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71.
Fowler JS Wang GJ Volkow ND Franceschi D Logan J Pappas N Shea C MacGregor RR Garza V 《The American journal of psychiatry》2000,157(11):1864-1866
OBJECTIVE: The authors' goal was to replicate a previous finding that smokers have lower brain monoamine oxidase B (MAO-B) levels than comparison nonsmoking subjects and to determine if levels recover after overnight cigarette abstinence. METHOD: Brain MAO-B levels were measured by means of positron emission tomography in six smokers who were scanned twice: 11.3 hours (baseline) and 10 minutes after smoking one cigarette. RESULTS: Average MAO-B levels in smokers in the present study were similar to those found in the previous study and averaged 39% (SD=17) lower than those found in a comparison group of nonsmokers. Brain MAO-B levels did not differ between baseline levels and 10 minutes after smoking. CONCLUSIONS: This study reinforces the need to investigate whether MAO-B inhibition may account for some of the behavioral and epidemiological features of smoking. 相似文献
72.
Gerald E Hanks Thomas F Pajak Arthur Porter David Grignon Harmart Brereton Varagur Venkatesan Eric M Horwitz Colleen Lawton Seth A Rosenthal Howard M Sandler William U Shipley 《Journal of clinical oncology》2003,21(21):3972-3978
PURPOSE: Radiation Therapy Oncology Group (RTOG) Protocol 92-02 was a randomized trial testing long-term (LT) adjuvant androgen deprivation (AD) after initial AD with external-beam radiotherapy (RT) in patients with locally advanced prostate cancer (PC; T2c-4) and with prostate-specific antigen level less than 150 ng/mL. PATIENTS AND METHODS: Patients received a total of 4 months of goserelin and flutamide, 2 months before and 2 months during RT. A radiation dose of 65 to 70 Gy was given to the prostate and a dose of 44 to 50 Gy to the pelvic lymph nodes. Patients were randomly assigned to receive no additional therapy (short-term [ST]AD-RT) or 24 months of goserelin (LTAD-RT); 1,554 patients were entered onto the study. RESULTS: The LTAD-RT arm showed significant improvement in all efficacy end points except overall survival (OS; 80.0% v 78.5% at 5 years, P =.73), compared with the STAD-RT arm. In a subset of patients not part of the original study design, with tumors assigned Gleason scores of 8 to 10 by the contributing institutions, the LTAD-RT arm had significantly better OS (81.0% v 70.7%, P =.044). There was a small but significant increase in the frequency of late radiation grades 3, 4, and 5 gastrointestinal toxicity ascribed to the LTAD-RT arm (2.6% v 1.2% at 5 years, P =.037), the cause of which is not clear. CONCLUSION: The RTOG 92-02 trial supports the addition of LT adjuvant AD to STAD with RT for T2c-4 PC. In the exploratory subset analysis of patients with Gleason scores 8 to 10, LT adjuvant AD resulted in a survival advantage. 相似文献
73.
Colleen J. Gilbert William P. Petros James Vredenburgh Atif Hussein Maureen Ross Peter Rubin Randy Fehdrau Colleen Cavanaugh Donald Berry Craig McKinstry William P. Peters 《Cancer chemotherapy and pharmacology》1998,42(6):497-503
Purpose: Both ondansetron and cyclophosphamide are thought to be metabolized by hepatic microsomal processes. The purpose of this
study was to evaluate the potential pharmacokinetic interactions between ondansetron and high-dose alkylating agent chemotherapy.
Methods: A total of 54 breast cancer patients receiving high-dose cyclophosphamide, cisplatin and carmustine were treated prospectively
in four sequential cohorts. Cohorts I and II received continuous infusions of both ondansetron and prochlorperazine, and cohorts
III and IV received a continuous infusion of ondansetron alone at the same doses. All patients received lorazepam every 4 h.
A group of 75 matched historical controls had received a continuous infusion of prochlorperazine with lorazepam. Pharmacokinetic
monitoring of each drug used in the high-dose chemotherapy regimen was conducted. Results: Median AUCs of cyclophosphamide in patients receiving ondansetron (73.6 mg/ml · min) were lower than those of the control
patients (88.3 mg/ml · min, n = 75, P = 0.0004), but the median cisplatin AUC was approximately 10% higher and no difference in the disposition of carmustine was
demonstrated. Patients treated with ondansetron displayed a higher frequency of headaches than the controls. The frequency
of achieving complete emetic control was greater in the ondansetron + prochlorperazine groups compared to the ondansetron
alone groups and was greater in both these groups than in the prochlorperazine alone group on the first day of therapy only.
Conclusion: Ondansetron altered the systemic exposure to cyclophosphamide when these agents were administered concomitantly. Ondansetron
did not substantially improve overall emetic control when used alone but may improve control in combination with prochlorperazine.
Future randomized studies are needed to delineate the effect of ondansetron on the disposition of the active cyclophosphamide
metabolites so that clinical implications can be addressed.
Received: 28 October 1997 / Accepted: 9 March 1998 相似文献
74.
Hyperglycemia in the critically ill. 总被引:2,自引:0,他引:2
Hyperglycemia is frequently seen in acutely ill patients and has historically been viewed as a normal response to stress. Treatment is often not initiated unless blood glucose exceeds 200 to 250 mg/dL. Recent evidence suggests that hyperglycemia is associated with worse outcomes within the population of medical and surgical intensive care units. Hyperglycemia in this population of patients develops from increased gluconeogenesis and insulin resistance. Although the specific mechanisms by which hyperglycemia contributes to poor outcomes are as yet unknown, disruption of normal mitochondrial respiration, direct glucose toxicity, accumulation of asymmetric dimethylarginine, and impairment of immune cell function are among the possibilities implicated. Studies demonstrate that intensive insulin therapy to achieve euglycemia reduces mortality and morbidity in critically ill patients. In addition to recognizing and treating hyperglycemia, it is as important to identify other frequently overlooked factors that contribute to hyperglycemia, such as medications, intravenous fluids, and enteral and parenteral nutrition. 相似文献
75.
