. A meta-analysis of the 6 trials comparing more with less chemotherapy with combination was possible and included 1135 patients. Progression-free survival (PFS) was significantly improved (Hazard Ratio (HR) = 0.80, 95% Confidence Interval (CI) 0.71 to 0.90, p = 0.004), but there was only a trend toward improved survival (HR = 0.90, 95% CI 0.80 to 1.03). Toxicity was in general higher with the combination chemotherapy regimens. Only one trial showed a significant survival benefit from the addition of paclitaxel to combination chemotherapy, but this was at the expense of increased toxicity. There was insufficient evidence to assess whether there was any benefit from cytotoxic chemotherapy in terms of symptom control or quality of life (QOL) compared with best supportive care. There were no comparative trials of chemotherapy with endocrine therapy AUTHORS' CONCLUSIONS: The optimum cytotoxic drug regimen for advanced endometrial adenocarcinoma has still to be defined although our review suggests that it may contain paclitaxel or platinum. These mainly North American and European trial populations represent a highly selected subgroup of the 10, 000 women dying annually from this disease. Future trials should include measures of QOL and symptom control in addition to PFS and overall survival (OS). They should should also consider comparison of of endocrine therapy and cytotoxic chemotherapy in patients with no prior drug therapy. Stratification of patients should take into account other prognostic factors including co-morbidity and prior radiation treatment.

Antineoplastic Agents↗

Age-related pituitary volumes in prepubertal children with normal endocrine function: volumetric magnetic resonance data.

BACKGROUND: Evaluation of the size of the pituitary gland on magnetic resonance imaging (MRI) may be difficult, considering the wide variation in normal gland morphology. Given the paucity of age-related biometric data, our purpose was to obtain standard normal reference values for pituitary volumes in prepubertal children using three-dimensional MRI data. METHODS: Children under the age of 10 yr undergoing brain MRI for seizures or idiopathic developmental delay and who had no endocrine abnormality were recruited prospectively over 2 yr. All MRI studies included a three-dimensional sequence. Only subjects with normal studies were included. One hundred thirty-nine children were eligible (mean age, 5.2 yr). Direct pituitary volumes were measured from contiguous 1-mm thick reconstructed coronal and sagittal images. Estimated pituitary volumes were calculated using pituitary height, width, and length. RESULTS: Volumes obtained from reconstructions in either plane were essentially identical. There was a linear increase in log-transformed pituitary volume with age, but relatively weak correlations with height or body mass index. There was no gender difference and only weak correlations between pituitary height and pituitary volume and between estimated pituitary volume calculation and measured pituitary volume. We provide age-related reference ranges for pituitary volumes in graphical and tabular forms.

Body Height↗

Clindamycin in the treatment of group G beta-haemolytic streptococcal infections.

We report a case of severe streptococcal cellulitis in a healthy 47 year old male, where the sole microbial isolate was a beta-haemolytic group G Streptococcus. Treatment failure with high dose penicillin was observed despite in vitro sensitivity. The addition of clindamycin resulted in dramatic clinical improvement. This may indicate an Eagle-type effect (whereby antibiotics exhibit paradoxically reduced bactericidal activities at high drug concentrations), in group G beta-haemolytic infections. Although well documented with group A streptococcal infections, this phenomenon has not been fully recognised with group G beta-haemolytic streptococcal infections. This may have important implications for clinical management.

Abscess↗

Muscle metabolism, temperature, and function during prolonged, intermittent, high-intensity running in air temperatures of 33 degrees and 17 degrees C.

