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1. Experiments performed on isolated hepatocytes and perfused liver of starved chickens showed that gluconeogenesis from lactate, glycerol and fructose was inhibited by 22-100% on addition of urate precursors. 2. The inhibition was associated with an increased rate of urate formation. 3. 2,4-Dinitrophenol (40 microM), 2-bromooctanoate (2 mM) and 3-mercaptopicolinate (3MPA) (0.5 mM) were inhibitory with respect to gluconeogenesis but did not significantly affect the rate of urate formation. 4. The possible interrelationships between gluconeogenesis and uricogenesis are considered in terms of a competition for ATP and for other metabolites between the two pathways. 5. An interplay of both pathways at the level of anion transfer across the inner mitochondrial membrane is also discussed.

In order to determine prognostic factors in noncardiac medical patients treated by mechanical ventilation in a Veterans Administration hospital, 78 patient records were reviewed. Disease severity was scored by the Acute Physiology and Chronic Health Evaluation (APACHE) II system. Physicians' prior impressions of prognostic factors were compared with the actual results of this study. Most patients were middle-aged men with respiratory diseases. Fifty-nine patients (76 percent) died in the hospital. Survivors of hospitalization and nonsurvivors had similar age, diagnoses, emergency intubations, duration of ventilation, and pH and oxygen tension after 24 hours of ventilation. However, only one of 31 patients with a serum albumin level of 2.5 g/dl or less at the initiation of mechanical ventilation survived (p less than 0.001). Of 24 patients requiring a fractional inspired oxygen concentration greater than 50 percent at 24 hours, none survived (p less than 0.005). At all APACHE II scores, the mortality rates documented in this study were higher than predicted. Physicians overestimated the impact of several variables, including age and presence of pneumonia, on mortality. At the San Francisco Veterans Administration Medical Center, a low serum albumin level may aid in the decision whether to begin mechanical ventilation, and a high fractional inspired oxygen concentration at 24 hours may aid in the decision regarding further aggressive care. These findings need to be validated in other patients before being applied. Conversely, certain older patients, and those undergoing emergency intubation or intubation for a prolonged time, may have as good a prognosis as patients without these factors.

We describe the occurrence of hyperkalemia in a stable hemodialysis patient who developed digoxin toxicity. The patient had been receiving digoxin for 2 years. His maintenance digoxin dose was increased from 0.125 to 0.25 mg three times a week, which resulted in a toxic serum level of 4.9 ng/mL (therapeutic range is 0.8 to 2.0 ng/mL). As a consequence of the digoxin toxicity, he became hyperkalemic (7.8 mEq/L), and this value returned to normal only after the digoxin level was lowered by a combination of oral charcoal and dialysis. This study shows how readily hyperkalemia can occur in an anephric patient manifesting digoxin toxicity. Thus, potentially lethal hyperkalemia can occur in hemodialysis patients who ingest therapeutic quantities of digoxin. Digoxin toxicity should be added to the differential diagnosis of hyperkalemia in patients with renal failure. This can occur despite the absence of a history of massive ingestion of a cardiac glycoside.

Phosphate-activated glutaminase (PAG) and glutamic acid decarboxylase (GAD) were assayed in homogenates and synaptosomes obtained from starved (48 hr or 120 hr) and diabetic (streptozotocin) rat brain cortex. Glutamine synthetase (GS) was assayed in homogenates, microsomal and soluble fractions, from brain cortex of similarly treated rats. L-Glutamate uptake and exit rates were determined in cortex slices and synaptosomes under the same conditions. The specific activity (s.a.) of PAG, a glutamate producing enzyme, decreased (50%) in the homogenate after 120-hr starvation. In synaptosomes it decreased (25%) only after 48-hr starvation. The s.a. of GAD and GS, which are glutamate-consuming enzymes, were progressively increased with time of starvation, reaching 39% and 55% respectively after 120 hr. GS in the microsomes or the soluble fraction and GAD in the synaptosomes showed no change in s.a. under these conditions. Diabetes increased (40%) microsomal GS s.a. and decreased GAD s.a. (18%) in the homogenate. The L-glutamate uptake rate was decreased (48%) by diabetes in slices but no in synaptosomes. It is suggested that a) enzymes of the glutamate system respond differently in different subcellular fractions towards diabetes or deprivation of food and b) diabetes may affect the uptake system in glial cells but not in neurons.

Physicians routinely order urinary ketone testing for most patients with diabetes mellitus upon hospitalization, even in the absence of a history of diabetic ketoacidosis. To determine whether testing for urinary ketones is clinically useful in patients with non-insulin-dependent diabetes mellitus (NIDDM), a retrospective review was undertaken of 152 charts of patients admitted to the hospital during a 6-mo period with the diagnosis of diabetes mellitus. Of the 135 patients with NIDDM, 96% had routine testing performed for urinary ketones. Surprisingly, 26% of the patients with NIDDM had positive urine ketones at some time during hospitalization, and the degree of ketonuria was markedly greater did not reflect diabetic ketoacidosis. Ketonuria was accompanied by significant hyperglycemia and most likely reflects relative insulinopenia. Only 23% of the episodes of ketonuria were acknowledged in the progress notes. Although NIDDM patients who had ketonuria in the hospital were more likely to be transiently treated with insulin than patients without ketonuria, in no instance did the progress notes state that a diagnostic test or change in therapy was ordered because of the presence of a positive test for urinary ketones. The primary goal for therapy of patients with NIDDM should remain good control of blood glucose. In the hospitalized patient in whom frequent blood glucose determinations are made, it is not clear that urinary ketone testing needs to be routinely done.