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Biomedical subjects

J Ambrose

Publications and source records attributed to J Ambrose.

At least 19 recordsLinked to original sources
PubMed2006

Pioglitazone improves endothelial function in non-diabetic patients with coronary artery disease.

OBJECTIVE: To test the hypothesis that pioglitazone, a peroxisome proliferator-activated receptor-gamma agonist, will improve endothelial function in non-diabetic subjects with coronary artery disease, we conducted a prospective study to evaluate the effect of this medication on the brachial artery vasomotor function and circulating markers of endothelial activation. METHODS: Baseline characteristics were collected. After initial endothelial function assessment, patients were treated with pioglitazone hydrochloride 30 mg daily. The medication was continued for 12 weeks and endothelial function was reassessed as well as the inflammatory markers. The study medication then was stopped, and all the tests were repeated 12 weeks later. RESULTS: Seventeen subjects completed all three-study phases. Mean age was 58 (range: 36-77 years). Compared with the baseline, the endothelium-dependent vasodilation improved significantly with the treatment (p < 0.001) from 4.4 +/- 3.9 to 8.4 +/- 4.1%, a relative increase of 91%. After withdrawal of treatment, the endothelium-dependent vasodilation returned towards baseline values. There was no change in endothelium-independent vasodilatation (12.27 +/- 6.35 to 13.9 +/- 9.23%, to 12.42 +/- 5.35%, p = 0.177). The urine asymmetric dimethlyarginine levels decreased significantly with the treatment, but also returned to the initial values after the wash-out period (1.27 +/- 0.5 micromol/ml to 0.97 +/- 0.3 micromol/ml to 1.34 +/- 0.5 micromol/ml, p = 0.017). No difference in the lipid profile, C-reactive protein, erythrocyte sedimentation rate, or fibrinogen levels was seen. CONCLUSION: Pioglitazone rapidly improves endothelial function in non-diabetic patients with coronary artery disease. This improvement is associated with a change in mean urinary asymmetric dimethylarginine levels, although a cause and effect cannot be determined from this investigation.

Adult↗
PubMed2005

Role of oral rapamycin to prevent restenosis in patients with de novo lesions undergoing coronary stenting: results of the Argentina single centre study (ORAR trial).

OBJECTIVE: To assess the role of oral rapamycin in the prevention of coronary restenosis in patients undergoing coronary stenting. METHODS: From December 2001 through February 2003, 76 patients with 103 de novo lesions treated percutaneously with bare stents received a loading dose of oral rapamycin 6 mg followed by a daily dose of 2 mg during 28 days in phase I (49 arteries in 34 patients) and 2 mg/day plus 180 mg/day of diltiazem in phase II (54 arteries in 42 patients). Rapamycin blood concentrations were measured in all patients. A six month follow up angiogram was performed in 82.5% (85 of 103 arteries). Follow up angiographic binary restenosis (> 50%), target vessel revascularisation, late loss, treatment compliance, and major adverse cardiovascular events were analysed and correlated with rapamycin concentrations. RESULTS: Rapamycin was well tolerated and only three patients discontinued the treatment for mild side effects. Angiographic restenosis was found in 15% of the arteries with angiographic restudy (13 of 85). The target vessel had been revascularised at follow up in 13.6% of the 103 vessels initially treated (14 of 103) and in 18.4% of the 76 patients (14 of 76). In-stent restenosis in phase I was 19% compared with 6.2% in phase II (p = 0.06). Angiographic in-stent restenosis in lesions of patients with rapamycin blood concentrations > or = 8 ng/ml was 6.2% and with rapamycin concentrations < 8 ng/ml was 22% (p = 0.041). Late loss was also significantly lower when rapamycin concentrations were > or = 8 ng/ml (0.6 mm v 1.1 mm, p = 0.031). A Pearson test showed a linear correlation between follow up late loss and rapamycin blood concentration (r = -0.826, p = 0.008). CONCLUSION: Oral rapamycin administered for one month after percutaneous coronary intervention was safe and with few minor side effects. High rapamycin blood concentrations were associated with significantly lower late loss and angiographic in-stent restenosis.

