Oral Tryptophan Challenge Studies in Cirrhotic Patients: No Evidence of Neuropsychiatric Changes

Hepatic encephalopathy is a frequent complication of cirrhosis. Abnormalities of5-hydroxytryptamine (5-HT) and its metabolites are recognized and may contribute to its pathogenesis. We therefore studied the effect of an oral tryptophan load (6–18 g) upon psychometric test scores and analyzed EEG's in alcoholic cirrhotic patients. Eight patients had had previous encephalopathic episodes related to variceal bleeds and one patient was awaiting a liver transplant. Five out of the 10 patients had at least one abnormal baseline psychometric test. Following tryptophan challenge there were no changes in blood ammonia but plasma tryptophan levels were elevated approximately 10-fold (p <0.01× 10^–7). Nevertheless, there were no statistically significant changes in psychometric testing or analyzed EEG frequency distribution. All patients reported nausea or vomiting while one patient developed a short-lived serotonin like syndrome. We conclude that in this group of patients, an oral tryptophan load does not induce or worsen subclinical hepatic encephalopathy. If the high blood levels of tryptophan seen in these studies are able to influence cerebral neurotransmitter synthesis, the results do not support a primary role for abnormalities of 5-HT neurotransmission in hepatic encephalopathy.     

根除幽门螺杆菌对肝硬化患者血氨和脑电图变化的临床观察

目的 探讨肝硬化患者的幽门螺杆菌(Hp)感染情况并观察根除Hp后肝硬化患者血氨和脑电图的变化.方法 确诊的肝硬化患者52例,经胃镜或14C尿素呼气试验明确Hp感染情况,对Hp阳性者进行Hp根除治疗(一周标准三联疗法),方案为奥美拉唑40 mg/d,克拉霉素1.0 g/d,阿莫西林2.0 g/d,停药4周后复查12C尿素呼气试验,转阴性者判断为Hp根除,记录根除治疗前后血氨和脑电图情况.结果 Hp阳性者血氨水平83.04±20.81 mmol/L及脑电图异常发生率为86.1%,均明显高于Hp阴性者(P＜0.01＜);根除Hp后血氨水平49.10±9.80 mmol/L及脑电图异常发生率3.1%,均明显下降(P＜0.01).结论 Hp感染是引起肝硬化患者高血氨及脑电图异常的重要原因之一.根除Hp有助于治疗和预防肝性脑病.     

Effects of Simulated Upper Gastrointestinal Hemorrhage on Ammonia and Related Amino Acids in Blood and Brain of Chronic Portacaval-shunted Rats

Gastrointestinal (GI) hemorrhage during compromised liver function is known to precipitate portal-systemic encephalopathy (PSE). Hypothetically, the induced hyperammonemia depletes cerebral glutamate pools. To investigate this hypothesis, rats were studied 14 days after portacaval shunt (PCS) or sham surgery (SHAM). Rats received 3 mL bovine erythrocytes or saline at t=0, 1, 2, and 3h via a previously placed gastrostomy catheter. At t=0, 2, 4, 6 and 8h arterial blood and at t=8h cerebral cortex were sampled for determination of ammonia and amino acids. Control rats (NORM) were sampled without previous surgery. Repeated intragastric blood administration increased the already elevated arterial ammonia levels in PCS rats further. This resulted in higher cerebral cortex ammonia and glutamine,levels after blood administration. Despite the accumulation of ammonia and glutamine, cerebral cortex glutamate concentrations remained unaltered. Yet, PCS rats became more encephalopathic after blood gavages, suggesting that there is not a clear-cut relation between cerebral cortex glutamate concentrations and degree of PSE. Interestingly, cerebral cortex concentrations of GABA, tyrosine and phenylalanine were markedly increased. Whether these observations are pathogenetically related to PSE remains to be established. The present model of simulated GI hemorrhage in PCS rats seems to be a suitable, clinically valid model for future research regarding hepatic encaphalopathy.     

