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991.
Rationale: Facial expressions appear to be processed by at least partially separable neuro-cognitive systems. Given this functional
specialisation of expression processing, it is plausible that these neurocognitive systems may also be dissociable pharmacologically.
Objective: The present study therefore compared the effects of diazepam (15 mg) with placebo upon the ability to recognise emotional
expressions. Methods: A double blind, independent group design was used to compare the effects of diazepam and matched placebo in32 healthy volunteers.
Participants were presented morphed facial expression stimuli following a paradigm developed for use with patients with brain
damage and asked to name one of the six basic emotions (sadness, happiness, anger, disgust, fear and surprise). Results: Diazepam selectively impaired subjects’ ability to recognise angry expressions but did not affect recognition of any other
emotional expression. Conclusions: The findings are interpreted as providing further support for the suggestion that there are dissociable systems responsible
for processing emotional expressions. It is suggested that these findings may have implications for understanding paradoxical
aggression sometimes elicited by benzodiazepines.
Received: 27 May 1999 / Accepted: 7 July 1999 相似文献
992.
Activation of 5-HT1B receptors in the nucleus accumbens reduces amphetamine-induced enhancement of responding for conditioned reward 总被引:2,自引:2,他引:0
Previously, we have demonstrated that 5-hydroxytryptamine (5-HT) injected into the nucleus accumbens attenuates the potentiating
effects of d-amphetamine on responding for conditioned reward (CR). The present studies examined the 5-HT receptor involved in this effect
by investigating the effects of 5-HT agonists with differing affinities for 5-HT1 and 5-HT2 receptors on d-amphetamine-induced potentiation of responding for CR. Rats were trained to associate a light/tone stimulus (subsequently
the CR) with water delivery. In a test phase, they were allowed access to a lever delivering the CR, and an inactive (NCR)
lever. Responding on the CR lever was greater than responding on the NCR lever, indicating that the light/tone stimulus functioned
as a CR. Responding for the CR was selectively potentiated by injections of d-amphetamine (10 μg) into the nucleus accumbens. This effect was reduced by injections into the nucleus accumbens of 5-CT
(0.5 and 1 μg), RU24969 (10 μg), CP93,129 (1.25 and 2.5 μg) but not by DOI (10 μg) or 8-OH-DPAT (5 μg). The lower doses of
5-CT and CP93,129 did not reduce baseline responding for CR, or responding for water in a separate group of animals, indicating
that the effects of these drugs were behaviourally selective. The higher doses abolished the CR effect, and in the case of
5-CT and RU24969 also reduced responding for water. All of the effective drugs share in common the ability to stimulate 5-HT1B receptors, albeit with differing selectivities. The effect of CP93,129, the most selective of the 5-HT1B agonists, to inhibit the response-potentiating effect of d-amphetamine was reversed by the5-HT1B/1D antagonist GR127935 (3 mg/kg). The results indicate that activation of 5-HT1B receptors within the nucleus accumbens attenuates the effects of a dopamine-dependent behaviour, and that activation of these
receptors can oppose the behavioural effects of elevated mesolimbic dopamine transmission.
Received: 22 April 1998/Final version: 28 July 1998 相似文献
993.
Barrett JS Hochadel TJ Morales RJ Rohatagi S DeWitt KE Watson SK DiSanto AR 《American journal of therapeutics》1996,3(10):688-698
This open-label, two-phase cross-over study compared the safety and pharmacokinetics of transdermally administered selegiline and orally administered selegiline hydrochloride in elderly men and women (n = 6/gender). Single oral doses of 10 mg selegiline hydrochloride and single 1/2 and 1 selegiline transdermal system (STS) (delivering similar3.4 and 6.3 mg over 24 h) administered topically were safe and well tolerated in all subjects. Plasma concentrations of selegiline (SEL) and its N-desmethylselegiline (DMS), L-amphetamine (AMP), and L-methamphetamine (MET) metabolites were measured using an HPLC/MS/MS method with lower quantitation limits of 10, 50, 200, and 200 pg/mL, respectively. No significant gender-related differences were observed following single 10-mg oral doses of selegiline hydrochloride or single 24-h applications of 1/2 and 1 STS to elderly males and females. The low level of dermal irritation as assessed by erythema and edema rating scales suggests that the STS was similar to Band-Aid (Johnson & Johnson, Skillman, NJ) controls. The transdermal administration of SEL bypasses the first-pass metabolism, that is significant after oral administration (first-pass extraction >90%). Peak plasma levels of 1.19, 23.22, 4.78, and 14.08 ng/mL were observed for SEL, DMS, AMP, and MET after a single 10-mg oral dose to the elderly. By contrast, peak plasma levels of 2.10, 0.85, 1.06, and 2.71 ng/mL were observed for SEL, DMS, AMP, and MET after a single 24-h application of 1 STS. Comparison of dose-corrected areas under the curve (AUCs) (made under the assumption of linear pharmacokinetics) indicate the SEL exposure after transdermal application was more than 50-fold greater than that obtained orally. This increase in systemic SEL exposure at the expense of metabolite formation that is reduced to <70% of that obtained orally for N-DMS, L-AMP, and L-MET is hypothesized to be of therapeutic value in patients with a variety of neurodegenerative and psychiatric disorders. 相似文献
994.
