肝炎后肝硬化患者血浆内皮素的测定及其临床意义

为了解血浆内皮素(ET)水平在肝硬化及其发展中的变化,初步探讨其意义,应用放射免疫均相竞争法测定70例肝炎后肝硬化患者血浆ET水平。结果示,(1)血浆ET水平在肝硬化肝功能Chile-Pugh评分分级A患者(57.7±21.5pg/ml)、B级患者(40.7±23.1pg/ml)和C级患者(25.2±18.4pg/ml)均明显低于正常人(78.4±21.9pg/ml)(P<0.01)。B级和C级患者均低于A级患者(P<0.01),C级患者低于B级患者(P<0.01)。肝硬化患者肝功能Child-Pugh评分分数与血浆ET水平呈负相关(γ=-0.465,P<0.05)。(2)有腹水的肝硬化患者血浆ET水平明显低于无腹水的患者(33.7±23.9pg/ml vs 52.6±20.3pg/ml,P<0.01)。(3)肝硬化患者血浆ET水平与血清白蛋白水平呈正相关(γ=0.446,P<0.05),与血清胆红素,尿素氮、血浆凝血酶原时间无明显相关。提示血浆ET的减少可能在肝炎后肝硬化体循环血管扩张的维持中起一定作用,是水钠潴留、腹水形成的因素之一。血浆ET水平与肝硬化的严重程度和循环高动力状态有密切关系。     

Urinary Excretion and Plasma Levels of Sulphonamides in Patients with Renal Impairment

Urine and plasma levels and the clearance of two sulphonamides have been studied in patients with varying degrees of renal failure. In patients with renal impairment there is a decreased sulphadiazine clearance and a reduced 24 hour excretion after a single intravenous dose of sulphadiazine. In 4 patients on 7 occasions on continuous sulphadiazine or sulphamethizole therapy for three days there was an accumulation in the plasma of free and conjugated sulphonamide. In three of these patients elevated sulphonamide levels were associated with toxic side effects. Urine concentrations of free sulphonamide were much reduced in patients with renal impairment. Low urine concentrations and high plasma levels limit the use of sulphonamides in patients with renal damage.     

Serum Leptin Levels in Patients with Liver Cirrhosis and Chronic Viral Hepatitis

Background: The aim of the present study was to investigate serum leptin levels in relation to anthropometric features in patients with liver cirrhosis (LC) and chronic viral hepatitis (CVH), and to determine the effect of the severity and aetiology of the LC on serum leptin levels. Methods: Forty-nine patients with LC, 32 patients with CVH and 69 control subjects were age, body mass index (BMI) and sex-matched and included in the study. Plasma glucose, serum leptin and insulin levels were determined. Insulin resistance was assessed using homoeostasis model assessment (HOMA). Body composition was estimated by skinfold thickness. Results: Female patients with Child-A LC had higher levels of leptin, and female and male patients with Child-A LC had higher absolute leptin (leptin/BFM) levels compared to patients with Child-C LC and control subjects. Serum leptin levels of the patients with alcohol LC were higher than the control subjects, but the absolute leptin levels were comparable. When alcoholic and post-viral hepatitis cirrhotic patients were compared with each other on an aetiologic basis, there was no significant difference between them in leptin and absolute leptin levels. There were significant correlations between leptin and BMI, body fat percentage (BFP), BFM (body fat mass) in all three groups in both sexes. Conclusions: These data suggest that the physiologic correlations among serum leptin level, sex, BMI and BFM were well preserved in patients with chronic liver disease. Patients with alcohol LC had higher leptin levels. In early stages of liver disease, leptin levels and absolute leptin levels are higher than in normal subjects. However, in advanced stages of the disease the significant decline in leptin levels and similar levels of leptin expressed in relation to BFM compared to control subjects predominantly represent the expression of fat mass.     

Plasma Levels and Urinary Excretion of Nalidixic Acid in Patients with Renal Failure*

Summary: The excretion of nalidixic acid (α 1, 8, naphthyridine) has been studied in patients with renal impairment. The clearance of the therapeutically active naphthyridines was not related to renal function. The clearance of inactive conjugates of nalidixic acid was decreased in patients with renal failure resulting in a rise in plasma levels during continuous therapy. Despite severe renal failure therapeutic levels of active naphthyridines in the urine were usually obtained. Sodium bicarbonate administered orally in conjunction with nalidixic acid appeared to increase the absorption and the urinary clearance of the active naphthyridines.     

