Panic and phobic anxiety: defining phenotypes for genetic studies

OBJECTIVE: With recent advances in molecular genetics, the rate-limiting step in identifying susceptibility genes for psychiatric disorders has become phenotype definition. The success of psychiatric genetics may require the development of a "genetic nosology" that can classify individuals in terms of the heritable aspects of psychopathology. The authors' aim is to begin to apply this analysis to the anxiety disorders, focusing on panic and phobic disorders. METHOD: Two parallel traditions of defining anxiety phenotypes are reviewed: the first, more closely identified with clinical psychiatry, has identified categorical diagnoses (e.g., panic disorder and social phobia). The other, more closely identified with psychological studies of personality development, has examined dimensional traits (e.g., neuroticism) and anxious temperament (e.g., behavioral inhibition). RESULTS: The authors suggest that a genetic nosology of panic and phobic disorders may incorporate features of both traditions and discuss strategies for optimizing genetic approaches to anxiety including 1) studying phenotypic extremes, 2) identifying biological trait markers, and 3) using animal models to identify candidate loci. CONCLUSIONS: An important dividend from the effort to define the boundaries of heritable phenotypes for genetic studies of anxiety may be a refinement of the nosology of anxiety disorders.     

Deviant auditory stimuli activate human left and right auditory cortex differently

Infrequent "deviant' auditory stimuli embedded in a homogeneous sequence of "standard' sounds evoke a neuromagnetic mismatch field (MMF), which is assumed to reflect automatic change detection in the brain. We investigated whether MMFs would reveal hemispheric differences in cortical auditory processing. Seven healthy adults were studied with a whole-scalp neuromagnetometer. The sound sequence, delivered to one ear at time, contained three infrequent deviants (differing from standards in duration, frequency, or interstimulus interval) intermixed with standard tones. MMFs peaked 9-34 msec earlier in the right than in the left hemisphere, irrespective of the stimulated ear. Whereas deviants activated only one MMF source in the left hemisphere, two temporally overlapping but spatially separate sources, one in the temporal lobe and another in the inferior parietal cortex, were necessary to explain the right-hemisphere MMFs. We suggest that the bilateral MMF components originating in the supratemporal cortex are feature specific whereas the right-hemisphere parietal component reflects more global auditory change detection. The results imply hemispheric differences in sound processing and suggest stronger involvement of the right than the left hemisphere in change detection.     

Rerouting of the intratemporal facial nerve: an analysis of the literature

Anterior rerouting of the intratemporal facial nerve in the infratemporal fossa approach is employed to access to the jugular bulb, hypotympanum, and lateral skull base, whereas posterior rerouting of the facial nerve, as employed in the transcochlear craniotomy, is most frequently used for surgery of the posterior fossa, cerebellopontine angle, prepontine region, and petrous apex. Facial nerve rerouting may lead to facial paresis or paralysis. This review of the literature is intended to define the physiologic "cost" of these procedures, so that the neurotologic surgeon can determine if the morbidity incurred in these techniques is worth the resultant exposure. Inconsistencies in reporting facial function places into question the validity of some of the cumulative data reported. Postoperatively, grades I-II facial nerve function was seen in 91% of patients undergoing short anterior rerouting, 74% of patients undergoing long anterior rerouting, and 26% of patients undergoing posterior complete rerouting. Although facial nerve rerouting allows unhindered exposure to previously inaccessible regions, it is achieved at the cost of facial nerve function. Facial nerve dysfunction increases with the length of facial nerve rerouted.     

生态建造：教育套餐和环境手册

生态建造是一个关注于传播建成环境中可持续性的需要以及促成可持续性的方式的项目。它针对于两个群体：16-19岁的学生，为他们制作了一个交互式的光盘；建造行业中的专业人员。光盘中提出了这样的问题--你的家和学校有多绿色？它说明了类似于建筑尺度和朝向的设计决策如何影响到建筑在能耗方面的表现和CO2的排放量。光盘包括了衡量如往宅温室节能效果的术语表，来解释它们对建筑的影响。这样学生们就可以对他们自己的学校和家进行评估，并提出怎样的设计可以提高它们的节能效果。如果我们想全球化地实现可持续性的未来，下一代的介入至关重要。环境手册中更深入地研究了这些问题，并关注到了其他建筑类型，如办公建筑。本文描述了正趋于完成的教育光盘和环境手册中涉及的一些根本的环境和教育因素。     

