Ethanol regulated preference in rats

A series of experiments evaluated the determinants of preference for mixtures of ethanol plus sucrose relative to sucrose in rats. One dipper served 10% ethanol mixed with 10% sucrose, and the second dipper served 10% sucrose. Lever presses operated each dipper according to a variable-interval 5-s schedule. In three experiments the subjects were given pre-session meals of sucrose (2.5–20 ml) or sucrose (20 ml) plus chow (5 or 10 g). Pre-session meals decreased responding maintained by sucrose but not responding maintained by ethanol mixture. In two experiments body weight was varied from 85% to 125% of the initial free-feeding values. Increases in body weight, like pre-session meals, decreased responding reinforced by sucrose, but typically did not decrease responding reinforced by ethanol mixture. Throughout most of the study, ethanol consumption remained at about 1.25 ml per half hour session (3–4 g/kg per 30 min). For example, pre-session access to ethanol mixture decreased within-session ethanol consumption, but total consumption, counting both sources, remained about 1.25 ml/session. The within-session patterns of responding also differed. Responding reinforced by ethanol mix decreased as a function of ethanol consumption, whereas responding reinforced by sucrose was relatively constant throughout the session. The simplest explanation of the results is that ethanol's pharmacological consequences regulated preference.     

The ensemble-averaged impedance cardiogram: An evaluation of scoring methods and interrater reliability

The interrater reliability and concurrent validity of two methods of scoring the ensemble-averaged impedance cardiogram were evaluated. Impedance cardiographic and electrocardiographic signals were recorded from 40 undergraduate men and women during a baseline rest period and a vocal mental arithmetic task period. Recordings were scored by four raters using a conventional method, involving ensemble averaging after careful editing of beat-to-beat waveforms, and a streamlined method, involving ensemble averaging without beat-to-beat editing. Intraclass correlations for interrater reliability exceeded .92, whereas intraclass correlations for concurrent validity exceeded .97, indicating excellent agreement between raters and scoring methods for all cardiac measures. The streamlined method was significantly faster than the conventional method. The results indicate that variations in beat-to-beat editing do not constitute a serious source of error in the ensemble-averaged impedance cardiogram and support the interrater reliability and concurrent validity of the two scoring methods.     

A retrospective study of the therapeutic efficacy of doxycycline on concurrent canine ehrlichiosis and babesiosis in a veterinary hospital population

Doxycycline has a well known broad spectrum activity against bacteria and rickettsia, as well as Ehrlichia spp. However, the use of doxycycline for the treatment of concurrent ehrlichiosis and babesiosis has rarely been evaluated, especially in veterinary hospital populations. A retrospective study of 70 canine ehrlichiosis and 12 canine babesiosis concurrent infections from Out Patient Department patients at Chulalongkorn Small Animal Teaching Hospital, admitted during 2001–2003, were studied. The results showed a complete curative effect of doxycycline on both canine ehrlichiosis and canine babesiosis concurrent infections. The red blood cell indices after treatment were significantly higher in canine ehrlichiosis (P < 0.05). The platelet cell counts after treatment were significantly higher in concurrent canine ehrlichiosis and babesiosis infections (P < 0.05). Doxycycline can be recommended as the drug of choice for both canine ehrlichiosis and canine babesiosis and concurrent infections of both conditions in veterinary hospitals.     

Concurrent infections ofTrichinella spiralis andToxoplasma gondii in mice

Concurrent infections with two parasites: a nematode,Trichinella spiralis, and a protozoon,Toxoplasma gondii, were investigated. Antibody production (total immunoglobulin and IgM) was similar in double and single infections. However, the number ofToxoplasma cysts in the brains of mice infected withTrichinella and challenged 1–6 weeks later withToxoplasma was higher than in mice infected withToxoplasma alone, while mice infected withToxoplasma and challenged 4–14 days later withTrichinella had lower worm burdens in the intestine than animals infected withTrichinella alone. Greater loss in body weight was observed in mice infected with both parasites than in those infected with either parasite alone.     

