前列腺癌TSP-1的表达与血管新生的关系及意义

目的：探讨良性前列腺增生及前列腺癌中血管生成与血小板反应素-1（TSP-1）表达的相关性。方法：应用免疫组织化学方法检测32例良性前列腺增生和32例前列腺癌组织中TSP-1的表达及微血管密度（MVD）。结果：前列腺癌组织中TSP-1表达显著低于良性前列腺增生（P〈0．05）,MVD则明显升高（P〈0．05）;随着肿瘤分期的进展,浸润转移性癌中TSP-1的表达降低甚至缺失,而MVD却逐渐升高。结论：TSP-1在前列腺癌中呈低表达,与前列腺癌的血管新生相关;作为一种内源性血管新生抑制剂,它具有抑制肿瘤生长及血管新生的作用。     

乳腺癌微血管生成及nm23表达的临床意义

目的探讨乳腺癌组织中微血管生成及nm23表达的关系及其临床意义。方法应用SP免疫组织化学染色方法 ,以CD3 4单克隆抗体标记6 5例乳腺癌肿瘤组织中微血管,计数微血管密度(MVD),同时检测肿瘤组织中nm23的表达,分析乳腺癌组织血管生成和nm23的表达及两者与肿瘤生物学行为的关系。结果全部肿瘤标本有不同程度的微血管生成,并表现出明显的异质性。MVD计数为3～33个/400倍视野(平均11.6±7.0),nm23阳性表达率为81.5%。MVD与nm23的表达呈负相关(P=0.011),且两者分别与患者年龄、肿瘤大小无明显关系,而与肿瘤淋巴转移有关(P=0.0 1 4,0.0 0 5)。nm2 3的表达与肿瘤临床分期有关(P=0.0 3 8)。结论乳腺癌肿瘤组织中的微血管生成促进了淋巴转移,而nm23的表达可抑制淋巴转移;联合检测MVD及nm23对评估肿瘤淋巴转移风险具有一定的临床意义,可预测患者的预后。     

Plexin A1在胃癌中的表达及其与肿瘤细胞增殖和血管生成的关系

目的探讨PlexinA1在胃癌组织中的表达及其与肿瘤细胞增殖和血管生成的关系。方法应用RT-PCR检测20例胃癌患者的癌组织及胃切缘正常胃黏膜组织Plexin A1的mRNA表达;免疫组织化学方法检测50例胃癌组织和20例胃正常黏膜中PlexinA1、肿瘤细胞增殖指数Ki-67、血管内皮生长因子(VEGF)和第Ⅷ因子微血管密度(MVD)的表达。结果RT-PCR示胃癌组织中的PlexinA1mRNA的表达明显高于胃正常黏膜(0.71±0.37vs0.60±0.25,P<0.05)。胃癌组织中MVD随着PlexinA1的mRNA表达的增强(r=0.8736,P<0.01)和蛋白表达的增高而增高(P<0.01);Ki-67的表达也与PlexinA1存在明显的一致性(r=0.4851,P<0.01);而VEGF的表达与PlexinA1的表达无关。结论PlexinA1在胃癌发生发展中发挥重要作用,与调节血管生成和促进肿瘤细胞增殖有关。     

膀胱移行细胞癌Mta-1基因与蛋白表达及其临床意义

目的:检测膀胱移行细胞癌(BTCC)中Mta-1mRNA与蛋白表达,分析其与BTCC临床分期、病理分级、转移及复发的关系。方法:原位杂交、免疫组化方法检测42例BTCC组织Mta-1mRNA与蛋白的表达;CD34标记血管内皮细胞,计数肿瘤组织微血管密度(MVD);结合临床病理资料,分析Mta-1与BTCC的侵袭转移、血管生成及复发间的关系。结果:①Mta-1mRNA与蛋白在BTCC中高度表达,其表达阳性率分别为78.6%、73.8%,与正常组织比较差异有统计学意义(P<0.01),且随BTCC临床分期及病理分级的升高而增加,肿瘤复发组高于无复发组,肿瘤转移组高于无转移组(P<0.05)。②经非参数相关分析发现,Mta-1蛋白与Mta-1mR-NA表达呈高度正相关,Rs为0.945,P=0.000;CD34标染的微血管密度(MVD)与Mta-1mRNA与蛋白表达亦呈正相关,相关系数分别为0.712、0.683,P=0.000。结论:①Mta-1在膀胱移行细胞癌中高度表达,并随着肿瘤临床分期和病理分级的升高而增加,与肿瘤的转移及复发密切相关。②Mta-1参与膀胱移行细胞癌的侵袭、转移,可能与促进血管生成有关。     

