Biomedical subjects

M R Bell

Publications and source records attributed to M R Bell.

At least 55 records · Page 3Linked to original sources

PubMed1997

Validation of a new UNIX-based quantitative coronary angiographic system for the measurement of coronary artery lesions.

We describe a method of validation of computerized quantitative coronary arteriography and report the results of a new UNIX-based quantitative coronary arteriography software program developed for rapid on-line (digital) and off-line (digital or cinefilm) analysis. The UNIX operating system is widely available in computer systems using very fast processors and has excellent graphics capabilities. The system is potentially compatible with any cardiac digital x-ray system for on-line analysis and has been designed to incorporate an integrated database, have on-line and immediate recall capabilities, and provide digital access to all data. The accuracy (mean signed differences of the observed minus the true dimensions) and precision (pooled standard deviations of the measurements) of the program were determined x-ray vessel phantoms. Intra- and interobserver variabilities were assessed from in vivo studies during routine clinical coronary arteriography. Precision from the x-ray phantom studies (6-In. field of view) for digital images was 0.066 mm and for digitized cine images was 0.060 mm. Accuracy was 0.076 mm (overestimation) for digital images compared to 0.008 mm for digitized cine images. Diagnostic coronary catheters were also used for calibration; accuracy.varied according to size of catheter and whether or not they were filled with iodinated contrast. Intra- and interobserver variabilities were excellent and indicated that coronary lesion measurements were relatively user-independent. Thus, this easy to use and very fast UNIX based program appears to be robust with optimal accuracy and precision for clinical and research applications.

Algorithms↗

PubMed1997

Interventional cardiology and intracoronary stents--a changing practice: approved vs. nonapproved indications.

Our objective was to document change in stent usage in a single practice over time and to study "off-label" compared to Food and Drug Administration (FDA)-approved indications. Although only two intracoronary stents have been approved by the FDA, the relatively limited approved indications do not account for the dramatic increase in stent implantation. This increase has important implications for patient health care delivery. This study of stent usage in a single center over a 36-mo period included all patients treated with coronary stents at the Mayo Clinic from January 1993-December 1995, and evaluated the relative difference in frequency between "off-label" and FDA-approved indications for implantation. During the 36-mo period of study, 3,614 interventional procedures were done and one or more stents were placed in 25.4% of patients. The proportion of patients receiving stents increased throughout this time: during the first 6-mo period, stents were placed in 6.2% of procedures; during the last 6-mo period, stents were placed in 46.3% of procedures, an eightfold increase. During the final 6 mo, an unapproved device or an unapproved indication for an approved device constituted 59.4% of all stent procedures. In addition, use of the non-FDA-approved adjunctive treatment regimen without warfarin increased from 2.9% in the first 6-mo period of observation to 82.7% in the last 6 mo. The use of stents increased strikingly over a 36-mo period, from 6% to 46% of all procedures. The majority of implantations were performed either for an "off-label" unapproved indication or with an unapproved device.

Angioplasty, Balloon, Coronary↗

PubMed1997

Quantitative evaluation of regional myocardial perfusion using fast X-ray computed tomography.

Clinical quantitation of regional myocardial perfusion using a minimally invasive and easily applied technique could allow for ready quantitation of the functional significance of coronary disease, allow for further understanding of flow reserve in various cardiomyopathic and hemodynamic overload (pressure versus volume) conditions, and possibly provide basic information needed regarding the development and clinical significance of coronary collateral vessels and diseases of the myocardial microcirculation. Electron beam CT (EBCT) is a unique cardiac imaging modality that allows for rapid acquisition tomographic slices of the heart with excellent spatial resolution. It has been demonstrated to provide accurate measurements of cardiac anatomy, biventricular function, myocardial mass, and estimates of mural atherosclerotic plaque burden via quantification of coronary calcium. The application of classical indicator techniques for use by fast x-ray computed tomography techniques such as electron beam CT has been shown to allow quantitative analysis of regional myocardial perfusion throughout the myocardium. Initial studies using central intravenous contrast injection in experimental animals showed a close correlation of regional myocardial perfusion as quantitated by electron beam CT with measurements using radiolabeled microspheres at resting and moderately increased flow states. At high flow states, however, electron beam CT significantly underestimated absolute myocardial perfusion and thus myocardial flow reserve. Using another fast CT device, the Dynamic Spatial Reconstructor (DSR), concepts of intramyocardial vascular blood volume and its relation to myocardial flow have been established. By adapting these concepts to electron beam CT scanning and accounting for the increase in intramyocardial vascular blood volume at vasodilatation, the ability to correctly quantitate perfusion states up to approximately 400 mL.min-1. 100 g-1 using central intravenous contrast administration was demonstrated. This implies that studies can be done with intravenous injection methods for characterization of regional myocardial perfusion up to the normal flow reserve of approximately 4:1. Important physiologic and clinical abnormalities in flow reserve generally result in a ratio < 3:1. Electron beam CT offers the capability to quantitate regional myocardial perfusion in both the clinical and research setting. Of particular interest is the ability to provide quantitative regional myocardial perfusion which can be coupled to the evaluation of cardiac anatomy and function as well as mural coronary atherosclerotic calcium burden during the same scanning session. Thus, electron beam CT has the potential to become a valuable, minimally invasive clinical tool for comprehensive analysis of cardiac function and coronary status.

