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Biomedical subjects

P J Ell

Publications and source records attributed to P J Ell.

At least 19 recordsLinked to original sources
PubMed1992

Clozapine, single photon emission tomography, and the D2 dopamine receptor blockade hypothesis of schizophrenia.

According to the dopamine hypothesis of schizophrenia, D2 receptor blockade is essential for a drug to have antipsychotic potency, and antipsychotic potency and D2 blockade are linearly related in vitro. To test this assumption in vivo, we have compared clinical response with central D2 dopamine receptor availability measured by 123I-iodobenzamide single photon emission tomography in two groups of schizophrenic patients. 6 patients were on typical antipsychotic drugs and 10 were on the atypical antipsychotic clozapine, including 2 patients from the first group. The patients on typical antipsychotics showed poor therapeutic response despite D2 receptor blockade. Significant clinical improvement occurred in all patients on clozapine, but at a lower level of D2 blockade by the drug. These findings suggest a more complex relation between D2 blockade and clinical efficacy than was previously thought.

Adult↗
PubMed1992

Magnetic resonance imaging during dobutamine stress in coronary artery disease.

Cine magnetic resonance imaging (MRI) provides a tomographic method of assessing regional ventricular function in any desired plane. It has not been possible to obtain adequate images during dynamic exercise, and this has limited its value in patients with coronary artery disease (CAD). Therefore, an infusion of dobutamine was used to study 25 patients with exertional chest pain and abnormal exercise electrocardiograms. Areas of abnormal wall motion were compared with areas of abnormal myocardial perfusion imaged by dobutamine thallium emission tomography and with coronary arteriography. Twenty-two patients had significant CAD. Twenty-one (96%) of these patients had reversible myocardial ischemia shown by dobutamine thallium tomography, and 20 (91%) had reversible wall motion abnormalities shown by dobutamine MRI. Comparison of abnormal segments of perfusion and wall motion showed 96% agreement at rest, 90% agreement during stress, and 91% agreement for the assessment of functional reversibility. The normalized magnetic resonance signal intensity of the ischemic segments showed a small but significant reduction when compared with that of normal segments (-67 units [9.2%]; p less than 0.05). Dobutamine infusion was well-tolerated, despite causing chest discomfort in 24 patients (96%). Nine patients (36%) developed a minor dysrhythmia that was usually ventricular premature complexes, but this did not limit infusion, and other side effects were mild. The short plasma half-life of dobutamine makes it ideal as a stress agent for imaging techniques (such as MRI), and these results suggest that it is more effective in the provocation of wall motion abnormalities than is dipyridamole in patients with CAD.

Adult↗
PubMed1992

Preoperative imaging of colorectal cancers. Targeting the epithelial membrane antigen with a radiation-labeled monoclonal antibody.

The epithelial membrane antigen (EMA) is expressed by the majority of colorectal cancers but has not previously been investigated as a target for radiation-labeled monoclonal antibodies (MoAb) in the imaging of patients with colorectal cancer. A rat IgG2a MoAb that recognizes EMA, ICR2, was labeled with Indium-111 (100 megabecquerel per milligram [MBq/mg]MoAb) using the bicyclic anhydride of the chelating agent diethylene triamine pentacetic acid (ccDTPA) and was administered intravenously to 22 patients known to have or thought to have colorectal cancer. Daily gamma camera imaging was performed for 3 days during the time between the administration of the radiation-labeled antibody and surgical procedure. At operation, the biopsies were done of the tumors and the normal colon, and the uptake of radiation-labeled MoAb was measured in a gamma well-counter. Immunocytochemistry for EMA expression also was done on resected tumors. Independent unblinded and blinded reporting was done on all scans. The sensitivity of 111In-ICR2 for detecting cancers preoperatively was 80% and 60%, respectively, on unblinded and blinded reporting, and the corresponding specificity 20% and 60%. The low unblinded specificity was attributable to a false-positive localization in severely dysplastic benign tumors (n = 2) and inflammatory tissue (n = 2). Liver metastases present in three patients were cold relative to normal liver. Lymph node metastases were localized in 1 of 6 patients preoperatively. The mean absolute uptake of 111In-ICR2 in tumor tissue was 7.75 +/- 3.77 x 10(-3) percent of injected dose per gram, and the ratio to normal colon was 2.10 +/- 0.92:1. On immunohistochemistry, EMA was expressed by 16 of the 17 primary cancers, both dysplastic adenomas, and all nodal metastatic deposits. EMA-negative tumors (1 cancer + 1 colonic lipoma) had negative antibody scans, and patients whose tumor was negative or only focally positive for EMA expression had lower tumor/normal colon ratios of radioactivity (1.30 +/- 0.26 versus 2.45 +/- 0.65, P = 0.005) on gamma well-counting of excised specimens. These results suggest a possible role for 111In-ICR2 in the detection of colorectal cancer and metastases but not its liver deposits.

