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Biomedical subjects

R W Harper

Publications and source records attributed to R W Harper.

At least 19 recordsLinked to original sources
PubMed2001

Cobrahead malformation of the Amplatzer septal occluder device: an avoidable compilation of percutaneous ASD closure.

During deployment of an Amplatzer atrial septal occluder device to close a secundum ASD, the right atrial disk and waist of the device twisted, resulting in the cobrahead malformation. Postulated mechanisms for this complication include twisting of the device during loading into the delivery catheter and catching of leading edge of the device on the LA free wall or appendage, causing twisting during deployment. Retrieval of the device into the catheter and even removal of the device from the patient to allow manual untwisting may be required to allow the device to return to its original conformation for successful redeployment.

Aged↗
PubMed2001

Agreement between coronary flow velocity reserve and stress echocardiography in intermediate-severity coronary stenoses.

Visual and quantitative assessments of percent diameter stenosis on coronary angiography correlate poorly with functional testing, particularly in intermediate-severity (40%-70%) lesions, yet are frequently relied on to make decisions regarding revascularization. Coronary flow velocity reserve (CFVR) and relative CFVR (RCFVR) are promising methods for on-line functional assessment of lesion severity in the catheterization laboratory. We sought to determine the agreement between maximal, mean, and relative CFVR and stress echocardiography in intermediate-severity stenoses. The results of exercise or dobutamine stress echocardiography and CFVR measured by intracoronary Doppler were compared in 28 patients referred for assessment of intermediate-severity stenoses, using 15 patients with either angiographically normal coronary arteries or diameter stenoses > 70% as reference groups. CFVR was measured at least three times in response to a bolus of adenosine in the target vessel distal to the stenosis. RCFVR (target/normal vessel CFVR) was also measured in 27 patients. Maximal, mean (of three measures), and relative CFVR were calculated. CFVR > or = 2.0 and RCFVR > or = 0.75 were accepted as normal. A minority (29%) of patients in the intermediate-severity stenosis group had a positive test by either method. There was good to very good agreement between stress echocardiography and maximal CFVR (84%, kappa = 0.62, P < 0.0001) and RCFVR (81%, kappa = 0.59, P < 0.001) across the entire patient cohort, though in the intermediate subgroup concordance was only fair. Using the mean (of three measures of) CFVR for the same comparison improved the agreement in the intermediate subgroup to good (86%, kappa = 0.58, P = 0.002), and in the entire cohort the agreement was very good (88%, kappa = 0.74, P < 0.0001). There was only fair correlation between measures of CFVR and percent coronary stenosis. CFVR improved from 1.8 +/- 0.8 to 2.7 +/- 0.7 after percutaneous intervention (n = 12, P < 0.0001). These results suggest that there is good agreement between CFVR and stress echocardiography across a wide range of coronary lesion severity. The mean of three CFVR measurements distal to the target vessel stenosis increases diagnostic accuracy. Intracoronary Doppler flow velocity measurements at the time of cardiac catheterization may facilitate improved decision-making by providing the ability to assess the functional significance of coronary stenoses on-line.

Adult↗
PubMed2001

Echocardiologists' role in the deployment of the Amplatzer atrial septal occluder device in adults.

Use of the Amplatzer Septal Occluder device to close selected secundum atrial septal defects is ever-increasing. This article illustrates the central role of the echocardiologist before, during, and after percatheter closure with the Amplatzer Septal Occluder device. Figures, diagrams, and tables detail each stage of the evaluation, procedure, and postprocedural assessment.

Cardiac Catheterization↗
PubMed2000

Costs, charges and revenues of elective coronary angioplasty and stenting: the public versus the private system.

