Differentiation between mu and kappa receptor-mediated effects in opioid drug discrimination: apparent pA2 analysis

Apparent pA2 values for the opioid antagonist, quadazocine, were used to characterize differential involvement of mu and kappa opioid receptors in the discriminative stimulus effects of opioid agonists. Rhesus monkeys were trained to discriminate s.c. injections of either codeine or ethylketazocine from sham injections. In tests of drug generalization, morphine, levorphanol and alfentanil all produced dose-dependent increases in codeine-appropriate responding, and ethylketazocine produced dose-dependent increases in ethylketazocine-appropriate responding. Quadazocine antagonized the discriminative stimulus effects of each of the agonists. Apparent pA2 values for quadazocine (and slopes of the regression lines fit to the data in "Schild Plot" analysis) were 7.8 (-1.0) with morphine, 7.7 (-1.4) with levorphanol, 7.9 (-0.92) with alfentanil and 5.7 (-0.93) with ethylketazocine. If regression line slopes were constrained to equal -1, 7.8 was the apparent pA2 value with all agonists except ethylketazocine (5.7). This difference in apparent pA2 values for quadazocine confirms that different receptors (mu and kappa, respectively) mediate the discriminative effects of opioid agonists in codeine- and ethylketazocine-trained rhesus monkeys. Also, when the antagonism data were reanalyzed separately for each individual monkey, apparent pA2 values from individual animals were found to be similar to values from other animals in the same group and to values based on grouped data.     

Toward ‘seeing’ critically: a Bayesian analysis of the impacts of a critical pedagogy

Advances in Health Sciences Education - Critical reflection supports enactment of the social roles of care, like collaboration and advocacy. We require evidence that links critical teaching...     

High-altitude pulmonary edema

Lay summary: High Altitude Pulmonary Edema (HAPE) is a potentially fatal disease of altitude, in which the lungs can become filled with fluid. In this article we explore the mechanisms causing this condition and how it can be viewed as a condition of a mismatch between current environment and evolutionary experience.     

Variation in histomorphometric estimates across different sites of the iliac crest.

Bone specimens were obtained from four different sites in the ilium of necropsy cases using a Jamshidi 8G trephine needle. Undecalcified histological sections were prepared and two structural histomorphometric parameters were estimated. Estimates of the percentage of trabecular bone volume (%TBV) deviated systematically, with variation of the biopsy site around the usual location, increasing in magnitude from the anterior to the posterior ilium. Such differences highlight the importance of understanding the degree of variation which exists in histomorphometric data. The histomorphometry of a vertical biopsy specimen of the iliac crest did not differ significantly from that of a transilial biopsy specimen of similar diameter taken from an adjacent site. When taken at the standard site, and when providing a long core of cancellous bone, with minimal discomfort to the patient, the vertical biopsy specimen compares well with the transiliac biopsy specimen for use for investigating metabolic bone disorders.     

Kufor-Rakeb syndrome, pallido-pyramidal degeneration with supranuclear upgaze paresis and dementia, maps to 1p36

Kufor-Rakeb syndrome is an autosomal recessive nigro-striatal-pallidal-pyramidal neurodegeneration. The onset is in the teenage years with clinical features of Parkinson's disease plus spasticity, supranuclear upgaze paresis, and dementia. Brain scans show atrophy of the globus pallidus and pyramids and, later, widespread cerebral atrophy. We report linkage in Kufor-Rakeb syndrome to a 9 cM region of chromosome 1p36 delineated by the markers D1S436 and D1S2843, with a maximum multipoint lod score of 3.6.


Keywords: Kufor-Rakeb syndrome; autozygosity mapping; Parkinson's disease; chromosome 1p36     

Clinical comparison of freeze-dried and fresh frozen patellar tendon allografts for anterior cruciate ligament reconstruction of the knee