Aged↗
PubMed1992

Physical assessment of the GE/CGR Neurocam and comparison with a single rotating gamma-camera.

The GE/CGR Neurocam is a triple-headed single photon emission tomography (SPET) system dedicated to multi-slice brain tomography. We have assessed its physical performance in terms of sensitivity and resolution, and its clinical efficacy in comparison with a modern, single rotating gamma-camera (GE 400XCT). Using a water-filled cylinder containing technetium-99m, the tomographic volume sensitivity of the Neurocam was 30.0 and 50.7 kcps/MBq.ml.cm for the high-resolution (HR) and general-purpose (GP) collimators, respectively; the corresponding values for the single rotating camera were 7.6 and 12.8 kcps/(MBq/ml)/cm. Tomographic resolution was measured in air and in water. In air, the Neurocam resolution at the cente of the field-of-view (FOV) is 9.0 and 10.7 mm full width at half-maximum (FWHM) with the HR and GP collimators, respectively, and is isotropic in the three orthogonal planes; the resolution of the GE 400XCT with 13 cm radius of rotation is 10.3 and 11.7 mm, respectively. For the Neurocam with the HR collimator, the transaxial FWHM values in water were 9.7 mm at the centre and 9.5 mm radial (6.6 mm tangential) at 8 cm from the centre. The physical characteristics of the Neurocam enable the routine acquisition of brain perfusion data with technetium-99m hexamethyl-propylene amine oxime (99mTc-HMPAO) in about 14 min, yielding better image quality than with a single rotating camera in 40 min.

Brain↗
PubMed1992

Atrial fibrillation after intravenous dipyridamole for thallium imaging.

Dipyridamole 0.56 mg/kg was administered intravenously for thallium tomography after myocardial infarction. Fast atrial fibrillation developed which failed to resolve with aminophylline. Sinus rhythm returned within 3 days. Myocardial tomography revealed apical infarction without reversible ischaemia. Atrial fibrillation after dipyridamole is rare and may be caused by direct electrophysiological effects on the atrial myocardium.

Atrial Fibrillation↗
PubMed1992

The use of thallium-201 lung/heart ratios.

This survey gives an overview of the methodology of thallium-201 lung/heart uptake ratios often used as an independent factor in the assessment of patients with coronary artery disease undergoing myocardial perfusion scintigraphy. Different techniques have been used in the past. The most sensitive method is one which calculates a lung/heart ratio from scintigraphy obtained immediately after cessation of exercise. If single photon emission tomography (SPET) is routinely performed the anterior projection of the data set obtained during tomographic acquisition should be used in preference to a separate planar anterior static images recorded before or after the SPET procedure. The lung/heart ratio is useful as a prognostic indicator of outcome as it accurately mimics the degree of left ventricular dysfunction. With the increasing popularity of pharmacological stress testing there is evidence that this ratio still offer valid information. Additional work in this field is nevertheless required to further confirm this observation. In routine clinical practice, the lung/heart ratio should help and enable physicians to prioritise patients for urgent intervention.

