Effectiveness of 99mTc-tetrofosmin for assessment of heart functions in micropigs

This study examined the suitability of a nuclear imagingtechnique using 99mTc-tetrofosmin as an agent to assess theheart functions of healthy micropigs. The mean age of thepigs was 360 days (male), and the mean body weight was35.3kg ranging from 34.5-36kg. There were no significantperfusion defects in any of the reconstructed images.Gated single-photon emission computed tomographyimaging can be used to calculate the ventricular volumeand ejection fraction (EF). In this case, an EF of 79% wascalculated from the ventricular volume of the end-systolicimage (10 ml) subtracted from that of the end-diastolicvolume (49 ml). A perfusion defect (particularly the apex,lateral wall) is unlikely because of the presence of apreserved wall motion in a segment with a defect. It isconcluded that quantitative cardiac scintigraphy, using99mTc-tetrofosmin is an adequate technique for estimatingthe heart functions of healthy micropigs.

Development and Evaluation of Classification Codes and Retrieval Program of the Interpretation of Nuclear Medicine Imaging Studies / 대한의료정보학회지

OBJECTIVE: To evaluate usefulness of the classification codes and retrieval program of the interpretation of nuclear medicine imaging studies. METHODS: We retrieved specific results of the interpretation of 3,613 nuclear medicine imaging studies from database server of the Chonnam National University Hwasun Hospital using classification code retrieval program or by searching narrative phrases using structured query language(SQL). Accuracy of the retrieved results as well as retrieval time in each group were compared. RESULTS: Retrieved results using SQL showed lower accuracy than those using classification codes. There was no delay of response or overload of network traffic whether we used either retrieval program or SQL. CONCLUSION: Retrieval of specific results from database of the interpretation of nuclear medicine imaging studies using classification codes with retrieval program was more accurate and convenient than searching narrative phrases using SQL.

Recent Progress in Medical Imaging: Mloecular Imaging in Living Subjects / 대한의료정보학회지

Recent progress in the development of non-invasive imaging technologies continues to strengthen the role of molecular imaging biological research. These tools have been validated recently in variety of research models, and have been shown to provide continuous quantitative monitoring of the location(s), magnitude, and time-variation of gene delivery and/or expression. This article reviews the use of radionuclide, magnetic resonance, and optical imaging technologies as they have been used in imaging gene delivery and gene expression for molecular imaging applications. The studies published to date demonstrate that noninvasive imaging tools will help to accelerate pre-clinical model validation as well as allow for clinical monitoring of human diseases.

Differential Effects of Green Tea Polyphenol in the gamma-irradiation Induced Human Leukemic and Lymphoblastic Cell Damage / 대한핵의학회잡지

PURPOSE: The green tea polyphenol (GTPP) has been known to exert antioxidant activity as a radical scavenger as well as cancer preventive and cancer growth inhibition effect. The aim of this study was to identify whether GTPP not only potentiate the growth inhibition effect in gamma-irradiated human cancer cell but also exert protection action for irradiated human normal cell. MATERIALS AND METHODS: GTPP (80% catechin including > 45% EGCG) added in the HL60, human leukemia, and NC37, human lymphoblast, before irradiation. After establishing the amount of GTPP and the dose of radiation, the cells were treated with the GTPP for 6 hours and irradiated with the determined doses. RESULTS: Viability when 10 mug/ml GTPP added before gamma-irradiation with 1 Gy to NC37 cells was not different in comparison with control but it when was irradiated with 3 Gy significantly different (1 Gy; P=0.126, 3 Gy; P=0.010). 20 mug/ml GTPP did not show significant difference in both NC37 cells irradiated with 1 Gy and 3 Gy (1 Gy; P=0.946, 3 Gy; P=0.096). Viabilities were significantly decreased with concentration of additional GTPP in HL60 with 1 or 3 Gy (1 Gy; 69.0+/-1.7% vs 42.4+/-1.3%, 3 Gy; 66.9+/-3.9% vs 44.2+/-1.6 %). CONCLUSION: In vitro study, we certified that when the cells were irradiated with dose below 3 Gy, GTPP provide not only anticancerous effect against cancer cells but also radioprotective effect in normal cells simultaneously. Theses results suggest the possibility that consumption of green tea could give the radioprotective effect and maximize the effect on internal radiation such as radioiodine therapy concomitantly.

