Biomedical subjects
P Dawson
Publications and source records attributed to P Dawson.
Creating original HIM Week celebrations.
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Massive osteolysis of the chest in children: an unusual cause of respiratory distress.
Massive osteolysis, also called Gorham's disease, is an uncommon disease in which bone virtually disintegrates and is replaced by vascular fibrous connective tissue. The authors treated two children with massive osteolysis of the chest. Both conditions responded well to radiation therapy; one even showed evidence of reossification. Massive osteolysis should be considered in children who have spontaneous hemothorax. The bony structures should be examined for evidence of lytic lesions.
Aerobic versus strength training for risk factor intervention in middle-aged men at high risk for coronary heart disease.
To compare the effects of strength training (ST) to those of aerobic training (AT) for coronary heart disease (CHD) risk factor intervention, we studied 37 previously untrained males (aged 50 +/- 9 years, mean +/- SD) before and after 20 weeks of either ST (N = 14), AT (walk/jog, N = 13), or no exercise (inactive controls, N = 10). Lipoprotein and lipid profiles, blood pressure, and glucose and insulin responses to an oral glucose tolerance test (OGTT) were assessed before and after the training period in all three groups. The ST program produced significant reductions in plasma glucose levels at 60, 90, and 120 minutes (P < .05) after glucose ingestion, whereas the AT program resulted in significant reductions only at 90 and 120 minutes (P < .05). ST also decreased insulin levels during fasting (P < .05) and at 90 and 120 minutes (P < .01) after glucose ingestion. AT decreased insulin levels at 90 and 120 minutes (P < .01) after glucose ingestion. Both training programs reduced the total area under the glucose tolerance curve for glucose (both P < .05) and insulin (both P < .05), but there were no significant differences in these changes between the two groups. None of the glucose or insulin values were significantly altered in the control group. There were no significant changes in lipoprotein and lipid profiles or blood pressure in any of the three groups. These results suggest that ST and AT have comparable effects on risk factors for CHD.(ABSTRACT TRUNCATED AT 250 WORDS)
Diagnostic iodised oil embolisation of liver tumours--the Hammersmith experience.
Oily embolisation of the liver as a diagnostic technique in the management of liver tumours has not proved reliable in our hands. In our study of 20 patients we found: (1) The technique was not risk-free, with complications in four patients, one of whom required emergency surgery. (2) The Bruneton classification is far too simplistic to be relied upon. (3) Residual Lipiodol, particularly in the left lobe of the liver is problematic, making it difficult to distinguish normal from diseased liver. (4) The technique did not contribute to decisions about surgical management in any one of our 20 cases though we accept it might occasionally do so. Our experience was disappointing and in marked contradistinction to enthusiastic reports by some other authors.
Is there a role for corticosteroid prophylaxis in patients at increased risk of adverse reactions to intravascular contrast agents?
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Intravenous cholangiography revisited.
The efficacy and safety of IVC with the new agent has not, in our opinion, been firmly established. In these circumstances we do not feel its routine use preoperatively in patients being considered for laparoscopic cholecystectomy is justified. We remain uncertain about its ultimate safety and are unconvinced that it is able, reliably, to demonstrate ductal anomalies which might increase the risk of iatrogenic injury. If imaging of ductal anatomy is important then it is best to obtain it intraoperatively. The radiologist often acts as an essential guide to the surgeon; as interventionist he frequently actually usurps the surgeon's role; and occasionally has to come to his rescue. In our opinion, he should not be asked to perform a procedure of unproven efficacy and uncertain safety in order to allow the surgeon willfully to abandon good surgical practice.
Absence of an angiogenic factor in large systemic arteriovenous malformations.
RATIONALE AND OBJECTIVES: Large symptomatic arteriovenous malformations (AVMs) are currently managed by a combination of surgery, embolization, and supportive measures. If patients with such lesions should have a circulating factor responsible for their growth and development, the evolution of a more rational therapy might be possible. METHODS: To explore this possibility, sera from 14 patients with high-flow systemic AVMs, widely distributed anatomically, were tested for the presence of a circulating growth factor using an assay already successfully used to isolate such a factor in diabetics with proliferative retinopathy. RESULTS: None of the patients tested positive for such a factor. CONCLUSIONS: This result, although negative, contributes to our knowledge of the biology of these uncommon but important lesions and leads us to conclude that, for the foreseeable future, embolization is likely to remain the most effective form of treatment for high-flow AVMs.
