Clinical evaluation of patients with hypertension and exercise-induced renal dysfunction.

An exercise-mediated renal omicron-iodohippurate transport abnormality was recently identified in patients with hypertension. The disturbance was not observed in normotensive controls. To learn more about this transient functional disturbance of the kidney, we obtained gamma camera hippurate renograms in 45 patients with hypertension. The final diagnoses indicated that 27 patients had essential hypertension, 15 had renal parenchymal or renovascular hypertension, 2 had malignant hypertension, and 1 had hypertension of pregnancy. We documented age, height, weight, global and unilateral renal function, blood pressure status, and antihypertensive medication used at time of scintigraphy. We also noted the serum catecholamine, sodium, and potassium levels. All patients were scintigraphed at rest and during exercise. The scintigraphic examination documented exercise-induced renal dysfunction in 28 (62%) patients (abnormal exercise renogram), while 17 (38%) had renograms not noticeably influenced by the exercise protocol (normal exercise renogram). When the results of scintigraphy were compared with the clinical data, a weak correlation was found between patient overweight and an abnormal response to exercise. There was no significant difference between groups with normal and abnormal exercise renograms with respect to the other parameters assessed. Exercise renography was not useful for differentiating renal and essential hypertension. Renography appears to demonstrate an exercise-mediated, transient, renal perfusion disturbance in certain patients with hypertension. The examination appears to assess a new parameter in hypertensive disease. Thus, the gamma camera renogram should be reevaluated in the patient with hypertension.

Predictive value of exercise renography for presurgical evaluation of nephrogenic hypertension.

Functional omicron-iodohippurate scintigrams were obtained in 18 hypertensive patients. Each patient was examined in the prone position and during exercise. An exercise-induced transient, bilateral, hippurate transport disturbance was sought as an expression of an exercise-mediated cortical perfusion abnormality. The study sought to test the hypothesis that patients who present evidence for an exercise-induced renal perfusion disturbance would have stabilized hypertension that was no longer surgically curable because of morphological changes of the peripheral vasculature. All 18 patients continued on to therapy: 13 proceeded to renovascular reconstructive surgery, 2 had a unilateral nephrectomy, and 3 were treated with percutaneous transluminal renal angioplasty. During preoperative exercise renography, evidence of bilateral renal dysfunction developed in 10 of 18 hypertensive patients during ergometric stress (abnormal exercise response). Following surgical therapy nine of these patients with abnormal exercise scintigrams continued to have hypertensive disease, while one patient was cured. The exercise renograms of eight hypertensive patients were not influenced by the exercise protocol, and operation cured seven of these eight patients. The results suggest that an accentuated vascular response to exercise occurs in the maintenance phase of renovascular hypertension, a disturbance not observed while the hypertension is curable by surgical therapy.

Radioisotope therapy of cystic craniopharyngomas.

Eighteen patients suffering from cystic craniopharyngeoma were treated with intracavitary irradiation. The beta-emitting radioisotope 90y (2.25 MeV) was instilled into the cyst following stereotactic puncture of the space-occupying lesion. The surgical approach was planned using angiograms and reconstructed transmission computer tomography (TCT) coronal and saggital sections. Therapy was devised to deliver 20,000 rad to the cyst's wall. Eleven patients received follow-up TCT examinations after four months. Eight of 11 patients had a significant volume decrease in the craniopharyngeoma cyst. In two patients, the cystic volume remained unchanged; one had progression of disease. It is concluded that the intracavitary treatment of cystic craniopharyngeoma will result in a reduction of the size of the space-occupying lesion.

Repeat exercise renograms in hypertension identify persistent renal dysfunction.

