Edward A. Carr

The direct diagnosis of myocardial infarction by photoscanning after administration of cesium-131☆

Abstract 1. 1. It is possible to visualize the left ventricular myocardium of the intact, living patient, without discomfort or danger to the patient, by photoscanning after the administration of cesium-131. 2. 2. The normal left ventricular myocardium appears as a full, even density, with a smooth contour. Myocardial infarcts appear as “cold” areas of decreased uptake. 3. 3. In 6 patients with unequivocal fresh myocardial infarcts, the scans were positive in 5 and doubtful in 1. In 2 patients who probably had suffered recent myocardial infarctions, the scan was positive in 1 and negative in 1. In 2 patients who had heart disease but who had probably not had recent myocardial infarctions, the scan was negative in 1 and doubtful in 1. The scan was negative in each of 3 patients with normal hearts.

The detection of experimental myocardial infarcts by photoscanning. A preliminary report.

T he heart shadow as visualized roentgenographically is the result of superimposition of several tissues, including the blood content of the heart. Other roentgenographic and radioisotopic techniques used to visualize the heart show only its cavities. The studies of Burch and his associates,‘sz which indicated rapid uptake of rubidium-86 by the myocardium, suggested the possibility of demonstrating the myocardium by photoscanning after administration of this radioisotope. Our previous work” confirmed the feasibility of demonstrating the myocardium of the beating heart of living dogs by this technique. Furthermore, in photoscintigrams of the excised hearts of dogs previously subjected to coronary artery ligation, the area of infarction was demonstrable as a “cold” area of relatively decreased uptake of rubidium-86 (Fig. 1). The successful use of mercury-203labeled chlormerodrin (Neohydrinj in the demonstration of brain tumors by photoscanning4-6 suggested the possible use of this compound to demonstrate myocardial infarcts as “hot” areas of relatively increased concentration of radioisotope in photoscintigrams of the heart. The present communication describes experiments designed to explore this possibility.

The effect of drug therapy on the uptake of radioactive fluorine by osseous metastases.

RadioisotopiC techniques are potentially of considerable value to clinical pharmacology. Scintigrams and uptake studies are of particular interest, as they permit one to visualize lesions in many organs and to obtain simultaneously quantitative information on the degree of abnormality in the area of the lesion. Bone metastases take up increased amounts of fluorine‐18; the present study was an investigation of the effect of therapy on this abnormal uptake. In eight patients with metastatic lesions to bone, chemotherapy or hormonal therapy produced temporary improvement in five, as ;udged by roentgenographic or clinical criteria, during the first four months after initiation of therapy. Serial scintigrams and quantitative uptake studies throughout this period showed that the abnormal ratio in fluorine uptake remained unchanged, despite the other evidence of emporary regression of metastases. Although the duration of time chosen for this study was consistent with that commonly used by physicians for evaluation of the effect of a given type of chemotherapy, our results suggest that such short‐term studies must be interpreted cautiously.

The use of radio-iodinated toluidine blue for myocardial scintigrams

A lthough heart disease is the principal cause of death in many countries and its diagnosis is of major importance, methods for direlct visualization of the myocardium in intact subjects are few. The roentgenogram of the heart shows the myocardium plus other tissues, especially the blood contained in the cardiac cavities, as a single shadow. Various techniques show cavities and vessels rather than the myocardium itself. On the basis of the important earlier studies which had demonstrated mycvardial uptake of potassium and its analogues,’ it was possible to develop a method for myocardial scintigrams,‘J using salts of cesium-131. This method permitted the demonstration of the left ventricular myocardium through the intact chest wall, without significant contribution to the image from the cardiac blood pool or adjacent non-cardiac tissues. After original developrnent of the technique in dogs, it was extended to humans and the myocardial scintigram has subsequently been shown capable of demonstrating myocardial infarcts,2-g aneurysm of the left ventricle,2j6 cardiomyopathies,7,8 neoplasm in the ventricular wall,‘O and rejection of the transplanted heart.” However, the long biologic half-life of cesium creates difficulties, not only from the standpoint of radiation dose, but also through interference with performance of serial scintigrams. As skeletal muscles retain cesium much longer than cardiac muscle,12,13 the uptake by intercostal muscles interferes with serial myocardial scintigrams during the days that follow injection of a single dose of cesium-131. Moreover, its principal emission, a 29.4 KEV x-ray, poses a considerable problem as a result of its low energy and consequent high absorption in tissues. Therefore, although cesium131 has proved an important radionuclide by permitting the demonstration of the validity of the myocardial scintigram for diagnosis, the general clinical usefulness of the myocardial scintigram would be greatly increased by the availability of a more convenient radioactive compound for this

Mechanical Support of the Circulation by a Modified Pulsatile Roller Pump

Abstract A modified roller pump capable of delivering pulsatile blood flow synchronized with diastole provided satisfactory assisted circulation in 14 newborn calves. Hemodynamic studies showed a marked decrease in cardiac stroke work, while cardiac output and coronary flow were maintained at or near control levels. Postperfusion 131 Cs uptake studies showed increased circulation to ischemic myocardium in assisted calves when compared with controls.

