Dynamic antral scintigraphy to characterize gastric antral motility in functional dyspepsia.

UNLABELLED: We evaluated intragastric food distribution and antral motor activity in patients with functional dyspepsia. METHODS: A standard gastric emptying test and dynamic imaging of the antrum were used to characterize gastric antral motility disturbances and to correlate them with total and compartmental gastric emptying in 25 dyspeptic patients. RESULTS: We found a 40% prevalence of gastroparesis in functional dyspepsia. Solid gastric emptying delay is indicated by a prolonged lag phase and an increase in frequency and amplitude of gastric contractions, resulting in nonexpulsive antral contractions and/or antropyloric dyscoordination. Food retention in the distal stomach and antral distention appears to account for patients' dyspeptic symptoms. CONCLUSION: This study demonstrates that scintigraphy not only detects abnormalities of food distribution in the stomach but also provides information on antral motor activity noninvasively. Dynamic antral scintigraphy and compartmental gastric emptying are useful tools to define the pathophysiology of dyspeptic patients with or without gastroparesis.

Scintigraphic imaging of oncogenes with antisense probes: does it make sense?

Based on the specificity of the Watson-Crick base pairing formation, antisense deoxyoligonucleotides have been used to inhibit the expression of oncogenes in various cancer cells. Activation of an oncogene by means of amplification leads to an increased, detectable amount of the mRNA transcript in the cytoplasm. The aim of this study was to demonstrate that cells which are expressing a particular mRNA transcript do preferentially and specifically retain the antisense probe targeting that mRNA. Using a mouse plasmacytoma cell line (MOPC315) which produces high levels of IgA heavy chain mRNA, a control mouse pre B cell line (7OZ/3B), a human mammary cell line (MCF7) which expresses the erbB2 or neu oncogene, MOPC315 cells as neu-negative controls, and antisense DNA oligonucleotides complementary to the 5' region of the mRNAs and the sense sequence, we have shown that there is a preferential, specific retention of the IgA and neu antisense sequence in MOPC315 and MCF7 cells, respectively. We have further demonstrated that this retention is time and concentration dependent with a maximum at 24 h. We conclude that cancer cells which express a particular oncogene are suitable targets for radiolabeled antisense deoxyoligonucleotides directed toward the oncogene transcript. This work and recent developments in the antisense field lead to the expectation of a new class of radiopharmaceuticals with unique specificity.

Characterization of gastric antral motility disturbances in diabetes using a scintigraphic technique.

In this study, food distribution in the stomach and gastric antral motor activity in patients with longstanding diabetes have been evaluated. With use of a standard gastric emptying test with an acquisition protocol and a refined Fourier algorithm to analyze the data, antral contractions have been characterized and gastric motility parameters were correlated to gastric retention in 20 diabetic patients with or without gastroparesis and in 10 healthy subjects. The results of this study show that, in longstanding diabetes, gastric emptying retardation is accounted for by a retention of food in the proximal stomach, which is reflected by a prolonged lag phase as well as by a reduction in antral motor activity that is determined by a decrease in the amplitude of the antral contractions. This study demonstrates that scintigraphy can noninvasively characterize abnormalities of food distribution in the stomach and provides information similar to that obtained from manometry.

Effect of ethyl alcohol on motor function in canine stomach.

The aim of this study was to elucidate the effects of ethanol on gastric emptying and the trituration of solid food. With the use of a noninvasive physiological imaging technique, gastric processing of a radiolabeled solid meal was evaluated in unanesthetized dogs which ingested 6-8% ethanol solutions or received intravenous alcohol before the meal. Oral alcohol (resulting in blood levels up to 174 mg/dl) decreased the amplitude of antral contractions or completely abolished them. Alcohol did not significantly affect the fundamental frequency of contractions except at high doses, at which contractions were abolished. Alcohol lengthened the mean time to 50% of gastric emptying in a dose-dependent manner, from 132 +/- 3 min without alcohol to 160 +/- 10 min with oral alcohol at blood levels of 80-120 mg/dl (P less than 0.05). This was manifested by a lengthening of the lag phase, but there was no effect on the terminal slope of emptying (emptying rate) of the processed meal. At equal blood levels up to 120 mg/dl, orally administered alcohol had a more pronounced effect than intravenous alcohol. These data suggest that even low doses of dilute alcohol affect the ability of the antrum to process solid food and thereby contribute to impairment of gastric emptying.

