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A range of tamoxifen derivatives substituted in the 4-position of the 1-phenyl ring are described. The key steps in the synthesis of 4-iodo-, 4-bromo-, and 4-(methylthio)tamoxifen were reactions of 1,2-diarylbutanones with the (4-halogenophenyl)lithium or [4-(methylthio)phenyl]magnesium bromide. Oxidized precursors of 4-(methylthio)tamoxifen were used to prepare the methylsulfinyl and methylsulfonyl derivatives. Further derivatives (formyl, hydroxymethyl, oxirane, mercapto) were prepared from 4-bromotamoxifen via the 4-lithio derivative. Several of the derivatives (Br, I, SMe, SOMe, SO2Me, oxirane, CHO, CH2OH) displayed a higher affinity for estrogen receptors (ER) of calf uterine cytosol than did tamoxifen, but there was no relationship between affinity to ER and the ability to inhibit the growth of the MCF-7 breast cancer cell line in vitro.

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This study compares the performance of three chromogenic culture agar plates, chromID MRSA, MRSA-Screen and MRSA-Select, by challenging with a collection of Staphylococcus aureus strains and screening samples obtained from hospitalised patients. All chromogenic media showed excellent sensitivity (>95%) and specificity after 18 h on the methicillin-resistant Staphylococcus aureus (MRSA) collection strains, but the specificity of MRSA-Screen decreased markedly after 42 h. Sixty-eight of 1,002 screening specimens yielded MRSA on at least one medium. The sensitivity of all media to detecting MRSA after 18 h was <50%, but this increased to 75% (chromID MRSA), 81% (MRSA-Screen) and 72% (MRSA-Select) after 42 h and 85% after enrichment and plating on the same media. The specificity at 18 h was excellent, but was significantly lower for MRSA-Screen after 42 h and enrichment. In conclusion, all media showed equivalent sensitivities after 18 h of incubation and performed better when enriched before inoculation. MRSA-Screen was more sensitive but less specific than the two other media after 42 h of incubation.

The predictive value of the estrogen receptor (ER) assay with regard to the response to hormonal treatment was analyzed in women with advanced breast carcinoma. The significance of ten clinical variables of putative prognostic value was also investigated. A total of 49 courses of endocrine therapy were available for study. The respective merits of using the receptor information as a qualitative or a quantitative variable were compared. Linear logistic regression analysis showed that the quantitative information was significantly related to the therapeutic response (P < 0.0001) and proved to be superior to the qualitative information. Compared with the clinical variables tested with the logistic model, receptor concentration was by far the most important single predictor of response. Nevertheless, introduction of two of these clinical variables (i.e., age and menopausal status) into the model in addition to receptor concentration improved its predictive value. Presented in graphic form, the improved model provides a simple means to estimate the probability that a given patient will respond to endocrine therapy. Successive ER assays were available in a series of patients who had received no systemic treatment. In ER+ cases, there was a significant correlation between receptor concentrations in the consecutive assays. There was no influence of the time interval between tissue samplings. Data were also consistent in ER- patients. These results give support to the practice of routine receptor determination in the primary tumor at the time of mastectomy. It is concluded that the distinction between hormone-responsive and hormone-resistant tumors appears artificial. The therapeutic implications of a continuous gradient of hormone-dependency among breast cancers are discussed.