Cardiomyopathies↗

PubMed1997

Clinical outcome of patients undergoing endoluminal coronary artery reconstruction with three or more stents.

OBJECTIVES: We sought to evaluate the outcome of patients undergoing multiple (three or more), contiguous stent implantation within a single native coronary artery. BACKGROUND: The implantation of multiple stents within a single coronary artery is increasing in frequency, although the outcome of such patients is not well described. METHODS: Forty-five patients without previous coronary artery bypass graft surgery (CABG) undergoing multiple, contiguous stent implantation in a single coronary artery were identified. Clinical and angiographic characteristics and outcomes were analyzed. RESULTS: The angiographic success rate was 97.8%. The procedural success rate was 91.1%; stent occlusion during the initial hospital period occurred in four patients (8.9%). Death, myocardial infarction (MI), CABG, repeat target vessel intervention or severe angina occurred in 10 (23.3%) of 43 hospital survivors at 6-months follow-up. The indication for stent placement was threatened or abrupt closure in 30 patients (66.7%). Of the 25 patients with abrupt or threatened closure whose clinical and angiographic data would have indicated emergent CABG had stents not been available, the frequency of in-hospital death and Q wave MI was similar to that of a matched consecutive series of patients at our institution who underwent emergent CABG after failed angioplasty. At 1 year, the frequency of death, Q wave MI, CABG and severe angina at 1 year was similar in the two groups; the need for repeat percutaneous intervention was more common in the stent group (25% vs. 0%, p = 0.01). CONCLUSIONS: Implantation of multiple, contiguous intracoronary stents was associated with a high initial success rate, although the incidence of early stent closure was relatively high. Adverse events at 6 months of follow-up were more frequent than previously reported for elective single-stent implantation; however, adverse angiographic characteristics such as dissection and thrombus were frequent in this group. In addition, the strategy of multiple stent implantation in the setting of failed angioplasty is a reasonable alternative to emergent CABG, although the need for further percutaneous intervention must be anticipated.

Angioplasty, Balloon, Coronary↗

PubMed1997

Comparison of immediate and long-term outcome of coronary angioplasty performed for unstable angina and rest pain in men and women.

OBJECTIVE: To determine whether a sex-related difference in outcome is present among patients who undergo percutaneous transluminal coronary angioplasty (PTCA) for unstable angina. DESIGN: We retrospectively analyzed the results after PTCA was performed between January 1981 and June 1993 in a series of 2,073 men and 941 women with unstable angina and rest pain. RESULTS: The success rates of PTCA were similar for women and men (87.9% and 87.2%, respectively), as were the in-hospital mortality rates (4.1% and 3.2%, respectively) and the need for emergency coronary artery bypass operation (3.1% and 3.5%, respectively). Fewer women than men had Q-wave myocardial infarction (0.5% versus 1.6%; P = 0.02). During the follow-up period (mean, 4 years), no significant differences were noted between women and men in overall survival (81% and 85% at 6 years, respectively) or survival free of Q-wave myocardial infarction (81% and 83% at 6 years, respectively) with use of the Kaplan-Meier method. Women were less likely than men to have had coronary artery bypass grafting (19% versus 22% at 6 years; P = 0.02), and the occurrence of severe angina was higher in women than in men (52% versus 44% at 6 years; P = 0.001). A subgroup analysis of patients who had myocardial infarction within 7 days preceding PTCA showed a similar pattern of results. CONCLUSION: After PTCA performed for unstable angina and rest pain, survival rates were excellent in both women and men, and no difference was observed in subsequent myocardial infarction rates. During follow-up, however, women were more likely to have severe angina and were less likely to have had coronary artery bypass grafting. Concerns about possible sex-related complications should not dissuade physicians from performing PTCA when clinically indicated for unstable angina and rest pain.

