Blood cell superoxide dismutase and enolase activities as markers of alcoholic and nonalcoholic liver diseases.

Monitoring of chronic alcoholism would be facilitated by using sensitive biochemical markers in blood cells, mainly to detect differences between alcoholic subjects with or without liver injury. We propose two types of markers: the first one is superoxide dismutase (SOD) activity involved in the conversion of superoxide radicals (O2-.) formed during acetaldehyde oxidation by xanthine oxidase after chronic alcohol consumption; the second one is enolase activity with both isoenzyme forms: nonneuronal enolase (NNE) and neuron specific enolase (NSE) which has been shown to be modified in many injuries related to the glycolytic pathways. For SOD activity we found a significant increase in alcoholic patients with liver injury and mainly in cirrhotic patients with ascitis. Both enolase activities were also found to be significantly increased in alcoholic patients with liver injury but NNE activity was also increased in alcoholics without apparent liver disease. Our results suggest that increased activity of SOD and NSE in blood cells may be related to liver injury mainly in alcoholism while increased NNE activity may also be a marker of alcohol abuse without liver injury.

Frequencies of glyoxalase I phenotypes as biological markers in chronic alcoholism.

Biological markers for alcoholism would be a valuable tool for early diagnosis. We have studied the phenotype frequencies of genetically determined erythrocyte enzymes in 397 alcoholics, including two populations with liver disease: steatosis (n = 86) and cirrhosis (n = 128) and a population of alcoholics without apparent liver disease (n = 183) compared to a well selected control population (n = 177). Only for Glyoxalase I (GLO) phenotypes (1,2 and 2-1) were significant differences found between the male controls and the male alcoholics. In the total male alcoholic population the frequency of phenotype 1 was significantly increased (23.2% vs. 11%, p less than 0.02), and the frequency of phenotype 2 was significantly decreased (32.3% vs. 46.3 p less than 0.02) compared to the male control population. For normal women the frequency of phenotype 1 and 2 was significantly different from normal men. (1: +177% p less than 0.001, 2: -45% p less than 0.01), but no significant differences were found between alcoholic and normal women. Our results suggest that in male subjects Glyoxalase I phenotype 1 may provide a marker for predisposition to alcoholism.

[Hyperammonemia induced by propranolol in cirrhotic patients. Role of the kidney and influence of the severity of the cirrhosis]. / Hyperammoniémie induite par le propranolol chez le cirrhotique. Rôle du rein et influence de la gravité de la cirrhose.

The effect of the intravenous injection of 0.1 mg/kg of propranolol on arterial ammonemia was studied in 30 patients with alcoholic cirrhosis comparatively with 10 healthy volunteers. Moreover, in 20 patients in the cirrhotic group (10 were Pugh's grade A or B and 10 others were grade C), left renal vein catheterization was performed to follow the changes in ammonemia and glutaminemia levels simultaneously with those occurring in arterial blood. After 30 min, arterial ammonemia was significantly increased in the controls (p less than 0.02) and in the cirrhotic patients (p less than 0.001). The renal venous ammonemia was also significantly increased in all of the cirrhotic patients (p less than 0.01). In the grade A and B patients, the increase in ammonemia was more marked in the renal vein as compared with that in arterial blood (p less than 0.001). In contrast, in the grade C patients, the increase in ammonemia did not differ significantly between the two sectors. The difference in ammonia concentration between arterial and renal venous blood increased significantly after 30 min in the grade A and B patients (p less than 0.001) whereas it was stable in the grade C patients. The changes of glutaminemia in arterial and renal venous blood were not significantly different in the two groups of cirrhotic patients. These data show that, in our experimental conditions, propranolol induces arterial hyperammonemia in cirrhotic patients and that the kidney could interfere with the mechanism of hyperammonemia, at least in grade A and B patients.

[In vitro demonstration of a deficit in suppressor T-cell function in alcoholic cirrhosis. Role of hepatitis B virus infection]. / Mise en évidence in vitro d'un déficit de la fonction lymphocytaire T suppressive dans la cirrhose alcoolique. Rôle de l'infection par le virus de l'hépatite B.

