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.

Calculation of relative glomerular filtration rate and correlation with delayed technetium-99m DMSA imaging.

The relative renal uptake of Tc-99m DMSA was compared with the relative glomerular filtration rate (GFR) in ten patients with serum creatinines ranging from 0.3 to 2.5 mg/dl. Relative GFR was based on the renal uptake of Tc-99m DTPA determined by two methods: 1) integrating the counts from 1 to 3 minutes postinjection and correcting for background. 2) Totalizing the individual renal counts in a single 15-second frame from 2:45 minutes to 3:00 minutes postinjection and correcting for background. The two methods of determining relative DTPA uptake showed excellent correlation, r = 0.98. Relative DMSA uptake determined at 24 hours post-injection using computer-assisted regions of interest showed excellent correlation with the relative GFR determined by either the integral or single-frame method, r = 0.98. The addition of background subtraction for the DMSA images at 24 hours did not improve the correlation.

Plantar compartmental infection in the diabetic foot. The role of computed tomography.

This review discusses the role of computed tomography (CT) in the evaluation of extent of plantar soft tissue infection in the diabetic foot. CT abnormalities are correlated with conventional radiography, results of preoperative aspiration cultures, intraoperative assessment, and bone, gallium, and 111In-leukocyte scan findings. Plantar soft tissue disease respects compartmental boundaries in general, with transcompartmental spread possible along musculotendinous units that normally transgress the intervening fascial septae. CT correlates well with the extent of infection as determined by other modalities, but cannot precisely predict its proximal boundary due to gradual transition between unequivocally abnormal and normal tissue. CT may be useful in establishing an appropriate level for contemplated amputation and can detect extension of superficial diabetic foot infections at an earlier stage than existing clinical methods, potentially resulting in less extensive surgical procedures.

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.

Function of the pericardium and pericardioperitoneal canal in elasmobranch fishes.

Previous studies of cardiac function in elasmobranch fishes have not included the influence of the pericardioperitoneal canal on pericardial pressure and volume and thus on cardiac function. Accordingly, we studied the function of the pericardium and pericardioperitoneal canal in sharks and rays. We found negative pericardial pressure that rose to a plateau of approximately 0 mmHg when fluid was infused into the pericardium with the canal undisturbed. However, this pericardial pressure elevation caused severe cardiac tamponade. After the canal was occluded, the pressure plateau was substituted with an exponential rise. We injected radioisotopes into the pericardial cavity and obtained scintigrams several hours later. The scans and counts of body fluids and tissues indicated absorption, disputing the suggestion that the primary function of the canal may be inadequate absorption of pericardial fluid. We conclude that the pericardioperitoneal canal maintains negative pericardial pressure, which is a prerequisite in elasmobranch fishes and may serve to regulate pericardial pressure level to optimize cardiac function in relation to changes in cardiac size.

Positive In-111 white cell scan in a patient with multiple metastases.

A case of increased uptake of In-111-labeled leukocytes in bony metastases from adenocarcinoma of the prostate is presented. Bone scintigraphy, subsequent to the white cell study, showed virtually identical abnormalities as the indium scan. Clinical course and laboratory data supported the diagnosis of widespread metastatic carcinoma. Although the exact cause(s) is unclear, possible mechanisms are discussed.

Krypton-81m imaging of the right ventricle.

We report the development of a method for obtaining right-ventricular radionuclide angiograms using continuous peripheral intravenous infusion of the ultra-short-lived nuclide krypton-81m. This tracer has a half-life of 13 sec, emits a single 190-keV photon, and is extremely insoluble. During infusion into a peripheral vein, Kr-81m achieves stable count rates over the right heart, and it is essentially completely cleared by the lungs during its initial pulmonary transit. Thus no interfering activity is present in the systemic circulation. Initial studies provide excellent data on right-heart anatomy and function.

Expanded 99mTc-methylene diphosphonate (MDP) bone scan.

Patients with prostatic cancer frequently require evaluation of bony metastases as well as renal function. 99mTc-methylene diphosphonate, a commonly used bone-imaging agent, is about 60 per cent localized in the bony skeleton and about 40 per cent excreted by the kidneys. Immediate imaging after intravenous injection of the isotope may yield high-quality radionuclide nephrourograms, which provide excellent visual and graphic displays of renal anatomy and excretory function. Our preliminary studies suggest that the immediate 99mTc-methylene diphosphonate scan may usefully expand the value of a routine bone scan to screen for ureteral obstruction. Patients with underlying malignancy who require simultaneous evaluation and follow-up of bony metastases and renal function might be conveniently served by the dual functions of the expanded bone scan to include immediate imaging of the kidneys.

Can areas of myocardial ischemia be localized by the exercise electrocardiogram? A correlative study with thallium-201 scintigraphy.

In order to determine whether areas of ischemia identified by thallium-201 scintigraphy could be localized by exercise ECG, we studied 54 patients with stable coronary heart disease. All 54 patients had exercise-induced thallium-201 scintigraphic defects. Their exercise ECG test results were compared to their thallium-201 images and also to 14 low-risk normal subjects. Exercise data were analyzed for spatial ST vector shifts, using a computer program in order to most accurately classify ST segment depression and elevation. Thallium-201 ischemic defects detected in our patients included areas in the septum and the inferior, lateral, and anterior walls. Twenty-six of these 54 patients also had coronary angiography for classification and comparison as having either localized or generalized disease. None of the scintigraphic ischemic sites or angiographic diseased areas could be specifically identified by exercise-induced ST vector shifts. Therefore, the surface exercise ECG has limitations in localizing ischemia to specific areas of the myocardium.

A randomized trial of exercise training in patients with coronary heart disease.

In order to determine whether or not regular exercise could alter myocardial perfusion or function, we randomized 146 male volunteers with stable coronary heart disease to either a supervised exercise program (n = 72) or to a usual care program (n = 74). Subjects underwent exercise tests initially and one year later. Significant differences between the two groups included improved aerobic capacity, thallium ischemia scores, and ventricular function in the exercise intervention group. It was not possible to classify the conditions of patients as to the likelihood of improvement or deterioration. This study demonstrated changes in myocardial perfusion and function in a select group of middle-aged men with coronary heart disease who underwent a medically appropriate exercise program lasting one year, but these changes were relatively modest.

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.