Cryptosporidium oocysts on fresh produce from areas of high livestock production in Poland.

Samples of fresh vegetables and soft fruit were collected from farmers' markets in the Lublin Area of Poland during 2006-2007; the produce was grown in areas of high to moderate livestock production. Cryptosporidium sp. oocysts were eluted from food surfaces, separated from residual food materials by IMS and identified by immunofluorescence and Nomarski differential interference contrast microscopy. Cryptosporidium sp. oocysts were detected in 6 of 128 vegetable samples (range 1-47 oocysts), but not in any of 35 fruit samples. Both empty and intact oocysts were detected. Species identity of oocyst-positive samples was performed by molecular analysis at four genetic loci. One of two 18S rRNA loci amplified DNA from 5 of the 6 oocyst-positive samples, but insufficient DNA for RFLP or sequencing analysis was available from 4 of these samples. An oocyst-positive celery sample generated an RFLP pattern consistent with C. parvum at two loci, but insufficient DNA was available for subtyping (GP60 sequencing) this isolate. Oocyst-contaminated foods originated from districts with the highest numbers of homesteads possessing cattle herds and no contaminated produce was detected from districts containing lower numbers of cattle-owning homesteads, strengthening the assumption that the origin of the contamination was livestock. The results of this study strengthen the evidence for the potential for zoonotic foodborne transmission of Cryptosporidium.

The influence of rifle carriage on the kinetics of human gait.

The influence that rifle carriage has on human gait has received little attention in the published literature. Rifle carriage has two main effects, to add load to the anterior of the body and to restrict natural arm swing patterns. Kinetic data were collected from 15 male participants, with 10 trials in each of four experimental conditions. The conditions were: walking without a load (used as a control condition); carrying a lightweight rifle simulator, which restricted arm movements but applied no additional load; wearing a 4.4 kg diving belt, which allowed arms to move freely; carrying a weighted (4.4 kg) replica SA80 rifle. Walking speed was fixed at 1.5 m/s (+/-5%) and data were sampled at 400 Hz. Results showed that rifle carriage significantly alters the ground reaction forces produced during walking, the most important effects being an increase in the impact peak and mediolateral forces. This study suggests that these effects are due to the increased range of motion of the body's centre of mass caused by the impeding of natural arm swing patterns. The subsequent effect on the potential development of injuries in rifle carriers is unknown.

Tumour location and prognostic characteristics as determinants of survival of women with invasive breast cancer: South Australian hospital-based cancer registries, 1987-1998.

Survivals from breast cancer varied by location of lesion (P<0.001), with 10-year survivals of 61% applying for central (n=772), 73% for medial (n=350), and 72% for lateral (n=966) lesions. Univariate analyses of determinants of central locations indicated that the following were predictive: a more advanced TNM stage (P<0.001); a larger tumour diameter (P=0.002); a higher grade (P=0.032); a negative oestrogen receptor status (P=0.004); a negative progesterone receptor status (P=0.004); and histological type (P=0.011), with more of the lobular lesions being located centrally. Cox proportional hazards regression indicated that the relative risk (95% confidence limits) of case fatality for central, as opposed to other, lesions reduced from 1.46 (1.20, 1.78) to 1.16 (0.95, 1.41) when stage was added to the model, with no other factor having an additional conditioning effect. It is concluded that central lesions have worse outcomes, mostly due to their more advanced stages. Means of finding these tumours earlier should be investigated.

Androgen receptor agonist activity of the synthetic progestin, medroxyprogesterone acetate, in human breast cancer cells.

Medroxyprogesterone acetate (MPA), which is frequently used as second line hormonal therapy for the treatment of metastatic breast cancer, binds with high affinity to the progesterone receptor (PR). However, the androgenic side-effects of MPA suggest that it may also activate androgen receptor (AR) regulated pathways. Treatment of the human breast cancer cell lines MDA-MB-453, ZR-75-1 and T47-D with high dose (100 nM) MPA resulted in 26-30% inhibition of cell growth, which was partially reversed by co-treatment with a 10-fold excess of the synthetic antiandrogen, anandron. Scatchard analysis demonstrated specific, high affinity (non-PR) binding of [3H]MPA to cytosols prepared from the PR-/AR+ MDA-MB-453 and PR+/AR+ ZR-75-1, but not the PR-/AR- BT-20 breast cancer cell lines. Competition of [3H]MPA binding to MDA-MB-453 cytosols by equimolar concentrations of androgens (5alpha-dihydrotestosterone (DHT), R1881) and the antiandrogen, anandron was consistent with binding of MPA to the AR. In ZR-75-1 cell cytosol fractions, DHT, R1881 and anandron only partially competed out [3H]MPA binding, suggesting that androgens displace [3H]MPA binding to AR but not to PR. Induction by MPA of AR transactivation was demonstrated in MDA-MB-453 and ZR-75-1 cells, and in the CV-1 cell line transfected with a full-length AR. In these cell lines the increased activity of the androgen responsive reporter gene (MMTV-CAT) by 1 nM MPA was fully (MDA-MB-453, CV-1) or partially (ZR-75-1) inhibited by co-culture with 1 microM anandron. These findings indicate that MPA is an AR agonist and suggest that the in vivo effects of MPA in breast cancer patients may in part be mediated by the AR.

