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Objective: To describe a case of behavioral changes induced by indomethacin in an elderly man with a history of senile dementia of the Alzheimer type., Case Summary: A 92-year-old white man with a history of senile dementia of the Alzheimer type, glaucoma, and constipation was treated with indomethacin for an episode of pseudogout. After six doses of indomethacin 25 mg, the patient became very agitated, confused, and was physically and verbally aggressive to the nurses. Indomethacin was discontinued and the patient recovered after receiving haloperidol 0.5 mg/d p.o. over a period of 10 days., Discussion: Only a few cases of psychosis have been reported in the literature concerning the use of indomethacin in patients over the age of 60 years. The mechanism by which indomethacin causes psychosis is not well understood, but it is postulated that the acute psychosis may be related to the similarity between the molecular structure of indomethacin and serotonin. Both indomethacin and serotonin have an indolic moiety, which may explain the development of acute psychosis in this patient., Conclusions: Healthcare providers should be aware that patients with a history of dementia who are receiving indomethacin may be at risk of developing severe behavior problems along with gastrointestinal and renal adverse effects.

Fractional hepatic extraction of glucose was determined from the appearance in the systemic circulation of ingested 3-[3H]glucose. Using the glucose clamp technique, studies were done under steady-state conditions of basal glycemia and insulinemia, normoglycemia (0.8 mg/mL) and mild hyperinsulinemia (approximately 40 microU/mL), hyperglycemia (2 mg/mL-1) and hyperinsulinemia (approximately 100 microU/mL). Based on previous results in the dog, an oral glucose load of 2 g was used to label the portal vein glucose; this amount was chosen so as to minimize disturbance of the portal steady state but still avoid excessive loss during absorption. Additional subjects with hyperglycemia and hyperinsulinemia received an oral load of 50 g of glucose. Fractional extraction in normal subjects under near-basal conditions of glycemia and insulinemia was 19% in normal subjects and in patients with noninsulin-dependent diabetes mellitus (NIDDM) elevation of serum insulin, with or without hyperglycemia, which led to an average extraction rate of 32% of the ingested glucose. Absolute hepatic glucose uptake, calculated from the fractional extraction the plasma glucose concentration, and hepatic plasma flow accounted for 50% to 72% of total glucose use during the various steady states and following ingestion of 50 g of glucose. It is concluded that hepatic uptake or extraction, as opposed to net uptake, proceeds actively even when plasma glucose and insulin are within the normal basal range; it is increased in the presence of hyperinsulinemia, with or without hyperglycemia; and it is unaltered in NIDDM.

Forearm perfusion studies were carried out to determine the responsiveness to insulin of the superficial forearm tissues in non-obese Type 2 (non-insulin-dependent) diabetics, and the interrelationships among plasma concentrations of glucose, insulin and non-esterified fatty acids (NEFA), tissue uptake of glucose and insulin and tissue release of NEFA. It was found that: (1) in normal subjects, uptake of glucose was dependent on glucose concentration. It was also dependent on insulin concentration in the range of 0-30 mU/l, but not over a wider range of insulin concentration (less than 66 mU/l), indicating that the insulin effect was maximal at approximately 30 mU/l. In contrast, glucose uptake in diabetics was independent of glucose concentration but dependent on insulin uptake over an insulin concentration range up to 140 mU/l; glucose uptake reached the same levels as in control subjects but only at higher concentration and higher uptake of insulin. (2) Insulin uptake was directly dependent on insulin concentration and the regression coefficients were very similar in the two groups. (3) NEFA concentration fell to comparable levels in the two groups of subjects in response to insulin. It is concluded that in Type 2 diabetes: (1) the superficial forearm tissues show decreased responsiveness to the stimulatory effect of both hyperglycaemia and hyperinsulinaemia on glucose utilization but the NEFA-lowering effect of insulin is undiminished, and (2) tissue uptake of insulin is normal, despite the decrease in receptor capacity that has been demonstrated by others.

First-pass hepatic retention of glucose had previously been measured indirectly from the appearance of ingested labelled glucose into the systemic circulation. To determine the accuracy of the procedure, results obtained by this indirect method were compared with those of direct measurement of hepatic retention of labelled glucose given by instantaneous injection into the portal vein. In the rat, the indirect procedure gave a value of 13.7 +/- 2.3%. In the direct method, [14C]glucose was injected intraportally together with [3H]sucrose as a marker of extracellular distribution. Hepatic content of both labels was maximal immediately after administration; the content of sucrose fell to basal values by 15 s, indicating that the injected bolus had passed through the liver; the content of [14C]glucose continued to fall for 90 s. The difference in tissue retention between glucose and sucrose, representing intracellular glucose, was constant from 90 to 180 s, and indicated a first-pass retention of 13 +/- 0.7%. Thus the indirect procedure gives a reliable estimate of hepatic uptake and retention of glucose. Comparison of the time courses of hepatic content of [14C]glucose, [2-3H]glucose and [3H]sucrose indicated that 50% of portal-vein glucose enters the hepatic cells; subsequently 15% traverses the glucose/glucose 6-phosphate futile cycle, 22% is released without undergoing metabolic change and 13% is retained for metabolic purposes.

Absorption of glucose from the gut was estimated in trained unanesthetized dogs given a glucose load of 1-25 g (14C)glucose by stomach tube. The rate of absorption of glucose was calculated from the concentration and specific activity of glucose in the portal vein and in an "arterialized" peripheral vein. When the rate was integrated over time it was found that 94 +/- 4% of the administered glucose was recovered from the portal vein as glucose; this was unrelated to the size of the glucose load. It is concluded that absorption does not entail a significant loss or conversion to glucose metabolites.