Concurrent progressive-ratio schedules to compare reinforcing effectiveness of different phencyclidine (PCP) concentrations in rhesus monkeys

  Rationale: Progressive ratio (PR) schedules have become well accepted for testing the reinforcing effectiveness of drugs. This study extends the methods to concurrent PR schedules with different concentrations of orally delivered phencyclidine (PCP). Objective: The sensitivity of the procedure is tested by presenting different PCP concentrations with independently-operating PR schedules. Method: PCP self-administration was investigated in seven rhesus monkeys. Six different PCP concentrations (0.03–1.0 mg/ml) and water were randomly paired (21 pairings). Liquid delivery (24 ml) was contingent upon lip-contact responses on solenoid-operated drinking spouts; whereby, the response requirement or fixed-ratio (FR) increased (from 8 to 16, 32, 64, 128... to 4096) after each successful completion of a previous FR and subsequent liquid delivery. Monkeys self administered PCP during daily 3-h sessions, and each pair of concentrations was held constant until behavior had stabilized for at least 4 days. Results: The higher of the two PCP concentrations always maintained greater responding, PR break point (BP), or the last ratio completed, and liquid deliveries than did the lower concentration. However, the monkeys did not exclusively respond on the drinking spout that yielded the higher drug concentration. When examined across all drug pairings, the percentage of total available deliveries of the higher concentration was significantly greater than those of the lower concentration. The monkeys maximized the amount (mg) consumed for the response output. Responding, BPs and liquid deliveries maintained by 0.12 and 0.25 mg/ml PCP were significantly greater than other PCP concentrations; however, drug intake (mg) increased directly with PCP concentration. Conclusion: These results indicate that concurrent PR schedules using oral drug self-administration and a concurrent choice paradigm reliably provide an estimation of relative reinforcing strength, and behavior maintained by these schedules is sensitive to small changes in PCP concentration. Received: 18 September 1998 / Final version: 28 December 1998     

The prediction of late rectal complications in patients treated with high dose-rate brachytherapy for carcinoma of the cervix

: The aim of this work is to invetigate an unusually high rate of late rectal complications in a group of 43 patients treated with concomitant irradiation and chemotherapy for carcinoma of the cervix between December 1988 and April 1991, with a view to identifying predictive factors.

: The biologically effective dose received by each patient to the rectal reference point defined by the International Commission of Radiation Units and Measurements, Report 38, were calculated. Radiotherapy consisted of 46 Gy external beam irradiation plus three dose-rate intracavitary treatments of 10 Gy each prescribed to point A. Cisplatin 30 mg/m² was given weekly throughout the duration of the irradiation. The results have been compared to data from 119 patients treated with irradiation alone to assess the cofounding effect of the cisplatin.

: The relationship between the biologically effective dose delivered to the rectal reference point and the development of late complications shows a strong dose-response with a threshold for complications occurring at aproximately the same biologically effective dose threshold as that found for external beam irradiation in the head and neck region. The date from the group of patients treated wihout cisplatin is comparable to the date from the first group of patients in the lower dose ranges; the higher doses were not used and thus are not available for comparison.

: Using the linear quadratic model applied to our clinical results, we have established a threshold for late rectal complications for patients treated with external beam irradiation and high dose-rate brachytherapy for carcinoma of the cervix. This threshold is consistent with similar data for external irradiation in the head and neck region.     

康莱特加同步放化疗治疗局部晚期非小细胞肺癌的临床研究

目的:观察康莱特注射液(KLT)联合同步放化疗对局部晚期非小细胞肺癌的治疗效果。方法:48例局部晚期非小细胞肺癌患者,随机分为两组,综合组25例:采用盖诺 顺铂方案同步放化疗,放疗予常规分割,2Gy/f,总量56～60Gy,同时加用康莱特注射液200ml/d静脉滴入,21天为1个疗程,共2个疗程。对照组23例:采用盖诺 顺铂方案同步放化疗。2疗程后评价疗效,通过KPS评分、体重变化观察生存质量改善情况。结果:两组完全缓解率分别为24.0%(6/25)和13.0%(3/23)(P>0.05);有效率分别为76.0%(19/25)和69.6%(16/23)(P>0.05);综合组3级以上骨髓抑制发生率为40.0%(10/25),而对照组为69.6%(16/23)(P<0.05);综合组3级以上消化道不良反应发生率为8.0%(2/25),对照组为34.8%(8/23)(P<0.05);综合组无3级以上放射性肺炎发生(0/25),而对照组为4.4%(1/23)(P>0.05);综合组3级以上放射性食管炎发生率16.0%(4/25),对照组为43.5%(10/23)(P<0.05);综合组治疗前后KPS评分及体重评分明显高于对照组(P<0.05)。结论:康莱特联合同步放化疗可以减轻放化疗引起的胃肠道反应,减少3级以上骨髓抑制和3级以上放射性食管炎的发生,使患者的生存质量得到改善,并有可能进一步提高局部晚期非小细胞肺癌同步放化疗的疗效。     

