Biomedical subjects
Publications and source records attributed to A Y Fung.
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The BANG (MGS Research Inc., Guilford, CT) polymer gel has been used as a dosimeter to determine the three-dimensional (3D) dose distribution of a ruthenium-106 (Ru-106) ophthalmologic applicator. An eye phantom made of the BANG gel was irradiated with the Ru-106 source for up to 1 h. The phantom and a set of calibration vials were scanned simultaneously in a GE 1.5 T MR imager using the Hahn spin-echo pulse sequence with a TR of 2000 ms and two TEs of 20 ms and 100 ms. The T(2) values were evaluated on a pixel-by-pixel basis using custom-built software on a DEC alpha workstation and converted to dose using calibration data. Depth doses and isodose lines of the Ru-106 eye-plaque were generated. It is concluded that the BANG gel dosimetry offers the potential for measuring the 3D dose distributions of an ophthalmologic applicator, with high spatial resolution and relatively good accuracy.
PURPOSE: To compare the target coverage and dose to normal tissues after I-125 transperineal permanent implantation (TPI) of the prostate in 90 patients treated with one of three different transperineal techniques. METHODS AND MATERIALS: Detailed postimplant dosimetric evaluations of permanent I-125 implantation procedures were performed on 30 consecutive patients treated between 1995-1996 who underwent TPI using a preplanning CT-based technique, on 30 consecutive patients treated in 1997-1998 who underwent an ultrasound-guided approach with intraoperative determination of seed distribution based on an I-125 nomogram, and on 30 consecutive patients in 1998-1999 who underwent TPI with intraoperative computer-based 3-dimensional conformal optimization. For all three techniques, postimplant CT scans were obtained 4-6 hours after TPI. Dosimetric parameters included V(100), V(90), V(150), D(100), D(90), D(80), as well as maximal and average doses to the urethra and rectal wall. These parameter outcomes are reported as a percentage of the prescription dose. RESULTS: The intraoperative 3D-optimized technique (I-3D) provided superior target coverage with the prescription dose for all dosimetric variables evaluated compared to the other treatment techniques. The median V(100), V(90), and D(90) values for the I-3D technique were 96%, 98%, and 116%, respectively. In contrast, the V(100), V(90), and D(90) values for the CT preplan and ultrasound manual optimization approaches were 86%, 89%, and 88%, respectively and 88%, 92%, and 94%, respectively (I-3D versus other techniques: p < 0.001). The superior target coverage with the I-3D technique was also associated with a higher cumulative implant activity required by the optimization program. A multivariate analysis determined that the treatment technique (I-3D versus other approaches) was an independent predictor of improved target coverage for each parameter analyzed (p < 0.001). In addition, higher cumulative implant activities and smaller prostate target volumes were independent predictors of improved target coverage. The maximum and average urethral doses were significantly lower with the I-3D technique compared to the other techniques; a modest increase in the average rectal dose was also observed with this approach. CONCLUSION: Three-dimensional intraoperative computer optimized TPI consistently provided superior target coverage with the prescription dose and significantly lower urethral doses compared to two other techniques used. These data provide proof-of-principle that improved therapeutic ratios can be achieved with the integration of more sophisticated intraoperative planning for TPI and may potentially have a profound impact on the outcome of patients treated with this modality.
PURPOSE: To describe a treatment-plan optimization system for temporary implant of soft-tissue sarcomas using a genetic algorithm, and evaluate its potential advantages over manual planning. METHODS AND MATERIALS: A planning system that optimizes the distribution of radioactive seeds needed for adequate coverage of the target in the treatment of soft-tissue sarcomas has been designed and implemented. The treatment-planning procedures include simulation, film digitization, target-volume definition, optimized planning, and plan evaluation. The input to the optimization program consists of seed coordinates reconstructed from isocentric films, prescription points, and a list of available seed activities. The optimization is performed using a genetic algorithm. RESULTS: Case studies are presented, which compare plans generated by computer optimization or by trial and error (manually). As expected, computer-optimized plans are often (but not always) superior to manual plans. This is particularly evident for situations where (unavoidably) catheters are far apart or irregularly spaced, in which case the advantages of optimized planning in terms of tumor coverage can be quite dramatic. When the target volume is well contained, the optimized plan minimizes the dose to normal tissue. Computer-based optimization has the additional advantage of being much faster than manual planning; this is valuable because it often reduces the total time the patient will spend in the hospital before implantation. CONCLUSION: Optimized planning with a genetic algorithm and seeds of different activities significantly improves planning efficiency and generally results in improved plan quality. The utility of this optimization system is not limited to sarcoma implants.
