Use of a decision-analytic model to support the use of a new oral US contrast agent in patients with abdominal pain.

RATIONALE AND OBJECTIVES: The authors performed this study to compare the cost and diagnostic abilities of ultrasound (US) performed with and without the use of an oral contrast material recently approved by the U.S. Food and Drug Administration. MATERIALS AND METHODS: An interactive decision-analytic model was constructed to compare US performed with and without contrast material (SonoRx; Bracco Diagnostics) for the evaluation of patients with abdominal pain who were suspected of having pancreatic disease. The model considered all resources that might be used to evaluate a patient suspected of having pancreatic disease (eg, US, computed tomography [CT], endoscopic retrograde cholangiopancreatography, fine-needle aspiration biopsy, and open biopsy). The literature and an expert panel were the clinical data sources. Cost estimates were based on Medicare and non-Medicare reimbursements. The primary cost-effectiveness measure was the cost to achieve a diagnosis. RESULTS: SonoRx-enhanced US was less expensive than unenhanced US ($714 vs $808, respectively, with Medicare costs; $1,612 vs $1,878, respectively, with non-Medicare costs) and as effective (0.785 vs 0.782, respectively). SonoRx-enhanced US was more cost-effective than unenhanced US ($909 vs $1,034, respectively, with Medicare costs; $2,052 vs $2,401, respectively, with non-Medicare costs). This relationship was maintained throughout extensive sensitivity analyses. CONCLUSION: SonoRx-enhanced US is more cost-effective than unenhanced US, primarily because it avoids the need for CT. CT may be avoided owing to the higher probability of obtaining optimal US scans with oral contrast material.

Safety and pharmacokinetic profile of gadobenate dimeglumine in subjects with renal impairment.

RATIONALE AND OBJECTIVES: To determine the safety and pharmacokinetics of gadobenate dimeglumine in a group of subjects with moderate or severe renal impairment. METHODS: The safety and pharmacokinetic profile of gadobenate dimeglumine, a gadolinium (Gd3+) chelate complex in development as a contrast agent for MRI, were evaluated in a placebo-controlled, double-blind, multicenter trial. Subjects with moderate or severe renal impairment (creatinine clearances of 31 to 60 or 10 to 30 mL/min, respectively) received a 0.2-mmol/kg intravenous bolus of Gd3+ or saline placebo. Blood samples (up to 72 hours) and urine and fecal samples (up to 216 hours) were assayed for total Gd3+ content by inductively coupled plasma atomic emission spectroscopy. Gd3+ blood concentration/time data were analyzed nonparametrically and parametrically using the software program WinNonlin VI.1. RESULTS: Mean (SD) values for Gd3+ area under the curve, blood clearance, steady-state volume of distribution, renal clearance, and creatinine clearance for the moderate group were 862 (392) micrograms.h/mL, 56 (25) mL/min, 21 (5) L, 47 (23) mL/min, and 46 (16) mL/min. Values for the severe group were 1347 (366) micrograms.h/mL, 31 (7) mL/min, 19 (6) L, 22 (7) mL/min, and 21 (8) mL/min. No Gd(3+)-related adverse events occurred. Mean values for Gd3+ recovery in urine and feces for moderate and severe groups were 74% and 6%, and 69% and 8% of the dose, respectively. Linear regression analysis demonstrated a significant relation between the level of renal function and blood clearance of Gd3+. CONCLUSIONS: Although mean blood clearance and renal clearance values progressively declined with increasing degree of renal impairment, based on the safety profile and the fact that the administered dose was double the standard dose used for MRI purposes, there appears to be no need for dose reduction in this population.

Bone mineral density of eating disorder subgroups.

