Prognostic value of monitoring tumour markers CA 15-3 and CEA during fulvestrant treatment

BACKGROUND: At many centres tumour markers are used to detect disease recurrence and to monitor response to therapy in patients with advanced disease, although the real value of serial observation of marker levels remains disputed. In this study, we evaluated the prognostic value of tumour markers for predicting response (partial response [PR], stable disease [SD] ≥ 6 months), de novo disease progression (PD) and secondary PD in patients receiving fulvestrant ('Faslodex') 250 mg/month for the treatment of metastatic breast cancer (MBC). METHODS: Changes in cancer antigen 15–3 (CA 15-3) and carcinoembryonic antigen (CEA) were prospectively monitored (monthly) and were also evaluated for the 3 months preceding secondary PD. Data from 67 patients with previously treated MBC participating in a Compassionate Use Programme were analysed. RESULTS: In patients with a PR (n = 7 [10.4%]), a non-significant increase in CA 15-3 occurred during the first 6 months of treatment; CEA was significantly reduced (P = 0.0165). In patients with SD ≥ 6 months (n = 28 [41.8%]), both CA 15-3 (P < 0.0001) and CEA (P = 0.0399) levels increased significantly after 6 months treatment. In those experiencing de novo PD (n = 32 [47.8%]), CA 15-3 increased significantly (P < 0.0001) after 4 months; CEA also increased significantly (P = 0.0002) during the same time period. Both CA 15-3 (P < 0.0001) and CEA (P < 0.0001) increased significantly in the 3 months preceding secondary PD. CONCLUSION: CA 15-3 increases in patients progressing on fulvestrant but may also increase in those experiencing clinical benefit; this should not be taken as a sign of PD without verification. Overall, both CA 15-3 and CEA appear to be poor prognostic markers for determining progression in patients receiving fulvestrant

ArteFill® Permanent Injectable for Soft Tissue Augmentation: II. Indications and Applications

Patients ask for procedures with long-lasting effects. ArteFill is the first permanent injectable approved in 2006 by the FDA for nasolabial folds. It consists of cleaned microspheres of polymethylmethacrylate (PMMA) suspended in bovine collagen. Over the development period of 20 years most of its side effects have been eliminated to achieve the same safety standard as today’s hyaluronic acid products. A 5-year follow-up study in U.S. clinical trial patients has shown the same wrinkle improvement as seen at 6 months. Long-term follow-up in European Artecoll patients has shown successful wrinkle correction lasting up to 15 years. A wide variety of off-label indications and applications have been developed that help the physician meet the individual needs of his/her patients. Serious complications after ArteFill injections, such as granuloma formation, have not been reported due to the reduction of PMMA microspheres smaller than 20 μm to less than 1% “by the number.” Minor technique-related side effects, however, may occur during the initial learning curve. Patient and physician satisfaction with ArteFill has been shown to be greater than 90%

The sense of smell, its signalling pathways, and the dichotomy of cilia and microvilli in olfactory sensory cells

Smell is often regarded as an ancillary perception in primates, who seem so dominated by their sense of vision. In this paper, we will portray some aspects of the significance of olfaction to human life and speculate on what evolutionary factors contribute to keeping it alive. We then outline the functional architecture of olfactory sensory neurons and their signal transduction pathways, which are the primary detectors that render olfactory perception possible. Throughout the phylogenetic tree, olfactory neurons, at their apical tip, are either decorated with cilia or with microvilli. The significance of this dichotomy is unknown. It is generally assumed that mammalian olfactory neurons are of the ciliary type only. The existance of so-called olfactory microvillar cells in mammals, however, is well documented, but their nature remains unclear and their function orphaned. This paper discusses the possibility, that in the main olfactory epithelium of mammals ciliated and microvillar sensory cells exist concurrently. We review evidence related to this hypothesis and ask, what function olfactory microvillar cells might have and what signalling mechanisms they use

IL-4 receptor-alpha-dependent control of Cryptococcus neoformans in the early phase of pulmonary infection