Dynamic contrast bolus computed tomography for the assessment of renal function.
RATIONALE AND OBJECTIVES: We preliminarily investigated whether dynamic contrast bolus computed tomography (CT) could be used to measure glomerular filtration rate. METHOD: After bolus intravenous contrast injection, rapid sequence CT scans were performed at a fixed level through the kidneys and aorta in three patients with biochemically normal renal function who underwent routine CT examination. A mathematical technique developed initially for positron-emission tomography was adapted for analysis of the CT data for measurement of renal contrast clearance per unit renal volume and of the fraction of renal tissue occupied by blood volume. RESULTS: Renal blood volumes in the 3 patients were 0.28, 0.29, and 0.31 of total renal volume, respectively, and the corresponding contrast clearances were 0.44, 0.41, and 0.35 mL per min per mL of renal tissue. CONCLUSIONS: This preliminary study in normal patients demonstrates that dynamic contrast CT might be developed for clinical physiological renal studies. Further work to validate the accuracy and reliability of the method in comparison with established isotope methods is suggested.
Contrast bolus dynamic computed tomography for the measurement of solid organ perfusion.
RATIONALE AND OBJECTIVES: The authors have investigated the aortic responses to various intravenous bolus injections of nonionic and ionic contrast media and have presented data illustrating the potential of ultrafast computed tomography (CT) to quantify perfusion in the kidney, liver, and spleen. METHODS: Bolus Dynamics Study: Performed in 3 healthy dogs (weight: 35 kg to 36 kg). In 2 dogs, 15 mL of the nonionic agent iohexol and the ionic agent sodium-meglumine diatrizoate were injected at 5, 10 and 20 mL/sec via a venous catheter placed in the superior vena cava; the order of injection was alternated between the 2 dogs. In the third dog, 25 mL of iohexol 300 mg I/mL was compared with diatrizoate 370 mg I/mL with injection rates of 10 and 20 mL/sec. Computed tomography scanning at the level of the midabdominal aorta was performed using an ultrafast CT scanner. Time-density curves were drawn for regions of interest over the aorta, and gamma-variate fits performed. Perfusion Studies: Dynamic perfusion scans of the upper abdomen were performed in more than 50 patients. A dose of 25 mL of iohexol 300 mg I/mL was injected at 10 mL/sec via an intravenous cannula in the antecubital fossa, followed immediately by 25 mL of saline, at the same rate. Scanning was performed at a single level using an ultrafast CT scanner. Regions of interest were drawn and gamma-variate fits were applied to the vascular time-density curves. RESULTS: Bolus Dynamics: Excellent curve fits for aortic time-density curves were obtained. A 10-mL/sec versus a 5-mL/sec bolus produced an 8% higher peak density. Nonionic contrast increased the peak density by a mean of 6%, increased the area under the corrected time-density curve by a mean of 22%, and lengthened the increase time by a mean of 21%. Perfusion Studies: Values obtained were reproducible and correlated well with values predicted from inert gas washout techniques. CONCLUSIONS: Changes in the CT number in a region after an intravenous injection of contrast medium may be used to calculate blood flow per unit volume of tissue. Ultrafast CT offers sufficient data points for accurate calculation. The quality of the aortic bolus is of great importance. Nonionic media offer several important advantages: hemodynamic perturbation is minimized, and they are better tolerated at the high injection rates needed. Low-osmolality nonionic agents produce "better" curves than conventional high-osmolality ionic agents, all other factors being equal. The resulting data are relevant to intravenous digital subtraction angiography and indirect portography as well as to perfusion measurement. The technique of quantitative dynamic CT is theoretically applicable to any cross-sectional modality, notably magnetic resonance.
Short communication: is some of our radiation dosimetry wrong?
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Dynamic designing.
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Securing effective media contacts.
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The clotting issue: etiologic factors in thromboembolism. I. Chemistry, pharmacology, and toxicity of angiographic contrast agents.
