Diethylenetriaminopentaacetic Acid Research Articles

Diethylenetriaminopentaacetic acid is unsuitable for long-term preservation of RBCs.

The addition of an appropriate metal chelator, such as diethylenetriaminopentaacetic acid (DTPA) to stored blood has been shown to be effective in a short-term (0-12 days) prevention of lipid peroxidation of stored RBCS: However, its long-term effectiveness has not been carefully evaluated. Blood was preserved in simulated blood bank conditions with or without the addition of DTPA for 4 weeks. Aliquots of stored blood were taken weekly from the storage bag and the deformability profile was determined using a custom-built laser viscodiffractometer. Malondialdehyde (MDA), an index of lipid peroxidation, and the extent of vesiculation of the stored blood were quantified concurrently. It was found that MDA values for DTPA-supplemented blood at the end of a 28-day storage period were significantly elevated compared with the DTPA-free counterpart (23.50 +/- 3.2 vs. 16.10 +/- 2.5 microM; p<0.05). In addition, DTPA-supplemented blood was more susceptible to vesiculation than its DTPA-free counterpart (31.26 +/- 4.1 vs. 10.26 +/- 1.5% of acetyl cholinesterase release, p<0.001). These data are also in accordance with the finding of the deformability profile result, indicating that DTPA-supplemented blood exhibits not only a decrease in deformability index, but also a tendency to shift the profile to a lower osmolality compared with that of controls (a dehydration phenomenon). Long-term (0-28 days) preservation of human RBCs with DTPA caused a gradual increase in MDA production, a progressive enhancement of the severity of vesiculation, and an alteration in the deformability profile. Free-radical-mediated oxidative damage is likely to be the culprit for this observed phenomenon. In addition, the direct effect of DTPA on RBC structural integrity must be considered.

Effect of metals on Candida albicans growth in the presence of chemical chelators and human abscess fluid

Calprotectin is a calcium- and zinc-binding protein that is present in abscess fluid supernatants and appears to inhibit microbial growth through competition for zinc. In the present study, growth inhibition by chemical chelators was compared with that produced by human abscess fluid to determine whether other chelators, perhaps with different metal specificities, would have the same or different patterns of metal reversibility as abscess fluid. Zinc was found to be more potent than the other metals tested in reversing C. albicans growth inhibition by human abscess fluid and three chemical chelators, even though in some cases the stability constants of certain of these chelators were higher for other metals. For example, in the presence of the chelator diethylenetriaminopentaacetic acid, zinc stimulated Candida growth at a 10-fold lower concentration than did iron, even though this chelator has a stability constant for iron that is almost 1010 higher than that for zinc. These results suggest that the zinc specificity of calprotectin's C. albicans growth inhibition can best be explained by the marked sensitivity of this organism to zinc deprivation rather than by selective binding of this metal by the protein. (J Lab Clin Med 2001;137:284-9)

Carbonic anhydrase inhibitors: synthesis of sulfonamides incorporating dtpa tails and of their zinc complexes with powerful topical antiglaucoma properties

Reaction of diethylenetriamino pentaacetic acid (dtpa) dianhydride with aromatic/heterocyclic sulfonamides possessing a free amino/imino/hydrazino/hydroxy group afforded bis-sulfonamides containing metal-complexing, polyamino-polycarboxylic acid moieties in their molecule. The corresponding mono-sulfonamide derivatives of dtpa were also obtained by an alternative method, from the free acid. Zn(II) complexes of these new sulfonamides were then prepared. Many of these derivatives showed nanomolar affinity towards isozymes I, II and IV of carbonic anhydrase (CA). Some of the best inhibitors were applied as 2% water solutions/suspensions into the eye of normotensive or glaucomatous albino rabbits, when strong and long-lasting intraocular pressure (IOP) lowering was observed.

Somatostatin receptor imaging, therapy and new strategies in patients with neuroendocrine tumours.

Somatostatin receptors have been found on a variety of neuroendocrine tumours, such as carcinoids and paragangliomas, as well as on most pancreatic endocrine and breast tumours. Somatostatin receptor scintigraphy with a radionuclide-labelled somatostatin analogue, [111Indium- diethylenetriaminopenta-acetic acid]octreotide, is a sensitive and specific technique for visualizing in vivo the presence of somatostatin receptors on various tumours. Material was identified from previous review articles, references cited in original papers and a Medline search of the literature. Additional material was obtained from recently published abstracts of meetings. Somatostatin receptor imaging of neuroendocrine tumours is essential in the diagnostic evaluation of most of these tumours. The expression of somatostatin receptors in vivo not only predicts the outcome of somatostatin analogue treatment but also opens the possibility of new therapeutic strategies. Because better information about spread of the disease can be obtained, more justifiable options for therapy can be proposed.