The aim of this study was to evaluate the clinical outcome of freeze-dried compared to fresh frozen allograft tissue used as a substitute for a ruptured ACL of the knee. In addition, the incidence of any graft rejection phenomena was recorded. Forty-one patients with ACL deficient knees underwent reconstructive surgery using a patellar bone-tendon-bone allograft that had been freeze-dried (Group 1, N = 14) or fresh frozen (Group 2, N = 27). All patients underwent the same implant technique and rehabilitation program. Followup ranged from 24 to 36 months. The evaluation consisted of subjective, objective, and instrumented laxity testing (KT-1000, MEDmetric, San Diego, CA; and Genucom, FARO Medical Technologies, Inc., Montreal, Canada). There were 31 males and 10 females. Eleven (79%) patients in Group 1 thought their knee was "normal" or "improved," and 25 (93%) in Group 2 thought the same. In addition, 10 (71%) patients in Group 1 denied any "giving way," compared to 26 (96%) in Group 2. The mean Lysholm knee score in Group 1 was 86/100 (range, 22 to 100) compared to 92/100 (range, 59 to 100). Clinical examination included the Lachman test and tests for anterior drawer sign and pivot shift. Postoperatively, Group 1 patients had the following results: Lachman test--seven Grade 0, six Grade 1, one Grade 2; anterior drawer sign--eight Grade 0, five Grade 1, one Grade 2; and pivot shift--seven Grade 0, five "trace," and two "present."(ABSTRACT TRUNCATED AT 250 WORDS)     

U-50, 488, saline and naltrexone discrimination in U-50, 488-treated pigeons

Pigeons treated with 10.0mg/kg/day of U-50,488 discriminated among intramuscular (i.m.) injections of U-50,488 (10mg/kg), saline, and naltrexone (0.178mg/kg), while responding under a fixed-ratio 20 schedule of food presentation. Training compounds occasioned responding on the appropriate keys with pigeons responding >/=90% on the naltrexone key at doses larger than 0.032mg/kg of naltrexone, >/=90% on the U-50,488 key at doses larger than 3.2mg/kg of U-50,488, and >/=90% on the saline key after saline. Several opioid agonists and antagonists were studied for their discriminative stimulus effects. None of the compounds substituted completely (>/=90%) for either training compound in all pigeons (n = 5); however, bremazocine substituted completely for U-50,488 in three out of five pigeons. Compounds with opioid antagonist actions under other conditions substituted for naltrexone in some subjects: levallorphan, two out of five; nalbuphine, one out of five; nalorphine, two out of five; and quadazocine, three out of four. Morphine did not substitute for naltrexone or U-50,488 in any of the subjects. When U-50,488 treatment was terminated and subjects were studied daily after injections of saline, responding occurred predominantly on the saline key; the absence of naltrexone key responding after termination of U-50,488 treatment suggests that this dosing regimen was not adequate for the development of dependence, or that the discriminative stimulus effects of abstinence-induced withdrawal were qualitatively different from the discriminative stimulus effects of naltrexone under these conditions.     

PTSD among vietnam veterans: An early look at treatment outcome using direct therapeutic exposure

Vietnam combat veteran inpatients were evaluated after being treated in a PTSD special treatment unit. Selected pretreatment measures that included mental and physical problems, combat variables, PTSD symptoms, and the standard MMPI scales found no clinically meaningful differences between a group that was found to be successes and another group found to be failures, based on predetermined cutoff scores on the VETS scale, a reliable outcome measure for veteran patients. At 3 months post-therapy, a significantly greater number of subjects treated with Direct Therapeutic Exposure (DTE) (flooding therapy) as compared to another group treated with a more conventional individual therapy, were identified as successes as opposed to failures, based on the VETs scale. Also, the number of failures was greater for those treated with the more conventional therapy and the number of successess was greater for those treated with DTE, when compared to all other subjects in the sample. These preliminary results were interpreted as indicating that DTE, when offered as part of an inpatient milieu, shows promise as an effective treatment for chronic/severe combat veteran PTSD sufferers.     

病灶清除内固定植骨治疗胸椎结核

目的;探讨手术治疗胸椎结核的更好方法。方法;自１９９０年以来,对２１例胸椎结核导致椎柱不稳的患者,应用病灶清除,哈氏棒内固定,椎间及椎板植骨的手术方法。本组平均３３．２岁。胸７椎体６例,胸８椎体８例,胸１０椎体７例,椎体压缩〈１／２椎体高度１３例,〉１／２椎体高度８例,并不全瘫１４例。手术中先行病灶清除,然后哈氏棒内固一,撑开后再次清除病灶,取肋骨和髂骨行椎间及椎板上植骨。术后化疗１２～１５月。结