PubMed Health⌕ Search

Biomedical subjects

J Deanfield

Publications and source records attributed to J Deanfield.

At least 19 recordsLinked to original sources
PubMed2006

Assessment of differential branch pulmonary blood flow: a comparative study of phase contrast magnetic resonance imaging and radionuclide lung perfusion imaging.

OBJECTIVES: To test whether magnetic resonance (MR) imaging can be used to assess differential lung blood flow as accurately as isotope lung perfusion studies in patients investigated for congenital heart disease. METHODS AND RESULTS: Radionuclide lung perfusion and MR imaging were performed in 12 children with suspected unilateral branch pulmonary artery stenosis (mean age 12.1 (5.9) years, range 3.1-17.2 years). A non-breath hold, fast gradient echo phase contrast MR sequence was used to measure flow in the pulmonary trunk and one pulmonary artery to calculate differential flow. Good agreement was shown between the two imaging methods by Bland-Altman analysis. There was excellent correlation between the radionuclide and MR phase contrast calculated total lung blood flow (r = 0.98, p < 0.0001). CONCLUSION: MR phase contrast is an accurate method for measuring differential total right and left lung blood flow. If MR imaging is performed to assess the branch pulmonary arteries, differential lung blood flow can be also measured, avoiding the need for an additional radionuclide lung perfusion scan and reducing the overall radiation burden to this group of patients.

Adolescent↗
PubMed2001

The relevance of tissue angiotensin-converting enzyme: manifestations in mechanistic and endpoint data.

Angiotensin-converting enzyme (ACE) is primarily localized (>90%) in various tissues and organs, most notably on the endothelium but also within parenchyma and inflammatory cells. Tissue ACE is now recognized as a key factor in cardiovascular and renal diseases. Endothelial dysfunction, in response to a number of risk factors or injury such as hypertension, diabetes mellitus, hypercholesteremia, and cigarette smoking, disrupts the balance of vasodilation and vasoconstriction, vascular smooth muscle cell growth, the inflammatory and oxidative state of the vessel wall, and is associated with activation of tissue ACE. Pathologic activation of local ACE can have deleterious effects on the heart, vasculature, and the kidneys. The imbalance resulting from increased local formation of angiotensin II and increased bradykinin degradation favors cardiovascular disease. Indeed, ACE inhibitors effectively reduce high blood pressure and exert cardio- and renoprotective actions. Recent evidence suggests that a principal target of ACE inhibitor action is at the tissue sites. Pharmacokinetic properties of various ACE inhibitors indicate that there are differences in their binding characteristics for tissue ACE. Clinical studies comparing the effects of antihypertensives (especially ACE inhibitors) on endothelial function suggest differences. More comparative experimental and clinical studies should address the significance of these drug differences and their impact on clinical events.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2001

Preterm birth, vascular function, and risk factors for atherosclerosis.

Low birthweight may predispose to the development of atherosclerosis later in life. We have tested the hypothesis that low birthweight as a result of preterm birth is associated with reduced flow-mediated endothelial-dependent vasodilation (FMD), which is an early stage in the development of atherosclerosis. Mean FMD in adolescents born preterm who had a low birthweight did not differ from that for controls born at term (0.225 mm vs 0.220 mm, SD 0.1 for both means, p=0.78). Our findings indicate that low birthweight attributable to prematurity does not increase the risk of vascular disease later in life.

Adolescent↗
PubMed2001

Ischemic preconditioning prevents endothelial injury and systemic neutrophil activation during ischemia-reperfusion in humans in vivo.

