Biomedical subjects
Publications and source records attributed to F X Sundram.
Reverse redistribution (RR) is the apparent worsening of a stress-induced defect or the appearance of a new defect in the myocardium in the delayed thallium images. This has been linked to the presence of coronary artery disease. In this article, we examine the incidence of this phenomenon in our local population, and its pathophysiological significance.
Nuclear cardiology at the Singapore General Hospital (SGH) had a humble beginning in 1983 when it was carried out by the joint staff of the departments of cardiology and nuclear medicine. At the onset the bulk of the scans were blood pool studies. In 1984, qualitative tomographic myocardial perfusion studies replaced the less accurate planar scans and this was carried out on a routine basis. Its superiority to conventional exercise electrocardiography in the detection, management and prognostication of coronary artery disease (CAD) has since been validated locally. We have since progressed to the fields of research involving pharmacological stress testing with intravenous dipyridamole and use of technetium-based isonitrile as an alternative to the conventional myocardial perfusion agent, thallous chloride. Our results mirror those from other research centres. On this encouraging note we are looking into newer areas such as the role of diastolic function for early detection of cardiac disease. In under a decade we are in a position to provide scintigraphic service expected of an established nuclear cardiac laboratory. This article provides an overview of our work in the management of CAD.
A number of chemically diverse substances is associated with the malignant transformation of cells. Though none of these can be said to be wholly specific they are operationally useful and this paper is a selective review of some of them. They arise from exposure of previously cryptic epitopes in membranes and secreted molecules and the amplification of normally small quantities of cellular components, such as oncogenes in chromosomes. Antibodies directed to these tumour markers are opening up new avenues of research, diagnosis and therapy of cancer patients. The use of radioisotope labelled antibodies has become sufficiently sensitive and specific to be useful for decision-making in their clinical management.
Serum levels of tissue polypeptide antigen (TPA) were measured in 233 patients at the time of initial diagnosis of nasopharyngeal carcinoma (NPC). Staging of NPC was done using Ho's recommendations together with computerised tomography (CT) of skull findings. The upper limit of normal serum TPA levels in our population was noted to be 112 U/1. In 126 patients with N0 and N1 lymph node staging, the mean level of TPA was 90 U/1 +/- 9 (standard error of mean, sem), while in 107 patients with N2 and N3 nodal disease the mean was 193 U/1 +/- 25.6 (p less than 0.001). Similarly, in 162 patients with T1 and T2 disease, the average TPA level was 119 +/- 13.4 while in 71 patients with T3 disease, the mean TPA was 179 U/1 +/- 29.8 (p less than 0.03). Of 200 patients without metastases, the mean TPA level was 112 +/- 12 U/l whereas in 33 patients with known metastases in liver, lung, bone or brain, the mean TPA level was 290 +/- 51 (p less than 0.001) with liver metastases producing the highest levels. The present study indicates rising values of TPA with advancing nodal and tumour stage in NPC, with high values in metastatic disease. There is a highly significant correlation between nodal stage and TPA levels. TPA is a useful marker in the staging and follow-up of NPC patients.
The study attempts to assess the accuracy of radionuclide scan, ultrasonography and fine-needle aspiration biopsy as diagnostic tools in distinguishing malignant from benign nodular thyroid lesions in Singapore. The medical case records of 537 patients referred to the Department of Nuclear Medicine were analysed. 94% of the solitary thyroid nodules delineated on scintiscan were "cold". The incidence of malignancy in solitary "cold" thyroid nodules was 8%, and that in multinodular goitres was 2.3%. The sensitivity of both radionuclide scan and ultrasonography in detecting cancer was 100%, but the specificity was disappointingly low, i.e. 3.6% for radionuclide scan and 21% for ultrasonography. The sensitivity for fine-needle aspiration biopsy was 85%, and the specificity 96%. Fine-needle aspiration cytology is indisputable as an accurate diagnostic tool in differentiating malignant from benign thyroid lesions, and should be the first test to be used in the diagnostic workup of nodular thyroid disease. However, both radionuclide scan and ultrasonography remain crucial in the subsequent management of patients with thyroidectomy done for thyroid cancer. The other major roles are in the management of thyroiditis, thyrotoxicosis and confirmation of ectopic thyroid tissue.