Administration, Oral↗
PubMed2001

Face processing occurs outside the fusiform 'face area' in autism: evidence from functional MRI.

Processing the human face is at the focal point of most social interactions, yet this simple perceptual task is difficult for individuals with autism, a population that spends limited amounts of time engaged in face-to-face eye contact or social interactions in general. Thus, the study of face processing in autism is not only important because it may be integral to understanding the social deficits of this disorder, but also, because it provides a unique opportunity to study experiential factors related to the functional specialization of normal face processing. In short, autism may be one of the only disorders where affected individuals spend reduced amounts of time engaged in face processing from birth. Using functional MRI, haemodynamic responses during a face perception task were compared between adults with autism and normal control subjects. Four regions of interest (ROIs), the fusiform gyrus (FG), inferior temporal gyrus, middle temporal gyrus and amygdala were manually traced on non-spatially normalized images and the percentage ROI active was calculated for each subject. Analyses in Talairach space were also performed. Overall results revealed either abnormally weak or no activation in FG in autistic patients, as well as significantly reduced activation in the inferior occipital gyrus, superior temporal sulcus and amygdala. Anatomical abnormalities, in contrast, were present only in the amygdala in autistic patients, whose mean volume was significantly reduced as compared with normals. Reaction time and accuracy measures were not different between groups. Thus, while autistic subjects could perform the face perception task, none of the regions supporting face processing in normals were found to be significantly active in the autistic subjects. Instead, in every autistic patient, faces maximally activated aberrant and individual-specific neural sites (e.g. frontal cortex, primary visual cortex, etc.), which was in contrast to the 100% consistency of maximal activation within the traditional fusiform face area (FFA) for every normal subject. It appears that, as compared with normal individuals, autistic individuals 'see' faces utilizing different neural systems, with each patient doing so via a unique neural circuitry. Such a pattern of individual-specific, scattered activation seen in autistic patients in contrast to the highly consistent FG activation seen in normals, suggests that experiential factors do indeed play a role in the normal development of the FFA.

Adult↗
PubMed2000

Generation of reactive oxygen species after exhaustive aerobic and isometric exercise.

UNLABELLED: Many studies have implicated elevated oxygen consumption (VO2) associated with aerobic exercise as contributing to oxidative stress. Only a few studies have investigated nonaerobic exercise and its relation to pro-oxidant and antioxidant activities. PURPOSE: The purpose of this study was to compare biomarkers of oxidative stress: lipid peroxidation, protein oxidation, and total antioxidants in blood after exhaustive aerobic (AE) and nonaerobic isometric exercise (IE). METHODS: Blood samples were collected from 12 subjects who performed a maximum AE and IE test and were analyzed for thiobarbituric acid (TBARS), carbonyls, lipid hydroperoxides (LH), and oxygen radical absorbance capacity (ORAC). RESULTS: VO2 increased 14-fold with AE compared with 2-fold with IE. Protein carbonyls increased 67% (P < 0.05) pre- to immediately and 1 h post-AE, and 12% pre- to immediately post-IE and returned to baseline 1 h post-IE. TBARS did not increase significantly with either treatment. LH increased 36% above rest during IE compared with 24% during AE (P < 0.05). ORAC increased 25% (P < 0.05) pre- to post-AE, compared with 9% (P < 0.05) pre- to post-IE. CONCLUSION: There was evidence of oxidative stress after both exhaustive aerobic and isometric exercise. Lipid hydroperoxides, protein carbonyls, and total antioxidants increased after both IE and AE. Due to the different metabolic demands of aerobic and isometric exercise, we can rule out a mass action effect of VO2 as the sole mechanism for exercise-induced oxidative stress.

