经腹膜外腹腔镜前列腺癌根治术（附9例报告）

目的探讨经腹膜外腹腔镜前列腺癌根治术的手术方法和疗效。方法我科自2006年1月至2008年10月对9例前列腺癌患者行经腹膜外途径腹腔镜前列腺癌根治术,手术经腹膜外路径顺行切除前列腺,切开膀胱颈部前先以1-0可吸收线缝扎背血管复合体。结果9例手术均获得成功,无中转开放手术。手术时间180-510min,平均322min,术中出血量200-1500ml,平均433ml,术后48h内胃肠功能恢复,术后2～3d下床活动,无直肠损伤和吻合口尿漏出现。标本切缘阳性1例。1例患者术后半年仍有轻度尿失禁。其中7例患者随访5～33个月,未发现肿瘤局部和生化复发和远处转移;术后3个月前列腺特异性抗原0～0．1ng／ml。结论经腹膜外腹腔镜前列腺癌根治术是一种安全有效的手术方法,手术创伤小,患者恢复快,腹腔并发症少。但该手术难度较大,需要具有丰富腹腔镜操作经验的医生完成。     

经腹膜外腹腔镜前列腺癌根治术的关键点及操作技巧（附33例报告）

目的：总结经腹膜外腹腔镜前列腺癌根治术治疗前列腺癌的手术经验和操作技巧.方法：2006年1月～2010年3月对33例前列腺癌患者行经腹膜外腹腔镜前列腺癌根治术,手术经腹膜外顺行路径切除前列腺,切开膀胱颈部前先以1-0可吸收线缝扎背血管复合体,采用单针连续吻合法进行膀胱与尿道的吻合.结果：33例手术均获得成功,无中转开放手术.手术时间120～575 min,平均234 min,术中出血量100～1500 ml,平均320 ml,术后48小时内胃肠功能恢复,术后1～2天下地活动,没有直肠损伤和吻合口尿漏出现.标本切缘阳性1例.2例术后出现轻度尿失禁.2例出现尿道狭窄.对其中31例患者随访3～51个月,未发现肿瘤局部和生化复发和远处转移;术后3个月前列腺特异性抗原0～0.1 μg/L.结论：经腹膜外腹腔镜前列腺癌根治术是一种安全有效的手术方法.熟悉前列腺局部解剖及熟练掌握各种腹腔镜下操作技术是手术成功的关键.     

经腹膜外途径腹腔镜前列腺癌根治术23例观察

目的探讨经腹膜外途径腹腔镜前列腺癌根治术(laparoscopic radical prostatectomy,LRP)治疗局限性前列腺癌的手术方法和临床疗效。方法回顾性分析23例前列腺癌患者行经腹膜外途径腹腔镜前列腺癌根治术的临床资料。23例患者病理诊断均为前列腺癌,TNM分期T1N0M0 9例,T2N0M0 14例,Gleason评分均≤7分。结果 23例手术均获得成功,无中转开放手术。手术时间105³00 min,平均150 min;术中出血量120300 min,平均150 min;术中出血量120⁸00 mL,平均240 mL。术后留置尿管时间16800 mL,平均240 mL。术后留置尿管时间16²2 d,平均18 d。3例出现轻度尿失禁,经提肛等辅助治疗,3个月后无真性尿失禁发生。术后病理报告示标本切缘阳性1例,术后行全激素阻断治疗3个月。术后前列腺特异性抗原(prostate specific antigen,P S A)均<4.0 ng/mL。1例因其他原因死亡。术后随访322 d,平均18 d。3例出现轻度尿失禁,经提肛等辅助治疗,3个月后无真性尿失禁发生。术后病理报告示标本切缘阳性1例,术后行全激素阻断治疗3个月。术后前列腺特异性抗原(prostate specific antigen,P S A)均<4.0 ng/mL。1例因其他原因死亡。术后随访3¹2个月,无生化复发。结论经腹膜外腹腔镜前列腺癌根治术具有创伤小,出血少,恢复快,并发症少等优点,是一种安全可行的手术方式,值得临床推广。     

