Modification of the Fe Protein of Nitrogenase in Natural Populations of Trichodesmium thiebautii.

The Fe protein of nitrogenase in the marine nonheterocystous cyanobacterium Trichodesmium thiebautii is interconverted between two forms, which is reminiscent of the ADP-ribosylation described in the purple bacterium Rhodospirillum rubrum. In natural populations of T. thiebautii during the day, when nitrogenase activity (NA) is present and while photosynthetic rates are high, a low-molecular-mass form of the Fe protein is present. In the late afternoon, the low-molecular-mass form is partially converted to a higher-molecular-mass form (approximately equal distribution of high- and low-molecular-mass forms of the Fe protein subunits), concurrent with cessation of NA. Some of the higher-molecular-mass form persists through the night until the very early morning, when the lower-molecular-mass form appears. New synthesis of both the Fe and MoFe proteins of nitrogenase appears to occur at this time. The higher-molecular-mass form of the Fe protein is also produced rapidly in response to artificially elevated external O(2) levels (40%) during the day. T. thiebautii is capable of recovery of NA in less than 1 h following exposure to 40% O(2), which is correlated with the return of the Fe protein to the lower-molecular-mass form. Recovery from exposure to O(2) is not dependent upon protein synthesis. The modification of the Fe protein is clearly involved in regulation of NA during the diel cycle of NA in T. thiebautii but may also be involved in protecting the Fe protein during transient O(2) concentration increases.

Prognostic value of indocyanine green and lidocaine kinetics for survival and chronic hepatic encephalopathy in cirrhotic patients following elective end-to-side portacaval shunt.

The objective of this study was to assess the prognostic value of spontaneous portosystemic shunting and liver function for survival and spontaneous hepatic encephalopathy after end-to-side portacaval shunt in cirrhotic patients. One hundred ninety-eight patients with variceal hemorrhage as shown by endoscopy were evaluated. Forty-five were excluded because of uncontrollable hemorrhage; 84 were rejected because they were poor operative risk, had portal vein thrombosis or had been previously treated with beta-blockers, sclerotherapy or surgery. The remaining 69 patients were enrolled in this prospective study. There were 43 patients with alcoholic cirrhosis, 23 with cryptogenic cirrhosis and three with primary biliary cirrhosis. The severity of liver disease was assessed according to the Pugh classification: 37 patients (54%) had Pugh's score 5 to 7, 26 (38%) had 8 to 10 and six (8%) had 11 to 12. Indocyanine green intrinsic clearance was used as a probe of preoperative liver function and lidocaine systemic availability as an index of spontaneous preoperative shunting. All the patients underwent an elective end-to-side portacaval shunt. The length of minimal follow-up was 40 months. One-year survival was 76% and 5-year survival was 46%. During follow-up, 25 patients died from their liver disease and 11 patients died from various causes unrelated to their liver disease. Spontaneous chronic encephalopathy occurred in 16 patients (23%). Age, Pugh's score, active alcoholism, indocyanine green intrinsic clearance and lidocaine systemic availability were tested as prognostic factors in a multivariate analysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Emergency portacaval shunt for variceal hemorrhage. A prospective study.

Emergency portacaval shunt for variceal bleeding is associated with a high operative mortality, particularly if used as a last resort. Because of this, a strong case has been made against emergency shunt. This report describes an experience with emergency portacaval shunt for the treatment of variceal bleeding when used systematically after hemodynamic stabilization and control of the bleeding episode with balloon tamponade, if necessary, in patients with mild or moderate liver disease. The population studied comprised 62 consecutive patients who rebled from varices while participating in a controlled trial of propranolol for the prevention of rebleeding. Of the 62 patients, nine died of massive hemorrhage and 53 survived the hemorrhage. Of the 53 survivors, 11 had severe liver disease and were not considered for shunt surgery. Of the remaining 42 patients with mild or moderate liver disease, 36 had emergency central portacaval shunt. The interval between endoscopic diagnosis of variceal bleeding and surgery averaged 19 +/- 3 hours (mean +/- SE). The operative mortality rate, defined as in-hospital mortality, was 19%. One- and 2-year survival rates were 78% and 71%, respectively. The incidence of postoperative hepatic encephalopathy was 36%; all patients responded favorably to protein restriction and lactulose. Thus, under specific conditions, emergency portacaval shunt results in an acceptable long-term survival rate. In patients with mild or moderate liver disease, emergency portacaval shunt should be considered when other forms of treatment for the prevention of variceal rebleeding have failed.

