According to current concepts, renal ammonia synthesis may be attributed to the renal extraction and catabolism of certain plasma amino acids. In 1943, Van Slyke and associates demonstrated in the dog that the amide nitrogen of glutamine was removed from arterial plasma in quantities sufficient to account for approximately 60 per cent of the urinary ammonia excreted during metabolic acidosis (1). It was proposed that the remaining 40 per cent of urinary ammonia could be accounted for by the renal uptake of plasma a-amino nitrogen. In agreement with this hypothesis, many investigators have since shown that the administration of several amino acids other than glutamine is associated with an increased urinary ammonia excretion (2-4). Loading experiments of this type have indicated thatbesides glutamine-glycine, alanine, asparagine, leucine. and histidine may serve as precursors of urine ammonia. The demonstration of appropriate enzyme systems within renal tissue capable of forming ammonia from these substrates has been offered as additional support for the thesis that several plasma amino acids may participate normally in the renal production of ammonia. Nevertheless, the specific amino acids that serve as renal ammonia precursors have not been identified clearly in conditions associated with normal acid-base balance and normal plasma amino acid concentrations. The present study was undertaken for two principal reasons: first, to characterize the' typical patterns of uptake or release * Investigation supported in part by U. S. Public Health Service research grants A-5930 and A-6306 from the National Institutes of Health, Bethesda, Md., and by the Veterans Administration Clinical Investigator Program; presented in part at the annual meeting of the Southern Section, Amer. Fed. Clin. Research, New Orleans, La., January 18, 1962. of individual amino acids by the normal human kidney, and second, to determine whether or not the adaptive increase of renal ammonia production during metabolic acidosis could be attributed to chances in the renal extraction of certain plasma amino acids.
METHODSTwelve renal clearance experiments were carried out on eleven healthy male volunteers between 21 and 38 years old. All studies were conducted with them in the recumbent position after an overnight fast. To facilitate the collection of timed urine specimens, urine flows of approximately 5 ml per minute were assured by the oral ingestion of 500 ml of tap water 1 hour before the test, followed immediately by a constant intravenous infusion of 5 per cent dextrose in water. After appropriate priming doses, an-intravenous maintainance infusion of a solution of inulin and para-aminohippurate (PAH) was begun 45 minutes before the first clearance period via a Bowman constant-infusion pump. During the equilibration period, a no. 7 or 8 cardiac catheter was introduced into a renal vein through either the right brachial or femoral vein under fluoroscopic control. An indwelling Cournand arterial needle was placed in the left brachial artery. Thr...
Existing data on the clinical outcome of maintenance dialysis for end-stage kidney disease focus mainly on the duration of life. We surveyed 18 dialysis centers to gain a broader overview of the current status of 2481 patients on dialysis, irrespective of the type or location of dialysis. The results suggest that 12 per cent of dialysis patients are diabetics and that 53 per cent are 50 years of age or older. There was considerable variation among centers in the degree of rehabilitation; nevertheless, only 60 per cent of the nondiabetic patients and 23 per cent of the diabetic patients were capable of a level of physical activity beyond that of caring for themselves. Only one quarter of the patients worked outside the home, whereas one third worked at home. These results suggest that a larger proportion of dialysis patients than previously suspected are severely debilitated. There is a need for improved data on the quality and length of life of patients on maintenance dialysis.
Two hundred and two patients with bone pain from metastatic cancer were treated with 40 , Ci/kg ofSr.89. Patients were followed with pain diaries, records ofmedication taken, sleep patterns, serial bone scans and a Karnofsky Index. One hundred and thirty-seven patients with adequate followup survived at least 3 months, including 100 with prostate and 28 with breast carcinoma. Eighty of the 100 patIents with prostate cancer responded, and 25 ofthe 28 breast cancer patients Improved. Ten patients wIth prostate cancer and five with breast cancer became pain free. Little hematologlc depression was noted. Sr89 kinetic studies showed that strontium taken up in osteoblastic areas remained for 100 days. The tumor#{149}to.marrow absorbed dose ratio was 10:1.
A B S T R A C T Previous studies in the mammalian proximal tubule have suggested that para-aminohippurate (PAH) secretion is -threefold greater in the straight segment, or pars recta, than in the convoluted segment, or pars convoluta. However, the possibility that the site of maximal PAH secretion might be related better to particular tubule segments as identified by cell type had not been explored. In addition, the presence or absence of differences in PAH secretion between morphologically identical regions of superficial (SF) vs. juxtamedullary (JM) proximal tubules has not been examined. These issues were studied using a combination of' histologic methods and measurement of' [3H]PAH secretion in isolated perfused tubules. Measturements of microdissected SF and JM proximal tubules from young and adult rabbits revealed that SF proximal tubules were slightly but significantly longer than JM tubtules ([young
As many as 80% of selected patients with painful osteoblastic bony metastases from prostate or breast cancer may experience some pain relief following 89Sr administration. In addition, as many as 10% or more may become pain free. Duration of clinical response may average 3 to 6 months in some cases. Hemotoxicity is mild. A decrease in treatment costs with administration of 89Sr to patients with painful osteoblastic bony metastases from prostate cancer may occur. These observations reflect the preliminary nature of knowledge in this field and point to the need for larger clinical trials of the use of 89Sr palliation.
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