Adult↗
PubMed1999

Angiotensin type 1 receptor antagonism with irbesartan inhibits ventricular hypertrophy and improves diastolic function in the remodeling post-myocardial infarction ventricle.

To evaluate the role of angiotensin II (AII) on diastolic function during post-myocardial infarction (MI) ventricular remodeling, coronary ligation or sham operation was performed in male Sprague-Dawley rats. Experimental animals were maintained on either irbesartan, a selective AT1-receptor antagonist, or no treatment. Measurement of cardiac hypertrophy, diastolic function, and sarcoendoplasmic reticulum adenosine triphosphatase (ATPase; SERCA) and phospholamban (PLB) gene expression was assessed at 6 weeks after MI. Myocardial infarction caused a significant increase in myocardial mass and left ventricular (LV) filling pressure, whereas LV systolic pressure and +dP/dt were reduced. The time constant of isovolumic relaxation (tau) was markedly prolonged after MI. Post-MI hypertrophy was associated with substantial increases in the messenger RNA (mRNA) expression of atrial natriuretic peptide (ANP), but no significant changes in SERCA or PLB levels. Although irbesartan treatment did not significantly alter post-MI LV systolic or filling pressures, it nevertheless effectively decreased ventricular hypertrophy, improved tau, and normalized ANP expression. These results demonstrate that AT1-receptor antagonism has important effects on myocardial hypertrophy and ANP gene expression, which are independent of ventricular loading conditions. In addition, the improvement in diastolic function was not related to changes in SERCA and PLB gene expression, suggesting that enhanced myocardial relaxation was related to the blockade of AII effects on myocyte function or through a reduction of ventricular hypertrophy itself or both.

Angiotensin Receptor Antagonists↗
PubMed1996

Randomized, double-blind, placebo-controlled dose-ranging study of tirofiban (MK-383) platelet IIb/IIIa blockade in high risk patients undergoing coronary angioplasty.

OBJECTIVES: The objectives of this double-blind, placebo-controlled, randomized dose-ranging study were 1) to examine the safety and tolerability of tirofiban (MK-383), a new nonpeptide platelet IIb/IIIa receptor antagonist, on a background of intravenous heparin and aspirin therapy; 2) to study the pharmacodynamics and pharmacokinetics of tirofiban; and 3) to evaluate the incidence of adverse cardiac outcomes (urgent repeat revascularization, myocardial infarction and death) with tirofiban versus placebo in a high risk subset of patients undergoing coronary angioplasty. BACKGROUND: Abrupt vessel closure complicates 4% to 8% of angioplasty procedures. Recent data have suggested that agents that antagonize the platelet glycoprotein IIb/IIIa receptor may reduce the incidence of adverse ischemic outcomes after coronary angioplasty. METHODS: Seventy-three patients received tirofiban in three sequential dose panels and 20 patients received placebo. Patients within each panel were randomized to receive either tirofiban or placebo in a 3:1 randomization design. Bolus doses of 5, 10 and 10 microg/kg and continuous infusion (16 to 24 h) doses of 0.05, 0.10 and 0.15 microg/kg per min were administered in panels I, II and III, respectively. Patients received concomitant heparin and aspirin for the angioplasty procedure. Data on patients receiving placebo (heparin and aspirin only) were pooled across panels for comparisons. The pharmacodynamic effect of tirofiban on ex vivo platelet aggregation to 5 micromol/liter adenosine diphosphate (ADP) and bleeding times were measured. Clinical outcomes were assessed in all patients, but the power to detect clinically meaningful differences (a one-third reduction in clinical events) between groups was limited (5%). RESULTS: Tirofiban was associated with a dose-dependent inhibition of ex vivo ADP-mediated platelet aggregation that was sustained during intravenous infusion and resolved rapidly after drug cessation. Adverse bleeding events, largely related to vascular access site hemorrhage, were slightly increased at the highest dose. Adverse clinical outcomes were infrequent in all patients and were not different among the small number of patients within each group. CONCLUSIONS: This study establishes a rational and generally well tolerated dosing regimen for administration of tirofiban as adjunctive therapy in high risk angioplasty patients. The impact of tirofiban on adverse clinical outcomes after angioplasty awaits definition by a larger clinical trial.

