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Biomedical subjects

M R Bell

Publications and source records attributed to M R Bell.

At least 91 records · Page 5Linked to original sources
PubMed1992

Relation of deep arterial resection and coronary artery aneurysms after directional coronary atherectomy.

OBJECTIVES: The aims of this study were to document the frequency of coronary artery aneurysm formation in patients undergoing directional coronary atherectomy and to determine the relation of such aneurysms to the depth of arterial resection. BACKGROUND: Deep arterial injury is relatively frequent with the use of directional coronary atherectomy, but the potential for subsequent coronary artery aneurysm formation is unknown. METHODS: Results in a consecutive series of 64 successfully treated patients (a total of 69 lesions; mean angiographic follow-up at 5 months) treated with directional coronary atherectomy were retrospectively analyzed with use of quantitative angiographic and histologic data. RESULTS: Coronary aneurysms (ratio of dilated vessel segment to the adjacent reference segment > 1.2:1) occurred in seven patients (10%). The only significant clinical correlate of aneurysm formation was a relatively shorter duration of angina. There were no significant preprocedural angiographic predictors of aneurysms, although 6 (86%) of the 7 aneurysmal lesions arose from restenosis lesions compared with 30 (48%) of 62 lesions with no subsequent aneurysm development (p = 0.06). Histopathologic examination of 414 specimens from 68 treated lesions showed no significant difference in the occurrence of subintimal resection (media +/- adventitia) between those with and without subsequent aneurysm (29% vs. 22%). Media alone was found in 14% of specimens from lesions that later became aneurysmal versus 15% of those that did not; adventitial resection was found in 14% and 7% of specimens, respectively (p = 0.08), with relatively more adventitia per specimen from those with aneurysm (55% vs. 30% without aneurysm, p = 0.08). CONCLUSIONS: Aneurysms occur relatively frequently after directional coronary atherectomy. Although there was no statistically significant correlation with the depth of arterial resection, the evidence from this study suggests that the role of adventitial resection in the occurrence of late aneurysm development should be explored further.

Aged↗
PubMed1992

Percutaneous transluminal coronary angioplasty and the changing indications for coronary artery bypass grafting for single-vessel coronary artery disease.

Patients with single-vessel coronary artery disease have a good long-term prognosis with either medical or surgical therapy. Because percutaneous transluminal coronary angioplasty has become widely available for treating patients with symptomatic single-vessel coronary artery disease, those who currently undergo coronary artery bypass grafting may be a select group. In this study, we examined the effects of the increasing use of percutaneous transluminal coronary angioplasty on the indications for coronary artery bypass grafting in patients with symptomatic single-vessel coronary artery disease and reviewed the type of procedures performed in such patients at our institution between 1983 and 1988. During this period, 115 patients underwent coronary artery bypass grafting for single-vessel coronary artery disease. The indication for revascularization was angina in 111 patients (88% were in class III or IV, Canadian Cardiovascular Society classification), acute myocardial infarction in 3, and a strongly positive result of an exercise test in 1. The number of surgical revascularization procedures annually for single-vessel coronary artery disease remained consistent throughout the study period. In a comparison of the first 3 years of the study with the last 3 years, the number of patients who underwent coronary artery bypass grafting for restenosis after coronary angioplasty increased, but the number who had surgical revascularization because of failure of coronary angioplasty decreased. In addition, more patients received internal mammary grafts during the second half of the study (42 or 72%) than during the first half (24 or 42%).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Conformationally restrained analogues of pravadoline: nanomolar potent, enantioselective, (aminoalkyl)indole agonists of the cannabinoid receptor.

