The 17-item Hamilton Rating Scale for Depression (HRSD 17 ) and the Montgomery Äsberg Depression Rating Scale (MADRS) are two widely used clinicianrated symptom scales. A 6-item version of the HRSD (HRSD 6 ) was created by Bech to address the psychometric limitations of the HRSD 17 . The psychometric properties of these measures were compared using classical test theory (CTT) and item response theory (IRT) methods. IRT methods were used to equate total scores on any two scales. Data from two distinctly different outpatient studies of nonpsychotic major depression: a 12-month study of highly treatment-resistant patients (n=233) and an 8-week acute phase drug treatment trial (n=985) were used for robustness of results.MADRS and HRSD 6 items generally contributed more to the measurement of depression than HRSD 17 items as shown by higher item-total correlations and higher IRT slope parameters. The MADRS and HRSD 6 were unifactorial while the HRSD 17 contained 2 factors. The MADRS showed about twice the precision in estimating depression as either the HRSD 17 or HRSD 6 for average severity of depression. An HRSD 17 of 7 corresponded to an 8 or 9 on the MADRS and 4 on the HRSD 6 .The MADRS would be superior to the HRSD 17 in the conduct of clinical trials.
Paroxetine doses of 40 mg/day and 60 mg/day (but not 20 mg/day) are effective in treating acute obsessive-compulsive disorder. Long-term treatment with paroxetine is effective and safe, decreases the rate of relapse, and lengthens the time to relapse.
A phase II prospective, randomized, double blind clinical trial of Bradycor, a bradykinin antagonist, was conducted at 31 centers within North America in severely brain injured patients. Patients of Glasgow Coma Score (GCS) 3-8 (n = 139) with at least one reactive pupil were randomized to receive either Bradycor, 3 microg/kg/min or placebo as a continuous intravenous infusion for 5 days, with the infusion beginning within 12 h of the injury. The primary objective was to assess the efficacy of a continuous infusion of Bradycor (3.0 mc/kg/min) in preventing elevation of intracranial pressure (ICP). Other efficacy measures included the effect of Bradycor on the Therapy Intensity Level (TIL), mortality, and functional outcome. A secondary objective was to evaluate the safety of Bradycor in patients with severe brain injury. Randomization was carried out according to a computer generated randomization list. Patients were followed for the first 14 days of hospitalization with long-term outcome assessed at 3 and 6 months after injury. During the infusion and while the ICP monitor was in place, ICP measurements were recorded hourly along with blood pressure and heart rate. A modified version of the TIL was used to record therapeutic interventions hourly, while the ICP was being monitored. Outcome was assessed at 3 and 6 months after injury using the Glasgow Outcome Score (GOS). Bradycor was well tolerated in this patient population, and no adverse events were attributable to the compound. Although positive trends were seen for both ICP and TIL in the Bradycor group, these differences analyzed on a daily basis were not significant. However, a mixed model of variance which included treatment, day, treatment by day interaction, age and GCS revealed that the percentage time ICP of >15 mm Hg on days 4 and 5 was significantly lower in the Bradycor group compared to placebo (p = 0.035). There were fewer deaths in the Bradycor group, which had a 28-day all cause mortality of 20% versus 27% on placebo. Patients treated with Bradycor showed a 10.3% improvement in favorable outcome at 3 months and a 12% improvement in dichotomized GOS at 6 months (p = 0.26). The consistent positive trends seen in ICP, TIL, neuropsychological tests, and, most importantly, 3- and 6-month GOS provide supportive evidence that a bradykinin antagonist may play a neuroprotective role in severe brain injury.
Cholecystokinin (CCK) and acetylcholine, at concentrations greater than those required for maximal pancreatic enzyme secretion, elicit a submaximal secretory response. The mechanism for this "secretagogue-induced unresponsiveness" is unknown. Using isolated pancreatic acini of the mouse, we now find that high concentrations of secretagogues also induce a profound alteration in acinar morphology, characterized by the formation of spherical protrusions on the basal surface of the cells. Since both the determination of cell shape and exocytosis may involve calcium and contractile proteins, we used a calcium-free medium and cytochalasin B (CB) to evaluate the importance of a contractile mechanism in the secretory and morphological effects of high concentrations of CCK-octapeptide (CCK8). Incubation in a calcium-free medium partially blocked CCK-induced unresponsiveness, but brought about dissociation of the acini. CB at a concentration of 3 micrograms/ml caused the disappearance of apical microfilaments and, most strikingly, completely prevented the morphological alteration induced by CCK8. Furthermore, CB converted the biphasic dose-response curve for CCK8-induced amylase release to a monophasic shape, such that the amylase release stimulated by a high concentration of CCK8 (10 nM) was augmented. It is concluded, therefore, that a contractile process involving microfilaments may mediate "secretagogue-induced unresponsiveness" in pancreatic acinar cells.
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