乳腺癌发病风险及侵袭特性与白细胞介素-8和CXCR2基因多态性的关系

目的 探讨细胞因子白细胞介素( 1L)-8(- 251)位点及其受体CXCR2(±1208)位点多态性与乳腺癌发病风险及侵袭特性的关系.方法 采用等位基因特异-聚合酶链反应(AS-PCR)分析方法检测228名乳腺癌患者和100例健康对照者的IL-8(- 251)位点及其受体CXCR2(±1208)位点多态性分布,并进行统计学分析.结果 IL-8(- 251)位点TA型和AA型以及CXCR2(± 1208) TT型是乳腺癌的高危基因型[比值比(OR)=1.57,95％可信区间(CI)=1.08～2.32;OR =2.68,95％ CI=1.26 ～2.99;0R=2.02,95％CI=1.08～3.62],在两组间表达频率的差异有统计学意义(P＜0.05).携带1个及以上高危基因型增加患乳腺癌的风险.分层分析表明携带IL-8(-251)等位基因A和CXCR2(± 1208)等位基因T增加乳腺癌的侵袭特性,其分布频率在肿瘤的高组织学分级(OR=1.95,P＜0.01;OR=1.52,P＜0.05)和淋巴结转移阳性(OR=1.65,P＜0.05;0R=1.66,P＜0.01)中差异有统计学意义.另外,IL-8(-251)A等位基因与ER( -)乳腺癌显著相关( OR=1.65,P＜0.05).结论 IL-8和CXCR2的基因多态性可能与女性乳腺癌的发生发展关系密切,可作为乳腺癌早期基因诊断的指标.     

乳腺癌分子亚型在预测新辅助化疗疗效及患者预后中的作用

目的 本研究旨在探讨乳腺癌的分子亚型与乳腺癌的病理完全缓解及患者预后的关系.方法 收集2007年1月-2010年1月在芜湖市第二人民医院接受新辅助治疗的101例乳腺癌患者的病例资料,按照ER、PR及Her-2的免疫组化的结果将其分为4型,单因素与多因素分析临床病理因素与病理完全缓解的关系.结果 19例(18.8％)患者取得病理完全缓解,三阴性乳腺癌是病理完全缓解的独立预测因素(OR=3.35,95％CI:1.25 ～ 9.79,P=0.012),而Her-2丰富型乳腺癌相比较于luminal A型乳腺癌则取得更高的病理完全缓解率(OR =3.11,95％CI:1.09 ～ 10.89,P=0.021).而病理缓解率与无病生存率密切相关(P =0.002).但三阴性乳腺癌的总生存期和无病生存期更短(P =0.008,P=0.0006).结论 三阴性乳腺癌和Her-2丰富型乳腺癌较luminal A型乳腺癌更容易获得新辅助化疗后的病理完全缓解,但三阴性乳腺癌的预后仍然较差,可能与其在治疗后仍有肿瘤残留有关.     

化疗及靶向药物治疗肉瘤样肾癌的Meta分析

目的 系统评价化疗及靶向药物治疗肉瘤样肾癌的有效性和安全性.方法 计算机检索PubMed、中国期刊全文数据库(CN KI)等,收集2000年1月～2013年12月国内外公开发表的有关化疗及靶向药物治疗肉瘤样肾癌的试验研究文献.根据Cochrane的质量评价标准评价,采用RevMan4.2软件进行统计学分析.结果 最终纳入5个文献,共128例患者.meta分析结果显示与化疗相比,靶向药物联合化疗不但显著提高了肉瘤样肾癌的疾病控制率(OR =2.11,95％ CI:1.30 ～2.61,P＜0.0001),还显著提高了有效率(OR =2.25,95％ CI:1.53 ～3.11,P＜0.0001).结论 与化疗相比,靶向药物联合化疗可进一步提高疗效,是肉瘤样肾癌较好的治疗方案.     