Development,amino acid utilization and cell allocation in bovine embryos after in vitro production in contrasting culture systems

The effects of protein-supplemented and protein-free media on amino acid uptake, protein synthesis and cell differentiation in bovine blastocysts were investigated. Four formulations of synthetic oviduct fluid were used. Each formulation was identified by the principal supplement: bovine serum albumin (0.4%, w/v); polyvinyl alcohol (0.3%, w/v); or either of two steer sera (10%, v/v). After zygote culture, blastocyst yields (day 7.5) were lowest in protein-free medium and highest in albumin-supplemented medium. Subsequent 12 h incubation in the presence of both essential and non-essential amino acids was used for the measurement of amino acid flux. All blastocysts released alanine but consumed aspartate (P < 0.001) and the extent was influenced by prior culture conditions. Aspartate uptake was lower in blastocysts produced in protein-free conditions (P < 0.05) than in blastocysts produced in albumin-supplemented conditions. Consumption indices for 16 other amino acids were not influenced by blastocyst source. Cell counts and hatching incidences were highest for albumin-supplemented blastocysts, but were similar among blastocysts from the protein-free and serum-dependent treatments. Crucially, the use of protein-free medium for zygote culture did not compromise resultant blastocysts in terms of either de novo protein synthesis ([3H]phenylalanine incorporation) or trophectoderm function (phenotype based on interferon-tau detection). Thus, although blastocyst yields were compromised after zygote culture in a protein-free (vis-à-vis albumin-supplemented) medium, amino acid flux was qualitatively conserved, and only quantitatively modified in the case of alanine and aspartate. Moreover, vital properties of blastocysts that were produced, including de novo protein synthesis and trophectodermal cell function, apparently were not adversely affected by protein deprivation.     

Analysis of grocery chain pharmacists' work-related behaviors

OBJECTIVE: To measure grocery chain pharmacists' work-related behaviors to assess the impact of a Pharmaceutical Care Certificate Program (PCCP) and other future interventions intended to alter pharmacists' practice behaviors. DESIGN: This study used multidimensional work sampling (MWS), a work measurement methodology that breaks "work" into three components: activity (what was done), contact (with whom the activity was performed), and function (the purpose or objective of the activity). Pharmacists were signaled at random intervals during the workday by a random signal generator. A selection was made from a list of items in each of the three dimensions of work to form an activity-contact-function combination code that described the work-related behavior at that point in time. SETTING AND PARTICIPANTS: Pharmacists in 15 grocery chain stores in the Indianapolis area; 20 pharmacists were enrolled in Purdue University's PCCP and 10 served as controls. Data were collected for a period of six weeks during April through June 1997 before the beginning of the PCCP program. MAIN OUTCOME MEASURES: Pharmacists' work-related behaviors. RESULTS: Writing/keyboarding was the most frequently recorded activity (22%), followed by one-to-one meetings (21.6%), and drug preparation (18%). Pharmacists spent most of their time working alone (62.9%), while a smaller but still substantial proportion of time was spent interacting with patients (17.9%). The most frequently recorded purpose (i.e., function) of pharmacists' activities was drug distribution (23.9%), followed by personal time (12.4%), receiving or transferring a medication order (10.2%), and patient counseling (6.6%). Out of a possible, 1,760 activity-contact-function combinations, 10 accounted for 46.3% of all reported observations, with "Prepare drug-Self-Drug distribution" representing the most frequently recorded activity-contact-function combination (15.7%). CONCLUSION: MWS is useful in helping grocery chain management better understand how pharmacy personnel are currently being utilized. This study provides a baseline for evaluating the impact of training programs or other alterations in the practice environment on pharmacists' work-related behaviors.     

Memory liabilities associated with hypnosis: does low hypnotizability confer immunity?