Prostate-specific antigen and gross cystic disease fluid protein-15 are co-expressed in androgen receptor-positive breast tumours.

Androgens regulate breast cancer cell proliferation via androgen receptor (AR)-mediated mechanisms. To investigate further the androgen-responsiveness of human breast tumours, we examined the immunohistochemical expression of the AR and two androgen-regulated proteins, prostate-specific antigen (PSA) and gross cystic disease fluid protein-15 (GCDFP-15), in 72 primary breast tumours. AR immunoreactivity was present in the nuclei of breast tumour cells and was correlated with oestrogen receptor (ER; P < 0.05) and progesterone receptor (PR; P < 0.01) status. PSA and GCDFP-15 immunoreactivity was present in the cytoplasm of tumour cells but not the adjacent stromal cells. AR-positive cells were present in 85% (61/72) of breast tumours, and 98% (43/44) of PSA-positive and 92% (44/48) of GCDFP-15-positive tumours were also positive for AR. Positive immunoreactivity for both PSA and GCDFP-15 in breast tumours was highly dependent on AR status (odds ratios of 24.0 and 4.5 respectively), but unrelated to age, ER and PR status and axillary lymph node involvement. PSA immunoreactivity was more frequently observed in moderate and well-differentiated tumours and was significantly (P < 0.001) associated with GCDFP-15 immunoreactivity. In conclusion, PSA and GCDFP-15 immunoreactivity was dependent on the presence of AR, but not ER or PR in primary breast tumours.

Role of the androgen receptor in human breast cancer.

Although the androgen receptor (AR)3 is often co-expressed with the estrogen receptor (ER) and progesterone receptor (PR) in human breast tumors, its role in breast cancer is poorly understood. Specific growth stimulatory and inhibitory actions of androgens have been described in human breast cancer cell lines. The mechanisms by which androgens exert these contrasting growth effects are unknown. A commonly utilized second line therapy for the treatment of advanced breast cancer is high dose medroxyprogesterone acetate (MPA). Although MPA, a synthetic progestin, was thought to act exclusively through the PR, the androgenic side-effects observed in women taking MPA suggest that its action may also be mediated in part by the AR. In support of this hypothesis, the level of AR measured by radioligand binding in primary breast tumors was correlated with the duration of response to MPA treatment following failure of tamoxifen therapy. Recent data suggest that the presence of structurally altered AR in breast cancers may account for unresponsiveness to MPA in some of these cases. Further studies are warranted to determine the role of AR mediated pathways in regulating breast tumor growth. In particular, identification of androgen-regulated genes may lead to new possibilities for the hormonal treatment of breast cancer.

Ward evaluations: should they be abandoned?

Even in the era of the objective structured clinical examination (OSCE), the predominant method of resident evaluation is the faculty ward evaluation (WE), despite many concerns about its reliability. The aim of this study was to determine the value of the WE as a measurement of clinical competence in terms of both reliability and validity. In a one-year period, surgery faculty members evaluated 72 residents. An average of 7 faculty members evaluated each resident. The evaluation form contained 10 specific performance ratings and an overall evaluation. Inter-rater reliability of the overall performance ratings was calculated by using the intraclass correlation. Validity of the WE was evaluated in four ways. Inter-rater reliability of the overall performance rating was 0.82; the reliability of a single overall rating was 0.39. (1) A discriminant function analysis indicated that residents at advanced levels of training received more positive evaluations than residents at less advanced levels (P < 0.0001). (2) The overall rating was significantly correlated (r = 0.55, P < 0.0001) with the overall score of a concurrent OSCE. (3) A factor analysis showed high correlations among the items, indicating a lack of discrimination between the skills. (4) Overall ratings were insensitive to performance deficiencies. Only 1.3% of the ratings were unsatisfactory or marginal. The WE was sufficiently reliable to estimate the faculty's view of each resident. The fact that the ratings tended to differentiate residents by level of training and that ratings significantly correlated with the OSCE provides strong evidence of their validity. However, factor analysis indicated that the faculty members were making one global, undifferentiated judgment and that these ratings did not identify deficient performance skills. We conclude that ward evaluations have a place in the assessment of residents.