Pravadoline (1) is an (aminoalkyl)indole analgesic agent which is an inhibitor of cyclooxygenase and, in contrast to other NSAIDs, inhibits neuronally stimulated contractions in mouse vas deferens (MVD) preparations (IC50 = 0.45 microM). A number of conformationally restrained heterocyclic analogues of pravadoline were synthesized in which the morpholinoethyl side chain was tethered to the indole nucleus. Restraining the morpholine diminished the ability of these pravadoline analogues to inhibit prostaglandin synthesis in vitro. In contrast, mouse vas deferens inhibitory activity was enhanced in [2,3-dihydro-5-methyl-3-[(4-morpholinyl)methyl] pyrrolo[1,2,3-de]-1,4-benzoxazin-6-yl]-(4-methoxyphenyl)methano ne (20). Only the R enantiomer of 20 was active (IC50 = 0.044 microM). An optimal orientation of the morpholine nitrogen for MVD inhibitory activity within the analogues studied was in the lower right quadrant, below the plane defined by the indole ring. A subseries of analogues of 20 and a radioligand of the most potent analogue, (R)-(+)-[2,3-dihydro-5-methyl-3-[(4-morpholinyl)methyl]pyrrolo [1,2,3-de]-1,4-benzoxazin-6-yl](1-naphthalenyl)methanone (21) were prepared. Inhibition of radioligand binding in rat cerebellar membranes was observed to correlate with functional activity in mouse vas deferens preparations. Binding studies with this ligand (Win 55212-2) have helped demonstrate that the (aminoalkyl)indole binding site is functionally equivalent with the CP-55,940 cannabinoid binding site. These compounds represent a new class of cannabinoid receptor agonists.

Analgesics↗
PubMed1992

Measurement of myocardial perfusion and cardiac output using intravenous injection methods by ultrafast (cine) computed tomography.

Ultrafast (or cine) computed tomography (CT) uses a novel scanning electron beam technology to obtain multi-level images of the beating heart in rapid succession. Recent investigations have demonstrated that it can be used to define the transit of iodinated contrast media through the cardiac chambers and myocardium. Using classical indicator dilution principles and rapid intravenous injection of iodinated contrast media, ultrafast CT can quantify cardiac output and, to a limited extent, myocardial perfusion. A caveat to the application requires that careful calibration be made on a subject-by-subject basis prior to quantification of cardiac output. Although global myocardial perfusion and flow reserve can be evaluated by ultrafast CT, spatially variable imaging artifacts may limit the application in all regions of the left ventricular myocardium. Advances in study design, image reconstruction and post-image processing continue. Ultrafast CT technology offers a means to define cardiac anatomy, function and flow in man rapidly, conveniently and accurately in a noninvasive fashion employing intravenous contrast media injection.

Cardiac Output↗
PubMed1992

Initial and long-term outcome of 354 patients after coronary balloon angioplasty of total coronary artery occlusions.

BACKGROUND: Coronary balloon angioplasty of chronic total occlusions is associated with relatively low success rates and a high incidence of restenosis. Whether there is long-term benefit in performing angioplasty of these lesions is unknown. The purpose of the present report was to analyze the long-term outcome of a large series of patients undergoing this procedure. METHODS AND RESULTS: A computerized database analysis of 354 consecutive patients (from 1979 to 1990) who underwent coronary angioplasty of a chronic total coronary occlusion was performed (mean age, 62.3 years). Initial technical success was achieved in 69%; in 66%, success was achieved without procedural death or need for coronary artery surgery. During hospitalization, six patients suffered myocardial infarction, nine required emergency bypass surgery, and nine patients died. During a mean follow-up period of 2.7 years, no difference was found in survival or freedom from myocardial infarction among 234 successfully dilated patients compared with 120 patients with a failed attempt. However, the use of coronary artery bypass surgery was significantly less after successful dilation (p less than 0.0001 versus failed attempt). No significant difference in the cumulative incidence of severe angina was observed between these two patient populations, with the majority remaining asymptomatic. Restenosis occurred in 59% of 69 patients who returned for follow-up angiography. CONCLUSIONS: Successful recanalization is achieved in the majority of patients undergoing angioplasty of chronic total occlusions and reduces the need for coronary artery bypass surgery. However, no major impact on either survival or incidence of myocardial infarction was noted after successful recanalization when patients with surgery were included.

Angioplasty, Balloon, Coronary↗
PubMed1992

Effect of completeness of revascularization on long-term outcome of patients with three-vessel disease undergoing coronary artery bypass surgery. A report from the Coronary Artery Surgery Study (CASS) Registry.

