Linda C. Knight

Gastric emptying of a non-digestible solid: assessment with simultaneous SmartPill pH and pressure capsule, antroduodenal manometry, gastric emptying scintigraphy

Abstract  Gastric emptying of digestible solids occurs after trituration of food particles. Non‐digestible solids are thought to empty with phase III of the migrating motor complex (MMC). The aim of this study was to determine if a non‐digestible capsule given with a meal empties from the stomach with return of the fasting phase III MMC or during the fed pattern with the solid meal. Fifteen normal subjects underwent antroduodenal manometry and ingestion of a radiolabelled meal and SmartPill wireless pH and pressure capsule. In five subjects, emptying of the SmartPill was studied in the fasting period by ingesting the SmartPill with radiolabelled water. The SmartPill emptied from the stomach within 6 h in 14 of 15 subjects. SmartPill pressure recordings showed high amplitude phasic contractions prior to emptying. SmartPill gastric residence time (261 ± 22 min) correlated strongly with time to the first phase III MMC (239 ± 23 min; r = 0.813; P < 0.01) and correlated moderately with solid‐phase gastric emptying (r = 0.606 with T‐50% and r = 0.565 with T‐90%). Nine of 14 subjects emptied the capsule with a phase III MMC. In five subjects, the SmartPill emptied with isolated distal antral contractions. In five subjects ingesting only water, SmartPill gastric residence time (92 ± 44 min) correlated with the time to the first phase III MMC (87 ± 30 min; r = 0.979; P < 0.01). The non‐digestible SmartPill given with a meal primarily empties from the stomach with the return of phase III MMCs occurring after emptying the solid‐phase meal. However, in some subjects, the SmartPill emptied with isolated antral contractions, an unappreciated mechanism for emptying of a non‐digestible solid.

Treatment of idiopathic gastroparesis with injection of botulinum toxin into the pyloric sphincter muscle.

OBJECTIVES:We aimed to determine if botulinum toxin injection into the pyloric sphincter improves gastric emptying and reduces symptoms in patients with idiopathic gastroparesis.METHODS:Patients with idiopathic gastroparesis not responding to prokinetic therapy underwent botulinum toxin (80–100 U, 20 U/ml) injection into the pyloric sphincter. Gastric emptying scintigraphy was performed before and 4 wk after treatment. Total symptom scores were obtained from the sum of eight upper GI symptoms graded on a scale from 0 (none) to 4 (extreme).RESULTS:Ten patients were entered into the study. The mean percentage of solid gastric retention at 4 h improved from 27 ± 6% (normal < 10%) before botulinum toxin injection into the pylorus to 14 ± 4% (p = 0.038) 4 wk after treatment. The symptom score decreased from 15.3 ± 1.7 at baseline to 9.0 ± 1.9 (p = 0.006) at 4 wk, a 38 ± 9% decrease. Improvement in symptoms tended to correlate with improved gastric emptying of solids (r = 0.565, p = 0.086).CONCLUSIONS:This initial pilot study suggests that botulinum toxin injection into the pylorus in patients with idiopathic gastroparesis improves both gastric emptying and symptoms.

Scintigraphic evaluation of gastric emptying

There has been recent, renewed interest in studies of gastric emptying due in part to the introduction of new therapies for peptic ulcer diseases and attempts to better understand gastric physiology. Of the methods available for studying gastric emptying patterns, nuclear medicine techniques are optimal due to their noninvasive character, reproducibility and quantitative ability. The modulation of gastric emptying is multifactorial, and includes motor control, electrical activity, hormonal influences, and the composition of the meal itself: liquid vs solid; protein, carbohydrate and fat content; fiber or particle size; osmolality; pH; and pharmacologic agents. Because of the ease of performing gastric emptying studies using radiolabeled physiologic meals, these tests are being employed with increasing frequency in the evaluation of patients with disorders such as diabetic gastroparesis, postgastrectomy gastroparesis or dumping syndrome, and in the study of normal gastric physiology in man. Present data suggests that combined liquid-solid, dual radionuclide studies afford the greatest information regarding simultaneous gastric emptying patterns of liquid and solid components of a meal, and that single radionuclide, solid tests of gastric emptying are the more sensitive technique for determining subtle abnormalities of gastric emptying, when only a single tracer is employed.

