Serum gamma-glutamyl transpeptidase: its specificity and clinical value.

The clinical import of the serum gamma-glutamyl transpeptidase (GGTP) level was evaluted in 162 prospectively studied patients. GGTP is helpful in determining the origin of alkaline phosphatase (AP); it clearly separates increased AP of bone and placental origin from that of liver origin. The GGTP level closely parallels the AP level in most instances, but it may be more sensitive in detecting liver disease in anicteric patients. The finding of significantly increased GGTP in patients with chronic aggressive hepatitis as compared to normal levels found in chronic persistent hepatitis may provide a prognostic clue in cases of unresolved hepatitis. The apparent specificity and sensitivity of the GGTP test, combined with ease of performance and low expense, make it a valuable addition to the evaluation of a patient with hepatic disease.     

Isoenzymes of alanine arylamidase (AAP, EC 3.4.11.2) and gamma-glutamyltranspeptidase (GGTP, EC 2.3.2.2) in chronic pancreatitis and pancreas neoplasm (author's transl)]

In 22 patients with chronic pancreatitis and 16 patients with pancreas neoplasms gamma-glutamyltranspeptidase (GGTP) and alanine arylamidase (AAP) in serum were measured and the isoenzymes were determined by gel electrophoresis on Agar. No specific isoenzyme pattern was found for chronic pancreatic diseases in a comparative investigation with a group of 19 patients suffering from hepatobiliary diseases. Two fractions of AAP and GGTP isoenzymes were found on agar gel electrophoresis: alpha-1 and alpha-2 (GGTP between alpha-2 and beta-globulin). The alpha-1 fraction of AAP and GGTP seems to be a specific liver isoenzyme. The slower fraction of both enzymes was also found in chronic pancreatic diseases and cholestatic diseases as in neoplasms of liver, pancreas and biliary tract. Practical importance of the findings is diminished by large variation coefficients of the results. A significantly low ratio of alpha-1 to alpha-2 fraction (or beta-globulin) on electrophoresis of the isoenzymes of AAP and GGTP was found in the group with neoplasm of pancreas (especially neoplasm of the pancreas head) as compared to the group with intrahepatic cholestasis. The possible causes and diagnostic importance of the findings are discussed.     

gamma-Glutamyl transpeptidase activity in liver disease: serum elevation is independent of hepatic GGTP activity

gamma-Glutamyl transpeptidase activity was measured in liver and serum from 110 patients undergoing diagnostic liver biopsy, including patients with alcoholic liver disease, fatty liver not due to alcohol, primary biliary cirrhosis, persistent hepatic disease, chronic active hepatitis and normal livers. Serum gamma-glutamyl transpeptidase was markedly elevated in patients with alcoholic liver disease and primary biliary cirrhosis while mean hepatic gamma-glutamyl transpeptidase activity was significantly increased only in the alcoholic liver disease group. There was considerable overlap of individual enzyme values among the different disease groups. There was no inhibitors or activators of liver gamma-glutamyl transpeptidase in any of these disorders. The increased liver activity was not related to the degree of hepatic fibrosis or cirrhosis. There was no correlation between hepatic and serum gamma-glutamyl transpeptidase activity. Hepatic and serum gamma activities were equally increased in individuals with alcoholic liver disease whether or not they were drinking at the time of the study. The data suggest that increased hepatic gamma-glutamyl transpeptidase activity is neither specific for alcoholic liver disease nor essential for serum GGTP to be elevated.     

The gamma-glutamyl transpeptidase (GGTP) as an index for the diagnosis of chronic alcoholic cholestatic hepatitis (author's transl)]

The GGTP is an enzyme localized, in the liver cell, inside microsome. At beginning the use of the GGTP was introduced for the diagnosis of chronic hepatitis; after it was noted as this was steady increased in the cholestasis and in the alcoholism. We have, hence, wanted to experiment if the changing of the level of the GGTP allowed to us a diagnosis of chronic alcoholic hepatitis. Our research is based on seventy-five patients with several liver diseases. It has been noted as the highest levels of the GGTP have appeared in cases of chronic alcoholic hepatitis with signs, histologicals and biochemicals, o cholestasis. In fact we have, on overage, levels of 955 mU/ml in the chronic alcoholic hepatitis with signs of cholestasis and of 135 mU/ml in that without it. In conclusion the GGTP is a good index for the diagnosis of chronic alcoholic cholestatic hepatitis.     

