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OBJECTIVE: To examine the incidence and the bacteriological and clinical significance of endotoxaemia in ICU patients with severe sepsis or septic shock. DESIGN: Prospective review. SETTING: A 15-bed general ICU in a university hospital. PATIENTS: One hundred sixteen patients hospitalised in our ICU fulfilling Bone's criteria for severe sepsis or septic shock and with an available early endotoxin assay (chromogenic limulus assay). INTERVENTIONS: None. MEASUREMENTS AND RESULTS: The clinical characteristics of the population were: age 63.6 +/- 11.4 years; SAPS II: 45.4 +/- 15.6; mechanical ventilation: 72.4%; septic shock: 51.7% (n = 60); bacteraemia: 28.4% (n = 33); gram-negative bacteria (GNB) infection 47.4% (n = 55); ICU mortality: 39.6% (n = 46). Detectable endotoxin occurred in 61 patients (51.2%; mean level: 310 +/- 810 pg/ml). There was no relationship between detectable endotoxin and severity of infection at the moment of the assay. Endotoxaemia was associated with a higher incidence of bacteraemia (39.3% vs 16.3%; p = 0.01). There was a trend (p = 0.09) towards an association between positive endotoxin and gram-negative bacteraemia or GNB infection but this was non-significant. This relationship became significant only in the case of bacteraemia associated with GNB infection irrespective of the site of infection. CONCLUSION: Early detection of endotoxaemia appeared to be associated with GNB infection only in cases of bacteraemic GNB infection. Early endotoxaemia correlated neither to occurrence of organ dysfunction nor mortality in patients with severe sepsis or septic shock. This study suggests that the use of endotoxaemia as a diagnostic or a prognostic marker in daily practice remains difficult.

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A case of hyperinsulinism occuring in a newborn, with a birthweight of 4,050 g, is reported. The hypoglycaemia was refractory to the usual therapy (increase of glucose administration per os, and I.V., corticosteroids, glucagon, diazoxide). At surgery, undertaken at 9 days of age, an adenomatous nodule was removed along with the left part of the pancreas. Death occurred at 18 days, after the child had developed a transitory acidoketosic diabetes and an encephalopathy. Measurement of insulin by radio-immunoassay revealed a strong increase in the ratio insulin/glycaemia, characteristic of nesidioblastoma, as well as a high concentration of insulin in the tumor as compared to normal tissue. On the ultrastructural level, the observed features differed from those seen in children and adults and showed an abnormal overload of dense deposits in the cytoplasm of some histiocytes.

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The effect of the nutritional state (fasted or fed) on the binding of glucagon and on the glucagon-stimulated cyclic AMP accumulation in the presence of theophylline was studied in isolated rat liver cells. The binding of glucagon was higher in cells from fed than in those from fasted rats at each concentration of glucagon tested between 0.1 and 36 nM. The specific binding of the hormone was about 2-fold higher in cells from fed than from fasted rats. At concentrations of glucagon between 0.1 and 2.2 nM, the accumulation of cyclic AMP in the presence of 1 mM theophylline was higher in the cells from fed rats. Furthermore, 4 times as much glucagon was required to elicit half-maximal cyclic AMP accumulation in the cells of fasted (1.47 nM) than in the cells of fed (0.35 nM) rats. These data suggest that, in isolated rat liver cells, both glucagon binding to receptor sites and glucagon-stimulated cyclic AMP levels in the presence of theophylline can be affected by the nutritional status of the animal.

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Insulin, proinsulin and glucagon extracted from lean rat pancreases were studied in radioimmunoassay, radioreceptorassay and bioassay systems. Extracted insulin behaved identically to a rat insulin used as a reference standard in radioimmunoassay. On the basis of its immunoreactivity, extracted insulin was slightly less potent (about 70%) than the rat standard insulin in competing with the binding of 125I-insulin to rat liver membranes (radioreceptorassay) and in stimulating glucose oxidation by rat fat cells (bioassay). Extracted glucagon and a pork glucagon used as a reference standard were indistinguishable in two radioimmunoassay systems for glucagon, in competing with the binding of 125I-glucagon to rat liver membranes (radioreceptorassay) and in stimulating adenylate cyclase in rat liver membranes (bioassay). Genetically obese rats (Zucker, "fatty") were compared to their lean littermates with respect to insulin, proinsulin and glucagon extracted from their pancreases. Proinsulin represented the same proportion of total immunoreactive insulin in both types of rats. In the radioimmunoassays, the radioreceptorassays and the bioassays, insulin, proinsulin and glucagon from obese rats were indistinguishable from insulin, proinsulin and glucagon from lean rats. It is concluded that the pancreatic hormones of obese ("fatty") rats possess the same immunoreactivity and biological potency as those of nonobese rats. This excludes the possibility that some alteration in the biological properties of pancreas insulin and/or glucagon of fatty rats could explain the metabolic abnormalities observed in this type of obesity.

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