Causes of death in a hospitalized geriatric population: an autopsy study of 3000 patients.

Macroscopic and histological studies of 3000 consecutive autopsies (43.9% of the registered deaths) were performed by the same pathologist in a geriatric institution over a period of 20 years. Bronchopneumonia (42.9%), malignant neoplasms--mainly of the gastrointestinal tract and its annexae and the lungs (28.1%)-pulmonary thrombo-embolism (21.2%) and acute myocardial infarction (19.6%), were the most prevalent fatal conditions observed. Next, in decreasing order were: urinary tract infection (12.3%), acute cerebrovascular disease (6.5%), internal haemorrhage (5.5%), and congestive cardiac failure (3.3%). Some "rare" causes of death noted included trauma, metabolic disease, acute asphyxia from foreign body obstruction of the upper respiratory tract and degenerative neurological diseases. Some potentially treatable disorders which led to death were unsuspected clinically: for example, acute pyelonephritis (87%), pulmonary thrombo-embolism (74%), acute myocardial infarction (74%) and active pulmonary tuberculosis (61%). With advancing age there is an increased frequency of multiple pathological processes in a given subject and interactions play an important role in morbidity and mortality. We observed that two or more co-existing conditions often determine the fatal event. We also emphasize the relevance of post-mortem examination to prevention of disease and to therapeutic medicine in a hospitalized geriatric setting.

Effects of sulfonamides on a metabolite-regulated ATPi-sensitive K+ channel in rat pancreatic B-cells.

Intracellular ATP (ATPi)-sensitive K+ [K+(ATP)] channels are now a recognized site of action of clinically useful hypoglycemic and hyperglycemic sulfonamides. We have further examined the action of these agents on single K+ channels in rat pancreatic B-cells 1) Tolbutamide and glyburide, two hypoglycemic sulfonylureas which decrease K+(ATP) channel activity in the cell-attached patch, affect the kinetics of K+(ATP) channel in a manner similar to glucose. They shorten the duration of the "burst," or cluster of open channel events, while lengthening the intervals between bursts. 2) The hyperglycemic vasodilator diazoxide increases mean K+(ATP) channel activity in the cell-attached patch as well as in the inside-out excised patch exposed to ATPi. It appears to lengthen channel bursts and shorten the intervals between them. Two structurally similar diuretics, hydrochlorothiazide and furosemide, which have mild hyperglycemic effects, do not increase K+(ATP) channel activity even at clinically toxic concentrations. 3) Neither the sulfonylureas nor diazoxide directly affect the activity of single delayed rectifier K+ channels or single calcium and voltage-activated K+ channels in normal B-cells.

Metabolite-regulated ATP-sensitive K+ channel in human pancreatic islet cells.

In patch-clamped surface cells of human islets, we identified an inwardly rectifying, voltage-independent K+ channel that may be a crucial link between substrate metabolism and depolarization-induced insulin secretion. It is the major channel open at rest. It closes on exposure of the cell to secretagogue concentrations of glucose or other metabolic fuels and oral hypoglycemic sulfonylureas but reopens on addition of either a metabolic inhibitor that prevents substrate utilization or the hyperglycemic sulfonamide diazoxide. Onset of electrical activity coincides with channel closure by the secretagogues. In excised patches, the activity of this channel is inhibited at its cytoplasmic surface by ATP. These results suggest that in humans, as in rodents, 1) rises in cytoplasmic ATP levels during substrate metabolism trigger K+-channel closure and cell depolarization and 2) clinically useful sulfonamides modulate glucose-induced insulin secretion, in part by affecting a readily identifiable resting conductance pathway for K+.