Protection against ischemia: a physiological function of the renin-angiotensin system.

The renin-angiotensin system (RAS) is involved in a complex mechanism that serves to preserve the blood supply to organs so that they can maintain cellular function. Angiotensin II exerts this effect, independently of the blood pressure generated, through two time-related events: a fast opening of the reserve collateral circulation and a much slower response of new vessel formation or angiogenesis. This effect is observed in rats with ligation of the abdominal aorta and in gerbils with abrupt or progressive unilateral carotid artery ligation. Inhibition of the angiotensin-converting enzyme (ACE) or the angiotensin II receptor represses this effect, and it appears that it is mediated through a non-AT1 receptor site of angiotensin II. Many tumors, both benign and malignant, express renin and angiotensin. It seems that the stimulating action of angiotensin II on angiogenesis could also be involved in preserving the blood supply to tumor cells. Administration of converting enzyme inhibitors increases survival and decreases tumor size in tumor-bearing rats. These observations support the hypothesis that the RAS, directly or indirectly, is involved in situations in which the restoration of blood supply is critical for the viability of cells and that it is present not only in normal but also in pathological conditions such as tumors. In view of the ubiquitous presence of renins and angiotensins, it is also likely to be involved in other conditions, such as inflammation, arthritis, diabetic retinopathy, and retrolental fibroplasia, among others in which angiogenesis is prominent. In addition, angiotensin II could be involved, through the counterbalance of the AT1 and AT2 receptors, in the rarefaction of blood vessels as an etiologic component of essential hypertension.

Indium-111 capromab pendetide (ProstaScint) uptake in neurofibromatosis.

We report on the demonstration of nonspecific accumulation of indium-111 capromab pendetide (ProstaScint) in neurofibromas in a patient with a rising prostate-specific antigen level after prostatectomy. Although the immunoconjugate is targeted to a specific membrane antigen present in human prostate carcinoma, nonspecific uptake can occur in other entities. Indium-111 capromab pendetide scintigraphy is a valuable diagnostic tool that should always be interpreted within the context of the clinical history and the laboratory and radiologic findings to avoid misinterpretation.

Value of scintigraphy in chronic peritoneal dialysis patients.

BACKGROUND: A variety of factors can adversely impact chronic peritoneal dialysis (CPD) as an effective renal replacement therapy for patients with end-stage renal disease. These factors include peritonitis, poor clearances, loss of ultrafiltration, and a variety of anatomic problems, such as hernias, peritoneal fluid leaks, loculations, and catheter-related problems caused by omental blockage. This study reviews our experience with peritoneal scintigraphy for the evaluation of some of these difficulties. METHODS: From 1991 to 1996, 50 peritoneal scintigraphy scans were obtained in 48 CPD patients. Indications for scintigraphy were evaluated, and the patients were placed into four groups: group I, abdominal wall swelling; group II, inguinal or genital swelling; group III, pleural fluid; and group IV, poor drainage and/or poor ultrafiltration. A peritoneal scintigraphy protocol was established and the radiotracer isotope that was used was 2.0 mCi of 99mtechnetium sulfur colloid placed in two liters of 2.5% dextrose peritoneal dialysis solution. RESULTS: Ten scans were obtained to study abdominal wall swelling, with seven scans demonstrating leaks; six of these episodes improved with low-volume exchanges. Twenty scans were obtained to evaluate inguinal or genital swelling, and 10 of these had scintigraphic evidence for an inguinal hernia leak (9 of these were surgically corrected). One of four scans obtained to evaluate a pleural fluid collection demonstrated a peritoneal-pleural leak that corrected with a temporary discontinuation of CPD. Sixteen scans were obtained to assess poor drainage and/or ultrafiltration. Five of these scans demonstrated peritoneal location, and all of these patients required transfer to hemodialysis. The other 11 scans were normal; four patients underwent omentectomies, allowing three patients to continue with CPD. CONCLUSION: Peritoneal scintigraphy is useful in the evaluation and assessment of CPD patients who develop anatomical problems (such as anterior abdominal, pleural-peritoneal, inguinal, and genital leaks) and problems with ultrafiltration and/or drainage.

Pleural effusions: patterns on ventilation-perfusion lung scans.