A rapid method for removal of [125I]iodide following iodination of protein solutions

Abstract A simple, highly effective, and rapid method for the removal of [ 125 I]iodide following iodination of protein solutions is described. Greater than 98% of free iodide is removed in approximately 2 min with protein recoveries in excess of 90%. An advantage of the procedure is the confinement of radioactive waste to small easily disposable tubes.

High molecular weight kininogen binds to unstimulated platelets.

Studies were performed to determine if the unstimulated platelet membrane has a site for high molecular weight kininogen (HMWK) binding. 125I-HMWK bound to unstimulated platelets. Zn++ was required for 125I-HMWK binding to unstimulated platelets and binding was maximal at 50 microM Zn++. Neither Mg++ nor Ca++ substituted for Zn++ in supporting 125I-HMWK binding to unstimulated platelets, and neither ion potentiated binding in the presence of 50 microM zinc. 125I-HMWK competed with equal affinity with HMWK for binding, and excess HMWK inhibited 125I-HMWK-platelet binding. Only HMWK, not prekallikrein, Factor XII, Factor XI, Factor V, fibrinogen, or fibronectin inhibited 125I-HMWK-platelet binding. 125I-HMWK binding to unstimulated platelets was 89% reversible within 10 min with a 50-fold molar excess of HMWK. Unstimulated platelets contained a single set of saturable, high affinity binding sites for 125I-HMWK with an apparent dissociation constant of 0.99 nM +/- 0.35 and 3,313 molecules/platelet +/- 843. These studies indicate that the unstimulated external platelet membrane has a binding site for HMWK that could serve as a surface to modulate contact phase activation.

Simultaneous Measurement of Gastric Emptying with a Simple Muffin Meal Using [13C]Octanoate Breath Test and Scintigraphy in Normal Subjects and Patients with Dyspeptic Symptoms

The objective of this study was to determine how the [13C]octanoate breath test (OBT) using a muffin meal correlates with gastric emptying scintigraphy (GES) in normal subjects and patients with dyspeptic symptoms. Ten normal subjects and 23 patients with dyspeptic symptoms underwent simultaneous GES and [13C]OBT. After an overnight fast, a muffin labeled with [99mTc]sulfur colloid and [13C]octanoate was ingested along with water labeled with [111In]DTPA. Breath samples and scintigraphic images were obtained at baseline and at regular postprandial intervals over 6 hr. In the normal subjects, the mean GES T1/2 of solids and liquids were 64 ± 17 and 55 ± 27 minutes, respectively. The calculated OBT T1/2 using the 6-hr breath collection was 138 ± 15 min and correlated with T1/2 for solids by GES (r = 0.664; P = 0.051), but did not correlate with T1/2 for liquids by GES (r = 0.13; P = 0.738). In dyspeptic patients, the T1/2 for GES was 87 ± 53 min and 81 ± 70 min for solids and liquids, respectively. The mean OBT T1/2 was 155 ± 57 min and correlated with GES T1/2 for solids (r = 0.86; P < 0.001) and GES T1/2 for liquids (r = 0.73; P < 0.001). Delayed gastric emptying (GE) of the muffin meal was identified by scintigraphy in seven patients. The sensitivity and specificity for OBT identifying delayed GE were 86% and 94%. Use of the initial truncated 4-hr OBT results also revealed a significant correlation between OBT and GES T1/2 for solids (r = 0.86; P < 0.001) with sensitivity and specificity for detecting delayed GE of 86% and 94%, respectively. In addition, a linear regression model was able to reduce the number of collection points to four, while maintaining the same sensitivity and specificity. In conclusion, the OBT for GE, using an easily prepared muffin meal, significantly correlates with GES for solids. This muffin-based OBT is a sensitive and specific method to detect delayed GE in dyspeptic patients.

Bladder permeability in interstitial cystitis is similar to that of normal volunteers: direct measurement by transvesical absorption of 99mtechnetium-diethylenetriaminepentaacetic acid.