In high dose rate prostate brachytherapy, inadequate reconstruction of catheter geometry in treatment planning may result in erroneous dose delivery. Catheters may be digitized with: (1) Parallel reconstruction: digitized at only one point and assumed parallel and horizontal: (2) Straight reconstruction: digitized at both ends and assumed straight while at an angle: (3) Slice-by-slice reconstruction: digitized on all slices to obtain exact geometry. Our results show that individual catheters are often not parallel to each other, but fairly straight. Parallel reconstruction is the least accurate for dosimetric planning, while slice-by-slice reconstruction is time-consuming. Straight (two-point) reconstruction represents a balance between accuracy and efficiency.
BACKGROUND: Previous clinical studies have shown that direct antithrombins can accelerate clot lysis after treatment with streptokinase in acute myocardial infarction (MI). Efegatran is a new direct antithrombin, which in experimental animals has been shown to enhance thrombolysis, reduce rate of reocclusion, and limit infarct size. This study was designed to compare the efficacy of efegatran plus streptokinase versus heparin plus accelerated tissue plasminogen activator (TPA) in coronary reperfusion in acute MI. METHODS AND RESULTS: In this randomized, dose-finding study (n = 245), we initially explored 4 doses of efegatran sulfate in combination with streptokinase (1.5 million U) given intravenously within 12 hours of symptom onset. The optimal dosage group of 0.5 mg/kg per hour was expanded and compared with heparin plus accelerated TPA. The primary end point was complete patency (Thrombolysis In Myocardial Infarction [TIMI] grade 3) at 90 minutes after thrombolytic therapy, assessed in a core angiographic laboratory. Infarct-related vessel patency (TIMI grade 2 or 3) and complete patency (TIMI grade 3) were 73% and 40% in the efegatran/streptokinase group versus 79% and 53% in the heparin/TPA group (P = not significant). In-hospital mortality rate was 5% for the efegatran/streptokinase group versus 0% for the heparin/TPA group (P = not significant). Major bleeding occurred in 23% of patients in the efegatran/streptokinase group versus 11% in the heparin/TPA group (P = not significant). No intracranial hemorrhage occurred. CONCLUSIONS: The combination of efegatran plus streptokinase is not superior to the current therapy of heparin and accelerated TPA in achieving early patency. In addition, there is no indication that this experimental treatment can achieve better clinical outcome.
BACKGROUND: There have been published reports from the United Kingdom of good responses to the use of traditional Chinese herbal medicine (Zemaphyte, Phytopharm Plc, Cambridge, UK) in treating recalcitrant atopic dermatitis. We conducted a double-blind, placebo-controlled, cross-over study among Chinese patients with recalcitrant atopic dermatitis using this same herbal preparation. METHODS: Forty patients were recruited. They were given Zemaphyte and placebo in random order, each for 8 consecutive weeks with a 4-week wash-out period in between. Scores based on the severity and extent of four clinical parameters (erythema, surface damage, lichenification and scaling) were recorded at baseline and at 4-weekly intervals throughout the 20-week trial period. RESULTS: Thirty-seven patients completed the trial. There was a general trend of clinical improvement with time throughout the trial period in both patient groups, irrespective of whether they received Zemaphyte or placebo first. Zemaphyte, however, offered no statistically significant treatment effect over placebo for all four clinical parameters, except for lichenification at week 4. There were no significant carry-over effects. Blood tests for hematologic, renal and liver functions were all normal throughout the trial. CONCLUSIONS: Zemaphyte did not seem to benefit Chinese patients with recalcitrant atopic dermatitis in our study. Further research is required to evaluate its efficacy.