Over the last forty years radionuclides have come to play a useful role in diagnosis and treatment of tumours. Radionuclide scintigraphy provides information on morphology and function of tumours; functional studies have become more relevant with advances in instrumentation such as digitised gamma-cameras, single-photon emission tomography (SPECT), position-emission tomography (PET), and with advances in radiopharmaceuticals. A significant contribution in recent years has been the use of radiolabelled antibodies in immunoscintigraphy and immunotherapy; an increasing role is envisaged also for the use of tests for tumour markers in vitro.
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Technetium-99m-(tin) colloid uptake in renal transplants was quantified to evaluate rejection. A dynamic acquisition following i.v. injection of 110 MBq of this radiopharmaceutical enabled quantification of 15 to 20 min transplant uptake (PU), in terms of percentage of an injected dose after allowing for attenuation in the patient. An uptake ratio (UR) i.e. the ratio of 15 to 20 min uptake over the 0 to 5 min uptake was also derived. Normal values were obtained in 20 stable functioning transplants (normal PU less than or equal to 1%, normal UR less than or equal to 0.7). In 66 patients, PU and UR were compared with clinical, biochemical, histological and radiological, evidence of rejection. A sensitivity of 70% and specificity of 85% was obtained for this 99Tcm-(tin) colloid study in the diagnosis of renal transplant rejection.
This study looks retrospectively at 113 patients with low back pain referred by orthopaedic surgeons for bone scanning. 79 scans (70%) were reported normal and 34 scans (30%) abnormal. 61 out of the 79 patients with normal scans were diagnosed and managed as "chronic back strain". Negative bone scans were also encountered in 3 patients with degenerative disease, 3 with prolapsed intervertebral disc and one with spondylolysis. In those patients with positive scans, a varied range of diagnoses was encountered, the main ones being bone metastases, previous trauma, osteomyelitis and degenerative disease. The scan was shown to be helpful in deciding on the presence or absence of pathology, and in identifying the sites of involvement, but not the nature of the disease. A higher likelihood of positivity is seen in the more elderly patients as well as those below 20 years of age. In interpreting the scan, the clinical context is important e.g. a history of trauma, previous surgery or of malignant disease. The bone scan may be normal in disc prolapse and in degenerative disease of the spine.
We prepared 99mTechnetium(V) DMSA (pentavalent form) as an imaging agent for eighteen patients with proven nasopharyngeal carcinoma. The head, neck, chest and abdomen were scanned. The nasopharyngeal tumour showed tracer accumulation in only 5 out of the 18 patients (28%). The study indicates that 99mTechnetium(V) DMSA is not a useful radiopharmaceutical for visualising nasopharyngeal tumours although it may have other useful properties.
57 patients with chest pain, had tomographic thallium-201 stress scintigraphy (TTSS), and coronary angiography within three months of the TTSS. The exercise images were compared with delayed images obtained at 3 hours post-exercise. The sensitivity and specificity of locating individual coronary artery disease was 88% and 100% for disease of left anterior descending artery (LAD), 89% and 83% for right coronary artery disease (RCA), and 24% and 96% for left circumflex artery (LCX) disease. Other than for LCX disease, our results compare favourably with other reports. The overall accuracies are 91%, 86% and 60% for LAD, RCA and LCX disease respectively.
The levels of tissue polypeptide antigen (TPA) and beta 2 microglobulin (beta 2-MG) were measured in the serum of 38 patients with nasopharyngeal carcinoma (NPC). Using sera from 35 normal volunteers and blood donors, a normal range for these two tumour markers was established. The normal range for TPA was 40-148 IU/L (mean = 93), while that for beta 2-microglobulin was 0.9-2.0 mg/L (mean = 1.3). In the patients with NPC but without known metastases the range was 63-178 IU/L for TPA (mean = 111) and for beta 2-MG, the range was 1.0-3.1 mg/L (mean = 1.7). For those NPC patients with metastases to bone or liver, the mean TPA was 464 IU/L and the mean beta 2-MG was 4.3 mg/L. It appears that TPA and beta 2-MG are useful markers for the monitoring of NPC patients for metastatic disease, particularly TPA.
