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Familial metaphysial dysostosis has been described as it occurred among 18 members of a family in seven generations. The roentgenologic changes were very similar to those seen in vitamin D resistant rickets. No biochemical defect could be detected. Studies of renal function with special reference to tubular reabsorption of phosphorus gave normal values. The treatment of choice is osteotomy, after epiphysial closure has occurred, to correct the pronounced bowing of the legs. Administration of vitamin D in high doses has no effect on the course of this disease.

Application of hemodialysis to dogs has been complicated by an acute reaction consisting of hypotension, bradycardia and respiratory depression followed by instability and a mortality rate of about 30 per cent. This reaction appears to be a response to homologous blood used to fill the dialyzers. Sensitization occurs in survivors, and accentuated reactions with marked hemolysis are noted on subsequent challenge. Cross matching the donor and recipient bloods has not permitted an adequate determination of compatibility under the conditions of hemodialysis. Satisfactory hemodialysis may be accomplished in dogs by using autogenous blood or blood substitutes to fill the dialyzers.

Four cases of hypertension secondary to lesions of the renal arteries are presented with comments on the history, results of physical and laboratory examinations and surgical findings. Points emphasized are as follows: 1. 1. Hypertension of renal or renal arterial origin should be suspected in the presence of: (A) acute hypertension in young patients with angiospastic ocular changes; (B) rapidly progressive symptomatic hypertension of recent onset; (C) abrupt acceleration of chronic essential hypertension; (D) a history suggestive of a recent renal vascular accident; (E) a continuous bruit over the superolateral area of the abdomen and (F) a disparity in the size and function of the kidneys on excretory urography. 2. 2. In our experience the isotope renogram has served as an excellent screening procedure for the evaluation of renal function in hypertensive patients. 3. 3. Renal arteriography is a highly desirable procedure which aids in the more complete evaluation of hypertensive patients in whom abnormalities suggestive of renal arterial disease are found on physical or urographic examination or in the isotope renograms. This is especially true when surgical intervention is planned. The vagaries of translumbar aorticorenal arteriography are legion. Retrograde aortographic technics for renal arteriography are technically more satisfactory in our experience. 4. 4. Evaluation of function of each kidney alone may on occasions prove not only of diagnostic help, but more importantly, it may provide evidence of the adequacy of function of the individual kidneys, and thus may prove decisive regarding the feasibility of surgical intervention.

Sodium ortho-iodohippurate (Hippuran) I 131 renography has been performed by a standardized technic in patients with renal artery stenosis, pyelonephritis, primary aldosteronism, pheochromocytoma, and renal tubular acidosis with nephrocalcinosis, as well as in patients in whom the hypertension was apparently not secondary. Fifty of 94 patients studied were found to have abnormal renograms. In patients with renal artery stenosis, all of 37 patients studied had values on the renogram that were outside the range for normal subjects. Although the renographic findings were not considered diagnostic of renal artery stenosis, certain abnormalities of the renogram were commonly observed in the presence of such lesions. When a unilateral delay in the appearance of maximal radioactivity was associated with delayed disappearance ot the medium, renal artery stenosis was frequently observed. Less pronounced differences in the function of the two kidneys were observed in patients with bilateral renal artery stenosis. A state of antidiuresis was often found helpful in the detection of less severe differences in renal function. In patients with predominantly unilateral pyelonephritis, the renographic abnormalities were qualitatively consistent with the degree of impairment of renal function. Bilateral abnormalities were observed in two patients who had bilateral parenchymal disease. The abnormalities on the renogram did not permit distinction between renovascular and renal parenchynal disease. Pyelonephritis associated with obstructive uropathy revealed findings highly suggestive of renal artery stenosis. Distinction from renovascular lesions could be determined with the aid of urographic studies. Only three of 44 patients with essential hypertension had abnormal renograms. The renograms, normal and abnormal, revealed essentially equal function of the two kidneys. The patients with abnormal renograms were not found by other technics to have evidence of secondary hypertension. The patients who were found to have pheochromocytoma and primary aldosteronism had normal isotope renograms. The patient with renal tubular acidosis and nephrocalcinosis had a bilaterally abnormal renogram and severe impairment of total renal function. The presence of a normal isotope renogram, as performed in our laboratory, is considered strong evidence against the existence of a renal or renovascular cause for secondary hypertension.