Coronary Disease↗
PubMed1992

Demonstration of human motor cortex activation using SPECT.

Recent advances in single photon emission computed tomography (SPECT) have allowed improved image resolution with lower doses of labelled tracer. Capitalizing on these improvements, the authors have developed a new SPECT protocol for imaging neuronal activation. We outline this technique and describe how it can demonstrate increased human motor cortex activity in normal subjects performing a motor task. The ability to accurately demonstrate neuronal activation with SPECT using this method may have important scientific and clinical implications.

Adult↗
PubMed1992

Direct effect of dobutamine on action potential duration in ischemic compared with normal areas in the human ventricle.

BACKGROUND AND OBJECTIVES: The arrhythmogenic effect of beta-adrenoceptor stimulation is complex and may differ in ischemic and normal myocardium. In this study we examined the differential effect of beta-adrenergic stimulation on ventricular action potential duration and, hence, dispersion of repolarization in potentially ischemic versus nonischemic human ventricular myocardium. METHODS: Simultaneous biventricular monophasic action potentials were recorded in 14 patients (28 recording sites) during infusion of dobutamine in incremental doses (low dose 5 micrograms/kg per min, high dose 10 to 15 micrograms/kg per min) during atrial pacing. Perfusion at the action potential recording site was assessed by incorporating myocardial perfusion scintigraphy with injection of technetium-99m hexakis-2-methoxy-2-methylpropyl-isonitrile during the recording at peak doses of dobutamine. Action potential duration during dobutamine infusion was compared with that during atrial pacing to identical rates in the absence of dobutamine. RESULTS: In 21 normal zone recordings, dobutamine produced a variable effect over that produced by atrial pacing to identical heart rates, either lengthening or shortening the action potential duration. The mean (+/- SEM) value for the additional effect of dobutamine was 0.9 +/- 2.5 ms with low doses and -4 +/- 2.6 ms with high doses (p = NS). In seven recordings from potentially ischemic zones, low dose dobutamine had a similar effect (mean change -3.4 +/- 6.5 ms; p = NS vs. normal zone values). However, the high dose dobutamine invariably shortened the action potential duration by a mean of -22.9 +/- 2.9 ms. (p less than 0.05 vs. low dose in ischemic areas, p less than 0.01 vs. normal zone recordings). Pacing alone or the addition of dobutamine had no significant effect on the normal dispersion of action potential duration between two nonischemic recording sites. In recordings in a normal and an abnormally perfused site, high dose dobutamine significantly altered the dispersion of action potential duration. CONCLUSIONS: These results suggest a different effect of beta adrenergic stimulation in potentially ischemic compared with nonischemic human ventricular myocardium. The abnormal dispersion of repolarization thus created may well be important in beta-receptor-mediated arrhythmogenesis during myocardial ischemia.

Action Potentials↗
PubMed1992

Elevated frontal cerebral blood flow in Gilles de la Tourette syndrome: a 99Tcm-HMPAO SPECT study.

Case reports, numerous brain imaging studies, and certain disease states suggest that the orbital frontal cortex and the striatum are dysfunctional in obsessive-compulsive disorder (OCD). Interest has also grown recently concerning the genetic, neuroanatomic, and clinical links between OCD, chronic motor tics, and Gilles de la Tourette Syndrome (GTS). To test the hypothesis of possible orbito-frontal/basal ganglia dysfunction in GTS, similar to OCD, we studied 20 unmedicated GTS subjects, 10 of whom also had comorbid OCD (GTS/OCD), and 8 control subjects. The subjects were examined with high-resolution single photon emission computed tomography (SPECT) and the labeled regional cerebral blood flow (rCBF) ligand technetium-99m-d,l-hexamethyl-propylene amine oxime (99Tcm-HMPAO). As a group, GTS subjects showed significantly elevated right frontal/visual cortex activity (mean = 0.879, SD = 0.107) compared with control subjects (mean = 0.798, SD = 0.049). A subanalysis comparing simple GTS versus GTS with comorbid OCD failed to reveal significant differences in regional flow.