脑卒中后睡眠障碍影响因素的Meta分析

目的 探讨脑卒中后睡眠障碍的影响因素.方法 在PubMed、Embase、Cochrane Library、Web of Science、中国知网、万方数据知识服务平台、维普网和中国生物医学文献数据库搜索相关文献,检索时限为建库至2021年1月3日,采用RevMan 5.3软件进行Meta分析.结果 共纳入10项研究,其中8项横断面研究、2项队列研究,共2 938例患者.Meta分析结果显示,卒中史[OR=1.30,95％CI(1.07～1.60)]、高血压[OR=2.20,95％CI(1.80～2.68)]、糖尿病[OR=1.55,95％CI(1.32～1.83)]、冠心病[OR=1.34,95％CI(1.09～1.65)]、高脂血症[OR=1.36,95％CI(1.14～1.62)]、吸烟史[OR=1.36,95％CI(1.07～1.73)]是脑卒中后睡眠障碍的主要影响因素(P＜0.05,P＜0.01).结论 脑卒中患者发生睡眠障碍的影响因素较多,应采取针对性措施预防和降低卒中后睡眠障碍的发生和发展.     

化疗对乳腺癌患者骨髓抑制的临床分析

目的：评估化疗后乳腺癌患者发生骨髓抑制的风险。方法：对219例乳腺癌患者化疗前后的部分血液学的指标进行比较,并探讨可能与骨髓抑制相关的危险因素。结果：化疗后患者的WBC、N、HB及PLT数值均下降;与骨髓抑制相关的主要因素有：骨髓转移（OR=2.395,P=0.04）、BMI（OR=0.279,P=0.008）、肿瘤分级（OR=2.876,P〈0.001）及化疗周期（OR=4.639,P=0.006）。结论：根据对骨髓抑制相关因素的评估,临床医生可预测乳腺癌患者发生骨髓抑制风险的大小,从而及时地进行预防或纠正。     

结直肠癌化疗患者自我同情发展轨迹及影响因素分析

目的 探讨结直肠癌化疗患者自我同情发展轨迹的类别及影响因素,为针对性干预提供参考。方法 选取179例结直肠癌化疗患者作为研究对象,采用一般资料调查表、自我同情量表、医院焦虑抑郁量表分别于化疗前(T1)、第1个周期化疗后(T2)、第3个周期化疗后(T3)及第6个周期化疗后(T4)进行追踪调查。采用潜类别增长分析模型识别自我同情变化轨迹的潜在类别,logistic回归分析其影响因素。结果 患者的自我同情变化轨迹可分为低水平上升组(45.8%)、高水平稳定组(23.5%)、中水平降低组(30.7%)。logistic回归分析结果显示,年龄、文化程度、家庭人均月收入、肿瘤临床分期、有无造口影响自我同情的轨迹类别(均P<0.05)。结论 结直肠癌化疗患者自我同情分为3种变化轨迹,自我同情存在群体异质性,应基于患者自我同情变化轨迹有针对性地进行评估和干预。     