The T lymphocyte suppressor cell activity has been evaluated in 33 alcoholic patients compared with 16 normal controls, using an in vitro test. Suppressor T cells were activated with concanavalin A, and suppressor effect was quantified by the inhibition of an autologous B cell culture response to Pokeweed Mitogen. When compared with controls, cirrhotic patients showed a significant defect of suppressor cell activity on B cell production of IgG (20 +/- 3 vs 46 +/- 5 p. 100, p less than 0.001) and IgM (26 +/- 4 vs 56 +/- 8 p. 100, p less than 0.05). In cirrhotic patients, defect of T cell suppressor function was independent of sex and severity of the cirrhosis (Child's staging). This defect was more marked in cirrhotics with serological markers of hepatitis B virus (HBV) infection (n = 11) than in cirrhotics without markers (n = 22) (9 +/- 5 vs 25 +/- 3 p. 100, p less than 0.05; 16 +/- 6 vs 30 +/- 5 p. 100, p less than 0.05 respectively for IgG and IgM production suppression). These results suggest that HBV and lymphocytes interact directly. This interaction could increase the T suppressor cell defect, and explain the promoting role of HBV infection in the constitution of the cirrhosis in alcoholics even when viral replication is not serologically apparent.

[Abetalipoproteinemia. Apropos of 2 cases]. / L'abêtalipoprotéinémie. A propos de deux cas.

The cases of two sisters with abetalipoproteinemia are reported. Both presented the complete clinical and biological features of the disease: ataxia, retinitis pigmentosa, lack of apolipoprotein B, chylomicrons, LDL and VLDL, reduced titers of serum cholesterol and triglycerides, acanthocytosis, very low levels of serum vitamin A and E. Abetalipoproteinemia is a rare autosomal inherited disease. It is usually revealed during early childhood by steatorrhea and failure to thrive; ataxia and retinitis pigmentosa appear later. The originality of these two cases stems from: 1) their late and fortuitous diagnosis: the first sister was investigated at the age of 42 after the discovery of a vitamin K induced coagulation disorder. The other sister was 39 when she was routinely examined as a family member; 2) the presence of constipation without any other suggestive digestive complaint. However, white discoloration of the duodenal mucosa seen at endoscopy and lipid droplets within the intestinal absorptive cells at biopsy were characteristic. Barium studies showed diffuse involvement of the small bowel which was displaced by an enlarged sigmoid. Treatment consists of administration of vitamin A and vitamin E which prevent or delay ocular and neurologic symptoms. Vitamin K is associated whenever necessary.

[Malnutrition and deficiency of insulin secretion in alcoholic cirrhosis. Study by the assay of urinary C-peptide]. / Dénutrition et déficit de l'insulinosécrétion au cours de la cirrhose alcoolique. Exploration par le dosage du peptide C urinaire.

In order to evaluate the relationship between nutritional status and insulin secretion in cirrhosis, the following parameters of caloric (tricipital skin fold, prealbumin) and proteic (arm muscle size, transferrin, 24 h-urinary creatinine excretion) nutritional status were compared in 20 alcoholic cirrhotics and 10 normal subjects. Insulin secretion was evaluated in both groups by insulin and C-peptide response to an intravenous glucose tolerance test and by 24 h urinary excretion of C-peptide. When compared to normals, cirrhotics have lower values for all nutritional status parameters and individually for at least three of those in 14 (70 p. 100) patients. In cirrhotics there is a significant decrease of the 4-min poststimulative response of insulin and C-peptide, contrasting with higher basal and late poststimulative values than in normals. This contrast could be explained by a reduced metabolic clearance rate of insulin (consistent with insulin resistance) and of C-peptide (the urinary clearance of which is 2.5 times lower in cirrhotics than in normals). The 24-h urinary excretion of C-peptide, probably weakly dependent of this reduced clearance, is 50 p. 100 lower in cirrhotics: 12.9 +/- 1.6 nM/24 h than in normals: 26.0 +/- 2.4 nM/24 h (p less than 0.001). In cirrhotics there is a significant linear correlation between 24 h urinary C-peptide excretion and all the nutritional status parameters but one (prealbumin). These results indicate that in cirrhosis: 1) urinary C-peptide excretion rate is a good index of insulin secretion; 2) urinary C-peptide indicates a marked deficit in insulin secretion.(ABSTRACT TRUNCATED AT 250 WORDS)