Prenatal treatment of cretinism: Preliminary studies of its value in postnatal development

In this study 4 mothers who had each prveiously given birth to at least 1 cretinous infant were given large doses of thyroid hormone during 6 subsequent pregnancies; 3 of the children born in these circumstances were euthyroid and apparently were not harmed by the treatment. Of the 3 cretins, 2 were probably benefited. It is possible, but unlikely, that hypothyroidism was caused by this therapy. More data on the subsequent development of cretins treated in the immediate neonatal period are needed.

Proposed aims, organization, and activities of a division of clinical pharmacology

The general aim of a division of clinical pharmacology is to provide opportunity for the work of present clinical pharmacologists, to encourage the development of improved methods of research, and, in particular, to foster the training of young men in this discipline. Specific areas of research, teaching, and service can already be foreseen. The best administrative home of the division will probably be a department of pharmacology, although special arrangements regarding budget, personnel, and appOintments will probably be necessary. Training in clinical pharmacology should be from 1 to 3 years. The trainee should have already received a background of clinical experience, and this may be further strengthened during his specific training in clinical pharmacology. Courses in advanced pharmacology and statistics are obviously necessary. Each division will probably find it necessary to create at least one new course dealing with the special problems of human pharmacology, discussed preferably in an informal seminar environment.

ROLE OF SCINTILLATION SCANNING IN DIAGNOSIS OF RENAL TUMORS

An evaluation was made of scintillation scanning in 18 patients suspected of having renal tumors. Neohydrin-Hg/sup 203/ was used in a single intravenous injection of 100 mu C. The method did not differentiate between tumors and cysts, and tumors which did not appreciably replace functioning renal tissue could not be detected. In spite of these limitations, it is of value when used in conjunction with routine excretory urography. (BBB)

The American Society for Clinical Pharmacology and Therapeutics: Its role in board certification in clinical pharmacology

Since the establishment of the first American board in a clinical specialty, the American Board of Ophthalmology in 1917, there has been a steady impetus toward the development of similar examining boards for other medical specialties and, more recently, subspecialties. Although the controlled clinical trial dates back at least to James Lind, and important nineteenth century pharmacologists such as Buchheim and Schmiedeberg were clearly interested in the clinical implications of their studies, the awakening (or reawakening) of interest in clinical trials and clinical pharmacology in the twentieth century is best exemplified by the work of Bradford Hill and Gold and Modell, respectively. Subsequent publications by Beecher and Lasagna called further attention to the new or renascent field of clinical pharmacology. Several training programs in clinical pharmacology were established in the 1950s and early 1960s. By 1965 clinical pharmacology as an identifiable discipline had progressed to the point where consideration of the possibility of some formal certification process was at least no longer facetious. Among the recipients of the Oscar B. Hunter Award, the highest award of the American Society for Clinical Pharmacology and Therapeutics (ASCPT), one finds, very appropriately, the names of at least four individuals who developed outstanding programs of research and training in clinical pharmacology: Albert Sjoerdsma, then working at the National Institutes of Health, Louis Lasagna, at Johns Hopkins University and later the University of Rochester, the late Leon Goldberg, at Emory University and subsequently at the University of Chicago, and John Oates, at Vanderbilt University.

Panel 2: Phase II investigations

At the end of Phase II, a decision must be made as to whether or not the drug should be developed as a therapeutic agent. Such a decision may be based on many criteria in addition to the scientific data derived from the Phase II study. At this point, expert judgment is needed. One should like to assume that if the decision is made to proceed with the increasingly expensive and laborious process of further development, the drug will, barring some completely unforeseen misadventure, ultimately find its way into clinical therapeutics. Phase II studies, therefore, are the most crucial stage in the course of drug development. Planning of these studies requires great care and investigators of the highest caliber should be used for their conduct. The escalating costs of new drug development are resulting in an undesirable imbalance of efforts in the direction of studies characterized more by easily defined end points than by therapeutic needs. Industry, academia, and the FDA must all be concerned with facilitationg studies in areas of most-needed therapeutic advances.