RATIONALE AND OBJECTIVES: In a decade of clinical use of nonionic contrast agents, only one scientific criticism of any significance has been leveled at them. That is, they may increase the risk of thromboembolism in diagnostic and interventional clinical angiography. The author examines the hypothesis that contrast molecules exert their intrinsic toxicity through hydrophobic and Coulomb interactions with biological molecules. Because nonionic molecules are hydrophilic and have no charge and therefore no Coulomb component, they should be less toxic. METHODS: The basic chemical and pharmacologic properties of iodinated contrast agents are outlined and their effects on hematology are discussed. The author also reviews studies on the development of ionic and nonionic agent formulations and the evolution of theories on their toxicity. The relative toxicity of ionic versus nonionic agents also is considered. RESULTS: Three factors are found to correlate well with contrast toxicity: partition coefficient, protein-binding capacity, and pi-electron density in the benzene ring system. Any increase in pi-electron density increases hydrophobicity, while any reduction in pi-electron density decreases hydrophobicity. The more hydrophobic molecules have a lower osmolality. Nonionic agents are observed to exhibit lower toxicity than low-osmolality ionic agents. Because of their greater hydrophilicity, based on better masking of the hydrophobic core by hydrophilic side chains, and their lack of charge, nonionic contrast agents have a reduced potential for interactions, rendering them more inert and less toxic. The uniformity of results in the different systems previously studied and the constant hierarchy of relative effects are striking. CONCLUSIONS: Fundamental understanding of the molecular basis of contrast toxicity indicates that it is not possible to synthesize a contrast molecule that will have strong anticoagulant effects and yet retain a low toxicity. Having marked anticoagulant effects is an indicator of toxicity: a more anticoagulant agent is more toxic. It is similarly not possible to manipulate incipients in the formulations to achieve strong anticoagulant properties without also modifying toxicity. There also is a trade-off between reducing chemotoxicity and reducing osmolality, since, if we successfully shield the hydrophobic core of the molecule, we limit the degree to which the osmolality of the solution will be reduced below that predicted on simple chemical considerations. These then are the essential points to bear in mind in any discussion of the clotting issue. For reasons of their structure and the nature of additives in their formulations, second-generation nonionic agents have little effect on biological systems. Therefore, they have only a limited impact on the coagulation cascade exactly in line with their low toxicity. Consequently, nonionic contrast agents have established themselves, with both radiologists and patients, as the agents of choice and are now accepted as better tolerated and safer than ionics--in terms of both a reduced incidence of idiosyncratic/anaphylactoid reactions and high-dose tolerance--in interventional radiology and pediatrics.
The clotting issue: etiologic factors in thromboembolism. II. Clinical considerations.
RATIONALE AND OBJECTIVES: The authors analyze the origins of the "clotting issue," the controversy that began in the 1980s when contrast media, once perceived as good flushing agents for catheters because of their assumed anticoagulant properties, came under attack for allegedly causing thromboembolism. Laboratory studies as well as a number of clinical reports seemed to substantiate this charge. Nonionic agents in particular were accused by some clinicians of being more likely to cause clots to form in syringes contaminated with blood than were ionic agents. The authors wanted to determine whether some lapse in operator technique rather than a fault in the contrast agent might be to blame. The theory that the syringe and catheter materials, and not the contrast agent itself, could be the source of thromboembolic problems in angiography also is examined. METHODS: The authors reviewed studies and reports on both sides of the issue and conducted laboratory and clinical studies of their own. For the syringe materials analysis, they used a fibrinopeptide A (FpA) enzyme-linked immunosorbent assay (ELISA) test to monitor levels as a marker of activation of coagulation. They tested catheter materials using the same technique. RESULTS: Clots were found only in nonionic agents, but under nonclinically relevant circumstances. If the anticoagulant effect of the nonionic contrast agent was maximized by mixing rather than layering blood and agent, clots did not form. In their materials analysis, the authors demonstrated that glass syringes are thrombogenic, causing vigorous contact activation, and that plastic is less so. Polyurethane catheters are more thrombogenic, polyethylene less so. One survey conducted in the 1970s on the clinical incidence of thromboembolism in coronary angiography suggested that the single most important factor in the etiology is poor angiographic technique. The authors' studies supported their thesis. CONCLUSIONS: In terms of the findings from laboratory studies, misinterpretation of data by nonclinicians is one problem. No evidence suggests that nonionic contrast agents are in any way prothrombotic or thrombogenic. On the contrary, in line with their greater inertness, nonionic agents have weaker effects. Ionic contrast media may cause more endothelial injury and associated localized platelet deposition than nonionic contrast media, and more anticoagulant contrast agents are more toxic. If anticoagulation is required, therefore, it should be achieved by such procedures as carefully controlled systemic heparinization rather than by resorting to more toxic materials. The activation of coagulation is caused by endothelial injury and by prolonged contact between blood and foreign surfaces such as syringes or catheters, but is inhibited by the contrast agent. Because a thrombus may form inside the catheter, whatever contrast agent is used, flushing is important. The authors agree with the findings of one study that the incidence of thromboembolism in coronary angiography, and probably in other catheter procedures, is markedly operator dependent. The materials of the syringes and catheters used, as well as the state of the patient's intrinsic clotting, are more important factors than the contrast agent. The authors conclude that materials other than the contrast agents are the cause of thromboembolic problems; and that, being anticoagulant, contrast agents are entirely helpful, if variably so, in angiographic procedures.
