Limitations of indirect methods of estimating small bowel transit in man.

Experiments were carried out in healthy volunteers to explore the utility of a new [14C]lactulose breath test for measuring small intestinal transit time in man and to use this procedure to test whether two antidiarrheal agents, codeine and clonidine, alter small intestinal transit time during digestion of a liquid meal. In an initial validation study performed in 12 subjects (three studies in each subject), a liquid test meal containing 10 g [14C]lactulose was administered and the colonic entry time estimated from the time course of 14CO2 excretion in breath compared with that of H2 excretion. There was a fair correlation (r = 0.77; P less than 0.001) between results obtained by the two methods; both methods gave similar results, but 14CO2 output was delayed when compared to H2 output and was incomplete. The meal also contained xylose and [13C]glycine, permitting the duodenal entry time of the meal to be estimated by the appearance of xylose in blood and 13CO2 in breath, respectively. The same liquid meal was then used to examine the effect on small intestinal transit time (colonic entry time minus duodenal entry time) of codeine or clonidine. 99Tc-sulphur colloid was also added to the meal to permit a comparison of small intestinal transit estimated by imaging with that estimated by the 14CO2-lactulose breath test. 99Tc radioactivity appeared in the cecum (as assessed using gamma scintigraphy) about 2 hr before 14CO2 radioactivity appeared in breath; the correlation between transit time estimated by the two methods was moderate (r = 0.61; P less than 0.05). Based on the [14C]lactulose data, small intestinal transit time ranged from less than 1 to 3 hr for a liquid meal containing 10 g lactulose; within-subject variation (coefficient of variation 17%) was considerably less than between-subject variation (coefficient of variation 56%). Codeine increased the small intestinal transit time significantly (from 2.7 +/- 0.3 hr to 5.0 +/- 0.9 hr; mean +/- SE), whereas clonidine did not alter small intestinal transit time, as estimated by the colonic entry time minus duodenal entry time. Neither drug influenced duodenal entry time. These results suggest that the [14C]lactulose breath test, which has only moderate accuracy, may have occasional utility as a convenient, noninvasive method for estimating small intestinal transit time in man. However, this study also suggests that indirect methods of estimating small bowel transit in man have limitations, variability, and possibly may lack the desired sensitivity.

Visual determination of differential renal function.

Forty patients (43 studies) referred for determination of differential renal function were imaged 24 hours after intravenous administration of Tc-99m-2, 3 DMSA. Visual assessment of relative renal uptake was estimated independently by three observers at three different hospitals from analog images on standard x-ray film. The results were compared with the relative DMSA uptake obtained by summing counts in computer-assisted regions of interest placed over each kidney. There was excellent correlation between the visual estimates of each observer and the computer-generated values (r = 0.98, 0.96, and 0.98, respectively). If a computer is not available, good visual estimates of differential uptake still may be obtained when static imaging agents such as DMSA are administered.

Limitations of indium-111 leukocyte scanning in febrile renal transplant patients.

Indium-111-labeled leukocyte scanning was evaluated as a technique for investigating possible abscess as the cause of fever in 10 renal allograft recipients under therapy for rejection, acute tubular necrosis, or urinary infection. The usefulness of the method in this setting was found to be limited by marked nonspecificity of renal, pulmonary, and other focal leukocyte accumulation. Although wound infections were correctly identified, false-positive scans resulted in multiple nonproductive consultations and radiologic procedures (some invasive) and contributed to the decision to perform one negative exploratory laparotomy. Such generalized nonspecificity in this patient population is in distinct contrast to the experience with this diagnostic test in nontransplant patients, and has not previously been reported. Possible explanations and implications of these findings are discussed. Consequently, great caution is recommended in the use of indium-111 leukocyte scans to diagnose infection in febrile renal transplant patients who present in a similar clinical setting.

Radioimmunodetection of melanoma utilizing In-111 96.5 monoclonal antibody: a preliminary report.

