Rats were subjected to 25 min of unilateral renal artery occlusion and were studied at 5, 15, and 30 min and at 1, 2, 4, 8, 16, 24, and 48 hr following ischemia. The patterns of epithelial injury and repair in proximal tubule (PT) segments S1, S2, and S3 were followed, and associated changes in renal function were determined. We found that S1 and S2 cells alike are only reversibly injured and recover completely to normalcy within 4 hr, whereas S3 cells selectively undergo progressive cell injury and death and are exfoliated into tubular lumina. The necrotic S3 cells are replaced by mitotic division of survivor cells 24 to 48 hr following the ischemic insult. In addition, there was selective damage within tubular cells. Wiithin 5 min of blood reflow following ischemia, the majority of brush border microvilli (MV) in all three PT segments underwent coalescence by membrane fusion and thus were interiorized into the cytoplasm of PT cells. A minority of MV fragmented and were shed into PT lumina, but nephron obstruction by shed membranes was only mild and transient, unlike in the 1-hr ischemia model. Loss of MV reached a maximum of 15 min. By 30 min, MV began to reappear; by 2 hr, large numbers of MV had been regenerated; and by 4 hr, S1 and S2 cells appeared normal. The regenerative process included the luminal repositioning of previously interiorized MV membrane. MV regeneration occurred in S3 segments also, but before the process was complete, the cells developed features of irreversible cellular injury. Glomerular filtration rate (GFR) was 22% of control at 30 min of reflow, rose progressively to 55% of normal by 7 to 8 hr, and was normal at 24 hr. Single nephron filtration rate (SNGFR) was not significantly different from normal throughout. Proximal tubular sodium reabsorption was depressed and urinary sodium excretion increased at 30 min and at 2 to 3 hr, i.e., at times when MV alterations were prominent, but both were normal by 7 to 8 hr when MV in S1 and S2 cells had been fully reconstituted. Our major conclusions are: 1) There is differential susceptibility by cell type to ischemic injury in rat PT. 2) A rapid brush border loss/regeneration cycle occurs after ischemic injury. 3) Intact brush border may be required for normal sodium reabsorption by PT. Reasons for the GFR/SNGFR discrepancy are unclear, but tubular malfunction may partly explain the phenomenon.

Among patients who died of cancer, chemotherapy was used frequently in the last 3 months of life. The cancer's responsiveness to chemotherapy does not seem to influence whether dying patients receive chemotherapy at the end of life.

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Medicare expenditures in the last year of life decrease with age, especially for those aged 85 years or older. This is in large part because the aggressiveness of medical care in the last year of life decreases with increasing age.

Medicare-insured decedents in California were more than 4 times more likely to be enrolled in MCOs, were 50% more likely to use a hospice, and had a 30% lower hospitalization rate than decedents in Massachusetts, yet there are few differences in out-of-hospital deaths or expenditures in the last year of life. However, patients with cancer using hospice did have significant savings.

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When dogs are fed or infused with sodium chloride, sodium excretion and glomerular filtration rate (GFR) both increase. Since filtered sodium usually increases more than sodium excretion (1, 2), it is commonly assumed that the sodium diuresis can be explained by the increase in filtered load (3). It has occasionally been suggested, however, that augmented sodium excretion is due to decreased tubular reabsorption of sodium rather than to increased filtration. For example, de Wardener, Mills, Clapham, and Hayter (4) recently reached this conclusion from experiments in which saline was infused into mineralocorticoid-treated dogs. In about one-half of their studies, sodium excretion increased in spite of apparent decreases in GFR.The error of measurement of GFR is probably about 5% (5). Since sodium excretion even at the height of a saline diuresis is usually a small fraction of filtered sodium, it is difficult to rule out the possibility that small errors in measurement are sufficient to account for occasional instances of apparent dissociation between filtered and excreted sodium. To circumvent this difficulty in the present experiments, an aortic clamp has been used to reduce GFR reproducibly below control levels after saline loading in dogs treated with mineralocorticoids. Since under these conditions sodium excretion is nevertheless increased above control rates, part of the sodium diuresis that follows saline administration in the dog must be due to a factor other than increased filtered load or decreased mineralocorticoid activity.*Supported by U. S. Public Health Service research grants HE-06795 (National Heart Institute) and A-5589 (National Institute of Arthritis and Metabolic Diseases), Bethesda, Md. t Address correspondence to: 15 Stoughton St., Boston 18, Mass. METHODSFemale mongrel dogs weighing 10 to 20 kg were anesthetized with iv sodium pentobarbital, 30 mg per kg; supplemental doses were given as necessary to maintain light anesthesia. The aorta was approached retroperitoneally by a left subcostal incision; a modified Blalock clamp was placed around the aorta above the renal arteries and fixed to supporting tissues. To confirm that the clamp was situated above both renal arteries, it was closed for a few moments to demonstrate that urine flow stopped completely. Urine was collected from a retention catheter in the bladder.Eighteen hours before an experiment, food and water were withdrawn. At this time, each dog was given 10 mg of desoxycorticosterone acetate (DOCA) in oil and 5 U of vasopressin tannate in oil intramuscularly. One-half hour before an experiment, each dog received 5 mg of DOCA in oil. (In a few cases, the medications 18 hours before the experiment were omitted. These dogs received 10 mg of DOCA in oil and 5 U of vasopressin tannate in oil i hour before the experiments.) Throughout each experiment all dogs received an infusion containing either 9a-fluorocortisol or 2-methyl-9a-fluorocortisol.1 In three experiments, d-aldosterone was also given intravenously. The approximate amounts...

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