血小板反应素-1在胃癌及转移淋巴结中的表达及其与血管生成相关性的研究

目的检测血小板反应素-1（TSP-1）在原发性胃癌及转移淋巴结组织中的表达情况,并分析其与胃癌临床病理学参数及血管生成的关系。方法应用免疫组织化学方法检测72例成对胃癌组织、癌旁正常组织（距离癌灶≥5cm）及胃周淋巴结组织中TSP-1及血管内皮生长因子（VEGF）的表达和微血管密度（MVD）的变化。采用半定量评分系统评估染色结果,并分析TSP-1蛋白表达与VEGF、MVD及胃癌临床病理学参数的关系。结果①TSP-1蛋白在胃癌组织中表达阳性率为45．8％（33／72）,在癌旁正常组织中为90．3％（65／72）,在转移淋巴结组织中为50．8％（30／59）,其在胃癌组织和转移淋巴结组织中的蛋白表达阳性率明显低于其在癌旁正常组织中的表达阳性率呼=32．710,P=0．000;）f=25．298,P=0．000）,其在胃癌组织中的蛋白表达阳性率与其在转移淋巴结组织中的表达阳性率比较,差异无统计学意义贸X=0．327,P=0．568）。②胃癌组织中TSP-1蛋白表达阳性率与淋巴结转移有关,即在有淋巴结转移的胃癌组织中TSP．1蛋白表达阳性率明显低于其在无胃周淋巴结转移组织中的表达阳性率（Z=-2．573,P=0．010）。③TSP-1在胃癌组织及转移淋巴结组织中的蛋白表达与VEGF表达（rs=-0．309,P=0．008;rs=-0．269,P=0．040）及MVD（rs=-0．348,P=0．003;rs=-0．272,P=0．037）呈负相关。结论TSP-1在胃癌组织及转移淋巴结组织中的蛋白表达均降低且与VEGF表达和MVD呈负相关,提示TSP-1可能是一个肿瘤血管生成抑制因子。     

人脑胶质瘤血管生成素-2表达及其与管生成和脑水肿的关系

目的 研究血管生成素.2(Ang-2)基因在人脑胶质瘤表达及其与胶质瘤血管生成及瘤周水肿的关系。方法 用半定量逆转录-聚合酶链反应(RT-PCR)、免疫组织化学方法测定42例人脑胶质瘤和8例正常脑组织中Ang-2 mRNA及其蛋白表达情况。用免疫组织化学方法检测肿瘤微血管密度(MVD)。结果 正常脑组织中无或弱表达Ang-2。42例胶质瘤组织中均有Ang-2 mRNA表达,不同级别间Ang-2 mRNA的表达差异有显著性(P<0.05)。随着脑胶质瘤恶性程度的增加,Ang-2 mRNA的表达增高(r=0.894,P<0.01)。免疫组织化学结果显示,胶质瘤细胞及肿瘤血管内皮细胞中均有Ang-2蛋白表达。Ang-2 mRNA表达与MVD、脑水肿指数(EI)显著相关(分别为r=0.853,P<0.01;r=0.784,P<0.01)。结论 Ang-2可能参与胶质瘤血管生成,对胶质瘤瘤周脑水肿及恶性进展有促进作用。     

胃癌组织中E26转录因子-1表达与血管生成的相关性研究

目的研究胃癌组织中E26转录因子-1(Ets-1)表达与血管生成的关系。方法应用免疫组织化学方法(SP法)检测86例胃癌标本中Ets-1的表达及微血管密度(MVD);建立裸鼠胃癌皮下种植瘤模型,分别应用Ets-1反义,正义寡核苷酸与PBS行瘤内注射,应用逆转录聚合酶链式反应检测瘤组织Ets-1mRNA的变化,并检测瘤组织Ets-1蛋白及微血管密度的差异。结果胃癌组织中Ets-1标记指数(LI)和MVD呈正相关(γ=0.495,P<0.05);经Ets-1反义寡核苷酸治疗后,裸鼠瘤组织Ets-1mRNA及Ets-1蛋白表达降低,反义组MVD显著低于正义组与PBS组(10.4±3.1VS24.5±8.4,20.6±7.5,P<0.01)。结论胃癌组织中Ets-1在促进血管生成中起重要作用。     

血管生成素-1、血管生成素-2及Tie-2表达在乳腺癌血管生成中的作用

血管生成素(Ang)在机体和肿瘤血管生成中发挥着重要的作用,其中Ang-1、Ang-2与它们的共同受体Tie-2与血管生成密切相关.血管生成不仅为肿瘤细胞的生长提供了营养,并为肿瘤的浸润和转移提供了通路.本研究应用免疫组织化学技术检测乳腺癌组织中Ang-1、Ang-2及其受体Tie-2的表达,同时计数癌组织微血管密度(MVD),探讨Ang-1、Ang-2及其受体Tie-2的表达与乳腺癌组织血管生成关系,以期有助于寻找有效抑制乳腺癌血管生成的可能途径.     

