Clinical research in the lay press: irresponsible journalism raises a huge dose of doubt.
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Biomedical subjects
Publications and source records attributed to Melissa Johnson.
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Results of five major randomized trials have increased our understanding of the role of aromatase inhibitors in the adjuvant setting. Two of these trials, the Anastrozole or Tamoxifen Alone or in Combination (ATAC) trial and the International Breast Cancer Study Group's BIG 1-98 trial compared an aromatase inhibitor versus tamoxifen as initial hormonal therapy. Three other trial were designed as cross-over studies; the Intergroup Exemestane Study (IES) and the Austrian Breast and Colorectal Cancer Study Group (ABCSG) Trial 8/German ARNO 95 trial compared a crossover from tamoxifen to an aromatase inhibitor versus continued tamoxifen in women who had completed 2 to 3 years of tamoxifen. The MA-17 trial compared the use of letrozole with placebo for 5 years, following 5 years of tamoxifen. Based on the results of these studies, the use of an aromatase inhibitor for the adjuvant treatment of postmenopausal women with hormone receptor-positive early breast cancer has largely replaced the previous standard of 5 years of tamoxifen. Still unanswered, however, are questions regarding optimal sequencing, selection of aromatase inhibitor, and duration of treatment. This review will provide an overview of the major studies with an emphasis on these important questions.
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We used event-related fMRI to identify the brain regions engaged during explicit and implicit sequence learning (ESL and ISL, respectively). Twenty-four subjects performed a concurrent ESL and ISL task. Behavior showed learning in both conditions. Prefrontal (PFC), striatal, anterior cingulate cortex (ACC) and visual regions (V1, V2 and V3) were engaged during both ESL and ISL. With ESL there was increased activity in the visual regions on the predictable (i.e. learned pattern) trials. With ISL, however, there was a relative decrease in activity in visual regions. The opposite patterns in the visual regions highlight the different effects of ESL and ISL. The learning process was distinguished from the result of learning, by fitting subjects' functional magnetic resonance imaging data to their learning curve. This analysis revealed more extensive PFC activity during ESL and caudal ACC activity specific for the result of learning analysis, when the expected response was violated. Our results suggest a relative dissociation of the brain regions engaged during ESL and ISL, whereby ESL and ISL can be viewed as partially distinct but overlapping parallel processes.
Although antigen-loaded dendritic cells (DC) are being investigated as antitumor vaccines, which DC differentiation state is most effective is not clear. Three DC functions that may be critical for immunization potential are expression of CD80/86, cytokine production following CD40 engagement, and migration to chemokine receptor 7-binding chemokines. We therefore examined highly purified human monocyte-derived immature and mature DC for these properties from normal donors and cancer patients. Although high expression of CD80/86 and migration to 6Ckine + macrophage-inflammatory protein-3beta were properties of mature DC, cytokine production following CD40 ligation was superior by immature DC. Loss of cytokine secretion occurred with multiple maturation conditions, was not apparently reversible, and was also seen with lipopolysaccharide stimulation in correlation with down-regulated Toll-like receptor expression. Our results suggest that the functions thought to contribute to optimal T cell priming are not coexpressed by the same DC population and that immature and mature DC likely possess distinct CD40-mediated signaling events.
Celecoxib is as effective as other nonsteroidal anti-inflammatory drugs (NSAIDs) for treating the symptoms of osteoarthritis or rheumatoid arthritis. However, patients taking celecoxib are less likely to discontinue the medication because of gastrointestinal upset than patients taking traditional NSAIDs. Nevertheless, celecoxib does not decrease the incidence of serious gastrointestinal adverse events with long-term therapy.
The aim of this study was to identify clinical parameters that may help distinguish periappendicitis from the more common clinical entity of acute appendicitis. Serosal inflammation of the appendix without mucosal involvement constitutes the condition known as periappendicitis. In most situations this is a sequel of extra-appendicular sepsis and is likely to benefit from treatment targeted to the underlying pathology. But the majority of these cases are initially treated for acute appendicitis as clinical distinction between the two conditions is difficult. In this study some commonly used clinical yardsticks have been analyzed with respect to their value in this subtle diagnosis. We reviewed 231 successive cases clinically diagnosed as acute appendicitis; of these 18 had histologically demonstrated periappendicitis. Eight parameters were studied: age, gender, temperature, white blood cell count, location and duration of pain, associated symptoms, and peritoneal signs. Significant statistical differences were found between the two groups with regard to pain location, pain duration, and the presence of peritoneal signs. It may be possible to suspect periappendicitis preoperatively with meticulous clinical assessment. This may be of value in avoiding missed nonappendicular pathologies.