Aged↗

PubMed1997

Determination of ventricular ejection fraction: a comparison of available imaging methods. The Cardiovascular Imaging Working Group.

Knowledge of left ventricular ejection fraction has been shown to provide diagnostic and prognostic information in patients with known or suspected heart disease. In clinical practice, the ejection fraction can be determined by using one of the five currently available imaging techniques: contrast angiography, echocardiography, radionuclide techniques of blood pool and first pass imaging, electron beam computed tomography, and magnetic resonance imaging. In this review, we discuss the clinical application as well as the advantages and disadvantages of each of these methods as it relates to determination of ventricular ejection fraction.

Angiocardiography↗

PubMed1996

Impact of stent size and indication for stent placement on immediate outcome.

The immediate outcome of 271 procedures involving the intracoronary implantation of 305 stents was determined. Data were analyzed with regard to indication for stenting and stent size. Elective indication was associated with a higher success rate than emergency indication (95.6% vs. 86.6%, P = 0.013) and a lower Q-wave infarction rate (0 vs. 6.4%, P = 0.006). Univariate analysis showed that the odds ratio for procedural success was significantly favored by elective indication (3.37, P = 0.018) but was unrelated to stent size (1.10, P = 0.087). These findings were confirmed on multivariate analysis. The likelihood of Q-wave infarction was lower for elective placement (P = 0.0008) but was not related to size. Requirement for emergency bypass surgery, incidence of subacute closure, and death were not related to indication or to stent size on either univariate or multivariate analysis. Therefore, the immediate outcome of stent placement is related to the indication for stenting, but not to the size of stent implanted. Procedural success is significantly favored by elective indication.

Adult↗

PubMed1996

Coronary angioplasty and intracoronary thrombolysis are of limited efficacy in resolving early intracoronary stent thrombosis.

OBJECTIVES: This study sought to evaluate treatment of early intracoronary stent thrombosis. BACKGROUND: Although refinements in intracoronary stent implantation technique and pharmacologic treatment have reduced the frequency of early stent thrombosis, stent thrombosis remains a feared complication of this procedure. Optimal treatment for stent thrombosis is still undefined. METHODS: Twenty-nine patients (44 stents) with early (< or = 30 days) coronary stent thrombosis over a 5-year period at our institution were identified. Treatment and outcome of stent thrombosis were analyzed. RESULTS: Mean (+/- SD) time from implantation to stent thrombosis was 6.1 +/- 5 days. Twenty-three patients were treated with catheter-based therapies (angioplasty alone in 14, angioplasty and intracoronary urokinase in 7, intracoronary urokinase alone in 2). Flow was restored without residual thrombus in 11 (48%) of the catheter-treated patients (6 of 14 with angioplasty alone, 4 of 7 with angioplasty and urokinase, 1 with urokinase alone). Of the 23 patients, 2 died despite restoration of anterograde flow, and 9 were referred for emergent or urgent bypass surgery because of residual thrombus and refractory angina despite restoration of blood flow. Of the remaining six patients, five were treated medically and one with coronary bypass surgery; three died. Acute myocardial infarction evolved in 26 patients (90%), including 20 (87%) of the 23 catheter-treated patients. CONCLUSIONS: Stent thrombosis is associated with severe adverse outcomes. Although catheter-based therapies are effective in restoring patency in a majority of patients, patients are referred frequently for coronary bypass surgery because of residual thrombus and refractory angina. These findings suggest that alternative or adjunctive therapies for stent thrombosis are needed.

Angioplasty, Balloon, Coronary↗

PubMed1996

Seizures and the long-QT syndrome.

We describe a case of idiopathic long-QT syndrome in a 4-year-old Hispanic girl. She had been seen previously at an outside hospital for possible new-onset seizure disorder but was brought to our emergency department after sustaining an unwitnessed fall. Her ECG was significant for changes consistent with long-QT syndrome. Emergency physicians should understand the necessity of electrocardiography in all pediatric patients who present with multiple spontaneous falls, episodes of dizziness, new-onset seizure activity and syncopal episodes.

Accidental Falls↗

PubMed1996

Influence of procedural success on immediate and long-term clinical outcome of patients undergoing percutaneous revascularization of occluded coronary artery bypass vein grafts.