OBJECTIVE: To calculate the costs of elective coronary angioplasty and stenting (CAS) in the public and private healthcare systems and to compare these costs with the charges levied and the revenues obtained. DESIGN: A prospective health economics study. SETTING: A tertiary care public hospital and a co-located tertiary care private hospital in the 12 months from February 1998. STUDY POPULATION: 186 consecutive patients (124 public, 62 private) undergoing elective CAS. MAIN OUTCOME MEASURES: Outcome of CAS; exact costs of CAS in the two hospitals; exact charges to private patients; estimated charges in a typical, not co-located, "industry standard private hospital"; estimated costs to the Federal Government of CAS in the public and private system. RESULTS: The immediate and six-month outcomes in the two groups were similar. The average cost of CAS in public patients was $5,516, compared with $5,844 in private patients. The length of stay, number of stents per case and use of nonstent consumables was similar for both groups. Average charges for CAS in patients in the co-located private hospital were $13,347, and estimated average charges for CAS in an industry standard private hospital were $14,978. Estimated current costs to the government for CAS in a public hospital, a co-located private hospital, and an industry standard private hospital were $5664, $5,394 and $6,201, respectively. CONCLUSIONS: Despite similar treatments and similar treatment costs, CAS in the private system, as a consequence of the charges levied, is more than twice as expensive as in the public system, with government costs similar for both systems. These data (together with data from other studies showing that CAS is performed more frequently in private patients) suggest that encouraging more people to take out private health insurance will, paradoxically, increase government costs for CAS as well as increasing overall health expenditure.

Angioplasty, Balloon, Coronary↗
PubMed2000

Diamino benzo[b]thiophene derivatives as a novel class of active site directed thrombin inhibitors. Part 6: further focus on the contracted C4'-side chain analogues.

Novel benzo[b]thiophene diamine thrombin inhibitors were investigated, focusing on a contracted C4'-side chain series. SAR studies identified compounds with either a pyrrolidino or morpholino group as potent, active site directed thrombin inhibitors when the amino group was connected to the C3-phenyl ring with a methylene linker at the C4' position of the phenyl ring.

Antithrombins↗
PubMed2000

Diamino benzo[b]thiophene derivatives as a novel class of active site directed thrombin inhibitors. 5. Potency, efficacy, and pharmacokinetic properties of modified C-3 side chain derivatives.

A systematic investigation of the structure-activity relationships of the C-3 side chain of the screening hit 1a led to the identification of the potent thrombin inhibitors 23c, 28c, and 31c. Their activities (1240, 903, and 1271 x 10(6) L/mol, respectively) represent 2200- and 2900-fold increases in potency over the starting lead 1a. This activity enhancement was accomplished with an increase of thrombin selectivity. The in vitro anticoagulant profiles of derivatives 28c and 31c were determined, and they compare favorably with the clinical agent H-R-1-[4aS, 8aS]perhydroisoquinolyl-prolyl-arginyl aldehyde (D-Piq-Pro-Arg-H; 32). The more potent members of this series have been studied in an arterial/venous shunt (AV shunt) model of thrombosis and were found to be efficacious in reducing clot formation. However, their efficacy is currently limited by their rapid and extensive distribution following administration.

Animals↗
PubMed2000

Long-term oestrogen treatment does not alter systemic arterial compliance and haemodynamics in biological males.