Quantitative distribution of radiolabeled 5-aminosalicylic acid enemas in patients with left-sided ulcerative colitis.

Rectally administered suspensions of 5-aminosalicylic acid (5-ASA) are topically effective in treating left-sided ulcerative colitis. The extent to which the contents of these enemas are distributed to inflamed mucosal linings has not previously been determined. This study was undertaken to validate a technique for labeling 5-ASA with 99mTc and to quantitate the distribution of [99mTc]5-ASA in eight patients with left-sided ulcerative colitis. Eight patients underwent three colonic scintigraphic exams within five days, receiving a 60-ml radiolabeled 5-ASA enema into the unprepared rectum for each study, with sequential anterior abdominal images obtained for 4 hr. Activity within the rectum, sigmoid, descending, transverse, and ascending colon was quantitated. Over 50% of the labeled enema had advanced beyond the rectum in five of eight patients and in six of eight patients by 30 min and 60 min, respectively. The distribution of [99mTc]5-ASA was quantitatively reproducible when repeated in the same patient on different days, despite apparent visual differences. By 2 hr, the amount of the enema present within the rectum decreased significantly (P less than 0.05) compared to the initial distribution. The amount of enema present within the descending colon was increased significantly at 0.5 hr (P less than 0.05) and at 2 hr (P less than 0.01). There were no significant changes in the distribution from initial values for the sigmoid, transverse, or ascending colon at any time. In each of these cases the spread of the enema to or beyond the extent of disease was documented. In patients with left-sided ulcerative colitis, small volume [99mTc]5-ASA enemas reliably reach the area of inflammation.

Cisapride accelerates colonic transit in constipated patients with colonic inertia.

A double-blind cross-over trial of oral cisapride 10 mg before meals and placebo was performed to determine its effects on colonic transit in patients with severe idiopathic constipation. Nine patients with less than 3 spontaneous bowel movements/wk were studied. After passing a tube to the cecum, 50 muCi of 111In-DTPA were instilled into the cecum and followed for 48 h using colonic transit scintigraphy. In the group as a whole, cisapride had little effect on transit. The patients were then divided into two groups based on transit: functional rectosigmoid obstruction (FRSO) and colonic inertia (CI). In the CI group, cisapride accelerated the half emptying time of the cecum and ascending colon from 2.50 to 1.21 h (p less than 0.05). The progression of the geometric center was also faster after cisapride in CI. In FRSO, the geometric center was unchanged by cisapride except at 48 h. Cisapride thus has a prokinetic effect on colonic transit in patients with severe idiopathic constipation, colonic inertia subtype. It may be a useful agent in the treatment of this group of patients.

Scintigraphic evaluation of gastric emptying: are radiolabeled solids necessary?

A standard, dual-isotope meal (Tc-99m-egg sandwich and In-111 DTPA in water) was administered to 14 normal volunteers and 37 patients, who had not undergone gastric surgery, to determine if the emptying characteristics of the liquid phase alone could accurately predict delayed solid emptying. Delayed gastric emptying was defined clinically as a solid half-emptying time more than two standard deviations greater than the mean for normal volunteers. Linear regression analysis was performed on the natural logarithm of liquid fractional retention at each time interval to yield a slope and y-intercept for each subject. There was no significant difference (0.6 less than P less than 0.8) between volunteers and patients with normal solid emptying for the liquid slope. In patients who exhibited delayed gastric emptying for solids, the liquid slopes were significantly different from the normal values (P less than .001). There was a high correlation of liquid slope to solid half-emptying time in all patients and volunteers (r = -0.80, P less than .001). Comparison of the liquid slope measurement to solid half-emptying time criteria revealed a sensitivity of 96%, a specificity of 100%, and a predictive value of 100% for the slope test. These results suggest that delayed gastric emptying can be accurately detected with a liquid-solid meal using only a single-liquid label.

The two-component stomach: effects of meal particle size on fundal and antral emptying.