[Study of insulin resistance in cirrhosis by the hyperinsulin euglycemia clamp]. / Exploration de l'insulinorésistance dans la cirrhose par le clamp euglycémique hyperinsulinique.

To explore the insulin resistance state in liver cirrhosis and to assess the respective role of insulin sensitivity and cellular metabolism alterations, an euglycemic glucose clamp was performed in 12 cirrhotic patients and 6 healthy volunteers with 3 successive hyperinsulinemic periods of 90 mn (infusions of 7, 20 and Iu/h). An artificial beta-cell model allowed to quantify the amount of glucose needed to keep glycemia at 4.70 mmol/l. In 7 cirrhotic patients, insulin secretion was tested by an intravenous glucose tolerance test. The dose-response curves showed a significant (p less than 0.01) decrease of the theoretical maximal metabolic clearance rate of glucose (capacity). The insulin concentration corresponding to the half-maximal response (ED50) did not differ between cirrhotic and control subjects because of a very important dispersion of individual values in cirrhotics. The ED50 value was lower than the values of control subjects in five cirrhotic patients and normal or enhanced in seven other patients; the former showed the most reduced values for capacity, and the latter a more marked hyperinsulinemia during the intravenous glucose tolerance test. The two subgroups of patients did not differ for clinical or biological parameters of cirrhosis, or for glucose tolerance. These results 1) show a constant and marked impairment of glucose metabolism capacity in liver cirrhosis, 2) and suggest that the insulin resistance inconstantly observed in this state is a consequence of chronic hyperinsulinemia.

[Determination of sub-populations of circulating T lymphocytes in alcoholic cirrhosis using monoclonal antibodies OKT3, 4, 5, Leu 2 and Leu 15. Effect of hepatitis B virus infection]. / Détermination des sous-populations lymphocytaires T circulantes au cours de la cirrhose alcoolique par les anticorps monoclonaux OKT3, 4, 8, Leu 2 et Leu 15. Influence de l'infection par le virus de l'hépatite B.

Peripheral T lymphocyte subpopulations were quantified in 24 alcoholic cirrhotic patients, 11 of them having anti-HBs and/or anti-HBc antibodies, and were compared with 35 healthy control subjects, 10 of them having anti-HBs and/or anti-HBc antibodies. The monoclonal antibodies utilized (OKT3, OKT4, OKT8 in simple staining, Leu 2 and Leu 15 in double staining) are considered as markers of mature (CD3), helper (CD4), cytotoxic/suppressor (CD8, Leu 2), suppressor (Leu [2+ 15+), and cytotoxic (Leu 2+ 15-) T cells. In cirrhotics, when compared to controls, the number of CD3 cells was reduced (p less than 0.01); the proportion of CD4 cells was within normal range, and that of CD8 cells diminished (p less than 0.001), contrasting with an increased proportion of Leu 2+ cells (p less than 0.01), related to an increased proportion of Leu 2+ 15+ cells. Leu 2+ 15- lymphocytes were within normal range. In control subjects, a decreased proportion of Leu 2+ 15+ cells was found (p less than 0.05) when Ac HBs and/or Ac HBc were present. In cirrhotics having at least one serologic marker of hepatitis B virus infection, when compared with negative ones, increased proportions of Leu 2+ (p less than 0.05) and Leu 2+ 15+ (p less than 0.05) cells were found. These results show that data concerning T lymphocyte subpopulations are conflicting when various types of antibodies are used. However, they suggest abnormalities of immune regulation, possibly a defect of T suppressor cell function. Hepatitis B virus infection probably modifies immune regulation in alcoholic cirrhosis, and perhaps in normal subjects.