BACKGROUND: Studies have shown that chronic oestrogen treatment improves both lipid profile and vascular reactivity in postmenopausal women, in whom it also appears to have a beneficial effect on vascular haemodynamics and compliance. Whether oestrogen has a similar effect in men is unknown. OBJECTIVE: To determine whether long-term oestrogen treatment alters arterial compliance and haemodynamics in biological males. METHODS: We compared the effects of chronic oestrogen treatment on blood pressure, heart rate and arterial compliance in 21 male-to-female transsexuals prescribed long-term oestrogen treatment with those in 20 age-matched healthy males. Systemic arterial compliance was assessed using the 'area method', by the simultaneous measurement of aortic flow and driving pressure. RESULTS: Mean systemic arterial compliance was similar in transsexuals and age-matched males (mean +/- SE 0.66 +/- 0.06 ml/mmHg compared with 0.58 +/- 0.05 ml/mmHg, P = 0.34). These results did not differ after the exclusion of transsexuals with coronary risk factors or vascular disease. Heart rate (67 +/- 2 beats/min compared with 64 +/- 3 beats/min, P = 0.41), systolic blood pressure (119 +/- 3 mmHg compared with 119 +/- 2 mmHg, P = 0.95), pulse pressure (55 +/- 3 mmHg compared with 50 +/- 2 mmHg, P = 0.13), diastolic blood pressure (64 +/- 2 mmHg compared with 69 +/- 2 mmHg, P = 0.06) and mean arterial pressure (84 +/- 2 mmHg compared with 89 +/- 2 mmHg, P = 0.09) were also similar at baseline between the two groups. Serum testosterone (an index of oestrogen treatment) was markedly suppressed in the transsexuals compared with the males (0.8 +/- 0.5 nmol/l compared with 25.3 +/- 12.6 nmol/l, P < 0.0001). Univariate analysis revealed that the best predictors of arterial compliance were the pulse pressure (rs = -0.41, P = 0.02) and the systolic blood pressure (rs = -0.35, P = 0.02). On multivariate analysis, the best combination of predictors of compliance were the pulse pressure, testosterone and low-density lipoprotein cholesterol concentrations (R2 = 0.29, P = 0.01). CONCLUSIONS: Although previous evidence suggests chronic oestrogen treatment can improve endothelium-dependent vasodilatation and favourably alter the lipid profile in biological males, these changes are not reflected in changes in systemic arterial compliance. Changes in arterial compliance may not be central to the beneficial effects of oestrogen on vascular function, at least in males.

Adult↗
PubMed2000

Increased left atrial thrombin generation in mitral stenosis is not reflected in arterial prothrombin fragment 1+2 levels.

A proportion of patients with mitral stenosis have increased left atrial thrombin generation, with elevated left atrial but normal peripheral venous levels of prothrombin fragment 1+2 (F1+2). Whether this pattern of left atrial and venous F1+2 levels is related to limited spillover of F1+2 from the left atrium into the systemic circulation, or to washout of increased left atrial F1+2 production into the arterial circulation with subsequent systemic clearance, is unclear. We examined the relationship between arterial and venous F1+2 levels in mitral stenosis patients without left atrial thrombus. The study group comprised 36 patients with either a normal (n=29) or prolonged (n=7) international normalized ratio (INR; a measure of clotting time) who were undergoing percutaneous balloon mitral valvuloplasty. Baseline arterial and venous blood samples were collected at the beginning of the valvuloplasty procedure, and left atrial and venous samples were collected after trans-septal puncture. The left atrial F1+2 level exceeded the corresponding venous level in patients with a normal INR (P<0.03); however, baseline arterial and venous F1+2 levels were similar. Arterial and venous F1+2 levels were also similar in the subgroup of patients with evidence of a regional increase in left atrial thrombin generation, and were not different from arterial and venous F1+2 levels in patients without such an increase. Baseline arterial and venous F1+2 levels were both lower in the presence of a prolonged INR. Thus the pattern of increased left atrial but normal venous F1+2 levels in mitral stenosis is due to limited spillover from the left atrium into the systemic circulation.

Adult↗
PubMed2000

Effects of balloon mitral valvuloplasty on systemic and regional left atrial levels of prothrombin fragment 1+2 in mitral stenosis.

