开展全程化药学服务,促进抗菌药物合理应用

目的探讨促进抗菌药物合理应用的有效途径。方法分析和评价全程化药学服务在促进抗菌药物合理应用中的作用。结果全程化药学服务是促进抗菌药物合理应用的有效途径。结论医院药学应积极开展全程化药学服务,以促进抗菌药物合理应用,使有限的抗菌药物资源得到最大限度的利用。     

Fetal striatal transplants reinstate the electrophysiological response of pallidal neurons to systemic apomorphine challenge in rats with excitotoxic striatal lesions

Previous studies with single-unit recording and 2-[14C]deoxyglucose quantitative autoradiography have shown that systemic administration of apomorphine increases the functional activity of pallidal neurons, and that the enhancement in the globus pallidus (GP) activity is abolished by striatal lesions. The present study employing electrophysiological techniques tested whether embryonic striatal tissue implanted in the excitotoxically damaged striatum of rats may affect the lesion-induced alteration in the neuronal response of GP to apomorphine. Systemically administered apomorphine significantly increased spontaneously firing rates of GP cells. The blockade of dopamine receptors with haloperidol reversed the increased rate to baseline levels. Quinolinate-induced striatal lesions attenuated the rate-increasing effect of apomorphine. Embryonic striatal grafts placed in the lesioned striatum restored the response of GP cells to systemic apomorphine. The graft-mediated restoration of the GP neuron response to apomorphine were accompanied by an improvement in the motor asymmetry induced by this drug. Considering previous anatomical data to demonstrate extensive innervation of the GP by embryonic striatal grafts, the present results suggest that the grafts reconstruct the functional striatopallidal pathway which is capable of transmitting apomorphine-induced changes in the neuronal activity.     

Ontogeny of aromatase and tyrosine hydroxylase activity and of aromatase-immunoreactive cells in the preoptic area of male and female Japanese quail

The aromatization of testosterone into oestrogens plays a key role in the control of many behavioural and physiological aspects of reproduction. In the quail preoptic area (POA), aromatase activity and the number of aromatase-immunoreactive (ARO-ir) cells are sexually differentiated (males > females). This sex difference is implicated in the control of the sexually dimorphic behavioural response of quail to testosterone. We analysed the ontogenetic development of this sex difference by measuring aromatase activity and counting ARO-ir cells in the POA of males and females from day 1 post hatch to sexual maturity. We investigated in parallel another enzyme: tyrosine hydroxylase, the rate limiting step in catecholamine synthesis. Between hatching and 4 weeks of age, aromatase activity levels were low and equal in males and females. Aromatase activity then markedly increased in both sexes when subjects initiated their sexual maturation but this increase was more pronounced in males so that a marked difference in aromatase activity was present in 6 and 8 week-old subjects. Tyrosine hydroxylase activity progressively increased with age starting immediately after hatching and there was no abrupt modification in the slope of this increase when birds became sexually mature. No sex difference was detected in the activity of this enzyme. The number of ARO-ir cells in the POA progressively increased with age starting at hatching. No sex difference in ARO-ir cell numbers could be detected before subjects reached full sexual maturity. The analysis of the three-dimensional organization of ARO-ir cells in the POA revealed that, with increasing ages, ARO-ir cells acquire a progressively more lateral position: they are largely periventricular in young birds but they are found at higher density in the lateral part of the medial preoptic nucleus in adults. These data indicate that aromatase activity differentiates sexually when birds reach sexual maturity presumably under the activating effects of the increased testosterone levels in males. The number of ARO-ir cells, however, begins to increase in a non sexually differentiated manner before the rise in plasma testosterone in parallel with the increased tyrosine hydroxylase activity. Whether this temporal coincidence results from a general ontogenetic pattern or from more direct causal links remains to be established.     

Voluntary sucrose ingestion, like corticosterone replacement, prevents the metabolic deficits of adrenalectomy

We tested whether corticosterone replacement causes increased sucrose drinking in adrenalectomized (ADX) rats compared to sham-ADX (sham) rats. ADX rats given high doses of corticosterone drank as much sucrose as sham rats, whereas at three lower doses of corticosterone, drinking was similar between groups and was only approximately 40% of that ingested by shams. Compared to sham rats, ADX rats drinking saline, or saline and saccharin, gain weight more slowly, contain less white adipose tissue, and have higher sympathetic outflow as assessed by uncoupling protein content in brown adipose tissue. Allowing sucrose as well as saline to drink restored all of these variables to normal in ADX rats with no- or low-corticosterone. All endpoints from sucrose-drinking ADX rats with no-or low-corticosterone were indistinguishable from those in water-drinking shams. By contrast, sucrose-drinking ADX rats that were given high doses of corticosterone exhibited the usual catabolic effects of corticosterone on body weight gain and, unlike sucrose-drinking shams, were obese. We conclude that (i) high corticosterone stimulates the potability of sucrose and inhibits sympathetic stimulation of uncoupling protein; (ii) sucrose, without corticosterone, normalizes metabolic deficits in ADX rats probably through actions mediated both peripherally and by the central nervous system; and (iii) ADX rats have a distinct sucrose appetite.     