OBJECTIVES: This study sought to determine whether successful recanalization of an occluded vein graft is associated with improvement in long-term clinical outcome. BACKGROUND: Coronary angioplasty of occluded vein grafts is associated with a lower initial success rate and a higher complication rate than angioplasty of vein grafts with subtotal stenoses and native coronary arteries. Whether successful angioplasty improves clinical outcome is unknown. METHODS: We analyzed 77 consecutive patients who underwent angioplasty of an occluded saphenous vein coronary artery bypass graft between August 1983 and June 1994. Patients with a myocardial infarction in the previous 24 h were excluded from the study. RESULTS: The mean age of the study cohort was 65 years; the mean (+/- SD) age of the treated grafts was 7.5 +/- 3.9 years. As an adjunct to balloon angioplasty, stents were used in 9% of procedures, laser in 30%, and atherectomy in 16%, and thrombolytic therapy was administered in 23% of patients. The angioplasty success rate was 71%. Major complications within 30 days of the procedure included death in 5.2% of patients, Q wave myocardial infarction in 1.3% and repeat bypass surgery in 7.8%; these events occurred with similar frequency in patients in whom angiographic success was and was not achieved. Kaplan-meier analysis comparing patients in whom angioplasty was successful (n = 55) and not successful (n = 22) revealed no differences in survival or occurrence of myocardial infarction or recurrent severe angina between the two groups in the 3 years after the procedure. Univariate analysis identified the age of the graft and use of newer interventional devices as predictors of death or myocardial infarction during this time period; procedural success was not associated with freedom from these adverse events after adjusting for these variables. CONCLUSIONS: Angioplasty of occluded vein grafts is associated with a low initial success rate and a high complication rate. Successful angioplasty does not appear to reduce the occurrence of adverse events in the 3 years after the procedure.

Aged↗

PubMed1996

Are there gender differences or issues related to angiographic imaging of the coronary arteries?

The use of coronary angiography and coronary interventions in women with suspected coronary artery disease has recently come under close scrutiny. Clear differences in the utilization of these procedures, including coronary artery bypass graft (CABG) surgery have led to concerns that a bias may exist against the use of these procedures in women. Alternative explanations of these perceived practice differences have focused on their propriety based on patients' ages, underlying disease severity, expected prevalence of coronary disease and comorbid conditions rather than physician bias. The possibility that these procedures are over utilized in men has also been suggested. Pertinent to this debate are historical observational data suggesting that women may be at higher risk of major complications of coronary interventions and CABG surgery. Because coronary artery disease is the most frequent cause of death among women in the United States, there is some sociopolitical urgency in addressing these important concerns. This article reviews the use and findings of diagnostic coronary angiography in women with suspected coronary artery disease. Specific risks to women who have coronary angiography performed are also discussed. Finally, the outcome of percutaneous coronary revascularization procedures in women compared to men is discussed.

Aged↗

PubMed1995

Endothelin in coronary endothelial dysfunction and early atherosclerosis in humans.

BACKGROUND: The endothelium modulates vascular tone through release of vasodilating substances, such as endothelium-derived relaxing factors, and vasoconstricting substances, such as endothelin. Endothelin concentrations are elevated in humans with atherosclerosis and in hypercholesterolemic pigs. Furthermore, the endothelium-dependent vasodilator acetylcholine increases endothelin in hypercholesterolemia in association with coronary vasoconstriction. The present study was designed to test the hypotheses that coronary endothelial dysfunction in humans is characterized by enhanced coronary and circulating endothelin and that the vasoconstriction associated with acetylcholine results in further release of coronary endothelin. METHODS AND RESULTS: Coronary and circulating endothelin concentrations were measured at baseline and during intracoronary acetylcholine administration in 20 patients undergoing diagnostic coronary angiography. Patients were divided into two groups on the basis of their response to intracoronary acetylcholine. Group 1 (n = 7) demonstrated a normal vasodilatory response, but group 2 (n = 13) demonstrated coronary vasoconstriction. Baseline coronary and circulating endothelin concentrations (as determined by coronary sinus and femoral artery measurements, respectively) were higher in patients who responded to acetylcholine with coronary vasoconstriction (group 2) than in group 1 patients (coronary sinus, 15.9 +/- 1.0 pg/mL versus 7.1 +/- 1.0 pg/mL; femoral, 14.1 +/- 0.9 pg/mL versus 6.8 +/- 1.0 pg/mL, respectively; P < .01). In response to intracoronary acetylcholine, a further increase in coronary endothelin was observed only in group 2; this increase correlated with changes in coronary artery diameter. CONCLUSIONS: This study demonstrates that endothelin immunoreactivity is enhanced in the coronary and systemic circulation in humans with coronary endothelial dysfunction. Moreover, acetylcholine further increased coronary endothelin concentration in patients with coronary endothelial dysfunction and was associated with coronary vasoconstriction. These observations strongly support a role for endothelin as an early participant in and marker for coronary endothelial dysfunction in humans.