Perfusion and ventilation abnormalities created by pleural effusions can interfere with the interpretation of the lung scan. This retrospective study identified and evaluated the specificity of scintigraphic patterns for pleural effusion. Ninety-two ventilation-perfusion lung scans were analyzed for the following signs of pleural effusion: presence of fissures, straightened or concave lung borders, costophrenic angle blunting, and attenuation of lung activity by interposed fluid. The findings later were correlated with chest radiographs. Of 25 pleural effusions detected by chest radiography, scintigraphy predicted 14 (specificity, 86%). In all of these cases, there was agreement with the chest radiograph (specificity, 100%). The fissure sign and the straight-concave border sign were equally reliable for the prediction of pleural fluid. Costophrenic angle blunting was never seen as the sole indicator of pleural fluid, and attenuation was seen alone in only one case. Another finding observed during this evaluation was absent ventilation at the lung base with preserved perfusion. Scintigraphic patterns may not be reliable in obstructive lung disorders and diseases with altered lung compliance. The recognition of scintigraphic patterns of pleural effusions on ventilation-perfusion scans can improve the clinical value of lung scintigraphy by reducing the number of indeterminate readings.

Compartmental analysis of the complete dynamic scan data for scintigraphic determination of effective renal plasma flow.

UNLABELLED: We have developed an image-based compartmental analysis for estimating effective renal plasma flow (ERPF in units of milliliters per minute) from the full time-activity curves of regions of interest (ROI) placed over the heart, kidneys and bladder. METHODS: Kidney or time-activity curves are corrected for physical attenuation using estimates of kidney depth derived from patient height and weight. Estimates of the calibration factors, Kp and Kb (mCl/counts/sec), for the plasma and bladder time-activity curves are determined by applying the following ROI analysis to each frame of the dynamic scan: (Kp)Pc(t) + (Kb)Bc(t) = Di - Rq(t), where P c(t) and Bc(t) represent the counting rates measured in ROI placed over the left ventricle blood pool and bladder at time t; Di is the known total injected dose, and Rq(t) represents the millicurie of tracer in the kidneys at time t. Once Kp and Kb have been determined by regression, the calibrated time activity curves are used to solve for the physiological parameter fERPF (min-1), which represents the fraction of the total body plasma cleared of mertiatide per min. The ERPF calculated by the product of fERPF and plasma volume, determined from patient weight, was compared to the ERPF as calculated by blood samples and the Schlegel and renal uptake plasma volume product scintigraphic techniques. RESULTS: Twenty-five adult patients with a wide range of ages and renal function were studied. The results of this image-based method for calculating ERPF correlated well with the values obtained from blood samples (linear regression slope = 1.06; y-int = -34.68 ml/min, r = 0.905) and offered a significant improvement over both the Schlegel and renal uptake plasma volume product estimates (p < 0.05). CONCLUSION: A scintigraphic estimation of ERPF without blood samples using time-activity data from the heart, kidneys and bladder acquired over the entire renogram is feasible and correlates well with more invasive techniques requiring blood samples.

Gallium scans in the management of patients with Hodgkin's disease: a study of 101 patients.

PURPOSE: To evaluate the utility of periodic gallium (67Ga) scans in the management of patients with Hodgkin's disease. PATIENTS AND METHODS: From 1990 to 1994, 101 patients treated for Hodgkin's disease (stage I to II, n = 67; stage III to IV, n = 34) had a positive 67Ga scan at the time of diagnosis. Treatment included chemotherapy in 27 patients, radiation therapy in 28, and combined modality therapy in 46. All patients underwent 67Ga scans at the time of diagnosis, near the end or just after treatment, and at periodic follow-up evaluation. RESULTS: After treatment, the 67Ga scan remained positive in four patients and was interpreted as negative in 97. Among the four patients with positive scans, two died of progressive disease and two relapsed. Among the remaining 97 patients with negative 67Ga scans, 16 patients relapsed, including five with stage I to II (7.5%) and 11 with stage III to IV (34.4%) disease. The negative predictive value of posttherapy 67Ga scan was 83.5% for all patients; however, when calculated according to stage, it was 92.4% for patients with stage I to II disease and 64.5% for patients with stage III to IV disease (P < .01). CONCLUSION: A positive 67Ga scan at the end of therapy is rarely seen in patients with Hodgkin's disease and should be considered a manifestation of gross residual disease. However, a negative 67Ga scan after therapy had a significantly lower predictive value in patients with stage III to IV disease compared with stage I to II disease. The predictive value of 67Ga scans, as well as newer imaging studies, should be analyzed according to pretreatment stage.

Pin-hole collimator, parallax, and the localization of mediastinal parathyroid adenoma.

A parathyroid adenoma was wrongly localized by pinhole Tc-99m sestamibl scintigraphy to the anterior mediastinum near a lower pole of the thyroid gland. After a failed surgical attempt to resect the adenoma, the patient was re-imaged with a parallel-hole collimator and SPECT. The adenoma was found to be near the heart, anterior to the carina. The pinhole findings were replicated using a phantom and measurements obtained from a CT of the chest. By placing the pinhole collimator at the sternal notch level, the lesion was correctly located deep in the chest. Moving the pinhole collimator cephalad or tilting the collimator toward the feet, maneuvers sometimes needed to clear the chest in large patients, projected the lesion closer to the sternal notch. Scintigraphy with a parallel-hole collimator is recommended and SPECT should be considered when the lesion is located below the sternal notch and when a lesion is not detected, despite the clinical and biochemical diagnosis of hyperparathyroidism.