Scintigraphic methods for liquid and solid gastric emptying were utilised to study normal patterns in 21 volunteers. Of these, 19 had solid emptying studies and 14 had liquid emptying studies. The liquid study lasted 1/2 hour, while the solid study was for 1 hour. The gastric emptying half-time (T 1/2), as well as percentage retention at 15 minutes (liquids), and at 60 minutes (for solids) were noted. The time-activity curves were also corrected for tissue attenuation. Results indicated normal average liquid emptying T 1/2 to be 14.2 minutes, while that for solids was 116 minutes.
It is generally agreed that the Technetium-Thallium Subtraction Scan is a reliable method for locating abnormal parathyroid glands in patients with clinical and biochemical evidence of parathyroid hyperactivity. This report illustrates the value of scintigraphy in diagnosis and in the subsequent surgical management of a patient with primary hyperparathyroidism.
In recent years, 99mTechnetium IDA hepatobiliary scintigraphy has been widely accepted as a highly sensitive and fairly accurate test in the diagnosis of biliary atresia and evaluation of neonatal jaundice. Over a period of 4 years from 1982 to 1986, a total of 110 paediatric patients had undergone 99mTechnetium IDA hepatobiliary scans in our department for prolonged neonatal jaundice. Their scans were reviewed to evaluate the role of this nuclear imaging technique in the diagnosis of biliary atresia. There were 43 true positive and 49 true negative scans. No false negative scan was encountered in our study. Hence the sensitivity was 100%. However, out of the 110 scans, there was misdiagnosis of biliary atresia in 18 cases. This gave a specificity of 73% with an accuracy of 84%. From this study we concluded that 99mTechnetium IDA imaging is a highly sensitive test in the screening of biliary atresia. However, its specificity is possibly limited by the short half life of the radioisotope 99mtechnetium in delayed 24 hr imaging and we feel that this could be improved by using slightly higher doses than what we are presently using.
Radioactive iodine (I-131) uptakes (RAIU) and serum T4 levels were observed in 72 patients referred for radioiodine therapy. Of 65 patients whose results could be evaluated 47 had these tests while on carbiomazole (CMZ). 17 of these 47 patients had repeat tests a week later and the differences were not significant. In the remaining 18 patients of the 65, the tests were performed after stopping the CMZ for 1-5 days and again at 8-12 days. The differences in the results were again not significant. The incidence of hypothyroidism at 1 year was noted in the group receiving radioiodine therapy while on CMZ as compared to those stopping the CMZ for 1-12 days. The difference was again not significant, though the number of these patients becoming hypothyroid was small. Serum T4 levels were measured in 21 patients, two weeks after treatment with radioiodine and there was no real difference from the baseline T4 levels.
A prospective study of 17 patients with fracture neck of femur was undertaken to study the vascularity of the femoral head by bone scan using Technetium-99m MDP, as well as to study the viability of the femoral head by histopathology, and therefore determine correlation, if any, between these two methods. Treatment was by primary endoprosthetic replacement (Moore's Arthroplasty). In 16 of the 17 patients the bone scan showed decreased vascularity of the head, but histopathological examination could not confirm non-viability of the head. It is likely that, since the majority of the patients were operated on within 4 days, there was insufficient time for histopathological evidence of ischemia to develop, prior to removal of the femoral heads.
Serum thyroglobulin antibodies (TgAb) and serum thyroglobulin (Tg) levels were measured in 28 normal controls and 32 patients with differentiated thyroid cancer. The TgAb and Tg levels were measured in the patients when they were on replacement thyroxine therapy prior to the whole body radioiodine I-131 scan (WBS), using immunoradiometric assay kits. The TgAb level in normal controls was from 0-4.8 micrograms/ml, with a mean of 0.6 microgram/ml, while the Tg level in these controls was from 0.0-48.0 ng/ml, with a mean of 4.2 ng/ml. In the patients with thyroid cancer, the TgAb levels were normal except for a few patients who had residual thyroid or tumour in the neck and had raised levels of TgAb. Their Tg levels were normal except for 7 patients who had elevated values. 2 of these 7 had no evidence of disease on X-ray, bone scan, or WBS (I-131) while the other 5 had evidence of metastases. However, 4 patients had metastatic disease with normal Tg levels, and 2 of these patients had residual thyroid in the neck and raised TgAb levels, while in the remaining 2 patients, both Tg and TgAb were low. Serum Tg is a useful tumour marker for recurrent or metastatic thyroid cancer, but the presence of residual normal thyroid would interfere with the results.