BACKGROUND: Endothelial dysfunction leading to neutrophil infiltration of tissues has been implicated in tissue injury caused by ischemia-reperfusion (IR). Tissue injury during IR can be reduced by prior ischemic preconditioning (IPC). In humans, it is unclear whether endothelial dysfunction occurs during IR or whether IPC offers protection against endothelial dysfunction and inflammatory cell activation. We studied the effects of experimental IR on endothelial and neutrophil function in the human forearm in vivo and examined the protection afforded by IPC. METHOD AND RESULTS: The forearm was made ischemic for 20 minutes by inflating a blood pressure cuff to 200 mm Hg. We assessed endothelial function of conduit (radial artery flow-mediated dilation) and resistance vessels (blood flow responses to intra-arterial infusion of the endothelium-dependent dilator acetylcholine) in healthy volunteers before and after IR. IR reduced flow-mediated dilation of the radial artery at 15 minutes of reperfusion (7.7+/-1.5% to 3.5+/-0.9%) and the dilator response of resistance vessels to acetylcholine at 15, 30, and 60 minutes of reperfusion. IR did not reduce the dilator response of the radial artery to glyceryltrinitrate and only caused a small reduction of glyceryltrinitrate-induced dilation of resistance vessels at 60 minutes of reperfusion. IR caused an increase in neutrophil CD11b expression and platelet-neutrophil complexes in the circulating blood. IPC (three 5-minute episodes of ischemia) before IR prevented endothelial dysfunction and neutrophil activation. CONCLUSIONS: A clinically relevant period of ischemia-reperfusion causes profound and sustained endothelial dysfunction and systemic neutrophil activation. IPC attenuates both of these effects in humans.

Acetylcholine↗
PubMed2000

Scientific, ethical, and logistical considerations in introducing a new operation: a retrospective cohort study from paediatric cardiac surgery.

OBJECTIVE: To review the initial impact on mortality of infants with congenital heart disease of a new surgical technique that is now taken for granted. DESIGN: Retrospective cohort study. SETTING: A tertiary paediatric cardiology centre. SUBJECTS: 325 consecutive neonates with simple transposition of the great arteries admitted before, during, and after the preferred management changed from the Senning operation to the arterial switch (1978-98); and 100 consecutive neonates requiring a different neonatal open heart operation that did not change in that period. MAIN OUTCOME MEASURES: Mortality before and early after operation reconstructed sequentially as the series evolved and retrospectively once the series was complete; actuarial survival associated with the different treatment strategies. RESULTS: For both the transposition and the comparison group, early mortality in 1998 was lower than in 1978. During that period, however, there was a phase temporally related to the adoption of the switch operation in which early mortality for transposition increased. Actuarial survival of recent patients with "intention to treat" with arterial switch is superior to those with intention to treat with the Senning operation, as predicted when the switch operation was first adopted. CONCLUSIONS: A period of increased hazard for individual patients may occur when a specialist community, a particular unit, and an individual surgeon are all learning a new technique concurrently. Obtaining informed consent during this time of uncertainty is helped by clarity about the objectives of treatment and availability of relevant local and international data.

Child↗
PubMed1999

Comparison of long-term outcomes of atrial repair of simple transposition with implications for a late arterial switch strategy.

BACKGROUND: We report the single-institution, long-term results of 358 patients with simple transposition of the great arteries surviving >30 days after a Mustard (n=226, 1965 to 1980) or Senning (n=132, 1978 to 1992) procedure. METHODS AND RESULTS: Outcome measures included late death, reintervention, ECG and ambulatory ECG rhythm, new arrhythmia, and functional status. Average follow-up was 13.4 (range 0.32 to 17.9) years for the Senning group and 11.7 (range 0.04 to 23.9) years for the Mustard group. The Senning group had a better survival rate at 5, 10, and 15 years (95% versus 86%, 94% versus 82%, and 94% versus 77%, respectively). In both groups, the majority of late deaths were sudden, without preceding ventricular dysfunction. Survival and survival free of reintervention were significantly better in the Senning group (relative risk [RR] 0.34, P=0.06 versus RR 0.39, P=0.027). Loss of sinus rhythm was comparable and unrelated to death. After era correction, the incidence of atrial flutter was similar and strongly associated with late death in both groups. Clinical systemic ventricular failure was uncommon, and at last follow-up, 92% of the Senning group and 89% of the Mustard group were in New York Heart Association class I. In a model exploring the implications of elective arterial switch conversion, this would only be beneficial if the hazard late after switch was markedly reduced and/or the hazard after the Senning procedure increased with time. CONCLUSIONS: Late outcomes after the Senning procedure are superior to those after the Mustard procedure. Both groups had late sudden deaths that were not associated with clinical systemic ventricular failure. Good functional status after the Senning procedure suggests that a strategy of elective switch conversion cannot be justified for patients with isolated transposition.