Assessment of the rate of uptake-plasma volume product to calculate glomerular filtration rate [corrected].

UNLABELLED: To further validate the rate of renal uptake of the 99mTc-DTPA-plasma volume product (RUPV) method to estimate glomerular filtration rate (GFR), 104 determinations were performed and compared to blood sample of GFR assays. The interassay consistency was also studied in 42 patients. METHODS: The studies were performed with 370-550 MBq (10-15 mCi) of 99mTc-DTPA and a gamma camera. The 3-min cumulative renal uptake was calculated from the renogram curves and expressed as the rate of renal uptake in min-1. The plasma volume, in milliliters, was estimated from the patient's body weight. The GFR (ml/min) was calculated from [RU] x [PV] and by using two blood samples. To study interassay consistency, two determinations of GFR were performed on separate days. RESULTS: The regression equation relating the rate of renal uptake (RU) in the abscissa and the GFR obtained from plasma samples in the ordinate is: y = 3.13 + 10.5x (n = 104; r = 0.90). The regression equation of RUPV estimated GFR (x) compared to the GFR calculated from blood samples (y) is: y = 6.9 + 0.91x (n = 104; r = 0.94). The interassay consistency study showed no statistically significant difference between measurements obtained on Days 1 and 2. The mean +/- s.e.m. GFR for each determination were 84.3 +/- 6.12 and 81.9 +/- 6.21. For the blood sample method, the mean s.e.m. for each day were 87.26 +/- 6.69 and 96.86 +/- 6.58 (p < 0.05). The percent variation coefficient for the RUPV method was: CV% = 6.8 +/- 2.7 and 12.1 +/- 3.3 (p < 0.03) for the blood sample method. CONCLUSION: The observed accuracy of the determination is comparable to that in our previous study of a separate patient population at another hospital. This method would be suitable for interinstitutional comparison and for longitudinal patient studies.

Angiotensin AT2 receptor stimulation increases survival in gerbils with abrupt unilateral carotid ligation.

Previous studies showed that angiotensin II (AII) infusion increased survival in gerbils subjected to abrupt unilateral carotid ligation. Recently, stimulation of the AII AT2 receptor, reportedly effectively extended the blood pressure (BP) range of cerebral blood flow (CBF) autoregulation. We evaluated the survival of gerbils treated with PD-123319, a ligand of AT2 receptors, to test the hypothesis that restoration of BF to ischemic cerebral tissue produced by AII is mediated through AT2 receptors. Abrupt unilateral carotid ligation was performed on 300 gerbils. In five experimental groups, animals received no drug pretreatment: (a) saline; (b)-(d) PD-123319 1.0, 3.0, and 10 mg/kg; and (e) losartan 10 mg/kg. In three additional experimental groups, animals were pretreated with enalaprilat: (f) saline; (g) PD-123319, 10 mg/kg, and (h) losartan, 10 mg/kg. Survival for 48 h was significantly improved by PD-123319 (10 mg/kg) (p < 0.05) and by losartan (10 mg/kg) (p < 0.05) as compared with animals injected with saline. Pretreatment with enalaprilat neutralized the protective effect of losartan. PD-123319 is an AT2 agonist and improved survival in this animal model of stroke. Losartan, an AT1 antagonist, also improved survival, possibly through renin release and AT2 stimulation by endogenous AII. This effect was neutralized by enalaprilat.

Gallium scans in patients with mediastinal Hodgkin's disease treated with chemotherapy.

PURPOSE: To determine the predictive value of gallium scans in patients with mediastinal Hodgkin's disease treated with chemotherapy or combined modality treatment. PATIENTS AND METHODS: A retrospective study was performed of 48 patients with mediastinal Hodgkin's disease treated with chemotherapy or combined modality therapy. Patients were monitored with whole-body planar scans (34 patients) or chest single-photon-emission computed tomography (SPECT) plus planar abdominal imaging studies (14 patients). Scans were performed at diagnosis, following three to eight cycles of chemotherapy, and after the end of treatment. The value of gallium scans in modifying treatment and predicting outcome was assessed. RESULTS: All patients studied at the time of diagnosis had abnormal gallium accumulation in the mediastinum. After chemotherapy, four patients had residual mediastinal activity; two patients with persistent activity on planar scans failed to enter remission and died of disease; two other patients with abnormal activity only seen on SPECT had therapy modified and remain in remission. After chemotherapy, 44 patients had a normal gallium scan. Twelve patients with negative scans relapsed, including nine patients with recurrence above the diaphragm. CONCLUSION: The use of gallium scans after several courses of chemotherapy resulted in a modification of treatment in four patients, including two patients who are apparently cured. However, after negative scans, 20% of patients relapsed above the diaphragm. These results suggest that gallium imaging, including SPECT, is of limited value in predicting disease sterilization, although the number of patients studied with SPECT was small. At present, the major value of gallium scans is to identify patients who may benefit from a modification of treatment.