Preoperative Cisternoscintigraphy As a Guide to Therapeutic Decision Making for Cystic Subdural Hygroma / 대한핵의학회잡지

We report a case of a patient with cystic subdural hygroma who underwent pre-operative Tc-99m DTPA cistrenoscintigraphy to determine the course of operation. A 68-year-old female was admitted to the department of neurosurgery because of acute subarachnoid hemorrhage. After emergency ventricular drainage, the hydrocephalus and cystic subdural hygroma in the right fronto-temporal area developed. She underwent Tc-99m DTPA cisternoscintigraphy to evaluate the type of hydrocephalus, which revealed obstructive communicating hydrocephalus and the communication between the subdural hygroma and the subarachnoid space. As a result of these findings, she underwent the ventriculo-peritoneal shunt operation without removal of the subdural hygroma. Post-operative brain CT showed nearly normalized shape and size of the right ventricle and disappearance of subdural hygroma. We recommend the pre-operative cisternoscintigraphy in patients with complex hygroma to evaluate the communication between subdural hygroma and the subarachnoid space.

Development of a Noble Dosimetry Using Metaphase Analysis and Micronuclei Assay of Bone Marrow Cells in Mice / 대한핵의학회잡지

PURPOSE: The purpose of this study was to develop in vivo dosimetries using both chromosomal aberrations and micronuclei in mice to assess biological effects of radiations. MATERIALS AND METHODS: Five each mice were irradiated with 0, 1, 2, 3, 4, 5, 10 Gy of Cs-137 gamma-rays. We scored numbers of chromosomal aberrations in metaphase spreads and numbers of micronuclei in bone marrow smears under light microscope, and obtained the dose-response relationships. We also examined the relationship between the two dose-response curves. RESULTS: The frequency of both chromosomal aberrations and micronuclei increased with dose, in a linear-quadratic manner. The delta, beta, and alpha coefficients were 0.0176, 0.0324, and 0.0567 for metaphase analysis (r=1.0, p<0.001) and 0.0019, 0.0073, and 0.0506 for micronuclei assay (r=1.0, p<0.001). The frequency of chromosomal aberrations and micronuclei in diffirent radiation doses was significantly correlated (r=0.99, p<0.01). CONCLUSION: In vivo dosimetry using either metaphase analysis or micronucleus assay was feasible in mice. These methods could be useful to evaluate biological effects of radiation.

Sialolithiasis Mimicking Metastatic Thyroid Cancer / 대한핵의학회잡지

We report a false positive case of I-131 scan due to a sialolithiasis in right submandibular gland. I-131 images showed not only remnant thyroid tissues and functional metastases in the anterior neck but also a hot uptake near right submandibular gland. We confirmed the sialolithiasis by radiologic studies. Sialolithiasis should be regarded as a false positive cause when I-131 scan shows a hot spot near salivary bed.

Relationship between Radiation Induced Activation of DNA Repair Genes and Radiation Induced Apoptosis in Human Cell Line A431 / 대한핵의학회잡지

PURPOSE: The purpose of this study was to evaluate the relationship between radiation-induced activation of DNA repair genes and radiation induced apoptosis in A431 cell line. MATERALS AND METHODS: Five and 25 Gys of gamma radiation were given to A431 cells by a Cs-137 cell irradiator. Apoptosis was evaluated by flow cytometry using annexin V-fluorescein isothiocyanate and propidium iodide staining. The expression of DNA repair genes was evaluated by both Northern and Western blot analyses. RESULTS: The number of apoptotic cells increased with the increased radiation dose. It increased most significantly at 12 hours after irradiation. Expression of p53, p21, and hRAD50 reached the highest level at 12 hours after 5 Gy irradiation. In response to 25 Gy irradiation, hRAD50 and p21 were expressed maximally at 12 hours, but p53 and GADD45 genes showed the highest expression level after 12 hours. CONCLUSION: Induction of apoptosis and DNA repair by ionizing radiation were closely correlated. The peak time of inducing apoptosis and DNA repair was 12 hours in this study model. hRAD50, a recently discovered DNA repair gene, was also associated with radiation-induced apoptosis.