OBJECTIVE: We tested nine hypotheses among eating disorder subgroups and a control group on spinal bone density and investigated the relationship of their spinal bone density with a critical fracture threshold and five clinical variables--age of onset, years ill, percentage of ideal body weight (IBW), months of amenorrhea, and hours per week of exercise. METHOD: Dual photon absorptiometry measured spinal bone density. RESULTS: Anorectic patients had significantly less spinal bone mass than bulimic patients with no history of anorexia nervosa or control patients. Eating disordered patients with past or present anorexia nervosa had significantly more spinal bone density values below a critical fracture threshold. Duration of amenorrhea and exercise significantly predicted spinal bone density. DISCUSSION: Anorectic women were unlikely to reach their peak bone density, thus possibly developing osteoporosis later in life, and were likely to be at risk for nontraumatic spinal fractures. Predicting spinal bone density of anorectic women could be done by knowing their duration of amenorrhea and exercise.

Altered cortical blood flow in HIV-seropositive individuals with and without dementia: a single photon emission computed tomography study.

OBJECTIVE: To quantitatively demonstrate the pattern of cerebral perfusion abnormalities in HIV-1-infected individuals described as 'patchiness' or inhomogeneity in previous qualitative emission tomographic imaging studies. DESIGN: We aimed to create a quantitative measure of inhomogeneity in HIV-infected individuals. High-frequency variance in cortical profiles is an indication of inhomogeneity in the distribution of radiotracer in the cerebral cortex. Therefore, the study analysis was designed to enable the estimation of variance frequencies in cortical profiles. METHODS: Regional cerebral blood flow was examined in nine mildly demented and 10 cognitively normal HIV-1-seropositive individuals and eight seronegative normal controls using single photon emission computed tomography with the radiotracer [I-123]-N-isopropyl-p-iodoamphetamine. Quantitative analysis was performed using circumferential profiles of cerebral cortical perfusion. Fourier transform power spectra of the profiles were examined as an index of patchiness in tracer distribution. RESULTS: Normal controls were characterized by strong middle frequency and weak high-frequency power. Both HIV-1-infected groups showed a significant power shift from middle to high frequencies. CONCLUSIONS: Increased high-frequency variations in both HIV-1-infected groups indicates diffuse cortical perfusion changes compared with normal controls. This study suggests that there are cerebral bloodflow abnormalities in HIV-1-infected individuals both with and without clinically severe dementia.

Effect of magnetic susceptibility contrast medium on myocardial signal intensity with fast gradient-recalled echo and spin-echo MR imaging: initial experience in humans.

PURPOSE: To show the effect of dysprosium diethylenetriaminepentaacetic acid bis-methylamine injection on the images of normal human myocardium. MATERIALS AND METHODS: T2-sensitive fast gradient-recalled echo (GRE) (repetition time [TR], 10.8 msec; echo time [TE], 4.2 msec) and spin-echo (SE) (TR, three RR intervals; TE, 60 msec) magnetic resonance (MR) imaging with driven equilibrium-preparation pulse was used to produce T2 contrast material enhancement. The contrast agent was injected into 12 healthy subjects at doses of 0.05, 0.1, 0.2, 0.4, and 0.6 mmol/kg. RESULTS: Driven equilibrium-prepared GRE images showed a transient decrease of myocardial signal intensity at doses of 0.2-0.6 mmol/kg. Postcontrast T2-weighted SE images showed a myocardial signal attenuation (30%-45% decrease) at a dose of 0.4 mmol/kg or higher. CONCLUSION: Dynamic MR imaging with a magnetic susceptibility contrast medium can be used to monitor the first pass of contrast media through human myocardium with a conventional MR imager and a fast GRE sequence.

Comparison of indium-111 antimyosin antibody and technetium-99m pyrophosphate localization in reperfused and nonreperfused myocardial infarction.