Cardiac Surgical Procedures↗
PubMed1997

Association of angiotensin-converting enzyme gene I/D polymorphism with change in left ventricular mass in response to physical training.

BACKGROUND: The absence (deletion allele [D]) of a 287-base pair marker in the ACE gene is associated with higher ACE levels than its presence (insertion allele [I]). If renin-angiotensin systems regulate left ventricular (LV) growth, then individuals of DD genotype might show a greater hypertrophic response than those of II genotype. We tested this hypothesis by studying exercise-induced LV hypertrophy. METHODS AND RESULTS: Echocardiographically determined LV dimensions and mass (n=140), electrocardiographically determined LV mass and frequency of LV hypertrophy (LVH) (n=121), and plasma brain natriuretic peptide (BNP) levels (n=49) were compared at the start and end of a 10-week physical training period in male Caucasian military recruits. Septal and posterior wall thicknesses increased with training, and LV mass increased by 18% (all P<.0001). Response magnitude was strongly associated with ACE genotype: mean LV mass altered by +2.0, +38.5, and +42.3 g in II, ID and DD, respectively (P<.0001). The prevalence of electrocardiographically defined LVH rose significantly only among those of DD genotype (from 6 of 24 before training to 11 of 24 after training, P<.01). Plasma brain natriuretic peptide levels rose by 56.0 and 11.5 pg/mL for DD and II, respectively (P<.001). CONCLUSIONS: Exercise-induced LV growth in young males is strongly associated with the ACE I/D polymorphism.

Adult↗
PubMed1997

Asymptomatic Cardiac Ischemia Pilot (ACIP) study two-year follow-up: outcomes of patients randomized to initial strategies of medical therapy versus revascularization.

BACKGROUND: Patients with ischemia during stress testing and ambulatory ECG monitoring have an increased risk of cardiac events, but it is not known whether their prognosis is improved by more aggressive treatment with anti-ischemic drugs or revascularization. METHODS AND RESULTS: The Asymptomatic Cardiac Ischemia Pilot study randomized 558 such patients who had coronary anatomy suitable for revascularization to three treatment strategies: angina-guided drug therapy (n=183), angina plus ischemia-guided drug therapy (n=183), or revascularization by angioplasty or bypass surgery (n=192). Two years after randomization, the total mortality was 6.6% in the angina-guided strategy, 4.4% in the ischemia-guided strategy, and 1.1% in the revascularization strategy (P<.02). The rate of death or myocardial infarction was 12.1% in the angina-guided strategy, 8.8% in the ischemia-guided strategy, and 4.7% in the revascularization strategy (P<.04). The rate of death, myocardial infarction, or recurrent cardiac hospitalization was 41.8% in the angina-guided strategy, 38.5% in the ischemia-guided strategy, and 23.1% in the revascularization strategy (P<.001). Pairwise testing revealed significant differences between the revascularization and angina-guided strategies for each comparison. CONCLUSIONS: A strategy of initial revascularization appears to improve the prognosis of this population compared with angina-guided medical therapy. A larger long-term study is needed to confirm this benefit and to adequately test the potential of more aggressive drug therapy.

Adrenergic beta-Antagonists↗
PubMed1997

Non-invasive measurement of endothelial function: effect on brachial artery dilatation of graded endothelial dependent and independent stimuli.

OBJECTIVE: To examine the relation between endothelial dependent and endothelial independent stimuli of varying intensity and measures of vascular function in the brachial artery of young healthy adults, to determine whether these responses are consistent and can be used to assess endothelial function. DESIGN AND SETTING: High resolution ultrasound was used to measure brachial artery diameter at rest, after reactive hyperaemia induced by forearm cuff occlusion, and after sublingual isosorbide dinitrate (ISDN). Each subject was assigned to a random order of six cuff occlusion times (30 seconds, 1.5, 2.5, 3.5, 4.5, and 8 minutes) and six doses of ISDN (10, 20, 50, 100, 200, and 400 micrograms). SUBJECTS: Three males and three females mean age 31 years (range 25 to 43) with no known risk factors for cardiovascular disease. MAIN OUTCOME MEASURES: Flow mediated, endothelial dependent dilatation was compared to duration of cuff occlusion, peak reactive hyperaemia, and duration of increased flow. Nitrate induced, endothelial independent dilatation was compared to dose of ISDN and change in flow. RESULTS: Vessel dilatation and duration of peak flow change increased with longer duration of cuff occlusion. After 4.5 minutes of occlusion, flow mediated dilatation was mean (SD) 96 (6)% of maximal response and did not increase significantly with longer occlusion times. No significant dilatation occurred after 10 or 20 micrograms of ISDN in any subject. With increasing doses up to 200 micrograms there was an increase in dilatation. Endothelial independent dilatation did not increase significantly with doses of ISDN above 200 micrograms. CONCLUSIONS: Measures of arterial function vary with duration of blood flow occlusion and ISDN dose. Maximum arterial response was reached in all subjects after 4.5 minutes of blood flow occlusion or 200 micrograms of ISDN. Therefore, these variables produce consistent reproducible measures of endothelial function.