Distinguishing Between Clinical and Minimal Hepatic Encephalopathy on the Basis of Specific Cognitive Impairment

It is well-known that liver cirrhosis is frequently accompanied by a wide range of neuropsychiatric abnormalities, including general and specific cognitive impairment. The aim of this study was to investigate which cognitive functions are selectively compromised in Hepatic Encephalopathy (HE) and to clarify the relationship between clinically overt or nonovert HE and the different forms and degrees of decay in cognitive deficits. Twenty-two patients without overt HE and 12 patients who showed overt HE at the first level of severity, along with matched control subjects, were compared in several cognitive domains. The results showed significant differences in some measures of attention between patients with minimal HE (mHE) and patients with overt HE. There were also notable differences in verbal short-term memory between patients with mHE and healthy subjects. Thus, we can hypothesize that there is a linear diminution in short-term memory and attentional performance starting from healthy patients, moving toward patients with mHE, and finally progressing toward patients with the first grade of overt HE. There are two types of diminution that we noted: between patients with mHE and the overt form, the decline in the attentional domain was more evident, while between healthy subjects and mHE patients, short-term memory showed a more evident decline.     

Oral Amino Acid Load Mimicking Hemoglobin Results in Reduced Regional Cerebral Perfusion and Deterioration in Memory Tests in Patients with Cirrhosis of the Liver

This study tests the hypothesis that administration of an oral amino acid load mimicking hemoglobin in patients with cirrhosis of the liver causes deterioration in neuropsychological function and a reduction in regional cerebral perfusion. Eight overnight fasted, metabolically stable cirrhotic patients with no evidence of overt hepatic encephalopathy were studied prior to and 4 h after simulating an upper gastrointestinal bleed by oral administration of 75 g of a solution mimicking the amino acid composition of hemoglobin. Neuropsychological function was measured using a test battery. Peripheral venous blood was collected for the measurement of ammonia and amino acid concentrations. Regional cerebral perfusion was measured using a head SPECT scanner following intravenous administration of technetium-99m hexamethyl propylamineoxime. The amino acid solution resulted in significant deterioration in the immediate and delayed story recall tests. Ammonia concentration increased from a median of 87 (range 67–94) mol/L to 105 (98–112) mol/L at 4 h after the simulated bleed (p < 0.01). The concentration of almost all amino acids increased; only isoleucine levels decreased following the upper gastrointestinal bleed. SPECT analysis showed a significant reduction in cerebral perfusion after the simulated bleed in both temporal lobes, left superior frontal gyrus, and right parietal and cingulate gyrus. An oral amino acid load mimicking hemoglobin in cirrhotic patients produces hyperammonemia and hypoisoleucinemia and causes a significant deterioration in memory tests, probably due to a reduction in regional cerebral perfusion. The model of simulating the metabolic effects of an upper gastrointestinal bleed in patients with cirrhosis of the liver seems to be useful in studying the metabolism of hepatic encephalopathy.     

The Effects of Ammonia Tolerance Tests on the Cerebrospinal Fluid Concentrations of Amino Acids and Indoleamines in Patients with Liver Cirrhosis

To study the effect of ammonia administration on amino acids and indoleamines in cerebrospinal fluid (CSF) and on amino acids, insulin, and glucagon in plasma in humans with liver cirrhosis, we performed seven ammonia tolerance tests on six patients with stable liver cirrhosis. The grade of encephalopathy was determined by psychometric tests. Only one of the patients had pronounced encephalopathy. The other patients had no or only slight encephalopathy. The plasma concentrations of valine, leucine, isoleucine, phenylalanine, tyrosine, and methionine decreased after the ammonia load, whereas no changes were found in the plasma concentrations of glucagon and insulin. In CSF the concentrations of glutamine, aromatic amino acids, and indoleamines increased only in the patient who had pronounced encephalopathy, whereas no changes were found in the other patients. The effect of an ammonia load on the concentrations of neutral amino acids in CSF in patients with pronounced encephalopathy remains to be demonstrated.     

Effect of Portacaval Anastomosis on Glutamine Synthetase Protein and Gene Expression in Brain, Liver and Skeletal Muscle

The effects of chronic liver insufficiency resulting from end-to-side portacaval anastomosis (PCA) on glutamine synthetase (GS) activities, protein and gene expression were studied in brain, liver and skeletal muscle of male adult rats. Four weeks following PCA, activities of GS in cerebral cortex and cerebellum were reduced by 32% and 37% (p<0.05) respectively whereas GS activities in muscle were increased by 52% (p<0.05). GS activities in liver were decreased by up to 90% (p<0.01), a finding which undoubtedly reflects the loss of GS-rich perivenous hepatocytes following portal-systemic shunting. Immunoblotting techniques revealed no change in GS protein content of brain regions or muscle but a significant loss in liver of PCA rats. GS mRNA determined by semi-quantitative RT-PCR was also significantly decreased in the livers of PCA rats compared to sham-operated controls. These findings demonstrate that PCA results in a loss of GS gene expression in the liver and that brain does not show a compensatory induction of enzyme activity, rendering it particularly sensitive to increases in ammonia in chronic liver failure. The finding of a post-translational increase of GS in muscle following portacaval shunting suggests that, in chronic liver failure, muscle becomes the major organ responsible for the removal of excess blood-borne ammonia.     