慢性肾脏病4～5期患者睡眠质量的随访研究

目的探讨慢性肾脏病(chronic kidney diseases,CKD)4期、维持性血液透析(maintenance hemodialysis,MHD)和持续非卧床腹膜透析(continuous ambulatory peritoneal dialysis,CAPD)患者睡眠质量的动态变化及其影响因素。方法选择我科住院并接受随访的128例患者,其中CKD4期(CKD 4期组)患者43例、MHD患者(MHD组)41例、CAPD患者(CAPD组)44例,随访1年,每6个月用匹兹堡睡眠指数量表评估睡眠质量,并记录实验室指标。单因素及多因素Logistic分析睡眠质量的影响因素。结果 3组患者间年龄、性别、社会经济因素、吸烟、体质量指数、Charlson合并症指数、原发肾脏病无统计学差异(P0.05)。基线和第6个月时,MHD组和CAPD组的睡眠质量总分均显著高于CKD 4期组(P0.05)。随访第12个月时,3组间睡眠质量总分无统计学差异(P0.05)。同基线值相比,随访第6个月时3组睡眠质量总分均显著升高(P0.05)。同随访第6个月时相比,随访第12个月时CKD 4期组睡眠质量总分显著升高(P0.05),透析组无显著改变(P0.05)。随着患者PSQI总分的动态变化,3组患者血红蛋白、钙磷乘积、全段甲状旁腺素和超敏C反应蛋白也发生改变。年龄(OR=1.83,P=0.01)、血红蛋白(OR=1.46,P=0.01)、钙磷乘积(OR=1.25,P=0.02)、全段甲状旁腺素(OR=1.17,P=0.03)、超敏C反应蛋白(OR=1.32,P=0.04)与睡眠质量差显著相关。结论 CKD 4期以上患者睡眠质量随着时间的推移逐渐恶化,老年、贫血、钙磷代谢紊乱及微炎症反应是影响睡眠质量差的独立危险因素。     

乳腺癌患者Ki-67表达水平对新辅助化疗后病理学完全缓解的预测价值

目的:探讨乳腺癌患者Ki-67表达水平对新辅助化疗(NAC)疗效的影响。方法:收集261例行NAC且临床病理资料相对完整的乳腺癌患者,分析患者Ki-67表达以及其他临床病理因素包括分子分型、激素受体状态等与患者NAC后病理学完全缓解(pCR)的关系。结果:单因素分析结果显示,患者NAC后pCR与孕激素受体(PR)及表皮生长因子受体2(Her-2)状态、分子分型与Ki-67水平明显有关(均P0.05);多因素分析显示,Ki-67表达水平是NAC后pCR独立预测因素(OR=5.476,95%CI=2.637~11.372,P0.05)。此外,在雌激素受体(ER)阳性患者中,Ki-67高表达患者pCR率为低表达患者的4.282倍(OR=4.282,95%CI=1.694~10.825,P=0.002),而PR阳性患者pCR率为阴性患者的0.303倍(OR=0.303,95%CI=0.113~0.810,P=0.017),Her-2阳性者的pCR率是Her-2阴性者的2.607倍(OR=2.607,95%CI=1.023~6.642,P=0.045)。结论:乳腺癌患者Ki-67高表达是NAC后高pCR率的预测因子,同时结合其他激素受体状态,将有助于更好的指导个体化NAC。     

原发性乳腺癌患者创伤后成长的纵向调查

目的了解和分析原发性乳腺癌患者不同治疗阶段创伤后成长的变化,为临床及延续护理提供参考。方法采用创伤后成长评定量表对80例原发性乳腺癌患者于手术前1d(T1)、手术后第3天(T2)、术后首次化疗(T3)及末次化疗(T4)进行调查。结果患者T1~T4的创伤后成长得分依次为83.04±20.90、62.84±19.21、59.58±13.78、67.85±13.51;不同时段总分及各维度得分比较,差异有统计学意义(P0.05,P0.01)。结论手术及化疗对患者的创伤后成长造成一定负性影响,随化疗结束及治疗效果的显现,患者创伤后成长呈上升趋势,护理人员应根据其特点实施针对性干预,以有效地提升其创伤后成长水平。     