Expression of the androgen receptor and an androgen-responsive protein, apolipoprotein D, in human breast cancer.

Little is known regarding the activity and function of the androgen receptor (AR) in human breast cancer. In the present study AR was evaluated in untreated primary breast cancers using antisera to the amino- and carboxy-termini of the receptor and quantitated using colour video image analysis. A strong correlation between tissue concentration and percentage AR-positive cells was observed for each antiserum. However, comparison of percentage positive cells using the amino- and carboxy-terminal AR antisera in individual breast cancer specimens revealed a subset of tumours with discordantly increased staining for the carboxy terminus. These findings suggest the presence of amino-terminal-truncated AR in a proportion of breast cancer cells or presence of AR mutations or associated protein alterations that affect binding of the amino-terminal AR antiserum. Immunohistochemical expression of the androgen-regulated glycoprotein, apolipoprotein D (apo-D), was also evaluated in the breast cancer specimens. Focal positivity of apo-D staining, which did not always co-localise with AR-positive cells, was observed within breast tumours. Furthermore, no correlation was evident between percentage positive cells stained for AR and apo-D in breast cancer specimens. These findings indicate that, although apo-D expression is androgen regulated in human breast cancer cell lines in vitro, its expression in primary breast cancers may be regulated by other factors. The expression of AR in primary breast cancers also suggests that the receptor may be involved in tumour responsiveness or in abnormal responses to endocrine therapies.

Medroxyprogesterone acetate therapy in advanced breast cancer: the predictive value of androgen receptor expression.

PURPOSE: To determine the predictive value of androgen receptor (AR) levels in primary tumors of women who undergo medroxyprogesterone acetate (MPA) therapy for advanced breast cancer after relapse on tamoxifen adjuvant therapy. METHODS: Between 1984 and 1987 at Flinders Medical Centre, South Australia, 136 postmenopausal women received adjuvant tamoxifen therapy for lymph node-positive breast cancer. Estrogen receptor (ER), progesterone receptor (PgR), and AR levels, tumor size, and degree of axillary node involvement were determined at the time of diagnosis. The median follow-up period was 81 months; 89 women developed metastatic disease, 83 of whom subsequently received MPA (500 mg/d). The objective response rate ([RR] ie, complete response [CR] and partial response [PR]) and progression-free interval (PFI) were assessed in response to MPA therapy. Associations between RR, PFI, and primary tumor characteristics including ER, PgR, and AR levels were examined using the Mann-Whitney U test, Kaplan-Meier product-limit estimator, and Cox proportional hazards regression, as appropriate. RESULTS: Thirty-two of 83 patients (38.6%) responded to MPA. RR was significantly associated with the presence of AR (P < .001), but not with other primary tumor characteristics or duration of tamoxifen therapy. After initiation of MPA treatment, PFI increased with increasing concentration of AR in the primary tumor. CONCLUSION: Response to MPA after adjuvant tamoxifen treatment for lymph node-positive breast cancer was positively associated with AR level in the primary tumor. This finding suggests that MPA action in breast cancer may be mediated in part by the AR.

Androgens induce divergent proliferative responses in human breast cancer cell lines.