BACKGROUND: Complete revascularization after coronary artery bypass surgery is a logical goal and improves symptomatic outcome and survival. However, the impact of complete revascularization in patients with three-vessel coronary disease with varying severities of angina and left ventricular dysfunction has not been clearly defined. METHODS AND RESULTS: The study was performed as a retrospective analysis of 3,372 nonrandomized surgical patients from the Coronary Artery Surgery Study (CASS) Registry who had three-vessel coronary disease. Group 1 (894 patients) had class I or II angina (Canadian Cardiovascular Society criteria) and group 2 (2,478 patients) had class III or IV angina. In group 1, adjusted cumulative 4-year survivals according to the number of vessels bypassed were 85% (one vessel), 94% (two vessels), 96% (three vessels), and 96% (more than three vessels) (log rank, p = 0.022). Adjusted event-free survival (death, myocardial infarction, definite angina, or reoperation) was not influenced by the number of vessels bypassed, nor was the anginal status among patients remaining alive after 5 years. In group 2, adjusted cumulative 5-year survivals were 78% (one vessel), 85% (two vessels), 90% (three vessels), and 87% (more than three vessels) (log rank, p = 0.074). Adjusted event-free survivals after 6 years were 23% (one vessel), 23% (two vessels), 29% (three vessels), and 31% (more than three vessels) (p = 0.025); at 5 years, those with more complete revascularization were more likely to be asymptomatic or free of severe angina. Among group 2 patients with ejection fractions less than 0.35, 6-year survival was 69% for those with grafts to three or more vessels versus 45% for those with grafts to two vessels (p = 0.04). Placing grafts to three or more vessels was independently associated with improved survival and event-free survival in group 2 but not group 1 patients. The case-fatality rates among 529 patients experiencing a myocardial infarction during follow-up was significantly higher for patients with less complete revascularization. CONCLUSIONS: Complete revascularization (grafts to three or more vessels) in patients with three-vessel coronary disease appears to most benefit those with severe angina and left ventricular dysfunction.

Angina Pectoris↗
PubMed1991

Antinociceptive (aminoalkyl)indoles.

The (aminoalkyl)indole (AAI) derivative pravadoline (1a) inhibited prostaglandin (PG) synthesis in mouse brain microsomes in vitro and ex vivo and exhibited antinociceptive activity in several rodent assays. In vitro structure-activity relationship studies of this new class of PG synthesis inhibitors revealed a correspondence in three respects to those reported for the arylacetic acids: (1) "alpha-methylation" caused an increase in PG inhibitory potency, (2) the (R)-alpha-methyl isomer was more active than the S isomer, (3) the hypothesized aroyl group conformation of the 2-methyl derivatives corresponded to the proposed and reported "active" conformations of the aroyl and related aromatic acetic acid derivatives. The 1H NMR chemical shift of the C-4 hydrogen of pravadoline in comparison to the deshielding seen with 50, which lacks a substituent at C-2, suggested that the carbonyl group of pravadoline is located near C-2 but is located near C-4 in 50. Associated with this conformational change of the carbonyl group of 1a is a diminution of PG synthetase inhibitory activity. The results of UV and difference nuclear Overhauser studies of the two compounds were consistent with these conformational assignments. The low eudismic ratios of the alpha-methyl derivatives and the observation that the side chain may be extended by three methylene groups without significant loss of PG inhibitory potency suggests that this class of inhibitors bound less strongly and less selectively to the active site of PG synthetase than do the arylacetic acids. Two AAIs, 1a and 30, were found to be metabolized to the corresponding acetic acid derivatives, both of which inhibited PG synthesis. An exception to the observation that the antinociceptive activity of the AAIs was associated with PG synthetase inhibitory activity was the 1-naphthoyl derivative 67 since neither it nor its acetic acid metabolite 74 inhibited PG synthesis. Yet 67 was antinociceptive in four different rodent assays. This naphthoyl derivative, like opioids, also inhibited electrically stimulated contractions in the mouse vas deferens (MVD) preparation. Unlike opioids, however, the inhibition was not antagonized by naloxone. A subseries of AAIs was identified, of which 67 was prototypic. These compounds lacked PG synthetase inhibitory activity, but their inhibitory potency in MVD preparations correlated roughly with their antinociceptive potency in vivo. Pravadoline was also inhibitory in the MVD. Its antinociceptive activity, therefore, may be a consequence of both its PG synthetase inhibitory potency and another antinociceptive mechanism, the latter associated with its inhibitory potency in the MVD.(ABSTRACT TRUNCATED AT 400 WORDS)

Analgesia↗
PubMed1991

The effect of a low-osmolar radiographic contrast medium on in vivo and postmortem renal size.