乳腺癌对患者配偶性功能的影响

目的:了解女性乳腺癌患者配偶的性行为及性功能变化与临床变量和社会人口学变量之间的潜在关系。方法:采用横断面研究,2020年5月至2020年10月收集病例,共纳入196例23～59岁的女性乳腺癌患者的男性配偶。通过在线问卷或电话访问方式,填写男性性功能问卷(BSFI),并收集社会人口学变量和临床变量。结果:受访者年龄(46.13±7.75)岁,至调查时患者患癌时间(1.58±0.48)年。受访者性功能障碍发生率在患者患癌前(9.68%)后(49.76%)存在显著差异(P<0.001);主要类型是性欲低下(38.3%)。患者接受乳腺根治性切除术(OR=5.533,P=0.017,95%CI=1.366～22.412)和接受放疗者(OR=3.439,P<0.044,95%CI=1.058～11.171)其配偶出现性欲低下问题概率更高。受访者性欲低下的发生率的受自身年龄(OR=1.134,P=0.001,95%CI=1.053～1.222)影响显著。结论:女性患乳腺癌及治疗情况可能影响配偶性功能状态。医务工作者有必要对影响患者及其配偶性功能的因素加以关注,以采取相应的干预措施。     

Vasopressor hormone response following mesenteric traction during major abdominal surgery

Background : We investigated the vasopressor hormone response following mesenteric traction (MT) with hypotension due to prostacyclin (PGI₂) release in patients undergoing abdominal surgery with a combined general and epidural anesthesia. Methods : In a prospective, randomized, placebo-controlled study we administered 400 mg ibuprofen (i.v.) in 42 patients scheduled for abdominal surgery. General anesthesia was combined with epidural anesthesia (T4-L1). Before as well as 5, 15, 30, 45, and 90 min after MT we recorded plasma osmolality, hemodynamics and measured 6-keto-PGFlα (stabile metabolite of PGI₂), TXB₂ (stabile metabolite of thromboxane A₂) active renin, and arginine vasopressin (AVP) plasma concentrations by radioimmunoassay. Catecholamine levels were assessed by high-pressure liquid chromatography (HPLC) with electrochemical detection. Results : Following MT, arterial hypotension occurred along with a substantial PGI₂ release. This was completely abolished by ibuprofen administration. Although plasma levels of 6-keto-PGF_1α (1133 (708) vs. 60 (3) ng/L, median (median absolute deviation), P=0.0001, placebo vs. ibuprofen) remained significantly elevated, blood pressure was restored within 30 min after MT in the placebo group. At the same point in time plasma concentrations of TXB² (164 (87) vs. 58 (1) ng/L, P=0.0001), epinephrine (46 (33) vs. 14 (6) ng/L, P=0.001), AVP (41 ± (18) vs. 12 (7) ng/L, P=0.0004), and active renin (27 (12) vs. 12 (4) ng/L, P = 0.001) were significantly higher in placebo-treated patients. Conclusion : Under combined general and epidural anesthesia arterial hypotension following MT due to endogenous PGI₂ release is associated with enhanced release of AVP, active renin, epinephrine and thromboxane A₂, presumably contributing to hemodynamic stability within 30 min after MT.     

A Teaspoon Pump for Pumping Blood with High Hydraulic Efficiency and Low Hemolysis Potential

Abstract: Virtually all blood pumps contain some kind of rubbing, sliding, closely moving machinery surfaces that are exposed to the blood being pumped. These valves, internal bearings, magnetic bearing position sensors, and shaft seals cause most of the problems with blood pumps. The original teaspoon pump design prevented the rubbing, sliding machinery surfaces from contacting the blood. However, the hydraulic efficiency was low because the blood was able to "slip around" the rotating impeller so that the blood itself never rotated fast enough to develop adequate pressure. An improved teaspoon blood pump has been designed and tested and has shown acceptable hydraulic performance and low hemolysis potential. The new pump uses a nonrotating "swinging" hose as the pump impeller. The fluid enters the pump through the center of the swinging hose; therefore, there can be no fluid slip between the revolving blood and the revolving impeller. The new pump uses an impeller that is comparable to a flexible garden hose. If the free end of the hose were swung around in a circle like half of a jump rope, the fluid inside the hose would rotate and develop pressure even though the hose impeller itself did not "rotate"; therefore, no rotating shaft seal or internal bearings are required.     

