2,6-Disubstituted aryl carboxylic acids, leaving groups "par excellence" for benzisothiazolone inhibitors of human leukocyte elastase.
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Carboxylic Acids↗
Biomedical subjects
M R Bell
Publications and source records attributed to M R Bell.
Time to reperfusion with direct coronary angioplasty and thrombolytic therapy in acute myocardial infarction.
An analysis was performed of the Mayo Clinic randomized trial of direct percutaneous transluminal coronary angioplasty and tissue-type plasminogen activator (t-PA) to determine the time required to achieve reperfusion with direct coronary angioplasty. Because patients in the Mayo trial assigned to t-PA did not undergo protocol coronary angiography, reperfusion rates from the Thrombolysis in Myocardial Infarction (TIMI) I trial in which patients underwent coronary angiography 30, 60 and 90 minutes after thrombolytic therapy were used for comparison. TIMI perfusion grade 2 or 3 flow in the infarct artery was considered to represent reperfusion after thrombolysis. In the 56 patients assigned to t-PA, the mean time from randomization to initiation of the t-PA infusion was 20 minutes. Twenty minutes were therefore added to the previously reported 30-, 60- and 90-minute reperfusion rates to express these in terms of time from randomization (50, 80 and 110 minutes). In the 48 patients who had direct angioplasty, the mean time from randomization to arrival in the cardiac catheterization laboratory was 45 minutes; it took a mean of 6 additional minutes for patients to be prepared and draped and arterial access obtained, and a mean of 27 additional minutes to complete angiography and achieve reperfusion. At 50, 80 and 110 minutes after randomization, the reperfusion rates for direct coronary angioplasty were 12, 54 and 83%, similar to previously reported TIMI reperfusion rates with t-PA (24, 57 and 71%, respectively, p = NS) but significantly greater at 80 and 110 minutes than was reported for streptokinase (8, 23 and 31%, respectively, p = 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
Angioplasty, Balloon, Coronary↗
Does the use of new intracoronary interventional devices prolong radiation exposure in the cardiac catheterization laboratory?
OBJECTIVES: The aim of this study was to compare the duration of radiation exposure associated with new percutaneous coronary interventional devices with that associated with conventional balloon angioplasty. BACKGROUND: Radiation exposure levels have been documented to be higher with coronary balloon angioplasty than with routine diagnostic coronary angiography. However, the effect of new interventional devices on radiation exposure has not been studied. METHODS: Fluoroscopic and cineangiographic data from the Mayo Clinic cardiac catheterization laboratory data base of patients having single-segment coronary intervention during a recent 46-month period were retrospectively analyzed. Of 897 patients studied, 646 underwent balloon angioplasty, 138 directional coronary atherectomy (42 with adjunctive balloon angioplasty), 76 excimer laser angioplasty (50 with adjunctive balloon angioplasty) and 37 placement of an intracoronary stent (16 emergencies). RESULTS: Duration of fluoroscopy during balloon angioplasty was 24 +/- 18 min, which was longer than with directional atherectomy (18 +/- 8 min; p = 0.001). Fluoroscopy time was 25 +/- 17 min with laser angioplasty and 29 +/- 15 min with elective stent placement (neither time was significantly different from that with balloon angioplasty). When atherectomy or laser angioplasty was performed with adjunctive balloon angioplasty or if emergency intracoronary stent placement was performed, the duration of fluoroscopy was significantly prolonged compared with balloon angioplasty alone. CONCLUSIONS: Fluoroscopy duration is not prolonged with the use of new interventional coronary devices compared with conventional angioplasty unless adjunctive balloon angioplasty is used or emergency stent placement is required.
Aged↗
"Rescue" directional coronary atherectomy after unsuccessful percutaneous transluminal coronary angioplasty.
