M. Donald Blaufox

A metaanalysis of 18F-2-deoxy-2-fluoro-D-glucose positron emission tomography in the staging and restaging of patients with lymphoma.

In recent years, the use of positron emission tomography (PET) has become widespread for the staging and follow‐up of several malignancies. In the current study, the authors conducted a metaanalysis of the published literature to evaluate the diagnostic performance of 18F‐2‐deoxy‐2‐fluoro‐D‐glucose PET (FDG‐PET) in the staging of patients with lymphoma.

Sustained beneficial effects of oral amrinone on cardiac and renal function in patients with severe congestive heart failure

Although effectiveness of oral amrinone has been demonstrated in animals, amrinone has been shown in human subjects to improve cardiac performance in the failing heart only after acute intravenous administration. Therefore, we studied the hemodynamic and renal effects of orally administered amrinone (50 to 300 mg) in 10 patients with advanced congestive heart failure. Cardiac index increased from 1.56 ± 0.41 (mean ± standard deviation) to 2.20 ± 0.43 liters/min per m2 (p < 0.001); pulmonary wedge pressure decreased from 26.1 ± 5.7 to 17.0 ± 5.7 mm Hg (p < 0.001). Mean arterial pressure decreased from 86.0 ± 8.4 to 81.3 ± 7.7 mm Hg (p < 0.001) and systemic vascular resistance from 2,406 ± 603 to 1,693 ± 261 dynes sec cm−5 (p < 0.001). Heart rate was unchanged. The onset of action ranged from 30 to 120 minutes and the duration of action from 4 to 7 hours after a single oral administration. After 24 hours of continuous therapy, no tachyphylaxis to amrinone was observed. A correlation (r = 0.62, p < 0.001) was found between the oral dose of amrinone and the percent increase in cardiac index. Left ventricular ejection fraction, determined in five patients, increased from 14 ± 8 to 21 ± 8 percent (p < 0.01). Effective renal plasma flow, measured in six patients, increased from 186.0 ± 72.0 to 231.1 ± 88.8 ml/min (p < 0.05) and the glomerular filtration rate from 82.2 ± 14.9 to 110.0 ± 20.6 ml/min (p < 0.05). Thus, this study demonstrates the cardiotonic efficacy of orally administered amrinone in human subjects and recommends its further investigation as a therapeutic agent for the continued treatment of congestive heart failure.

Postnatal Changes in Renal Glomerular Blood Flow Distribution in Puppies

The intrarenal distribution of radionuclide microspheres injected into the thoracic aorta was used to examine glomerular blood flow distribution (GBFD) in 26 healthy, unanesthetized puppies, ranging in age from 5 h to 42 days, and in 5 adult dogs. For analysis, the cortex was divided into four equally thick zones designated zone I (subcapsular) to zone IV (juxtamedullary). During the first 36 h of life, the highest flow rate was in zone II, which received 35.5+/-2.0%/g, compared with 26.8+/-1.4% to zone I, 23.7+/-1.4% to zone III, and 13.4+/-1.4% to zone IV. At age 6 wk, zone I had the highest rate of perfusion (48.6+/-2.1%, compared with 28.8+/-1.4% in zone II, 15.8+/-0.8%, in zone III, and 6.8+/-0.6% in zone IV). The 6-wk old animals resembled the adult animals, except for relatively greater perfusion per gram of zone I in the former group. Changes in relative GBFD did not correlate with those in arterial pressure or peripheral hematocrit. The distribution of glomeruli among the four zones of the cortex followed its own pattern of development. At birth and at 6 wk, the greatest density of glomeruli was in zone I (50.6+/-5.4 and 42.7+/-3.9%/g respectively, as compared with 24.1+/-2.9% in adults); in adults zone II contained the greatest density (39.1+/-1.6%). At birth the relative perfusion of glomeruli in zone I was only one-fifth that of glomeruli in zone IV, with intermediate values in zones II and III. By 6 wk of age, increased perfusion of the outer cortical glomeruli resulted in rates of flow in the four zones that did not differ significantly from each other. Relative perfusion in zone I continued to increase, so that in the adult animals perfusion in that zone was significantly greater than in the three deeper zones. These data demonstrate the marked hemodynamic changes that take place within the kidney during the first few weeks of life. The relatively greater blood flow of the most deeply situated nephrons in the early postnatal period suggests ascendancy of this population of nephrons and may have important functional implications.