Microspheres Based Detoxification System: A New Method in Convective Blood Purification

Abstract: A variety of protein-bound or hydrophobic substances, accumulating as a result of pathologic conditions such as exogenous or endogenous intoxications, are removed poorly by conventional detoxification methods because of low accessibility (hemodialysis), insufficient adsorption capabilities (hemosorption), low efficiency (peritoneal dialysis), or economic limitations (high-volume plasmapheresis). Combining advantages of existing methods with microspheric technology, a module-based system was designed. Major operating parameters of the latter can be modified to allow for adjustment to individual clinical situations. An extracorporeal blood circuit including a plasmafilter is combined with a secondary high-velocity plasma circuit driven by a centrifugal pump. Different microspheric adsorbers can be combined in one circuit or applied in sequence. Thus, a prolonged treatment can be tailored using specially designed selective adsorber materials. Comparing this system with existing methods (high-flux hemodialysis, molecular adsorbent recycling system), results from our in vitro studies and animal experiments demonstrate the superior efficiency of substance removal.     

Tissue perfusion in relation to cardiac output during continuous positive-pressure ventilation and administration of propranolol or verapamil

Background : Our objective was to determine whether administration of propranolol or verapamil modifies the hemodynamic adaptation to continuous positive-pressure ventilation (CPPV), in particular the regional distribution of cardiac output (CO).
Methods : General hemodynamics and regional blood flows assessed by microsphere technique (15 (μm) were recorded in 16 anesthetized pigs during spontaneous breathing (SB) and CPPV with 8 cm H₂O end-expiratory pressure (CPPV8) before and after intravenous administration of propranolol (0.3 mg · kg⁻¹ followed by 0.15 mg · kg⁻¹ · h⁻¹, n=8) or verapamil (0.1 mg · kg⁻¹ followed by 0.3 mg · kg⁻¹ · h⁻¹, n=8).
Results : CPPV8 depressed CO by 25% without shifts in its relative distribution with the exception of a noteworthy increase in adrenal perfusion. Propranolol increased arterial blood pressure, and due to a fall in heart rate, CO dropped by 25%. The kidneys and, to a lesser extent, the splanchic region and central nervous system received increased fractions of the remaining CO at the expense of skeletal muscle flow. Similar patterns were seen during SB and CPPV8 such that the combination of propranolol and CPPV8 depressed CO by 50%. The circulatory effects of verapamil were less evident but myocardial perfusion tended to increase.
Conclusions : The combination of propranolol or verapamil with CPPV does not result in any specific hemodynamic interaction in anesthetized pigs, except that the combined effect of propranolol and CPPV may severely reduce CO.     

Volatile anaesthetics reduce adhesion of blood platelets under low-flow conditions in the coronary system of isolated guinea pig hearts

Background : Inhibitory effects of volatile anaesthetics on platelet aggregation have been demonstrated in several studies. However, the influence of volatile anaesthetics on intracoronary platelet adhesion has not been elucidated so far.
Methods : Isolated hearts of guinea pigs were perfused with buffer in the absence or presence of volatile anaesthetics (0.5 and 1 MAC) at constant coronary flow rates of 5 ml/min for 25 min, then 1 ml/min for 30 min and again 5 ml/min for 10 min. Before, during and after low-flow perfusion, a bolus of human platelets was applied into the coronary system. To simulate thrombogenic conditions, 0.3 U/ml human thrombin was infused during low-flow perfusion and reperfusion. The number of platelets sequestered to the endothelium was calculated from the difference between coronary in- and output of platelets. The myocardial production of lactate and consumption of pyruvate and coronary perfusion pressure were also determined.
Results : At a flow rate of 5 ml/min only about 3% of the applied platelets did not emerge from the coronary system, in any group. In contrast, 13.1±1.2% (mean±SEM) of infused platelets became adherent in low-flow perfusion in the control group without anaesthetic. The adherence was reduced with each 1 MAC isoflurane (to 6.2±1.2%), sevoflurane (to 4.4±0.9%) or halothane (to 3.2±1.5%) (each P <0.05 vs. control). Volatile anaesthetic, 0.5 MAC, did not inhibit platelet adhesion to a statistically significant extent in any case. Perfusion pressure and metabolic parameters were not statistically different between the control and the hearts exposed to anaesthetics.
Conclusion : Volatile anaesthetics in a concentration of 1 MAC can reduce the adhesion of platelets in the coronary system under reduced flow conditions. This action does not arise from vasodilation or inhibition of ischaemic stress.     