The murine 96.5 monoclonal antimelanoma antibody (MoAb) was labeled with In-111, and 1-20 mg were administered to 21 patients who had proved or suspected melanoma metastases. One patient was studied twice. In four patients, unlabeled 96.5 MoAb was administered prior to the radiopharmaceutical. All of the patients tolerated the procedure without toxicity regardless of the mass of MoAb administered. The scans were interpreted by two observers, one with full knowledge, the other with no knowledge of the cases. Increasing the MoAb mass or preinfusing unlabeled MoAb prior to the administration of In-111 MoAb resulted in a prolongation of the serum half time, and appeared to improve tumor detection. Lesions were best seen at 72 hours after infusion or later. In all patients who had metastatic disease, at least one tumor site was apparent. Fifty-six per cent of known lesions 1.5 cm or greater in size were detected by the physician who had knowledge of the cases when data from all doses were considered. There were eight lesions detected that were not suspected in the workup of the patient. When these are included, the detection rate rises to 61%. Forty-nine per cent were detected by the other physician. Subtraction techniques were not employed. Lesions were often better seen with single photon emission computed tomography than with planar imaging techniques. The 96.5 In-111 MoAb appears to have utility for the detection of metastatic melanoma. Further clinical evaluation of 96.5 In-111 MoAb is warranted.

In-111-leukocyte scintigraphy for detection of infection associated with peritoneal dialysis catheters.

In-111-labeled leukocytes were administered to 13 patients on continuous ambulatory peritoneal dialysis in order to locate catheter-associated infections. Using a marker to indicate the catheter exit site, infections of the catheter tunnel were correctly identified prior to surgery in 4 patients with relapsing peritonitis and infections of the exit site were diagnosed in 5 out of 7 patients. There were no false positives or negatives as documented by surgery or follow-up. The authors conclude that In-111-leukocyte scintigraphy appears to be accurate in diagnosing peritoneal infections of the dialysis catheter tunnel.

The flare phenomenon on radionuclide bone scan in metastatic prostate cancer.

The radionuclide bone scan 3 months after the initiation of treatment for advanced cancer of the prostate occasionally shows apparent progression of individual lesions despite clinical improvement. To determine the incidence and clinical significance of this so-called flare phenomenon, serial bone scans were reviewed in 33 patients with carcinoma of the prostate and bony metastases, who were receiving endocrine treatment for the first time. A flare reaction was seen in two (6%) of 33 bone scans obtained 3 months after initiation of treatment. A flare reaction on bone scan is an unusual phenomenon in prostatic cancer; in general, serial scans accurately depict the activity of bony metastases in these patients.

Single photon emission computed tomograms of the liver: normal vascular intrahepatic structures.

Because of the high target-to-background contrast obtained with single photon emission computed tomography (SPECT), normal intrahepatic vessels approximately 2 cm in diameter may appear as distinct focal defects in tomographic sections throughout the liver even though normal vessels rarely cause such defects on planar images. To assess this problem, five subjects without evidence of liver disease underwent tomography of the liver with Tc-99m sulfur colloid (TSC) and on a separate occasion tomography of the intrahepatic blood pool with Tc-99m autologous red blood cells (RBC). In each case, well demarcated defects were obvious in contiguous TSC liver tomograms in various planes. Direct comparison with RBC tomograms showed that all of these defects corresponded to intrahepatic veins, typically the right portal vein, its posterior branch, and the left portal vein. Knowledge of the intrahepatic vascular anatomy in a variety of tomographic planes, with examination of each defect in multiple orthogonal planes is necessary to avoid false positive interpretations. In some instances a study with RBC may also be required for more conclusive evaluation of defects seen on TSC liver tomograms.

Computer-assisted versus visual lung gallium-67 index in normal subjects and in patients with interstitial lung disorders.

The pulmonary uptake of 87Ga citrate has been proposed as an index that assists clinical decision-making in patients with certain interstitial lung diseases. Such use, however, requires definition of the range of normal values, the range of values in patients with various interstitial diseases, and interobserver and intraobserver variability. We studied 9 normal subjects and 15 patients with interstitial lung diseases. The 87Ga indexes were determined by visual analysis and by a computer-assisted method. We found that the variation among experienced observers in visual index values was substantial in both normal subjects and patients, and that the computer-assisted indexes were less variable. These data suggest that if this approach is to be used in clinical decision-making: (1) the variability of visual indexes, and of normal values, should be recognized; (2) consideration should be given to a less subjective, computer-assisted method of index calculation; (3) each institution should establish standardized methodology and consider determination of its range of variability and normal index values.

Cholecystokinin cholecystography, sonography, and scintigraphy: detection of chronic acalculous cholecystitis.