Measurement of Gd-DTPA diffusion through PVA hydrogel using a novel magnetic resonance imaging method.

Polyvinyl alcohol-cryogel (PVA-C) is a hydrogel that is an excellent tissue mimic. In order to characterize mass transfer in this material, as well as to demonstrate in principle the ability to noninvasively measure solute diffusion in tissue, we measured the diffusion coefficient of the magnetic resonance (MR) contrast agent gadolinium diethylene triaminopentaacetic acid (Gd-DTPA) through PVA-C using a clinical MR imager. The method involved filling thick-walled rectangular PVA-C "cups" with known concentrations of Gd-DTPA solutions. Then by using a fast inversion recovery spin echo MR imaging protocol, a signal "null" contour was created in the MR image that corresponded to a second, known concentration of Gd-DTPA. By collecting a series of MR images through the PVA-C wall as a function of time, the displacement of this second known isoconcentration contour could be tracked. Application of Fick's second law of diffusion yielded the diffusion coefficient. Seven separate experiments were performed using various combinations of initial concentrations of Gd-DTPA within the PVA-C cups (3.2, 25.6, or 125 mM) and tracked isoconcentrations contours (0.096, 0.182, or 0.435 mM Gd-DTPA). The experimental results and the predictions of Fick's law were in excellent agreement. The diffusivity of Gd-DTPA through 10% PVA hydrogel was found to be (2.6 +/- 0.04) x 10(-10) m(2)/s (mean +/- s.e.m.). Separate permeability studies showed that the diffusion coefficient of Gd-DTPA through this hydrogel did not change with an applied pressure of up to 7.1 kPa. Accurate measurements could be made within 30 min if suitable Gd-DTPA concentrations were selected. Due to the excellent repeatability and fast data acquisition time, this technique is very promising for future in vivo studies of species transport in tissue.

An interleaved T1-T2* imaging sequence for assessing myocardial injury.

We developed a sequence by which T1- and T2*-weighted images can be acquired simultaneously and demonstrated its validity for assessing myocardial injury. The interleaved T1-T2* imaging sequence consisted of one preparatory pulse (a 90 degrees pulse) and a gradient-echo imaging sequence with a dynamically variable echo time varying between 4.2 msec for T1-weighted imaging and 15 msec for T2*-weighted imaging. The sequence was tested and validated on isolated blood-perfused pig hearts (n = 4). We found that contrast agent-induced T1 and T2* effects were clearly delineated during the first-pass and steady-state periods of a contrast agent (gadolinium diethylenetriaminopentaacetic acid). With a bolus injection of contrast agent, the maximum changes in T2* signal intensity occur significantly earlier than the changes in T1 signal. We also found that the maximum change in T1 signal intensity during the first pass of contrast agent was significantly greater in a reperfused-infarcted region than in normal regions. The suppression of T2* signal was similar in both regions. At steady state of contrast agent, T2* signal intensities gradually recovered to a significantly higher level in the reperfused-infarcted region than in normal regions. This suggests that the contrast agent diffused into the intracellular space, indicating the loss of cell membrane integrity. As a result, T1 signal intensity was also higher in the reperfused-infarcted myocardium than in normal myocardium. T1- and T2*-weighted images can be acquired simultaneously. The interleaved T1-T2* sequence is useful in assessing myocardial injury.

Quantitative regional blood volume studies in rat myocardium in vivo.

Many pathophysiological processes in the myocardium are in close relation to changes of the regional blood volume and regional myocardial blood flow or perfusion. Only few methods exist to obtain quantitative values for these parameters. Quantitative regional blood volume (RBV) studies in rat myocardium are presented using snapshot fast low angle shot (FLASH) inversion recovery T1 measurements with two different blood pool contrast agents, gadolinium diethylenetriaminopentaacetic acid (Gd-DTPA) albumin and Gd-DTPA polylysine. In contrast to previous attempts, each snapshot FLASH image acquisition was ECG-triggered under breathhold conditions. To measure relaxation times shorter than a heart cycle, each T1 sequence was repeated two times with different delays between inversion pulse and first image acquisition. The experiments were performed on a Bruker Biospec 70/21 using a homogeneous transmitter coil and a circularly polarized surface receiver coil, a special ECG trigger unit, and a respirator that is controlled by the pulse program. Based on a fast exchange model RBVm maps were calculated from the relaxation time maps for different concentrations of the two blood pool contrast agents. A significant dependence of the RBVm values on blood T1 was found. This is in accordance with a model that has been developed recently relating the dependence of RBVm on T1 of blood to perfusion. For Gd-DTPA albumin, the application of the model to the experimental data yields realistic values for RBV and perfusion. The values, which are in accordance with literature data, were obtained at highest contrast agent concentrations i.e., lowest relaxation times of blood (ca. 200 ms).