Renal radiopharmaceuticals—An update

Noninvasive radionuclide procedures in the evaluation of renal disease have been accepted increasingly as effective and valuable alternatives to older clinical methods. The development of suitable radiopharmaceuticals labeled with high photon intensity radionuclides and with 99mTc in particular has stimulated this modality during the last few years. Currently several nearly ideal agents are available for anatomical and functional studies of kidney imparting very low absorbed radiation doses. These include 99mTc-GHA and 99mTc-DMSA for renal morphology and differential function evaluation, 99mTc-DTPA for GFR and 123I orthoiodohippurate for ERPF measurements. A suitable agent as a replacement for the latter labeled with 99mTc is actively being sought. Computer-assisted processing of dynamic renal function studies enables the observer to obtain a wealth of information related to the renal extraction, uptake, parenchymal transit and pelvic transit parameters of the agent administered into the bloodstream. Each of these parameters either globally or differentially contributes to a detailed evaluation of renal disease states. Several of these procedures have been validated against classical techniques clinically but more detailed information is being sought with the recently introduced radiopharmaceuticals. With the detailed validation and increasing recognition of the clinical utility of several of the radionuclidic procedures at many centers, it is hoped that radionuclide assessment of renal disorders ultimately will be made available routinely at all medical facilities.

Physiologic responses of the transplanted human kidney.

Abstract The denervated, transplanted kidneys of six patients who had received kidneys from live, related donors (one identical twin) were able to maintain normal sodium balance. Peripheral plasma renin activity on a high-salt diet was 354 ± 28 mμg of angiotensin ∥ (±SE) in the donors and 291 ± 39 mμg per 100 ml in the recipients. Renin activity (low-salt diet) averaged 620 ± 50 mμg in the donors and 700 ± 52 mμg per 100 ml in the recipients. Aldosterone secretory rates were normal in the patients studied as were exchangeable sodium, potassium and body water. The denervated, transplanted human kidney can maintain clearance comparable with the donor kidney, and sodium regulation and renin secretion as evaluated in this study appear to be normal.

Trial of antihypertensive intervention and management: Greater efficacy with weight reduction than with a sodium-potassium intervention

The Trial of Antihypertensive Intervention and Management evaluated nine diet-drug combinations in 878 mildly hypertensive, moderately obese participants using a 3 x 3 factorial design. Drugs evaluated were placebo, diuretic (chlorthalidone), and beta-blocker (atenolol); diets were usual (no intervention), weight reduction, and low sodium/high potassium (Na/K). This article reports 6-month dietary changes and the effect of dietary change on blood pressure. Six-month mean weight change was -4.7 kg in the weight reduction group, -0.3 kg in the Na/K group, and -0.5 kg in the usual-diet group. At 6 months, daily electrolyte excretion had changed in the Na/K intervention group. Daily sodium excretion decreased from 138.0 to 112.0 mmol in the Na/K group and increased from 134.1 to 138.4 mmol in the weight reduction group and from 129.1 to 137.0 mmol in the usual-diet group. Daily potassium output increased from 58.7 to 71.4 mmol in the Na/K group, from 57.0 to 60.5 mmol in the weight reduction group, and from 55.3 to 59.1 mmol in the usual diet group. Analysis of 3-day food records indicated that sodium intake decreased from 141.1 to 85.8 mmol and potassium intake increased from 76.4 to 90.5 mmol. Our results indicate that the goal for weight reduction was more easily achieved than the goal for electrolyte modification.

The renin angiotensin system in newborn dogs: developmental patterns and response to acute saline loading.