Cryptococcus neoformans is an opportunistic fungal pathogen that causes lung inflammation and meningoencephalitis in immunocompromised people. Previously we showed that mice succumb to intranasal infection by induction of pulmonary interleukin (IL)-4Rα-dependent type 2 immune responses, whereas IL-12-dependent type 1 responses confer resistance. In the experiments presented here, IL-4Rα −/− mice unexpectedly show decreased fungal control early upon infection with C. neoformans , whereas wild-type mice are able to control fungal growth accompanied by enhanced macrophage and dendritic cell recruitment to the site of infection. Lower pulmonary recruitment of macrophages and dendritic cells in IL-4Rα −/− mice is associated with reduced pulmonary expression of CCL2 and CCL20 chemokines. Moreover, IFN-γ and nitric oxide production are diminished in IL-4Rα −/− mice compared to wild-type mice. To directly study the potential mechanism(s) responsible for reduced production of IFN-γ, conventional dendritic cells were stimulated with C. neoformans in the presence of IL-4 which results in increased IL-12 production and reduced IL-10 production. Together, a beneficial role of early IL-4Rα signaling is demonstrated in pulmonary cryptococcosis, which contrasts with the well-known IL-4Rα-mediated detrimental effects in the late phase

Parallel Odor Processing by Two Anatomically Distinct Olfactory Bulb Target Structures

The olfactory cortex encompasses several anatomically distinct regions each hypothesized to provide differential representation and processing of specific odors. Studies exploring whether or not the diversity of olfactory bulb input to olfactory cortices has functional meaning, however, are lacking. Here we tested whether two anatomically major olfactory cortical structures, the olfactory tubercle (OT) and piriform cortex (PCX), differ in their neural representation and processing dynamics of a small set of diverse odors by performing in vivo extracellular recordings from the OT and PCX of anesthetized mice. We found a wealth of similarities between structures, including odor-evoked response magnitudes, breadth of odor tuning, and odor-evoked firing latencies. In contrast, only few differences between structures were found, including spontaneous activity rates and odor signal-to-noise ratios. These results suggest that despite major anatomical differences in innervation by olfactory bulb mitral/tufted cells, the basic features of odor representation and processing, at least within this limited odor set, are similar within the OT and PCX. We predict that the olfactory code follows a distributed processing stream in transmitting behaviorally and perceptually-relevant information from low-level stations

Neuroimaging in anxiety disorders

Neuroimaging studies have gained increasing importance in validating neurobiological network hypotheses for anxiety disorders. Functional imaging procedures and radioligand binding studies in healthy subjects and in patients with anxiety disorders provide growing evidence of the existence of a complex anxiety network, including limbic, brainstem, temporal, and prefrontal cortical regions. Obviously, “normal anxiety” does not equal “pathological anxiety” although many phenomena are evident in healthy subjects, however to a lower extent. Differential effects of distinct brain regions and lateralization phenomena in different anxiety disorders are mentioned. An overview of neuroimaging investigations in anxiety disorders is given after a brief summary of results from healthy volunteers. Concluding implications for future research are made by the authors

Subjecting Elite Athletes to Inspiratory Breathing Load Reveals Behavioral and Neural Signatures of Optimal Performers in Extreme Environments

Background: It is unclear whether and how elite athletes process physiological or psychological challenges differently than healthy comparison subjects. In general, individuals optimize exercise level as it relates to differences between expected and experienced exertion, which can be conceptualized as a body prediction error. The process of computing a body prediction error involves the insular cortex, which is important for interoception, i.e. the sense of the physiological condition of the body. Thus, optimal performance may be related to efficient minimization of the body prediction error. We examined the hypothesis that elite athletes, compared to control subjects, show attenuated insular cortex activation during an aversive interoceptive challenge. Methodology/Principal Findings: Elite adventure racers (n = 10) and healthy volunteers (n = 11) performed a continuous performance task with varying degrees of a non-hypercapnic breathing load while undergoing functional magnetic resonance imaging. The results indicate that (1) non-hypercapnic inspiratory breathing load is an aversive experience associated with a profound activation of a distributed set of brain areas including bilateral insula, dorsolateral prefrontal cortex and anterior cingulated; (2) adventure racers relative to comparison subjects show greater accuracy on the continuous performance task during the aversive interoceptive condition; and (3) adventure racers show an attenuated right insula cortex response during and following the aversive interoceptive condition of non-hypercapnic inspirator

Engagement Across Developmental Periods

The goal of this chapter is to provide a cohesive developmental framework and foundation for which to understand student engagement across early childhood, middle childhood, and adolescence. Guided by the bioecological theory of human development and the person-environment fit perspective, this chapter extends Finn\u27s participation-identification model of engagement by mapping student engagement within a larger developmental sequence. This chapter discusses student engagement within specific developmental periods that are tied to the developmental tasks, opportunities, and challenges unique to early childhood, middle childhood, and adolescence. Student engagement is found to be a nuanced developmental outcome, and the differences may be a result of the maturation of biological, cognitive, and socioemotional developmental tasks and the changing contextual landscape for the children and adolescents. Recommendations for future research as well as policy implications are also discussed