High osmolar radiographic contrast media (CM) are known to cause an increase in renal size. To examine the effect of low-osmolar CM on renal size, 14 anesthetized dogs received 12 intravenous bolus injections of 0.5 mL/kg iohexol (541 mOsm/L). The postmortem renal, cortical, and medullary volumes were determined by fluid displacement. Renal volumes of 18 control dogs were determined similarly. The mean (+/- SEM) postmortem renal volumes were 66.1 +/- 2.2 mL for the CM group and 52.3 +/- 3.3 mL for the control group (P = 0.003), whereas the cortical and medullary volumes were similar. Six dogs were also scanned by fast computerized tomography before and after iohexol administration. The in vivo whole renal and medullary volumes enlarged from 67.4 +/- 3.0 to 77.1 +/- 2.8 mL (P = 0.006), and from 28.5 +/- 2.0 to 35.1 +/- 1.1 mL (P = 0.026), respectively, while the cortical volume remained unaltered. These results suggest that even low osmolar CM may significantly increase renal volume, probably by causing tubular expansion.

Animals↗
PubMed1990

Combined percutaneous coronary atherectomy and coronary angioplasty: experience in 19 consecutive patients.

Among 82 patients undergoing coronary atherectomy, 19 (23%) underwent this procedure in combination with coronary angioplasty. The most frequently involved vessel was the left anterior descending coronary artery. In 11 patients (58%), attempted atherectomy preceded coronary angioplasty. In 6 of the 11, angioplasty was used after the atherectomy catheter could not be positioned across the lesion; 4 patients underwent "rescue" angioplasty after developing vessel occlusion related to atherectomy and 1 patient had an unsatisfactory result of atherectomy. The success rate of the combined intervention was 82% for these 11 patients. In eight patients (42%), atherectomy was performed after initial angioplasty. In four of the eight, atherectomy was a rescue procedure to manage vessel occlusion by thrombus or intimal dissection and was successful in three. In the other four, angioplasty was performed to establish an easier passage for the atherectomy catheter and was successful in three. Thus, the success rate of the combined intervention was 75% for these eight patients. The overall success rate for all 19 patients was 79%; there was one in-hospital death and one non-Q wave infarction, and one patient required immediate coronary artery surgery. Two other patients underwent coronary artery surgery before hospital discharge. Combined intervention with coronary angioplasty and atherectomy seems to be a relatively safe and effective approach in selected patients when either of these procedures alone is unsuccessful or is accompanied by acute coronary complications.

Adult↗
PubMed1990

Restenosis after directional coronary atherectomy: differences between primary atheromatous and restenosis lesions and influence of subintimal tissue resection.

Rates of restenosis were evaluated in 70 patients (74 lesions) after successful directional coronary atherectomy. The extent of vascular tissue resection was correlated with restenosis rates for coronary (n = 59) and vein bypass graft (n = 15) lesions. After 6 months, the overall restenosis rate was 50% (37 of 74 lesions); it was 42% (15 of 36 lesions) when intima alone was resected, 50% (7 of 14 lesions) when media was resected and 63% (15 of 24 lesions) when adventitia was resected. Subintimal tissue resection increased the restenosis rate for vein grafts (43% with intimal resection versus 100% with subintimal resection, p = 0.01) but not for coronary arteries (50% versus 48%). There was no overall difference in restenosis rates after atherectomy between primary lesions and restenosis lesions that occurred after balloon angioplasty (46% versus 54%). Among postballoon angioplasty restenosis lesions, a higher rate of restenosis after atherectomy was found with subintimal than with intimal resection (78% versus 32%, p = 0.01). Tissues from patients undergoing a second atherectomy for restenosis after initial atherectomy (n = 8) demonstrated neointimal hyperplasia that appeared histologically identical to restenotic tissue developing after balloon angioplasty (n = 37). These data suggest that the cellular response to directional coronary atherectomy is characterized by neointimal proliferation similar to that which may develop after balloon angioplasty. The extent of fibrous hyperplasia appears to be related to the depth of tissue resection in vein graft lesions and coronary artery restenosis lesions that occur after balloon angioplasty but not in primary atheromatous coronary artery lesions.