Acetylcholine↗

PubMed1995

Time to reperfusion and other procedural characteristics of emergency coronary artery bypass surgery after unsuccessful coronary angioplasty.

A databank search was performed and 148 consecutive patients (mean age 59.5 +/- 10.4 years) were identified who underwent emergency coronary artery bypass surgery at the Mayo Clinic between November 20, 1979, and February 12, 1992, immediately after unsuccessful coronary angioplasty. At the end of the angioplasty procedure, there was no anterograde coronary blood flow in the treated artery in 54%, ongoing chest pain in 78%, and hemodynamic compromise requiring intravenous vasopressor therapy in 25% of patients; 127 patients (86%) had at least 1 of these adverse characteristics. After leaving the catheterization laboratory, the median time to arrival in the operating room was 12 minutes. Median time from arrival in the operating room to initiation of cardiopulmonary bypass was 86 minutes, to administration of cardioplegia was 98 minutes, and to removal of the aortic cross-clamp was 135 minutes. In-hospital mortality was 11%, and 18% developed nonfatal Q-wave myocardial infarction. Thus, significant time is required to achieve surgical reperfusion after unsuccessful coronary angioplasty.

Aged↗

PubMed1995

Aminoalkylindoles: structure-activity relationships of novel cannabinoid mimetics.

Aminoalkylindoles (AAIs) are a novel series of cannabinoid receptor ligands. In this report we disclose the structural features of AAIs which are important for binding to this receptor as measured by inhibition of binding of [3H]Win 55212-2 (5). Functional activity in the mouse vas deferens is also noted and used to distinguish agonists from potential antagonists. The key structural features for potent cannabinoid activity in this series are a bicyclic (naphthyl) substituent at the 3-position, a small (H) substituent at the 2-position, and an aminoethyl (morpholinoethyl) substituent at the 1-position. A 6-bromo analog, Win 54461 (31), has been identified as a potential cannabinoid receptor antagonist. Modeling experiments were done to develop a pharmacophore and also to compare AAI structures with those of classical cannabinoids. The fact that the cannabinoid AAIs arose out of work on a series of cyclooxygenase inhibitors make sense now that an endogenous cannabinoid ligand has been identified which is a derivative of arachidonic acid. Because of their unique structures and physical properties, AAIs provide useful tools to study the structure and function of the cannabinoid receptor(s).

Animals↗

PubMed1995

Long-term outcome of women compared with men after successful coronary angioplasty.

BACKGROUND: Women who undergo coronary angioplasty have a higher in-hospital mortality than men, although much of this difference can be accounted for by their poorer clinical characteristics at the time of their procedures. However, whether or not there are important long-term differences in outcome between women and men after coronary angioplasty is not clear. METHODS AND RESULTS: A retrospective analysis was performed of 3027 consecutive patients (824 women and 2203 men) who underwent successful angioplasty and who have been followed continuously for a mean of 5.5 years (range, 0.5 to 14 years). Follow-up is 100% complete. Event-free survival was assessed by the Kaplan-Meier method, and clinical end points were also examined by Cox proportional-hazards models to account for important baseline differences when appropriate. There was a trend toward lower survival among women during follow-up, but this was not significant (P = .06). The relative risk of death among women compared with men after adjustment for baseline differences was 0.94 (CI, 0.76 to 1.15; P = NS). No significant sex differences in occurrence of Q-wave myocardial infarction were observed. Women were less likely to remain free of angina after 10 years (34% versus 37%, respectively; P = .008), but after adjustment for baseline differences, this difference was not significant (relative risk of angina, 1.07; CI, 0.95 to 1.21). Women tended to have less coronary artery bypass surgery performed during follow-up (P = .06); adjusting for baseline differences made this difference more significant (relative risk, 0.79; CI, 0.64 to 0.96; P = .02). Among patients who were not treated in the setting of acute infarction, no sex differences in survival and freedom from myocardial infarction were noted. CONCLUSIONS: After successful coronary angioplasty, the long-term prognosis for women is excellent and is similar to that observed in men. Risk-adjusted survival did not differ significantly between the sexes, but less frequent use of subsequent surgical revascularization was observed in women.

