A randomized trial of specialist genetic assessment: psychological impact on women at different levels of familial breast cancer risk

The aim was to compare the psychological impact of a multidisciplinary specialist genetics service with surgical provision in women at high risk and those at lower risk of familial breast cancer. Women (n=735) were randomized to a surgical consultation with (trial group) or without (control group) specialist genetic risk assessment and the possible offer of presymptomatic genetic testing. Participants completed questionnaires before and immediately after the consultation to assess anxiety, cancer worry, perceived risk, interest in genetic testing and satisfaction. Responses of subgroups of women stratified by clinicians as low, moderate, or high risk were analyzed. There were no significant main effects of study intervention on any outcome variable. Regardless of risk information, there was a statistically significant reduction in state anxiety (P50.001). Reductions in cancer worry and perceived risk were significant for women at low or moderate risk (P50.001) but not those at high risk, and satisfaction was significantly lower in the high risk group (P50.001). In high risk women who received specialist genetic input, there was a marginally significant trend towards increased perceived risk. The effect of risk information on interest in genetic testing was not significant. Breast care specialists other than geneticists might provide assessments of breast cancer risk, reassuring women at reduced risk and targeting those at high risk for specialist genetic counselling and testing services. These findings are discussed in relation to the existing UK Calman-Hine model of service delivery in cancer genetics

Communication and information-giving in high-risk breast cancer consultations: influence on patient outcomes

This longitudinal study aimed to document (i) the information-giving and patient-communication styles of clinical geneticists and genetic counsellors (consultants) in familial breast cancer clinics and (ii) assess the effect of these styles on women`s knowledge, whether their expectations were met, satisfaction, risk perception and psychological status. A total of 158 women from high-risk breast cancer families completed self-report questionnaires at 2 weeks preconsultation and 4 weeks postconsultation. The consultations were audiotaped, transcribed and coded. Multivariate logistic regressions showed that discussing prophylactic mastectomy (P = 0.00) and oophorectomy (P = 0.01) led to women having significantly more expectations met; discussing genetic testing significantly decreased anxiety (P = 0.03) and facilitating understanding significantly decreased depression (P = 0,05). Receiving a summary letter of the consultation significantly lowered anxiety (P = 0.01) and significantly increased the accuracy of perceived risk (P = 0.02). Women whose consultant used more supportive communications experienced significantly more anxiety about breast cancer at the 4 weeks follow-up (P=0.00), These women were not significantly more anxious before genetic counselling. In conclusion, this study found that consultants vary in the amount of information they give and the way they communicate; and this variation can result in better or worse psychosocial outcomes. Greater use of supportive and counselling communications appeared to increase anxiety about breast cancer. Identifying methods to assist consultants to address emotional issues effectively may be helpful

MAPK pathway activation in pilocytic astrocytoma

Pilocytic astrocytoma (PA) is the most common tumor of the pediatric central nervous system (CNS). A body of research over recent years has demonstrated a key role for mitogen-activated protein kinase (MAPK) pathway signaling in the development and behavior of PAs. Several mechanisms lead to activation of this pathway in PA, mostly in a mutually exclusive manner, with constitutive BRAF kinase activation subsequent to gene fusion being the most frequent. The high specificity of this fusion to PA when compared with other CNS tumors has diagnostic utility. In addition, the frequency of alteration of this key pathway provides an opportunity for molecularly targeted therapy in this tumor. Here, we review the current knowledge on mechanisms of MAPK activation in PA and some of the downstream consequences of this activation, which are now starting to be elucidated both in vitro and in vivo, as well as clinical considerations and possible future directions

Current and prospective pharmacological targets in relation to antimigraine action

Migraine is a recurrent incapacitating neurovascular disorder characterized by unilateral and throbbing headaches associated with photophobia, phonophobia, nausea, and vomiting. Current specific drugs used in the acute treatment of migraine interact with vascular receptors, a fact that has raised concerns about their cardiovascular safety. In the past, α-adrenoceptor agonists (ergotamine, dihydroergotamine, isometheptene) were used. The last two decades have witnessed the advent of 5-HT1B/1D receptor agonists (sumatriptan and second-generation triptans), which have a well-established efficacy in the acute treatment of migraine. Moreover, current prophylactic treatments of migraine include 5-HT2 receptor antagonists, Ca2+ channel blockers, and β-adrenoceptor antagonists. Despite the progress in migraine research and in view of its complex etiology, this disease still remains underdiagnosed, and available therapies are underused. In this review, we have discussed pharmacological targets in migraine, with special emphasis on compounds acting on 5-HT (5-HT1-7), adrenergic (α1, α2, and β), calcitonin gene-related peptide (CGRP 1 and CGRP2), adenosine (A1, A2, and A3), glutamate (NMDA, AMPA, kainate, and metabotropic), dopamine, endothelin, and female hormone (estrogen and progesterone) receptors. In addition, we have considered some other targets, including gamma-aminobutyric acid, angiotensin, bradykinin, histamine, and ionotropic receptors, in relation to antimigraine therapy. Finally, the cardiovascular safety of current and prospective antimigraine therapies is touched upon

The molecular structures of the three disilylbenzenes determined in the gas phase, the solid state and by ab initio calculations

Mitzel NW, Brain PT, Hofmann MA, Rankin DWH, Schrock R, Schmidbaur H. The molecular structures of the three disilylbenzenes determined in the gas phase, the solid state and by ab initio calculations. ZEITSCHRIFT FUR NATURFORSCHUNG SECTION B-A JOURNAL OF CHEMICAL SCIENCES. 2002;57(2):202-214.The molecular structures of four silylbenzenes (benzenes with H3Si-substituents), viz. silylbenzene, 1,2-, 1,3- and 1,4-disilylbenzene, were studied by electron diffraction in the gas phase and by ab initio calculations. The structures of 1,2- and 1,4-disilylbenzene were also determined by X-ray diffraction experiments on single crystals grown in situ. The results are compared and discussed with the focus on the evaluation of the SARACEN method for the analysis of gas-phase data, and particularly on its ability to deal with small structural distortions. Important experimental structural parameters are the Si-C bond lengths [A] and the ipso C-C-C angles [deg], which are 1.863(3) / 118.2(2) for gaseous silylbenzene (r(alpha)), 1.875(2) / 119.9(2) for gaseous and 1.870(2) / 118.7(av) for solid 1,2-disilylbenzene, 1.871(1) / 119.4(3) for gaseous 1,3-disilylbenzene, 1.870(2) / 119.0(2) for gaseous and 1.866(3) / 117.4(2) for solid 1,4-disilylbenzene. The angle distortions in the benzene ring geometries are analysed and interpreted in terms of an additivity rule of the distortion caused by each of the silyl substituents. This additivity scheme predicts excellently the observed structures of the silylbenzenes and is in best agreement with the structures calculated ab initio. The slight distortion of molecular symmetry in the crystal structures makes a detailed comparison of the solid-state values impossible, but on average they are in good agreement with theory and predictions of the additivity model. The gas-phase values obtained by the SARACEN method show less pronounced distortions of the benzene ring geometries than observed or predicted by the other methods, but the trends of distortion are fully consistent