[Granular cell tumors of the esophagus. Apropos of a case associated with bronchial carcinoma and treated by endoscopic excision]. / Les tumeurs à cellules granuleuses de l'oesophage. A propos d'un cas associé à un carcinome bronchique et traité par exérèse endoscopique.

The case of a granular cell tumor of the lower esophagus associated with a bronchial carcinoma is reported. The esophageal tumor was discovered by radiological and endoscopic examination for symptoms of gastroesophageal reflux and caused dysphagia after 6 1/2 years. An associated bronchial carcinoma led to the endoscopic removal of the esophageal tumor immediately prior to the thoracotomy. Eight days after operation the patient presented an hematemesis probably related to the endoscopic polypectomy. The course can be considered favorable after 17 months concerning the esophageal as well as the pulmonary situation. Histologically the esophageal tumor was a typical granular cell tumor and the bronchial tumor a squamous cell carcinoma. Seventy-nine cases of granular cell tumors of the esophagus have been published; 10 p. 100 of the cases are associated with bronchial, digestive or otorhinolaryngeal carcinoma. The onset of the carcinoma is usually subsequent to the esophageal tumor, justifying prolonged surveillance. This is the third case of a granular cell tumor of the esophagus treated by endoscopic polypectomy; this type of treatment requires close short-term follow-up because of the risk of hemorrhage as well as long-term follow-up because of the possibility of a second esophageal localization.

[Hepatitis B virus, serological markers of viral infections and humoral immunity in alcoholic cirrhosis]. / Virus de l'hépatite B, marqueurs sérologiques d'infections virales et immunité humorale au cours de la cirrhose alcoolique.

In order to define the role of hepatitis B virus (HBV) in alcoholic liver disease and to study the relationship between HBV and other common viruses, the serological markers of viral disease (HBV, Rubella, Polio, Herpes, and Cytomegalovirus-CMV) were compared in 163 patients with alcoholic cirrhosis (group C), 100 patients with alcoholic steatosis (group S) and in 168 non-alcoholic control subjects (group NA). A significantly increased prevalence of HBV markers in group C was related to the presence of anti-HBc antibodies, in 10.5 p. 100 of cirrhotic patients, vs. 1.2 p. 100 in group S and 1 p. 100 in group NA (p less than 0.01). In cirrhotic patients with HBV markers (HBV +) incidence of alcoholic hepatitis was 4 times lower and the total duration of alcohol overconsumption was significantly lower than in cirrhotic patients without these markers (HBV-). Hepatic function tests were not different in HBV + and HBV- cirrhotic patients, excepted for the ASAT/ALAT ratio (1.55 +/- 0.10 vs. 1.92 +/- 0.12; p less than 0.05). Prevalence of anti-CMV antibodies, and anti-herpes greater than 1/100 antibodies, was significantly increased in S and C groups (p less than 0.01). Anti-Rubella, Polio, and CMV antibody titers were higher (p less than 0.05) in HBV + than in HBV- cirrhotic patients. In cirrhotic subjects, titers of these 3 anti-virus antibodies were not related to alcoholic hepatitis or to IgG and IgM concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

[Consequences of hyperglycemia on glucose and nitrogen metabolism in liver cirrhosis. A study using a hyperglycemic clamp]. / Conséquences de l'hyperglycémie sur le métabolisme glucidique et azoté dans la cirrhose. Exploration par une épreuve de clamp hyperglycémique.