Although the majority of primary human breast cancers express the androgen receptor (AR), the role of androgens in breast cancer growth and progression is poorly understood. We have investigated the effects of the naturally occurring androgen, dihydrotestosterone (DHT), and a synthetic non-metabolizable androgen, mibolerone, on the proliferation of six human breast cancer cell lines. The anti-proliferative and proliferative effects of androgens were only observed in cell lines that expressed the AR. Two of the AR-positive cell lines, T47-D and ZR-75-1 were growth inhibited in the presence of either DHT or mibolerone, while the proliferation of MCF-7 and MDA-MB-453 cells was increased by both androgens. Co-incubation of cultures with 1 nM DHT and a 100-fold excess of the androgen receptor antagonist, hydroxyflutamide, resulted in reversal of both inhibitory and stimulatory effects of DHT on T47-D, MCF-7 and MDA-MB-453 cell proliferation, indicating that DHT action is mediated by the AR in these lines. Hydroxyflutamide only partially reversed the DHT-induced growth inhibition of ZR-75-1 cultures, which suggests that growth inhibition of these cells may be mediated by non-AR pathways of DHT (or DHT metabolite) action. Mibolerone action on breast cancer cell growth was similar to that of DHT, with the exception that growth stimulation of MCF-7 and MDA-MB-453 cells was only partially reversed in the presence of a 100-fold excess of hydroxyflutamide. Anandron, another androgen receptor antagonist, was able to reverse all inhibitory and stimulatory actions of the androgens. AR antisense oligonucleotides reduced the level of immunoreactive AR expression in MDA-MB-453 and ZR-75-1 cells by more than 60%, but only reversed the growth inhibitory action of mibolerone in ZR-75-1 cultures. The results suggest that androgen action in breast cancer cell lines may not be solely mediated by binding of androgen to the AR. For example, metabolites of DHT with oestrogenic activity, or androgen binding to receptors other than the AR, may explain the divergent responses to androgens observed in different breast cancer cell lines.

Paraduodenal hernia.

Over a 10 year period, four patients with paraduodenal hernia were encountered. Two had small hernias that were incidental findings at the time of surgery for an unrelated abdominal condition; these were managed by suture closure of the neck of the sac. The other two patients presented with intestinal obstruction and are discussed here with a review of the literature.

MDA-MB-453, an androgen-responsive human breast carcinoma cell line with high level androgen receptor expression.

The role of androgens and the androgen receptor (AR) in the development and progression of breast cancer is poorly understood. To further define a potential model for androgen action in breast cancer, MDA-MB-453 cells, which express AR in the absence of oestrogen receptors and progesterone receptors, were further characterised in terms of AR expression and androgen responsiveness. High level expression of AR was confirmed by northern blot analysis, radioligand binding and immunocytochemistry, and could not be accounted for by AR gene amplification. Three endogenous androgen-responsive genes (fatty acid synthetase, gross cystic disease fluid protein of 15 kDa and prolactin receptor) and a transfected reporter gene, containing an androgen-responsive element, were induced following androgen administration. A synthetic androgen, mibolerone, induced moderate (27% above control) stimulation of MDA-MB-453 cell proliferation, which was abrogated by the simultaneous administration of the synthetic androgen antagonist, anandron, demonstrating that the effect was AR-mediated. In summary, MDA-MB-453 cells express high levels of functional AR, and thus provide a valuable in vitro model for further studies on androgen regulation of gene expression, and perhaps cell proliferation in breast cancer.

Discourses on the gender/sport relationship: from women in sport to gender relations.

In any developing field such as the one that began as "women in sport," key developments can be traced through the evolution of the language we use and the concepts we develop to express our new understandings. Thus the discourse has moved from considerations of sex differences and sex roles, to gender differences and gender roles, to the sex/gender system, and finally to patriarchy and gender relations, and we have progressed from seeing gender as a variable or as a distributive category to conceiving of it as a set of relations created through human agency and sustained or reproduced through cultural practices including, but not limited to, sport. At the same time, our understanding of sport has grown from seeing it as a static social institution, defined in terms of its separation from the real world, to the comprehension of sport as a social practice produced through human agency and reproduced through ideological work. Finally, our view of gender relations has moved from a focus on sex differences, conceived as relatively innate, to an outraged response to sexism, to a deeper understanding of just how complex and culturally situated are the relations of domination and subordination that characterize gender relations in partriachal cultures. As our consciousness has grown, our questions have changed from "why aren't more women involved in sport?" to "why are women excluded from sport?" to "what specific social practices accomplish the physical and ideological exclusion of women from sport?", "how and why have women managed to resist the practices that seek to incorporate them?", and "how do women work to transform sport to an activity that reflects their own needs as women?" The study of gender relations and sport has come a long way in a short time. In less than 20 years, the field has transformed itself from often angry, always well-intentioned, but generally atheoretical investigations of the patterns of women's involvement and the psychological factors that kept women from full participation, to a theoretically informed, critical analysis of the cultural forces that work to produce the ideological practices that influence the relations of sport and gender. Clearly, the direction for the future lies in the development and application of more critical analyses capable of capturing the complexity of the gender/sport relation.