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Biomedical subjects

E McFadden

Publications and source records attributed to E McFadden.

At least 19 recordsLinked to original sources
PubMed2001

The human G-protein beta3 subunit C825T polymorphism is associated with coronary artery vasoconstriction.

AIMS: Abnormal coronary vasomotion plays a role in the clinical expression of coronary artery disease. We hypothesized that the functional C825T polymorphism located in the ubiquitous G-protein beta3 subunit, implicated in the cellular signal transduction of many receptors, could modify artery coronary vasomotion. We assessed the potential association of the pertussis toxin-sensitive G protein beta3 subunit (GNB3) gene C825T polymorphism on coronary vasomotion in humans. METHODS AND RESULTS: We examined the response of angiographically normal human coronary arteries (n=131) after intravenous injection of methylergonovine maleate, a vasoconstrictor, followed by injection of isosorbide dinitrate, a vasodilator, according to GNB3 genotypes. Coronary vasomotion was assessed with quantitative coronary angiography. Subjects bearing at least one T allele had greater susceptibility to vasoconstriction in response to methylergonovine maleate than CC subjects, whereas vasodilation in response to isosorbide dinitrate did not differ among the different genotypes. CONCLUSION: The C825T polymorphism of the G-protein beta3 subunit may be a genetic determinant of coronary artery vasomotion in humans.

Coronary Angiography↗
PubMed2000

Paraoxonase polymorphism (Gln192Arg) as a determinant of the response of human coronary arteries to serotonin.

Background-Oxidation of LDL plays a role in endothelial dysfunction. Paraoxonase, an enzyme present on HDL, protects LDL against oxidation. Paraoxonase activity is genetically determined in part, and 3 genotypes have been described with variable enzymatic activity. We hypothesized that the paraoxonase polymorphism might influence endothelial function. Methods and Results-Twenty-seven patients with clinical manifestations of coronary artery disease underwent provocative testing by intracoronary administration of serotonin. None of the coronary arteries studied had significant (>50%) stenosis. Ten patients had the QQ genotype and 17 had the QR genotype. At proximal segments, the mean percentage reduction in lumen diameter in response to serotonin was greater in QQ patients than in QR patients (10(-5) mol/L: P<0.05; 10(-4) mol/L: P<0.006). Similarly, at distal segments, constriction in response to serotonin was greater in QQ patients than in QR patients (10(-6) mol/L: P<0. 03; 10(-5) mol/L: P<0.07). Conclusions-These results suggest a higher synthesis or release of endothelium-derived relaxing factors to counteract the vasoconstrictor effect of serotonin in patients with the R allele. These findings provide evidence that the paraoxonase polymorphism may play a role in the regulation of coronary vasomotor tone.

Aged↗
PubMed1999

Angiographically documented late reocclusion after successful coronary angioplasty of an infarct-related lesion is a powerful predictor of long-term mortality.

BACKGROUND: Late reocclusion of an infarct-related artery (IRA) that was patent in the early days after acute myocardial infarction (MI) is a frequent event; the reocclusion rate may be as high as 30%. Few studies have been designed to analyze the impact of late reocclusion of the IRA on late survival. METHODS AND RESULTS: We studied 528 patients who all had a patent IRA after a successful PTCA procedure 10+/-6 days after MI and who underwent systematic 6-month angiographic follow-up to assess late patency of the IRA. We compared long-term survival of patients with and without late reocclusion. Based on the results of 6-month follow-up angiography, 2 groups of patients were defined: (1) 90 patients (17%) with reocclusion (Thrombolysis In Myocardial Infarction [TIMI] flow 0 or 1) and (2) 438 patients (83%) without reocclusion. Long-term clinical follow-up was obtained for all 528 patients at a median of 5.7 years after follow-up angiography (6.4 years after PTCA). The overall actuarial 8-year total mortality rate was 13%. At the end of follow-up, there were 35 deaths (8%) among the 438 patients without reocclusion and 18 deaths (20%) among the 90 patients with reocclusion (P=0.002). The actuarial 8-year total mortality rate was 10% in patients without reocclusion and 28% in patients with reocclusion (P=0.0003). The actuarial cardiovascular mortality rate was 7% in patients without reocclusion and 25% in patients with reocclusion (P<0.0001). The impact of reocclusion on long-term mortality was greater in patients with anterior MI. CONCLUSIONS: Late IRA patency is strongly associated with long-term survival after MI. These observations should encourage prospective studies to evaluate the impact of strategies designed to prevent late reocclusion in postinfarction patients.

Adult↗
PubMed1999

Role of nitric oxide in restenosis after experimental balloon angioplasty in the hypercholesterolemic rabbit: effects on neointimal hyperplasia and vascular remodeling.