海洛因依赖者的脑CT表现及不同戒毒治疗方法的疗效研究

目的了解海洛因依赖者脑CT表现及不同戒毒治疗方案的疗效。方法对72例海洛因依赖者与50例正常对照者的脑CT表现进行对照研究,分析不同戒毒治疗方法的效果。结果部分海洛因依赖者内囊后肢、丘脑及侧脑室周围脑白质、小脑齿状核CT值有不同程度的减低(P0.05);提示海洛因依赖者可能有脑实质损害,此损害与吸毒时间长短、吸毒量多少无显著性差异;海洛因依赖者采用单独美沙酮戒毒治疗和综合治疗的效果有显著性差异。结论海洛因依赖者的戒毒治疗应考虑脑实质损害,辅以营养脑细胞、修复脑损害、恢复脑功能等综合性治疗手段。     

美沙酮维持治疗患者滥用苯二氮卓类药物调查与护理

目的:调查美沙酮维持治疗者滥用苯二氮卓类药物的发生率及相关因素。方法:对参加美沙酮维持治疗的海洛因依赖者进行尿苯二氮卓及吗啡检测,将苯二氮卓尿检结果与患者性别、婚姻状态、文化程度、滥用海洛因方式、年龄、海洛因滥用时间、美沙酮维持治疗剂量、参加美沙酮维持治疗的时间及尿吗啡检测结果等共九个因素进行Logistic回归分析。结果:共调查160例,尿苯二氮卓阳性率是8.1%,尿吗啡阳性率是36.3%,苯二氮卓阳性与吗啡阳性及注射使用海洛因相关(OR=27.328,P<0.005),与性别、年龄、海洛因依赖时间、服用美沙酮剂量等其他因素无相关性。结论:美沙酮维持治疗者存在滥用苯二氮卓类药物的现象,尤其是注射使用海洛因,并且在治疗期间仍滥用海洛因的患者。     

Monooxigenase activity in liver diseases (study based on data of antipyrine metabolism)

Hydroxylase and demethylase activity of cytochrome P450-dependent liver monooxygenases was estimated in healthy persons and patients with chronic diseases of the hepatobiliary system. Metabolite urine content and 4-hydroxyantipyrine and norantipyrine clearance were measured within 24 h after oral antipyrine administration (10 mg/kg). It was shown that progressive antipyrine metabolic derangements depended on the form and stage of chronic diffuse liver lesion, which was especially marked in patients with chronic active viral hepatitis, liver cirrhosis with or without ascites and with signs of encephalopathy. More considerable inhibition of N-demethylase monooxygenase activity as compared to hydroxylase activity in patients with chronic active viral hepatitis showed different sensitivity of some cytochrome P450 forms to pathogenetic factors. It could be of diagnostic value. The authors put forward the idea of interaction between the oxygenase and immune systems in drug detoxication in liver diseases.     

Lysosomal enzyme activities in normals and in patients with chronic liver diseases

The maximal activities of liver lysosomal enzymes (acid phosphatase and cathepsin D) were found to be increased in patients with chronic active hepatitis, cirrhosis and primary hepatocellular carcinoma. The ratio between maximal and basal activity (an expression of the degree of retention of the enzymes to lysosome) of acid phosphatase was significantly decreased in patients with chronic active hepatitis and cirrhosis whereas that of cathepsin D did not show any significant changes between normal and various liver disorders. Serum levels of both the enzymes were elevated significantly in patients with cirrhosis and primary hepatocellular carcinoma.     

Clinical and diagnostic aspects of drug-induced hepatitis

Drug-induced hepatitides (DIH) may manifest with a wide range of symptoms from insignificant activation of the enzymes with asthenic syndrome to severe disease with jaundice. The most informative tests for early diagnosis of medicinal lesion of the liver are biochemical tests of blood serum with determination of activity of the enzymes AlAt, AsAT, AP, GGTP. Long-term use of the drug and late diagnosis of DIH endanger drug damage to the liver. Treatment of acute drug hepatitides consists in administration of medication stimulating metabolic ability of hepatic cells. Acute DIH is characterized by the absence of splenomegaly.     