Retrospective analyses of data from the authors' program of research on hypnosis and memory are presented, with special emphasis on effects observed among low hypnotizable individuals. In Experiment 1, participants completed seven forced-recall trials in an attempt to remember a series of pictures that had been shown 1 week earlier. For half the participants, the middle five trials were carried out using hypnotic procedures; the remaining participants performed all recall attempts in a motivated waking condition. Hypnosis failed to enhance correct recall for either high or low hypnotizable participants beyond the hypermnesia and reminiscence effects associated with repeated retrieval attempts over time. However, whereas high hypnotizable participants produced substantial numbers of confident recall errors (i.e., intrusions) independent of the use of hypnosis, low hypnotizable participants exposed to hypnotic procedures reported significantly more intrusions than their counterparts in the waking condition. In Experiment 2, participants were asked to identify whether specific recollections, reported during two forced-interrogatory recall tests conducted 1 week earlier, had originated in the first or second of those tests. A general bias to misattribute previously reported recollections to the first of two recall occasions was observed; however, the effect was greatest among low hypnotizables who had undergone the second recall attempt in hypnosis. The findings imply that highly hypnotizable individuals are not unique in their vulnerability to distortions of memory induced by hypnotic techniques. Individuals of lesser hypnotic capacity also manifest memory alterations when exposed to such procedures.     

Fixation of acetabular cups without cement in total hip arthroplasty. A comparison of three different implant surfaces at a minimum duration of follow-up of five years

OBJECTIVE: To investigate the roles of brain angiotensin II and C-type natriuretic peptide (CNP) in the hypertensive mechanism of deoxycorticosterone acetate (DOCA)-salt hypertension. METHODS: We injected 50 microg/kg CV-11 974, an angiotensin II type-1 receptors antagonist, 30 nmol/kg CNP-22, or the vehicle (artificial cerebrospinal fluid) into the cerebral ventricle or intravenously 5 min before the intracerebroventricular infusion of 1.5 mol/I NaCl solution for 30 min into either male normotensive Wistar rats or DOCA-salt hypertensive rats anesthetized with urethane, and their arterial pressures and heart rates were continuously recorded. Blood (2 ml) was collected at the end of the infusion for the measurement of plasma concentration of arginine vasopressin. We infused 10 or 50 microg/kg per day CV-11 974, 10 or 50 nmol/kg per day CNP-22, or the vehicle (1 microl/h) into the cerebral ventricles of DOCA-salt hypertensive rats for 7 days by using osmotic minipumps, and measured their systolic arterial pressures, pulse rates, and urinary excretions of vasopressin. RESULTS: Intracerebroventricular pre-administrations of CV-11 974 and of CNP-22 inhibited increases in mean arterial pressure, heart rate, and plasma vasopressin concentration induced by intracerebroventricular infusion of 1.5 mol/l NaCl into normotensive rats; increases in hemodynamics and plasma level of vasopressin induced by intracerebroventricular infusion of 1.5 mol/l NaCl were suppressed by intracerebroventricular pre-injections of CV-11 974, but not of CNP-22, into DOCA-salt hypertensive rats. Continuous intracerebroventricular infusions of 50 microg/kg per day CV-11 974 attenuated hypertension in DOCA-salt treated rats, accompanied by a reduction in urinary excretion of vasopressin. Continuous intracerebroventricular infusions of 50 nmol/kg per day CNP-22, however, affected neither hypertension nor urinary excretion of vasopressin in DOCA-salt hypertensive rats. CONCLUSION: Brain angiotensin II could play a role in the pressor mechanism of DOCA-salt hypertension by increasing release of vasopressin via type 1 receptors. That brain CNP has an inhibitory effect on release of vasopressin in acute experiments indicates that the impairment of this inhibitory effect of brain CNP on secretion of vasopressin could be involved in the pathogenesis of DOCA-salt hypertension in rats.     

Kainate-induced apoptosis in cultured murine cerebellar granule cells elevates expression of the cell cycle gene cyclin D1

Recent evidence suggests that neuronal apoptosis is the consequence of an inappropriate reentry into the cell cycle. Expression of the cell cycle gene cyclin D1, a G1-phase cell cycle regulator, was examined in primary cultures of murine cerebellar granule cells (CGCs) during kainate (KA)-mediated apoptosis. Using cultures of CGCs, we found that a 24-h exposure to KA (1-3,000 microM) induced a concentration-dependent cell death with neurons exhibiting characteristic apoptotic morphology and extensive labeling using the terminal transferase-mediated nick end-DNA labeling (TUNEL) method. KA induced a time- and concentration-dependent increase in expression of cyclin D1 as determined by immunocytochemistry and western blot analysis. KA-induced apoptosis and cyclin D1 expression exhibited a similar concentration dependence and were significantly attenuated by the non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (50 microM), indicating a KA receptor-mediated effect. Here we present evidence for the first time that KA-induced apoptosis in cultured CGCs involves the induction of cyclin D1, suggesting its involvement in excitotoxic receptor-mediated apoptosis.