The effects of dopamine on renal function were studied in 10 patients with cirrhosis and various degrees of impairment of renal function. Dopamine caused a consistent increase in effective renal plasma flow but little change in glomerular filtration rate or sodium and water excretion. The hemodynamic change is attributed to a direct effect on the renal vasculature, resulting in reduction in both preglomerular and postglomerular resistance. Unlike other drugs, dopamine partially corrects the renal hemodynamic disturbance in cirrhosis, although its role as a therapeutic agent is limited.

In health, the human kidney is capable of maintaining body water, electrolyte, and acid-base equilibrium in spite of wide dietary variation. Renal disease, primary to the kidney or as part of a systemic process, is commonly accompanied by blood pressure elevation or edema, or both. Oral diuretic drugs have won general acceptance as primary therapeutic agents in mild or moderate hypertension and as part of a broader drug program for severe hypertension. Intermittent oral or parenteral diuretic therapy has greatly augmented primary therapy of edema of cardiac, hepatic, and renal origin. Attention has been called to the potential hazard of their use when impairment of renal function is severe; however, restriction is not necessary in the absence of azotemia. Frequent or excessive use of oral or parenteral diuretics is commonly associated with hypokalemic, hypochloremic alkalosis, or other electrolyte disturbances. Potassium depletion may be avoided with concurrent use of aldosterone antagonists. The use of diuretic agents in patients with impaired renal function carries distinct risks of plasma volume depletion or hypotension and further diminution of glomerular filtration. Existing electrolyte and acid-base disorders are easily aggravated. Careful sodium restriction will commonly prevent edema; however, intermittent diuretic therapy can be helpful. Hypertension can be more effectively and safely managed with sodium restriction and sympathetic nervous system inhibitors or vasodilators; however, care must be taken not to lower pressure to the point of diminishing glomerular filtration. Digitalis has proved to be not only ineffectual but also hazardous and thus contraindicated in patients with acute cardiac decompensation and renal failure; such a clinical problem constitutes an ideal indication for the use of furosemide or ethacrynic acid, which will commonly offer prompt symptomatic relief.

l, 2 with the glass electrode for the continuous measurement of the acidity of the contents of the stomach and duodenum were primarily concerned with extraneous factors that might influence such records. In these early studies concentration of acid in the stomach and duodenum was recorded under basal conditions and after stimulation. In addition, the effects of commonly used antacids were noted, although these were not reported. The rather minor pH responses to antacids that we observed have not been completely confirmed by others. 3-11 Differences in instrumentation, principally the use of electrode shields and pumps, may account for some of the differences between our findings and the results of these investiga­ tors, whose studies deserve careful review. Aspiration studies have in some instances l2 - l4 shown only small changes in pH after the administration of antacids and are more in agreement with our findings. The purpose of this paper is to describe the changes in intragastric and intra­ duodenal pH during the use of diet, antacids, and anticholinergic drugs in the treatment of patients with duodenal ulcer.

In a previous communication, Snell and we have presented our studies of serum colloid changes in hepatobiliary disease, as measured by the turbidimetric procedures of Kunkel. The present paper extends these studies to patients whose diseases are not directly related to the liver or biliary tract. On the basis of our findings in 236 blood bank donors, we have established our upper limits of normal for gamma globulin turbidity (16 units), for thymol turbidity (3.5 units), and for total serum lipids (880 mg. per 100 cc. of serum). An evaluation of normality should be carried out in each laboratory using these tests, because of possible variation inherent in the barium sulfate suspensions employed as turbidity standards. Carter and Maclagan have reported a similar investigation of "liver function" tests in extrahepatic disease, based principally on the thymol turbidity and colloidal gold tests. These workers have found a high incidence of positive values in malaria, rheumatoid arthritis, congestive heart failure, glandular fever and subacute bacterial endocarditis. The higher degree of positivity noted with the colloidal gold reaction is ascribed to the narrower dependence of this test on gamma globulin. The data of these workers are in accord with the results obtained by Kunkel with the thymol turbidity reaction. In agreement with Carter and Maclagan, we have found elevated values for gamma globulin and for thymol turbidity in several disease entities not directly related to the hepatobiliary system. It has not been shown that these reactions are specifically indicative of liver damage. Elevated values may reflect liver damage secondary to systemic toxemia, increased antibody production or variable combinations of these possibly with other factors as yet unknown. We cannot as yet describe the basic mechanisms underlying these serum colloid changes. The clinical interpretation of these tests should nevertheless consider those conditions other than hepatobiliary disease in which elevated values may be expected. With caution, the tests may be of aid in the evaluation of liver changes secondary to those conditions.

