Diazepam antagonizes effects on dopamine metabolism produced by PCP receptor agonists.

1. Male rats were injected with either saline, diazepam, MK-801, or diazepam plus MK-801. 2. In previous work with phencyclidine (PCP), diazepam significantly reduced the increase in homovanillic acid (HVA) in olfactory tubercle and prefrontal cortex. 3. Diazepam also lowered the HVA increase following MK-801 in caudate, olfactory tubercle, and prefrontal cortex. 4. Benzodiazepine receptors may modify dopaminergic function at PCP receptors that affect dopamine neurotransmission.     

The pharmacology of GR203040, a novel, potent and selective non-peptide tachykinin NK1 receptor antagonist.

1. The in vitro and in vivo pharmacology of GR203040 ((2S, 3S)-2-methoxy-5-tetrazol-1-yl-benzyl-(2-phenyl-piperidin-3-y l)-amine), a novel, highly potent and selective non-peptide tachykinin NK1 receptor antagonist, was investigated in the present study. 2. GR203040 potently inhibited [3H]-substance P binding to human NK1 receptors expressed in Chinese hamster ovary (CHO) and U373 MG astrocytoma cells, and NK1 receptors in ferret and gerbil cortex (pKi values of 10.3, 10.5, 10.1 and 10.1 respectively). GR203040 had lower affinity at rat NK1 receptors (pKi = 8.6) and little affinity for human NK2 receptors (pKi < 5.0) in CHO cells and NK3 receptors in guinea-pig cortex (pKi < 6.0). With the exception of the histamine H1 receptor (pIC50 = 7.5). GR203040 had little affinity (pIC50 < 6.0) at all non-NK1 receptors and ion channels examined. Furthermore, GR203040 produced only weak inhibition of Na+ currents in SH-SY5Y neuroblastoma and superior cervical ganglion cells (pIC50 values < 4.0). GR203040 produced only weak antagonism of Ca(2+)-evoked contractions of rat isolated portal vein (pKn = 4.1). The enantiomer of GR203040, GR205608 (2R, 3R)-2-methoxy-5-tetrazol-1-yl-benzyl-(2-phenyl-piperidin-3-y l)-amine), had 10,000 fold lower affinity at the human NK1 receptor expressed in CHO cells (pKi = 6.3). 3. In gerbil ex vivo binding experiments, GR203040 produced a dose-dependent inhibition of the binding of [3H]-substance P to cerebral cortical membranes (ED50 = 15 micrograms kg-1 s.c. and 0.42 mg kg-1 p.o.). At 10 micrograms kg-1 s.c., the inhibition of [3H]-substance P binding was maintained for > 6 h. In the rat, GR203040 was less potent (ED50 = 15.4 mg kg-1 s.c.) probably reflecting, at least in part, its lower affinity at the rat NK1 receptor. 4. In guinea-pig isolated ileum and dog isolated middle cerebral and basilar arteries, GR203040 produced a rightward displacement of the concentration-effect curves to substance P methyl ester (SPOMe) with suppression of the maximum agonist response (apparent pKB values of 11.9, 11.2 and 11.1 respectively). 5. In anaesthetized rabbits, GR203040 antagonized reductions in carotid arterial vascular resistance evoked by SPOMe, injected via the lingual artery (DR10 (i.e. the dose producing a dose-ratio of 10) = 1.1 micrograms kg-1, i.v.). At a dose 20 fold greater than its DR10 value (i.e. 22 micrograms kg-1, i.v.), significant antagonism was evident more than 2 h after GR203040 administration. 6. In anaesthetized rats, GR203040 (3 and 10 mg kg-1, i.v.) produced a dose-dependent inhibition of plasma protein extravasation in dura mater, conjunctiva, eyelid and lip in response to electrical stimulation of the trigeminal ganglion. 7. It is concluded that GR203040 is one of the most potent and selective NK1 receptor antagonists yet described, and as such, has considerable potential as a pharmacological tool to characterize the physiological and pathological roles of substance P and NK1 receptors. GR203040 may also have potential as a novel therapeutic agent for the treatment of conditions such as migraine, emesis and pain.     

It happened to an ICU nurse : an experience on the receiving end of intensive care.

After working in intensive care for thirteen years, I believed I understood some of the experiences of our patients and their families. However, my own experience on the receiving end of intensive care has demonstrated how little I knew and has changed not only my own views and perceptions, but has stimulated changes to practice in one icu.     

