Adinazolam affects biogenic amine release in hippocampal CA1 neuronal circuitry.

The new triazolobenzodiazepine, adinazolam, which has dual anxiolytic and antidepressant activities, was studied for its effects on hippocampal CA1 norepinephrine and serotonin release in chloral hydrate-anesthetized rats, with in vivo voltammetry. Norepinephrine signals were further characterized in vivo by the detection of a significantly increased norepinephrine signal (mean = 25.8%) (p less than 0.003) after intraperitoneal administration of the alpha 2 adrenoreceptor antagonist, yohimbine, and by the detection of a significantly decreased norepinephrine signal (mean = 20.1%) (p less than 0.037) after intraperitoneal administration of the alpha 2 adrenoreceptor agonist, clonidine. Time course studies showed that the anxiolytic-antidepressant drug adinazolam (10 mg/kg IP) significantly decreased hippocampal norepinephrine release (mean = 26.2%) (p less than 0.007). The norepinephrine signal was further significantly decreased by adinazolam (mean = 16.4%) (p less than 0.009) after an additional 2 mg/kg IP injection. Serotonin release, which was detected with norepinephrine in sequence, was also significantly decreased by adinazolam (10 mg/kg IP) (mean = 22.4%) (p less than 0.002). The supplemental dose of adinazolam (2 mg/kg IP), however, did not significantly alter serotonin release any further (p less than 0.307). The findings show that the mechanism of action of adinazolam occurs simultaneously on presynaptic release mechanisms for norepinephrine and for serotonin in CA1 region of hippocampus. These findings implicate that noradrenergic and serotonergic release mechanisms may be responsible in part for the dual anxiolytic-antidepressant efficacy of adinazolam.     

Early Stroke Recognition: Developing an Out-of-hospital NIH Stroke Scale

Objective : To develop an abbreviated and practical neurologic scale that could assist emergency medical services or triage personnel in identifying patients with stroke.
Methods : A prospective, observational, cohort study was performed at university-based EDs. Participants were 74 patients treated in a thrombolytic stroke trial and 225 consecutive non-stroke patients evaluated during 4 random 12-hour shifts in the ED. Scores on the NIH Stroke Scale were obtained for all patients by physicians. Items of this scale were modified and recoded to a binomial (normal or abnormal) scale. Serial univariate analyses using χ² were performed to rank items. Recursive partitioning was then performed to develop the decision rule for predicting the presence of stroke.
Results : Three items identified 100% of patients with stroke: facial palsy, motor arm, and dysarthria. An Abbreviated NIH Stroke Scale based on these items had a sensitivity of 100% and a specificity of 92%. A proposed Out-of-hospital NIH Stroke Scale consisting of facial palsy, motor arm, and a combination of dysarthria and best language items (abnormal speech) had a sensitivity of 100% and a specificity of 88%.
Conclusion : Using the derivation data set, a proposed Out-of-hospital NIH Stroke Scale had a high sensitivity and specificity for identifying patients with stroke when performed by physicians in this group of 299 ED patients. Prospective studies of other health care professionals using the scale in the out-of-hospital arena are needed.     

A novel canine model of partial outlet obstruction secondary to prostatic hypertrophy

Summary Benign prostatic hyperplasia (BPH) is a major medical problem in the United States. The primary medical complication of BPH is progressive obstruction of the urethra and a subsequent in reduction the ability or the bladder to empty efficiently. The urodynamic characteristics associated with BPH include hyperreflexia, increased bladder capacity, increased frequency, decreased flow rate, and increased residual volume. Although there currently are individual animal models of prostate enlargement and animal models of partial outlet obstruction, there is no model of progressive obstruction secondary to prostate enlargement. The primary objective of the current study was to develop a canine model of BPH that would secondarily result in partial urethral obstruction and impaired urodynamics. Our model consists of encapsulating the prostate in a nylon mesh to prevent the growth of the prostate into the peritoneal cavity and then treating the dog with steroids to induce prostate growth and subsequently produce urethral constriction. The results demonstrate that encapsulation of the dog prostate and administration of steroids results in an increase in prostate mass simultaneously with an increase in urethral pressure and in changes in bladder contraction consistent with the presence of partial outlet obstruction. This preliminary study demonstrates that by preventing the outward growth of the steroid-stimulated prostate, urethral obstruction resembling BPH can be produced.This work was supported in part by grants from the Veterans Administration, NIH grants RO-1-DK 26508 and RO-1-DK33559, and the Stterling Winthrop Pharmaceuticals Research Division.     

Ultra-early evaluation of intracerebral hemorrhage

The authors evaluate eight patients with intracerebral hemorrhage (ICH) who underwent computerized tomography (CT) within 2 1/2 hours after symptom onset and then again several hours later. The second CT scan was performed within 12 hours after onset for seven of the patients and 100 hours after onset for the eighth patient. In four patients, the second CT scan was obtained prospectively. The mean percentage of increase in the volume of hemorrhage between the first and second CT scans was 107% (range 1% to 338%). In each of the six patients with a greater than 40% increase in hemorrhage volume, neurological deterioration occurred soon after the first CT. A systolic blood pressure of 195 mm Hg or greater was recorded during the first 6 hours in five of the same six patients. The data from this study indicate that, in ICH, bleeding may continue after the 1st hour post-hemorrhage, particularly in patients with early clinical deterioration.