Quantitative assessment of urea generation and elimination in healthy dogs and in dogs with chronic kidney disease.

BACKGROUND: Kinetic assessment of urea, the main end product of protein metabolism, could serve to assess protein catabolism in dogs with chronic kidney disease (CKD). Protein malnutrition and catabolism are poorly documented in CKD and they often are neglected clinically because of a lack of appropriate evaluation tools. HYPOTHESIS: Generation and excretion of urea are altered in dogs with CKD. ANIMALS: Nine dogs with spontaneous CKD (IRIS stages 2-4) and 5 healthy research dogs. METHODS: Endogenous renal clearance (Clrenal) of urea and creatinine was measured first. Exogenous plasma clearance (Clplasma, total body clearance) of the 2 markers then was determined by an IV infusion of urea (250-1,000 mg/kg over 20 minutes) and an IV bolus of creatinine (40 mg/kg). Extrarenal clearance (Clextra) was defined as the difference between Clplasma)and Clrenal. Endogenous urea generation was computed assuming steady-state conditions. RESULTS: Median Clrenal and Clextra of urea were 2.17 and 0.21 mL/min/kg in healthy dogs and 0.37 and 0.28 mL/min/kg in CKD dogs. The proportion of urea cleared by extrarenal route was markedly higher in dogs with glomerular filtration rate<1 mL/kg/min than in normal dogs, reaching up to 85% of the total clearance. A comparable pattern was observed for creatinine excretion, except in 1 dog, Clextra remained<20% of Clplasma. CONCLUSION: Extrarenal pathways of urea excretion are predominant in dogs with advanced CKD and justify exploring adjunctive therapies based on enteric nitrogen excretion in dogs. A trend toward increased urea generation may indicate increased catabolism in advanced CKD.

Bremsstrahlung radiation exposure from pure beta-ray emitters.

UNLABELLED: With increasing therapeutic use of radionuclides that emit relatively high-energy (>1 MeV) beta-rays and the production in vivo of bremsstrahlung sufficient for external imaging, the potential external radiation hazard warrants evaluation. METHODS: The exposure from a patient administered beta-ray-emitting radionuclides has been calculated by extending the National Council on Radiation Protection and Measurement model of a point source in air to account for biologic elimination of activity, the probability of bremsstrahlung production in vivo and its mean energy and the absorption by the patient's body of the bremsstrahlung thus produced. To facilitate such calculations, a quantity called the "specific bremsstrahlung constant" (in C/kg-cm2/MBq-h), betaBr, was devised and calculated for several radionuclides. The specific bremsstrahlung constant is the bremsstrahlung exposure rate (in C/kg/h) in air at 1 cm from a 1 MBq beta-ray emitter of a specified maximum beta-ray energy and frequency of emission in a medium of a specified effective atomic number. RESULTS: For pure beta-ray emitters, the retained activities at which patients can be released from medical confinement (i.e., below which the effective dose equivalent at 1 m will not exceed the maximum recommended value of 0.5 cSv for infrequently exposed members of the general public) are extremely large: on the order of hundreds of thousands to millions of megabecquerels. CONCLUSION: Radionuclide therapy with pure beta-ray emitters, even high-energy beta-ray emitters emitted in bone, does not require medical confinement of patients for radiation protection.

Effect of prior radiopharmaceutical administration on Schilling test performance: analysis and recommendations.

UNLABELLED: Previously administered diagnostic and therapeutic radiopharmaceuticals may interfere with performance of the Schilling test for prolonged periods of time. Additionally, presence of confounding radionuclides in the urine may not be suspected if baseline urine measurements have not been performed before the examination. METHODS: We assumed that a spurious contribution of counts corresponding to 1% of the administered Schilling dose would begin to contribute clinically significant interference. Based on the typical amounts of radiopharmaceuticals administered, spectra of commonly used radionuclides and best available pharmacokinetic models of biodistribution and excretion, we estimated the interval required for 24-hr urinary excretion of diagnostic and therapeutic radiopharmaceuticals to drop below this threshold of significant interference. RESULTS: For previously administered 99mTc-based radiopharmaceuticals and 123I-Nal, the interval required for urinary levels of activity to fall below thresholds of allowable interference are between 2-5 days. For 67Ga-citrate, several 111In compounds, 131I-MIBG and 201Tl-thallous chloride, periods of 12-44 days are estimated. Estimates for 131I-Nal vary greatly between 4 and 115 days, depending on the amount administered, and the degree of thyroid uptake. CONCLUSION: Patients should be interviewed before performing the Schilling test to ensure that interfering radiopharmaceuticals have not been recently administered. The estimates developed in this paper can serve as guidelines for the necessary waiting time between prior radiopharmaceutical administration and the Schilling examination.