肝硬化患者血浆一氧化氮和内毒素水平及相互关系

本试验测定了４０例肝硬化患者和１０例正常人的血浆内毒素和一氧化氮含量。结果示：无复水组血浆ＮＯ和内毒素高于正常人,有腹水组高于无腹水组,肾功能损害组高于无肾功损害组。血浆内毒素和ＮＯ含量呈正相关,提示二者与肝硬化及腹水形成有一定关系,与肾功损害有关。     

肝硬化患者血浆内皮素及血管紧张素Ⅱ测定的临床意义

肾素 血管紧张素系统 (renin angiotensinsys tem ,RAS)不仅在调节全身血压维持电解质体液平衡方面起着重要作用 ,而且对心血管、消化、内分泌等其他系统疾病的病理生理方面 ,也有极大的影响 ,尤其是RAS的最终生理活性物质—血管紧张素Ⅱ(angiotensin ,AT Ⅱ ) ,通过内分泌、自分泌、旁分泌及胞内分泌发挥上述各种作用[1,2 ] 。内皮素 (AT )是一种由 2 1个氨基酸残基组成的多肽 ,是机体在缺血、缺氧的状态下 ,体内产生的一种致损因子 ,参与体内许多疾病的病理生理过程[3] 。它是一种内生的、持久的 ,具有强大缩血管和促血管平滑肌增殖…     

Plasma Levels of Atrial Natriuretic Peptide in Patients with Chronic Liver Disease

The plasma levels of atrial natriuretic peptide were determined by radioimmunoassay in 24 patients with chronic liver disease, including three patients with alcoholic liver disease, four with chronic active hepatitis, 13 with liver cirrhosis, and four with hepatocellular carcinoma. When compared with normal subjects (180 +/- 12 pg/ml), the plasma levels of atrial natriuretic peptide in cirrhotic patients (349 +/- 64 pg/ml) were significantly elevated (p less than 0.001) but not in other disease groups. In patients with chronic liver disease the plasma levels of atrial natriuretic peptide were correlated significantly with plasma renin activity but not with plasma aldosterone, and furthermore showed a negative correlation with indocyanine green disappearance rate. These results suggest that the increased plasma levels of atrial natriuretic peptide, which appear to be associated with an increase in plasma renin activity and with hepatic dysfunction, may participate in maintaining homeostasis of sodium and fluid volume in patients with chronic liver disease.     

Low Plasma Levels of Docosahexaenoic Acid Are Associated with an Increased Relapse Vulnerability in Substance Abusers

Low levels of some polyunsaturated fatty acids (PUFAs) could influence behaviors leading to the abuse of substances through their actions on serotonergic and dopaminergic mechanisms. Because substance abusers tend to have poor dietary habits, the possibility that a deficient intake of n‐3 PUFAs, available from dietary sources only, and subsequent low n‐3 plasma levels would predict their relapse rates was explored. Thirty‐five patients admitted to substance abuse clinics were enrolled and followed for one year. Dietary questionnaires and blood samples were collected at baseline and on a quarterly basis, and relapse rates monitored on a monthly basis. Six patients dropped out shortly after study entry, 11 relapsed in the course of the study and dropped out, 7 relapsed but completed the study, and 11 did not relapse and completed the study. Non‐relapsers were found to have significantly higher levels of docosahexaenoic acid (DHA) calculated as μ g/ml and % TFA, when compared to relapsers (p = .031 and p = .010, respectively) and to relapsers and non‐completers combined (p = .014 and p = .009, respectively). These pilot data suggest, but do not prove, the existence of a relationship between low levels of DHA and relapse vulnerability in some individuals who abuse substances. The study of the efficacy of n‐3 supplements or of dietary modifications on relapse appears warranted.     

Coronary Artery Disease in Patients with Liver Cirrhosis

Background The prevalence of coronary artery disease (CAD) has been reported to be low in patients with liver cirrhosis. Previous studies have, however, included mostly patients with cirrhosis due to hepatitis C. We aimed to determine the prevalence and predictive factors of CAD in a cohort of consecutive patients with cirrhosis of various etiologies compared to the general population. Methods A total of 127 patients with cirrhosis were evaluated for a history of CAD and cardiovascular risk factors. Arterial blood pressure, fasting plasma glucose, and serum cholesterol were measured. Nutritional status was assessed by anthropometry and estimation of recent weight change. A group of 203 subjects from the general population with similar age and gender distribution, as well as smoking habits as the cirrhotic patients, served as controls. Results CAD was more common in cirrhotics compared to controls (20% vs. 12%, P = 0.001). Compared to controls, cirrhotics had lower mean arterial blood pressure and serum cholesterol and a higher prevalence of diabetes, but did not differ significantly in the prevalence of hypertension or family history for CAD. In regression analysis, CAD was independently related to diabetes (odds ratio [OR] 5.47, 95% confidence interval [CI] 2.44–12.28), but not to liver cirrhosis. In the cirrhosis group, only alcoholic cirrhosis (OR 9.50, 95% CI 1.08–83.4) and age (OR 1.23 per year, 95% CI 1.06–1.43) were independently related to CAD. Conclusions Liver cirrhosis, per se, does not seem to confer a protective effect against CAD. In cirrhotics, older age and alcoholic etiology were independently related to CAD.     