Functional imaging in computed tomography. The use of contrast-enhanced computed tomography for the study of renal function and physiology.
RATIONALE AND OBJECTIVES: Computed tomography (CT) numbers may provide the raw material for calculations of important physiologic parameters, such as organ regional perfusion and glomerular filtration rate. Because, except in cases of severe renal dysfunction, iodinated intravascular contrast agents are excreted primarily by passive glomerular filtration, the decline in their concentration in blood or tissues will reflect renal function. The time evolution of contrast agent distribution within the kidney, from blood to tubules, can also be seen as a measure of renal function. The authors illustrate how CT numbers may be employed to obtain useful data regarding renal function. METHODS: Two CT methods were used to yield information on renal function. Delayed CT: 2 hours after administration of 200 mL of a contrast agent (iohexol) for a routine CT, a patient with normal renal function was brought back to the scanner, and a single fixed section through the abdomen, including the psoas muscles, was imaged; the scan was repeated at 2, 3, and 4 hours. Large regions of interest were selected in soft tissue, and six measurements of CT numbers were taken and averaged for each time; after taking logs, these were plotted against time. Dynamic CT: A rapid bolus of 40 mL nonionic contrast agent was injected into an antecubital vein at 5 mL/sec. At a fixed level, images were taken through the center of the kidneys at 5-second intervals for 2 minutes after injection. The patient was allowed to breathe gently throughout the examination. Regions of interest were selected over the kidney and the aorta, and curves of CT numbers against time were generated; a Patlak plot was performed using the parameters measured. Using the renal CT numbers collected during the first 2 minutes after injection, it was possible to analyze the handling of the contrast agent and to obtain a measure of the glomerular filtration rate. RESULTS: Delayed CT: Data yielded good values for glomerular filtration rate; the typical patient illustrated had a glomerular filtration rate per unit extracellular fluid volume of 0.005 min-1. Dynamic CT: The correlation coefficient for the line fit was 0.97, a value typically found in these studies, indicating the efficacy and ruggedness of this method in spite of the patient's shallow breathing throughout the examination. CONCLUSIONS: Computed tomography offers the potential for quantitative and physiologic measurement that has not been widely explored. The problem with the delayed CT technique is that since measurements are made at 2 hours and onward, it is applicable only to patients who have received larger doses of contrast. Otherwise, the CT numbers are low and the measurement error, large. Also, bringing the patient back to the scanner 2 hours later may be inconvenient to both patient and radiologist, and may disrupt case scheduling. This method is, however, less inconvenient than the established blood-level measurement. The dynamic CT method yields a new measure of renal clearance, namely, clearance per unit volume of kidney. The disadvantages of this method are the radiation burden involved in repeated rapid CT scans and the fact that, if renal disease is uneven, a nonrepresentative slice could be chosen. Its advantages are its simplicity and that it can be completed within the first 2 minutes of a CT examination. It may be expected to have an interesting application to situations in which there is known renal disease. Although difficulties are associated with both of these techniques that could prevent their general adoption as clinical routines, they nevertheless should find application in selected patients and should prove useful research tools in the study of renal disease.
Magneto-optical studies of screened excitons in GaAs/AlxGa1-xAs modulation-doped quantum wells.
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