Variations in maternal behaviour are associated with differences in oxytocin receptor levels in the rat

Female Long-Evans rats exhibit stable individual differences in maternal behaviours such as pup licking/grooming and arched-back nursing posture (LG-ABN). These variations in maternal behaviour are accompanied by differences in lactation-induced increases in oxytocin receptor levels in brain regions known to mediate the expression of maternal care in this species (i.e. the bed nucleus of the stria terminalis, the medial preoptic area and the lateral septum). Oxytocin receptor levels in the central nucleus of the amygdala were significantly higher in high compared to low LG-ABN females regardless of reproductive status. These findings suggest that individual differences in maternal behaviour may be directly related to variations in oxytocin receptor expression.     

Practitioner Review: Unguided and guided self-help interventions for common mental health disorders in children and adolescents: a systematic review and meta-analysis

Mental health problems are common in children and adolescents, yet evidence-based treatments are hard to access. Self-help interventions can increase such access. The aim of this paper was to conduct a systematic review and meta-analysis of the use of guided and unguided self-help for children and young people with symptoms of common mental health disorders. In contrast to previous reviews of self-help in children, all types of self-help and multiple mental health disorders were investigated in order to increase power to investigate potential moderators of efficacy. Importantly, studies with control arms as well as those comparing against traditional face-to-face treatments were included. Fifty studies (n = 3396 participants in self-help/guided self-help conditions) met the inclusion criteria. Results demonstrated a moderate positive effect size for guided and unguided self-help interventions when compared against a control group (n = 44; g = 0.49; 95% CI: 0.37 to 0.61, p < .01) and a small but significant negative effect size when compared to other therapies (n = 15; g = −0.17; 95% CI: –0.27 to –0.07, p < .01). Few potential moderators had a significant effect on outcome. Most comparisons resulted in significant heterogeneity and therefore results are interpreted with caution.     

Pharmacokinetics and pharmacodynamics of topotecan given on a daily-times-five schedule in phase II clinical trials using a limited-sampling procedure

 Topotecan is a novel semisynthetic derivative of the anticancer agent camptothecin and inhibits the intranuclear enzyme topoisomerase I. The lactone structure of topotecan, which is in equilibrium with the inactive ring-opened hydroxy acid, is essential for this activity. We performed a pharmacokinetics study as part of phase II clinical trials in patients with various types of solid tumors, giving topotecan at 1.5 mg/m² per day by 30-min infusion for 5 consecutive days, with courses being repeated every 3 weeks. Previously validated limited-sampling models, using concentration measurements in samples obtained 2 h after infusion, were used to calculate the area under the plasma concentration-time curves (AUCs) for both chemical forms. Samples were obtained from a total of 36 patients over 136 treatment days. The mean AUC of the closed-ring form (AUC_closed) was 8.74 (range 2.3–16.3)  μM min per day, and the mean AUC of the ring-opened form (AUC_open) was 11.5 (range 3.2–46.0)  μM min per day (interpatient variability 34–61%). In each patient the AUC values achieved on the 1st day of administration were similar to and, thus, predictive for those achieved during the following days, with a day-to-day variation of 7.39% being recorded for the AUC_closed and that of 12.6%, for the AUC_open. There was no drug accumulation during the 5 consecutive treatment days of each cycle. However, despite the large interpatient pharmacokinetic variability, the importance of regular drug monitoring on this schedule can be questioned, as the pharmacodynamic variability was relatively small. Received: 15 June 1995/Accepted: 19 October 1995     

三七种子贮藏习性研究

目的研究三七种子的贮藏习性,为三七种子的保存提供科学依据。方法用TTC法测定不同水分和不同温度贮藏三七种子生活力。结果三七种子对干燥脱水的忍耐能力类似顽拗型种子,其最低安全含水量为17%。结论三七种子为顽拗型种子,对低温极为敏感,不适宜采用低温贮存。     

A multicenter phase II study of carboplatin and paclitaxel with a biweekly schedule in patients with advanced non-small-cell lung cancer: Kyushu thoracic oncology group trial

Purpose: This multicenter phase II study was conducted to investigate the efficacy and safety of carboplatin in combination with paclitaxel administered according to a biweekly schedule as a first-line chemotherapy for advanced non-small-cell lung cancer (NSCLC). Patients and methods: Eligibility criteria included histologically or cytologically confirmed NSCLC (stage IIIb or IV), no prior treatment, and measurable or evaluable disease. Paclitaxel (140 mg/m²) was administered intravenously on day 1, in combination with carboplatin at an area under the concentration time curve (AUC) of 3, every 2 weeks. Results: Seventy-four patients (45 men) with a median age of 62 years (range 40–74) and a median ECOG performance status of 1 (range 0–2) were enrolled. The response rate was 35.1% [95% confidence interval (CI): 24.4–47.1%], with 26 partial responses. The median survival was 357 days, and the median time to progression was 218 days. Toxicity was generally mild; National Cancer Institute-Common Toxicity Criteria (NCI-CTC) grades 3 and 4 neutropenia was observeded in 50.0% of the patients, and grades 3 and 4 nausea/vomiting in 4.1%. Conclusions: Biweekly carboplatin combined with paclitaxel demonstrated anti-tumor activity in advanced NSCLC, with response and survival rates similar to those of carboplatin combined with paclitaxel administered every 3 weeks but with a more favorable toxicity profile, and the present data indicate that the regimen is suitable for use on an outpatient basis.