OBJECTIVES: The purpose of this study was to assess the effects of L-arginine and N(G)-nitro-L-arginine methyl ester (L-NAME) on neointimal hyperplasia and vascular remodeling after balloon angioplasty in the hypercholesterolemic rabbit. BACKGROUND: Restenosis after balloon angioplasty is a consequence of both neointimal hyperplasia and vessel remodeling. Nitric oxide inhibits neointimal hyperplasia, but its effect on vessel remodeling is unknown. METHODS: Six weeks after induction of bilateral iliac atherosclerosis, 48 rabbits underwent successful angioplasty in 75 vessels. Eight rabbits (acute group) were sacrificed immediately after angioplasty. The remaining animals received either placebo (chronic control group), or a diet supplemented with either L-arginine (1.5 g/kg/day), or L-NAME (15 mg/kg/day) for 4 weeks after angioplasty. RESULTS: The intimal area was significantly greater in the chronic control group compared to the acute group (2.60+/-1.03 mm2 vs. 1.35+/-0.62 mm2). This increase in intimal area was lower in the L-arginine group (1.79+/-0.61 mm2), and greater in the L-NAME group (3.23+/-0.92 mm2). The area circumscribed by the internal elastic lamina (IEL) increased significantly in the control group compared to the acute group (from 2.52+/-0.66 to 3.33+/-0.85 mm2); a more marked increase occurred in the L-NAME group (3.90+/-0.85 mm2). By contrast, IEL area was unchanged in the L-arginine group (2.41+/-0.62 mm2). As a result, there was no significant difference in lumen area after 4 weeks in the chronic groups (control: 0.74+/-0.38 mm2; L-arginine: 0.50+/-0.43 mm2; L-NAME: 0.48+/-0.42 mm2). CONCLUSIONS: Our results demonstrate that L-arginine inhibits whereas L-NAME stimulates neointimal hyperplasia after experimental balloon angioplasty in the hypercholesterolemic rabbit. However, the lack of vessel enlargement in the L-arginine group resulted in a similar final lumen size in the L-NAME and L-arginine groups.

Angiography↗
PubMed1999

Fibromuscular dysplasia of the renal arteries: comparison of helical CT angiography and arteriography.

OBJECTIVE: We evaluated the role of helical CT angiography rendering techniques in the assessment of renal artery fibromuscular dysplasia. MATERIALS AND METHODS: Twenty hypertensive patients (mean age, 56 years) with angiographically proven renal artery fibromuscular dysplasia were studied by CT angiography. The acquisition protocol was collimation, 3 mm; table speed, 3 mm/sec; and incremental algorithm, one. Maximum-intensity-projection and shaded-surface-display reconstructions and transverse sections were reviewed by a consensus panel to determine the sensitivity and specificity of each technique in revealing renal artery fibromuscular dysplasia. RESULTS: Helical CT angiography enabled successful diagnosis of fibromuscular dysplasia in all 20 patients. Helical CT angiography showed 31 of 34 pathologic arteries and 33 of 38 lesions. Aneurysms (>6 mm) on arteriography (n = 12) were revealed in 83% of transverse sections, 75% of maximum-intensity-projection reconstructions, and 58% of shaded-surface-display reconstructions. Lesions that had a string of pearls appearance on arteriography (n = 19) were shown in 53% of transverse sections, 84% of maximum-intensity-projection reconstructions (p < .05 compared with transverse sections), and 74% of shaded-surface-display reconstructions. Stenoses (n = 7 on arteriography) were revealed in 57% of transverse sections, 71% of maximum-intensity-projection reconstructions, and 57% of shaded-surface-display reconstructions. Maximum intensity projection alone revealed 30 (79%) of the 38 angiographic lesions; however, using both maximum intensity projections and transverse sections increased the sensitivity to 87%. CONCLUSION: Helical CT angiography, especially the combination of transverse sections and maximum-intensity-projection reconstructions, can reliably reveal renal artery fibromuscular dysplasia. However, because some lesions may not be shown, arteriography with pressure measurements remains the only technique that can assess the physiologic significance of the dysplasia.

Adult↗
PubMed1999

[Restenosis after angioplasty].

Restenosis remains the main limitation of endocoronary methods of revascularisation. It is observed in 20 to over 50% of cases, depending on the prevailing risk factors and techniques used. The mechanism of post balloon angioplasty restenosis consists of neointimal hyperplasia, vascular remodelling and thrombosis. Intra-stent thrombosis is mainly caused by the neointimal hyperplasia. The strategies developed to prevent restenosis may be grouped in two categories: mechanical and pharmacological strategies. Stenting is the only mechanical method to have been shown to be effective. With respect to pharmacological methods, the general impression is rather negative even if some positive results have been reported recently. Of the new strategies which may provide a solution in the coming years, gene therapy and endocoronary irradiation justify a special mention.