OBJECTIVE: To evaluate the outcome in patients who underwent directional coronary atherectomy after unsuccessful balloon angioplasty. DESIGN: We conducted a retrospective computerized data bank search of patients in whom unsuccessful balloon angioplasty and subsequent "rescue" coronary atherectomy had been performed at the Mayo Clinic between Nov. 1, 1988, and May 1, 1993. MATERIAL AND METHODS: Among the 336 patients who underwent directional coronary atherectomy during the study period, in 16 the procedure was a rescue attempt. The mean age of these 16 study patients was 67 years. The following vessels were treated: left anterior descending coronary artery, six patients; right coronary artery, six; circumflex artery, two; and saphenous vein graft, two. Coronary angioplasty had failed because of dissection in eight patients, elastic recoil without evident dissection in seven, and recurrent thrombus without evident dissection in one. RESULTS: After coronary atherectomy, the mean stenosis was 41% (in comparison with 90% before coronary angioplasty and 71% after coronary angioplasty). Both angiographic success (20% or more decrease in stenosis after tissue removal and a final stenosis of less than 50%) and clinical success (angiographic success without in-hospital Q-wave myocardial infarction, bypass operation, or death) were achieved in 10 patients. Adventitia was obtained in two patients, both of whom underwent atherectomy for elastic recoil. In six patients, a stenosis of more than 50% remained after atherectomy; one patient suffered a Q-wave myocardial infarction, and one underwent emergent coronary artery bypass grafting. No deaths occurred in the study group. During follow-up (mean, 22 +/- 19 months), one patient suffered a non-Q-wave myocardial infarction, and two others underwent elective coronary artery bypass grafting. Eleven patients were asymptomatic at last contact. Repeated angiography, done in five patients a mean of 3.4 +/- 3.1 months after the procedure, showed restenosis in three. CONCLUSION: Rescue directional coronary atherectomy seems to be safe and effective in achieving angiographic and clinical successes in carefully selected patients after unsuccessful coronary angioplasty.
Aged↗
Immediate and long-term outcome after directional coronary atherectomy: analysis of gender differences.
OBJECTIVE: To compare the short-term and long-term outcomes of directional coronary atherectomy in women and men. DESIGN: We retrospectively analyzed 291 consecutive directional atherectomy procedures performed in 61 women and 230 men at the Mayo Clinic between October 1988 and November 1992. MATERIAL AND METHODS: The baseline clinical and angiographic characteristics, including extent of coronary artery disease and left ventricular ejection fraction, were compared for the male and female patients, and the short-term and long-term complications associated with atherectomy were summarized on the basis of gender. RESULTS: At baseline, women were older than men (67 +/- 12 versus 61 +/- 11 years; P = 0.001), and more women than men had class III or IV angina (90% versus 64%; P < 0.001); slightly more women than men had rest pain (64% versus 52%). Overall clinical success (improvement in luminal diameter of 40% or more and no death, Q-wave myocardial infarction, or emergency coronary bypass operation) was achieved in 89% of women and 95% of men (P = 0.054). In-hospital mortality was similar in women and men (1.6% and 1.7%, respectively), but acute myocardial infarction occurred more frequently in women than in men (4.9% versus 0.4%; P = 0.03). Significant peripheral vascular complications occurred in 6.6% of women versus 0.9% of men (P = 0.02). During long-term follow-up (mean, 2.9 years), survival and freedom from recurrent angina were similar among women and men. CONCLUSION: Directional coronary atherectomy is associated with slightly lower success and a higher frequency of myocardial infarction among women than among men. The higher postprocedural rate of myocardial infarction among women may reflect their worse clinical status at time of initial assessment. Despite these observations, women and men seem to have comparable survival and freedom from recurrence of angina during extended follow-up.
Aged↗
Coronary angioplasty in acute myocardial infarction: primary, immediate adjunctive, rescue, or deferred adjunctive approach?
OBJECTIVE: To address the current clinical applications, outcomes, and limitations of coronary angioplasty in the setting of acute myocardial infarction. DESIGN: We review the results of several large trials in which various strategies of thrombolysis and primary, immediate adjunctive, rescue, or deferred adjunctive coronary angioplasty were used in patients with acute myocardial infarction. MATERIAL AND METHODS: Four strategies for the utilization of angioplasty in myocardial infarction have been developed and are based on the timing and concurrent use of thrombolytic therapy. RESULTS: Primary coronary angioplasty without prior thrombolytic therapy is as effective as thrombolytic therapy for salvaging myocardium. Results of a meta-analysis of recent trials suggest potential benefits of increased survival and decreased reinfarction in comparison with the results of thrombolysis in recent trials. Immediate adjunctive angioplasty after thrombolytic therapy has been tested in three large, randomized trials. The results suggest that this strategy is associated with increased risks without benefits of increased survival or improved left ventricular function. Rescue angioplasty may be helpful after failed thrombolytic therapy. Ongoing randomized trials might further clarify the benefits of rescue angioplasty. Because of the inherent difficulty in the noninvasive identification of patients with persistent reocclusion, diagnostic coronary angiography early after thrombolytic therapy may be necessary. Deferred adjunctive angioplasty during the weeks after infarction to prevent recurrent ischemia was not shown to decrease mortality or reinfarction in two large trials. CONCLUSION: Primary coronary angioplasty is the treatment of choice for patients with contraindications to thrombolytic therapy. Certain high-risk subgroups may also benefit from primary angioplasty.
