Identification of the first trans-(3R,4R)- dimethyl-4-(3-hydroxyphenyl)piperidine derivative to possess highly potent and selective opioid kappa receptor antagonist activity.

A structurally novel opioid kappa receptor selective ligand has been identified. This compound, (3R)-7-hydroxy-N-((1S)-1-[[(3R,4R)-4-(3-hydroxyphenyl)-3,4-dimethyl-1-piperidinyl]methyl]-2-methylpropyl)-1,2,3,4-tetrahydro-3-isoquinolinecarboxamide (JDTic, 10) demonstrated high affinity for the kappa receptor in the binding assay (kappa K(i) = 0.3 nM) and highly potent and selective kappa antagonism in the [(35)S]GTP-gamma-S assay using cloned opioid receptors (kappa K(i) = 0.006 nM, mu/kappa ratio = 570, delta/kappa ratio > 16600).

Effect of a clinical pathway for severe traumatic brain injury on resource utilization.

BACKGROUND: The usefulness of clinical pathways for the complex trauma patient is unclear. We analyzed the effect of a clinical pathway for severe traumatic brain injury (TBI) on resource utilization. METHODS: A clinical pathway for severe TBI (Glasgow Coma Scale (GCS) score < or = 8 at 24 hours) was developed by a multidisciplinary team and used for all patients with severe TBI. Data were gathered prospectively for 15 months and compared with data from historical controls from the previous year. Patients who survived < 48 hours were excluded. RESULTS: The clinical pathway was used for 84 patients with severe TBI and compared with 49 historical controls. No differences in Injury Severity Scores (27 vs. 27) or GCS scores at 24 hours (6.2 vs. 6.5) existed between control or pathway patients. There was an overall increase in the mortality rate of pathway patients (from 12.2 to 21.4%), but this was entirely attributable to withdrawal of care that was initiated by family members in patients with an average age of 71 years, an average GCS score of 4.7, and an average Injury Severity Score of 29. Among survivors, pathway patients had a significant decrease in ventilator days (11.5 +/- 0.9 vs. 14.6 +/- 1.2; p < 0.05), intensive care unit days (16.7 +/- 1.0 vs. 21.2 +/- 1.4; p < 0.05), and hospital days (23.4 +/- 1.2 vs. 31.0 +/- 3.0; p < 0.05). There were no differences in the incidence of complications or functional outcomes. CONCLUSION: The use of a clinical pathway for severe TBI resulted in a significant reduction in resource utilization. This study suggests that clinical pathways may be a useful component of patient care after blunt trauma.

Focal leptomeningeal rhabdomyomatosis of the posterior fossa.

We describe two infants with heterotopic skeletal muscle in the leptomeninges of the posterior fossa. In one case, the heterotopic muscle was accompanied by adipose tissue. Leptomeningeal rhabdomyomatosis may be more common than is apparent from the literature, since these lesions are missed if the meninges become denuded from the brain stem at autopsy or brain cutting.

Theophylline interferes with ligand binding in radioimmunoassays for somatostatin.

Theophylline is often utilized as a secretagogue in studies on the in vitro release of somatostatin and other hormones. We report here on the effect of theophylline on ligand binding in somatostatin radioimmunoassays performed with three different antisera. For all three radioimmunoassays, tracer binding both in the presence and absence of unlabelled somatostatin was inhibited by the addition of theophylline to the RIA reaction mixture. This effect occurred at final assay concentrations of theophylline which may likely be encountered when assaying samples obtained in studies of theophylline-induced hormone release in vitro. The possible interfering effect of theophylline in radioimmunoassays should be considered whenever theophylline is used as a tool to study hormone release.