To study the consequences of hyperglycemia on glucose and nitrogen metabolism in cirrhosis, an hyperglycemic clamp was performed in 5 cirrhotic patients and 5 normal controls during two subsequent periods of 90 min, at 7.78 and then at 13.89 mmol/l. In the first period, glucose infusion and metabolic clearance rates were decreased in cirrhotics vs controls (p less than 0.05). In the second period, this difference between the two groups disappeared because of a more important enhancement in cirrhotics. Baseline plasma C peptide levels and those during hyperglycemia were the same during hyperglycemia in both groups, but plasma insulin level rose more in cirrhotics (p less than 0.05). Baseline insulin secretion following IV glucagon was reduced in cirrhotics vs controls (p less than 0.05), but became normal in the hyperglycemic state. Plasma glucagon levels were enhanced at all times in cirrhotics vs controls (p less than 0.01), but dropped more in cirrhotics vs controls (p less than 0.05). Insulin responsiveness, defined as the "glucose consumption: plasma insulin concentration" ratio was reduced in cirrhotics at 7.78 mmol/l (p less than 0.01), but was the same in both groups at 13.80 mmol/l because of a more important enhancement in cirrhotics, reflecting an improvement of insulin action probably at the post-receptor level and of non-insulin-mediated glucose transport. Hyperglycemia induced a drop in plasma concentration and muscular release of all aminoacids, excepted alanine, between the basal state and the end of the study. Aminoacid concentration rose only in cirrhotics, without any change in muscular output. In the same time, blood ammonia level rose only in cirrhotics, without reduction of muscular uptake.(ABSTRACT TRUNCATED AT 250 WORDS)

[Hepatic undifferentiated (or embryonal) sarcoma. Diagnostic and therapeutic problems apropos of botryoid rhabdomyosarcoma]. / Sarcomes indifférenciés (ou embryonnaires) hépatiques. Problèmes diagnostiques et thérapeutiques à propos d'un rhabdomyosarcome botryoïde.

Primary undifferentiated sarcomas (also called embryonal sarcomas or malignant mesenchymomas) are an exceptional form of cancer of the liver, occurring preferentially in children or adolescents. They can exhibit poor differentiation, embryonal rhabdomyosarcoma being the most frequent. To date, therapeutic success has been reported only rarely. The authors describe the case of a 16 year old boy with primary hepatic sarcoma showing a rhabdomyoblastic differentiation, who is in complete remission two years after total surgical resection and polychemotherapy.

[Effects of discontinuous intravenous infusion of ramified amino acids on blood insulin, blood glucagon and protein metabolism in cirrhotic patients after 10 days. Results of a controlled comparative study with sorbitol]. / Effets de la perfusion intraveineuse discontinue d'acides aminés ramifiés sur l'insulinémie, la glucagonémie et le métabolisme protidique chez le cirrhotique après dix jours. Résultats d'une étude contrôlée comparative avec le sorbitol.

In order to evaluate the effects of ramified amino acids on insulinaemia, glucagonaemia and protein metabolism, a 3-hour infusion of ramified amino acids (24 g in a 750 ml solution) was given daily during 10 days to 10 cirrhotic patients without hepatic encephalopathy (group I). Changes between the first and tenth day in plasma concentrations of plasma insulin, glucagon, ammonium, ramified and aromatic amino acids and 3 proteins (albumin, prealbumin and transferrin) markers of protein malnutrition were measured comparatively with 10 other cirrhotic patients who received daily a 750 ml infusion of 5 p. 100 sorbitol (group II). The patients, who had been randomized to group I or II, had à 2,200 calorie/day diet representing a 6 to 12 g nitrogen intake. The ramified amino acid infusions were well tolerated. They produced a significant (p less than 0.001) increase in glucagonaemia without significant change in insulinaemia, and a non-significant decrease of the plasma insulin/glucagon molar ratio. The arterial blood ammonium level was significantly (p less than 0.05) lowered in group I as compared to group II. The plasma ramified/aromatic amino acid molar ratio significantly (p less than 0.01) increased in group I but did not reach normal values; this increase was not significant when compared to group II. Finally, plasma concentrations of the 3 proteins indicating protein malnutrition remained low in both groups. These results suggest that daily intravenous administration of ramified amino acids for 10 days, to supplement a conventional diet failed to correct the protein hypercatabolism associated with cirrhosis; induced, however, a decrease in arterial blood ammonium levels.(ABSTRACT TRUNCATED AT 250 WORDS)

[Primary malignant melanoma of the digestive tract: esophagus and rectum. Apropos of 2 cases]. / Les mélanomes malins primitifs du tractus digestif: oesophage et rectum. A propos de 2 observations.