Summary Renal performances during clinical cardiopulmonary bypass, with and without hemodilution, were compared. The major difference consisted of a significantly larger rate of urine flow and a lower osmolality of urine during and immediately after cardiopulmonary bypass when hemodilution was utilized. Explanations for these phenomena were discussed. Glomerular filtration rate, effective renal plasma flow, and postoperative urine electrolyte excretion and osmolality patterns were generally similar in both groups of patients. It was concluded that the increased production of urine associated with hemodilution perfusion might well protect renal-tubular integrity during stressful situations, such as intracardiac surgery.

The rate and extent of return of renal function and its maintenance after initial improvement and factors influencing renal recovery were studied in 186 patients with acute renal failure. ...

Renal performance of seven patients undergoing replacement of the aortic valve was investigated. The initial portion of cardiopulmonary bypass was characterized by low arterial blood pressure and anuria. With a subsequent rise in arterial pressure during bypass, urine flow suddenly increased in five patients. In two patients urine flow did not resume until immediately after cardiopulmonary bypass. The high rate of urine flow at these times is thought to be partially due to a glucose-induced osmotic diuresis. The glomerular filtration rate (inulin clearance) and the effective renal plasma flow (PAH clearance) fell with induction of anesthesia and opening of the chest, but there was no further drop in these functions as a result of total body perfusion. Urine osmolality fell significantly during and immediately after cardiopulmonary bypass. The changes in urine osmolality are thought to be due in part to the osmotic diuresis and in part to a temporary reduction in the renal medullary hyperosmolality secondary to hemodynamic changes. All of the alterations in renal function were reversible in the patients studied.

A technique for measuring effective renal plasma flow based on a single injection of sodium iodohippurate I 131 was compared with para-aminohippuric acid clearance determined simultaneously in 25 patients. On the average, the clearance by the single-injection technique was about 19 ml (5%) less than that by the standard procedure. The results indicate that there is a good correlation between the methods. It is suggested that further study with this simpler technique may prove it to be a reliable substitute for the more cumbersome standard method.

Acute renal failure was treated by hemodialysis in 15 patients. Five of these underwent more than one period of treatment. The apparatus used operates as an ultrafilter as well as a hemodialyzer and is portable. Methods of sterilizing and testing the apparatus, preparing the solution for perfusion, administering anticoagulants and anesthetics, cannulating the blood vessels (radial or brachial artery and long saphenous vein), and regulating the flow are described in detail. In each case the hemodialysis was instituted primarily because of the appearance of the uremic syndrome; in nine cases hyperkalemia was prominent. Biochemical analyses showed that the hemodialysis materially lowered the level of the plasma potassium during the first hour and that the removal of urea continued steadily as long as six hours. A blood flow of approximately 200 ml. per minute was sought, with a urea clearance of about 150 ml. per minute. The period of dialysis was six hours in all but four cases. Preexisting complications made recovery impossible in eight cases, even though the immediate biochemical and clinical results of the hemodialysis were fair to excellent. In the remaining seven cases the hemodialysis carried the patient through the period of renal insufficiency, and recovery followed.