Enhanced magnetic resonance imaging for tissue characterization of liver abnormalities with hepatobiliary contrast agents: an overview of preclinical animal experiments.

Because of the demand for an extension of the range of diagnostic uses for currently available extracellular magnetic resonance imaging (MRI) contrast agents, a new generation of tissue-specific (i.e., hepatobiliary) contrast agents have been successfully developed to enhance the performance of hepatic MRI. These agents include mangafodipir trisodium (formerly manganese dipyridoxal diphosphate [Mn-DPDP]), gadoxetic acid (formerly gadolinium ethoxybenzyl diethylenetriaminopentaacetic acid [Gd-EOB-DTPA]), and gadolinium butylbenzyl diethylenetriaminepentaacetic acid (MS-264). In a series of experiments in animals, the potential of these agents for noninvasive characterization of liver lesions was evaluated with the use of a comprehensive methodology. The purpose of this report was to summarize the observed imaging behaviors of these agents toward different types of cholestasis and focal liver lesions, compare the similarities or dissimilarities of these agents in their possible mechanisms of action, and discuss the clinical implications of the results of the experiments. In summary, through intravenous administration of these agents, both global and local obstructive cholestases can be identified on the postcontrast image. With certain reliability, liver tumors of different origins and grades of cellular differentiation can be detected and classified according to their contrast enhancement patterns occurring at certain postcontrast phases. The invasiveness or degree of a malignancy of the liver tumor can also be suggested by the presence or absence of a peritumoral rim sign. Such diagnostic information, otherwise only invasively achievable, may prove to be invaluable in clinical decision making.

The Effect of Apotransferrin on Iron Release From Caco-2 Cells, an Intestinal Epithelial Cell Line

AbstractThe Caco-2 cell line grown in bicameral chambers was used to study the effect of transferrin in the basal chamber on the transepithelial transport of iron. We have shown that when iron was offered as59Fe on the apical surface of the Caco-2 cells, transport of 59Fe into the basal chamber was stimulated by 50 μmol/L apotransferrin. Here, we examined the effect on59Fe transport of lower concentrations of apotransferrin, as well as the effects on transport of ovo-, cobalt-, and ferri-transferrin and of iron chelators with an affinity for iron greater than that of transferrin. The stimulation of 59Fe transport was more sensitive to the presence of apotransferrin with a Km of 0.078 ± 0.008 μmol/L compared with ferri-transferrin with a Km of 1.24 ± 0.39 μmol/L (P < .006). 59Fe transport was less sensitive to diethylenetriaminopenta-acetic acid (DTPA) than apotransferrin with Kms of 1.52 ± 0.70. The chelator nitrilotriacetic acid (NTA) exhibited no stimulation of59Fe transport. Analysis of laser scanning confocal micrographs showed that apotransferrin labeled with Texas Red is internalized by Caco-2 cells from the basal side and localizes in distinct vesicles above the nucleus. The sensitivity of apotransferrin in stimulating Fe transport suggests a unique interaction of apotransferrin with the basal surface of the intestinal epithelium.

The Effect of Apotransferrin on Iron Release From Caco-2 Cells, an Intestinal Epithelial Cell Line

The Caco-2 cell line grown in bicameral chambers was used to study the effect of transferrin in the basal chamber on the transepithelial transport of iron. We have shown that when iron was offered as59Fe on the apical surface of the Caco-2 cells, transport of 59Fe into the basal chamber was stimulated by 50 μmol/L apotransferrin. Here, we examined the effect on59Fe transport of lower concentrations of apotransferrin, as well as the effects on transport of ovo-, cobalt-, and ferri-transferrin and of iron chelators with an affinity for iron greater than that of transferrin. The stimulation of 59Fe transport was more sensitive to the presence of apotransferrin with a Km of 0.078 ± 0.008 μmol/L compared with ferri-transferrin with a Km of 1.24 ± 0.39 μmol/L (P &lt; .006). 59Fe transport was less sensitive to diethylenetriaminopenta-acetic acid (DTPA) than apotransferrin with Kms of 1.52 ± 0.70. The chelator nitrilotriacetic acid (NTA) exhibited no stimulation of59Fe transport. Analysis of laser scanning confocal micrographs showed that apotransferrin labeled with Texas Red is internalized by Caco-2 cells from the basal side and localizes in distinct vesicles above the nucleus. The sensitivity of apotransferrin in stimulating Fe transport suggests a unique interaction of apotransferrin with the basal surface of the intestinal epithelium.