Nine unacclimatized university sportsmen performed a prolonged, intermittent, high-intensity shuttle running test in hot (HT) (33 degrees C, dry bulb temperature, approximately 28 %, relative humidity) and moderate (MT) (17 degrees C, 63 %) environmental conditions. Subjects performed 60 m of walking, a 15-m sprint, 60 m of cruising ( approximately 85 % V.O (2max)), and 60 m of jogging ( approximately 45 %V.O (2max)) for 14.8 +/- 0.1 min followed by a 3-min rest, repeated until volitional exhaustion. The hot trial was performed first followed, 14 days later, by the moderate trial. During exercise subjects drank water ad libitum. Subjects ran almost twice as far in the moderate as in the hot trial (HT 11216 +/- 1411, MT 21644 +/- 1629, m, p < 0.01), and the decline in average 15-m sprint performance was greater in the heat (HT, 0.17 +/- 0.05, MT, 0.09 +/- 0.03, s, p < 0.05). Average heart rates, blood lactate and glucose, and plasma adrenaline and noradrenaline concentrations were greater in the HT (main effect trial, p < 0.01), as were serum cortisol concentration (main effect trial p < 0.05, n = 5) and muscle temperature (HT exhaustion vs. same time point in MT, 40.2 +/- 0.3 vs. 39.3 +/- 0.2, degrees C, p < 0.01). Peak torque during knee flexion and extension was not different pre-and post-exercise in the HT. Muscle glycogen utilization tended to be greater in the heat (HT 193.2 +/- 19.5, MT 143.8 +/- 23.9, mmol . kg dry wt (-1), p = 0.055, n = 8). In 7 out of the 8 subjects the increase in utilization was between 19 and just over 200 % greater in the HT. Glycogen remaining in the muscle at exhaustion was greater in the hot than moderate trial (HT 207.4 +/- 34.3, MT 126.5 +/- 46.8, mmol . kg dry wt (-1), p < 0.01, n = 8). Rectal temperature (T (rec)) was higher in the HT at exhaustion than at the same point in time in the moderate trial (HT, 39.60 +/- 0.15 vs. MT 38.75 +/- 0.10, degrees C, interaction trial-time, p < 0.01). There was a very strong negative relationship between rate of rise in T (rec) and distance completed in the HT (HT r = - 0.90, p < 0.01, MT r = - 0.76, p < 0.05). Thus, the earlier onset of exhaustion during prolonged intermittent shuttle running in the heat is associated with hyperthermia. However, while muscle glycogen utilization may be elevated by heat stress, low whole muscle glycogen concentrations would not seem to be the cause of this earlier exhaustion.

Adult↗

Ovarian Leydig cell tumor in a peri-menopausal woman with severe hyperandrogenism and virilization.

The authors report a case of Leydig cell tumor in a 46-year-old woman who first presented with severe clinical hyperandrogenism and associated complex medical history. Investigations revealed markedly raised serum concentrations of testosterone (28.3 nmol/l) and free androgen index (54.4), whereas sex hormone binding globulin, random cortisol, androstenedione, 17-hydroxyprogesterone and dehydroepiandrosterone sulphate concentrations were all within the normal range. Transabdominal ultrasound and computed tomography scan of the pelvis and abdomen showed a slightly bulky right ovary, but no other abnormalities. An ovarian source of androgens was suspected and surgery was arranged. Following a three-year history of defaulting appointments due to agoraphobia, she underwent total abdominal hysterectomy with bilateral salpingo-oophorectomy and intraoperative selective ovarian venous sampling. Histopathological examination revealed a 2 cm Leydig cell tumor within the right ovary. Successful intraoperative ovarian venous sampling demonstrated significantly elevated testosterone levels (>260 nmol/l) from the right ovarian vein. Hyperandrogenaemia normalized post-operatively. The patient showed significant regression of clinical signs and symptoms, including the anxiety disorder. Clinical presentation, biochemistry and imaging modalities should allow to detect androgen-secreting ovarian tumors, while selective venous sampling should be reserved for patients whom uncertainty remains. The present case confirms that androgen-secreting ovarian tumors represent a diagnostic and therapeutic challenge. They have to be considered in the differential diagnosis of severe hyperandrogenism even in peri-menopausal women. Although selective venous sampling is of diagnostic value, however, its impact on future management should be considered on individual basis.

Androgens↗

The acceptability of isoflavones as a treatment of menopausal symptoms: a European survey among postmenopausal women.

OBJECTIVE: To investigate determinants of the acceptability of isoflavone products among postmenopausal women with regard to social and lifestyle factors, dietary habits, health concerns, food beliefs, menopausal symptoms and therapies, and to elucidate preferences for specific products. METHODS: A consumer survey was conducted among postmenopausal women in four European countries (Germany, Denmark, Italy and the UK), including a total of 465 respondents. RESULTS: The declared acceptability of isoflavones was highest in Germany (80%), followed by Italy (75%), the UK (59%) and Denmark (55%; p < 0.001). Among other factors, prior information about isoflavones (odds ratio (OR) 2.64, 95% confidence interval (CI) 1.54-4.51, p < 0.001) and belief that foods can be used to treat medical conditions (OR 2.18, 95% CI 1.17-4.05, p = 0.014) were the strongest predictors of potential acceptability. The preferred forms in which isoflavones might be taken differed markedly between countries. CONCLUSIONS: Information about the health effects of isoflavones and health-diet links should be considered the most important factors in attempts to influence the potential acceptability of isoflavone products. Foods enriched with isoflavones need to be developed with regard to specific cultural demands in order to assure consumer acceptance on the marketplace.

Age Factors↗