BACKGROUND: Hypertensives may develop bilateral trapping of para-aminohippurate analogues in the tissue of the kidneys during light exercise, as can be demonstrated using radioactively labelled [131I]-hippurate or [99mTc]-mercaptoacetyl-triglycine. Tracer accumulation in the kidneys during exercise results in a typical renographic pattern, the bilateral-abnormal exercise renogram. The disturbance is common during exercise, being found in almost 60% of all hypertensives, regardless of aetiology. OBJECTIVE: To determine whether bilateral-abnormal exercise renograms are spurious phenomena, or whether the results of exercise renography are reproducible. DESIGN: We reviewed the renographic examinations of 27 hypertensive patients, each of whom had undergone at least one resting and two [131I]-hippurate or [99mTc]-mercaptoacetyl-triglycine gamma-camera exercise renograms. The status of the renal artery at the time of scintigraphy was documented, using available arteriograms. The causes of vascular lesions were noted, as were revascularization procedures and the antihypertensive medication being taken at the time of scintigraphy. RESULTS: The average time between exercise renograms was 15.5 months, and 24 of the 27 hypertensive patients had comparable results in the first and the follow-up exercise renogram, divergent results being noted for the other three patients. Re-evaluation of the scintigrams of the three hypertensive patients with divergent results suggested that intermittent pelvic retention might have caused errors of interpretation in two. We found it notable that neither revascularization nor a change in antihypertensive drug therapy influenced the results of exercise renography. Exercise renograms were reproducible over long periods, and potential extraneous influences on blood flow, such as antihypertensive drugs or revascularization, failed to alter the results. CONCLUSION: The results are considered relevant, because a direct relationship appears probable between hypertension and the disturbance investigated. Reproducible results suggest that the exercise-mediated disturbance is fixed to the kidneys, that it can be reactivated repeatedly and that it may play a role in maintaining hypertension.

The exercise renogram. A new approach documents renal involvement in systemic hypertension.

Hippurate functional scintiscans were obtained in 51 hypertensive patients and in 15 controls. We investigated the influence that posture and exercise have on hippurate kinetics in patients with hypertension. A posture- or exercise-induced disturbance of renal hippurate transport was sought. All persons were examined in prone and standing positions, as well as during exercise. When prone and upright renograms were compared, 24% of the hypertensives demonstrated bilateral orthostatic renal dysfunction. Exercise caused the hippurate transport disturbance to increase. Fifty-seven percent of all hypertensives developed evidence of marked, bilateral, renal dysfunction during ergometric stress, so that exercise renography was shown to be a more sensitive test of the presence of transient tubular dysfunction in hypertension than the standing renogram. In normotensive controls the hippurate functional scintigram failed to be influenced by posture and exercise. The results suggest presence in hypertension of transient, posture- and exercise-mediated alterations of renal cortical blood flow.

Single photon emission computerized tomography (SPECT) for estimates of liver and spleen volume.

A simple procedure is described for estimates of liver and spleen volume using the imaging data obtained during single photon emission computerized tomography ( SPECT ). In vitro studies were carried out to obtain correlation and regression coefficients for volume estimations. Using these regression coefficients, we estimated liver and spleen volumes in 50 patients. Phantom and organ volumes were also calculated from transmission computed tomography (TCT), whose results served as the reference procedure against which SPECT -determined volumes were compared. The influence of radiotracer uptake on scintigraphic volume predictions was also assessed. For the in vitro measurements, SPECT volumes predicted the true volumes with a coefficient of correlation of 0.997. When in vivo SPECT volumes were correlated with those obtained by TCT, a coefficient in excess of 0.9 was achieved. SPECT volume determinations proved to be influenced by organ uptake of tracer; high liver uptake and low spleen-to-liver ratios gave the best results. It is concluded that SPECT imaging offers access to rapid and exact volume estimation.

[131I] Hippuran renography in the detection of orthostatic hypertension.

Scintigrams in prone and standing positions were done in 11 hypertensive women. All had nephroptosis with ventral rotation. On the basis of the renograms, seven patients were identified as suffering from orthostatic hypertension. Nephropexy resulted in normalization of blood pressure in six of the seven patients and normalization of the renograms of all seven. We believe that sequence scintigrams in prone and standing positions offer a simple method of identifying patients with orthostatic hypertension.

Renovascular hypertension: a perfusion disturbance that escaped recognition.

