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81.
Cao J Prisinzano TE Okunola OM Kopajtic T Shook M Katz JL Newman AH 《ACS medicinal chemistry letters》2010,2(1):48-52
A series of modafinil (1) analogues was synthesized wherein 1) para-halo-substitutents were added to the aryl rings, 2) the sulfoxide function was removed, and 3) the primary amide group was replaced with secondary and tertiary amides and amines to investigate the effects of these chemical modifications on DAT, SERT and NET binding. In addition, the locomotor-stimulant effects in mice of (±)-modafinil (1), its R- and S-enantiomers and its para-chloro sulfinylacetamide analogue (5c) were compared to those of cocaine. 相似文献
82.
Gastrointestinal teratomas are uncommon, benign neoplasms that occur primarily in children. A retrospective review of five cases (two gastric, one pancreatic, one mesenteric, and one in the lesser omentum) is presented with emphasis on the computed tomographic and ultrasonographic appearances. Principal findings are a well-defined mass with separate cystic and solid components of varying proportions, discrete areas with densities similar to that of fat, or coarse, globular calcifications within the solid component. Recognition of these findings may allow the radiologist to make a correct preoperative diagnosis of teratoma. 相似文献
83.
I Puls K Hauck K Demuth A Horowski M Schliesser P D?rfler P Scheel K V Toyka K Reiners M Sch?ning G Becker 《Stroke; a journal of cerebral circulation》1999,30(11):2291-2295
BACKGROUND AND PURPOSE: The diagnosis and quantification of microangiopathy in dementia is difficult. The assessment of small-vessel disease requires expensive and sophisticated nuclear medicine techniques. This study was performed to identify microangiopathy related to the integrity of cerebral microcirculation by sonographic measurements (arteriovenous cerebral transit time [cTT]). METHODS: We performed transcranial color-coded duplex sonography in 40 patients with vascular dementia, 20 patients with Alzheimer's disease or Lewy body disease, and 25 age-matched controls. The clinical diagnosis was established by history of dementia and neuroimaging findings. Cognitive impairment was assessed by the Mini-Mental State Examination and Alzheimer's Disease Assessment Scale. cTT is defined as the time required by an ultrasound contrast agent to pass from a cerebral artery to a vein. This was measured by recording the power-Doppler intensity curves in the P2 segment of the posterior cerebral artery and the vein of Galen. Previous studies have shown a prolongation of cTT in patients with cerebral microangiopathy. RESULTS: cTT was substantially prolonged in patients with vascular dementia (5.8 seconds; 25th percentile 4.5; 75th percentile 7.5; U test, P<0.001) compared with controls (3.1 seconds; 2.3; 3.4) but not in patients with degenerative dementia (3.7 seconds; 3.7; 4.2). In patients with vascular dementia, cTT was significantly correlated with cognitive impairment. CONCLUSIONS: cTT may be useful tool to disclose small-vessel disease in demented patients. Examination is noninvasive and quickly performed. It may be also useful in follow-up examinations in patients undergoing therapy. 相似文献
84.
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86.
Gitlin LN Schinfeld S Winter L Corcoran M Boyce AA Hauck W 《Disability and rehabilitation》2002,24(1-3):59-71
PURPOSE: This article reports on an interrater reliability and preliminary validity study of an investigator-developed tool, the Home Environmental Assessment Protocol (HEAP) for use in homes of persons with dementia. METHOD: The HEAP consists of 192 items that are summed into separate indices representing the number of hazards, adaptations, and level of clutter and comfort in eight areas of the home. Interrater reliability was examined among four raters, two environmental experts and two non-experts, who observed 22 dementia households. RESULTS: The Kappa statistic was used to evaluate agreement level for each measured item and found that agreement ranged from slight to almost perfect. Intraclass correlations (ICCs), were used to evaluate agreement level for indices. The hazard index in each room ranged from fair (0.36) to moderate (0.66) for all raters. For the adaptation, clutter and comfort indices in each room, ICCs ranged from 0.51 to 0.90 for all raters. Agreement level between expert and non-expert raters differed minimally for all indices. Adaptations to dining rooms (r= -0.080, p = 0.001), kitchens (r = -0.52, p = 0.02) and bedrooms (r = -0.76, p = 0.001) were associated with patient deficits such that more adaptations were made in homes of dependent persons. Low Mini-Mental Status Examination scores were associated with fewer hazards, more adaptations, and less clutter. CONCLUSION: Findings show that both experts and non-expert raters use the HEAP consistently. Also, measured attributes are related to cognitive and functional status in the expected direction. 相似文献
87.