Comparison of Radiation Adaptive Responses in Peripheral Lymphocytes of Patients Undergoing Tc-99m MDP and Tc-99m DTPA Scintigraphies / 대한핵의학회잡지

PURPOSE: The purpose of this study was to compare the radiation adaptive response (RAR) in peripheral lymphocytes (PL) of patients induced by Tc.-99m MDP and Tc-99m DTPA scintigraphies. MATERIALS AND METHODS: Lymphocytes from 45 patients (25 males, 20 females, mean age 44+/-18 years) were collected before and after scintigraphies using 740 MBq Tc-99m MDP (n=22) or Tc-99m L)TPA (n=23). Lympho-cytes from 20 controls (12 males, 8 females, mean age 43+/-7 years) were also callected. They were exposed to challenge dose of 2 Gy gamma-rays using a Cs-137 cell irradiator, Number of ring-form (R) and dicentric (D) chromosomes was counted under the light microscope. From them a representative score, Ydr, was calculated as Ydr=(D+R)/cells. Adaptation index (AI) was defined as difference of Ydr between unconditioned and conditioned lymphocytes. Ydr was also measured after an administration of cyclohexi-mide (CHM), a protein synthesis inhibitor, before challenge dose. RESULTS: RAR was induced in both groups of patients. CHM abolished the adaptive response in both groups. AI of Tc-99m MDP group was significantly higher than that of Tc-99m DTPA group. CONCLUSION: Tc-99m MDP induced RAR was more prominent than those induced by Tc-99m DTPA.

Role of Dacryoscintigraphy in the Diagnosis and Treatment of Pediatric with Epiphora / 대한핵의학회잡지

PURPOSE: We conducted this study to evaluate the role of dacryoscintigraphy in the diagnosis and treatment of pediatric patients with epiphora. MATERIALS AND METHODS: In 58 patients aged from 2 months to 15 years (mean age 2.8+/-2.3 years), dacryoscintigraphy was performed using a gamma camera with 4 mm pinhole collimator. We correlated symptoms with dacryosicntigraphic findings in all patients. In 37 patients who underwent ophthalmologic procedures, we analyzed the agreements of dacryoscintigraphic findings with the operation. RESULTS: High rates of agreements between epiphora and obstruction on dacryoscintigraphy (69/72, 95.8%), and between scintigraphic obstructive findings and operation sites (44/47, 93.6%) were noted. Nine of fourty-four (20.5%) asymptomatic eyes showed obstructive findings on dacroscintigraphy. CONCLUSION: In pediatric patients with epiphora, dacryoscintigraphy is a useful tool not only in diagnosing nasolacrimal duct obstruction but also in making a decision for therapeutic procedures.

Change of Cerebral Blood Flow Distribution and Vascular Reserve according to Age in Koreans Measured by Tc-99m HMPAO Brain SPECT / 대한핵의학회잡지

PURPOSE: The aim of this study was to evaluate the normal values of regional cerebral blood flow (rCBF) and cerebrovascular reserve (CVR) in normal children to aged volunteers using Tc-99m HMPAO. MATERIALS AND METHODS: Thirty four right-handed normal volunteers (20 males, 14 females, mean age 40.3+/-24.9 years, range 4 to 82 years) were underwent rest/acetazolamide (ACZ) brain SPECT using Tc-99m HMPAO and the sequential injection and subtraction method. rCBF was estimated on the basis of a semiquantitative approach by means of right/left ratio, region/cerebellum and region to whole brain ratios in frontal, parietal, temporal, and occipital lobes, basal ganglia, thalami, and cerebellum. CVR was measured by means of % perfusion increase calculated as % mean count change compared to rest rCBF in each regions. RESULTS: Mean values of right to left ratios range from 1.004 to 1.018. rCBF was highest in cerebellum and lowest in basal ganglia and thalami. Frontal and temporal rCBF decreased while occipital and thalamic rCBF increased according to age. No sexual difference of rCBF was noted. Mean CVR was 29.9+/-12.9%. Mean CVR significantly increased to late teens, and declined thereafter. After 6th decade, CVR in both frontal lobes, left parietal lobe and right basal ganglia decreased significantly with advancing age. There was no sexual difference of CVR. CONCLUSION:: Quantitative assessment of CVR was possible by ACZ Tc-99m HMPAO brain SPECT. It revealed that rCBF and CVR changed according to age in normal Korean volunteers. There was no sexual difference.