Using a dual-headed gamma camera and a standardized egg test meal labeled with 99mTc-sulfur colloid, the quantitative emptying of the total, proximal and distal stomach in five normal subjects was characterized. The same egg meal was given to the volunteers in 3 different forms: homogenized, and as 2.5 mm and 5.0 mm cubes on 3 separate occasions for a total of 15 studies. For the total stomach emptying, the lag phase and half emptying time (T1/2) obtained using a power exponential model were significantly shorter for the homogenized test meal than for the 2.5 mm and 5.0 mm cubed egg particles; the lag phases were 29 +/- 19 min (mean +/- SD) vs 55 +/- 26 (P less than 0.05) and 64 +/- 24 min (P less than 0.01), the T1/2's were 71 +/- 30 min vs 91 +/- 26 (P less than 0.05) and 104 +/- 30 min (P less than 0.05), respectively. For the proximal stomach, no statistically significant difference was observed among the 3 test meals; the T1/2s for the homogenized, 2.5 mm and 5.0 mm cubed meals were 65 +/- 26 min, 53 +/- 18 min and 64 +/- 20 min, respectively. For the distal stomach, both the peak activity (%) and time to peak activity (min) were significantly higher for the 2.5 mm cubes (43%, 54 min) and the 5.0 mm cubes (38%, 60 min) than for the homogenized eggs (16.4%, 30 min) (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Quantitative measurement of feline colonic transit.

Colonic transit scintigraphy, a method for quantitatively evaluating the movement of the fecal stream in vivo, was employed to evaluate colonic transit in the cat. Scintigraphy was performed in duplicate in five cats and repeated four times in one cat. After instillation of an 111In marker into the cecum through a surgically implanted silicone cecostomy tube, colonic movement of the instillate was quantitated for 24 h using gamma scintigraphy. Antegrade and retrograde motion of radionuclide was observed. The cecum and ascending colon emptied rapidly, with a half-emptying time of 1.68 +/- 0.56 h (mean +/- SE). After 24 h, 25.1 +/- 5.2% of the activity remained in the transverse colon. The progression of the geometric center was initially rapid, followed later by a delayed phase. Geometric center reproducibility was found to be high when analyzed using simple linear regression (slope = 0.92; r = 0.73; P less than 0.01). Atropine (0.1 mg/kg im) was found to delay cecum and ascending colon emptying and delay progression of the geometric center. These results demonstrate both 1) the ability of colonic transit scintigraphy to detect changes in transit induced by pharmacological manipulation and 2) the fact that muscarinic blockade inhibits antegrade transit of the fecal stream. We conclude that feline colonic transit may be studied in a quantitative and reproducible manner with colonic transit scintigraphy.

Role of opiate receptors in the regulation of colonic transit.

The effects of morphine and the opiate antagonist naloxone on human colonic transit were investigated. In a crossover, double-blind fashion, two groups of 6 normal volunteers were studied using colonic transit scintigraphy during the administration of a test drug or control. The test drugs were morphine (0.1 mg/kg every 6 h s.c.) or naloxone (0.8 mg every 6 h s.c.); control was saline (1 ml every 6 h s.c.). Morphine significantly delayed transit in the cecum and ascending colon (p less than 0.05), slowed the progression of the geometric center (p less than 0.01), and decreased the number of bowel movements per 48 h (p less than 0.005). Naloxone accelerated transit in the transverse colon and rectosigmoid colon (p less than 0.05) and accelerated the progression of the geometric center (p less than 0.05), but had no effect on the number of bowel movements per 48 h (p greater than 0.05). These results suggest that narcotic analgesics may cause constipation in part by slowing colonic transit in the proximal colon and by inhibiting defecation. Acceleration of transit by naloxone suggests that endogenous opiate peptides may play an inhibitory role in the regulation of human colonic transit.

Use of 111In-labeled alginate to study the pH dependence of alginic acid anti-esophageal reflux barrier.

Mixtures of alginic acid and antacid, when given orally, react with gastric acid to form a viscous barrier (raft) which floats on the surface of the gastric contents. 111In was used to label magnesium alginate in order to study the effect of gastric acidity on the extent of formation of the raft. In vitro, acid concentrations less than 0.05 N diminished raft formation. In vivo, raft formation was significantly better in normal subjects who ingested dilute acid with the labeled alginate/antacid than in subjects who ingested the labeled alginate/antacid with plain water. Gastric emptying of the labeled alginate was also slowed by the presence of acidified gastric contents. These results suggest that the formation of an effective alginic acid antireflux barrier requires acidic gastric contents.

Biphasic nature of gastric emptying.