Anticoagulation Therapy in Patients with Liver Cirrhosis is Associated With an Increased Risk of Variceal Hemorrhage

ObjectiveThe belief that cirrhotic patients are “auto-anticoagulated” often results in anticoagulation therapy being withheld in these patients. We aimed to understand patterns of use of anticoagulation and to determine the risk of bleeding complications in cirrhotic patients.MethodsWe retrospectively analyzed 320 cirrhotic patients treated with anticoagulation therapy from July 15, 2014 to January 30, 2018. We performed bivariate and multivariate analyses to identify risk factors for clinically relevant bleeding. We conducted a separate analysis using propensity score matching to compare bleeding rates of a noncirrhotic cohort group on anticoagulation to anticoagulated patients with cirrhosis.ResultsNonalcoholic steatohepatitis (47%) was the most common cause of cirrhosis, and 49% were classified as Child-Pugh class B, a mean model for end-stage liver disease score of 14 and Charlson comorbidity index of 7. Anticoagulation was initiated for atrial fibrillation/atrial flutter in 56% of patients; warfarin was used in 57% of patients and concomitant use of antiplatelet therapy in 25%. Bleeding occurred in 18%, with upper gastrointestinal bleeding (53%) being the most common source. In the propensity-matched cohort, bleeding rates were higher in cirrhotics than in control patients who were matched for baseline characteristics. In multivariate analysis of the cirrhotic patients, the presence of esophageal varices was associated with higher odds of clinically relevant bleeding.ConclusionAnticoagulated cirrhotic patients who have esophageal varices are at an increased risk of bleeding. We recommend that patients with cirrhosis and esophageal varices who require anticoagulation have their varices managed carefully prior to initiation of anticoagulation.     

Gastroduodenal Vascular Ectasia in Patients with Liver Cirrhosis

The purpose of this study was to determine the incidence of hemorrhage due to vascular ectasia of the upper gastrointestinal tract in patients with liver cirrhosis and to assess the prevalence in cirrhotic patients without clinically overt gastrointestinal bleeding. Out of 96 cirrhotic patients with upper gastrointestinal bleeding, vascular ectasia was diagnosed in 6 patients (6.3%) as the cause of bleeding. These 6 patients had numerous spotty or confluent erythemas consisting of ectatic and tortuous capillaries throughout the antrutn and 4 patients required blood transfusion before diagnostic en-doscopy. Several sessions of endoscopic electrocoagulation resulted in eradication of almost all the abnormal vascular lesions and marked improvement of their anemia without further transfusion. The procedure was well tolerated and no resultant complications were encountered. Among 206 cirrhotic patients without clinically overt gastrointestinal bleeding 25 patients (12.1%) were diagnosed with vascular ectasia. The hemoglobin level was significantly lower in patients with vascular ectasia than those without vascular ectasia but the other features did not differ between the two groups. Vascular ectasia is an important cause of upper gastrointestinal bleeding and anemia in patients with liver cirrhosis. Endoscopic electrocoagulation may be a safe and effective treatment for controlling blood loss from gastroduodenal vascular ectasia in this subset of patients. (Dig Endosc 1999; 11: 241–245)     

Plasma Vitronectin Levels in Patients with Coronary Atherosclerosis are Increased and Correlate with Extent of Disease