Adult↗
PubMed1996

Treatment effects on the total ischaemic burden and prognostic implications.

Anginal symptoms alone are not a reliable guide to the extent of patients' ischaemic heart disease and silent episodes of ischaemia are associated with increased morbidity and mortality. It is becoming apparent that effective treatment of ischaemia will have to target the pattern of ischaemic events seen in patients' daily lives and treatment strategies are now being developed which aim to eliminate both silent and symptomatic episodes of ischaemia over the whole 24-h period. For example, the Circadian Anti-ischaemia Program in Europe (CAPE) trial has shown that significant improvements in objective and subjective measures of ischaemia occurred over 24 h when the once-daily third-generation dihydropyridine calcium antagonist amlodipine was added to background medical therapy. In addition, the Canadian Amlodipine/Atenolol in Silent Ischaemia Study (CASIS) has clearly shown the complementary effects of combination therapy with amlodipine and the long-acting beta-blocker atenolol. Ongoing and future outcome studies will determine the impact of such approaches on the prognosis for patients with ischaemic heart disease.

Amlodipine↗
PubMed1996

The acute rise in plasma fibrinogen concentration with exercise is influenced by the G-453-A polymorphism of the beta-fibrinogen gene.

We have investigated the effects of chronic physical training and acute intensive exercise on plasma fibrinogen levels and the relationship of these responses to beta-fibrinogen G-453-A polymorphism genotype. One hundred fifty-six male British Army recruits were studied at the start of their 10-week basic training, which emphasizes physical fitness. Cohorts were restudied between 0.5 and 5 days after a major 2-day strenuous military exercise (ME) undertaken in their final week of training. Changes in fibrinogen concentration were adjusted for the effects of age, body mass index, and smoking history. Compared with baseline values, fibrinogen concentrations were significantly lower (11.9%, P=.04) at day 5 after ME, consistent with the beneficial effect of training. However, they were higher on days 1 through 3 after ME (suggesting an "acute-phase" response to strenuous exercise) and were maximal on days 1 and 2 (27.2%, P<.001 and 37.1%, P<.001 respectively). Fibrinogen genotype was available in 149 individuals. As expected from previous studies, men with one or more fibrinogen gene A-453 alleles had plasma fibrinogen concentration slightly but significantly higher at baseline (4.5%, P=.11). During the acute-phase response (days 2 and 3), however, the degree of rise was strongly related to the presence of the A allele, being 26.7+/-5.4% (mean+/-SE), 36.5+/-11.0%, and 89.2+/-30.7 for the GG, GA, and AA genotypes, respectively (P=.01). These results confirm that chronic exercise training lowers plasma fibrinogen levels, that intensive exercise generates an acute-phase rise in levels, and that this acute response is strongly influenced by the G/A polymorphism of the beta-fibrinogen gene.

Adolescent↗
PubMed1995

Comparison of cardiopulmonary adaptation during exercise in children after the atriopulmonary and total cavopulmonary connection Fontan procedures.