Angioplasty, Balloon, Coronary↗
PubMed1995

Adaptation mechanisms during myocardial ischemia in chronic unstable angina pectoris.

Unstable angina with a clinical duration of < 2 months is characterized angiographically by a high incidence of complex lesions. Some patients have ischemic rest pain syndromes of longer duration. Thus, we retrospectively analyzed, in blinded fashion, the clinical and angiographic findings in 52 patients with unstable angina of < 2 months' duration (group A), and compared the results with those of 32 patients with unstable angina of > 6 months' duration (group B). Group B had a greater number of diseased vessels and better collateral circulation, but had fewer eccentric lesions. There were no differences in age, left ventricular function, or history of prior myocardial infarction. Thus, chronic unstable angina is associated with more extensive coronary disease than unstable angina of shorter duration. The role of different anatomic substrata and collateral circulation is discussed.

Adaptation, Physiological↗
PubMed1989

Balloon valvuloplasty in adult aortic stenosis: determinants of clinical outcome.

STUDY OBJECTIVE: To determine the clinical variables affecting outcome after balloon aortic valvuloplasty. DESIGN: Longitudinal follow-up of consecutive case series. PATIENTS: Consecutive sample of 36 patients with severe calcific aortic stenosis, and without active infection or left ventricular mural thrombus. INTERVENTIONS: Percutaneous transluminal dilatation of the aortic valve until the peak gradient was reduced by 50% or a maximal balloon size was used. Hemodynamic measurements taken before and after dilatation. MEASUREMENTS AND MAIN RESULTS: Thirty-three patients had a successful dilatation. Eighty-nine percent (95% confidence interval [CI]. 74% to 97%) improved symptomatically at 2 weeks, but by 26 weeks only 56% (CI, 35% to 76%) remained improved (P = 0.0078). Mortality rates were high at 8 (9%) and 26 (28%) weeks. Predictors of adverse events included left ventricular ejection fraction (P = 0.04, r = 0.46), pulmonary artery systolic pressure (P = 0.048, r = 0.65), pulmonary vascular resistance (P = 0.008, r = 0.69), and right ventricular end-diastolic pressure (P = 0.009, r = 0.43) at 8 weeks and all these factors except left ventricular ejection fraction at 26 weeks. These clinical outcomes were unrelated to other cardiac or pulmonary diseases. CONCLUSIONS: Symptomatic improvement is only temporary in many patients undergoing balloon aortic valvuloplasty, and the mortality rate in the mid-term follow-up period is high. Valve surgery remains the treatment of choice for aortic stenosis in the adult.

Aged↗
PubMed1989

Late thrombolytic therapy preserves left ventricular function in patients with collateralized total coronary occlusion: primary end point findings of the Second Mount Sinai-New York University Reperfusion Trial.

The change in left ventricular ejection fraction from preintervention to predischarge was prospectively assessed in 393 patients with acute myocardial infarction. Within 12 h of symptom onset (mean 6.3 +/- 2.7 h), patients were randomly assigned to a double-blind intracoronary infusion of streptokinase, nitroglycerin, both streptokinase and nitroglycerin or conventional therapy without acute cardiac catheterization. Treatment effects were also assessed in prospectively defined angiographic subsets. There was a significant interaction between streptokinase and nitroglycerin (p less than 0.01), resulting in an increase in ejection fraction of 3.9 percentage units in the combined treatment arm (p less than 0.001). Patients with collateral flow to a totally obstructed infarct-related artery showed a significant improvement over those without collateral flow in the streptokinase (5.4 +/- 2.5%) and streptokinase-nitroglycerin (10.6 +/- 2.7%) arms, but not in the nitroglycerin arm. Time to treatment did not influence the change in ejection fraction. In patients with initial subtotal occlusion, thrombolytic therapy was of no short-term benefit because ejection fraction increased by 6% in all three intervention arms. These findings indicate that relatively late thrombolytic therapy results in significant myocardial salvage in those patients with collateralized total coronary occlusion. This benefit is potentiated by concomitant nitroglycerin therapy.

