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Research has established the benefits of early warnings signs monitoring in the prevention of relapse for individuals with psychosis. This study explored staff views (n = 8) of the implementation of an early warning signs clinic within a day hospital of an adult mental health service. A qualitative methodology using focus groups was adopted and content analysis was used to discover themes arising from the data. Overall, the data indicated a positive view of the early warning signs clinic, with benefits for clients, staff and their relationship; and for service delivery and resources. The clinical and service implications are discussed.

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Meningiomas account for 18-20% of all intracranial tumours and often recur despite surgical resection. Hydroxyurea is under evaluation as adjuvant therapy of meningiomas. In the authors' initial report of 17 patients with meningioma, hydroxyurea demonstrated modest efficacy, with a median time to progression (TTP) of 80 weeks. In the current study, 21 patients with meningioma have been placed on hydroxyurea (20 mg/kg/day orally), with extended follow-up of the original cohort. Eighteen of 20 evaluable patients (90%) responded with stable disease ranging from 20 to 328 + weeks (median TTP 176 weeks; 11 patients censored). Five of the stabilized patients progressed after 20, 56, 36, 216 and 56 weeks, respectively. Two patients had progressive disease after 10 weeks. Toxicity was mainly haematological. Hydroxyurea has modest activity against meningiomas and should be considered for patients who are poor surgical candidates, have unresectable or large residual meningiomas, or have progressed after surgical resection or irradiation, or both.

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Feedback modulation of voltage-dependent Ca2+ channels by ATP is a well documented phenomenon in bovine chromaffin cells. However, its influence in the control of hormone release is at present poorly understood. By using combined patch-clamp and fura-2 fluorescence measurements we provide evidence that the three Ca2+ channel types (L, N and P/Q) expressed in bovine chromaffin cells are inhibited by ATP (30 microM), and that their involvement in the secretory response, as assayed by capacitance measurements, is roughly proportional to their contribution to the whole-cell Ca2+ current (ICa) both in the absence and presence of ATP. ATP did not modify the capacitance increase observed in cells dialyzed with Ca(2+)-EGTA buffers (1.5 microM free Ca2+), thus excluding a direct effect of ATP on the secretory machinery. Voltage predepolarizations or long chemical (2 s, 70 mM KCl) depolarizations attenuate the effect of ATP on exocytosis by partially relieving the inhibition of ICa Likewise, a strong stimulation that depletes the readily releasable pool of vesicles prevents an inhibitory effect of ATP on the secretory response. While these results lend support to the hypothesis of autocrine modulation of exocytosis by endogenously released ATP acting on P2y-purinoceptors to inhibit ICa, feedback regulation of the rate of release will be a complex function of the occupancy of those receptors and of the electrical and secretory activity of the cell.

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The role of ATP in both the activation of store-operated Ca2+ current ICRAC and in Ca2+-dependent vesicular fusion was examined in a study of rat basophilic leukaemia (RBL) cells using the whole-cell patch-clamp technique. Fusion was monitored via changes in plasma membrane capacitance. Following a decrease in the levels of intracellular ATP, achieved using the mitochondrial poison antimycin and the ATP synthase inhibitor oligomycin, as well as a reduction of glycolysis by removal of external glucose, ICRAC activated in a manner similar to control cells when stores are depleted by dialysis with a pipette solution containing either inositol 1,4, 5-trisphosphate (InsP3) or ionomycin together with a high concentration of EGTA. Dialysis of cells for 150 s with the non-hydrolysable ATP analogue 5'-adenylylimidodiphosphate (AMP-PNP) (2 mM) in addition to the mitochondrial inhibitors also failed to prevent activation of ICRAC following external application of ionomycin and thapsigargin, when compared with control recordings obtained with 2 mM ATP instead. Ca2+-dependent vesicular fusion was triggered by dialysing cells with 10 microM Ca2+ and guanosine-5'-O-(3-thiotriphosphate (GTP[gamma-S]). The capacitance increase was unaffected by inhibition of glycolysis, mitochondrial inhibitors or dialysis with either AMP-PNP or adenosine 5'-O-(3-thiotriphosphate) (ATP[gamma-S]) instead of ATP. We conclude that ATP hydrolysis does not seem to be necessary for the activation of ICRAC or for the capacitance increases elicited by high concentrations of intracellular Ca2+.

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The ontogeny of the cerebral pyruvate recycling pathway and the cellular localization of associated enzymes, malic enzyme (ME) and phosphoenolpyruvate carboxykinase (PEPCK), have been investigated using a combination of 13C NMR spectroscopy, enzymatic analysis, and molecular biology approaches. Activity of the pathway, using [1,2-(13)C2]acetate as a substrate, was detected by 13C NMR in brain extracts 3 weeks after birth, increasing progressively up to the third month of age. In whole-brain homogenates, ME activity increased to adult levels with the same time course as the recycling pathway. PEPCK activity was low during the first 2 weeks of life and decreased further toward adulthood. ME and PEPCK activity were found in primary cultures of astrocytes and in synaptosomal fractions of adult brain. Primary cultures of cortical neurons showed PEPCK activity but no detectable ME activity. The cytosolic ME gene was expressed in primary cultures of neurons and in astrocytes as well as in the neonatal and adult brain. The PEPCK gene was expressed both in primary cultures of cortical neurons and in astrocytes, but the level of its expression in the neonatal and adult brain was undetectable.

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Preliminary findings are presented regarding Visi-Pitch settings in relation to automatically derived perturbation values (jitter). Jitter values were estimated from sustained phonation of /a/ at each of four filter settings for three subjects using Visi-Pitch. Data were compared to values obtained by hand measuring the same signals and employing Koike's formula. Results indicated that the magnitude of difference between jitter estimated by Visi-Pitch and hand measurement was small. Findings support the use of the manufacturer's recommended filter settings as opposed to alternative settings suggested by Karnell.

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This clinical investigation was designed to study the influence of age on stereoselective drug disposition using hexobarbital as a model marker. The disposition of hexobarbital enantiomers was investigated in 10 young and 10 elderly, healthy male volunteers. Mean oral clearance (+/- SD) of d-hexobarbital (1.9 +/- 0.5 vs. 1.7 +/- 0.3 ml/min/kg; P greater than 0.05) did not differ significantly between the young and elderly subjects, respectively. However, despite wide intersubject variability, l-hexobarbital mean oral clearance (+/- SD) was approximately twofold greater in the young than in the elderly subjects (16.9 +/- 11.9 vs. 8.2 +/- 3.2 ml/min/kg; P less than 0.05). This resulted in a significantly greater enantiomeric oral clearance ratio in the young when compared with the elderly subjects (8.3 +/- 3.4 vs. 4.7 +/- 1.4; P less than 0.01). No significant difference (P greater than 0.05) in pharmacologic response after hexobarbital administration was found between the two groups. Demonstration of an age-related preferential decline in metabolism of one enantiomer over another has not been reported previously for any racemic drug in animals or humans.

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The growth in single-person households is a pervasive behavioral phenomenon in the United States in the post-war period. In this paper we investigate determination of the propensity to live alone, using 1970 data across states for single men and women ages 25 to 34 and for elderly widows. Income level appears to be a major determinant of the propensity to live alone. The estimated cross-state equations track about three-quarters of the increase in the propensity to live alone between 1950-1976 and suggest that income growth has been the principal identified influence. Other variables found to affect (positively) the propensity to live alone include mobility, schooling level, and for young people a measure of social climate; non-whites appear to have a somewhat lower propensity to live alone.

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