Background: Acute thrombosis after atherosclerotic plaques disruption is a major complication of primary atherosclerosis, leading to acute ischemic syndromes and atherosclerotic proression. Vitronectin (VN) is multifunctional glycoprotein in blood and in the extracellular matrix. It binds glycosaminoglycans, collagen, plasminogen and urokinase receptor. VN stabilizes the inhibitory confirmation of plasminogen activation inhibitor-1 (PAI-1). Vitronectin may control the clerance of vascular thrombi by binding and stabilizing PAI-1, a key regulator of fibrinolysis. Therefore, VN is generally regarded as a cofactor for PAI-1 activity. On the other hand vitronectin binds to platelet glycoproteins may mediate platelet adhesion and aggregation at sites of vascular injury. Previous studies showed that anti-VN antibodies inhibit platelet aggregation in vitro, suggesting that vitronectin contributes to platelet accumulation at sites of vascular injury. In this study; we investigated the levels of plasma vitronectin in patients with Coronary Artery Disease (CAD) and control group. Methods: The patient group was divided into four subgroups: patients with no, single, double and triple vessel disease according to their angiography results. ELISA procedure (Technoclone) was used to determine the plasma vitronectin levels. Results: Plasma vitronectin levels in patient with CAD (% 125.87 ± 58.38) were found to be significantly higher than control group (% 89.47 ± 25.3) (p:0.000). In addition, in patients with double vessel disease (% 146.03 ± 71.69) plasma vitronectin levels were significantly higher than no vessel disease (% 87.84 ± 22.30) and control group, triple vessel disease (% 160.81 ± 57.02) significantly higher as compare with no, single vessel disease (% 111.68 ± 45.34) and control group (p < 0.05). There was no correlation between vitronectin and lipid parameters. Conclusion: These findings suggested that vitronectin is a marker of CAD. Elevated levels may indicate its role in the genesis and/or progression of CAD or may be the results of a compensatory mechanism.     

Increased Plasma Malondialdehyde in Patients with Viral Cirrhosis and Its Relationships to Plasma Nitric Oxide,Endotoxin, and Portal Pressure

Background and Aim  

Increased oxidative stress is involved in the development of portal hypertension in cirrhosis. Our study aimed to assess the relationship between oxidative stress and hemodynamic parameters in cirrhotic patients.     

Evaluation of Gallbladder Motility in Patients with Liver Cirrhosis

To investigate the postprandial gallbladder motility, including emptying and refilling, in cirrhotic patients and to evaluate the relationship to the presence of gallstones and various humoral mediators, 82 patients with liver cirrhosis and 40 age- and sex-matched healthy subjects were enrolled into this study. Postprandial gallbladder volumes were measured with ultrasonography every 15 min for 2 hr. Plasma levels of estradiol, testosterone, substance P, and nitrate/nitrite were also measured. Cirrhotic patients showed a higher prevalence of gallstones than healthy subjects (41% vs 15%, P = 0.003), and the prevalence increased with the progression of liver cirrhosis (Child-Pugh class A: 26%, B: 44%, and C: 65%, P = 0.02). Plasma levels of estradiol, testosterone, and substance P, and nitrate/nitrite and estradiol/testosterone ratios were not different between cirrhotic patients with and without gallstones. However, postprandial refilling of the gallbladders was significantly impaired in patients with cirrhosis, especially in those combined with gallstones. There was no significant difference in the postprandial gallbladder motility between cirrhotic patients with and without elevated plasma levels of estradiol, testosterone, and substance P and nitrate/nitrite, and estradiol/testosterone ratios. Gallstones were common in patients with liver cirrhosis and the prevalence increased with the progression of liver diseases. Sex hormones, substance P, and nitrate/nitrite did not play major roles in the formation of gallstones in cirrhotic patients. Refilling of the gallbladder was significantly impaired in patients with liver cirrhosis, especially in those with gallstones, and may play an important role in the pathogenesis of gallstones.     

Hepatic Function and Portal Hemodynamics in Patients with Liver Cirrhosis

We investigated the distribution of portal blood flow per kilogram of body weight (PBF/BW) in 112 healthy volunteers and 90 patients with liver cirrhosis using an ultrasonic Doppler duplex system. The PBF/BW in healthy volunteers showed a log-normal distribution, while the distribution was irregular and showed two peaks in patients with cirrhosis. This irregular distribution was thought to reflect their complex physiopathological state. We next analyzed the relationship between PBF/BW and the data from hepatic function tests (serum albumin, total bilirubin, indocyanine green 15-min retention rate, and indocyanine green plasma disappearance rate) in 48 patients with liver cirrhosis. The patients were divided into four groups according to their portal blood flow: group A with a hepatofugal or stagnant portal blood flow, group B with a hepatopetal PBF/BW of less than 12 ml/min/kg, group C with a hepatopetal PBF/BW of 12 or more but less than 20 ml/min/kg, and group D with a hepatopetal PBF/BW of 20 ml/min/kg or more. Among patients with cirrhosis, group A showed the worst results in hepatic function tests, group D the second worst, and group C the best. The effective hepatic blood flow was thought to have decreased because of the development of extrahepatic portosystemic shunts in the patients in groups A and B, whereas it decreased because of the development of intrahepatic shunts in patients in group D. The results of hepatic function tests deteriorated as a consequence of the decrease in the effective hepatic blood flow.