Aged↗

PubMed1995

Orally bioavailable benzisothiazolone inhibitors of human leukocyte elastase.

Human leukocyte elastase (HLE) has been proposed as a primary mediator of pulmonary emphysema and other inflammatory airway diseases. HLE is capable of cleaving many proteins, including elastin, other components of connective tissue, certain complement proteins, and receptors. Under normal conditions an appropriate balance exists in the lung between HLE and endogenous inhibitors, which scavenge the released enzyme before it exerts deleterious effects in the lung. Emphysema is thought to result from an imbalance in the lung between HLE and endogenous inhibitor (elevated elastase or insufficient inhibitor) that leads to the destruction of alveoli. We have identified WIN 64733 (2) and WIN 63759 (3) as potent (Ki* = 14 and 13 pM, respectively), selective, mechanism-based inhibitors of HLE which are orally bioavailable in the dog (absolute bioavailability 46% and 21%, respectively). In this series the in vitro stabilities of the inhibitors in blood, jejunal homogenates, and liver S9 homogenates are useful predictors of oral bioavailability. After being administered orally (30 mg/kg) to dogs, compounds 2 and 3 are found in the lung, being detected in the epithelial lining fluid obtained by bronchoalveolar lavage (Cmax of 2.5 and 0.47 microgram/mL, respectively).

Administration, Oral↗

PubMed1995

Referral for coronary artery revascularization procedures after diagnostic coronary angiography: evidence for gender bias?

OBJECTIVES: We sought to determine whether there is a gender bias in the selection of patients for coronary revascularization once the severity of the underlying coronary artery disease has been established with angiography. BACKGROUND: It has been suggested that women with coronary artery disease are less likely to be referred for coronary angiography and coronary artery bypass surgery than men. Whether such a referral bias for revascularization procedures, including coronary angioplasty, is present once angiography has been performed is not clear. METHODS: We retrospectively analyzed 22,795 patients with suspected coronary artery disease who underwent coronary angiography between 1981 and 1991 and compared the numbers of women and men who underwent either coronary artery bypass surgery or coronary angioplasty within 30 days of coronary angiography. RESULTS: Angiography revealed significant (one-vessel or more) disease in 15,455 patients (52% of women, 76% of men). Despite worse symptoms, women had less extensive coronary disease than men as judged by the number of vessels diseased. Women were also more likely to have other co-morbid diseases. An equal proportion of women (54%) and men underwent revascularization procedures. After adjustment for baseline differences and age, differences in the two individual revascularization strategies were very small: More women tended to have coronary angioplasty ([absolute difference +/- 1 SD] + 3.3 +/- 0.7%, p < 0.0001), but fewer had coronary artery bypass surgery than men (-2.5 +/- 0.8%, p = 0.003). When the two revascularization strategies were considered together, there was no significant gender difference in overall adjusted use of revascularization (+ 0.8 +/- 0.9%, p = 0.41). CONCLUSIONS: Once diagnostic coronary angiography had been performed, no major differences in the overall utilization of revascularization procedures were noted for women compared with men.

Aged↗

PubMed1994

Androgen receptor affinity of 5'-acyl furanosteroids.

Syntheses of 5'-acyl furanosteroids are described from the corresponding unsubstituted [3,2-b]furanosteroids using acid anhydrides and acid chlorides in the presence or absence of Lewis acids. New methods have been developed to prepare 5'-acetyl derivatives: reduction of a 5'-trichloroacetyl intermediate either by sodium formaldehyde sulfoxylate or with 10% Pd/C. Most of these 5'-acyl derivatives bind to the rat ventral prostate androgen receptor. However the antiandrogenic activity was diminished when compared with 4,5'-methylsulfonyl furanosteroid. Biological studies revealed that 5'-acyl furanosteroids were either androgens or modest antiandrogens. The electrostatic potential maps of the substructures of 3, 4, and 5'-acetyl syn- and anti-furanosteroids showed striking differences which may explain, to some extent, the lack of significant antiandrogenic activity of 5'-acyl furanosteroids.

Androgen Antagonists↗