The existence of a lag phase during the gastric emptying of solid foods is controversial. It has been hypothesised that among other early events, the stomach requires a period of time to process solid food to particles small enough to be handled as a liquid. At present no standardised curve fitting techniques exist for the characterisation and quantification of the lag phase or the emptying rate of solids and liquids. We have evaluated the ability of a modified power exponential function to define the emptying parameters of two different solid meals. Dual labelled meals were administered to 24 normal volunteers. The subjects received meals consisting of either Tc-99m in vivo labelled chicken liver or Tc-99m-egg, which have different densities, and In-111-DTPA in water. The emptying curves were biphasic in nature. For solids, this represented an initial delay in emptying or lag phase followed by an equilibrium emptying phase characterised by a constant rate of emptying. The curves were analysed using a modified power exponential function of the form y(t) = 1-(1-e-kt)beta, where y(t) is the fractional meal retention at time t, k is the gastric emptying rate in min-1, and beta is the extrapolated y-intercept from the terminal portion of the curve. The length of the lag phase and half-emptying time increased with solid food density (31 +/- 8 min and 77.6 +/- 11.2 min for egg and 62 +/- 16 min and 94.1 +/- 14.2 min for chicken liver, respectively). After the lag phase, both solids had similar emptying rates, and these rates were identical to those of the liquids. In vitro experiments indicated that the egg meal disintegrated much more rapidly than the chicken liver under mechanical agitation in gastric juice, lending further support to the hypothesis that the initial lag in emptying of solid food is due to the processing of food into particles small enough to pass the pylorus. We conclude that the modified power exponential model permits characterisation of the biphasic nature of gastric emptying allowing for quantification of the lag phase and the rate of emptying for both solids and liquids.

Selenium-75-labeled sucralfate: comparison with other radiolabels and initial clinical studies.

Sucralfate was synthesized to include a 75Se label, then compared with 111In-sucralfate and 99mTc-Human serum albumin (HSA)-sucralfate in vitro and in an animal ulcer model. The 75Se label was the only one of the three that was stable in both human gastric juice and simulated intestinal fluid in vitro. In rats with gastric ulcers, ulcer:nonulcer ratios of bound radioactivity averaged 15.4, 6.3, and 5.6 for 75Se, 111In, and 99mTc-HSA labels, respectively. Biodistribution studies of 75Se-sucralfate indicated that little is absorbed from the gastrointestinal tract, and the distribution is similar to that of 14C-sucralfate. Selective binding of 75Se sucralfate was successfully imaged in patients with esophagitis (esophageal mean T1/2 binding = 65 +/- 32 min), gastritis (gastric mean T 1/2 binding = 118 +/- 34 min), and gastric ulcers (ulcer mean T 1/2 binding = 135 +/- 59 min). Duodenal ulcers were not successfully imaged. Normal subjects showed no abnormal localization of sucralfate, and esophageal and gastric clearances were rapid.

Effects of meal composition on gallbladder and gastric emptying in man.

Cholecystogastric scintigraphy, utilizing [99mTc]HlDA to label the gallbladder contents and [111In]DTPA to label different meals, was utilized to determine the relationships between gallbladder and gastric emptying after meals of differing composition. Gallbladder emptying was determined in response to a multicomponent meal and to monocomponent fat, carbohydrate, and protein meals and in response to isotonic and hypertonic dextrose and isotonic and hypertonic saline. Also, the gallbladder emptying responses to equivalent multicomponent solid and liquid meals were compared. Significant gallbladder emptying was observed in response to the multicomponent meal and the monocomponent fat, carbohydrate, and protein meals. The most rapid and complete gallbladder emptying was seen with the multicomponent meal and the monocomponent fat meal. Significant gallbladder emptying was stimulated, not only by isotonic and hypertonic dextrose, but also by hypertonic saline. The gallbladder emptied more rapidly after a liquid than after a solid meal.

MR imaging in thyroid disorders: correlation of signal intensity with Graves disease activity.

Thirty-six patients with a variety of thyroid disorders and eight healthy subjects were studied with T1- and T2-weighted magnetic resonance (MR) imaging. Solid benign nodules, malignant tumors, and inflammatory conditions were not distinguishable by thyroidal MR signal intensity, but almost all patients with Graves disease had a moderate to marked diffuse increase in signal intensity at both settings. Quantitative evaluation showed that in these patients, the thyroid-muscle signal intensity contrast ratio was linearly related to both the serum thyroxine (T4) level and the 24-hour radioactive iodine uptake. In three patients treated with iodine 131, this contrast ratio rose or fell in parallel with the serum T4 level and 24-hour radioactive iodine uptake. Either parenchymal changes or increased vascularity in Graves disease, or both, could produce these findings. In patients without Graves disease, signal intensity was not correlated with serum T4 levels. These findings suggest that MR signal intensity may reflect the activity of the stimulatory process in Graves disease and may therefore be a useful measure of thyroid function in this disorder, with both diagnostic and prognostic value.