Measurement of the Expiratory Ammonia Concentration and its Clinical Significance

Alghough gaseous ammonia (NH₃) can freely enter cells through the plasma membrane where NH₃ is cyto(neuro)toxic, NH₃ and ionic ammonia (NH₄ ⁺) contents have not been studied in biological materials. We developed a new method for measurement of expiratory NH₃ concentration, which may reflect blood NH₃ concentrations. The method is a sensor tube type-gas assay system. Expiratory NH₃ concentrations in patients with chronic liver diseases increased when their blood ammonia (NH₄ ⁺+NH₃) concentrations increased above 90 μg/dl (normal range; 12–66 μg/dl). However, cirrhotic patients, who had relatively higher expiratory NH₃ concentration compared to blood NH₃ concentrations (calculated from Henderson-Hasselbalch formula), were found to have subclinical encephalopathy. Measurement of experatory NH₃ concentration may be of clinical significance for the diagnosis of encephalopathy associated with hyperammonemia.     

Effect of Endoscopic Injection Sclerotherapy on Acute Bleeding from Esophageal Varices in Cirrhotic Patients with Advanced Hepatocellular Carcinoma

Abstract: The effect of endoscopic injection sclerotherapy (EIS) on acute bleeding from esophageal varices in sixteen cirrhotic patients with advanced hepatocellular carcinoma (HCC) was analysed using the Cox proportional hazard model. Only EIS was found to have independently and significantly affected the survival rate (P = 0.0385), while clinical variables such as the extent of HCC, the presence of ascites and portal thrombosis, laboratory data and therapeutic modalities other than EIS showed no significant effect. EIS should be considered one of the treatments of choice when a cirrhotic patient with advanced HCC has acute bleeding from his/her esophageal varices.     

Effect of Metoclopramide on Portal Blood Flow in Patients with Liver Cirrhosis,Measured by the Pulsed Doppler System

The effect of metoclopramide on portal blood flow, the maximal diameter of the portal vein, and some cardiovascular haemortynamic variables was studied in 10 patients with cirrhosis of the liver and portal hypertension. Portal vein haemo-dynamics were studied by the pulsed Doppler system. Within 15 min of intravenous administration of 20 mg metoclopramide, portal blood velocity and portal blood flow decreased significantly, from 11.2 ± 1.1 to 10.8 ± 1.2 cm/sec and from 769.0 ± 87.7 to 707.9 ± 84.2 ml/min, respectively (p < 0.001). Within about 30 min portal blood velocity and portal blood flow returned to basal values (p >0.05). The maximal diameter of the portal vein, systolic and diastolic blood pressure, and heart rate remained unchanged. These results support the hypothesis that metoclopramide, which raises lower oesophageal sphincter pressure and reduces intravariceal blood flow, significantly decreases the portal blood flow in cirrhotic patients with portal hypertension.     

软肝冲剂对肝硬变过程中细胞周期DNA含量的影响

目的 :研究软肝冲剂对 CCl4 肝硬变过程中各期细胞周期 DNA含量的影响 ,从分子水平探讨其促进肝细胞再生、阻止肝纤维化、肝硬变形成的作用机制。方法 :采用流式细胞仪检测 CCl4 肝硬变大鼠各期细胞周期DNA含量。结果 :定量 DNA图像分析发现模型组中处于 G1 期的细胞数明显多于其他各组 (均 P <0 .0 1) ,软肝冲剂大剂量组中处于 G1 期的细胞数明显少于小剂量组 (在实验的第 12、 4 5、90天 ,均 P <0 .0 1)。结论 :软肝冲剂能调节 CCl4 肝硬变过程中细胞周期各时相 DNA含量 ,促进肝细胞再生 ,抑制肝纤维化、肝硬变的形成。     

Attention Dysfunction in Cirrhotic Patients: An Inquiry on the Role of Executive Control,Attention Orienting and Focusing