Marisa L Kreider Justin E Aldridge Mandy M Cousins Colleen A Oliver Frederic J Seidler Theodore A Slotkin 《Neuropsychopharmacology》2005,30(10):1841-1855
Glucocorticoids are the consensus treatment for the prevention of respiratory distress in preterm infants, but there is evidence for increased incidence of neurodevelopmental disorders as a result of their administration. We administered dexamethasone (Dex) to developing rats at doses below or within the range of those used clinically, evaluating the effects on forebrain development with exposure in three different stages: gestational days 17-19, postnatal days 1-3, or postnatal days 7-9. At 24 h after the last dose, we evaluated biomarkers of neural cell acquisition and growth, synaptic development, neurotransmitter receptor expression, and synaptic signaling mediated by adenylyl cyclase (AC). Dex impaired the acquisition of neural cells, with a peak effect when given in the immediate postnatal period. In association with this defect, Dex also elicited biphasic effects on cholinergic presynaptic development, promoting synaptic maturation at a dose (0.05 mg/kg) well below those used therapeutically, whereas the effect was diminished or lost when doses were increased to 0.2 or 0.8 mg/kg. Dex given postnatally also disrupted the expression of adrenergic receptors known to participate in neurotrophic modeling of the developing brain and evoked massive induction of AC activity. As a consequence, disparate receptor inputs all produced cyclic AMP overproduction, a likely contributor to disrupted patterns of cell replication, differentiation, and apoptosis. Superimposed on the heterologous AC induction, Dex impaired specific receptor-mediated cholinergic and adrenergic signals. These results indicate that, during a critical developmental period, Dex administration leads to widespread interference with forebrain development, likely contributing to eventual, adverse neurobehavioral outcomes. 相似文献
76.
This study examined the influence of parental, school, and peer bonding for rural youth making the transition into middle school. Survey data were collected from 225 adolescents and their mothers answering parallel items on family cohesion, school attachment, and attitudes toward substance use by minors. Adolescents also reported on social support from friends, and mothers reported on the family's involvement in religious activities. Using structural equation modeling, greater family cohesion at the start of middle school / junior high was directly and indirectly related to negative attitudes toward substance use by the adolescent one year later. Factors that mediated family cohesion were school and peer attachment, the family's involvement in religious activities, and the mothers' attitudes toward substance use by minors. Implications for prevention and recommendations for parents are discussed. 相似文献
77.
Neuropsychological functioning in end-stage renal disease. 总被引:2,自引:0,他引:2
H N Bawden P Acott J Carter D Lirenman G W MacDonald M McAllister M C McDonnell S Shea J Crocker 《Archives of disease in childhood》2004,89(7):644-647
AIMS: To compare the neuropsychological functioning and behaviour of children with non-syndromic end-stage renal disease (ESRD) and sibling controls. METHODS: The study was carried out at two tertiary care paediatric teaching hospitals, in Halifax and Vancouver, Canada. Children with ESRD were on a renal transplant waiting list and either pending dialysis or on dialysis therapy. Twenty two patient-sibling pairs were evaluated. Neuropsychological assessments consisting of measures of intelligence, academic achievement, memory, and motor abilities were carried out. Maternal ratings of behaviour and self-report rating of self-esteem were collected. RESULTS: The Verbal, Performance, and Full Scale IQs of patients with ESRD were significantly lower than the IQs of the sibling controls. The mean differences were 8.6, 11.7, and 10.9 points, respectively. ESRD patients also had significantly more difficulty on measures of fine motor coordination and ability to copy geometric designs than sibling controls. There were no differences between groups on measures of academic achievement, memory, behaviour, or self-esteem. CONCLUSIONS: Although children with ESRD exhibited mild deficits on measures of intelligence and some measures of motor abilities, their neuropsychological outcome was more favourable than earlier reports indicated. 相似文献
78.
Recent advances in modern perinatal and neonatal intensive care have led to an increase in the survival of premature infants. This increased survival, unfortunately, has not been accompanied by an improvement in neurodevelopmental outcomes. Premature infants, especially those with an extremely low birth weight (less than 1000 g) or those born at less than 28 weeks’ gestation, are at increased risk of major disabilities and complex, ‘low severity’ dysfunctions that have significant, lasting effects on their school function, academic performance and behaviour, as well as on family function. Neonatal follow-up programs provide a number of functions to centres providing neonatal intensive care, including quality assurance and audits, research and follow-up clinical care to neonatal intensive care unit survivors and their families. The challenge for neonatal follow-up programs is to meet the often competing objectives of providing clinical services to children and their families while providing quality assurance and audits, and high-quality long-term outcome research components, given the available resources. There is also a need for ongoing research to develop and evaluate effective postdischarge intervention programs to improve the long-term outcome of prematurity and other neonatal complications. Developmental paediatricians – with their background and training in the provision of specialized health care to children and their care-givers with respect to developmental and psychosocial well-being, and in conducting developmental and behavioural disabilities research – play a valuable role in the follow-up assessment and care of neonatal intensive care unit graduates, and strengthen the multidisciplinary research groups necessary to assess long-term outcomes and the effects of perinatal and postdischarge interventions. 相似文献
79.
80.