Myocardial perfusion modeling using MRI.

In the present study, it is shown that it is possible to quantify myocardial perfusion using magnetic resonance imaging in combination with gadolinium diethylenetriaminopentaacetic acid (Gd-DTPA). Previously, a simple model and method for measuring myocardial perfusion using an inversion recovery turbo-FLASH (fast low-angle shot) sequence and Gd-DTPA has been presented. Here, an extension of the model is presented taking into account fast and slow water exchange between the compartments, enabling the calculation of the unidirectional influx constant (Ki) for Gd-DTPA, the distribution volume of Gd-DTPA (lambda), the vascular blood volume (Vb), and the time delay through the coronary arteries (delta T). The model was evaluated by computer simulation and used on experimental results from seven healthy subjects. The results in the healthy volunteers for a region of interest placed in the anterior myocardial wall were (mean +/- SD) Ki = 54 +/- 10 ml/100 g/min, lambda = 30 +/- 3 ml/100 g, Vb = 9 +/- 2 ml/100 g, delta T = 3.2 +/- 1.1 s. These results are in good agreement with similar results obtained by other methods.

Albuminuria predicts renal functional outcome after intervention in atheromatous renovascular disease.

Atheromatous renovascular disease is increasingly recognized as a cause of renal failure; however, the benefit of intervention on renal function outcome cannot be clearly anticipated. To identify reliable predictor(s) of renal functional outcome after revascularization in patients with atheromatous renovascular disease. The effect of percutaneous transluminal renal angioplasty (n = 5) or surgery (n = 18) on glomerular filtration rate ([99mTc]-diethylene triaminopenta-acetic acid clearance) and renal haemodynamics was prospectively assessed in 23 patients with atheromatous renovascular disease (unilateral occlusion in five, unilateral stenosis in four, stenosis of a single kidney in five, unilateral occlusion associated with contralateral stenosis in six, bilateral stenosis in three). Renal function was altered in 18 patients. At early follow-up study (5 +/- 1 months) after intervention, glomerular filtration rate improved (i.e. increased by more than 15%) in six patients, deteriorated in five and remained unchanged in 12 patients. The change in glomerular filtration rate associated with intervention was inversely correlated with the pre-intervention level of urinary albumin excretion and positively with the change in effective renal plasma flow after intervention. Stepwise regression analysis showed that pre-intervention urinary albumin excretion was the only predictor of the glomerular filtration rate response to intervention. At late follow-up study (32 +/- 6 months, n = 13), glomerular filtration rate was stable compared with early follow-up determination in non-proteinuric patients whereas it had deteriorated further in proteinuric patients. In patients with atheromatous renovascular disease, albuminuria may be considered as a marker of pre-existing intra-renal vascular and glomerular damage and a reliable predictor of renal functional outcome after intervention.

Magnetic resonance fluoroscopy using spirals with variable sampling densities.

The imaging of dynamic processes in the body is of considerable interest in interventional examinations as well as kinematic studies, and spiral imaging is a fast magnetic resonance imaging technique ideally suited for such fluoroscopic applications. In this manuscript, magnetic resonance fluoroscopy pulse sequences in which interleaved spirals are used to continuously acquire data and reconstruct one movie frame for each repetition time interval are implemented. For many applications, not all of k-space needs to be updated each frame, and nonuniform k-space sampling can be used to exploit this rapid imaging strategy by allowing variable update rates for different spatial frequencies. Using the appropriate reconstruction algorithm, the temporal updating rate for each spatial frequency is effectively proportional to the corresponding k-space sampling density. Results from a motion phantom as well as in in vivo gadolinium diethylenetriaminopentaacetic acid (Gd-DTPA) bolus tracking studies in a rat model demonstrate the high temporal resolution achievable using these techniques as well as the tradeoffs available with nonuniform sampling densities. This paper focuses on the acquisition of real-time dynamic information, and all images presented are reconstructed retrospectively. The issues of real-time data reconstruction and display are not addressed.