中药脑心同治药理学研究平台构建及丹红注射液脑心同治机制研究

脑心同治理论是基于中医传统理论并结合临床实践发展而来,该文提出了在脑心同治理论基础上,构建中药脑心同治药理学研究平台的思路,包括脑心同治网络建模、药效物质发现、作用机制研究以及脑心同治方药体内过程研究等。该文以脑心同治网络建模为例,采用数据库以及文献搜索收集疾病相关基因,并通过网络构建与模块分析,最终发现心、脑血管疾病相关的关键生物过程包括氧化应激、代谢、炎症等,其中GSK3B,NOTCH1,CDK4等基因占据网络子簇中关键节点。运用该研究平台,获得了丹红注射液主要成分调控的生物分子网络模型,从而发掘其治疗心脑血管疾病的共有靶点与作用途径。其中,GSK3B在网络中与丹红注射液成分相关性最多,且其所在的子簇涉及到的生物功能有细胞氧化应激。根据分析结果,在氧化损伤心肌细胞与神经细胞模型上验证了丹红注射液可显著提高氧化损伤后心肌细胞与神经细胞的存活率,其保护机制与提高GSK3β蛋白磷酸化水平有关,且丹参与红花配伍具有协同效应。以上结果显示,采用网络建模等方法,可研究揭示丹红注射液等脑心同治方药治疗心脑血管疾病的作用机制。该研究提出的中药脑心同治药理学研究平台框架,为综合运用现代科技手段科学揭示"脑心同治"的机制提供了可行途径。     

3种方案同步放化疗治疗中晚期宫颈癌的疗效对比观察

目的:探讨治疗中晚期宫颈癌同步放化疗的化疗方案选择.方法:96例中晚期宫颈癌患者同步放化疗随机分成顺铂组(30例)、多西紫杉醇组(34例)及顺铂联合多西紫杉醇组(32例),观察3组的治疗效果和副反应,并进行比较.结果:外照射结束时3组的有效率分别为96.67%、100%及100%,差异无统计学意义(P＞0.05);顺铂组的4年生存率、局部复发率、远处转移率与另两组比较,差异有统计学意义(P＜0.05);多西紫杉醇组与顺铂联合多西紫杉醇组差异无统计学意义(P＞0.05);顺铂组及顺铂联合多西紫杉醇组有较明显的骨髓抑制和消化道反应,而且肾功损害明显,与多西紫杉醇组比较差异有统计学意义(P＜0.05).结论:多西紫杉醇单药同步放化疗与顺铂单药及两药联合同步放化疗比较,能明显提高患者的生存率,降低局部复发率及远处转移率,同时副反应相对较轻.     

局部晚期宫颈癌临床治疗新进展

宫颈癌是严重威胁女性健康的恶性肿瘤之一,其中局部晚期宫颈癌（LACC）有病灶大、手术困难、预后差等特点,关于其治疗方案争议不断,主要推荐的治疗方案有：盆腔外照射+顺铂同期化疗+阴道近距离放疗,广泛性子宫切除术+盆腔淋巴结切除±主动脉旁淋巴结取样,放化疗后进行辅助性子宫切除术。而在临床治疗中,由于各地区放疗水平不同和患者个体化差异,目前对LACC的治疗方案仍存在多样性。预防性半扩展区域调强适形放疗可以在达到与传统扩展区域放疗相似治疗效果的同时减少并发症的发生,同步放化疗同时加局部热疗可以增强患者对治疗的耐受性。腹主动脉旁淋巴结清扫或活检不一定改善LACC的预后,但可帮助判断预后,对已有髂总动脉旁淋巴结转移的患者有积极意义。对于腔内放疗技术不成熟地区的患者,盆腔外照射加同步化疗后行Ⅰ型筋膜外子宫切除术是可行的治疗方案。