A bilateral, exercise-mediated, hippurate transport disturbance was previously described when patients with fixed renovascular hypertension were imaged with o-iodo-hippurate. This study sought to test the hypothesis that patients with an abnormal exercise scintigram have a perfusion abnormality characterized by dysregulation of renal blood flow. We imaged 23 patients with hypertension and angiographically documented renovascular disease in the supine position, as well as during upright exercise. Seven normotensive volunteers served as controls. We measured the resting glomerular filtration rate (GFR) and the effective renal plasma flow (ERPF) with a single compartment radiotracer infusion clearance. The clearance examination also included a measurement period with 25 watt ergometric exercise. Nine hypertensive patients had normal exercise renograms. These patients had age-appropriate clearance values at rest and during exercise, as well as age-appropriate best-organ (generally without stenosis) GFR and ERPF values. The filtration fraction (FF) was 0.21 at rest and 0.22 during exercise. Fourteen hypertensive patients had a bilateral, exercise-induced disturbance of hippurate transport. In these patients, the global resting GFRs and ERPFs were decreased 40% from age-appropriate predicted values. The FF remained at 0.20. Light exercise caused a pronounced contraction of GFR and a less severe reduction in the ERPF. During exercise the mean filtration fraction was only 0.12. The exercise-induced reduction in the clearance values was bilateral, which indicated that the perfusion of nonstenosed organs was compromised as well. We suggest that the described perfusion abnormality occupies a relevant position during the maintenance phase of fixed renovascular hypertension.

The exercise renogram and its interpretation.

UNLABELLED: The exercise renogram is a rarely used diagnostic procedure, but it may visualize an exercise-induced change in renal function related to the pathophysiology of essential hypertension, which could greatly increase interest in this examination. The aim of this study was to demonstrate the interpretative approach and the terminology which is used to describe results of exercise renography, using a population of hypertensives with renovascular disease. METHODS: We reviewed the examinations of 70 hypertensives who had supine renography as well as exercise renography with a 60-80 W work load. Forty-eight patients were examined with 99mTc-MAG3 and 22 with 131I hippurate. The renographic and angiography results were recorded as well as the antihypertensive drugs used and the site of vascular lesions. RESULTS: Thirty-three hypertensives developed a bilateral-abnormal exercise renogram, which appears to be associated with primary hypertension. Eight individuals responded to exercise with a unilateral-abnormal exercise renogram, in a kidney behind a stenosis. Only 19 patients had a normal exercise renogram, and 10 had only one functioning kidney. Pathology recognized but unrelated to the intervention included nonfunctioning and small kidneys and pelvic retention. CONCLUSION: Exercise renography's only indication is for recognition of pathology unique to hypertension, since other function disturbances were recognized in resting renograms.

A Ga-68-labeled tetrabromophthalein (Ga-68 BP-IDA) for positron imaging of hepatobiliary function: concise communication.

We describe the chemical synthesis of an iminodiacetic-acid-substituted tetrabromo-o-cresolphthalein (BP-IDA), which complexes Ga-68 tightly. The liver uptake, bile excretion, and urinary excretion of the complex were examined in rats. Maximum liver uptake reached 60%, and 1-hr cumulative bile excretion was 75% of injected dose. Urinary excretion in rats with ligated common bile duct remained below 1%. Competitive action of exogenous bilirubin on hepatobiliary excretion of the Ga complex was less pronounced than that of bromosulfophthalein. The absolute activity determination of the positron emitter Ga-68, the high accumulation in the liver, the low urinary excretion, and the weak competition from exogenous bilirubin are promising features of this radiopharmaceutical for the quantitative study of hepatobiliary function.

Single-photon emission computed tomography (SPECT) for assessment of hepatic lesions.

Single-photon emission computed tomography (SPECT) and conventional scintigraphy were compared in 130 patients examined to assess hepatic involvement in malignant disease. Transmission computed tomography (TCT) served as the reference method against which SPECT and conventional scintigraphy were compared. The sensitivity of SPECT was calculated for lesions grouped according to diameter as well as location. The Bayesian theorem was used to assess the reliability of both SPECT and conventional scintigraphy. SPECT identified only 52% of lesions with a diameter of 1.5-2.0 cm. It was also shown that the sensitivity of SPECT was lowest for small lesions in the middle third of the liver. A comparison of the final diagnosis demonstrated that SPECT had greater sensitivity, specificity, and accuracy than conventional scans, and is superior at low disease prevalence. At high disease prevalence, SPECT has a lower rate of false negatives. SPECT appears to be the superior imaging modality for evaluation of the liver in malignant disease.

Posture-induced disturbance of pertechnetate flow and I-123 iodohippurate transport in some renal graft recipients with hypertension.

Iodohippurate renography and rapid serial scintigrams with pertechnetate were done in 27 allograft recipients in supine and standing positions. Posture-dependent iodohippurate transport and/or disturbance of pertechnetate flow pattern was found in nine of those examined. Patients demonstrating these abnormalities were found to be hypertensive. We suggest a causal relationship between posttransplant hypertension and the described posture-induced alterations of tracer transit.