The authors report two cases of primary malignant melanoma. These primary neoplasms are exceptional on the GI tract. The diagnostical problems are discussed. The radiological features are a nodular lesion like an under-mucosa tumor.

[Oesogastrointestinal involvement in Behcet's disease. A report of one case (author's transl)]. / Localisations digstives de la maladie de Behçet. A propos d'une observation.

The authors describe the radiological features of a patient with Behcet's disease, who had oesogastric ulcers and a terminal ileitis as major part of this clinical syndrome. The radiologic appearance of these localisations are discussed. The similarities of Behcet's disease to Crohn's disease are outlined.

[Disturbances in glycoregulation and plasma amino acids in alcoholic hepatopathies. Study using the arginine test]. / Pertubations de la glycorégulation et de l'aminogramme plasmatique au cours des hépatopathies alcooliques. Exploration par le test à l'arginine.

In order to investigate disturbances in glycoregulation and plasma amino acids and their possible relationship in alcoholic liver diseases, plasma concentrations of insulin, C-peptide, glucagon and branched-chain (valine, leucine, isoleucine) as well as aromatic (phenylalanine, tyrosine) amino acids were measured during an arginine test (i.v infusion of arginine chloride 0.5 g/kg over 30 min) in 21 alcoholic patients: 11 with cirrhosis (group C) and 10 with steatosis (group S). Insulin responses to arginine was reduced in both groups, whereas glucagon response was increased in group C and reduced in group S. Plasma concentrations of branched-chain amino acids were reduced in both groups, irrespective of the degree of hyperinsulinism. Plasma concentrations of aromatic amino acids were increased only in cirrhotic patients; the increase was independent of the degree of hyperglucagonism and of the plasma insulin/glucagon molar ratio. These results suggest that disturbances of glycoregulation in plasma amino acids imbalance do not play a major role in alcoholic cirrhosis and steatosis.

[Evaluation of malnutrition and immunity in alcoholic liver diseases]. / Evaluation de la dénutrition et de l'immunité au cours des maladies alcooliques du foie.

Disorders of immunity and nutritional status are known to be present in alcohol-induced diseases of the liver, but their significance is still debated. Nutrition and immunity were evaluated at different stages of the disease in 58 alcoholic patients with steatosis (n = 20), alcoholic hepatitis (n = 14) or cirrhosis (n = 24). Most of the anthropometric data and biochemical values relating to nutrition were altered to the same degree in these 3 groups. Only patients with cirrhosis had significantly lower blood albumin and zinc levels (P less than 0.01). Humoral immunity was altered in cirrhosis only and cellular immunity in all 3 liver diseases. There was no correlation between immunity and nutrition (except for blood zinc and E rosettes; P less than 0.01) or between these and alcohol consumption. Like several nutritional parameters, blood lymphocyte values correlated negatively with a liver disease severity index. It is concluded that disorders of nutrition and immunity are broadly comparable in alcohol-induced liver diseases; there is no direct statistical correlation between these disorders which seem to be independent of the type of liver disease.

[Hemorrhage complications of acute pancreatitis (author's transl)]. / Les complications hémorragiques des pancréatites aiguës.

The authors report 11 cases of hemorrhage due to vascular ulcerations arising early or late in the course of acute pancreatitis. The seriousness of these hemorrhages, the difficulties of their therapy are pointed out. In all cases, bleeding should be controlled by surgery. Therefore, attention is drawn to the need for prompt laparotomy in all the shocked patients who failed to respond to conservative measures, for in such cases, a fatal outcome may rapidly occur. The respective advantages and inconveniences of the 2 main surgical treatments, ligation of bleeding vessels or pancreatectomy removing the source of bleeding, are discussed, basing on the presently reported cases and the data of the literature.