Molecular Interaction of Droperidol with Human Ether-a-go-go-related Gene Channels: Prolongation of Action Potential Duration without Inducing Early Afterdepolarization

Background: The cardiac safety of droperidol given at antiemetic doses is a matter of debate. Although droperidol potently inhibits human ether-a-go-go-related gene (HERG) channels, the molecular mode of this interaction is unknown. The role of amino acid residues typically mediating high-affinity block of HERG channels is unclear. It is furthermore unresolved whether droperidol at antiemetic concentrations induces action potential prolongation and arrhythmogenic early afterdepolarizations in cardiac myocytes.

Methods: Molecular mechanisms of HERG current inhibition by droperidol were established using two-electrode voltage clamp recordings of Xenopus laevis oocytes expressing wild-type and mutant channels. The mutants T623A, S624A, V625A, Y652A, and F656A were generated by site-directed mutagenesis. The effect of droperidol on action potentials was investigated in cardiac myocytes isolated from guinea pig hearts using the patch clamp technique.

Results: Droperidol inhibited currents through HERG wild-type channels with a concentration of half-maximal inhibition of 0.6-0.9 [mu]m. Droperidol shifted the channel activation and the steady state inactivation toward negative potentials while channel deactivation was not affected. Current inhibition increased with membrane potential and with increasing duration of current activation. Inhibition of HERG channels was similarly reduced by all mutations. Droperidol at concentrations between 5 and 100 nm prolonged whereas concentrations greater than 300 nm shortened action potentials. Early afterdepolarizations were not observed.     

Bilateral field advantage in visual crowding

Thirty randomly oriented T’s were presented in a circle around fixation at an eccentricity of 11° such that each T was crowded by its neighbors. Two locations within the same hemifield (unilateral condition) or one location in each hemifield (bilateral condition) were precued for subsequent probing. Observers were then asked to report the orientation of a target T at one of these locations. A bilateral field advantage was found: target identification was better when the two precued targets were in different hemifields than when they were within the same hemifield. This bilateral advantage was absent when only targets were presented, without any distracters. Further controls showed that this advantage could not be attributed to differences between horizontal and vertical target alignments or to visual field anisotropies. A similar bilateral advantage has been reported for multiple object tracking (Alvarez, G. A., & Cavanagh, P. (2005). Independent resources for attentional tracking in the left and right visual fields. Psychological Science 16(8), 637-643) and other attentional tasks. Our results suggest that crowding also demonstrates separate attentional resources in the left and right hemifields. There was a cost to attending to two targets presented unilaterally over attending to a single target. However, this cost was reduced when the two crowded targets were in separate hemifields.     

Decreased amygdala CRF-binding protein mRNA in post-mortem tissue from male but not female bipolar and schizophrenic subjects.

Stressful life events are commonly associated with the onset and maintenance of psychopathology and much research has focused on the role of the corticotropin-releasing factor (CRF) system in mediating psychopathology. Since CRF serves to integrate the stress response, it is possible that the CRF system plays a role as a neurochemical linkage between stress and psychopathology. CRF-binding protein (CRF-BP) is thought to modulate CRF activity by decreasing its actions. Therefore, in some psychopathological states, alterations in CRF-BP function may contribute to dysregulation of the CRF system. Since the amygdala CRF system mediates stress- and anxiety-related behaviors and alterations in amygdala function are associated with psychopathology, we examined amygdala CRF-BP gene expression in post-mortem brains from subjects with major depression, bipolar disorder, and schizophrenia as well as in controls. In addition to characterizing the anatomic distribution of CRF-BP mRNA in the human amygdala and medial temporal lobe region, we found a significant decrease in CRF-BP mRNA levels in the basolateral amygdala of male bipolar and male schizophrenic subjects and the lateral amygdala of male bipolar subjects. These results raise the possibility that men with decreased amygdala CRF-BP may be more vulnerable to the effects of stress exposure on the etiology or maintenance of bipolar disorder or schizophrenia.     

Precursors of schizophrenia

Several likely precursors of schizophrenia have been identified. These range from possibly causative features, such as exposure to perinatal insults, to features that are the effects of an underlying vulnerability, such as abnormal childhood behaviors. Unfortunately none of these precursors is specific enough to be used in identifying individuals for targeted preventive treatment. A more useful strategy is to combine risk factors for psychotic disorders in a population seeking help for psychiatric problems. Thus, individuals who are possibly prodromal are identified. Research into this group has found high rates of onset of psychotic disorders, particularly schizophrenia, within a short time frame. Preliminary treatment trials suggest that symptoms can be reduced and psychosis onset possibly delayed or averted.     

Frontal Slab Composite Magnetic Resonance Neurography of the Brachial Plexus: Implications for Infraclavicular Block Approaches

Background: Magnetic resonance neurography (MRN) is an imaging method by which nerves can be selectively highlighted. Using commercial software, the authors explored a variety of approaches to develop a three-dimensional volume-rendered MRN image of the entire brachial plexus and used it to evaluate the accuracy of infraclavicular block approaches.