Angioplasty, Balloon, Coronary↗
Quantification of global and regional renal blood flow with electron beam computed tomography.
Alterations in renal blood flow distribution may occur in a variety of pathophysiologic situations; however, quantification of global and regional renal blood flows has been limited because of the lack of reliable, noninvasive techniques. To determine the feasibility of flow measurements with electron-beam computed tomography (EBCT), six anesthetized dogs were scanned by EBCT during basal conditions, after renal vasodilation, and at recovery. Flow (mL/min/cm3 tissue) was calculated from EBCT-derived time-density curves using three different algorithms and compared with simultaneously obtained electromagnetic flow (EMF) probe measurements after indexing to EBCT-derived renal volume. EBCT-determined flow correlated well with EMF measurements regardless of the algorithm used. An algorithm using the area under the time-density curve was concluded to be the most suitable for calculation of renal blood flow; it correlated with EMF as EBCT flow = 44.5 + 1.05 EMF (r = 0.885, SEE = 31.2 mL/min, P < .0001). Consistent overestimation of flow by EBCT resulted probably from retention of contrast media in the renal parenchyma. EMF showed an increase of 20 +/- 10% in renal blood flow after vasodilation. EBCT-derived global, cortical, and medullary flows increased by 33.8 +/- 10.3%, 24.8 +/- 17.8%, and 99.0 +/- 73.8%, respectively. In conclusion, EBCT was found feasible for credible quantitation of renal blood flow in the physiologic range studied.
Algorithms↗
Non-steroidal glucocorticoid-like substances: receptor binding and in vivo activity.
Compounds of general structure I, prepared by a Diels-Alder reaction with diene 3, are relatives of the known potent glucocorticoid II but possess a markedly modified C- and D-ring environment. Despite these structural changes, 4, 5, 9, 10, 12a, 13, and 14 bound to the glucocorticoid receptor with an affinity which approximated that of the reference standard, 6-alpha-methylprednisolone. Four of these compounds not only exhibited antiinflammatory activity in the alpha-tocopherol pouch test but also exhibited marked adrenal suppression and other typical glucocorticoid properties at doses in the same range as the effective antiinflammatory doses.
Animals↗
Initial results and long-term outcome of coronary angioplasty in chronic mild angina pectoris.
To analyze the clinical and anatomic findings of patients undergoing coronary angioplasty for mild angina, and determine the short- and long-term outcome, a retrospective data bank analysis of 3,729 patients who underwent coronary angioplasty at the Mayo Clinic between July 31, 1980 and January 30, 1991 was performed. Of these patients, 217 (6%) had stable Canadian Heart Association class I or II angina at the time of the procedure and constitute the study population. Patients were followed for a median of 37 months after the procedure. The mean age of patients was 60 years; 82% were men. Prior myocardial infarction occurred in 22% of patients. Multivessel disease was present in 68% of patients, and mean left ventricular ejection fraction was 65 +/- 11%. Angioplasty was clinically successful in 196 patients (90%), 271 of 318 lesions (85%) were successfully dilated. There were no in-hospital deaths. Coronary artery bypass was performed during hospitalization in 12 patients (5.5%), and myocardial infarction occurred in 3 (1.4%); bypass or infarction occurred in 13 patients (5.9%). During follow-up of the 196 successfully treated patients, there were 9 deaths (4.5%), 16 patients (7%) developed myocardial infarction, 30 (15%) underwent coronary artery bypass surgery, and 36 (17%) developed severe angina. The probability of having any of these adverse cardiac events after 6-year follow-up was 39%; an additional 24% of patients developed recurrent mild angina during follow-up. It is concluded that mild stable angina was an infrequent indication for coronary angioplasty at the Mayo Clinic.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Predictors of major ischemic complications after coronary dissection following angioplasty.