Studies with positron emission tomography after systemic administration of fluorine-18-uracil in patients with liver metastases from colorectal carcinoma.

Fluorouracil (FU) is the most common cytostatic agent used for chemotherapy in patients with colorectal tumors. Fifty patients with 78 hepatic metastases from colorectal tumors were examined with positron emission tomography (PET) following intravenous infusion of 18F-FU. The uptake of the cytostatic agent was evaluated in normal liver parenchyma, liver metastases and the aorta. Tracer uptake was expressed with the standardized uptake value (SUV). The maximum liver activity was 11.3 SUV (mean value) with a standard deviation of 1.85 SUV. The highest activity concentrations were noted 30 min (mean value) postinjection. In comparison, the activity concentration of individual metastasis was low. Two hours after tracer injection, the mean activity in metastases was 1.3 SUV, but notable individual variation in uptake was seen. Fluorine-18 concentration values 2 hr after FU infusion were approximately 44% of the FU uptake 20 min postinfusion. Fifty-three metastases were also examined with 15O-labeled water. The examination was performed to compare the uptake of the nonmetabolized tracer with FU uptake. We noted a statistically significant correlation between 15O-water concentration, uptake of nonmetabolized FU 8 min after the end of the infusion and FU retention (120 min postinjection) in a subgroup of metastases. The results suggest that FU retention in different metastases is highly variable and mainly dependent on early FU uptake into tumor cells.

Renal graft evaluation with pertechnetate and I-131 Hippuran. A comparative clinical study.

This retrospective study compared standard clinical and biochemical data from 50 graft recipients against 533 I-131 Hippuran sequential scintigrams and 515 [99mTc]pertechnetate serial scintigrams. All grafts included in this study are cadaver kidneys. The majority of the studies were made during the early posttransplantation period. Anuria or oliguria of at least 4 days duration was seen in 18 patients. The study spans 574 days of oliguria during which 136 dual-tracer studies were made. I-131 Hippuran renography of functioning grafts was carried out 397 times, and the Tc-99m sequential scintigraphy 379 times. In all, 47 espisodes of actue rejection were registered clinically in functioning gfafrs, 36 of which were recognized during Hippuran renography and 38 with the pertechnetate study. False-positive errors were seen 12 times during renography. The study also demonstrated that furosemide will significantly and predictably influence renography and the pertechnetate study. This seems noteworthy since furosemide is extensively used in posttransplant management.

Contribution of paramagnetic trace elements to the spin-lattice relaxation time in the liver.

The relaxation times of water protons in rat liver tissue were measured with a NMR spectrometer at 20 MHz. The paramagnetic trace elements Cu, Fe, and Mn were determined by neutron activation analysis. No shortening of T1 could be observed when liver Cu or Fe concentration was increased in the microgram range. T1 was strongly correlated with the liver Mn concentration of untreated animals and animals whose liver Mn concentration was artificially increased or decreased by intravenous injection of manganous acetate or a metal chelating agent with high affinity for hepatobiliary excretion. Deviations from this Mn-T1 correlation were found in the initial phase of liver cirrhosis induced by thioacetamide (elongated T1, normal Mn concentration) and after stimulation of liver growth by phenobarbital (normal T1, decreased Mn concentration). An increased or decreased enhancement factor for Mn may have contributed to the observed deviations during phenobarbital and thioacetamide treatment.

Afferent-efferent vessel dysfunction appears to be a specific characteristic of a large subset of patients with essential hypertension.

Exercise renography makes it possible to subdivide essential hypertensives (EHs) into two distinct populations. Fifty to 60% develop exercise-mediated renal dysfunction and a transitory, severe reduction of glomerular filtration. The other subset of EHs does not have exercise-mediated renal dysfunction. We hoped to learn whether the disturbance is also present while EHs rest. Twenty-six EHs and 21 normotensive controls were studied with a resting sequential renogram using Tc-99m-mercaptoacetyl-triglycine (MAG3), a tracer excreted primarily by proximal tubular cells. EHs also had an exercise renogram. All persons had three consecutive 10-min dual-tracer infusion clearance determinations with 111In-DTPA and 131I-hippurate, for the simultaneous determination of glomerular filtration rate (GFR) and effective renal plasma flow (ERPF). To demonstrate the accuracy of the clearance procedure we sought to reproduce Hollenberg's results which show greater flow variability in EH than in normotension. Following this, the variability (VAR) of the GFR and ERPF as well as the variability fraction (VF), the ratio of GFR variability divided into the ERPF variability, were calculated. Hollenberg's results were reproduced. Sixteen of 26 essential hypertensives developed exercise-mediated renal dysfunction. GFR-VAR in EH differed from controls. The VF suggests that EHs with a bilateral abnormal exercise renogram have a more pronounced GFR variability than those EH with a normal exercise renogram. The results point to intraglomerular pressure fluctuations in patients with EH, and the VF suggests that this may be more pronounced in EHs with a bilateral abnormal exercise renogram than in those with a normal exercise renogram. It is hypothesized that the variable GFR provokes renin secretion in EH.