Neuroimaging in drug and substance abuse part II: opioids and solvents

The central nervous system is one of the primary targets for the detrimental effects of drugs of abuse. Diagnostic imaging, especially MRI, plays an important role in the detection of complications associated with drug abuse. We present the imaging findings associated with the abuse of opioids and other morphine derivatives, as well, as solvents. Of the morphine derivatives, heroin is the most commonly abused. Several CNS pathologic effects have been described in association with its abuse. These include neurovascular complications such as microvascular ischemic changes or ischemic stroke. A rare form of leukoencephalopathy has been described in those abusers who inhale heroin vapors. Other neurologic complications include atrophy and various infectious processes. Solvent inhalation is a common practice among adolescents and young adults secondary to its ease of access and low cost. The most important component of industrial solvents is toluene. Complications of toluene abuse may be either acute, showing no neuroradiological changes, or chronic, characterized by cerebral and cerebellar demyelination as well as atrophy.     

The prevalence of antibody to delta virus in western Canada

To assess the prevalence and pathological role of hepatitis D virus (HDV) infection in western Canada, we tested a total of 310 sera from the province of Alberta, Yukon and Northwest Territories for antibody to HD (anti-HDV) by commercial solid phase radioimmunoassay. Two hundred and forty-five sera were hepatitis B surface antigen (HBsAg) positive. These were classified on the basis of clinical and biochemical data as either acute hepatitis, chronic hepatitis or in the healthy carrier phase of infection Sixty-five HBsAg negative sera from patients with other forms of chronic liver diseases served as controls. Anti-HDV was detected in only four of the HBsAg positive sera (1.6%) and in none of the controls. The prevalence of anti-HDV was significantly higher in patients with chronic hepatitis, three of twenty-two (13.6%) than in patients with acute hepatitis (0%) (p less than 0.05) or healthy carriers (0%) (p less than 0.005). Two of the four anti-HDV positive sera were obtained from patients with a history of parenteral drug abuse. These results indicate that HDV infection is uncommon in western Canada but, when it does occur, is more likely to be associated with chronic inflammatory liver disease. Parenteral drug abuse appears to be the major risk factor for HDV infection in western Canada at this time.     

Reversal of changes in lipoprotein A and lipoprotein B cholesterol during and for a year after a detoxication treatment program in chronic alcoholism

We studied the individual and occasional changes in lipid metabolism induced by chronic alcohol abuse. In addition, the influence of a detoxication treatment program on the evolutionary changes in some serum lipidic components was studied for a one-year period. Before this program, total cholesterol was above normal, with high values for LP-A cholesterol, whereas for some patients LP-B cholesterol was increased. After the program, there was an increase in total cholesterol, LP-B cholesterol, and apolipoprotein B, with a decrease in LP-A cholesterol. These evolutionary changes continued during the one-year period after the end of the inpatient program.     

A pilot study of the effectiveness of buprenorphine and methadone as detoxication agents when choice is given to the consumer

A study was undertaken which provided for patients attending a community drug team (CDT) in the English Midlands the opportunity to decide for themselves whether they received methadone or buprenorphine on a comparable five-week fixed dose regime for detoxication from opiates. All but one of the 26 participants chose which drug they would use with 13 choosing buprenorphine. Those who chose buprenorphine were more likely to be married or cohabiting. There was no difference in prior drug use. Those on buprenorphine reported less severe withdrawal symptoms from Week Three onwards. There was no difference in attrition rates between the two groups, but those on buprenorphine reported external reasons for defaulting from the study whereas those on methadone cited severity of withdrawal symptoms. Most participants used 'street drugs' on top of the prescribed regime, notably cannabis and heroin. Alcohol consumption in both groups increased during detoxication.     