Summary: Plasma renin (PRC) and aldosterone concentrations are known to be high during early postnatal life. Whether this is related to the low rates of renal blood flow or to sodium homeostasis remains unknown. Measurements of PRC, renal blood flow, and its intrarenal distribution were performed in 1- to 3-wk-old puppies subjected to maneuvers known to stimulate or inhibit renin release. In the awake state, PRC was observed to be higher in 2-wk-old puppies than in older or younger dogs, (P < 0.0001). Significant differences in PRC were also found between litters (P < 0.0001), but they did not account for the age-related changes. Anesthesia resulted in a 3- to 5-fold rise in PRC, whereas saline expansion suppressed PRC at all ages, the fall tending to become progressively greater with age (P < 0.09). There was no significant correlation between the age-related changes in PRC and those in renal blood flow or its intrarenal distribution. The results of these experiments demonstrate that in the newborn from a qualitative point of view, PRC changes appropriately in response to various stimuli. However, quantitative age-related differences exist in this regard, reflecting an initial immaturity of the feedback system.Speculation: The lack of correlation between plasma renin concentration and the intrarenal distribution of blood flow, corroborated with the existence of a relationship between plasma renin and the state of the extracellular fluid volume, suggest that during development the renin-angiotensin-aldosterone system is geared toward the maintenance of the positive sodium balance intrinsic to the process of growth.

Renal Blood Flow and Renin Activity in Renal Venous Blood in Essential Hypertension

The intrarenal distribution of blood flow measured by the133xenon washout method and the renin activity of renal venous blood were determined in 16 patients with early essential hypertension. None of the patients had evidence of systemic disease except for the elevation in blood pressure (> 150/100 mm Hg). Fifteen of the subjects received a controlled sodium diet during 7 to 9 days before study, at the time of renal angiography. An inverse relationship was noted between the cortical component of the renal blood flow and renin activity of renal venous blood (r = 0.64, P < 0.02). Renin secretion rates were also calculated in 12 patients confirming the inverse relationship between cortical distribution of blood flow and renin secretion (r = 0.763, P < 0.01). The cortical renal blood flow in 10 patients on a low salt intake was 79.6% ± 2.6 (SE) of the total renal blood flow. The cortical blood flow in five patients on a high salt diet was 87.6% ± 1.9 (SE); the statistical difference between the two groups is significant (P < 0.05). A direct relationship was noted between cortical blood flow and the logarithm of the 24-hour urinary sodium excretion from the day preceding the study (r = 0.54, P < 0.05). Renin secretion rate and renin in renal venous blood were directly correlated (r = 0.813, P < 0.01). Changes in corticomedullary distribution of flow were inversely related to the changes in cortical distribution. The degree of reduction of cortical renal blood flow correlated with the degree of increase in renin secretion and in renin activity in renal venous blood. Our data are compatible with reduced cortical renal blood flow mediating renin release or vice versa. Either mechanism would result in more efficient conservation of salt and water by the kidney.

Radiopharmaceuticals for renal studies

A review of the wide spectrum of radiopharmaceuticals developed over the last 15 yr for application in the evaluation of diseases of the kidney and urinary tract is presented below. The radiolabeled contrast agents including Hippuran have been extensively applied for renal function assessment. The kinetics of clearance of many of these agents are not yet satisfactorily established, and there is no ideal agent for routine clinical application, particularly by external counting methods. Many agents for intrarenal blood flow measurement have been reported that have yet to be adapted for obtaining clinical information. Renal morphology has been studied using several radiopharmaceuticals that are either fixed in the renal tubules for a sufficiently long time (chlormerodrin, 99m Tc-Fe ascorbic acid) or cleared from the kidneys fairly rapidly (Hippuran). These agents suffer from several disadvantages because of suboptimum energy of the radiolabel for use with imaging equipment, or relatively high radiation dose, or slow rate of excretion with inadequate organ specificity. It is hoped that the development of new radiopharmaceuticals tagged with radionuclides that have ideal imaging characteristics ( 99m Tc or 111 In) and satisfactory renal clearances will provide a major breakthrough in the continuing search for satisfactory renal agents for imaging and function tests in the near future.

Radionuclide scintigraphy for detection of vesicoureteral reflux in children

The use of technetium 99m pertechnetate combined with scintiphotography for thedetection of vesicoureteral reflux in children is described. Forty-seven children have been studied with this method in conjunction with conventional radiographic cystourethrography. Five hundred microcuries of technetium 99m pertechnetate is instilled into the urinary bladder, following which the bladder is distended gradually with saline. With the use of the Anger camera, the distribution of radioactivity in the bladder and renal areas is recorded on Polaroid film during filling and overdistention of the bladder. The study requires an average of 15 minutes to perform and results in an estimated gonadal radiation dosage of 4 or 5 millirads. There is good correlation with conventional cystourethrography. The procedure is recommended as an adjunct to conventional radiographic techniques for the study of vesicoureteral reflux in children.