BACKGROUND: There are several potential physiological differences between the atriopulmonary (AP) and the total cavopulmonary connection (TCPC) Fontan circulations. Studies suggest that the TCPC reduces energy loss due to turbulence and may have more dependence on respiratory movement for pulmonary blood flow. We compared cardiopulmonary physiology during rest and exercise in patients who had undergone the AP Fontan procedure with those who had undergone the TCPC Fontan procedure. METHODS AND RESULTS: Forty-three children were studied more than 6 months after undergoing a Fontan procedure (23 AP and 20 TCPC); 106 healthy children were also studied as a control group. Measurements of effective pulmonary blood flow, stroke volume, arteriovenous oxygen difference, minute ventilation, heart rate, and oxygen and carbon dioxide consumption were made with an Innovision quadrupole mass spectrometer. Data from the control group allowed calculation of z scores for the Fontan groups matched for age, sex, pubertal stage, and body surface area. Maximal exercise performance was equal in the two Fontan groups, but it was below normal. However, adaptation to exercise was different in the Fontan groups. After 9 minutes of exercise, pulmonary blood flow rose less in the AP group than in the TCPC group (P < .01), and the stroke volume in the AP group also tended to be lower (P = .057) and their arteriovenous oxygen difference was significantly greater (P < .01). Although minute ventilation per unit of carbon dioxide production was similar in the Fontan groups at this level of exercise, children in the TCPC group breathed faster by approximately 10 breaths per minute (P < .005). CONCLUSIONS: At submaximal exercise, children who had undergone the TCPC Fontan procedure had pulmonary hemodynamics superior to those of children who had undergone the AP procedure, largely because of respiratory adaptation that permitted blood to be "sucked" into the lungs. To achieve the same maximal exercise performance, children who had undergone the AP procedure had a superior metabolic adaptation to exercise stress.

Adaptation, Physiological↗
PubMed1994

Angiotensin-converting enzyme genotype is not associated with endothelial dysfunction in subjects without other coronary risk factors.

The DD genotype is a polymorphism of the angiotensin-converting enzyme (ACE) gene, and is associated with a significantly increased risk of myocardial infarction. As endothelial dysfunction is an important event in both early atherogenesis and late atherosclerosis, we hypothesised that the adverse effect associated with the ACE/DD genotype might be mediated via endothelial damage. Using high resolution ultrasound, we studied the brachial arteries of 184 subjects aged 15-73 (mean 38 +/- 14) years, who were all normotensive, non-diabetic lifelong non-smokers. Arterial diameter was measured at rest, during reactive hyperaemia (with flow increase causing endothelium-dependent dilation) and after sublingual glyceryl trinitrate (GTN, an endothelium-independent vasodilator). The ACE genotype was determined in each case by DNA amplification; 49/184(27%) had DD, 89 (48%) had ID and 46 (25%) had II genotype. Flow-mediated dilation (FMD) was 8.5% +/- 3.9% in the DD, 7.8% +/- 4.1% in the ID and 7.8% +/- 4.1% in the II subjects (P = NS). GTN-induced dilation was also similar in the 3 groups. On multivariate analysis, endothelium-dependent dilation was inversely related to age (r = -0.33, P < 0.001), vessel size (r = -0.41, P < 0.001) but not ACE genotype (r = 0.002, P = 0.97). The ACE genotype is unrelated to endothelium-dependent dilation in the systemic arteries of clinically well adults. This suggests that the risk associated with this polymorphism may be mediated by other mechanisms.

Adolescent↗
PubMed1993

Cardiomyopathy of glycogen storage disease type III.

To identify the severity of cardiac involvement in glycogen storage disease type III (GSDIII), and its relation to skeletal muscle involvement and age, 23 patients were studied. The median age was 10 years. Echocardiography, electrocardiography, and creatine phosphokinase (CK) levels were used to assess cardiac and skeletal muscle involvement. Septal and left ventricular posterior wall measurements were compared with normal data. Shortening fraction was derived from left ventricular cavity dimensions. In some patients the echocardiogram resembled that of hypertrophic cardiomyopathy. Thirteen of 20 electrocardiograms (ECG) were abnormal. Eleven patients had septal and/or posterior wall thickness > 95% confidence limits (CL). Despite this, cardiac symptoms were uncommon. The CK levels were not directly associated with cardiac abnormalities. Older patients (> 20 years) had more abnormal measurements of posterior wall thickness than did younger ones (< 20 years). This finding, albeit in a cross-sectional series, suggests progressive myocardial involvement with age despite the absence of symptoms.

Adolescent↗
PubMed1992

Attenuation of the circadian patterns of myocardial ischemia with nifedipine GITS in patients with chronic stable angina. N-CAP Study Group.