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1. The hypotensive effect of green beans, common rue and kelp was recently shown in normotensive rats in vivo. A number of mechanisms of action of these aqueous extracts was identified. The present study examined these actions at the tissue level in vitro with possible interactions of these extracts. 2. Rue showed positive chronotropic and inotropic effects on isolated right atria. Green beans and kelp alone showed negative chronotropic effects on isolated right atria but no effect on atrial tension (AT). A combination of green beans and kelp showed no additive effect on the decrease in atrial rate (AR) nor any negative inotropic responses. Combinations of rue and green beans and of rue and kelp showed responses that were either positive or negative chronotropically, were not dose dependent and were less than the sum total of their individual responses (i.e., subtractive). A combination of all three showed subtractive effects on the decrease in AR that were dose related. No change in AT was observed upon treatment with a combination of the three plant extracts in spite of the positive inotropic effect of true. 3. Rue and kelp alone relaxed KCl preconstricted rat tail artery strips probably by a direct effect of vascular smooth muscle. Green beans had no effect. The combination of rue and kelp exerted a subtractive relaxation effect. These plants therefore contained cardiovascular active substances that had a direct effect on the cardiovascular system. These substances further interacted to modify their cardiovascular effects. 4. Data explained why herbs, as in herbal medicine, should be used together therapeutically.
BACKGROUND: In patients with acute coronary syndromes, it is desirable to identify a sensitive serum marker that is closely related to the degree of myocardial damage, provides prognostic information, and can be measured rapidly. We studied the prognostic value of cardiac troponin I levels in patients with unstable angina or non-Q-wave myocardial infarction. METHODS: In a multicenter study, blood specimens from 1404 symptomatic patients were analyzed for cardiac troponin I, a serum marker not detected in the blood of healthy persons. The relation between mortality at 42 days and the level of cardiac troponin I in the specimen obtained on enrollment was determined both before and after adjustment for baseline characteristics. RESULTS: The mortality rate at 42 days was significantly higher in the 573 patients with cardiac troponin I levels of at least 0.4 ng per milliliter (21 deaths, or 3.7 percent) than in the 831 patients with cardiac troponin I levels below 0.4 ng per milliliter (8 deaths, or 1.0 percent; P < 0.001). There were statistically significant increases in mortality with increasing levels of cardiac troponin I (P < 0.001). Each increase of 1 ng per milliliter in the cardiac troponin I level was associated with a significant increase (P = 0.03) in the risk ratio for death after adjustment for the base-line characteristics that were independently predictive of mortality (ST-segment depression and age > or = 65 years). CONCLUSIONS: In patients with acute coronary syndromes, cardiac troponin I levels provide useful prognostic information and permit the early identification of patients with an increased risk of death.
BACKGROUND: Ligand binding to the platelet membrane receptor glycoprotein (GP) IIb/IIIa, the final and obligatory step to platelet aggregation, can now be inhibited by pharmacological agents. This study was designed to evaluate the potential of lamifiban, a novel nonpeptide antagonist of GP IIb/IIIa, for the management of unstable angina. METHODS AND RESULTS: In a prospective, dose-ranging, double-blind study, 365 patients with unstable angina were randomized to an infusion of 1, 2, 4, or 5 micrograms/min of lamifiban or of placebo. Treatment was administered for 72 to 120 hours. Outcome events were measured during the infusion period and after 1 month. Concomitant aspirin was administered to all patients and heparin to 28% of patients. Lamifiban, all doses combined, reduced the risk of death, nonfatal myocardial infarction, or the need for an urgent revascularization during the infusion period from 8.1% to 3.3% (P = .04). The rates were 2.5%, 4.9%, 3.3%, and 2.4% with increasing doses. At 1 month, death or nonfatal infarction occurred in 8.1% of patients with placebo and in 2.5% of patients with the two high doses (P = .03). The highest dose of lamifiban additionally prevented the need for an urgent intervention. Lamifiban dose-dependently inhibited platelet aggregation. Bleeding times were significantly prolonged with platelet inhibition of > 80%. Major (but neither life-threatening nor intracranial) bleedings occurred in 0.8% of patients with placebo and 2.9% with lamifiban. CONCLUSIONS: The nonpeptide GP IIb/IIIa antagonist lamifiban protected patients with unstable angina from severe ischemic events during a 3- to 5-day infusion and reduced the incidence of death and infarction at 1 month, suggesting considerable promise for this new therapeutic approach.