ING4和CD34蛋白在人前列腺癌组织中的表达及其相关性研究

目的探讨ING4及CD34蛋白在人前列腺癌组织中的表达及相关性。方法采用免疫组织化学Elivsion TM Plus二步法检测28例人前列腺癌及32例良性前列腺增生组织中ING4及CD34的表达情况,分析其结果与前列腺癌病理分级及危险等级关系。结果 ING4基因蛋白在人前列腺癌组织中的阳性表达率明显低于良性前列腺增生组织,且随肿瘤病理分级、PSA及临床分期的增加而降低。而CD34标记的微血管密度(microvessle density,MVD)在前列腺癌组织中表达明显较良性前列腺增生组织高,其MVD值随肿瘤病理分级及危险等级增加而升高。前列腺癌组织中ING4表达与MVD值呈负相关,r值为-0.827,相关性具有统计学意义(P0.05)。结论 ING4基因蛋白在人前列腺癌组织表达异常,可能参与了肿瘤的发生及进展,同时可以作为前列腺癌临床评价诊断、指导治疗的辅助指标之一。     

前列腺癌PTEN蛋白表达和微血管密度的相关性研究

目的　研究前列腺癌组织中PTEN蛋白的表达和微血管密度(MVD)的相关性及其意义。方法　应用免疫组化SP法检测3 2例前列腺癌及5例良性前列腺增生组织中PTEN蛋白表达及微血管计数,分析其意义和相关性。结果　3 2例前列腺癌中8例PTEN蛋白表达阳性(2 5 % ,8/3 2 ) ,并随病理分级升高阳性表达率下降,高分化组同中分化组间差异无显著性(P >0 .0 5 ) ,但高分化、中分化组同低分化组之间差异有显著性(P <0 .0 5 ) ,且在浸润型肿瘤(C D)期与局限性肿瘤(A B)期的差异有显著性(P <0 .0 1)。前列腺癌组织中MVD(5 2 .86±17.87) ,MVD随病理分级和临床分期的升高而升高,并同PTEN蛋白的表达成负相关(r =-0 .65 3 ,P <0 .0 1)。结论　PTEN蛋白低表达和微血管的形成在前列腺癌的发生、发展中起重要作用。检测PTEN蛋白的表达和MVD有助于判断病情及预后。PTEN蛋白的低表达与肿瘤微血管的形成相关。     

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.     

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.     

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.     

Reduction of Plasma Fibrinogen, Immunoglobulin G, and Immunoglobulin M Concentrations by Immunoadsorption Therapy with Tryptophan and Phenylalanine Adsorbents

Abstract Immunoadsorption (1A) therapy with tryptophan (TR-350) or phenylalanine (PH-350) adsorbents has been used to reduce the concentration of serum antibodies in human lymphocyte antigen (HLA)-immunized patients. Other forms of plasma purification have been reported to reduce the level of fibrinogen, which affects the blood properties. In this study we investigated the effects of IA therapy using both adsorbents on plasma fibrinogen and immunoglobulins G and M in 13 patients (8 patients were treated with TR-350, and 5 patients were treated with PH-350). During each session 1 plasma volume (2.8 ± 0.4 L of plasma) was processed through the immunocolumn and then returned to the patient together with the blood cells. Compared with the pretreatment values, the plasma fibrinogen, IgG, and IgM concentrations were significantly reduced after IA therapy (p < 0.01 for TR-350; p < 0.04 for PH-350). There was a positive correlation between the degree of reduction of plasma proteins and the number of IA treatments given. A nonpara-metric test (Wilcoxon's signed-rank test or the Mann-Whitney test) was used for statistical analysis. We conclude from our study that IA therapy effectively lowers the plasma levels of fibrinogen, IgG, and IgM and thus can be considered a valuable alternative to other blood purification methods.     

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.     

Dilemma of Membrane Biocompatibility and Reuse

Abstract: Numerous articles have been published on the multiple use of dialyzers and on the effect of different reprocessing chemicals and techniques on the dialyzer biocompatibility and performance. The results often appear contradictory, especially those comparing standard biocompatibility parameters. Despite this confusion, a discerning review of the published works allows certain limited conclusions to be drawn. Reprocessing of used hemodialyzers changes the biocompatibility profile of a dialyzer as defined by the parameters complement activation. leukopenia, and cytokine release. The effect of reprocessing depends on the chemicals and reprocessing technique applied and also on the type of membrane polymer being subjected to the reprocessing procedure. Reports of pyrogenic reactions indicate that the flux of the membrane also influences how suitable it is for safe reuse. An increased risk of allergic and pyrogenic reactions appears to be associated with dialyzer reuse. Furthermore, there has been a lack of investigations into the immunologic effect of the layer of adsorbed and chemically altered proteins that remains on the inner surface of reprocessed dialyzers. We conclude that the clinical benefit of dialyzer reuse cannot be generally accepted from a biocompatibility point of view.