Surveillance and simulation of bovine spongiform encephalopathy and scrapie in small ruminants in Switzerland

BACKGROUND: After bovine spongiform encephalopathy (BSE) emerged in European cattle livestock in 1986 a fundamental question was whether the agent established also in the small ruminants' population. In Switzerland transmissible spongiform encephalopathies (TSEs) in small ruminants have been monitored since 1990. While in the most recent TSE cases a BSE infection could be excluded, for historical cases techniques to discriminate scrapie from BSE had not been available at the time of diagnosis and thus their status remained unclear. We herein applied state-of-the-art techniques to retrospectively classify these animals and to re-analyze the affected flocks for secondary cases. These results were the basis for models, simulating the course of TSEs over a period of 70 years. The aim was to come to a statistically based overall assessment of the TSE situation in the domestic small ruminant population in Switzerland. RESULTS: In sum 16 TSE cases were identified in small ruminants in Switzerland since 1981, of which eight were atypical and six were classical scrapie. In two animals retrospective analysis did not allow any further classification due to the lack of appropriate tissue samples. We found no evidence for an infection with the BSE agent in the cases under investigation. In none of the affected flocks, secondary cases were identified. A Bayesian prevalence calculation resulted in most likely estimates of one case of BSE, five cases of classical scrapie and 21 cases of atypical scrapie per 100'000 small ruminants. According to our models none of the TSEs is considered to cause a broader epidemic in Switzerland. In a closed population, they are rather expected to fade out in the next decades or, in case of a sporadic origin, may remain at a very low level. CONCLUSIONS: In summary, these data indicate that despite a significant epidemic of BSE in cattle, there is no evidence that BSE established in the small ruminant population in Switzerland. Classical and atypical scrapie both occur at a very low level and are not expected to escalate into an epidemic. In this situation the extent of TSE surveillance in small ruminants requires reevaluation based on cost-benefit analysis.

Estrogen receptor modulators and down regulators: optimal use in postmenopausal women with breast cancer

Endocrine treatments have been used in breast cancer since 1896, when Beatson reported on the results of oophorectomy for advanced breast cancer. In the second half of the last century, different endocrine-based compounds were developed and, in this review, the role of the selective estrogen receptor modulators (SERMs) and selective estrogen receptor down regulators (SERDs) in the postmenopausal setting are discussed. Tamoxifen is the most investigated and most widely used representative of these agents, and has been introduced in the advanced disease, in the neoadjuvant and adjuvant setting, and for the prevention of the disease. Its role has been challenged in recent years by the introduction of third-generation aromatase inhibitors that have proven higher activities than tamoxifen with different toxicity patterns. Several other SERMs have been investigated, but none have been clearly superior to tamoxifen. SERDs act as pure estrogen antagonists and should compare favourably to tamoxifen. For the time being, they have been used in the treatment of advanced breast cancers and their role in other settings still needs investigation. The increased use of aromatase inhibitors as first-line endocrine therapy has resulted in new discussions regarding the role that tamoxifen and other SERMs or SERDs may play in breast cancer. The sequencing of endocrine therapies in hormone-sensitive breast cancer remains a very important research issue.