Intensive care unit delirium is an independent predictor of longer hospital stay: a prospective analysis of 261 non-ventilated patients 总被引:5,自引:2,他引:5
Thomason JW Shintani A Peterson JF Pun BT Jackson JC Ely EW 《Critical care (London, England)》2005,9(4):R375-R381
Introduction
Delirium occurs in most ventilated patients and is independently associated with more deaths, longer stay, and higher cost. Guidelines recommend monitoring of delirium in all intensive care unit (ICU) patients, though few data exist in non-ventilated patients. The study objective was to determine the relationship between delirium and outcomes among non-ventilated ICU patients.Method
A prospective cohort investigation of 261 consecutively admitted medical ICU patients not requiring invasive mechanical ventilation during hospitalization at a tertiary-care, university-based hospital between February 2002 and January 2003. ICU nursing staff assessed delirium and level of consciousness at least twice per day using the Confusion Assessment Method for the ICU (CAM-ICU) and Richmond Agitation-Sedation Scale (RASS). Cox regression with time-varying covariates was used to determine the independent relationship between delirium and clinical outcomes.Results
Of 261 patients, 125 (48%) experienced at least one episode of delirium. Patients who experienced delirium were older (mean ± SD: 56 ± 18 versus 49 ± 17 years; p = 0.002) and more severely ill as measured by Acute Physiology and Chronic Health Evaluation II (APACHE II) scores (median 15, interquartile range (IQR) 10–21 versus 11, IQR 6–16; p < 0.001) compared to their non-delirious counterparts. Patients who experienced delirium had a 29% greater risk of remaining in the ICU on any given day (compared to patients who never developed delirium) even after adjusting for age, gender, race, Charlson co-morbidity score, APACHE II score, and coma (hazard ratio (HR) 1.29; 95% confidence interval (CI) 0.98–1.69, p = 0.07). Similarly, patients who experienced delirium had a 41% greater risk of remaining in the hospital after adjusting for the same covariates (HR 1.41; 95% CI 1.05–1.89, p = 0.023). Hospital mortality was higher among patients who developed delirium (24/125, 19%) versus patients who never developed delirium (8/135, 6%), p = 0.002; however, time to in-hospital death was not significant the adjusted (HR 1.27; 95% CI 0.55–2.98, p = 0.58).Conclusion
Delirium occurred in nearly half of the non-ventilated ICU patients in this cohort. Even after adjustment for relevant covariates, delirium was found to be an independent predictor of longer hospital stay. 相似文献88.
