[Extrahepatic portal vein thrombosis following laparoscopic cholecystectomy]. / Extrahepatische Pfortaderthrombose nach laparoskopischer Cholezystektomie.

Postoperative portal vein thrombosis is a rare complication, which occurs most often after hepatic surgery, but has not yet been described in combination with laparoscopic cholecystectomy. We present a case where thrombotic occlusion of the portal vein was diagnosed on the 6th day following laparoscopic cholecystectomy. Treatment with high-dose anticoagulant and antibiotic therapy was successful and without further complications.

Effect of aging on hepatic carbohydrate metabolism in septic rats.

Aged individuals have diminished resistance to severe sepsis and septic shock. Past work with animals suggested that an important determinant of survival was the ability of the liver to supply glucose. In this study, young adult (3 to 4 months) and old (24 months) Fischer 344 rats were fasted and subjected to cecal incisions producing a rapidly lethal peritonitis. We then determined gluconeogenic intermediates in the liver. In the old rats with peritonitis, hexosemonophosphates (HMP) increased 50% relative to control liver, whereas in the young animals with peritonitis, the substrate decreased 50%. The accumulation of HMP in the old rat liver cells indicates a failure to dephosphorylate glucose-6-phosphate (G6P). This increase in HMP is associated with a decline in hepatic glucose-6-phosphatase (G6Pase), the final enzyme in the gluconeogenic pathway, and is reflected in a significant reduction in serum glucose in old Fischer 344 rats when compared to young Fischer rats.

Hepatic glycolytic intermediates in fed and fasted rats after severe hemorrhage.

The responses of key liver carbohydrate intermediates to severe hemorrhage were investigated in fed and fasted young adult male rats. Forty per cent of intravascular blood was withdrawn and liver was sampled by freeze-clamp at 0, 0.25, 1.0, 3.0, and 4.0-5.0 hours. Fed rats with abundant glycogen showed a threefold increase in glucose-6-phosphate (G6P) concentration, and fasted rats showed a 75% decline in G6P immediately after hemorrhage. This significant difference in response traces to the fact that G6P is one of the first catabolites in fed liver formed by glycogenolysis but is the last intermediate of the gluconeogenic pathway in fasted animals. Phosphoenolpyruvate (PEP), the high-energy intermediate, was markedly depleted in both fed and fasted rats at zero time. In the fasted animal, however, the PEP was rapidly restored, and by 1.0 hour was threefold above normal. The ability of fasted rats to rapidly synthesize glucose from accumulated lactate is attributed to increased amount of gluconeogenic enzymes induced by fasting. In prolonged shock states, this synthetic capacity plays a protective role. Contrariwise, in brief shock states such as hemorrhage, the immediate availability of glucose from stored glycogen appears to be a more important determinant of survival. In the present experiments, fed rats were more resistant to the hemorrhage protocol.

A molecular hypothesis on parallel memory function with relevance to senile dementias.

The hypothesis is presented that closely associated memories can be coded and decoded in a parallel manner analogous to genetic deoxyribonucleic acid (DNA) forming two or more different proteins from a single polynucleotide strand. Iconic, aural, and lexical stimuli could be imprinted and recovered from the same storage molecule. The described process which involved the decoding of the same neuronal DNA macromolecule two or more times but from slightly shifted reading frames has the advantage of promoting fidelity of coding and decoding. The suggested mechanism also explains why it is possible for some mnemonic elements to survive during aphasia and senile dementias, while closely linked synonymous engrams are lost.

Endotoxin lethality is intensified by inhibited gluconeogenesis.

There are two major etiologies regarding the lethal element in the pathophysiology of endotoxemia and severe gram-negative sepsis: 1) metabolic lesions culminating in terminal hypoglycemia and 2) circulatory deficits resulting in early peripheral and late vital organ perfusion failure. Although not mutually exclusive, a direct test of the relative importance of either hypothesis is needed. The impact of inhibited gluconeogenesis on endotoxin lethality in young adult male rats (180-220 g) was investigated. Fasted rats received 20 mg/kg intravenous E. coli endotoxin (LD10) simultaneously with 500 mg/kg intraperitoneal L-tryptophan. This amino acid rapidly forms quinolinic acid, which blocks liver glucose synthesis. Endotoxin together with tryptophan caused hypoglycemic convulsions, killing 22 of 24 rats, 75% within 6 hours. In parallel studies, liver intermediates were assayed in freeze-clamped samples obtained at 5 hours from ether anesthetized rats. The high-energy intermediate phosphoenolpyruvate was 222 +/- 79 nmole/gm +/- 1 S.D. wet liver in the moderately endotoxic rats (N = 8). In the endotoxin-plus tryptophan group (N = 7), the PEP intermediate had fallen to 58 +/- 24 nmole/gm liver (P = 0.005). Liver lactate was increased 2.8-fold over the value in the endotoxin-only group, to 4390 nmole/gm wet tissue, showing the failure to utilize gluconeogenic precursors. Tryptophan given alone was not lethal. It is concluded that inhibited gluconeogenesis greatly intensifies the hepatic metabolic derangement of endotoxemia.

The mediated effect of endotoxin and lead upon hepatic metabolism.

A test was made of the possibility that gram-negative bacterial cell wall lipopolysaccharides acted directly on key glucoregulatory enzymes in rat liver cytosol to cause the characteristic hypoglycemia of severe endotoxemia. Fasted male rats were sensitized to endotoxin by the simultaneous intravenous injection of lead acetate. The minimum systemic dosage of endotoxin necessary to perturb the normal pattern of hepatic glycolytic intermediates was determined by serial testing with diminishing dosages of endotoxin. The hepatocyte concentration of endotoxin was then calculated from this minimum dosage by use of literature data on the fraction of endotoxin delivered to liver cells after a systemic intravenous injection of radiochromium labeled lipopolysaccharides. Accepting a molecular weight of 118,000 daltons for the smallest endotoxin monomer capable of evoking a physiologic response, the molar amount of endotoxin present in 1 gram of hepatocytes was readily calculated. The concentration of glucoregulatory enzymes in parenchymal cells was then estimated from other literature sources. It was found that the amount of endotoxin in the hepatocytes was insufficient to combine directly with even 1 per cent of the quantity of a single key glucoregulatory enzyme in liver parenchyma. Since a one to one stoichiometric reaction between endotoxin and enzyme could not occur in the liver cytosol, a direct interaction mechanism between agonist and biocatalyst can be ruled out. It is concluded that bacterial endotoxin must act on hepatic glucoregulation by an indirect mechanism presumably based upon the release and operation of mediators.