Attention alterations are reported in cirrhotics. Aiming at clarifying attention functioning in cirrhotics, an inquiry on the functioning of the anterior (AAS) and the posterior (PAS) attention system was performed. Thirty-six cirrhotics without overt hepatic encephalopathy (24 with EEG or TMT-A alterations) and 16 matched control subjects were enrolled. The AAS was studied by the Stroop task measuring selective attention control, the PAS was studied by the Posner task and the Focus task measuring automatic covert orienting and visual focusing of attention respectively.Cirrhotics presented a task-dependent psychomotor slowing (Stroop > Posner > Focus) with an increased percentage of errors in the incongruent condition of the Stroop task [F(1, 57) = 4.9, p < 0.03]. Class C patients had both a selective slowing [F(1, 33) = 4.3, p < 0.05] and an increased percentage of errors in the incongruent condition [F(1, 34) = 5.1, p < 0.05] compared to Class A–B patients and controls. The patients with an altered EEG performed the Stroop test significantly slowly than those without EEG alterations [F(1, 41) = 8.9, p < 0.01] and with a clear trend for a higher number of errors in the incongruent condition [F(1, 39) = 3.8, p < 0.06]. In contrast, attention orienting and focusing were maintained. In conclusion, the AAS is more sensitive than the PAS to the early stages of hepatic encephalopathy.     

氨水对大白鼠胃粘膜长期作用的影响：胃粘膜屏障功能的变化

本实验使用0.01％及0.02％的氨水,以自由饮水的形式经口长期喂养大白鼠,观察了氨水对胃粘膜血流、胃粘膜电位差及胃粘膜前列腺素E_2的影响。结果表明:由HP分泌的悄素酶所分解产生的氨长期作用于胃粘膜,可以导致大白鼠的胃粘膜血流和前列腺E_2减少,使胃粘膜电信差降低,破坏胃粘膜的防御机能,可能是HP导致慢性胃炎及胃溃疡的一个重要因素。     

谷氨酰胺预处理对体外循环下心脏瓣膜置换术患者心肌的保护作用

目的 研究谷氨酰胺预处理对体外循环下心脏瓣膜置换术患者心肌的保护作用.方法 将60例择期在体外循环下行二尖辩和/或主动脉辩置换术患者随机分为谷氨酰胺预处理组(n=30)和对照组(n=30),谷氨酰胺预处理组患者在手术前4天开始经外周静脉给予谷氨酰胺0.5 g/kg,每天一次,手术当天在麻醉诱导后切皮前经中心静脉给予相同剂量的谷氨酰胺,总计5次;对照组仅给予等量的生理盐水.两组麻醉方法及用药相同.分别于麻醉后切皮前(T_1)、开放主动脉后60 min(T_2)、6 h(T_3)、12 h(T_4)、24 h(T_5)分别抽取桡动脉血10 mL测定心肌肌钙蛋白Ⅰ.并于开放主动脉后30 min取右心耳心肌组织约1～2 g,做病理切片检查.记录各个时点患者的血压以及患者停转流后多巴胺及硝普钠的用量.结果 光镜下,对照组心肌间隙及血管周围有大量白细胞浸润,而谷氨酰胺预处理组则明显少于对照组;两组心肌肌钙蛋白Ⅰ从T_2时,最开始显著增加(P<0.05),T_4时点达到峰值,以后逐渐下降,且谷氨酰胺预处理组自T_2时点开始较对照组显著降低(P<0.05);两组在硝普钠用量差别不大的情况下,谷氨酰胺预处理组多巴胺的用量显著低于对照组.结论 谷氨酰胺预处理对体外循环下心脏瓣膜置换术患者心肌具有保护作用.     

The Effect of Adrenaline,Noradrenaline, Isoprenaline and Salbutamol on the Resting Levels of White Blood Cells in Man

Adrenaline, noradrenaline, isoprenaline and salbutamol were infused at the rate of 7 μg/min for 30 min into 5 healthy subjects. Pulse rates showed a marked increase after isoprenaline, a moderate increase after adrenaline and salbutamol, and a consistent decrease after noradrenaline. The total leucocyte counts increased in response to adrenaline and noradrenaline but remained unchanged after isoprenaline and salbutamol. The absolute lymphocyte counts showed significant increases after all the four agonists. Neutrophils increased in response to adrenaline and noradrenaline but remained unchanged after isoprenaline and salbutamol. ‘Stress’ lymphocyte counts rose in response to adrenaline, isoprenaline and salbutamol but not to noradrenaline. From these and other reported observations it is suggested that both α- and β- receptors are involved in the mobolization of lymphocytes, while neither has any specific role in the mobilization of neutrophils.     

