Relationship between the number and type of alcohol outlets and mortality due to liver cirrhosis and traffic accidents

The aim of the study was to determine the effect on liver cirrhosis and driver and motorcyclist mortality of changing the alcohol outlet rates in New South Wales relative to the adjacent control State of Victoria. A longitudinal study design with a six year before period (1968-1973) and a nine year after period (1974-1982) was used. A 10.5% relative increase in the total outlet rate for New South Wales during the after period was associated with significant increases in liver cirrhosis mortality (males + 22.1%, females + 17.7%) and driver and motorcyclist mortality (males + 19.8%, females + 18.9%) in comparison to the control state. The analyses also indicated that the increases in the dependent variables were apparently due to the higher outlet rates for restaurants and stores rather than for hotels and taverns. Attention is drawn to a number of limitations of the study design.     

The effect of arachidonic acid on the M current of NG108-15 neuroblastoma × glioma hybrid cells

The M current, I _M, a voltage-dependent non-inactivating K⁺ current, was recorded in NG108-15 neuroblastoma × glioma hybrid cells, using the whole-cell mode of the patch-clamp technique. We studied the effect of arachidonic acid, other fatty acids and inhibitors of the arachidonic acid metabolism. In relatively high concentrations (25–50 M) arachidonic acid first increased and later decreased the current, I _h, which holds the membrane potential at –30 mV and mainly flows through open M channels. It shifted the midpoint potential, V _o, of the relation between M conductance, g _M, and membrane potential, V, to more negative values and decreased the maximum conductance ¯g _M and the time constant _M. In smaller concentrations (5–10 M) arachidonic acid merely decreased I _h and ¯g _M with little effect on V _o and _M. Eicosatetraynoic acid and docosa-hexaenoic acid acted similarly to arachidonic acid whereas stearic acid had no effect. Of the three enzyme inhibitors studied, nordihydroguaiaretic acid acted similarly to arachidonic acid. i. e. caused a biphasic change in I _h. Indomethacin and quinacrine caused, respectively, a pure increase and a pure decrease of I _h and ¯g _M. Possible explanations are build-up of internally produced arachidonic acid, depletion of eicosanoid products or an inhibitory effect unrelated to arachidonic acid metabolism.     

α1-adrenergic receptors in the liver parenchyma in children: Changes associated with cirrhosis

All-Russian Research Center for Molecular Diagnosis and Treatment, Ministry of Health of Russia. Research Institute of Pediatrics, Russian Academy of Medical Sciences, Moscow. (Presented by Academician of the Russian Academy of Medical Sciences M. Ya. Studenikin.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 114, No. 8, pp. 134–135, August, 1992     

Hepatic levels of prostaglandins F2α and I2 (prostacyclin) and of thromboxane A2 in dogs developing hemorrhagic shock

Professorial Department of Surgery, L'vov Medical Institute. L'vov Branch, Kiev Research Institute of Hematology and Blood Transfusion. (Presented by Academician of the Academy of Medical Sciences of the USSR V. S. Savel'ev.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 113, No. 2, pp. 134–135, February, 1992.     

Artificial liver

Without transplantation, approximately 90% of patients with fulminant hepatic failure die. If patients receive a liver transplant, there is often a lag between the need for and the availability of a donor liver. Therefore, there is a definite need for a liver support system to support the patient's own liver function in fulminant hepatic failure and while awaiting transplantation. We have developed an artificial liver system that not only eliminates lipophilic toxins such as phenols, fatty acids, and mercaptans, but also hydrophilic ones such as ammonia. This artificial liver system consists of a monitor, an extracorporeal blood circuit that uses a hydrophilic polysulfone high-flux dialyzer to remove water-soluble metabolites, and a novel hydrophilic liquid membrane filter to remove lipophilic toxins. In more than 100 in vitro experiments using porcine (5 I) blood, the system was evaluated for its ability to remove toxins that are normally increased in hepatic failure. We found that phenol, cresol, and short- and medium-chain fatty acids can be almost completely eliminated from the blood within 5 h. In animal experiments using pigs, we also found no significant changes of blood gases, liver parameters, electrolytes, and blood cell counts.     

The role of spontaneous portosystemic shunts in the course of orthotopic liver transplantation

Spontaneous portosystemic shunts are commonly found in cirrhotic patients. Not yet established is their role after orthotopic liver transplantation (OLTx), especially when an increase in portal pressure develops, as during early acute rejection. In this study, 34 cirrhotic patients in a series of 70 OLTx are considered. Each patient had preoperative angiographic assessment, and, in 21 (62%), large spontaneous portosystemic shunts were evident. In 12 cases the shunts were not affected by the surgical procedure and were present during the postoperative period; in 9 the hepatectomy itself involved interruption of the shunts. The patient population was divided into two groups: patients with postoperative shunts (n=12) and those without (n=22). The two groups were similar in age, sex, Child's stage, transplantation variables, and number and grade of rejection episodes. However, mean transaminases (AST) values in the first 2 weeks were significantly higher levels in shunt versus nonshunt patients (421±335 vs 183±126; P<0.025), and this was even more evident when rejection occurred (626±375 vs 195±129; P<0.001). Furthermore, during an acute rejection reaction, three cases showed a true steal phenomenon through the large reopened shunts with ischemic damage to the grafts. The data indicate a possible detrimental effect of the spontaneous shunts on graft perfusion and suggest the prophylactic surgical interruption of the residual shunts during the transplantation.     