A proportion of mitral stenosis patients with left atrial spontaneous echo contrast but without thrombus exhibit a regional hypercoagulable state, characterized by increased left atrial levels, but normal venous levels, of prothrombin fragment 1+2 (F1+2), a marker of thrombin generation. Valve dilatation by balloon mitral valvuloplasty has beneficial effects on left atrial spontaneous echo contrast, but its effect on left atrial thrombin generation is unknown. We examined the effects of balloon mitral valvuloplasty on venous and left atrial levels of F1+2 in 37 patients with mitral stenosis, divided into those with normal (group 1; n=22) and those with increased (group 2; n=15) regional left atrial thrombin generation, as described previously. The mitral valve area increased by a similar degree after the valvuloplasty procedure in the two groups. In group 1, the venous (P<0.005) and left atrial (P<0.0005) levels of F1+2 increased similarly after valvuloplasty, and as a result the left-atrial-venous F1+2 difference was unchanged. The venous F1+2 level also increased after valvuloplasty in group 2 (P<0.005); however, in contrast with group 1, the left atrial level decreased (P<0.03) and as a result the left-atrial-venous difference fell (P<0.05). These results show that balloon mitral valvuloplasty results in an immediate increase in thrombin generation, but a decrease in the left-atrial-venous F1+2 difference, in patients with increased left atrial thrombin generation. The divergent changes in venous and left atrial levels of F1+2 further highlight the limitations of assessing regional changes in coagulation activity by measuring venous levels of coagulation markers.

Adult↗
PubMed2000

Percutaneous coronary intervention in the elderly: a comparison of procedural and clinical outcomes between the eighth and ninth decades.

AIMS: To compare short-term safety and outcome of percutaneous coronary intervention (PCI) in the elderly in their ninth decade with those in their eighth decade. METHODS: Five-hundred and eighty-nine patients aged 70 years undergoing coronary angioplasty were stratified into two groups, those 80 years old (Group 1, n = 65) and those 70Eth 79 years old (Group 2, n = 524). RESULTS: Group 1 comprised more females than Group 2 (57% vs. 40%, respectively; p = 0.009), patients with hypertension (70% vs. 56%, respectively), untreated hyperlipidemia (18% vs. 7%, respectively), acute coronary syndromes (75% vs. 53%, respectively) and multi-vessel disease (63% vs. 54%, respectively). Angiographic success per lesion was similar in Groups 1 and 2 (96% vs. 99%, respectively) as was clinical success per lesion (89% vs. 89%, respectively). Groups 1 and 2 also had a similar incidence of in-hospital death (1.5% vs. 1.1%, respectively), Q-wave myocardial infarction (0.0% vs. 0.6%, respectively), non-Q wave myocardial infarction (6.2% vs. 2.9%, respectively), emergency coronary artery bypass surgery (0.0% vs. 1. 3%, respectively), repeat PCI (3.0% vs. 1.7%, respectively), stroke (1.5% vs. 0.4%, respectively) and local vascular complications (4.6% vs. 4.4%, respectively). However, Group 1 had a longer in-hospital stay (4 days) than Group 2 (2 days) (p < 0.001). CONCLUSION: Our data suggest that short-term procedural and clinical outcomes after PCI are similar for patients in their eighth decade compared to those in their ninth decade.

Age Factors↗
PubMed1999

Contribution of vasodilator prostanoids and nitric oxide to resting flow, metabolic vasodilation, and flow-mediated dilation in human coronary circulation.