临床路径对ST段抬高心肌梗死患者再灌注治疗疗效的影响

目的评价临床路径对急性ST段抬高心肌梗死患者就诊至球囊扩张时间、梗死心肌的再灌注治疗疗效的影响。方法随机选择100例实施急性ST段抬高心肌梗死急诊冠状动脉介入术临床路径的患者作为试验组,同时随机选择100例同期未实施临床路径的急性ST段抬高心肌梗死急诊冠状动脉介入术的住院患者为对照组。主要观察指标是就诊至球囊扩张时间、90 min目标时间内完成球囊扩张的比例、术中心肌梗死介入治疗后3级血流获得率及术后90 min ST段回落的比例、肌酸激酶同工酶酶峰值、住院病死率。结果试验组就诊至球囊扩张时间显著短于对照组(中位数,65 min比95 min,P<0.001),就诊90 min内完成球囊扩张的比例显著高于对照组(98%比65%,P<0.001)。临床路径显著提高术中心肌梗死介入治疗3级血流获得率(94%比81%,P<0.05)及术后90 min ST段回落>50%的比例(88%比67%,P<0.05),肌酸激酶同工酶酶峰值也明显提前(7.8±0.5比10.1±0.4,P<0.05),试验组住院病死率显著低于对照组(2%比7%,P<0.001)。结论临床路径可显著缩短就诊至球囊扩张时间,增加了90 min目标时间内完成球囊扩张的比例,能够更好地改善梗死区域心肌的微循环,显著提高梗死心肌的再灌注治疗疗效,这一作用对于降低住院病死率也具有非常显著的帮助,证实了临床路径管理是一种新的行之有效的服务管理模式。     

Effect of Blood Pump Flow and Arteriovenous Fistula Blood Flow on the Blood Pressure and Cardiac Function in Patients Undergoing Maintenance Hemodialysis

The effect of blood pump flow rate on the cardiac functions of hemodialysis patients with arteriovenous fistula (AVF) is largely unknown. This study aimed to investigate if blood pump flow rate (Qb) and AVF access flow rate (Qa) can affect the cardiac function of Chinese hemodialysis patients. A total of 72 patients undergoing AVF hemodialysis were included from March 2010 to June 2014 and dichotomized into the high‐ and low‐flow groups using the medians of Qb (220 mL/min) and Qa (1000 mL/min) as the cutoffs. The cardiac function parameters were measured by ultrasound dilution technique within the first (t + 30) and the last (t ? 30) 30 min of dialysis. At t + 30, Qb‐high group had significantly higher systolic blood pressure (SBP) and mean arterial pressure (MAP) than Qb‐low group. At t ? 30, Qb‐high group had higher SBP, diastolic blood pressure (DBP), and MAP than Qb‐low group. Qa‐high group had higher SBP, MAP, cardiac output (CO), cardiac index (CI), central blood volume (CBV), and lower peripheral resistance than Qa‐low group. Multiple linear regression showed that at t ? 30, Qb was positively correlated with SBP and MAP. Qa was positively correlated with CO, CI, CBV, and PR but negatively correlated with heart rate. Although Qb > 220 mL/min and Qa >1000 mL/min would elevate some parameters, the means of SBP, DBP, MAP remain within the normal range, indicating that appropriate increase in blood pump flow rate has little effect on the cardiac function of hemodialysis patients.     

红细胞分布宽度对非ST段抬高型心肌梗死患者冠状动脉侧支循环形成的临床意义

目的研究红细胞分布宽度(RDW)、平均血小板体积(MPV)与非ST段抬高型心肌梗死患者冠状动脉侧支循环形成的关系,探讨相关指标对冠状动脉侧支循环的预测价值。方法选取南阳市中心医院和河南省人民医院心血管内科非ST段抬高型心肌梗死患者166例,采用Rentrop分级方法,对冠状动脉侧支循环进行分级,分为侧支循环不良组(n=98)和侧支循环良好组(n=68)。红细胞分布宽度值和平均血小板体积值采用全自动血细胞分析仪测定。结果侧支循环不良组红细胞分布宽度水平显著高于侧支循环良好组(18.20%±1.83%比13.17%±0.84%),平均血小板体积值显著低于侧支循环良好组(8.16±1.22 fl比11.31±1.34 fl)(P0.05)。多因素Logistic回归分析显示高水平的红细胞分布宽度、肌酸激酶同工酶、低水平的平均血小板体积和无梗死前心绞痛与不良侧支循环密切相关。结论高红细胞分布宽度、低水平的平均血小板体积、高肌酸激酶同工酶、无梗死前心绞痛是非ST段抬高型心肌梗死患者冠状动脉侧支循环不良的独立预测因子。