Receptor-recycling model of clearance and distribution of insulin in the perfused mouse liver

Summary After perfusion of mouse livers with A₁₄-¹²⁵I-insulin for designated intervals, an acid-wash technique was employed to separately measure the surface-bound (X_s) and intracellular (X_i) A₁₄-¹²⁵I-insulin, as well as intracellular degradation products (X_deg) of labelled insulin. From the perfusate concentrations (C_p) of A₁₄-¹²⁵I-insulin, the apparent intrinsic hepatic clearance of labelled insulin at a high dose (0.2 nmol/l) was shown to be 60% smaller than that at a low dose (0.018 nmol/l), indicating that the cellular uptake of insulin is remarkably nonlinear at the concentration range examined. From the time courses of C_p, X_s, X_i and X_deg, the hepatic insulin disposition was shown to be largely accounted for by the receptor-mediated endocytosis. The observed data at the low dose were analysed to estimate biochemical parameters, (i.e., total receptor number, endocytotic rate constant and intracellular degradation rate constant) according to receptor-recycling and non-receptor-recycling models, using a computer-aided optimization procedure. The receptor-recycling model could not only adequately explain the C_p, X_s, X_i and X_deg at the low dose, but also predict the C_p at the high dose. On the other hand, a non-receptor-recycling model, in which recycling of receptors was not assumed, could also explain the observed data at the low dose, but failed to predict the C_p at the high dose, indicating that the receptor recycling process is necessary to explain the hepatic insulin clearance at high insulin concentrations, at which hepatic insulin clearance should be limited by the rate of receptor recycling. However, the applicability of our model might be limited within the physiologic insulin concentrations, because of the negative co-operativity of insulin-receptor interaction and a high-capacity, non-degradative and more rapidly recycling pathway for receptors that may occur at high concentrations of insulin. In conclusion, we have developed a mathematical model of hepatic insulin clearance and distribution under physiological conditions, including receptor binding, receptor-mediated endocytosis and receptor recycling, which has been so far demonstrated using isolated hepatocytes.     

Prognostic value of galactose elimination capacity,aminopyrine breath test,and ICG clearance in patients with cirrhosis

Seventy-eight patients with cirrhosis were prospectively followed for up to 20 months, on the average. At entry into the study, galactose elimination capacity, aminopyrine breath test, and ICG clearance were measured. At the end of the study, 27 patients had died. Univariate analysis using the Kaplan-Meier method showed that both quantitative liver function tests (galactose elimination capacity:P<0.025; aminopyrine breath test:P<0.001; ICG clearance:P<0.005) and common clinical and biochemical data (encephalopathy:P<0.001; ascites:P<0.001; serum bilirubin:P<0.005; serum albumin:P<0.001; prothrombin index:P<0.05) were significant predictors of survival. To investigate whether quantitative liver function tests could contribute to a better definition of the prognosis, once Pugh score had already been taken into account, a multiple regression analysis according to the Cox model was performed. Pugh score and galactose elimination capacity resulted in the only independent prognostic covariates. From them a prognostic index was calculated, and the model was validated in an additional sample of 70 patients investigated according to the same protocol. The contribution GEC gave to the assessment of overall prognosis over that obtained using the Pugh score was slight, as estimated by the statistical parameters of the Cox's model, but was significant as assessed by a ROC curve analysis (P=0.05). These data show that all quantitative liver function tests were predictors of survival in cirrhosis, and that the galactose elimination capacity added some new prognostic information to those already available using the Child-Turcotte-Pugh classification.This study was supported in part by a grant from the Italian Ministry of Education (National Project Liver Cirrhosis). Part of this study was presented at the 22nd Meeting of the European Society for Clinical Investigation, Graz, Austria, April 20–23, 1988.     

Protooncogenes and growth factors associated with normal and abnormal liver growth

Hepatocyte replication during liver regeneration depends on extrinsic (circulating) and intrinsic (intrahepatic) factors. Two important growth factors produced in the regenerating liver are discussed, TGF, an autocrine, stimulatory growth factor, and TGF, a paracrine inhibitory factor. The balance between the activities of these factors is likely to play an important role in regulating hepatocyte proliferation. The experession of some protooncogenes occurs sequentially during the first few hours after partial hepatectomy and is a marker for the entry of hepatocytes into the cell cycle (proliferative competence). As hepatocytes become competent to proliferate, they respond to TGF and other growth factors and enter a proliferative phase. It is possible that TGF1 serves as a stop signal for liver regeneration but the mechanisms by which TGF inhibits hepatocyte DNA synthesis are still unknown.Presented at the Proceedings of the International Meeting on Normal and Neoplastic Growth in Hepatology, Bari, Italy, June 1989.     

Cutting oil dermatitis on guinea pig skin

The effect of repeated exposure of cutting oil on 8 guinea pigs' skin was evaluated by visual scoring for erythema and skin water vapour loss (SVL) measurement over a 6-week period. The visual scores (measuring severity of erythema) and SVL values were significantly higher on skin treated with cutting oils (positive control) compared to untreated skin (negative control) throughout the study period. The scores and SVL values returned to near-baseline values when cutting oil application was stopped. In addition, the effect of 2 "after-work" emollient creams on 8 guinea pigs' skin repeatedly treated with a cutting oil was assessed by similar methods. The visual scores and SVL values of guinea pig skin that was repeatedly treated with the cutting oil and moisturized with "after-work" emollient creams, were significantly higher than negative and positive control guinea pig skin. It appeared that the 2 "after-work" emollient creams do not alleviate the irritant effect of the cutting oil on guinea pig skin. They appeared to aggravate the irritant effect of the cutting oil.