Inhibition of liver regeneration by chronic alcohol administration.

Liver regeneration is the common mechanism whereby a patient recovers form a liver injury. In the western world, ethanol is the single most important aetiological factor associated with liver disease, and it appears crucial to determine if ethanol interferes with liver regeneration. We studied the response to a 70% hepatectomy in 240 rats receiving a nutritionally adequate diet containing 36% of their calories as ethanol for three weeks and their pair-fed controls receiving a liquid diet where ethanol is isocalorically replace with carbohydrates. Criteria of liver regeneration were: incorporation of 3H-thymidine in hepatocyte DNA (cpm/10 microgram DNA) and number of hepatocyte labelled nuclei on autoradiography per 100 high power fields. Controls displayed the usual response with peak activity of liver regeneration at 24 hours. Consumption of ethanol was associated with a statistically significant reduction of liver regeneration by both criteria for up to 72 hours after a 70% hepatectomy and delayed the peak of regenerative activity by 24 hours. This inhibiting effect was not related to the presence of alcohol in blood nor to hepatic microsomal enzyme induction by ethanol nor to widespread necrosis of hepatocytes. This effect was reversible after one week of abstinence. This impairment of liver cell renewal by ethanol may be of major significance in the severity and outcome of alcohol-related liver injury.

Blood-brain transport of tryptophan and phenylalanine: effect of portacaval shunt in dogs.

The blood-brain uptake process for tryptophan and phenylalanine was investigated using the multiple-indicator dilution technique in 13 unanesthetized dogs with and without portacaval shunts. Tracer doses of labeled albumin (extracellular reference) and tryptophan or phenylalanine, prepared in autologous dog plasma, were injected into one carotid artery, and dorsal sagittal sinus dilution curves were obtained. Portacaval shunting was not associated with significant changes in the initial brain uptake ratio U for tryptophan or phenylalanine, despite increases in plasma phenylalanine and tyrosine. In the 13 dogs, U was not significantly correlated with the plasma levels of either the different branched-chain or aromatic amino acids or the molar ratio between these groups. These findings do not support the current hypothesis that the active transport of aromatic amino acids across the blood-brain barrier is increased after portacaval shunt. Our data suggest, instead, that the blood-brain uptake process for aromatic amino acids is linear and increases in shunted animals because their plasma levels are increased.

Symposium on portal hypertension and its complications: current management. Preoperative assessment and predictors of encephalopathy.

None of the preoperative predictors of encephalopathy proposed so far to evaluate the risk of portacaval shunting in cirrhotic patients has been of value. The authors have found, in preliminary studies, that measurement of the hepatic extraction of indocyanine green (ICG), which correlates highly with the "functional" portal blood supply, could be of prognostic value: cirrhotic patients with a near-normal value for ICG extraction often have encephalopathy after portacaval shunting whereas those with a low ICG extraction value seldom have encephalopathy. These preliminary data suggest that cirrhotic patients with markedly decreased ICG extraction have a lesser risk of encephalopathy since their portal blood supply is already shunted away from hepatocytes before the operation because of anatomic changes in the liver microcirculation.

Criteria for selection of patients for emergency portacaval shunt.

A computer program analysis of the effect on survival of 74 preoperative factors was performed as part of a prosepctive study of the emergency portacaval shunt in 146 unselected patients with bleeding esophageal varices due to alcoholic cirrhosis. Only ascites, a serum glutamic oxalacetic transaminase level of 100 units or more, and a requirement for 5,000 ml or more of blood transfusion were associated with a statistically significant decrease in survival. However, none of these factors are contraindications to operation because their presence permits a survival rate of 37 to 40%. The only contraindication to emergency portacaval shunt is the combined presence of ascites, jaundice, encephalopathy, and severe muscle wasting, a constellation that was incompatible with survival beyond one year.