Angioplasty, Balloon, Coronary↗
PubMed1990

Percutaneous transluminal angioplasty in patients with multivessel coronary disease: how important is complete revascularization for cardiac event-free survival?

The relative influences of revascularization status and baseline characteristics on long-term outcome were examined in 867 patients with multivessel coronary disease who had undergone successful coronary angioplasty. These patients represented 83% of a total of 1,039 patients in whom angioplasty had been attempted with an in-hospital mortality and infarction rate of 2.5% and 4.8%, respectively. Emergency coronary bypass surgery was needed in 4.9%. Of the 867 patients, 41% (group 1) were considered to have complete revascularization and 59% (group 2) to have incomplete revascularization. Univariate analysis revealed major differences between these two groups with patients in group 2 characterized by advanced age, more severe angina, a greater likelihood of previous coronary surgery and infarction, more extensive disease and poorer left ventricular function. Over a mean follow-up period of 26 months, the probability of event-free survival was significantly lower for group 2 only with respect to the need for coronary artery surgery (p = 0.004) and occurrence of severe angina (p = 0.04). The difference in mortality was of borderline significance (p = 0.051) and there were no significant differences between groups 1 and 2 in either the incidence of myocardial infarction or the need for repeat angioplasty. Multivariate analysis identified independent baseline predictors of late cardiac events that were then used to adjust the probabilities of event-free survival. This adjustment effectively removed any significant influence of completeness of revascularization on event-free survival for any of the above end points including the combination of death, myocardial infarction and need for coronary artery surgery. Therefore, late outcome in these patients is not significantly influenced by revascularization status but depends more on baseline patient characteristics.

Age Factors↗
PubMed1990

Does intracoronary infusion of Fluosol-DA 20% prevent left ventricular diastolic dysfunction during coronary balloon angioplasty?

Distal intracoronary infusion of the perfluorochemical Fluosol-DA 20% has been shown to prevent systolic dysfunction during coronary artery balloon occlusion in coronary angioplasty. To assess its effect on global diastolic dysfunction, a randomized, single-blind, crossover protocol comparing intracoronary infusion of Fluosol or no infusion (control) was performed during 60 s balloon inflations in 10 patients (mean age 67 years) undergoing coronary angioplasty. Assessment of global systolic and diastolic function was obtained with high fidelity micromanometer measurements of left ventricular pressure. Eighteen pairs of balloon inflations (Fluosol versus control) were analyzed. Patients reported significantly less severe chest pain during inflations accompanied by Fluosol compared with control. However, during coronary balloon occlusion, no significant differences in the changes from baseline values were observed between Fluosol and control with regard to ventricular relaxation, including the time constant of early ventricular relaxation (tau) and maximal rate of fall in left ventricular pressure (maximal negative dP/dt). No differences between Fluosol and control were observed in terms of the increase in end-diastolic pressure or minimal diastolic pressure during balloon inflation. Mean systolic pressure decrease from baseline values was greater during control than during Fluosol inflations (-9.0 +/- 3.3 mm Hg, p = 0.013), but no significant difference was observed in the change in maximal rate of rise in left ventricular pressure (maximal positive dP/dt). These results suggest that Fluosol does not preserve global left ventricular diastolic function during coronary balloon occlusion, possibly because of its limited oxygen delivery capability relative to arterial blood.

Aged↗
PubMed1990

Antiandrogenic steroidal sulfonylpyrazoles.