The Nifedipine Gastro-Intestinal Therapeutic System (GITS) Circadian Anti-ischemia Program (N-CAP) was designed to test the effect of nifedipine GITS as monotherapy or in combination with a beta-adrenergic blocking agent on the circadian pattern of angina and silent ischemia in patients with chronic stable angina. At 118 sites in the United States, 1,174 patients were screened for entry into this study. To be eligible for participation patients were required to have at least two episodes of angina a week and at least two episodes of myocardial ischemia during 48-h ambulatory electrocardiographic (ECG) monitoring during the baseline placebo period. A total of 207 patients completed all phases of the study. Beta-blockers were continued in those patients already receiving them. In this 7- to 10-week single-blind placebo withdrawal study, a 1-week placebo run-in was followed by up to 5 weeks of single-blind titration with nifedipine GITS, a 4-week efficacy phase with an established dose and a final single-blind 2-week placebo withdrawal period. Ambulatory ECG monitoring was performed at the end of each placebo phase and at the end of the efficacy phase with a digital monitoring device that was validated in a pilot study. Overall, nifedipine GITS significantly reduced the weekly number of anginal episodes from 5.7 to 1.8 (p = 0.0001) and the number of ischemic events from 7.3 to 4 (p = 0.0001) reported during the 48-h monitoring periods, with a significant increase in both during the placebo withdrawal period. The baseline circadian pattern of ischemia showed an early morning peak and a secondary peak in the afternoon. Nifedipine GITS significantly reduced ischemia during the 48-h period when administered as monotherapy or in combination with a beta-blocker. Patients were also randomized to receive nifedipine GITS in either a morning or an evening dose. The two regimens resulted in equal anti-ischemic benefit. The primary side effect of nifedipine GITS was edema, which was dose related. In summary, nifedipine GITS reduced the number of anginal and ischemic episodes when given alone or in combination with a beta-blocker. Nifedipine GITS had a sustained effect: a single daily dose was effective over 24 h regardless of whether it was administered in the morning or evening. This study also suggests that combination therapy with nifedipine GITS and a beta-blocker is especially efficacious in reducing ischemia.

Adrenergic beta-Antagonists↗
PubMed1991

Avoidance of tolerance and lack of rebound with intermittent dose titrated transdermal glyceryl trinitrate. The Transdermal Nitrate Investigators.

OBJECTIVES: To investigate the efficacy of transdermal glyceryl trinitrate given continuously and with a nocturnal nitrate free period. DESIGN: Double blind placebo controlled study with two parallel limbs. SETTING: Multicentre trial. PATIENTS: 52 patients randomised to receive either continuous treatment (23 patients) or intermittent treatment with an individually titrated dose (29 patients) for 14 days: both treatments were compared with placebo in a cross-over fashion. INTERVENTION: Continuous treatment with 10 mg per 24 hours of transdermal glyceryl trinitrate or intermittent transdermal glyceryl trinitrate titrated to give an arbitrary 10 mm Hg drop in systolic blood pressure (mean dose 18.2 mg) given over approximately 16 hours. MAIN OUTCOME MEASURE: Treadmill exercise stress testing and ambulatory monitoring of the ST segment after 14 days' treatment. RESULTS: After 14 days' intermittent treatment resting supine and standing systolic blood pressure fell by 7.5 mm Hg (95% confidence interval 2.7 to 12.2) and 9.0 mm Hg (95% CI 3.4 to 14.5) respectively (p less than 0.01); resting heart rate was unchanged. Mean heart rate at 1 mm ST segment depression rose by 11.9 beats/min (CI 1.1 to 23.7) (p less than 0.05), mean time to onset of angina increased by 59 seconds (CI 10.8 to 108) (p less than 0.05), and total exercise duration increased by 40 seconds (p less than 0.05). These changes were not seen after continuous treatment. The frequency of ischaemic episodes was not reduced with either regimen nor was the circadian distribution of these episodes altered, in particular nocturnal episodes did not increase during intermittent treatment. CONCLUSION: Tolerance to glyceryl trinitrate was avoided by the use of individually titrated doses administered with a nocturnal nitrate free period. There was no evidence of "rebound" on ambulatory monitoring during this treatment.

Administration, Cutaneous↗