Angioplasty, Balloon, Coronary↗
PubMed1998

Renal artery vasomotion: in vivo assessment in the pig with intravascular Doppler.

Intravascular Doppler is widely used for experimental studies in the coronary circulation. We designed this study to assess baseline bloodflow and arteriolar resistance in the porcine renal circulation and to study the vasomotor responses of vasoactive drugs. In anesthesized piglets (n = 15), renal arterial diameter was measured with quantitative angiography and blood flow velocity with a Doppler wire (Cardiometrics). Bloodflow and resistances were calculated at baseline and after injection of vasoactive drugs (isosorbide dinitrate, papaverine). This allowed us to determine the renal bloodflow reserve (the capacity of the kidney to augment basal bloodflow). Injection of isosorbide dinitrate was associated with an increase in average peak velocity of 64% (P < 0.01) and a small (from 4.5 to 4.74, P < 0.01) but significant increase in renal artery diameter, resulting in an increase in bloodflow of 82% (P < 0.01) and a decrease in arteriolar resistance of 46% (P < 0.01). Bloodflow returned to baseline (4.76 +/- 1.48 mL/s) approximately 5 min after isosorbide injection. Average Peak Velocity increased almost twofold after papaverine injection (60 +/- 10 to 108 +/- 24 cm/sec, P < 0.01). There was a significant (P < 0.01) increase in arterial bloodflow of 96% in the right and 79% in the left renal artery after injection of papaverine with a corresponding significant (P < 0.01) decrease in arteriolar resistance of 49% in the right and 44% in the left renal artery. Using a combination of quantitative angiography and intravascular Doppler allows easy measurement of baseline renal blood flow and of the effects of vasodilator drugs on bloodflow and resistance. The results show that a vasodilatator reserve exists in the renal circulation but is less marked than that reported in the coronary circulation.

Animals↗
PubMed1998

[Current data on atheromatous plaques and their evolution].

The modes of evolution of atheromatous plaques are now better understood. The process may start very early and continue for several decades. The severity of atherosclerosis lies in the results of phases of rapid progression involving a thrombotic mechanism. An initial mechanical accident (rupture or erosion of the plaque) is followed by a phenomenon of arterial thrombosis of variable severity. The vulnerability of an atheromatous plaque (defined as its potential for acute complication) is related to: 1) the risk of rupture, 2) the risk of thrombosis in case of rupture. A number of intrinsic properties influence the degree of plaque vulnerability. A thorough understanding of these mechanisms is essential for the development of new treatments to improve the prognosis of coronary patients.

Arteriosclerosis↗
PubMed1997

Association of angiotensin converting enzyme and angiotensin II type 1 receptor genotypes with left ventricular function and mass in patients with angiographically normal coronary arteries.

OBJECTIVE: To analyse the potential association of the angiotensin converting enzyme (ACE) and angiotensin II type 1 receptor (AT1R) gene polymorphisms on left ventricular function and mass in patients with normal coronary arteries. DESIGN: Consecutive sample. SETTING: University hospital. SUBJECTS: 141 consecutive white patients referred for coronary angiography and with angiographically normal coronary arteries. Patients with valvar diseases, cardiomyopathies, or a history of myocardial infarction were excluded. MAIN OUTCOME MEASURES: Left ventricular variables were measured for all patients. The ACE and AT1R genotypes were determined with a polymerase chain reaction based protocol using DNA prepared from white blood cells. A general linear model was used to compare data according to the ACE and to the AT1R genotypes. RESULTS: A strong association was observed between left ventricular mass and systemic hypertension (mean (SD) hypertension: 114 (31) g/m2; no hypertension 98 (23) g/m2; P < 0.003). However, no influence of ACE and AT1R polymorphisms on left ventricular mass was found, regardless of systemic hypertension. The subjects homozygous for the AT1R CC mutation had a significantly lower ejection fraction than those with allele A (AC+AA) (mean (SD) 62(12)% and 68(10)%, respectively, P < 0.05). No synergistic interaction of ACE and AT1R gene polymorphisms on left ventricular function and mass was found. CONCLUSIONS: These data do not support an association of the ACE and AT1R genotypes on left ventricular hypertrophy in white patients with normal coronary arteries.

Angiotensin II↗
PubMed1997

Rate of temporal discounting decreases with amount of reward.

The present, subjective value of a delayed reward is a decreasing function of the duration of the delay. This phenomenon is termed temporal discounting. To determine whether the amount of the reward influences the rate of temporal discounting, we had subjects choose between immediate and delayed hypothetical rewards of different amounts ($100, $2,000, $25,000, and $100,000 delayed rewards). As predicted by psychological models of the choice process, hyperbolic functions described the decrease in the subjective value of the delayed reward as the time until its receipt was increased (R2s from .86 to .99). Moreover, hyperbolic functions consistently provided more accurate descriptions of the data than did exponential functions predicted by an economic model of discounted utility. Rate of discounting decreased in a negatively accelerated fashion as the amount of the delayed reward increased, leveling off by approximately $25,000. These findings are interpreted in the context of different psychological models of choice, and implications for procedures to enhance self-control are discussed.