Because the efficacy of cholecystokinin cholecystography in the detection of chronic acalculous cholecystitis remains in doubt, the procedure is rarely used in clinical practice. However, the ability to observe gallbladder contraction with sonography and 99mTc-para-isopropylacetanilido-iminodiacetic acid cholescintigraphy (PIPIDA) offers a possibility to improve the sensitivity of the test. To determine if the degree of gallbladder contraction after cholecystokinin is the same as measured by the three techniques and if it differs in symptomatic patients compared to the normal population, cholecystokinin cholecystography, cholecystokinin sonography, and cholecystokinin PIPIDA were performed in 10 symptomatic patients and 10 normal volunteers. The mean maximum contraction of the gallbladder during the three studies was 63%, 61%, and 68%, respectively, for the volunteers, and 72%, 63%, and 73%, respectively, for the patients. The mean maximum gallbladder contraction during all three procedures was 64% +/- 26% SD in the volunteers and 74% +/- 17% SD in the patients. The differences were not statistically significant. Although there was good correlation in the degree of maximum gallbladder contraction among cholecystokinin cholecystography, cholecystokinin sonography, and cholecystokinin PIPIDA, marked variation in both the volunteers and the patients makes it unlikely that the degree of contraction as observed by any of these techniques can be used to indicate the presence of chronic acalculous cholecystitis.

Right and left ventricular response to subcutaneous terbutaline in patients with chronic obstructive pulmonary disease: radionuclide angiographic assessment of cardiac size and function.

To assess the response of the right and left ventricles to the subcutaneous administration of terbutaline sulfate, a beta-2 selective agonist, we evaluated 14 patients with chronic obstructive pulmonary disease (COPD) with equilibrium radionuclide angiography (RNA). Prior to injection, eight patients (57%) had an abnormal right ventricular ejection fraction (RVEF), four (29%) had a low left ventricular ejection fraction (LVEF), and three (21%) had low ejection fractions of both ventricles. After terbutaline injection, RVEF increased in 13 of 14 patients (93%) by 17 +/- 8% (p less than 0.001) while LVEF increased in all patients by 15 +/- 7% (p less than 0.001). Both left and right ventricular end-diastolic volumes decreased (p less than 0.01), while stroke volume was unchanged. Cardiac output rose by 0.8 +/- 1.3 L/min (p less than 0.05), primarily due to the increase in heart rate (10 bpm, p less than 0.001), since stroke volume did not significantly change. We conclude that in patients with COPD subcutaneous terbutaline has significant beta-1 cardiac effects; it increases the heart rate and decreases cardiac size.

A noncomputerized count-based technique for the determination of resting left ventricular ejection fraction.

A noncomputerized, count-based technique for the determination of left ventricular ejection fraction (LVEF), which does not use geometric assumptions of left ventricular shape, was developed. The noncomputerized technique and computerized multigated ventriculography using both fixed and variable region-of-interest (ROI) methods were performed on 16 patients. The LVEFs obtained with the noncomputerized technique correlated well with both the fixed ROI computerized technique (r = .87) and the variable ROI computerized technique (r = .86). It is concluded that when a computer is not available, the noncomputerized technique is a valid alternative for the determination of LVEF in resting patients in stable sinus rhythm.

Clinical estimation of infarct size by 201thallium perfusion scintigraphy and by creatine kinase-MB in early myocardial infarction.

201Thallium (201Tl) perfusion scintigraphy was performed in 22 patients with first acute transmural myocardial infarction within the initial 12 h after onset of symptoms. The size of the abnormally perfused area on 201Tl images was estimated by visual analysis and by a computer-assisted technique. 201Tl values for infarct size were compared to a biochemical estimate of infarct size using the cardiac specific esoenzyme creatine kinase-MB (CK-MB) and total creatine kinase (CK). Estimates of myocardial damage obtained from the visual and computer-assisted analysis of the 201Tl images showed a statistically significant correlation with the enzymatic estimates of infarct size. These results suggest that quantitative evaluation of 201Tl image defects may provide useful information regarding the degree of myocardial damage in the very early stages of acute infarction before biochemical estimates of infarct size are available, and that sequential imaging with 201Tl might provide an independent method of monitoring evolutionary changes in myocardial damage.

Diagnosis of coronary artery disease with 201Tl. Computer analysis of myocardial perfusion images.

The diagnostic sensitivity of visually interpreted and computer-analyzed 201Tl myocardial perfusion images was compared to that of exercise electrocardiograms in 8 angiographically normal subjects and 24 patients with significant coronary artery disease. Visual interpretation was not significantly better than exercise ECGs. An index of perfusion homogeneity, derived from computer analysis of the 201Tl images, was more sensitive than visual interpretation (79% vs. 58%) and much more sensitive (p less than 0.05) than the exercise ECG (79% VS. 46%). The best overall sensitivity (88%) and specificity (75%) were achieved by combining computer analysis with exercise electrocardiography. The computer also permits enhanced detection of subtle perfusion changes which may not seem significant to the eye.