Meltzer RS Rinkevich D Reisner SA Motro M Becker B Vered Z 《Echocardiography (Mount Kisco, N.Y.)》1996,13(1):35-44
Echocardiographic left ventricular mass (LVM) estimates are strong predictors of subsequent mortality and cardiovascular events. It is known that blood pressure (BP), weight (WT), and age are significantly correlated with LVM. We hypothesized that stroke volume (SV) measured by Doppler echocardiography would also be correlated with LVM. Two hundred and thirteen patients referred for routine echocardiography had determination of LVM, cuff BP, and Doppler SV. Those with localized LV disease, valvular disease, or cor pulmonale were excluded. In both men and women, systolic BP (SBP) was more closely correlated with LVM than was diastolic blood pressure or mean arterial pressure, and SV was more closely correlated with LVM than cardiac output or cardiac index. Stepwise regression, followed by multiple regression showed that four variables (WT, SV, SBP, and AGE) explained 32.3% of the variability in LVM in men and 48.5% of the variability in LVM in women. WT and SV were significant determinants of LVM in both men and women. Age was also significant in men and SBP was also significant in women. For both men and women, SV was more significantly correlated with LVM than was SBP. The changes in LVM associated with 1 SD increments of SV and SBP, respectively, were 8 and 5 g for men and 13 and 11 g for women. We conclude that men and women have different patterns of variables influencing LVM. Doppler echocardiographic SV is a newly described determinant of LVM that has a greater correlation with LVM than does SBP. This study reemphasizes the importance of WT as the major determinant of LVM. (ECHOCARDIOGRAPHY, Volume 13, January 1996) 相似文献
995.
Pharmaceutical Research - 相似文献
996.
Honn KV Aref A Chen YQ Cher ML Crissman JD Forman JD Gao X Grignon D Hussain M Porter AT Pontes JE Powell I Redman B Sakr W Severson R Tang DG Wood DP 《Pathology oncology research : POR》1996,2(1-2):98-109
Rates of prostate cancer (PCa) have increased so dramatically over the last decade that the age adjusted incidence rate for PCa is now greater than that any other cancer among men in the United States. This review, published as a three part series, provides a state-of-art assessment of the PCa problem in its divergent aspects.Part 1 covers epidemiology, incidence and progression. Several epidemiological studies have demostrated that first degree male relatives of men with PCa are at increased risk of developing the disease. Familial and genetic factors as well as medical, anthropometric, dietary, hormonal and occupational factors involved in PCa are discussed. Postmortem examination of the prostate in men without evidence of PCa documented a high frequency of adenocarcinoma. Latent disease occurred as early as the second decade of life. Although there is no significant difference in incidence between Caucasian and African-American males, high grade prostatic intraepithelial neoplasia (HGPIN) is higher in the latter group. While dietary fat, androgens and certain environmental factors may be determinants for PCa, the exact mechanism of tumorigenesis is still relatively unknown. The current thinking of the role of genomic instability, chromosomal alterations, tumor suppressor genes and the androgen receptor are explored. 相似文献
997.
BACKGROUND: Alcohol risk and harm reduction is a public health approachthat goes beyond specialized treatments for alcoholism. Thegreatest potential for reducing alcohol risk and harm in a populationdepends on the extent to which health care practitioners usesecondary prevention programmes. OBJECTIVE: We aim to assess the factors that affect the prospects of disseminatingcomprehensive, secondary prevention programmes into mainstreampractice. METHOD: A decision balance was used to assess the prospects of practitionersimplementing comprehensive programmes systematically. The stages-of-changemodel provides perspectives about behaviour change with regardto patients, practitioners and practice settings. RESULTS AND CONCLUSIONS: Programme implementation is extremely unlikely given the currentorganization of health care settings. To maintain the use ofsuch programmes, we need to change the "unit of leverage" inthe system: from the clinical encounterthat is, practitionersworking with individual patients in a case-finding mannertoan organizational levelthat is, the appropriate use ofmanagerial and information systems supporting health care settingsto identify at-risk patients systematically as they enter primarycare and hospital settings. With appropriate infrastructuresupport, practitioners will be able to fulfil the potentialfor as well as maintain the use of comprehensive, secondaryprevention programmes to reduce alcohol risk and harm in thepopulation. Keywords. Alcohol abuse, general practice, implementation, secondary prevention. 相似文献
998.