Branch retinal vein occlusion. A clinicopathologic case report

The eyes of a 72-year-old woman with a history of two branch retinal vein occlusions involving the left eye, were obtained postmortem and studied histopathologically. Prior to her death, she had been enrolled in the multicentered, prospective, randomized clinical trial on branch vein occlusion and treated with peripheral argon laser photocoagulation for disc neovascularization. Routine fluorescein angiograms and fundus photographs were available for clinical correlation. Despite photocoagulation, the patient had frequent recurrent episodes of vitreous hemorrhage. On histologic examination, both venous occlusions were found at arteriovenous crossings and associated with moderately sclerotic retinal arterioles. One occlusion was recanalized. Retinal inner ischemic atrophy was observed distal to the site of both venous occlusions and corresponded to areas of nonperfusion. Cystoid macular edema was not present. Three areas of neovascularization were found; one at the optic nerve head, one at the peripapillary retina, and one at the fovea. It is likely the patient's repeated vitreous hemorrhages were from one or all three areas of neovascularization demonstrated histopathologically.     

Mental object rotation in Parkinson's disease.

Deficits in visual-spatial ability can be associated with Parkinson's disease (PD), and there are several possible reasons for these deficits. Dysfunction in frontal-striatal and/or frontal-parietal systems, associated with dopamine deficiency, might disrupt cognitive processes either supporting (e.g., working memory) or subserving visual-spatial computations. The goal of this study was to assess visual-spatial orientation ability in individuals with PD using the Mental Rotations Test (MRT), along with other measures of cognitive function. Non-demented men with PD were significantly less accurate on this test than matched control men. In contrast, women with PD performed similarly to matched control women, but both groups of women did not perform much better than chance. Further, mental rotation accuracy in men correlated with their executive skills involving mental processing and psychomotor speed. In women with PD, however, mental rotation accuracy correlated negatively with verbal memory, indicating that higher mental rotation performance was associated with lower ability in verbal memory. These results indicate that PD is associated with visual-spatial orientation deficits in men. Women with PD and control women both performed poorly on the MRT, possibly reflecting a floor effect. Although men and women with PD appear to engage different cognitive processes in this task, the reason for the sex difference remains to be elucidated.     

Transforming electrocortical mapping data into standardized common space.

Subdural grid electrodes are implanted routinely for the pre-surgical work up of epilepsy. While different approaches are available, many centers, including ours, visualize electrode locations by co-registering pre-operative 3-D MR images with post-implantation 3-D CT images. This method allows the determination of the electrode positions in relation to the individual patient's anatomy, but does not easily allow comparison across patients. The goal of this study was to develop and validate a method for transforming electrode positions derived from 3-D CT images into standardized space. We analyzed data from twelve patients with subdurally implanted electrodes. Volumetric CT and MRI images were co-registered and then normalized into common stereotactic space. Electrode locations were verified statistically by comparing distances between the anterior commissure and a representative sampling of 8 electrode sites per patient. Results confirm the accuracy of our co-registration method for comparing electrode locations across patients.     

36例踝关节骨折合并下胫腓联合分离的治疗体会

0 引言 踝关节骨折是临床上较常见的关节内骨折,包含了腓骨骨折,内踝骨折,后踝骨折和下胫腓联合的损伤. 处理不当可导致踝穴的变形,下胫腓联合分离后期出现创伤性关节炎.     

"Crack smoke" is a respirable aerosol of cocaine base

The smoking of cocaine base [corrected] ("crack") has emerged as a significant substance abuse problem. A detailed characterization of cocaine smoke is a prerequisite for studies of its pharmacokinetics, abuse potential and toxicity. Model pipes were used to generate cocaine smoke analogous to that inhaled by human "crack" abusers. Using procedures to minimize pyrolysis, cocaine base smoke was determined to be 93.5% cocaine particles with the remainder being cocaine vapor. The average particle size generated from all model pipes was 2.3 mu which is small enough to ensure deposition into the alveolar region of the human lung. Although this particle size is eminently respirable [corrected] by primates, a much smaller fraction will reach the alveolar region of rodents. Special generating procedures would therefore be required to expose rodents to meaningful doses of airborne cocaine that mimic the rapid absorption achieved by "crack" smokers.     

Incidence of Hyperpronation in the ACL Injured Knee: A Clinical Perspective

Assessing abnormal biomechanics when treating various lower extremity pathologies provides the athlete with comprehensive management and promotes injury prevention. However, there have been few previous investigations of abnormal biomechanical forces on ligamentous pathologies of the knee. During this clinical study we investigated the incidence of hyperpronation in subjects who have had an anterior cruciate ligament (ACL) injury. Fifty subjects with a past medical history of ACL rupture and 50 subjects without a history of lower extremity pathology participated in our study. Hyperpronation of the foot and ankle complex was measured with the navicular drop test. The ACL injured subjects had greater navicular drop test scores than noninjured subjects. This suggests that hyperpronation of the foot and ankle complex may increase the risk of injury to the ACL. There is a need for further investigation into possible pre-loading stresses on knee ligaments.