Everyone needs some dream topping

Adding on to existing provision by a community drug team with a long waiting list, a regime which gave rapid access to a structured detoxication regime had a number of consequences. Of the 58 people who were invited to take part in the rapid detox, 18 people did not attend initial appointments and 14 people declined. Twenty-six agreed to undertake the structured detoxication but only six completed the entire regime. One year after the project, of the 12 who requested methadone, two are currently back in contact and five are on the waiting list for case management, i.e. for long-term methadone maintenance. Of the 13 who requested buprenorphine, six are currently back in contact, one is on the waiting list and two have received a second detoxication and are currently closed cases. A condition of the project was that the drug regime would continue to be prescribed, regardless of whether the subjects continued to use other drugs or used the drugs provided as prescribed. Whilst undergoing detoxication, participants may rediscover the 'value' and 'pleasure' that he/she may get from the drug, which may have been masked by the disadvantages of habitual substance use, as that use became more routine and consequences became less acceptable. It may be helpful to allow subjects to have more input and control over the change from using heroin daily (at possibly dangerous levels) to a return to drug use at controllable levels. That may produce better compliance and higher satisfaction with services. But it would be of more value to understand better how the customers of such a service actually view the process of detoxication and what they mean by it.     

Elevation of serum beta 2 microglobulin in liver diseases

beta 2 Microglobulin levels were measured by radioimmunoassay in the serum of 160 patients with liver disease and compared to 63 normal controls and 75 asymptomatic HBs-Ag carriers. All the latter subjects had normal values. Elevated serum beta 2 microglobulin levels were found in most of the other categories: acute viral hepatitis (35/45); chronic persistent (8/26) or active (35/41) hepatitis and liver cirrhosis (27/38). beta 2 Microglobulin values were significantly lower in chronic persistent hepatitis than in the three other groups (p less than 0.05). Steroid therapy was followed by reduction of serum beta 2m levels in 11/11 cases of chronic active hepatitis, eight of whom returned to normal value. Although linked to the course of the disease, variations of beta 2 microglobulin were independent of transaminases, bilirubin and gamma globulins. Elevated serum beta 2 microglobulin correlated with demonstration of rheumatoid factor but not with detection of circulating immune complexes, hepatitis B virus markers or autoantibodies. The results suggest that elevation of serum beta w microglobulin is encountered mostly in the active forms of inflammatory liver diseases.     

Clonidine maintains intrathecal self-administration in rats following spinal nerve ligation

Clonidine is approved for spinal administration against neuropathic pain, and reverses both spontaneous and elicited pain in humans following spinal administration. Rodent studies that seek to model pharmacology in pain states have historically relied on reflexive withdrawal from noxious stimuli as the primary endpoint. Drug self-administration studies have face validity in the drug abuse field for modeling drug abuse in humans, however, this methodology has not been applied to address issues related to drug seeking behaviors that may be relevant for other human populations, such as patients with neuropathic pain. Rats without spinal nerve ligation (SNL) failed to acquire intrathecal clonidine self-administration over 10 days of access. Rats were found to self-administer intrathecal infusions of clonidine following SNL in a stable and dose-responsive manner, however, and clonidine was self-administered throughout the day with 66% of total drug intake occurring during the dark cycle. Substitution of clonidine with saline or with clonidine and the alpha2-adrenoceptor antagonist idazoxan resulted in extinction of responding in SNL animals. Food reinforcement was initially decreased in SNL rats self-administering clonidine compared to normal animals, however, tolerance developed to this effect of clonidine in SNL rats after 5 days. These data demonstrate that drug self-administration can be applied to questions other than drug abuse, and provides an additional measure for development of novel therapeutic strategies for chronic pain treatment.     

Clinical, biochemical, and morphological characteristics of chronic hepatitis with various etiology

AIM: To investigate clinicomorphological features in patients with chronic diffuse lesions of the liver with consideration of the etiological factor. MATERIAL AND METHODS: Clinical, laboratory, serological and pathohistological examinations were performed in 67 patients with chronic hepatitis (CH). RESULTS: Out of 48 patients with chronic viral hepatitis (CVH), 32(66.6%) demonstrated association of hepatic lesion with alcohol or drug abuse. Knodell activity in the liver was prevalent in drug abusers with CVH. Fat dystrophy and high de Ritis index were typical for alcoholics. CONCLUSION: Viral hepatic lesions associated neither with alcohol nor drug abuse occur only in 1/3 of patients with CH.     