Bladder permeability was directly measured with the radionuclide used clinically for detecting vesicoureteral reflux (99mtechnetium-diethylenetriaminepentaacetic acid, 99mTc-DTPA) in 10 interstitial cystitis patients diagnosed according to National Institute of Arthritis, Diabetes, Digestive and Kidney Diseases criterion and compared to 9 sex matched, symptom-free, normal volunteers. After functional bladder capacity was determined (capacity at which the patient demands fluid inflow to stop), the bladder was emptied and 5 mCi. 99mTc-DTPA in 10 ml. of saline were infused followed by normal saline to 80% of functional capacity. This was done to normalize the patients to the same low bladder pressure, since previous studies of rabbits indicated that bladder permeability is low and not significantly different at 20% and 60% of anesthetized bladder capacity (defined as the volume producing an intravesical pressure of 20 cm. water). Radioactivity of 1 ml. serum specimens taken at 0, 2, 15 and 30 minutes after radionuclide infusion was determined in a gamma counter, corrected for radioactive decay and converted to per cent of instilled dose per whole body based on blood volume estimated from body weight for each individual. There was considerable interindividual variability in the absorption between the patients and the volunteers. Analysis of variance of these data showed no statistically significant difference between the patients and controls at any time sampled. These results indicate that while some interstitial cystitis patients have a more permeable bladder than others, the same is true for normal, symptom-free volunteers. Thus, the concept of increased bladder permeability in interstitial cystitis is not supported by this direct measurement of bladder permeability.

Labeling of platelet surface proteins with 125I by the iodogen method.

A procedure for the 125I-iodination of platelet suspensions is described. The procedure utilizes Iodogen, a solid-phase oxidizing agent similar to chloramine-T. Platelets were labeled under a variety of conditions, including in the presence of 0.1% albumin, and showed between 7 and 28% incorporation of 125I. Best labeling results were obtained at low platelet concentrations (3-5 x 10(8) platelets/ml), short reaction times (15 min), and with 2-ml glass vials coated with 100 micrograms of Iodogen. Analysis of the labeled platelet proteins by sodium dodecyl sulfate-polyacrylamide gel electrophoresis followed by autoradiography revealed that the same major protein bands were labeled by this procedure as were labeled by the lactoperoxidase procedure. At low platelet concentrations, the Iodogen procedure gives twice the amount of iodine incorporation.

Radiopharmaceuticals for thrombus detection.

Most of the components of the thrombotic and fibrinolytic systems have at some time been evaluated as a means of carrying a radiolabel specifically to thrombi, although very few have been promising enough to emerge from investigational status to routine clinical use. New approaches are being explored, including improved methods of labeling platelets, chemically modified forms of previously tested plasma proteins, and new biomolecules, including monoclonal antibodies specific for fibrin and platelets. The current goal is to find one or more radiotracers that bind specifically and rapidly to thrombi, and that also have a rapid blood disappearance rate, permitting a clear diagnosis within a few hours after injection. Because this test may be needed to assess the course of therapy in an anticoagulated patient, the ideal radiopharmaceutical should be able to locate thrombi without interference by anticoagulants. Until a suitable thrombus-specific radiopharmaceutical becomes generally available, many hospitals will continue to attempt to make a diagnosis with nonspecific radiopharmaceuticals that can at best provide blood pool images to indicate filling defects. Several of the new approaches seem likely to provide the radiopharmaceutical sought, although clinical trials are at an early stage.

Radiation-Guided Targeting of Combretastatin Encapsulated Immunoliposomes to Mammary Tumors

PurposeRadiation upregulates expression of endothelial cell adhesion molecules providing a potential avenue for targeting drugs to irradiated tissue. Induced upregulation of E-selectin can be used to target immunoliposomes to solid tumors. The effects of targeting immunoliposomes containing the antivascular drug combretastatin disodium phosphate (CA4P) to irradiated mammary tumors were investigated in this study.MethodsMice bearing transplanted MCa-4 mouse mammary tumors were assigned to one of the factorial treatments permuting the administration of free CA4P, tumor irradiation, CA4P encapsulated liposomes, and CA4P encapsulated immunoliposomes (conjugated with anti-E-selectin). Single and fractionated dosing of radiation and/or CA4P was evaluated.ResultsFor single dose treatments the group that received a single dose of radiation plus a single dose of immunoliposomes showed a significant delay in tumor growth compared to all other treatment groups. Fractionated radiation plus fractionated doses of immunoliposomes resulted in further tumor growth delay; however, it was not significantly different from other fractionated dose treatment groups that combined radiation and CA4P.ConclusionsTargeting of antivascular drugs to irradiated tumors via ligand-bearing liposomes results in significant tumor growth delay. This effect can be further potentiated using a fractionated irradiation dosing schedule combined with fractionated immunoliposome treatments.