腹膜外入路腹腔镜下前列腺癌根治术41例

目的熟悉腹膜外入路腹腔镜下前列腺癌根治术的手术方法,降低前列腺癌根治术的手术并发症的发生率。方法对2005年11月至2012年6月的41例腹腔镜下前列腺癌根治术患者的临床资料进行回顾性分析,患者年龄65-78岁,平均72岁,所有患者术前均获确诊,前列腺特异性抗原3.4-45.6ng/ml,〈4.0ng/ml3例,4-20ng/ml30例,〉20ng/ml8例。结果除1例中转开腹手术,其余均由腹腔镜完成,手术时间65-240min,平均125min,术中出血量80-700ml,平均120ml。术后轻度尿失禁6例,通过尿道括约肌锻炼后1-3个月后可满意控尿,术中保留性神经26例,其中19例术后勃起功能恢复,可以完成性交。术后病理均证实为前列腺癌,Gleason评分4-9分,切缘阳性1例,术后加用内分泌治疗。术后随访2个月-6年,生化复发9例,予内分泌治疗后控制满意,1例因其他疾病死亡。结论腹膜外入路腹腔镜前列腺癌根治术是治疗前列腺癌的重要方法,把握好关键步骤,仔细操作,可以达到安全、有效、创伤小的目的。     

经腹膜外腹腔镜下前列腺癌根治术及其控尿技术

目的 探讨腹膜外途径腹腔镜前列腺癌根治术及其控尿技术的应用价值。方法 前列腺癌患者28例，年龄60～75岁，平均68岁。PSA0．7～23．6ng／ml。TNM分期：T1N0M011例，T2N0M015例，T3aN0M2例。均行腹膜外途径腹腔镜前列腺癌根治术。，术中充分剪开盆筋膜，分离至前列腺尖部，缝扎背血管复合体。分离膀胱颈部（前列腺交界处），横断并尽可能保护颈部括约肌。仔细观察盆底肌肉并于近端剪开前列腺尖部，尽可能保护盆底括约肌，最后缩小并重建膀胱颈口，间断吻合膀胱和尿道。结果 28例手术均顺利完成，手术时间180～380min，平均240min；出血量400～1200ml，平均800ml，15例出血量〉500ml者输血200～800ml。术后病理示切缘阴性25例，3例前列腺尖部切缘阳性者术后加用全雄激素阻断治疗3个月。患者均于术后2周拔除导尿管，3例术后出现轻度尿失禁，经提肛训练等辅助治疗3个月后好转，能自主排尿。术后3个月时PSA0．02～0．10ng／ml。随访1个月～2年，未见肿瘤复发转移。结论 腹腔镜下经腹膜外途径前列腺癌根治术安全、有效，值得临床推广。     

经腹膜外入路腹腔镜前列腺癌根治术(附16例报告)

目的总结经腹膜外入路腹腔镜前列腺癌根治术的临床体会。方法回顾性分析2010年10月至2011年12月,采用四孔经腹膜外入路行腹腔镜前列腺癌根治术治疗局限性前列腺癌患者16例的临床资料。结果本组16例手术全部顺利完成,9例同期行盆腔淋巴结清扫术,无一例中转开放。手术时间150～420min,平均270min。术中出血量50～2000ml,平均534ml,4例术中输血400～800ml,输血率25%。术后病理报告切缘阳性1例(6.2%)。术后4～15d出院,平均8d。所有患者留置尿管2周,拔除尿管后无真性尿失禁。随访3～17个月,8例昼夜控尿良好,8例白天偶有压力性尿失禁,其中1例术后4个月出现吻合口狭窄。9例患者术后可勃起,其中1例行保留神经的前列腺癌根治术患者术后1个月可正常进行性生活。结论经腹膜外入路腹腔镜前列腺癌根治术具有创伤小、出血少、操作容易、并发症少等优点,是开展腹腔镜前列腺癌根治术的较好选择。     

腹膜外径路腹腔镜前列腺癌根治术(附12例报告)

目的探讨腹膜外途径腹腔镜前列腺癌根治术的临床效果。方法回顾性分析总结2009年5月至2011年7月经腹膜外径路进行腹腔镜前列腺癌根治术患者12例,年龄60～75岁,平均年龄68岁。血清前列腺特异性抗原(prostate specific antigen,PSA)为0.7～23.6ng/ml。TNM分期T1N0M08例,T2N0M03例,T3aN0M01例。所有患者均于术前行前列腺穿刺活组织检查,证实为前列腺癌。结果 12例患者均顺利完成手术,手术时间为130～360min,平均270min;术中出血量为150～900ml,平均390ml,1例患者术中输血。术后病理检查结果显示肿瘤切缘为阳性的2例患者术后加用全雄激素阻断治疗3个月。术后留置尿管时间14～22d,平均18.6d,无直肠损失病例,3例术后出现轻度尿失禁的患者经提肛训练等辅助治疗3个月后好转,能自主排尿。术后3个月时PSA为0.02～0.10ng/ml,术后随访8例,随访时间为3～24个月,未发现肿瘤局部复发和远处转移。结论腹膜外径路腹腔镜前列腺癌根治术视野清晰、创伤小、恢复快,是一种安全、有效的治疗方法,值得临床推广。     