Exercise activates renal dysfunction in hypertension.

A bilateral, exercise-mediated renal functional abnormality was first described more than a decade ago. The disturbance is specific for hypertension, is seen in different forms of hypertension, and has been studied most extensively in hypertensives with renovascular disease. The bilateral-abnormal exercise renogram identifies the disturbance. Hypertensives with unilateral renovascular disease were studied in the continuing evaluation of the bilateral function disturbance. We examined 31 hypertensives with documented unilateral renovascular disease, all of whom had renography at rest and during 60 to 80 W ergometric exercise. An additional seven normotensives and 17 essential hypertensives served as controls, and had the same sequence of studies. All patients reported upon continued on to an infusion clearance with 131I-hippurate and 111In-diethylenetriamine pentaacetic acid to determine glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) at rest, and during 25 W ergometric exercise. Eighteen of 31 hypertensives with unilateral renovascular disease were found to have a bilateral-abnormal exercise renogram. Clearance examinations in these identified a prominent reduction of the GFR and a lesser decrease in the ERPF during exercise. Hypertensives with normal exercise renograms did not have the exercise mediated abnormal clearance pattern. Similar results were observed in the control population of essential hypertensives, 65% of whom developed the functional disturbance. The seven normotensives controls did not exhibit the exercise mediated function changes. We conclude that an exercise-mediated bilaterally occurring functional disturbance exists in certain hypertensives, who then have a bilateral-abnormal exercise renogram. Associated with this is a distinctly abnormal clearance during exercise which is characterized by a low filtration fraction.

Parametric imaging of blood flow.

The calculation of functional images was based on recorded fluoroscopic sequences. The Fourier coefficients of the first harmonic were calculated for each matrix element, and the amplitude and phase values were used for the generation of two synthetic images. The amplitude image demonstrated the maximum change in opacification with high image contrast. Phantom studies showed that a high correlation exists between the inverse phase differences and flow. The clinical application of the Fourier method revealed substantial additional information to conventional angiography in one of ten patients. While the morphological evaluation demonstrated no significant stenosis, the functional images showed a residual stenosis.

Computed tomography for staging bronchogenic carcinoma.

One hundred and fourty patients with a primary lung neoplasm underwent transmission computed tomography (TCT) for staging prior to therapy. TCT results were compared with the post-operative T- and N-stage. The preoperative TCT examination correctly classified 70% of all tumors. 73% of T1, 63% of T2 and 74% of T3 tumors did not require restaging after surgery. TCT correctly staged 80% of the patients with respect to the N-stage. Ninety-seven percent of the patients with N0, 42% with N1 and 79% with N2 tumors were correctly classified. Serious over- and understaging was observed in patients with centrally located bronchogenic carcinoma. This was due to the difficulty of distinguishing tumor tissue from enlarged lymph nodes and atelectasis.

Imaging positron emitting radionuclides generated during radiation therapy.

In vivo generated positron emitting radioisotopes, primarily C-11 and N-13, have been documented following therapy with accelerators larger than 10 MeV. Six patients had positron emission tomography 15 to 25 minutes after radiation therapy with a 42 MeV accelerator. Five patients had recurrent colorectal malignancy, and one required therapy for a carcinoma of the common bile duct. We sought to determine whether state-of-the-art PET technology could be used to monitor the three-dimensional activity distribution of radiation-induced radioactivity. At the time of the examination all six patients had sufficient concentrations of C-11 and N-13 activity in the irradiated volume to permit the evaluation of the activity distribution. We found significant activity at the body surface, which permitted field delineation. We conclude that the in vivo generated radioactivity can be monitored with PET.