Theory of 1/T1 and 1/T2 NMRD profiles of solutions of magnetic nanoparticles

Organically coated iron oxide crystallites with diameters of 5-50 nm ("nanoparticles") are potential magnetic resonance imaging contrast agents. 1/T1 and 1/T2 of solvent water protons are increased dramatically by magnetic interactions in the "outer sphere" environment of the nanoparticles; subsequent diffusive mixing distributes this relaxation throughout the solvent. Published theory, valid for the solute magnetic energy small compared with thermal energy, is applicable to small magnetic solutes (e.g., gadolinium and manganese diethylenetriaminopentaacetic acid, and nitroxide free radicals) at generally accessible fields (< or = 50 T). It fails for nanoparticles at fields above approximately 0.05 T, i.e., at most imaging fields. The authors have reformulated outer sphere relaxation theory to incorporate progressive magnetic saturation of solute nanoparticles and, in addition, indicate how to use empirical magnetization data for realistic particles when their magnetic properties are not ideal. It is important to handle the effects of rapid thermally induced reorientation of the magnetization of the nanoparticles (their "superparamagnetism") effectively, including their sensitivity to particle size. The theoretical results are presented as the magnetic field dependence (NMRD profiles) of 1/T1 and 1/T2, normalized to Fe content, for three sizes of particles, and then compared with the limited data extant for well-characterized material.

An improved assay for antibody dependent cellular cytotoxicity based on time resolved fluorometry

A new and faster assay for antibody dependent cellular cytotoxcity based on release of europium from target cells is described. This has a number of important advantages over the traditional assays based on release of chromium-51 ( 51Cr). The new method involves labelling of Wein 133 target cells (B cell non-Hodgkin's lymphoma cells) which express the antigen, CD w52, with the chelate europium diethylenetriaminopentaacetic acid (EuDTPA) according to the method of Blomberg et al. (1986). Labelled cells are sensitised (coated) with the anti-lymphocytic monoclonal antibody, Campath-1H. Human peripheral blood mononuclear cells are added to mediate lysis of EuDTPA labelled Wein 133 cells by ADCC. Release of EuDTPA from lysed cells is determined by mixing supernatants with enhancement solution containing 2-naphthoyl trifluoroacetone, 2-NTA, to form a highly fluorescent chelate which is measured using time resolved fluorometry. Results obtained with the new EuDPTA release assays were comparable to traditional assays based on the release of the radioisotope 51Cr. It is anticipated that this assay will have a widespread application among laboratories performing ADCC assays. The method is non-hazardous and has been used routinely for over 2 years to monitor production and purification of Campath-1H.

Comparison of monoclonal biotin-avidin enzyme immunoassay and monoclonal time-resolved fluoroimmunoassay in detection of respiratory virus antigens

Background: Detection of respiratory viruses by time-resolved fluoroimmunoassay based on monoclonal antibodies were developed in our laboratories in the late 1980s and they have been successfully used in daily diagnosis for more than seven years. Later, similar Biotin-EIAs were developed but the sensitivities were unsatisfactory. Objectives: Further optimization of monoclonal Biotin-EIAs and comparison of the optimized assays with TR-FIAs. Study design: Variations in test format, diluents, incubation times and temperatures, and different monoclonal antibodies were tested, and the final comparisons were made with TR-FIA using stored nasopharyngeal aspirates. Results: The improvements in Biotin-EIA featured four changes which increased sensitivity in the assay: (a) test diluent contained diethylenetriamino-pentaacetic acid; (b) antigen and biotinylated detector antibody were added simultaneously; (c) reaction time was extended from 1 h at 37°C to overnight at 4°C; (d) from the thirteen monoclonal antibodies used in TR-FIA, ten were optimal also in Biotin-EIA, but in the parainfluenza 1 and 2 assays other monoclonals proved more sensitive. Out of 257 originally positive specimens tested in the comparison studies, 192 (74.7%) were again positive and 54 (21.0%) were negative in both assays; nine were negative in TR-FIA but positive in Biotin-EIA, while two specimens were negative in Biotin-EIA but positive in TR-FIA. The overall agreement between the two assays was 95.7%. Conclusions: All monoclonal Biotin-EIAs can be optimized to the same sensitivity as TR-FIAs for the detection of respiratory viruses. Laboratories which have no TR-FIA expertise may use Biotin-EIA in the diagnosis of acute respiratory infections.