David Esrig John A. Freeman Donald A. Elmajian John P. Stein Su-Chiu Chen Susan Groshen Anne Simoneau Eila C. Skinner Gary Lieskovsky Stuart D. Boyd Richard J. Cote Donald G. Skinner 《The Journal of urology》1996,156(3):1071-1076
Purpose
We investigated the effect on survival of transitional cell carcinoma of the prostatic urethra, ducts and stroma, and determined the difference between prostatic stromal involvement occurring via direct extension through the bladder wall versus stromal invasion arising intraurethrally.Materials and Methods
Between August 1971 and December 1989, 489 men underwent radical cystoprostatectomy for transitional cell carcinoma, including 143 (29.2 percent) identified with prostate involvement by transitional cell carcinoma in the cystectomy specimen. Patients were separated into 2 groups: 1–19 in whom the primary bladder tumor extended full thickness through the bladder wall to invade the prostate (classified as P4a) and 2–124 in whom prostate involvement arose from within the prostatic urethra.Results
Five-year recurrence-free and overall survival rates were 25 and 21 percent, respectively, in group 1 versus 64 and 55 percent, respectively, in group 2. In the 124 patients in group 2 survival rates were similar for those with prostatic urethral tumors or carcinoma in situ and ductal tumors (no stromal invasion). Five-year overall survival rates without and with stromal invasion were 71 and 36 percent, respectively (p less than 0.0001). Transitional cell carcinoma of the prostatic urethra or ducts does not alter survival predicted by primary bladder stage alone. Prostatic stromal invasion arising intraurethrally significantly decreases survival, which varies based on primary bladder stage (64.6 percent in stage P1, 30.8 percent in stages P2/P3a and 13.6 percent in stage P3b, p = 0.0001). P1 bladder tumors with prostatic stromal invasion arising intraurethrally had a significantly higher survival rate than P4a tumors (64.6 versus 21 percent, p = 0.0001). P3b bladder tumors with stromal invasion had a survival rate similar to that of P4a tumors (p = 0.78).Conclusions
Prostatic urethral or ductal transitional cell carcinoma does not alter survival determined by primary bladder stage alone and it should not be classified as P4a. Prostatic stromal involvement arising intraurethrally significantly decreases survival predicted by primary bladder stage alone. P1 bladder tumors with prostatic stromal invasion arising intraurethrally have a significantly higher survival rate than P4a tumors and they should be separately classified as P1str. Muscle invasive (P2/P3a) bladder tumors with stromal invasion have a higher survival rate than P4a tumors (no statistical significance) and they should be designated separately (that is P2str). P3b bladder tumors with prostatic stromal invasion arising intraurethrally are indistinguishable from P4a tumors. 相似文献999.
The Correlation Between the New Rigiscan Plus Software and the Final Diagnosis in the Evaluation of Erectile Dysfunction 总被引:1,自引:0,他引:1
Alexandru E. Benet Jamil Rehman Richard G. Holcomb Arnold Melman 《The Journal of urology》1996,156(6):1947-1950
Purpose
The computer generated recordings for 2 nights in 40 patients studied with the RigiScan† device were reevaluated using the new RigiScan Plus software to test its value in improving the discrimination between psychogenic and organic erectile dysfunction.Materials and Methods
Each man was evaluated for erectile dysfunction with a detailed medical and sexual history, physical examination, biothesiometry, plethysmography, 2 nights of ambulatory RigiScan monitoring and a psychological evaluation that usually included a private interview with the sexual partner. At the conclusion of evaluation each patient was broadly classified as having organic or psychogenic erectile dysfunction. The RigiScan reports were initially independently analyzed without the investigator's knowledge of the final diagnosis by determining the single best erectile event, with a minimal cutoff value of 60 percent erection for 5 minutes as necessary to be considered normal and the sum of measurements from the 2 nights. The original reading and final diagnosis were correlated. At this point the data were processed with the new RigiScan Plus software using 2 new measurements: 1) rigidity activity units and 2) tumescence activity units at the base and tip of the penis, and the results were correlated with the final diagnosis.Results
Evaluation of the single best event again showed that tip rigidity was the best single predictor if the diagnostic criteria were modified to 70 percent tip rigidity for 5 minutes with an estimate of correct classification of 92.5 percent. Nearly the same accuracy was obtained by base single event rigidity, tip rigidity and base tumescence activity units (each 90 percent). The summary analysis of all erectile events during the 2 nights of evaluation that had a low correlation with the final diagnosis using the original software showed that the best overall predictor of final diagnosis was tip tumescence activity units (92.5 percent), followed by base rigidity and tumescence activity units (each 90 percent).Conclusions
The RigiScan Plus software introduced 4 new parameters that facilitate interpretation of the RigiScan data. The new software did not improve the correlation with the final diagnosis compared to the subjective single best event analysis but added new objective parameters, measured and displayed by the software, that facilitate use of the data by the physician. 相似文献1000.
Richard Hart Chellapa Rajgopal Arthur Plewes John Sweeney Ward Davies Daryl Gray Brian Taylor 《Canadian journal of surgery》1996,39(6):457-462