腹膜外腹腔镜下前列腺癌根治术106例报告

目的评估经腹膜外入路的腹腔镜下前列腺癌根治术的手术技巧、并发症情况和临床疗效。方法回顾性分析自2010年1月至2013年9月间,在我院行腹膜外腹腔镜下前列腺癌根治术治疗的106例患者的临床和病理资料。全组患者术前均无远处转移,术后均在门诊随访,由术者指导盆底肌锻炼,促进控尿功能恢复。结果患者年龄55~77岁,平均65岁。术前PSA3.2~55.8ng/mL。手术时间105~390min,时间长于240min的6例患者均发生在本组最初20例中。3例(2.8%)转开放手术,4例(3.8%)术中在腔镜下留置了输尿管支架管。术后早期并发症包括吻合口漏15例,闭孔神经麻痹1例,淋巴瘘3例,下肢深静脉血栓形成1例,均保守治疗治愈。75例(70.8%)术后3个月内恢复控尿功能,余者在3个月至1年时恢复控尿功能。结论腹膜外腹腔镜下前列腺癌根治术的手术操作较复杂,但经过20例以上的操作,就可以掌握其关键技术,可获得和开放手术相似的肿瘤学控制率和术后控尿功能。     

腹腔镜前列腺癌根治术42例报告

目的:探讨腹腔镜前列腺癌根治术(laparoscopic radical prostatectomy,LRP)治疗局限性前列腺癌的可行性并总结临床体会。方法:回顾分析2008年12月至2011年3月为42例前列腺癌患者行腹膜外入路腹腔镜前列腺癌根治术的临床资料。结果:42例手术均获成功,无一例周围脏器损伤。手术时间120～250 min,平均170 min。术中出血量120～750 ml,平均260 ml,11例术中输血400～600 ml。术后住院21～23 d,平均22 d。拔除导尿管时间18～22 d,平均20 d。6例患者术后7天内发生尿漏,均经充分引流和牵拉尿管后痊愈。25例出现轻～中度尿失禁,经提肛等辅助治疗,4～12周后明显缓解或消失。术后病检:pT1c14例,pT212例,pT3a16例。术后PSA均<4.0 ng/ml。结论:经腹膜外入路行腹腔镜前列腺癌根治术可行、安全、有效,患者创伤小、康复快、并发症少,值得推广应用。     

3D腹腔镜下前列腺癌根治术34例分析

目的 探讨经腹膜外3D腹腔镜下前列腺癌根治术的优缺点. 方法 收集分析2014年1月至2015年4月于我科行经腹膜外Storz及Viking 3D腔镜下前列腺癌根治术的34例患者的相关临床资料. 结果 34例手术均成功.手术时间78～195 min,平均115 min.出血量70～750 ml,平均约209 ml,2例输血.术中未出现直肠、双侧输尿管和其他脏器损伤.术中、术后未出现心肺并发症.13例患者拔出导尿管后轻度尿失禁,经治疗后12例痊愈,1例生物反馈治疗中.3例术后病理提示尿道切缘阳性.10例保留性功能手术中5例勃起功能3个月内恢复. 结论 3D腔镜技术在前列腺癌根治术中具有优势,尤其是在缝合及精细操作方面.     

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.     

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.     

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.     

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.     

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.     

Systemic analgesia adapted to the children's condition

A concept of balanced analgesia using nonsteroidal anti-inflammatory drugs (NSAIDs), paracetamol (acetaminophen), opioids, and corticosteroids can also be used in patients with pre-existing illnesses. NSAIDs are the most effective treatment for acute pain of moderate intensity in children; however, these drugs should be avoided in patients at increased risk for serious side effects, e.g. patients with renal impairment, bleeding tendency, or extreme prematurity. NSAIDs can be given with minimal risks to the younger child with mild to moderate asthma, and, in these patients, the use of steroids can be encouraged; in addition to their antiemetic and analgesic action, a beneficial effect on asthma symptoms can be expected. In the non-intubated child with cerebral trauma, exaggerated sedation caused by opioids and increased bleeding tendency caused by NSAIDs must be avoided. In neonates and small infants, the oral administration of sucrose or glucose is helpful to minimize pain reaction during short uncomfortable interventions.