Adult↗
PubMed1992

The interrelation between the monophasic action potential duration, cycle length and ischaemia in the human left ventricle.

Steady state monophasic action potentials were recorded from a single site in the left ventricular endocardium during incremental atrial pacing to the point of angina in 25 patients. Ischaemic areas of the left ventricle were documented using a perfusion marker (99mTc-MIBI) simultaneously with the action potential recording procedure. Recordings were obtained from an ischaemic area in 13 patients and from a non-ischaemic area in 12. A linear correlation between action potential duration and cycle length changes was demonstrated for both ischaemic and non-ischaemic zone recordings between cycle length changes of 750 and 428 ms. Ischaemia induced a shortening of the action potential duration significantly greater than that produced by cycle length changes (P less than 0.0001). Mean action potential duration shortening corrected for 100 ms change in cycle length for ischaemic zone recordings was 31.4 +/- 4.2 (SD) compared to 23.3 +/- 3.1 ms for non-ischaemic zone recordings. A range of values of action potential duration shortening in unit time was analysed for sensitivity and specificity for the detection of ischaemia. A value of 26.5 ms per 100 ms change in cycle length provided the optimum compromise with 88% sensitivity and specificity. Our data provide a means of employing the monophasic action potential duration to quantify early localized ischaemia in the presence of an alteration in cycle length.

Action Potentials↗
PubMed1992

Cerebral blood flow abnormalities in adults with infantile autism.

Structural brain abnormalities have recently been discovered using magnetic resonance imaging in infantile autism, a neurodevelopmental disorder of unknown etiology. However, functional neuroimaging studies in autism using positron emission tomography have had conflicting results and have not explained how the known structural brain abnormalities in autism act in a functioning brain to produce autistic behavior. Using a new technology, high-resolution brain single photon emission tomography, we studied and scanned four young adults with infantile autism and four age-matched controls using the labeled ligand 99mTc-D,L-hexamethyl-propylene amine oxime (99mTc-HMPAO). Total brain perfusion was significantly decreased in autism subjects (range, 58% to 72% of controls, p less than or equal to .02). In addition to the globally decreased perfusion, the autism group also had regionally decreased flow in the right lateral temporal and right, left, and midfrontal lobes compared with controls (p less than or equal to .02, Mann-Whitney t-test).

Adult↗
PubMed1992

Hepatobiliary scintigraphy in the diagnosis of AIDS-related sclerosing cholangitis.

Twenty human immunodeficiency virus (HIV)-positive patients were studied who presented with right upper quadrant abdominal pain, with or without abnormal biochemical liver function tests, in whom AIDS-related sclerosing cholangitis (ASC) was suspected. The results obtained from hepatobiliary scintigraphy using 99Tcm-IODIDA were compared with data from endoscopic retrograde cholangiopancreatography (ERCP), ultrasound and histological data from liver biopsy or post mortem. 99Tcm-IODIDA was abnormal in 14 patients. Liver biopsy, ERCP or post mortem confirmed ASC in 11 patients of whom 10 had an abnormal 99Tcm-IODIDA study. Ultrasound was performed in eight of the patients with confirmed ASC but was abnormal in only five of these. One patient with mild ASC on ERCP and Kaposi's sarcoma had a normal 99Tcm-IODIDA. In HIV-positive patients with right upper quadrant pain, imaging with 99Tcm-IODIDA provides a non-invasive screening test which may help to determine those patients who should be referred for ERCP.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Assessment of myocardial viability with 201Tl SPET and reinjection technique: a quantitative approach.