Martelle JL Claytor R Ross JT Reboussin BA Newman AH Nader MA 《The Journal of pharmacology and experimental therapeutics》2007,321(2):573-582
The present study examined the effects of two novel dopamine D3 receptor compounds, NGB 2904 [N-(4-(4-(2,3-dichlorophenyl)piperazin-1-yl)butyl)-9H-fluorene-2-carboxamide], an antagonist, and CJB 090 [N-(4-(4-(2,3-dichlorophenyl)piperazin-1-yl)butyl)-4-(pyridin-2-yl)benzamide], a partial agonist, in two models of cocaine abuse in rhesus monkeys. To establish a dose range and time course of effects, both compounds were shown to block quinpirole-induced yawning when administered i.m. 15, 30, or 120 min before quinpirole. Next, rhesus monkeys were trained to discriminate i.m. injections of saline (0.5 ml) and cocaine (0.3 mg/kg). Neither D3 compound (0.03-3.0 mg/kg; n=3) substituted for cocaine in any monkey. When given in combination with cocaine, CJB 090 but not NGB 2904 attenuated the discriminative stimulus effects of cocaine, shifting the cocaine dose-response curve to the right. In a separate group of monkeys, responding was maintained under a second-order schedule of either food (1.0-g pellets; n=3) or cocaine (0.1 mg/kg/injection; n=4) presentation. When responding was stable, a dose of NGB 2904 (1.0-5.6 mg/kg i.v.) or CJB 090 (0.3-3.0 mg/kg i.v.) was administered for 5 consecutive days, immediately before the session. CJB 090, but not NGB 2904, decreased cocaine- and food-maintained responding. These data indicate that compounds with relatively high affinity and selectivity for the D3 receptor can attenuate the discriminative and reinforcing stimulus effects of cocaine while not producing cocaine-like effects. The present findings support the continued examination of D3 compounds as pharmacological tools for better understanding the role of this receptor subtype in cocaine addiction and as potential lead compounds for novel therapeutic agents. 相似文献
89.
An interprofessional exploration of nursing and social work roles when working jointly with families
Elaine Bennett Yvonne Hauck Georgina Radford Sakina Bindahneem 《Journal of interprofessional care》2016,30(2):232-237
Ngala, an early parenting not-for-profit organisation in Western Australia, has provided services to families with young children since 1890. Child health nurses and mothercraft nurses were the primary workforce until the 1980s when a social worker was employed and a new era of interprofessional collaboration began. Evidence to date has focused on nursing workforce, interprofessional education, and interprofessional teams. Little is known about the roles of nursing and social work when working jointly with families. A new service commenced in 2012 for families with children with developmental delays. Social workers and child health nurses were employed for this service model. Our study aim was to explore the perceptions of how nurses and social workers work together with a family providing psychosocial support across a new service. The study was conducted alongside implementation of this new service. An exploratory case study approach was adopted to generate an in-depth understanding of the roles of nurses and social workers. In total, 22 semi-structured interviews and one focus group across the first year of implementing the new service were undertaken. Analysis of these data revealed four major themes. Findings presented in this article will inform further reflection and consideration into the future interprofessional workforce priorities and requirements for Early Parenting Services. 相似文献
90.
Ukairo OT Bondi CD Newman AH Kulkarni SS Kozikowski AP Pan S Surratt CK 《The Journal of pharmacology and experimental therapeutics》2005,314(2):575-583
Binding of cocaine to the dopamine transporter (DAT) protein blocks synaptic dopamine clearance, triggering the psychoactive effects associated with the drug; the discrete drug-protein interactions, however, remain poorly understood. A longstanding postulate holds that cocaine inhibits DAT-mediated dopamine transport via competition with dopamine for formation of an ionic bond with the DAT transmembrane aspartic acid residue D79. In the present study, DAT mutations of this residue were generated and assayed for translocation of radiolabeled dopamine and binding of radiolabeled DAT inhibitors under identical conditions. When feasible, dopamine uptake inhibition potency and apparent binding affinity K(i) values were determined for structurally diverse DAT inhibitors. The glutamic acid substitution mutant (D79E) displayed values indistinguishable from wild-type DAT in both assays for the charge-neutral cocaine analog 8-oxa-norcocaine, a finding not supportive of the D79 "salt bridge" ligand-docking model. In addressing whether the D79 side chain contributes to the DAT binding sites of other portions of the cocaine pharmacophore, only inhibitors with modifications of the tropane ring C-3 substituent, i.e., benztropine and its analogs, displayed a substantially altered dopamine uptake inhibition potency as a function of the D79E mutation. A single conservative amino acid substitution thus differentiated structural requirements for benztropine function relative to those for all other classical DAT inhibitors. Distinguishing the precise mechanism of action of this DAT inhibitor with relatively low abuse liability from that of cocaine may be attainable using DAT mutagenesis and other structure-function studies, opening the door to rational design of therapeutic agents for cocaine abuse. 相似文献