丁丙诺啡与氯硝西泮治疗海洛因依赖疗效分析

本文以盐酸丁丙诺啡(BUP)与氯硝西泮联合,按递减疗法8天为一疗程治疗海洛因依赖70例,戒断23例,显效38例,无效9例,脱毒率87％,与单独使用等量Bup对照组40例的脱毒率82％比较,两组无显著性差异(P>0.05)。结果表明,本疗法起效快、控制戒断症状完全,停药后无反跳现象,疗效满意。     

The activity of gamma-glutamyl transferase in the serum of multiple sclerosis and other neurological diseases.

1. In the sera of 142 neurological patients, including 35 cases with multiple sclerosis (MS), and 20 normal controls the gamma-glutamyltransferase (gamma-GT) activity was determined. The result of this investigation was compared with the "combined hippuric acid test" formely often used in MS patients. 2. The MS patients are the only group which significantly differs from the normal controls. There are also small differences between them and some of the other neurological patient groups. About one-third of the MS patients show moderately pathological serum activities. On the other hand, patients with a definite liver affection, especially chronic alcoholics, regularly show an even more important elevation of the values, which makes this test a sensitive tool for the screening of alcohol-induced liver intoxications. 3. Although the gamma-GT test in not quite as sensitive in indicating organic defects in MS patients, it seems to reflected a disturbed liver function in the same way as the more complicated "combined hippuric acid test". It may therefore be used as a simple tool of finding and following up organic defects in MS patients.     

Important role of proinflammatory cytokines/other endogenous substances in drug-induced hepatotoxicity: depression of drug metabolism during infections/inflammation states, and genetic polymorphisms of drug-metabolizing enzymes/cytokines may markedly contribute to this pathology

Analysis of literature data on drug-induced hepatotoxicity reveals that often upper respiratory febrile illnesses and/or inflammation states precede liver injury/diseases related to administration of drugs or hepatotoxicity associated with administration of therapeutic doses of acetaminophen in some genetically predisposed subjects. The goals of this paper are to review the potential role of alterations in the balance between TH1 cells producing cytokines associated with a cell-mediated response and TH2 cells associated with an antibody response, as well as other endogenous substances, eg, growth factors, leading to a shift in immune response to one that may participate in the liver cells injury during administration of certain drugs, especially in subjects with genetic polymorphisms in drug-metabolizing enzymes. The papers cited in this review were selected to illustrate specific issue related to how profuse and dysregulated production of cytokines, growth factors, and/or other endogenous substances during viral/bacterial infections and inflammation states play a role in the development of drug-induced liver injury. Several cases of liver injury related to administration of drugs appear to be initiated or intensified by upper respiratory febrile illnesses and/or inflammation states, which stimulate sometimes dysregulated production of interferon gamma and/or other proinflammatory cytokines/growth factors. This, in turn, results in down-regulation of various induced and constitutive isoforms of cytochromes P-450, and other enzymes involved in the metabolism of several exogenous (eg, drugs) and endogenous lipophilic (eg, steroids) substances, thus having an important impact on the alterations in bioactivation and detoxication processes in the body and on the balance between production, utilization, and elimination of endogenous bioproducts of these reactions. Activation of systemic host defense mechanisms results in down-regulation of various enzymes involved in drug metabolism and elimination, as well as in production, utilization, and excretion of many endogenous substances that have beneficial effects on vital processes in the body. It seems that treatment of acute and chronic infections and/or inflammations with, for example, antibacterials not metabolized in the liver, and use of medications that decrease proinflammatory cytokine levels (eg, pentoxifylline, a TNF-alpha synthesis inhibitor, directed against TNF-alpha-induced priming of human neutrophils, immunotherapy with IL-4, IL-1 receptor antagonists or factors inducing IL-1ra, dietary supplementation with long-chain n-3 fatty acids, and other antioxidant agents) may perhaps, in some cases, be helpful in the prevention and management of drug-induced hepatotoxicity. Drug-mediated injuries may eventually be prevented by screening methods that can identify genetic polymorphism of drug-metabolizing enzymes and gene polymorphisms or RNA-expression profiles of some proinflammatory cytokines before a patient uses a drug.