Recent imaging studies suggest that technetium-99m (Tc-99m) pyrophosphate yields a considerably larger estimate of myocardial infarct size than does indium-111 (In-111) monoclonal antimyosin antibody. To determine whether Tc-99m pyrophosphate may be taken up by reversibly injured myocytes, particularly in the setting of coronary reperfusion, the tissue localization of Tc-99m pyrophosphate and antimyosin antibody was compared in 11 dogs 24 to 68 h after anterior descending coronary artery occlusion (4 dogs with permanent occlusion, 7 with reperfusion). Technetium-99m pyrophosphate and In-111 antimyosin antibody content was determined in serial 2 to 3 mm wide endocardial and epicardial samples taken through the infarct zone in multiple short-axis left ventricular slices. The number of samples with increased In-111 antimyosin antibody (defined as greater than or equal to mean + 2 SD of normal) was not significantly different from that with increased Tc-99m pyrophosphate. This was true in both reperfused and nonreperfused infarcts. However, the intensity of uptake of Tc-99m pyrophosphate exceeded that of In-111 antimyosin antibody, particularly in the border zones of reperfused infarcts, and the area with moderate to marked increase in tracer uptake (greater than or equal to 2 times normal) was significantly larger with Tc-99m pyrophosphate than In-111 antimyosin antibody (p less than 0.001). A specific zone of abnormal Tc-99m pyrophosphate with normal In-111 antimyosin antibody content could not be identified. Histologic evidence of myocardial necrosis was found in virtually every sample with increased In-111 antimyosin antibody, Tc-99m pyrophosphate, or both.(ABSTRACT TRUNCATED AT 250 WORDS)

Indium-111 myosin-specific antibodies and technetium-99m pyrophosphate in the detection of acute cardiac rejection of transplanted hearts: studies in a heterotopic rat heart model.

111In-labelled myosin-specific antibodies were evaluated as an indicator of early changes in acute rejection in a rat heart heterotopic transplant model. Uptake of antibodies was measured in allograft and isograft hearts of animals undergoing different regimens of cyclosporine treatment and compared with the uptake of technetium-99m pyrophosphate. The data were correlated with histological estimation of the severity of myocyte necrosis and signs of early rejection (venous cuffing and endocardial inflammation, indicators of perivascular infiltrate and intermyocyte extension, respectively). Myocyte necrosis in transplanted hearts was reflected by increases in technetium-99m pyrophosphate accumulation (r = 0.88) but was poorly correlated with labelled antibody uptake (r = 0.58). There was no positive correlation between the degree of early cardiac rejection and uptake of either of the radiopharmaceuticals: accumulation of the labelled antibodies paradoxically declined with increased histological severity scores, whereas that of technetium-99m pyrophosphate remained unchanged. Cyclosporine treatment augmented the uptake of labelled antibodies in transplanted hearts. This may be due to alterations in plasma membrane permeability brought about by the drug, resulting in a rise in antibody binding to intracellular myosin.

Diagnosis of Campylobacter pylori gastritis.

Campylobacter pylori is a bacterium that inhabits gastric mucosa. It causes chronic active gastritis and is highly associated with duodenal ulcer. Campylobacter pylori has a urease enzyme (not present in man), which allows diagnosis by a [14C]urea breath test. We compared two noninvasive tests, the breath test and serum ELISA, to biopsy and histologic diagnosis. Twenty-two patients who underwent gastroduodenoscopy for evaluation of possible peptic ulcer disease entered the study. The breath test detected the organism in eight of eight patients biopsy-positive for the organism (sensitivity 100%). The breath test was negative in 12 of the 14 patients who were biopsy-negative (specificity 86%). The ELISA was performed in 14 patients. It was positive in 5 of 5 patients biopsy-positive for the organism (sensitivity 100%) and negative in 7 of 9 patients who were biopsy-negative (specificity 78%). We conclude that both the ELISA and the [14C]urea breath test are excellent noninvasive methods to detect Campylobacter pylori. However, only the breath test is suitable for following the response to treatment, as it detects the presence of the organism rather than an immune response to it.

Prevention of hypothyroidism related to mantle irradiation for Hodgkin's disease: preparative phantom study.

To decrease the incidence of hypothyroidism related to mantle irradiation for Hodgkin's disease, we initiated a study designed to protect the thyroid gland using a phantom. A thyroid phantom was filled with technetium-99m. The thyroid phantom was placed inside of its corresponding anterior neck position in a whole body phantom. An anterior scintiscan of the head and neck region demonstrated the radioactivity in the simulated thyroid. A mantle port included a focused block that would shield the thyroid from the anterior port. The phantom was exposed (4 MeV) to 180 cGy (AP-PA) at midplane with lithium fluoride dosimeters in the position of the thyroid. The thyroid received an average of 12 cGy from the anterior field and 48 cGy from the posterior field for a total of 60 cGy per treatment or 30% of the prescribed dose. A complete mantle field course of radiation of 4000 cGy would lead to a thyroid dose of 1200 cGy at a daily fractional dose of 60 cGy. We elected not to block the thyroid from the posterior field to prevent shielding and potential underdosage of involved nodal sites. The present study suggests a method of safe and effective thyroid shielding which needs to be tested clinically to determine whether it would reduce the incidence of chemical and clinical hypothyroidism or simply extend the period until occurrence.