Methods: With institutional review board approval, MRN of the brachial plexus was performed in 10 volunteer subjects. MRN imaging was performed on a GE 1.5-tesla magnetic resonance scanner (General Electric Healthcare Technologies, Waukesha, WI) using a phased array torso coil. Coronal STIR and T1 oblique sagittal sequences of the brachial plexus were obtained. Multiple software programs were explored for enhanced display and manipulation of the composite magnetic resonance images. The authors developed a frontal slab composite approach that allows single-frame reconstruction of a three-dimensional volume-rendered image of the entire brachial plexus. Automatic segmentation was supplemented by manual segmentation in nearly all cases. For each of three infraclavicular approaches (posteriorly directed needle below midclavicle, infracoracoid, or caudomedial to coracoid), the targeting error was measured as the distance from the MRN plexus midpoint to the approach-targeted site.

Results: Composite frontal slabs (coronal views), which are single-frame three-dimensional volume renderings from image-enhanced two-dimensional frontal view projections of the underlying coronal slices, were created. The targeting errors (mean +/- SD) for the approaches-midclavicle, infracoracoid, caudomedial to coracoid-were 0.43 +/- 0.67, 0.99 +/- 1.22, and 0.65 +/- 1.14 cm, respectively.     

Psychosocial factors at work and perceived health among agricultural meat industry workers in France

Objective  The objective of this study was to describe the perceived health status of the meat industry employees—i.e., working in the slaughtering, cutting, and boning of large animals and poultry—and its relation to their organisational and psychosocial constraints at work. Methods  This postal survey included all 3,000 employees of the meat industry (beef, pork and poultry) in four districts in Brittany, France, whose companies were affiliated with the agricultural branch of the national health insurance fund. The questionnaire asked for social and demographic data and information describing their job and the organisation of their work. The psychosocial factors at work were described according to Karasek’s questionnaire (demand, latitude and social support at work). Perceived health was measured with the Nottingham Health Profile perceived health indicator. Results  This study shows the high prevalence of poor health reported by the workers in this industry. This poor perceived health was worse in women and increased regularly with age. Among the psychosocial factors studied, high quantitative and qualitative demand at work, inadequate resources for good work and to a lesser extent, inadequate prospects for promotion appear especially associated with poor perceived health. Other factors often associated with poor perceived health included young age at the first job and work hours that disrupt sleep rhythms (especially for women). Conclusion  Our results show that this population of workers is especially vulnerable from the point of view of perceived physical and psychological health and is exposed to strong physical, organisational and psychosocial constraints at work. They also demonstrate that poor perceived health is associated with some psychosocial (such as high psychological demand and insufficient resources) and organisational factors at work. These results, in conjunction with those from other disciplines involved in studying this industry, may help the companies to develop preventive activities.     

Progressive myelopathy due to meningeal thickening in shunted patients: description of a novel entity and the role of surgery

INTRODUCTION: Spinal cord compression due to meningeal thickening is a rare occurrence in shunted patients. Because of the long delay to clinical onset, this complication has not been identified as yet. AIMS: We report on nine cases of shunt-related progressive myelopathy due to meningeal thickening (SPMMT). MATERIALS AND METHODS: We reviewed our database of shunted children, for cases having developed progressive tetraparesis due to cervical meningeal thickening. RESULTS: We identified nine observations of SPMMT, eight of these with hydrocephalus due to neonatal meningitis; the last case had Dandy-Walker malformation shunted at birth and suffered postoperative meningitis. The age of clinical onset of myelopathy was between 6 and 20 years (median 12.8). All patients presented with slowly progressive walking difficulties with falls and no spinal pain. Magnetic resonance imaging (MRI) showed typically a thickened dura mater with collapse of the arachnoid space, compensatory expansion of the epidural fat, and T2 hyperintensity in the spinal cord. We operated on seven patients for surgical decompression and arachnoidolysis: One died postoperatively because of shunt malfunction, and two others died later of complications of tetraplegia. Three patients were aggravated after surgery, three experienced partial improvement, but one of these subsequently deteriorated again. CONCLUSION: SPMMT appears to be a novel and well-defined clinical and pathological entity; its pathological and radiological features are stereotyped; however, the diagnosis is delayed because of the slow pace of the disease. Although surgical decompression may be the only option, its results were poor in our experience; earlier surgery might improve this grim prognosis.     

乳腺癌辅助内分泌治疗

内分泌治疗适用于激素敏感性肿瘤。70％乳腺癌细胞膜表面有雌激素或者孕激素受体表达，为激素敏感性肿瘤。     

Changes in the African American female profile as depicted in fashion magazines during the 20th century.

This study evaluated changes in the profiles of African American women presented in fashion magazines during the 20th century. Twenty-six variables were measured on a total of 119 profile photographs collected from various fashion magazines published in the 1940s through the 1990s. The photographs were divided into 6 groups corresponding to the decade in which they were published. A 1-way analysis of variance was performed, and between-group differences were examined with a Tukey multiple comparison procedure. Significant between-group differences (P <.01) were found for anteroposterior lip position, nasolabial angle, and interlabial angle, with increased fullness and more anteriorly positioned lips in the more recent decades. No significant differences were found for the frontonasal angle, the nasal tip angle, and the relationship of the chin to the upper face (total facial angle). Esthetic standards for the African-American female profile changed during the 20th century and, similar to the standards for the white profile, show a trend toward fuller and more anteriorly positioned lips.