Coronary dissection is a major cause of abrupt arterial closure after coronary angioplasty but may also be associated with no discernible event. Deciding which dissections should receive further treatment is often a dilemma if the artery remains patent. This case-control study examined predictors of major ischemic complications after coronary dissections. Fifty-eight patients with coronary dissections, but a patent artery at the completion of the angioplasty procedure, subsequently had in-hospital abrupt arterial closure, acute myocardial infarction, emergency coronary bypass surgery, or died; they were matched to 58 control subjects with dissection but no event. Analysis of each angiogram was performed with the examiner unaware of patient's history. Baseline angiographic and clinical characteristics of cases and controls were similar except for an excess of current smokers among the cases (31 vs 16%; p = 0.048). Residual luminal diameter at the dissection site was 1.2 +/- 0.6 mm (cases) versus 1.6 +/- 0.6 mm (controls; p = 0.001) with relative stenosis of 59 +/- 21% vs 43 +/- 21%, respectively (p = 0.0001). Dissections among cases were longer than among controls (11 +/- 7 mm vs 7 +/- 4 mm; p = 0.001). No significant difference was found in dissection morphology using 2 classification schemes or in final Thrombolysis in Myocardial Infarction study flow grade. Transient occlusion during the procedure, however, occurred in 47% of cases versus 5% of controls (p = 0.0001). Transient occlusion, residual percent stenosis > or = 70%, and dissections > or = 6 mm were independently predictive of major ischemic events.
Acute Disease↗
The changing in-hospital mortality of women undergoing percutaneous transluminal coronary angioplasty.
OBJECTIVE: To compare in-hospital mortality among women and men undergoing percutaneous transluminal coronary angioplasty (PTCA) and determine whether mortality differences have changed recently. DESIGN: A retrospective cohort study. SETTING: Tertiary referral institution. PATIENTS: Consecutive series of 3557 patients (27% women) who underwent 4071 PTCA procedures. Two cohorts were analyzed: patients treated between 1979 and 1987 (n = 1970) and those treated between 1988 and 1990 (n = 2101). MAIN OUTCOME MEASURES: In-hospital and periprocedural mortality. RESULTS: Women were older than men (P < .001) and more had class III or IV angina (P < .001), unstable angina (P < .001), angina at rest (P < .001), cardiac failure (P < .001), and diabetes mellitus, hypertension, and hypercholesterolemia (P < .001). The PTCA was successful in 85% of women and 86% of men with an in-hospital mortality rate of 4.2% and 2.7%, respectively (P = .005). No significant change in mortality occurred in men between the early (2.2%) and late (3.1%) eras in contrast to a significant increase among women, 2.9% to 5.4% (P = .04). Periprocedural mortalities for women and men between 1979 and 1987 were 1.0% and 1.2% (P = not significant) and between 1988 and 1990 were 2.9% and 1.4% (P = .02), respectively. The multivariate odds ratio of in-hospital mortality for women vs men was 1.51 (95% confidence interval, 1.00 to 2.29; P = .05), although six other baseline variables were more powerful predictors of in-hospital mortality. Accounting for body surface area resulted in no significant association between gender and in-hospital mortality. Periprocedural mortality was not independently associated with gender. CONCLUSIONS: In-hospital mortality among women has increased in recent years, but their higher mortality compared with men is related more to the severity of their underlying disease rather than gender alone.
Aged↗
Searching for therapeutic niches for new coronary interventional devices: the unyielding nature of chronic occlusions.
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Angioplasty, Balloon, Coronary↗
Results of directional atherectomy of primary atheromatous and restenosis lesions in coronary arteries and saphenous vein grafts.
Directional coronary atherectomy (DCA) was performed in 158 patients over a 2-year period at the Mayo Clinic. Primary atheromatous lesions were treated in 92 patients (group 1) and restenosis lesions were treated in 66 (group 2). Technical success (recovery of tissue and greater than or equal to 40% luminal enlargement with a residual stenosis of less than 50%) was achieved in 152 lesions (92%); clinical success (technical success and no in-hospital death, Q-wave myocardial infarction or coronary bypass surgery) was achieved in 143 patients (91%). Adjunctive balloon angioplasty was used in 41 patients. DCA was successful less often in group 1 than in group 2 (86 vs 97%; p = 0.038). A major complication occurred in 7% of patients; in-hospital death, Q-wave myocardial infarction and emergency coronary bypass surgery occurred in 3, 1 and 4% of patients, respectively. Major complications were more frequent in group 1 than in group 2 (10 vs 1; p = 0.02). During a follow-up period of 14 +/- 8 months, no difference between the groups was found in the incidence of late death (4%), Q-wave myocardial infarction (1%), recurrent severe angina (29%), bypass surgery (15%) or repeat interventional procedure of the same vascular segment (24%). Vein graft and restenosis lesions tended to have greater success and fewer complications. Angiographic restenosis (increase of greater than or equal to 30% in stenosis severity by visual assessment) occurred in 62% of patients and 58% of lesions with successful DCA, and was similar in the 2 groups; a tendency toward higher restenosis rates was seen in patients with vein graft DCA.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Antiandrogenic steroidal sulfonyl heterocycles. Utility of electrostatic complementarity in defining bioisosteric sulfonyl heterocycles.