Induction of Radiation Adaptive Response in Lymphocytes of patients Undergoing Bone Scintigraphy / 대한핵의학회잡지

PURPOSE: The purpose of this study was to ascertain whether radiation adaptive response could be induced by Tc-99m-methylene diphosphonate (Tc-99m-MDP) in peripheral lymphocytes of patients undergoing bone scintigraphy. MATERIALS AND METHODS: Lymphocytes from 22 patients (6 males, 16 females, mean age 50+/-14 years) were collected before and after bone scintigraphy using 740 MBq Tc-99m-MDP. Lymphocytes from 10 controls (6 males, 4 females, mean age 43+/-7 years) were also collected. They were exposed challenge dose of 2 Gy gamma rays using a cell irradiator Number of ring-form and dicentric chromosomal per 600 cells (chromosomal aberrations) was counted under the light microscope. RESULTS: Chromosomal aberrations in patients before bone scintigraphy (385.1+/-30.5) was not different from that of controls (367.8+/-36.6). However, chromosomal aberrations in patients after bone scintigraphy was significantly decreased 192.6+/-22.1 (p=0.0001). CONCLUSION: Low dose gamma-irradiation by Tc-99m-MDP used for bone scintigraphy induces a cytogenetic adaptive response in peripheral lymphocytes.

A Comparison Study of Metaphase Analysis of Chromosomal Aberration and Flow Cytometric Assessment of Radiation- induced Apoptosis in Human Peripheral Lymphocytes / 대한핵의학회잡지

PURPOSE: Radiation-induced chromosomal damage and apoptosis were compared in human lymphocytes. MATERIALS AND METHODS: Peripheral lymphocytes from 10 normal volunteers (6 males, 4 females, age range 23~41 years) were irradiated by gamma rays from a cell irradiator. Doses of irradiation were 0 (control), 0.18, 2, 5, 10, 20 and 25 Gy. Irradiated lymphocytes were examined by metaphase analysis for chromosomal aberrations and by flow cytometry for apoptosis. RESULTS of both studies were compared according to dose. RESULTS: Number of dicentric and ring chromosomes (D+R) was 0.5+/-0.53 at baseline, which was significantly increased after radiation according to the dose. The fraction of cells showing annexin V-fluore-scein isothiocyanate uptake was 0.55+/-0.39%, which increased to 3.58+/-1.85% by 2 Gy irradiation, and then decreased. The fraction of cells showing propidium iodide (PI) uptake was 0.52+/-0.12%, which significantly increased according to dose (upto 15.64+/-5.99% by 20 Gy irradiation). D+R and PI uptake were well correlated (r=0.84, p<0.001). CONCLUSION: Radiation-induced chromosomal aberration was correlated to nuclear uptake of PI, a marker of late apoptosis.

Alterations in Myocardial Perfusion and Regional Wall Motion in Patients with Permanent Pacemaker

BACKGROUND: The effect of right ventricular pacing on myocardial perfusion and regional wall motion is not well known, although some studies have suggested that it may be adverse. We investigated the effects of right ventricular pacing on myocardial perfusion and regional wall motion in patients with permanent pacemakers. METHOD: Thirty patients receiving permanent pacemakers for complete heart block or sick sinus syndrome were included in this study. All the patients showed normal coronary angiograms. Myocardial scintigraphy and two-dimensional echocardiography were performed to assess myocardial perfusion and to evaluate regional wall motion and global function of the left ventricle (LV). RESULTS: 1) Mean age was 66.2+/-8.2 (41-84) years, and the male-to-female ratio was 1 : 1.7 (11 male, 19 female). Indications for permanent pacemaker implantation were complete atrioventricular (AV) block in 21 patients and sick sinus syndrome in 9. The selected pacing modes were VVI in 14 patients, DDD in 8, VDD in 6, and AAI in 2. LV ejection fraction estimated by 2-dimensional echocardiography was 62.7+/-5.8 (53-86)%. 2) Perfusion defects were noted in 26 (87%) patients including 25 (89%) out of 28 patients with ventricular pacing modes such as VVI, DDD, and VDD, and 1 (50%) out of 2 patients with AAI mode. Locations of perfusion defects were septal in 19 (63%) patients, inferior in 17 (57%), apical in 16 (53%), lateral in 3 (10%), and anterior in 2 (7%). Extent of maximal perfusion defects was 17.0+/-9.5 (0-44)%. 3) Regional wall motion abnormalities were noted mainly over the apical region of the LV in 26 (93%) of 28 patients with ventricular pacing. However, LV ejection fraction did not differ significantly before and early after implantation of the pacemaker (62.7+/-5.8% vs. 61.0+/-5.8%, p-0.313). CONCLUSIONS: Right ventricular apical pacing frequently caused myocardial perfusion defects and regional wall motion abnormalities. These might be due to abnormal ventricular activation and abnormal interventricular septal motion. The long-term effects of these abnormalities remain to be determined, and the pacing technique to minimize these adverse effects should be developed.