Aged↗
PubMed1987

Restrictive-type hemodynamics following valve surgery for rheumatic heart disease.

Over a six-year period three patients with rheumatic valvular disease presented with congestive heart failure due to abnormalities in myocardial diastolic function. Each patient previously had been operated for mitral stenosis; one patient had additional aortic valve replacement for aortic insufficiency. The mean time for the development of symptoms following surgery was 4.7 years. In all patients, left ventricular systolic function was normal (radionuclide or angiographic ejection fraction greater than 0.50). Abnormalities in diastolic function involved the left ventricle in all patients. Biopsy material from right (one patient) and left (one patient) ventricles was nonspecific in its histologic appearance. Other disease processes, such as constrictive pericarditis and diabetic cardiomyopathy were considered to be clinically unimportant in these patients. Restrictive-type hemodynamics in patients with postoperative rheumatic heart disease may comprise a newly recognized entity.

Aortic Valve Stenosis↗
PubMed1984

Acute coronary hemodynamic response to cigarette smoking in patients with coronary artery disease.

The acute changes in coronary blood flow and coronary resistance that occur in response to cigarette smoking have not been accurately determined. To define the factors that affect this response, coronary sinus blood flow was measured in 16 patients (group I) with coronary artery disease and in 6 patients (group II) without angiographically detectable coronary disease. Seven patients (group IA) had severe (greater than or equal to 75%) proximal left coronary lesions and nine patients (group IB) had significant distal lesions with 50% or less proximal stenoses. Group I had a smaller overall increase (increases 1.6 +/- 5.3%) in coronary sinus blood flow than did group II (increases 7.7 +/- 6.1%) (p less than 0.05). Coronary resistance increased overall (increases 2.7 +/- 5.3%) in group I but decreased (decreases 2.4 +/- 3.4%) in group II (p less than 0.05). Patients in group IA had a highly significant increase in coronary resistance as compared with group IB (increases 7.0 +/- 4.2% versus decreases 0.9 +/- 2.6%) (p less than 0.001). Coronary sinus flow tended to decrease (decreases 1.2 +/- 4.6%) in group IA but to increase (increases 3.8 +/- 5.1%) in group IB (p = 0.06). It is concluded that smoking increases coronary resistance in patients with coronary artery disease. A greater impact is observed in patients with a severe proximal stenosis than in those with a distal stenosis. It is proposed that smoking increases coronary artery tone at the site of the stenosis, limiting the coronary flow response proportionally to the size of the affected vascular bed.

Adult↗
PubMed1984

Significance of contrast enhancement in cranial computerized tomography after subarachnoid hemorrhage.

Eighty patients with subarachnoid hemorrhage underwent computerized tomography (CT) scanning before and after administration of Conray contrast medium. Abnormal enhancement was seen in visual evaluation of the CT scans in 26 cases, in the regions bordering the subarachnoid spaces. Abnormal enhancement was associated with a poor clinical condition, angiographic spasm, and a poor outcome. Measurements of absorption values in the thalamus revealed significant increases in density after contrast enhancement in those patients whose scans showed abnormal enhancement in the regions bordering the subarachnoid spaces on visual evaluation. The authors suggest that the abnormal enhancement is parenchymal, in the gyri, and is not "subarachnoid." They suggest that it is due to gyral hyperemia or extravasation of contrast material into the cortex resulting from breakdown of the blood-brain barrier, or a combination of both factors.

Adult↗