Complementarity of electrostatic potential surface maps was utilized in defining bioisosteric steroidal androgen receptor antagonists. Semiempirical and ab initio level calculations performed on a series of methanesulfonyl heterocycles indicated the requirement for a partial negative charge at the heteroatom attached to C-3 of the steroid nucleus to attain androgen receptor affinity. Synthesis and testing of six heterocycle A-ring-fused dihydroethisterone derivatives support this hypothesis, and we have identified two new androgen receptor antagonists of this class.
Androgen Antagonists↗
Effect of restenosis after an earlier angioplasty at another coronary site on the frequency of restenosis after a subsequent coronary angioplasty.
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Aged↗
Synthesis and substance P receptor binding activity of androstano[3,2-b]pyrimido[1,2-a]benzimidazoles.
Several heterosteroids containing a dihydroethisterone skeleton were prepared and shown to displace substance P in a receptor binding assay. Further biochemical (kinetic and Scatchard analyses) and pharmacological evaluation (substance P-induced plasma extravasation and salivation in the rat) of a representative example in this series (5a) established that these compounds are competitive antagonists at the substance P receptor.
Androstanes↗
Balloon angioplasty of chronic total coronary artery occlusions: what does it cost in radiation exposure, time, and materials?
Coronary angioplasty of chronic total occlusions is known to have a lower success rate and higher frequency of restenosis than angioplasty of subtotal stenoses, but there are no data describing the additional time, resources, and radiation exposure associated with this procedure. The purpose of this study was to compare these features in 90 consecutive patients who underwent angioplasty of a total occlusion (group 1) to those of 100 consecutive patients who underwent angioplasty of a subtotal stenosis (group 2). Angioplasty was successful in 60% of group 1 and in 94% of group 2 patients. Procedures were longer in group 1 and significantly more guide catheters, angioplasty balloon catheters, and guide wires were required per patient compared to group 2. The volume of contrast media used in each group was similar. Estimates of radiation entry exposure, calculated from fluoroscopy exposure times and using data from phantom studies, were 53 R (roentgen) per patient in group 1 vs. 34 R in group 2. These procedures were performed using pulsed progressive fluoroscopy; radiation exposure would be considerably higher using conventional fluoroscopic systems. Cineangiographic radiation exposures were similar for each group and accounted for an average additional exposure of 14-22 R for each procedure. Total radiation exposure was reduced in both groups when the angioplasty procedure was combined with the diagnostic angiogram. These observations should be considered when dilation of a total occlusion is planned. Efforts to reduce the amount of radiation exposure should remain a priority in interventional catheterization laboratories.
Aged↗
Ventricular relaxation and myocardial ischemia: a comparison of different models of tau during coronary angioplasty.
This study compares the sensitivity and variability of four models of tau, the time constant of ventricular relaxation, to detect the presence of myocardial ischemia. High fidelity left ventricular pressure recordings were obtained in ten patients undergoing coronary angioplasty at baseline, during balloon inflation, and at recovery. Four models of tau were considered: 1) a semilogarithmic, zero asymptote model (TL), 2) a semilogarithmic model using data from the first 40 ms of isovolumic relaxation (T40), 3) an exponential non-zero asymptote model (TE), and 4) a derivative non-zero asymptote model (TD). TL, T40, and TE increased significantly during inflation and returned to near baseline values at recovery. TD showed no change during inflation. Comparisons of TL, T40, and TE using the derived relaxation half-time (T1/2), failed to reveal significant differences between the models at baseline, during inflation, or at recovery. The non-zero asymptote models were associated with a greater beat-to-beat variability than the semilogarithmic models. Thus, T1/2 using the semilogarithmic zero asymptote models (TL and T40) may be more useful and consistent when measuring the rate of isovolumic relaxation during myocardial ischemia.
Angioplasty, Balloon, Coronary↗