The possible influence of distorted plasma and fluid composition of tissue on the recovery of damaged kidneys is of concern in the management of acute renal failure and has a distinct bearing on the application of extracorporeal dialysis in this condition. We sought in this study to evaluate the results of repeated hemodialysis applied to dogs rendered uremic by severe experimental renal damage. Renal ischemia produced by occlusion of the renal artery has been shown to produce a lesion resembling that of the so-called crush syndrome, described by Oliver as acute ischemuric tubular necrosis.1In our hands, three hours of arterial occlusion, associated with the division of capsular vessels and perirenal sympathectomy, was followed by the spontaneous recovery of function of the kidney so treated. Van Slyke has reported a similar experience.2Six hours of occlusion under these conditions was followed by almost total infarction of the kidney

Serial determinations of electiolytes and crystalloids were done in 18 patnents undergoing whole-body perfusion with moderate hlypothermia In six patients, the perfusate used was whole blood, and in twelve patients the perfusate used was diluted and contained 60 per cent blood In six patients perfused with haemodilution, haematocrit and electrophoretic protein patterns were also studied

1. 1. Functional studies of the separate kidneys were undertaken in 165 hypertensive patients who had previously undergone excretory urography. Of these, 150 had isotope renography and 147 had renal arteriography. Complications consisted of acute or recurrent pyelonephritis in 4 patients; all responded promptly to appropriate chemotherapy. 2. 2. In 17 hypertensive patients with dominantly unilateral atrophie pyelonephritis, mean values revealed markedly diminished urine volume (54%), clearances of inulin and paraaminohippuric acid (PAH) (65 and 62%), and reabsorption of filtered sodium (1.5%) and water (1.6%) for the diseased kidney. Concentrations of sodium, PAH, and inulin and osmolality of the urine from the diseased side were usually slightly to moderately diminished. In two patients data on urine volume and sodium concentration met criteria for a positive Howard test. 3. 3. Patients with apparent essential hypertension had only minor differences between the kidneys in all parameters studied. The range of differences in those with essential hypertension and aberrant arteries was somewhat greater; however, mean differences were minimal except for greater clearances of inulin and PAH which correlated well with greater renal mass. 4. 4. Of 102 patients with stenosing lesions of the renal arteries, 53 had unilateral and 49 had bilateral obstruction. In patients with unilateral severe renal artery stenosis urine volume and sodium concentration were diminished along with usually diminished clearances of inulin and PAH on the involved side (mean values − 79, − 53, − 47 and − 47%, respectively). Urine osmolality was usually increased as were concentrations of inulin and PAH, the latter two usually by more than 100 per cent. The percentage reabsorption of filtered sodium and water was markedly increased on the involved side (mean values 3.1 and 2.6%, respectively). Patients with unilateral severe renal artery stenosis and aberrant renal arteries differed only in that the mean value for sodium concentration in the urine was only slightly diminished on the involved side (6%). Patients with unilateral renal artery stenosis and partial renal infarction usually could not hyperconcentrate urine on the involved side. Urine volume, sodium concentrations, and osmolality were diminished; however, inulin and PAH concentrations were slightly but consistently increased. When stenosis was severe on one side and mild on the other, functional characteristics were similar to those observed with unilateral stenosis, except for more variable sodium concentrations and osmolality. When stenosis was bilateral and equally severe, significant differences in functional characteristics were seldom observed. Patients with mild or moderate stenosis (less than 50% narrowing of the renal artery) seldom had more than slight differences in functional characteristics. 5. 5. With arteriographically demonstrated renal artery stenosis, (a) increased reabsorption of filtered sodium and water by 1 per cent or more on the involved side, a positive Howard test, and increased osmolality characterized functionally significant lesions and were not seen in essential hypertension; (b) differences in inulin and PAH concentrations largely reflected differences in water reabsorption; and (c) when sodium concentrations were greater on the involved side (negative Howard test), a high incidence of either a branch artery lesion, multiple arteries to the involved kidney, bilateral main artery stenosis, or partial renal infarction was observed.

The pharmacological and biochemical tests available for the diagnosis of pheochromocytoma were evaluated among 28 patients with proved tumors and 148 other patients in whom the diagnosis was suspected. Of the biochemical tests on urine, determinations of total metanephrines (MN) and of vanilmandelic acid (VMA) were much less subject to false-positive results than was determination of catecholamines (CA). Since urinary MN values changed the most in tumor patients, MN determination is preferred as the current screening test. Of the pharmacological tests, the histamine test continues to be the most valuable, especially when combined with determination of plasma CA concentration. The phentolamine (Regitine) test has not proved to be of any distinct value as a primary diagnostic aid. Any of the chemical or pharmacological tests occasionally may give a false-positive result. The urinary output of excessive amounts of homovanillic acid (HVA) was an indication of the presence of pheochromocytoma with some features histologically similar to other neural crest tumors but was not an indication of malignancy. Reliable diagnosis of pheochromocytoma still must be based on multiple studies in an appropriate clinical setting.