Gender Difference of Accuracy in Detecting Coronary Artery Disease by Myocardial Perfusion SPECT / 대한핵의학회잡지

PURPOSE: Myocardial SPECT is an effective test for detecting coronary artery disease in the general population. But the diagnostic accuracy between sexes is not defined. The purpose of this study is to compare the diagnostic accuracy between males and females. MATERIALS AND METHODS: One hundred and seventy seven male and 98 female patients who underwent myocardial SPECT within 1 month of coronary angiography were studied. Myocardial SPECTs were considered abnormal if fixed or reversible perfusion defects were detected. Stenosis severity of > or = 50% luminal diameter reduction of any artery defined coronary artery disease (CAD). RESULTS: Overall sensitivity for detection of CAD was 98% in men and 97% in women (p=not significant). However, specificities, accuracies, and positive predictive values (PPV) in men and women were 49% vs 31% (p<0.05), 81% vs 57% (p<0.01), 78% vs 48% (P<0.01), respectively Diagnostic accuracies for detection of right coronary artery disease were not different in both sexes, however, accuracies for detection of left anterior descending artery disease and left circumflex artery disease were significantly lower in female (p<0.05). CONCLUSION: A significant difference of diagnostic accuracy between sexes, especially in LAD and LCx disease, was noted. Artifacts from breast attenuation might be a cause for the lower diagnostic accuracy in female.

Comparison of 99mTc-tetrofosmin and 99mTc-sestamibi Myocardial Perfusion SPECT in Detecting Coronary Artery Fisease / 대한핵의학회잡지

PURPOSE: Tc-99m-tetrofosmin(TF) is a recently proposed myocardial imaging agent which has similar biokinetic characteristics to Tc-99m-sestamibi(MIBI). The aim of this study was to compare TF and MIBI myocardial perfusion SPECTs in detecting coronary artery disease. MATERIALS AND METHODS: One hundred and sixty patients(l0l males, 59 females, mean age 57+/-9 yr) who had undergone both myocardial perfusion SPECT (M- SPECT) and coronary angiography within 1 month were studied. M-SPECT was performed using TF in 115 patients and MIBI in 45 patients. Stress-rest one day protocol was used in all patients A coronary stenosis was considered significant when the luminal diameter > or =50% was compromised. The chi square test was used to compare, differences in sensitivity and specificity between the two groups. RESULTS: There was no difference in age and diseased coronary artery branches between the two groups. There were more male patients in TF group: Male-to-female ratios of TF and MIBI groups were 78:37 and 23:22, respectively (p<0.05). The overall sensitivity of TF study was 92% and specificity 36%. The overall, sensitivity and specificity of MIBI study were 93% and 30% respectively. There was no difference between TF and MIBI groups in identifying individual diseased coronary artery branches. CONCLUSION: One day stress-rest myocardial SPECT using either TF or MIBI was comparable and was a very sensitive test in detecting coronary artery disease.

Cytogenetic Radiation Adaptive Response Assessed by Metaphase Analysis and Micronuclei Test in Human Lymphocytes and Mouse Bone Marrow Cells / 대한핵의학회잡지

