Tauxe, W. Newlon

Radioisotope renograms with orthoiodohippurate-I131 were obtained for 41 children who had known renal or renovascular disorders. (Two patients had hypertension but no evidence of renal disease.) Values determined for various components of the renogram curves were considered abnormal when they exceeded two standard deviations from the mean values for normal children of similar body surface area or when time B (from injection to the point of maximal radioactivity) exceeded 6.5 minutes or differed from the contralateral kidney by more than 1 minute. The renogram was clearly abnormal in all 17 patients who had unilateral or predominantly unilateral renal disorders. Abnormalities associated with bilateral renal disorders varied with the disease and its severity. The clinical severity of impairment of renal function could be estimated from the renogram. The isotope renogram proved to be a simple, reproducible technique for determination of function of the separate kidneys.

Isotope renograms (ortho-iodohippurate-I were obtained from 30 children who had no evidence of renal disease. Determinations were made by a standardized technique with the subjects in a state of relative dehydration; in 15 children the renogram was repeated under conditions of hydration (14 children) or further dehydration (1 child). Values for the point of initial peak (point A), point of maximal radioactivity (point B), and the differences between these points (B-A) were calculated. These values were plotted arithmetically against surface area to obtain regression lines and estimates of the variability of the observations about the line. The time from appearance of radioactivity to peak radioactivity was calculated and found to fall into a relatively narrow range. Similar attempts to correlate mathematically the height of timed segments of the decreasing slope of the renogram with surface area were successful in children with a body surface area of 1.15 m2 or greater. The state of hydration appeared to influence the excretory slope of the renogram; this effect was most pronounced in children whose total body surface area was less than 1.15 m2.

Observations on two mongoloid children, one having primary hypothyroidism and the other having primary hyperthyroidism, have been reported. Primary hypothyroidism in the mongoloid child, in each of the three cases reported to date, has been associated with uterine bleeding attributed to hormonal overlap in the pituitary feedback mechanism. The significance of this phenomenon is not clean. A total of sixteen cases of mongolism with hyperthyroidism have been described. There is no evidence that altered thyroid function plays a role in the clinical manifestations of mongolism, and significant alteration in thyroid function is uncommon among such patients. Both of the carrier protein systems responded to the stresses of the superimposed disease processes in these mongoloid children as they do in normal children. Specifically, the values for the erythrocytic uptake of 1-I131-triiodothyronine and thyroxine and the triiodothynonine binding capacities (Case 2 only) were all in the expected ranges for both thyroid derangements involved. Similarly, in Case 2, where an iron-deficiency anemia was also present, the increase in the iron binding capacity and presumably in the level of transferrin was on the order of that to be expected for the degree of iron deficiency. The response to stress of both carrier protein systems in Down's Syndrome suggests that protein synthesis of transferrin and TBG is normal.

Normal values for the measurement of thyroidal function using the erythrocytic uptake of I131-labeled triiodothyronine and the thyroxine-binding capacity of the inter-alpha globulin were established. Paired maternal and cord blood samples collected at the time of delivery were studied with these methods. The erythrocytic uptake of labeled hormone was increased in cord blood as compared to maternal blood. Cord blood apparently binds exogenous triiodothyronine in a different manner than it does exogenous thyroxine. Whether this is a qualitative or quantitative difference was not shown in this study.

Abstract In 12 normal subjects, DNA and RNA synthesis by individual marrow cells was studied in vitro by autoradiography after short-term incubation with tritiated nucleosides. The DNA labeling index and RNA synthesis rate were highest in normal immature cells. The DNA index was zero in all mature cells, including small lymphocytes and plasma cells. In the most actively proliferating normal immature cells, the RNA synthesis rate was about 5 times higher than in normal plasma cells. Since both normal immature cells and plasma cells are characterized by a high content of RNA and active protein synthesis, the results of the present study suggest that a high RNA turnover may not be necessary for protein synthesis to proceed in nonproliferating, protein-producing marrow cells. In 10 patients with myeloma and in two patients with primary macroglobulinemia, the abnormal plasma cells were found to be labeled with H3thymidine in each instance. The RNA synthesis rate was about 3 times greater in plasmocytoid myeloma cells than in mature plasma cells of normal marrows, and also about 3 times greater in lymphocytoid myeloma cells than in mature lymphocytes of normal marrows. The abnormal cells in the lymphoplasmocytic disorders apparently differ from their counterparts in normal marrows not only by a higher proliferative potential, but also by a much greater rate of RNA synthesis. In actively dividing normal bone marrow cells, high values for both DNA and RNA synthesis were found. By contrast, in the neoplastic lymphoplasma cells studied, a discrepancy was noted between relatively low values of DNA synthesis and high values of RNA synthesis. Production of abnormal proteins within long-lived neoplastic plasmocytic cells may account for this finding.

Abstract Erythrocyte volume, plasma volume, hematocrit, lean body mass (from total body water), skinfold thickness (at three sites), arm circumference, height, and weight were measured in 40 normal males, 38 normal females, and 12 obese females. From these data on the normal subjects, equations for estimating erythrocyte and plasma volumes were derived. Equations utilizing combined height-weight, surface area, height-weight-skinfold thickness, or lean body mass were found to be the most accurate for predicting erythrocyte and plasma volumes in normal and in obese subjects. The body:venous hematocrit ratio (BH:VH) and the variability of this ratio in our subjects were determined and discussed. Errors in indirect estimates of blood volumes based on this ratio are presented. Erythrocyte and plasma volume standards based on height-weight regression equations or surface area ratio equation are suggested for use in clinical laboratories. Tables and a nomogram based on these equations have been prepared and are available on request.

A study was made of the disappearance of sodium diatrizoate-I131 from the plasma of ten dogs after single intravenous injections. The plasma disappearance curves suggested a two-compartment system. The renal plasma clearance of diatrizoate-I131 calculated from these curves and the conventional renal plasma clearance of creatinine were not statistically different. Clearances calculated from the urinary excretion and midperiod plasma concentration of radioactivity in four experiments yielded values averaging 10% less than the creatinine clearance. Chromatographic studies of commercially available diatrizoate-I131 revealed the presence of about 5% free iodide and of about 5% of unidentified impurities. These impurities seem to account, partly at least, for the differences found between diatrizoate clearance and creatinine clearance. Biliary excretion and erythrocytic uptake of diatrizoate were minimal and did not appear to influence the analysis.

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.

Simultaneous determinations of serum potassium and sodium, blood pH, blood pressure, and 12-lead electrocardiograms were obtained in hyperkalemic patients with chronic renal failure. Statistical investigation of the data showed a high correlation between serum potassium levels and ventricular repolarization abnormalities. "Mean intracellular potassium concentration" derived from total body potassium and total body water values was not accurate enough to show significant correlations to ECG changes and did not improve on the already significant correlations with serum potassium levels. Equations are presented which would permit the estimation of serum potassium levels (in a narrow range) from electrocardiographic findings in patients with chronic renal failure and suspected hyperkalemia.