A 50-yr-old man was evaluated using standard stress/rest 99mTc-methoxyisobutylisonitrile (MIBI) perfusion imaging, rest thallium infusion imaging and rest 99mTc-MIBI infusion imaging prior to revascularization. Resting 99mTc-MIBI infusion imaging demonstrated hibernating myocardium which was not detected with standard stress/rest 99mTc-MIBI imaging. The implication from this observation is that resting 99mTc-MIBI infusion scintigraphy can provide useful information when evaluating patients for the presence of hibernating myocardium. A prospective comparison of resting 99mTc-MIBI infusion scintigraphy with other noninvasive techniques used to identify viable myocardium may be warranted.
Unlike conventional thallium-201 myocardial imaging, technetium-99m methoxyisobutylisonitrile (MIBI) requires separate stress and rest injections. We prospectively studied 148 consecutive patients referred for myocardial perfusion studies to determine the diagnostic value of rest images once normal exercise or dipyridamole tomographic images had been obtained. In patients referred with no history of previous myocardial infarction in whom the diagnosis of coronary artery disease was suspected, 45 of 109 (41%) patients had normal stress tomographic images. Obtaining rest images did not alter the final interpretation in any of these cases. From this we infer that in patients with normal images after exercise or dipyridamole administration and no past history of myocardial infarction, 99mTc-MIBI rest images are not required. This provides several advantages including increased speed of diagnosis, decreased patient radiation exposure, improved cost efficiency and decreased demand on tomographic camera time.
The authors report a patient with diffuse pyogenic pericarditis and focal myoendocarditis initially detected using In-111 WBC scintigraphy. The patient was in septic shock after hemodialysis for the treatment of chronic renal failure. This was preceded by clinical signs and symptoms of pericarditis thought to be viral in nature. Initial investigations found no septic focus, and the patient was referred for In-111 WBC scintigraphy. This revealed a striking "halo" of increased activity around the heart, strongly suggesting bacterial pericarditis. A subsequent pericardiocentesis yielded 400 ml of purulent material, confirming the diagnosis.
Quantitative global and regional ventriculographic analysis was performed acutely and 1 week later in 46 patients undergoing reperfusion procedures within 6 hours of acute inferior myocardial infarction due to right coronary artery disease. While serial improvement in global left ventricular ejection fraction was not demonstrated for the group, infarct zone regional wall motion did improve (-2.7 +/- 0.9 vs -2.3 +/- 1.4 SD/chord, p less than 0.007). Serial improvement in global ejection fraction was demonstrated in the subgroup of patients treated within 2 hours of symptom onset (55 +/- 10 vs 62 +/- 10%; n = 5; p less than 0.03). Infarct zone regional wall motion improved serially only in the subgroup of patients treated within 3 hours of symptom onset (-2.4 +/- 1.1 vs -1.3 +/- 1.7 SD/chord; n = 11; p less than 0.007). Patients with initially patent arteries had a higher ejection fraction on follow-up catheterization than did those with initially occluded vessels (61 +/- 11 vs 55 +/- 7%; p less than 0.02), and patients with patent arteries at follow-up had a higher ejection fraction than did those whose arteries were occluded (60 +/- 9 vs 48 +/- 4%; p less than 0.0001). We conclude that significant improvement in global and regional left ventricular function in patients with inferior myocardial infarction is possible when reperfusion therapy is begun early or when arterial patency is achieved.