PURPOSE: Radiation adaptive response in human peripheral lymphocytes and mouse bone marrow cells was investigated using both metaphase analysis and micronucleus assay. We assessed the correlation between both tests. MATERIALS AND METHODS: Two groups of the human peripheral lymphocytes and mouse bone marrow cells were exposed to low dose (conditioning dose, 0.18 Gy) or high dose (challenging dose, 2 Gy) gamma-rays. The other 4 groups were exposed to low dose followed by high dose after several time intervals (4, 7, 12, and 24 hours, respectively). The frequencies of chromosomal aberrations in metphase analysis and micronuclei in micronucleus assay were counted. RESULTS: Chromosomal aberrations and micronuclei of preexposed group were lower than those of the group only exposed to high dose radiation. Maximal reduction in frequencies of chromosomal aberrations were observed in the group to which challenging dose was given at 7 hour after a conditioning dose (p<0.001). Metaphase analysis and micronucleus assay revealed very good correlation in both human lymphocytes and mouse bone marrow cells (r=0.98, p<0.001; r=0.99, p=0.001, respectively). CONCLUSION: Radiation adaptive response could be induced by low dose irradiation in both human lymphocytes and mouse bone marrow cells. There was a significant correlation between metaphase analysis and micronucleus assay

Tc-99m Myocardial Perfusion SPECT Findings of Angina Patients Showing Normal Coronary Angiography

BACKGROUND: Tc-99m myocardial perfusion imaging agents have recently found wide spread use as detecting agents of coronary diseases. Unfortunately, false positive results are not infrequent. METHODS: We analyzed Tc-99m myocardial perfusion SPECT (Tc-SPECT) findings in angina patients showing normal coronary angiography. Seventy patients who underwent myocardial SPECT wihin one month of coronary angiography which revealed no significant stenosis were studied. RESULTS: Forty six (65.7%) patients showed perfusion defects on Tc-SPECT. Eighteen were due to soft tissue attenuation, thirteen were due to technical problems such as low count rate, six were associated with intraventricular conduction abnormalities, four with coronary spasms, three with old infarctions, and one with slow coronary flow. CONCLUSION: Photon attenuation and inadequate count rates were the main causes of false positive results on myocardial SPECT imaging with Tc-99m agents. However, pathological conditions such as conduction disturbance, coronary spasm or slow coronary flow were also associated with positive SPECT findings in patients with normal coronary angiograms.

Comparison of Stress-rest and Rest-stress One Day Myocardial Perfusion Scintigraphies in Detecting Coronary Artery Diseases / 대한핵의학회잡지

It has been shown that both rest and stress myocardial perfusion imagings with technetium agents can be performed on the same day using two different doses injected within few hours. The purpose of this study was to compare the two protocols (stress-rest and rest-stress) in detecting coronary artery diseases. One hundred and sixty patients (101 males, 59 females, mean age 57+/-9 years) and 120 patients (79 males, 41 females, mean age 59+/-10 years) underwent stress-rest myocardial perfusion SPECT and rest-stress myocardial perfusion SPECT, respectively All of them underwent both myocardial perfusion SPECT and coronary angiography within 1 month. A coronary stenosis was considered significant when it compromised the luminal diameter by> or =50%. The chi square test was used to compare differences in sensitivity, specificity and accuracy between the two groups. The overall sensitivity, specificity and accuracy of stress-rest protocol were 99%, 35%and 68%, respectively. Those of rest-stress protocol were 96%, 47%, and 78%, respectively. There was no difference between the two protocols in identifying individual diseased coronary artery branches. Therefore, one day stress-rest and rest-stress myocardial SPECT using Tc-99m agents were comparable and were very sensitive tests in detecting coronary artery diseases.

Prognostic Implication of Normal Myocardial Perfusion Scintigraphy in Patients with Chest Pain / 대한핵의학회잡지

Myocardial scintigraphy is a widely used noninvasive procedure with high sensitivity for the detection of patients with suspected coronary artery disease. The purpose of this study was to determine the prognostic value of a normal myocardial scintigraphy in 292 patients (150 males, 142 females, mean age 53+/-12 years) with chest pain who were followed from 7 to 58 (mean 25) months. Myocardial SPECT was performed with Tc-99m MIBI in 173 patients, with Tc-99m tetrofosmin in 74 patients and with T1-201 in 45 patients. During the follow-up period, there were 2 cardiac deaths and 2 nonfatal myocardial infarctions resulting in cardiac event rate of 1.37% (0.66% per year). The cardiac event rate was not different in patients with angiographically normal coronary arteries (1/30, 3.3%) and in those who had significant coronary a disease (2/27, 7.4%) (p=0.60). In conclusion, patients with chest pain and normal myocardial scintigraphy have a low cardiac event rate, and there was no significant difference of cardiac event rates between patients with normal and abnormal coronary angiograms.