The steroidal sulfonylpyrazole 1 bound to the rat ventral prostate androgen receptor in vitro; it inhibited testosterone propionate induced increases in ventral prostate weight in vivo in the castrated, immature male rat with an ED50 of 15 mg/kg po. Compound 1 lacked androgenic activity in vivo in contrast to the parent steroidal pyrazole 5, which was both androgenic and antiandrogenic. The 2'- and 5'-methylsulfonyl isomers 6 and 6a did not bind to the androgen receptor. Introduction of an alkylsulfonyl at the N-1'-position has served, therefore, to isolate the intrinsic antiandrogenic properties of the steroidal heterocycle free of apparent hormone agonist properties. Structure-activity relationship studies revealed that a methylsulfonyl group at N-1' together with a C-17 alpha-substituent were the optimal combination for in vitro androgen receptor binding, in vivo antiandrogenic potency, and a lack of androgenic activity.

Androgen Antagonists↗
PubMed1990

Detection of mild coronary stenoses using the Dynamic Spatial Reconstructor.

The accuracy of the Dynamic Spatial Reconstructor (DSR) in the detection of moderate coronary artery stenoses was examined in 20 closed-chest dogs. Twenty-eight hollow plastic cylinders were embolized into the left coronary arteries and produced 25% to 56% reductions in arterial lumina diameter. For each dog, one three-dimensional (3-D) image of the heart was reconstructed from each DSR scan recorded during injection of contrast into the aortic root. Analysis involved blinded visual analysis by four independent observers of multiview projection images computed from the single 3-D image. Postmortem coronary angiograms of the isolated heart were considered definitive for location of the stenoses. Overall sensitivity of detection by DSR was 89% and specificity 81%. Sensitivity of detecting stenoses greater than or equal to 50% was 98%. Receiver operating characteristics (ROC) analysis showed that detection of stenoses in the left coronary arteries is of equal sensitivity and specificity.

Animals↗
PubMed1990

Quantitation of the in vivo kidney volume with cine computed tomography.

The authors examined the utility of cine computerized tomography (CT) for noninvasive determination of whole kidney, cortical, and medullary volumes. The right kidneys of 14 anesthetized dogs were scanned after an intravenous bolus injection of iohexol, and their volumes determined after boundary identification. After the scans, the kidneys were excised at postmortem examination and their volumes determined by fluid displacement. The mean (+/- standard error of the mean [SEM]) postmortem and in vivo renal volumes were 66.1 +/- 2.2 cc and 78.2 +/- 2.4 cc, respectively (r = 0.86; P less than 0.001). The difference was consistent with the blood, filtrate, and urine contents of the in vivo kidney. The in vivo cortical and medullary volumes correlated poorly with their postmortem volumes because of difficulties in boundary definition. These results demonstrate the feasibility for fast and reliable in vivo whole kidney volume quantitation by cine CT.

Animals↗
PubMed1990

Does the emergency room electrocardiogram identify patients with suspected myocardial infarction who are at low risk of acute complications?

To determine the early morbidity of patients admitted to the coronary care unit (CCU) with inconclusive evidence of acute myocardial infarction, the prognostic value of the emergency room electrocardiogram (ECG) was examined prospectively in a blinded fashion in 410 patients presenting with acute chest pain. One hundred and forty one patients (34.4%) had an ECG that was normal, showed ST segment changes less than 1 mm, or was unchanged from a previous recording (group 1). The remaining patients (65.6%, group 2) had ECGs considered abnormal. Thirty-nine patients in group 1 and 226 in group 2 had confirmed infarction. There was one CCU death in group 1 (0.7%) versus 27 (10.0%) in group 2 (p less than 0.001) and the overall hospital mortality for group 1 was 2.1% versus 13.0% in group 2 (p less than 0.001). Twenty-eight patients (19.9%) from group 1 suffered complications in the CCU versus 155 (57.6%) from group 2 (p less than 0.001). No life-threatening arrhythmias occurred in group 1 versus occurrence in 47 patients (17.5%) in group 2 (p less than 0.001). The need for acute intervention was also less for group 1 versus group 2 patients, 14 (9.9%) and 85 (31.6%) respectively (p less than 0.001) with no patient requiring electrical cardioversion in group 1. It is concluded that the emergency room ECG can reliably identify a group of low risk patients presenting with suspected myocardial infarction and so help in establishing priority for admission to the CCU. Furthermore, the risk-benefit of thrombolytic therapy in these low risk patients appears unacceptable.

Aged↗