Pharmacokinetic Mapping of the Breast: A New Method for Dynamic MR Mammography

A dynamic contrast-enhanced MRI technique for whole breast examinations is presented. The fast kinetics of tissue response during and after constant-rate intravenous infusion of gadolinium diethylenetriaminopentaacetic acid was resolved using a strongly T1-weighted saturation recovery TurboFLASH sequence that makes it possible to acquire signal-time courses sequentially from 15 adjacent slices with a temporal sampling rate of 21 s. On the basis of the mathematically established and experimentally verified linear relationship between the measured saturation recovery TurboFLASH signal variation and the gadolinium diethylenetriaminopentaacetic acid concentration in the tissue, the signal-time courses were analyzed within the framework of pharmacokinetic modeling. In our study, the tissue response was parameterized adequately using an open linear two-compartment model. With this approach, the tissue specific information contained in the signal-time course can be described using only two parameters: an amplitude A, reflecting the degree of MR signal enhancement, and an exchange parameter k21, characterizing vascular permeability and perfusion of the tissue. A clearly arranged representation of the large amount of data (480 saturation recovery TurboFLASH breast images/examination) was accomplished by means of color coding of the computed parameters, resulting in one color-coded pharmacokinetic parameter map/cross-section.

Practical Approach for Determining Glomerular Filtration Rate by Single-Injection Inulin Clearance

We compared the glomerular filtration rate as measured by a single-injection inulin clearance with that measured by a standard isotope method with 99mTc-labeled diethylenetriaminopentaacetic acid in 21 subjects with glomerular filtration rates greater than 35 mL/min. After a bolus injection of 5 g of inulin, blood samples were taken 20, 45, 90, 120, 145, 180, and 240 min afterwards. Inulin was measured by optimized chemical or enzymatic methods of high analytical sensitivity to determine inulin at low concentrations. We used the one-compartment model and inulin concentrations measured at two sampling times to calculate the glomerular filtration rate from the data of the disappearance curve of inulin. Inulin concentrations at 20 and 240 min after injection of the inulin bolus were suited to estimate glomerular filtration rate by this procedure, resulting in values (y) comparable with those obtained by isotope technique (x). The relationship to the isotope technique was characterized by the equation y = +4.80 mL/min + 0.92x (r = 0.97). The single-injection inulin clearance determination can detect a decrease of glomerular filtration rate at the beginning of kidney damage, given that our study included subjects with glomerular filtration rates greater than 35 mL/min. We conclude that the glomerular filtration rate can be determined by analyzing only two blood samples after a bolus injection of inulin.

Monoclonal Antibodies to a Soluble Metallic Radioisotope Chelator: Development and Characterization

Monoclonal antibodies (MAbs) have been prepared with specificity for diethylenetriaminopentaacetic acid (DTPA) used to chelate metal radioisotopes to immunoglobulins for radioimmunoimaging and radioimmunotherapy. The use of fusion partners of lymph node-derived B cells resulted more frequently in the isolation of IgG secreting hybridomas than with splenocytes. All MAbs have been selected for simultaneous recognition of chelated and unchelated DTPA, and have been characterized in their biochemical, physico-chemical and immunochemical features. In view of the potential use in development of bifunctional MAb, these novel MAbs were also proven to lack detectable cross-reactivity with normal human tissues.

Idiopathic gastroparesis in patients with unexplained nausea and vomiting

Nausea and vomiting are symptoms sometimes associated with motor dysfunction. We compared a group of young patients suffering from chronic nausea and/or vomiting and normal upper gastrointestinal x-ray series with a control group. The members of both groups underwent isotopic examinations of their stomachs. The aim of the study was to find a simple method of checking the stomach and proving a motor dysfunction in a group of patients with chronic, inexplicable nausea and vomiting. Patients and controls fasted for at least 6 hr were given 0.5 mCI of [99mTc] diethylene triaminopentaacetic acid orally in 150 cc milk with 50 g cornflakes. A time-activity curve was obtained and radioactivity over the stomach was recorded exponentially. The parameter of the T1/2 emptying time was used. In normal controls T1/2 emptying time ranged from 18 to 26 min. Twenty-five symptomatic patients were examined, three of whom achieved normal values, but 22 patients showed pathologic results ranging from 36 to 184 min. In patients with chronic nausea and/or vomiting an isotopic examination of the stomach may provide a simple and rapid diagnostic method of evaluation.