In 149 cases, blood pressure response to glucagon test did not exceed 20/10 mm Hg more than the response in the cold pressor test control and was considered negative. Plasma catecholamine level increases may be seen in 95% of patients without pheochromocytomas. Among six patients with pheochromocytomas, urinary metanephrine levels were of diagnostic importance in two with isolated pheochromocytoma and in one with the multiple endocrine neoplasia of type 2 (MEN-type 2). Urinary metanephrine determinations yielded falsenegative results in three patients with MEN-type 2, while vanilmandelic acid level was normal in one and nephrotomograms were positive in two of these three. These results suggest that the early diagnosis of pheochromocytoma in patients with MEN-type 2 may be difficult and may require multiple biochemical and roentgenographic investigations.

The tyramine hydrochloride test of Engelman and Sjoerdsma was compared with the standard cold pressorhistamine test in seven patients with pheochromocytoma, five with essential hypertension, and three with labile hypertension. Urinary and blood catecholamines and urinary vanilmandelic acid (VMA) and metanephrines were also determined. One nontumor patient had a systolic pressor response (20 mm Hg greater than cold pressor response) after histamine; none had a response greater than 15 mm Hg after tyramine injection. The blood and urine values were normal in nontumor patients. Among the tumor patients, five had a marked pressor response to histamine, five had a mild pressor response (> 20 mm Hg) to tyramine, and six had increased circulating pressor amine levels. All tumor patients had increased values for urinary metanephrines, six had increased catecholamine values, and five had increased VMA values.

Excerpt We have evaluated renal function and serum electrolytes in 13 patients before and immediately after surgical exploration of the neck for removal of parathyroid tumors. There were nine femal...

Excerpt Fluid retention accompanying advanced cirrhosis is characterized by secondary hyperaldosteronism and increased reabsorption of sodium by the kidney; the nature of the stimulus to increased ...

Excerpt In 100 hypertensive patients 18 to 64 years old, the function of each kidney was studied separately by means of ureteral catheterization. Determination was made of urinary minute volume, os...

The glucagon hydrochloride test of Lawrence was compared with the standard cold pressor-histamine test in 12 patients with pheochromocytoma and in 35 control patients without tumor. Urinary and blood catecholamine levels and the values for urinary vanilmandelic acid and total metanephrine were also determined. One patient without a tumor had a pressor response after receiving histamine; none had a pressor response after receiving glucagon. Eleven patients with tumor were given 1 mg of glucagon; six had a positive pressor response, and four of these six had a positive response after receiving histamine as well. One patient with tumor responded positively to histamine but not to 0.5 mg of glucagon. Although determination of the level of urinary metanephrine remains the preferred screening test for pheochromocytoma, when adjunctive studies are desired we recommend the cold pressor-glucagon test (1 mg) instead of histamine as the standard provocative pharmacologic test for pheochromocytoma.

Renal clearances of diatrizoate sodium I 125 or iothalamate sodium I 125 measure 90% to 100% of simultaneous classic clearances of inulin; clearances of iodohippurate sodium I 131 or iodopyracet I 131 are 84% and 79%, respectively, of simultaneous clearances of aminohippurate sodium. Plasma binding (8% to 27% of diatrizoate sodium I 125 or iothalamate sodium I 125; 64% to 70% of iodohippurate sodium I 131; 29% to 42% of iodopyracet I 131; 7% to 25% of aminohippurate) is revealed by ultrafiltration studies. Binding is labile and dissociable. Correcting clearances of diatrizoate sodium I 125 or iothalamate sodium I 125 for plasma binding yields values exceeding those of insulin clearances. Uncorrected, they are satisfactory substitutes for inulin clearance in man. Clearances of iodohippurate sodium I 131 or iodopyracet I 131 approximate adequately clearances of aminohippurate when carrier iodopyracet is added and the clearances are corrected for plasma binding to provide an estimate of total clearance.