Noninvasive cardiac imaging with echocardiography or thallium-201 scintigraphy utilizing pharmacologic agents as alternatives to exercise is gaining popularity. We investigated the physiologic rationale underlying the optimal choice of pharmacologic stress for functional versus perfusion imaging. With the use of an open-chest dog model, a critical stenosis of the left circumflex coronary artery was produced with total ablation of hyperemic response to a 15 sec period of complete occlusion. Regional left ventricular wall thickening was assessed by quantitative two-dimensional echocardiography. Regional myocardial blood flow was determined by microspheres in both the flow-restricted left circumflex area and the control area supplied by the left anterior descending artery. Eight dogs received 15 micrograms/kg/min dobutamine intravenously for 10 min, and nine dogs received 0.14 mg/kg/min dipyridamole intravenously for 4 min. Dobutamine induced wall thickening abnormalities in all dogs while dipyridamole induced dysfunction in only 55% of the animals studied (p less than .01). Subendocardial blood flow to the left circumflex area was unchanged after both dobutamine and dipyridamole when compared with baseline blood flow. However, subendocardial blood flow increased markedly after dipyridamole in the control area. Regional subendocardial blood flow ratio (left anterior descending/left circumflex) was 3.74 +/- 0.09 (mean +/- SEM) after dipyridamole versus 1.27 +/- 0.09 after dobutamine (p less than .001).(ABSTRACT TRUNCATED AT 250 WORDS)
The effect of sequential high-dose intravenous streptokinase (SK) (1.5 million units) followed by emergency percutaneous transluminal coronary angioplasty (PTCA) on preserving left ventricular function was assessed prospectively in 34 patients with acute myocardial infarction (AMI). Intravenous SK therapy was initiated 2.6 +/- 1.3 hours (mean +/- standard deviation) after the onset of chest pain. Urgent coronary angiography showed persistent total occlusion in 13 patients, significant diameter stenosis (70 to 99%) in 18 patients and a widely patent artery (less than 50% stenosis) in 3 patients. Emergency PTCA was performed in 29 patients 5.0 +/- 2.1 hours after symptom onset. Successful recanalization was achieved in 33 of the 34 patients (97%) treated with sequential therapy. Repeat contrast ventriculograms recorded 7 to 10 days after intervention in 23 patients showed that the left ventricular ejection fraction increased from 53 +/- 12% to 59 +/- 13% (area-length method, p less than 0.002). Regional wall motion of the infarcted segments improved from -2.7 +/- 1.1 to -1.5 +/- 1.7 SD/chord (centerline method, p less than 0.003). In the subgroup of patients with an occluded artery on initial angiography (group A, n = 10), both global left ventricular ejection fraction (49 +/- 12% vs 59 +/- 12%, p less than 0.002) and regional wall motion (-3.2 +/- 1.0 vs -1.9 +/- 1.7 SD/chord, p less than 0.002) improved significantly. In contrast, no significant improvement was seen in patients with a patent artery on initial angiography (n = 13). Thus, sequential intravenous SK and emergency PTCA is efficacious in achieving coronary reperfusion and in improving both global and regional left ventricular function.(ABSTRACT TRUNCATED AT 250 WORDS)
To compare the efficacy of emergency percutaneous transluminal coronary angioplasty and intracoronary streptokinase in preventing exercise-induced periinfarct ischemia, 28 patients presenting within 12 hours of the onset of symptoms of acute myocardial infarction were prospectively randomized. Of these, 14 patients were treated with emergency angioplasty and 14 patients received intracoronary streptokinase. Recatheterization and submaximal exercise thallium-201 single photon emission computed tomography were performed before hospital discharge. Periinfarct ischemia was defined as a reversible thallium defect adjacent to a fixed defect assessed qualitatively. Successful reperfusion was achieved in 86% of patients treated with emergency angioplasty and 86% of patients treated with intracoronary streptokinase (p = NS). Residual stenosis of the infarct-related coronary artery shown at predischarge angiography was 43.8 +/- 31.4% for the angioplasty group and 75.0 +/- 15.6% for the streptokinase group (p less than 0.05). Of the angioplasty group, 9% developed exercise-induced periinfarct ischemia compared with 60% of the streptokinase group (p less than 0.05). Thus, patients with acute myocardial infarction treated with emergency angioplasty had significantly less severe residual coronary stenosis and exercise-induced periinfarct ischemia than did those treated with intracoronary streptokinase. These results suggest further application of coronary angioplasty in the management of acute myocardial infarction.