In vitro model to evaluate the relative efficacy of catheter-directed thrombolytic strategies.

RATIONALE AND OBJECTIVES: Catheter-directed thrombolytic therapy has become an accepted treatment for many vascular occlusions. However, the relative rates of lysis of the different methods of drug administration have not been quantified. We developed an in vitro model to simulate and quantify local lytic therapy of a thrombotic vascular occlusion and tested it by evaluating three catheter-directed lytic strategies. METHODS: Seven-centimeter-long segments of 125I-fibrinogen-labeled thrombus made from recently expired human blood from a blood bank were formed in plastic tubes and were placed in a flowing stream of saline. Using multisidehole catheters, the clots were "treated" with intrathrombic saline or urokinase administered by drip infusion or forced injection using identical total doses of drug and volumes of fluid. Using endhole catheters, saline or urokinase was drip infused into the leading edge of the thrombus using the same protocol. A collimated scintillation detector was used to quantify the amount of activity remaining in the thrombus during each experiment, and the resultant time-activity curves for the different trials were compared. RESULTS: Forced-injection administration of urokinase using a multisidehole catheter produced the fastest lysis, resulting in a half-life of 42 min. The other infusion methods were slower, with half-lives of 153 min for multisidehole urokinase drip infusion, 365 min for endhole urokinase drip infusion, and more than 1,000 min for multisidehole catheter forced injection of saline and multisidehole and endhole saline drip infusion. The differences among these groups were reproducible and statistically significant. CONCLUSION: Results suggest that a simple and inexpensive in vitro model simulating lysis of a vascular occlusion can produce reproducible quantitative data. The data demonstrate that forced injection of lytic agents with a multisidehole catheter enhances the rate of thrombolysis and that the enhancement is not primarily attributable to the mechanical effect of this mode of administration.

Diagnosis of pulmonary embolism at a large teaching hospital.

Pulmonary embolism (PE) is a common clinical entity, although the signs and symptoms that accompany it are nonspecific. This has led to the development of several diagnostic algorithms for diagnosis of PE. These approaches combine noninvasive tests such as ventilation/perfusion (V/Q) lung scanning, impedance plethysmography, and ultrasound, with invasive techniques such as venography and pulmonary angiography. To investigate the manner in which clinicians select and use these various diagnostic strategies, we retrospectively reviewed 316 consecutive cases of suspected PE to determine the sequence and type of diagnostic strategy employed by clinicians. We found that in the majority of cases, physicians chose not to further pursue a diagnosis of PE if the V/Q scan was nondiagnostic. These results suggest that physician behavior is often at variance with published clinical recommendations and that the implementation of clinical practice guidelines needs to be further examined.

Scintigraphic criteria for the diagnosis of renal arteriovenous fistulas.

Visualization of the inferior vena cava (IVC) on renal perfusion imaging occurs in cases of renal arteriovenous (AV) fistulas. A review of consecutive renal scans demonstrated IVC visualization in three of 217 patients without AV fistulas. IVC visualization occurred 3-6 seconds after peak aortic activity in normal patients. With renal AV fistulas, an intrarenal focus of increased activity is seen and IVC visualization occurs coincident with peak aortic activity.

Accurate localization and surgical management of active lower gastrointestinal hemorrhage with technetium-labeled erythrocyte scintigraphy.