The technetium-99m-DTPA renal uptake-plasma volume product: a quantitative estimation of glomerular filtration rate.

An image-based method for estimating quantitative renal glomerular filtration rates (GFR) by calculating the product of the renal uptake rate and plasma volume is presented. By using the relationship GFR = F.PV/t, F represents renal 99mTc-DTPA uptake after bolus injection, PV is the plasma volume and t is time. This GFR evaluation was carried out on 96 patients and compared to GFR values determined in the same patients using radiotracer blood clearance techniques relying on two venous blood samples. When estimating patient plasma volumes using patient's weight and measured hematocrit values, the image-based method for calculating GFR accurately approximates the values obtained from blood samples (linear regression slope = 1.03; y-intercept = -2.81 ml/min). The two techniques correlate with a value of r = 0.89.

Incidental demonstration of pericardial fistula during hepatobiliary scintigraphy.

Biliary vomiting developed 16 mo after resection of adenocarcinoma of the esophagus in a patient with a complex postoperative course. A biliary scan revealed an outline of the pericardium, suggesting a fistula. The potential role of radionuclide imaging in this rare and potentially fatal complication is discussed.

Noninvasive staging of lung cancer. Indications and limitations of gallium-67 citrate imaging.

The results of evaluation of the hila and mediastinum with 67Ga scans are contradictory, as are the recommendations by different investigators on the use of 67Ga scintigraphy in the clinical evaluation of patients with primary lung carcinoma. Nevertheless, the economy and logistic simplicity of evaluating local and distant metastases with a single imaging procedure are attractive, especially because the symptoms may not enable the physician to make a correct identification of the organ systems affected by metastases. Neumann and Hoffer state that "at present conventional Ga-67 scanning techniques cannot be recommended for preoperative staging of mediastinal lymph node metastases in lung cancer patients." According to Waxman, 67Ga scintigraphy, relative to other imaging modalities, is a sensitive indicator of hilar spread of a tumor. However, because of the normally high background activity within the sternum and spine, mediastinal abnormalities may be poorly detected. Since most pulmonary tumors metastasize via regional nodes to the pulmonary hilum and then to the mediastinum, the high sensitivity for the detection of pulmonary hilar abnormalities and the high specificity for detection of mediastinal lesions suggest that gallium scintigraphy is a valuable adjunctive test when used appropriately. The results obtained locally are probably the best guide for individual physicians in the selection of diagnostic tests for their patients. Gallium scans may thus be helpful in the clinical evaluation of patients with lung cancer. Although gallium scans identify mediastinal node involvement, there is considerable controversy over the relationship between the sensitivity and specificity of the method. By detecting distant extrathoracic metastases, the 67Ga scan may identify a small group of patients who can be spared a needless operation. Gallium scanning fails specifically for metastases within the brain; thus, it does not supplant CT scans of the brain and it is less sensitive than bone scans in detecting osseous metastases. Gallium scanning of patients with small-cell lung cancer is not useful in the selection of therapy but does become important from a prognostic standpoint. Patients with extrathoracic involvement by small-cell carcinoma of the lung are known to have limited survival times compared with those of patients with thoracic involvement alone. In identifying patients with extensive disease, the oncologist is thus provided with prognostic information that may be useful in the counseling of the patient and the patient's family.

Single perfusion defect and pulmonary embolism: angiographic correlation.

One hundred and thirty-three ventilation-perfusion scans (V-P) with angiographic correlation were retrospectively reviewed to evaluate the frequency of pulmonary emboli (PE) in single perfusion defects (SPD), regardless of ventilation or radiographic findings. By angiography, 15 of 30 SPD cases had PE. Demographic data and clinical presentation were similar for PE and non-PE patients. However, 9 out of 15 patients with PE had recent surgery compared to none of the non-PE patients. SPD were seen in areas of ventilation and chest x-ray abnormalities in 12 of 15 PE and 11 of 19 non-PE cases. Size of the actual lesion was underestimated by scintigraphy in most cases. In 7 of 15 PE cases, the perfusion defect was larger than the corresponding ventilation abnormality. Most SPD were located at the bases. Twelve of 15 SPD in the PE group were at the posterior basilar segment. In the appropriate clinical setting, SPD carries at least a moderate probability for PE. When the clinical suspicion is high, a pulmonary angiography will be needed to confirm the diagnosis.