Bariatric Surgery in Some "Central and East-European (former Eastern bloc)"Countries - Current Status and Prediction for the Next Millennium

Background: Obesity is increasing globallly, including in the formerly "Eastern Bloc" countries. Methods: A survey was made of obesity and bariatric surgery. Results: In the 8 East and Central European countries studied, with total population 300 million, roughly 43% of the population was overweight (BMI 25-30), 23% obese (BMI > 30), with about 15 million people morbidly obese (BMI > 40). From 0-10 morbidly obese individuals/100,000/year undergo bariatric surgery. Conclusion: Most countries were found to provide inadequate treatment for obesity.The majority of the morbidly obese are not treated effectively. However, health-care awareness of obesity and bariatric surgeons are slowly increasing.     

Is the recovery profile of mivacurium independent of the rate of decay of its plasma concentration in patients with normal plasma cholinesterase activity?

Background: The duration of action of muscle relaxants is poorly correlated to the rate of decay of their plasma concentration. The plasma concentration of mivacurium may rapidly decrease below its active concentration because of the extensive hydrolysis of mivacurium. By inflating a tourniquet on one upper limb for 3 min after the administration of atracurium, mivacurium or vecuronium, we studied the influence of the initial decline of their plasma concentration on their effect. Methods: In 50 patients anaesthetised with thiopental, isoflurane and fentanyl, the effect of bolus doses of 0.15 or 0.25 mg . kg^?1 mivacurium (MIV 15, MIV 25), 0.3 or 0.5 mg . kg^?1 atracurium (ATR 30, ATR 50) and 0.06 or 0.1 mg . kg^?1 vecuronium (VEC 06, VEC 10) were measured on both arms (evoked response of the adductor pollicis to train-of-four stimulation every 12 s), a tourniquet being applied on one arm just before and during 3 min after the muscle relaxant bolus. Results: Tourniquet inflation of 3 min almost abolished the neuromuscular effect of mivacurium. In the vecuronium groups and in the ATR 50 group, tourniquet inflation did not modify the maximum degree of depression of the twitch response. Also, the duration of action of vecuronium was unaffected by the tourniquet. In the ATR 30 group, times to return of the twitch response to 25% (duration 25%) and 75% (duration 75%) of control response were significantly shorter in the cuffed arm, 23 min vs 27 min, and 41 min vs 45 min, respectively. In the ATR 50 group, only duration 25% was significantly shorter in the cuffed arm (41 min vs 45 min). Conclusion: The results suggest that the rate of decline of the plasma concentration of mivacurium is so rapid, that a very low and almost clinically ineffective concentration is present as soon as 3 min after its administration. The results also indicate that the recovery from a mivacurium-induced neuromuscular blockade is not influenced by the rate of decay of its plasma concentration in patients with genotypically normal plasma cholinesterase.     

Membranes in Artificial Organs

Abstract: Membrane processes play a pivotal and enabling role in modern replacement therapy for acute and chronic organ failure and in the management of immunologic diseases. In fact, virtually all contemporary extracorporeal blood purification methods employ membrane devices, and the next generation of artificial organs and tissue engineering therapies are almost certain to be similarly grounded in membrane technology. In this short essay, we comment on the similarities and differences among synthetic membranes and their natural counterparts and also provide a critical overview of the demographics and technology of hemodialysis, hemofiltration, apheresis, oxygenation, and emerging membrane technologies and applications.     