Reciprocal creatinine slopes often give erroneous estimates of progression of chronic renal failure.

In 10 of 22 observation periods (lasting an average of 15 months) in 17 patients with moderate to severe chronic renal failure (GFR 4 to 23 ml/min), rates of progression as estimated from the linear regression on time of reciprocal plasma creatinine concentration (multiplied by average 24 hr creatinine excretion) (b2) differed significantly from rates of progression as estimated from the regression on time of urinary clearance of 99mTc-DTPA (b1), during all or part of the period of observation, b2 exceeded b1 in six cases and was less than b1 in the other four. Owing to these changes, measurements of reciprocal creatinine concentration gave erroneous impressions of the rate or existence of progression, during all or a portion of the period of observation, in nearly half of these patients. However, in the 22 studies as a group, using the entire periods of observation, b2 indicated nearly the same mean rate of progression as b1, and had the same variance. We conclude that sequential plasma or serum creatinine measurements in individual patients are often misleading as measures of progression and should, when feasible, be replaced by urinary clearances of isotopes in following patients with chronic renal failure.

Local cerebral glucose abnormalities in mild closed head injured patients with cognitive impairments.

Mild-moderate closed head injury (CHI) can be followed by neuropsychological impairments in recent memory and attention, despite the absence of discernible structural abnormalities in a significant number of patients. To determine whether CHI may result in cerebral glucose metabolic abnormalities, we used fluorodeoxyglucose (FDG) technique with PET imaging to measure local cerebral metabolic rates for glucose (LCMRGlu) in three CHI patients and three matched normal controls. The CHI patients were between 3-12 months post-injury. All had deficits in attention and recent memory shown by neuropsychological testing. CT, MRI, EEG and drug screens were negative at the time of PET scanning. Subjects were engaged in a vigilance task throughout the initial 30 min following FDG administration. Group comparisons were made using t tests. There were no significant group differences found in global glucose metabolic rate. Nevertheless, the CHI group exhibited significantly decreased LCMRGLu in medial temporal, posterior temporal, and posterior frontal cortices, as well as in the left caudate nucleus. LCMRGlu was significantly increased, relative to controls, in anterior temporal and anterior frontal cortices. These results suggest that CHI patients can have regional glucose metabolic abnormalities, indicative of altered neuronal function, despite the absence of discernible anatomic abnormalities.

Homogeneity of bronchopulmonary distribution of 99mTc aerosol in normal subjects and in cystic fibrosis patients.

We characterized the bronchopulmonary distribution of a 0.9 percent saline aerosol (1.12 microM) labelled with 99mTc sulfur colloid in nine normal subjects and five patients with CF. Homogeneity of distribution was quantified using indices derived from computerized analysis of Anger camera pulmonary images including skew (a measure of distribution asymmetry) and kurtosis (a measure of distribution range). Aerosol clearance in 97 minutes (a measure of large, central airway deposition) was also assessed. Values of skew and kurtosis were reproducible for the patients with CF and were significantly elevated compared to the normal subjects. Reproducibility of skew and kurtosis were not studied in the normal subjects. Clearance was not significantly different in the two groups. We conclude that the bronchopulmonary distribution of this radioaerosol is nonuniform in patients with CF, compared to normal subjects, and clearance may be impaired in patients with CF who are severely ill.

Antimyosin imaging in acute transmural myocardial infarctions: results of a multicenter clinical trial.

