Vascular compartmentalization of plasma norepinephrine in normal man: the relationships between venous and arterial norepinephrine concentration and the urinary excretion of norepinephrine.

To examine whether the concentration of NE in human plasma is dependent on the vascular source of the sample and to examine the contribution of the kidney to urinary NE, 14 normal men were studied. Plasma samples were obtained from a superficial forearm vein, and radial artery and urine samples were obtained during 1 hr of recumbency and 1 hr of upright posture. The Vne was greater than Ane during both recumbency and upright posture in black males. Such differences were not seen in age-matched white subjects. Stimulation of the sympathetic nervous system by upright posture increased both Vne and Ane in all subjects. NE concentrations in simultaneously obtained arterial and venous samples were different during the time of cardiovascular adjustments to upright posture. The urinary Xne increased after standing. Endogenous CCr decreased, whereas apparent NE clearance, calculated from the Ane, increased after standing, suggesting that a major portion of the augmented urinary Xne induced by upright posture was from an intrarenal source. We conclude that the concentration of NE in human blood is related to the specific vascular bed from which the sample is obtained, and that urinary NE is not solely derived from plasma by glomerular filtration but also arises from an unidentified renal source.

Long term effect of cis-diamminedichloride platinum (CDDP) on renal function and structure in man.

To examine CDDP induced nephrotoxicity in patients with testicular carcinoma, we measured renal function prior to therapy and at six month intervals for twelve months in fifteen patients and twenty-four months in seven patients. CDDP was given iv at 20 mg/M2 per day for five days at three week intervals. Eight patients received three courses, four received four courses and three received more than four courses. The mean creatinine clearance +/- SD prior to treatment was 112 +/- 12 ml/min. By six months, it had decreased to 68.5 +/- ml/min (p less than 0.01) and it remained at that level. Plasma creatinine and blood urea nitrogen increased significantly. Subjects receiving other potential nephrotoxins in addition to CDDP developed a greater decrease in creatinine clearance (p less than 0.05). Proteinuria and functional tubular disturbances were not observed. Microscopic features were characterized by hydropic degeneration of the renal tubular epithelium, thickened tubular basement membranes and mild interstitial fibrosis. Electron microscopy revealed phagolysosomes filled with flocculent material. CDDP resulted in a permanant, nonspecific renal injury in our patients. Although the renal injury has remained subclinical, future courses of CDDP may lead to clinically important chronic renal failure.

Surgical treatment of infective endocarditis in hemodialysis patients.

Congestive heart failure following infective endocarditis in hemodialysis patients has been uniformly fatal in patients treated with antibiotics alone. Thirteen patients on chronic hemodialysis have undergone replacement of the infected valve with an overall survival of 61%. The aortic valve was involved in 10 patients and Staphylococcus aureus the responsible organism in nine. Recurrent bacteremia occurred in two of the eight long-term survivors and was successfully treated with antibiotics in one patient and replacement of the prosthesis in the other. The surgical treatment of infective endocarditis in the hemodialysis patient is an acceptable mode of therapy and its application should not be hindered by reservations concerning operative feasibility or postoperative longevity. As in non-dialysis patients with infective endocarditis and congestive heart failure early operative intervention may substantially improve survival.

An extrarenal source of "renin-like" activity in anephric man.

To examine extrarenal sources of "renin-like" activity plasma was obtained from 19 anephric males. Plasma renin activity (PRA), concentration (PRC) (obtained after addition of exogenous renin substrate) and total renin concentration (TRC) (obtained after acid-activation of plasma and subsequent incubation with exogenous renin substrate) demonstrated values for several anephric patients comparable or above those seen in plasma from 10 normal subjects. Incubation of untreated plasma (PRA and PRC) and acid-dialyzed plasma (TRC) for angiotensin I generation was performed at pH 7.5, at 37 degrees C with EDTA, dimercaprol, and 8-OH-quinoline as angiotensinase and converting enzyme inhibitors. The pH optimum for acid-activation of TRC in anephric plasma was the same as that in normal plasma (pH 3.3). Molecular weight determinations following Sephadex gel chromatography demonstrated that the renin-like enzyme in normal plasma had a molecular weight of about 42,000 before and after acid-activation, while that in anephric plasma had a molecular weight of approximately 61,000. A saliva sample from one anephric subject with the highest levels of PRA, PRC, and TRC in plasma also demonstrated measurable amounts of PRA, PRC, and TRC. The molecular weight of this salivary "renin-like" activity also was 61,000. These observations suggest a possible extrarenal source of "renin-like" activity in anephric man. The physiological significance of these studies remains to be clarified.