Influence of dopexamine hydrochloride on haemodynamics and regulators of circulation in patients undergoing major abdominal surgery

Background: Catecholaminergic support is often used to improve haemodynamics in patients undergoing major abdominal surgery. Dopexamine is a synthetic vasoactive catecholamine with beneficial microcirculatory properties. Methods: The influence of perioperative administration of dopexamine on cardiorespiratory data and important regulators of macro- and microcirculation were studied in 30 patients undergoing Whipple pancreaticduodenectomy. The patients received randomized and blinded either 2 μg · kg^?1 · min^?1 of dopexamine (n=15) or placebo (n=15, control group). The infusion was started after induction of anaesthesia and continued until the morning of the first postoperative day. Endothelin-1 (ET-1), vasopressin, atrial natriuretic peptide (ANP), and catecholamine plasma levels were measured from arterial blood samples. Measurements were carried out after induction of anaesthesia, 2 h after onset of surgery, at the end of surgery, 2 h after surgery, and on the morning of the first postoperative day. Results: Cardiac index (CI) increased significantly in the dopexamine group (from 2.61±0.41 to 4.57±0.78 1 · min^?1 · m^?2) and remained elevated until the morning of the first postoperative day. Oxygen delivery index (DO₂I) and oxygen consumption index (VO₂I) were also significantly increased in the dopexamine group (DO₂I: from 416±91 to 717±110 ml/m² · m²; VO₂I: from 98±25 to 157±22 ml/m² · m²), being significantly higher than in the control group. pHi remained stable only in the dopexamine patients, indicating adequate splanchnic perfusion. Vasopressive regulators of circulation increased significantly only in the untreated control patients (vasopressin: from 4.37±1.1 to 35.9±12.1 pg/ml; ET-1: from 2.88±0.91 to 6.91±1.20 pg/ml). Conclusion: Patients undergoing major abdominal surgery may profit from prophylactic perioperative administration of dopexamine hydrochloride in the form of improved haemodynamics and oxygenation as well as beneficial influence on important regulators of organ blood flow.     

Synergistic interaction between the effects of propofol and midazolam with fentanyl on phrenic nerve activity in rabbits

Background: It has been shown that the depressive effects of both propofol and midazolam on consciousness are synergistic with opioids, but the nature of their interactions on other physiological systems, e. g. respiration, has not been fully investigated. The present study examined the effect of propofol and midazolam alone and in combination with fentanyl on phrenic nerve activity (PNA) and whether such interactions are additive or synergistic. Methods: PNA was recorded in 27 anaesthetised and artificially ventilated rabbits. In three groups, propofol, fentanyl and midazolam were administered intravenously in incremental doses to construct dose-response curves for the depressant effects of each one on PNA. In another two groups, the effect of pretreatment with either fentanyl 1 μg · kg^?1 i. v. or midazolam 0.05 mg · kg^?1 i. v. on the effects of propofol and fentanyl respectively on PNA were studied. Results: Propofol and fentanyl caused a dose-dependent depression of PNA with complete abolition at the highest total doses of 16 mg · kg^?1 i. v. and 32 μg · kg^?1 i. v., respectively. In contrast, midazolam in incremental doses to a total of 0.8 mg · kg^?1 reduced mean PNA by 63%, but approximately 12% of PNA remained at a total dose as high as 6.4 mg · kg^?1. The mean ED₅₀s, calculated from dose-response curves, were 5.4 mg · kg^?1, 3.9 μg · kg^?1 and 0.4 mg · kg^?1 for propofol, fentanyl and midazolam, respectively. Initial doses of either fentanyl 1 μg · kg^?1 i. v. or midazolam 0.05 mg · kg^?1 i. v. acted synergistically with subsequent doses of either propofol or fentanyl to abolish PNA at total doses of 8 mg · kg^?1 and 8 μg · kg^?1, respectively. Conclusion: Fentanyl has a synergistic interaction with both propofol and midazolam on PNA and hence potentially on respiration.