Murine monoclonal antimyosin antibody has been shown experimentally to bind selectively to irreversibly damaged myocytes. To evaluate the safety and efficacy of monoclonal antimyosin for identifying acute transmural infarction, 50 patients with acute Q wave myocardial infarction were entered into a phase I/II multicenter trial involving three clinical sites. Indium-111 antimyosin was prepared from an instant kit formulation containing 0.5 mg of diethylene triamine pentaacetic acid (DTPA)-coupled Fab fragment (R11D10) and 1.2 to 2.4 mCi of indium-111. Average labeling efficiency was 92%. Antimyosin was injected 27 +/- 16 h after the onset of chest pain. Planar or tomographic imaging was performed 27 +/- 9 h after injection in all patients, and repeat imaging was done 24 h later in 39 patients. Of the 50 patients entered, 46 showed myocardial uptake of antimyosin (sensitivity 92%). Thirty-one of 39 planar scans performed at 24 h were diagnostic; 8 showed persistent blood pool activity that cleared by 48 h. Focal myocardial uptake of antimyosin corresponded to electrocardiographic infarct localization. No patient had an adverse reaction to antimyosin. In addition, 125 serum samples, including 21 collected greater than 42 days after injection, were tested for human antimouse antibodies, and all samples were assessed as having undetectable titers. Intensity of antimyosin uptake was correlated with infarct location and the presence or absence of collateral vessels. There was a significant correlation between faint uptake and inferoposterior infarct location. In 21 patients who had coronary angiography close to the time of antimyosin injection, there was a significant correlation between faint tracer uptake and closed infarct-related vessel with absent collateral flow.(ABSTRACT TRUNCATED AT 250 WORDS)

Radioisotopic measurement of glomerular filtration rate in severe chronic renal failure.

In order to determine the best method for routine measurement of glomerular filtration rate (GFR) in severe renal failure, we compared simultaneously the urinary clearances of [99mTc] diethylenetriaminepentaacetic acid (DTPA) (UD), [125I]iothalamate (UI), 24-hr creatinine clearance (UC) and plasma clearance of [99mTc]DTPA (PD), based on three plasma samples. In 60 studies in 22 patients with serum creatinine values of 2 to 8 mg/dl, UD and UI were almost identical: UD = 0.358 +/- 0.976 UI +/- 0.87 ml/min, r = 0.990. However, PD overestimated UD by a large and variable extent: PD = 11.3 +/- 0.843 UD +/- 5.5 ml/min, r = 0.694, and was inconsistent in sequential measurements in individual patients. UC also overestimated urinary isotope clearance: UC = 4.2 + 0.95 UI +/- 3.9 ml/min, r = 0.865. Sequential measurements of GFR in five patients with severe but stable renal failure (mean GFR 5.9 ml/min) showed an average standard deviation of only 0.83 ml/min. Thus both UD and UI appear to be reliable and precise measures of GFR in severe renal failure.

Creatinine measurements often yielded false estimates of progression in chronic renal failure.

In 9 of 22 observation periods (lasting an average of 15 months) in 17 patients with moderate to severe chronic renal failure (GFR 4 to 23 ml/min), rates of progression as estimated from the linear regression on time of 24-hour creatinine clearance (b1) differed significantly from rates of progression as estimated from the regression on time of urinary clearance of 99mTc-DTPA (b2), during all or part of the period of observation. b1 exceeded b2 in four cases and was less than b2 in the other five. Thus there were gradual changes in the fractional tubular secretion of creatinine in individual patients, in both directions. Owing to these changes, measurements of creatinine clearance gave erroneous impressions of the rate or existence of progression during all or a portion of the period of observation in nearly half of these patients. In the 22 studies as a group, using the entire periods of observation, b1 indicated significantly more rapid progression (by 0.18 +/- 0.06 ml/min/month, P less than 0.01) than did b2, and had a significantly greater variance. Measurements of progression based on the rate of change of reciprocal plasma creatinine (multiplied by an average rate of urinary creatinine excretion in each study) were equally misleading, even though less variable. We conclude that sequential creatinine measurements are often misleading as measures of progression and should, when feasible, be replaced by urinary clearance of isotopes in following patients with chronic renal failure.