Simulated home treatment of depression with nortriptyline

1. Twenty-two patients hospitalized for treatment of depression were treated under conditions simulating those of home treatment. 2. Full doses of nortriptyline, from 100 to 150 mg/day, were started after baseline observations were made. 3. Two patients were dropped from the study, one for orthostatic hypotension, one for an aberrant response to nortriptyline. Two additional patients developed orthostasis which was easily managed. Otherwise no unusual side effects were noted. 4. After six days of treatment, 9 of 20 patients showed significant improvement with an overall reduction in scores on the Hamilton Depression Scale of 49% for the entire group. 5. Using the weight-adjusted dosage schedule, 18 of the 21 patients attained plasma concentrations of nortriptyline within the presumed therapeutic range; however, no clear relationship could be established between plasma concentrations and clinical response. 6. With proper selection of patients, it should be possible to treat at home some patients who currently are considered to require hospitalization.     

The effect of pressurized carbon dioxide as a temporary plasticizer and foaming agent on the hot stage extrusion process and extrudate properties of solid dispersions of itraconazole with PVP-VA 64.

The aim of the current research project was to explore the possibilities of combining pressurized carbon dioxide with hot stage extrusion during manufacturing of solid dispersions of itraconazole and polyvinylpyrrolidone-co-vinyl acetate 64 (PVP-VA 64) and to evaluate the ability of the pressurized gas to act as a temporary plasticizer as well as to produce a foamed extrudate. Pressurized carbon dioxide was injected into a Leistritz Micro 18 intermeshing co-rotating twin-screw melt extruder using an ISCO 260D syringe pump. The physicochemical characteristics of the extrudates with and without injection of carbon dioxide were evaluated with reference to the morphology of the solid dispersion and dissolution behaviour and particle properties. Carbon dioxide acted as plasticizer for itraconazole/PVP-VA 64, reducing the processing temperature during the hot stage extrusion process. Amorphous dispersions were obtained and the solid dispersion was not influenced by the carbon dioxide. Release of itraconazole from the solid dispersion could be controlled as a function of processing temperature and pressure. The macroscopic morphology changed to a foam-like structure due to expansion of the carbon dioxide at the extrusion die. This resulted in increased specific surface area, porosity, hygroscopicity and improved milling efficiency.     

Critical illness polyneuromyopathy after artificial respiration.

Up to now, 71 critically ill patients have been reported with neuromuscular complications after artificial respiration. The authors review the literature and present data of a personal series of 22 patients all suffering from severe flaccid tetraparesis and muscle atrophy, which developed after an average of two weeks artificial respiration. The prognosis was relatively good in those surviving the primary disease. The multiconditional causes are discussed with emphasis on the combination of polyneuropathy and myopathy. Tumor necrosis factor (TNF), a key mediator of sepsis, which also has an influence on muscle and nerves, is mentioned as a possible cause of this illness.     

Differential ontogenesis of type I and II benzodiazepine receptors in mouse cerebellum

The ontogeny of type I and type II benzodiazepine binding sites was studied in mouse cerebellum by displacement of [3H]flunitrazepam binding by zolpidem, a ligand specific for the type I sites. Type I binding sites predominate throughout development and in the adult while type II sites account for 25% of total cerebellar benzodiazepine binding sites at birth and, during development, decrease to 10% or less in the adult. On a per cerebellum basis type II sites increase during the first postnatal week and then remain at a steady level while type I sites increase until adulthood. These results may indicate a specific localization of the type II sites (and of the corresponding alpha-protein subunits in the GABA/benzodiazepine receptor complex) in structures already present at birth and developing during a short early postnatal period. The affinity of zolpidem for its high affinity (type I) binding sites increases during cerebellar ontogeny, this increase possibly indicates an epigenetic (post-translational) 'maturation' process of the corresponding receptor molecule. Hill numbers indicate the existence of an additional binding site heterogeneity greater during development but still present in the adult; probably this is to be related to the simultaneous presence of different 'maturation' stages during development and with a certain variety of the final products.     

Effects of isometric exercise on blood cell adrenoceptors in essential hypertension

The effect of handgrip (HG) isometric exercise on plasma catecholamines, alpha 2-adrenoceptors on platelets and beta 2-adrenoceptors on lymphocytes was studied in normotensive subjects (NT) and essential hypertensive subjects (HT). Whereas systolic blood pressure (SBP) increases were similar in NT and HT subjects, diastolic blood pressure (DBP) and heart rate (HR) increased more in the former group. Baseline values and changes in plasma epinephrine (E) and norepinephrine (NE) did not differ between both groups. No differences were apparent in alpha 2-adrenoceptor density and affinity between NT and HT subjects before or after the test. HG isometric exercise induced a similar increase in beta 2-adrenoceptors on lymphocytes of 22 +/- 7 and 13 +/- 5% in NT and HT subjects, respectively. Affinity to the beta 2-adrenoceptors under baseline conditions was somewhat lower in HT (8.1 +/- 0.4 pM) than in NT subjects (6.5 +/- 0.5 pM), and this difference persisted during the test. Our results indicate that there are no differences in alpha 2- and beta 2-adrenoceptor densities either at baseline conditions or after HG isometric exercise between NT and HT subjects. Small differences noted in affinity to the beta 2-adrenoceptors require further investigation.