The definition of viable myocardium after an acute myocardial infarction (MI) is important as it will determine which therapeutic option will be best for the patient. In 201Tl scintigraphy it has been shown that late redistribution (8-24 h) or reinjection may help to identify viable myocardium which does not appear to reperfuse on the 4 h redistribution image. In a prospective study 20 patients with a persistent defect seen on both stress and redistribution images were imaged after reinjection of 201Tl. On visual analysis a total of 180 segments were studied, 85 were normal, 18 reperfused at redistribution and a further nine (in six patients) after reinjection. Bull's-eye analysis at stress demonstrated a mean defect size of 279 pixels, S.D. +/- 74. After redistribution, there was no significant change in mean defect size (227 +/- 96 pixels). At reinjection, there was a significant reduction in mean defect size (189 +/- 107 pixels) (P < 0.05, paired 't'-test). Quantification shows a significant reduction in defect size between stress and reinjection. The use of the 201Tl reinjection technique in patients with a fixed perfusion deficit on stress and redistribution images improves the detection of viable myocardium and is to be preferred to a method of redistribution analysis alone.

Adult↗
PubMed1992

Vasodilator myocardial perfusion imaging: demonstration of local electrophysiological changes of ischaemia.

OBJECTIVE: To examine the incidence and severity of myocardial ischaemia provoked in the course of perfusion scintigraphy by coronary vasodilators using endocardial recordings of steady state monophasic action potentials as an independent marker of early localised myocardial ischaemia. PATIENTS: 31 men undergoing routine cardiac catheterisation for investigation of chest pain were studied. SETTING: A tertiary cardiac referral centre. DESIGN: Single site monophasic action potentials were recorded from the left or right ventricle or both (50 recording sites) during intravenous infusion of dipyridamole (0.015 mg/kg/min) for four minutes. Heart rate was held constant with atrial pacing at 20% above the patient's resting rate. Technetium-99m hexakis-2-methoxy-2-methylpropyl-isonitrile (MIBI) was administered four minutes after dipyridamole, and single photon emission tomographic imaging was performed an hour later. Rest images were obtained the next day (two day, two dose protocol). Recordings were divided into three groups based on the scintigraphic perfusion characteristics and coronary anatomical data for the action potential recording site: group 1--recordings from areas with a normal perfusion pattern (n = 30), group 2--recordings from areas with a perfusion defect and subtended by significantly narrowed coronary arteries without obvious angiographic collateral supply (n = 10), and group 3--recordings from areas with a perfusion defect and subtended by occluded arteries with angiographically evident collaterals from adjacent vessels (n = 10). RESULTS: There were changes in the duration of the monophasic action potential indicative of ischaemia--that is, shortening of duration of steady state action potential--in 18 of the 20 recordings from areas of abnormal perfusion. Peak changes were apparent eight minutes from the start of the dipyridamole infusion. Mean (SEM) values for duration of the action potential between control and peak effect at eight minutes were 276.5 (5.3) ms v 276.6 (5.4) for group 1 (NS), 289.6 (4.7) ms v 278.4 (4.9) ms for group 2 (p less than 0.001), and 269.6 (5.7) ms v 242.0 (4.4) for group 3 (p less than 0.0001). These changes were significantly different between the three groups (p less than 0.01). ST segment changes on the surface electrocardiogram were seen in only eight patients, all with areas of viable myocardium supplied by collateral vessels. CONCLUSIONS: These data provide strong evidence for the presence of myocardial ischaemia in regions of reversible perfusion defects induced by dipyridamole. This study also shows that such ischaemia is more intense and more likely to be seen when myocardial viability is dependent on collateral circulation.

Action Potentials↗
PubMed1992

Effect of vigabatrin on striatal dopamine receptors: evidence in humans for interactions of GABA and dopamine systems.

Vigabatrin is a specific gamma-aminobutyric acid transaminase inhibitor. The clinical use of this drug in the treatment of epilepsy has been sporadically linked to the development of psychosis. Using 123I-IBZM, a specific dopamine D2 receptor ligand and single photon emission tomography (SPET), one month of treatment with vigabatrin was associated with a decrease in specific binding of 123I-IBZM to D2 receptors in the left hemisphere basal ganglia. This change may provide one explanation for the development of psychosis in vulnerable patients.

Adolescent↗
PubMed1992

Nuclear medicine.

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Bone Diseases↗