OBJECTIVE: There is disagreement over the reliability of technetium Tc 99m (99mTc)-labeled erythrocyte scintigraphy in the localization of active lower gastrointestinal hemorrhage. A previous study at The New York Hospital-Cornell Medical Center that showed a superior sensitivity for localization of scintigraphy versus angiography in surgical patients led the authors to emphasize scintigraphy as the diagnostic test of first choice in the clinical diagnostic algorithm. The authors hypothesized that tagged erythrocyte scintigraphy can be used accurately as the primary diagnostic modality in localizing acute bleeding and guiding surgical intervention. METHODS: The authors conducted a 5-year, retrospective analysis of 224 inpatients who underwent scintigraphic imaging for diagnosis and localization of active lower gastrointestinal bleeding. Using scintigraphy as the primary diagnostic test, with colonoscopy, upper endoscopy, and angiography as adjunctive studies, 99mTc-labeled erythrocyte scans were performed at the clinician's discretion and were reviewed again for study purposes by two nuclear radiologists who were blinded to clinical outcome. Adjunctive diagnostic tests also were ordered for clinical indications. RESULTS: Using delayed periodic scintigraphic imaging, results of 115 scans (51.3%) demonstrated bleeding, with 96 scans (42.9%) localizing to a specific anatomic site. Patients with positive scans were five times more likely to require surgery (p < 0.005) than patients with negative scans, and surgical patients were twice as likely to localize by scintigraphy (p < 0.0001). Fifty patients (22.3%) required surgical intervention to control hemorrhage and had a bleeding site confirmed by both clinical and pathologic examinations. Forty-eight of those patients (96%) had a bleeding site determined preoperatively. For 37 patients with bleeding sites localized preoperatively by scintigraphy, 36 (97.3%) had correct localization based on surgical pathology. Only one patient required a subtotal colectomy solely because of nonlocalized bleeding. No patient bled postoperatively, and there was no mortality in either operated or nonoperated patients. The mean volume of transfused erythrocytes was similar in both scan-localized and nonlocalized surgical patients. CONCLUSION: When performed correctly and interpreted conservatively, scintigraphy is a useful and safe means of guiding segmental resection, and should be the primary tool used in the diagnosis of patients with active lower gastrointestinal bleeding.

Assessment of bone grafts used for acetabular augmentation in total hip arthroplasty. A study using roentgenograms and bone scintigraphy.

Total hip arthroplasty was performed in 13 hips with acetabular bone grafts for secure component fixation. The incorporation and healing of acetabular bone grafts were investigated with the aid of roentgenograms, planar bone scans, and a newer scintigraphic technique, three-dimensional single photon emission computed tomography (SPECT). Conventional roentgenograms proved unreliable in evaluating bone graft reconstitution because of overlapping trabecular bone patterns of the graft and iliac wing. There was no evidence of graft failure or acetabular loosening. Bone grafts in the late follow-up group (four to seven years postoperation) exhibited normal radionuclide activity, whereas grafts less than one year postsurgery demonstrated patterns of increased activity. SPECT was helpful in producing an anatomic reconstruction of the acetabulum. The observation that bone grafts exhibited normal biological viability is crucial for ensuring secure acetabular component fixation on a long-term basis.

In vitro evaluation of the relative thrombolytic efficiency of forced intrathrombic injections: saline versus urokinase.

PURPOSE: To compare the rates of thrombolysis produced by forced intrathrombic injections of saline versus urokinase, as well as automated versus manual injections of urokinase, with use of an in vitro model of a vascular occlusion. MATERIALS AND METHODS: The rates of thrombolysis produced by forced intrathrombic injections of saline and urokinase were compared in an in vitro radiometric model utilizing I-125-labeled thrombus. Similar experiments were performed to compare manual and automated injections of urokinase. The dissolution of the thrombus was quantitatively monitored with use of a scintillation detector. Averaged time activity data for each type of experiment were fit to exponential functions and half times of lysis calculated. The differences in the half times for the experiments being compared were evaluated for significance with use of the Student t test. RESULTS: The half times of lysis produced by forced intrathrombic injections of urokinase were substantially and significantly shorter than those produced by forced saline injections. The half time of lysis produced by automated injections was not significantly different than that produced by manual injections. CONCLUSIONS: Forced intrathrombic injections of urokinase produce faster and substantially more thrombolysis when compared with similarly administered saline. Also, for forced intrathrombic injections of lytic agents, an automated injector is an equivalent alternative to manual injections.