Adolescent↗
PubMed1997

[Coronary angioscopy].

Coronary angioscopy evaluates the composition of the atherosclerotic plaque by direct examination of the arterial wall. The angioscope is fitted with a balloon which prevents assessment of the proximal segment of the vessels. The fibre optic system provides and excellent view of the mid and distal segments of the coronary arteries. The coronary arteries appear smooth and white on angioscopy. The atherosclerotic plaque is a white or yellowish incursion. Unstable plaques are characterised by the presence of thrombus. In unstable angina, thrombus is observed in 64% of cases and in 75% of cases during the first month after myocardial infarction. The colour of the plaque seems to be related to its fragility: the yellow plaque is much more common during myocardial infarction than in unstable angina (75% versus 47% of cases). Finally, after coronary angioplasty restenosis is more commonly white, covered by neo-intimal proliferation. Angioscopy has been shown to be feasible and safe and it is a better method of identifying thrombus. At present, it is a tool for clinical research in coronary thrombosis and interventional cardiology.

Angioplasty, Balloon, Coronary↗
PubMed1996

[Relation between progression of atherosclerosis and the phenomenon of restenosis after coronary angioplasty].

The authors undertook a retrospective study of medium-term coronary angiographic controls of a group (Gr) of patients (pts) who had undergone coronary angioplasty for rapidly progressive lesions, to determine whether the rate of progression of a coronary stenosis before angioplasty affected the risk of restenosis. 89 pts underwent primary angioplasty with absence of restenosis at 6 months, but required another angioplasty for another lesion. Angiographic follow-up after the 2nd procedure was performed in 86 pts (96%). The coronary lesion dilated at the 2nd angioplasty procedure was analysed quantitatively with four measurements: one immediately before angioplasty, one after, one at the 6 months control, and finally, one measurement 6 months before the angioplasty during the procedure on the 1st site. Multivariate statistical analysis showed that the only predictive factor of post-angioplasty loss in the general population was the immediate gain (F = 11.82; p < 0.005). On the other hand, no correlation was found between progression of the lesion before angioplasty and loss. The rapidly progressive nature of the lesion was defined with a threshold of 0.4 mm, corresponding to the variability of the quantitative angiographic system. Analysis of the procedure parameters showed a lower inflation pressure in the Gr with rapidly progressive lesions (6.58 +/- 21 atm vs 7.63 +/- 1.96 atm; p < 0.05). The immediate gain was significantly greater in the rapidly progressive lesion Gr (0.82 +/- 0.34 vs 0.67 +/- 0.29 mm; p = 0.05). The loss at the 6 months control was identical in the two Gr (0.31 +/- 0.50 vs 0.31 +/- 0.42 mm; p < 0.05). The loss/gain ratio was also comparable (0.37 +/- 0.76 vs 0.45 +/- 0.52; p > 0.05). These results show that rapidly progressive atherosclerosis does not increase the risk of post-angioplasty restenosis.

Aged↗
PubMed1995

Gunshot injuries of the temporal bone.

Despite an increasing incidence of gunshot wounds to the temporal bone, there is little in the literature regarding management of survivors of these serious injuries. Twelve patients were treated for such wounds between 1986 and 1994. The most frequent presentations were cranial nerve injury, especially facial paralysis (9 patients), hearing loss (7), vascular injury (4), and vestibular dysfunction (3). Persistent cerebrospinal fluid otorrhea was uncommon (1 patient) in this series. Computed tomography and audiovestibular testing were helpful in evaluating the severity of injury and guiding the surgical approach when necessary. Electroneurography was helpful in evaluating facial nerve function; however, documented disruption of the facial nerve canal in itself was considered an indication for surgical exploration. Other indications for surgical intervention included evidence of dural tear, vascular injury, and severe disruption of the external auditory canal.

Adolescent↗
PubMed1994

[Silent ischemia].

Silent myocardial ischaemia is a very common phenomenon in patients with coronary artery disease. It may occur in patients with clinical manifestations of angina, be detected during the post-myocardial infarction period or in patients totally asymptomatic. Whatsoever, it is well demonstrated that silent myocardial ischaemia has a very potent prognostic value. Therapeutic implications are similar to those in symptomatic ischaemia. Indications for myocardial revascularization by mean of angioplasty or bypass grafting may be discussed and depend on ventricular function and extension of coronary lesions.

Angina Pectoris↗