The effect of oral cisapride on colonic transit.

A prospective double-blind cross-over trial of oral cisapride 10 mg and placebo was performed to determine the effects of cisapride on the transit of colonic contents in normal humans. Six male volunteers were studied twice using colonic transit scintigraphy. After passing a tube to the caecum, 50 mu Ci of 111Indium diethylene triamine pentaacetic acid were instilled into the bowel lumen. The movement of radiolabelled material was followed using a gamma camera interfaced to a digital computer. Cisapride decreased the half-emptying of the caecum and ascending colon from 1.68 +/- 0.4 hours to 0.72 +/- 0.15 hours (P less than 0.05). The total colon half-emptying time was reduced from 38.5 +/- 7.2 hours to 11.1 +/- 2.9 hours on cisapride (P less than 0.05). Cisapride accelerated transit through the transverse colon, but not the descending colon. The progression of the geometric centre was faster during cisapride administration than with placebo (P less than 0.05). The number of bowel movements 48-hours-1 increased after cisapride from 2.5 +/- 0.8 to 5.0 +/- 0.4 (P less than 0.05). This study demonstrates that cisapride has a marked prokinetic effect on colonic transit in normal subjects. Cisapride may be a useful agent in the treatment of constipation.

Colonic transit scintigraphy. A physiologic approach to the quantitative measurement of colonic transit in humans.

Colonic transit scintigraphy was developed to quantitatively evaluate colonic transit. Using this technique the progression of a radiolabeled marker from cecal instillation to defecation was studied in 7 normal male volunteers. An 8-ml bolus containing 50 mu Ci of indium 111-diethylene triamine pentaacetic acid was instilled into the cecum via a 2-mm tube, which was passed orally, and serial scintigrams were obtained over 48 h. By 48 h, 70.7% +/- 9.1% (mean +/- SEM) of the instilled activity had been defecated. The cecum and ascending colon emptied rapidly, with a half-emptying time of 87.6 +/- 27.0 min. Geometric center analysis showed an initial logarithmic progression of activity in the proximal colon and a linear progression distally. This study suggests that the transverse colon, not the cecum and ascending colon, may be the primary site for fecal storage. Colonic transit scintigraphy is a safe, physiologic, and quantitative method for evaluating the colonic transit of fecal material and may provide a useful tool for evaluating normal and abnormal large intestinal physiology.

Infection in diabetic osteoarthropathy: use of indium-labeled leukocytes for diagnosis.

Indium-111 labeled leukocyte imaging was compared with three-phase skeletal scintigraphy as a means of determining whether osteomyelitis was complicating diabetic osteoarthropathy. Three-phase scintigraphy demonstrated increased activity in both infected and noninfected osteopathic bone, with a sensitivity of 75% and a specificity of 56% for osteomyelitis. Leukocyte imaging had the same sensitivity but was most helpful for excluding infection (specificity, 89%) when three-phase imaging could not. Abnormal leukocyte localization was seen at the primary site of infection in all cases within 4 hours after injection. Disadvantages of leukocyte imaging included long preparation time, low count rates resulting in poor spatial resolution, and absence of bone landmarks, which made it difficult to differentiate soft tissue from bone infection.

Gallbladder emptying response to sham feeding in humans.

Cholescintigraphy, using 99mTc-HIDA, was employed to determine the gallbladder emptying response to sham feeding of a steak and potato meal, and to compare it with the emptying responses to direct cholinergic stimulation by bethanechol and to ingestion of the test meal. The maximal cumulative gallbladder emptying response to sham feeding was 44.1% + 10.1%, which was not significantly different from the response to bethanechol. Cholinergic blockade with atropine eliminated the emptying response to sham feeding. Also, sham feeding did not stimulate gallbladder emptying in patients with vagotomy. This study suggests that intact vagus nerves and cholinergic pathways are required in order for the gallbladder to respond to sham feeding. The precise mechanism for this effect has not been elucidated.