BACKGROUND: Endothelial dysfunction is associated with atherosclerosis and may contribute to ischemic syndromes. We assessed the contribution of endothelium-derived nitric oxide (NO) and vasodilator prostanoids to resting blood flow, metabolic vasodilation, and flow reserve in the human coronary circulation. METHODS AND RESULTS: Coronary hemodynamics were assessed before and after inhibition of vasodilator prostanoids and NO with intracoronary aspirin (acetylsalicylic acid [ASA]) and N(G)-monomethyl-L-arginine (L-NMMA), respectively. Angiographically smooth or mildly irregular vessels, with normal adenosine-induced coronary flow reserve, were studied in 25 patients undergoing clinically indicated procedures. Coronary blood velocity was measured by Doppler flow wire, and coronary blood flow (CBF) was calculated. ASA reduced resting conduit vessel diameter by 11% (P = 0.003) and CBF by 27% (P = 0.008) and increased coronary vascular resistance (CVR) by 24% (P<0.0001). ASA attenuated pacing-induced hyperemia by 28% (45.0+/-4.6 versus 32.6+/-3.4 mL/min, P = 0.005) and increased minimum CVR by 39% (2.8+/-0.3 versus 3.9+/-0.5 mm Hg x mL(-1) x min(-1), P = 0.007). L-NMMA reduced resting conduit vessel diameter by 9% (P = 0.05) and CBF by 20% (P = 0.08) and increased CVR by 19% (P = 0.03). L-NMMA attenuated pacing-induced hyperemia by 20% (42.4+/-5.1 versus 34.1+/-3.4 mL/min, P = 0.04) and increased minimum CVR by 33% (2.9+/-0.4 versus 3.8+/-0.5 mm Hg x mL(-1) x min(-1), P = 0.02). ASA (7.7+/-2.3% versus -1.6+/-3.2%, P = 0.06) and L-NMMA (12.1+/-3.9% versus 0.0+/-2.9%, P = 0.02) abolished pacing-induced conduit vessel flow-mediated dilation. Conclusions-Tonic release of vasodilator prostanoids and NO contributes to resting conduit and resistance vessel tone and to peak functional hyperemia and flow-mediated dilation after metabolic stimulation. This underscores the importance of normal endothelial function for metabolic vasodilation and suggests that it may be a key mechanism for preventing myocardial ischemia in coronary artery disease.

Adenosine↗
PubMed1999

Inverse relation of haematocrit to cardiac index in mitral stenosis and atrial fibrillation.

We investigated the relationship between atrial fibrillation and the red cell parameters haematocrit, red cell concentration and mean corpuscular volume in 95 female patients with mitral stenosis (mean age 51+/-11 years, 38 patients in atrial fibrillation, 57 patients in sinus rhythm) who had undergone full blood examination and right and left heart catheterisation. Haematocrit was a positive correlate of atrial fibrillation (r=0.29, p<0.009) and a negative correlate of cardiac index (r=-0.37, p<0.003), but cardiac index was the only independent correlate of haematocrit on multivariate analysis (r2=0.14). The mean corpuscular volume was a positive correlate of age (r=0.42, p<0.0001) and atrial fibrillation (r=0.29, p<0.005) and a negative correlate of cardiac index (r=-0.22, p<0.04) and red cell concentration (r=-0.56, p<0.0001). On multivariate analysis, however, only age and red cell concentration were independent correlates of mean corpuscular volume (r2=0.43). Cardiac index was inversely correlated with both haematocrit and red cell concentration in the subgroup of patients with atrial fibrillation but not those with sinus rhythm. This study demonstrates that the major determinant of the higher haematocrit in mitral stenosis patients with atrial fibrillation is an associated reduction in cardiac index.

Adult↗
PubMed1999

Metabolic vasodilation in the human forearm is preserved in hypercholesterolemia despite impairment of endothelium-dependent and independent vasodilation.

OBJECTIVE: Hypercholesterolemia has been shown to impair endothelium-mediated, nitric oxide (NO)-dependent responses to acetylcholine (ACh), serotonin, substance P and flow-mediated dilation. We have recently shown that NO contributes to metabolic vasodilation in the human forearm. We sought to determine whether metabolic vasodilation is impaired in healthy subjects with hypercholesterolemia. METHODS: We compared the forearm blood flow (FBF) responses to isotonic exercise, ACh and the endothelium-independent vasodilator sodium nitroprusside in young, otherwise healthy volunteers with hypercholesterolemia and controls before and after the NO inhibitor NG-monomethyl-L-arginine (L-NMMA). FBF was measured using venous occlusion plethysmography. Hypercholesterolemic (n = 20) and control (n = 20) subjects were age- and gender-matched. RESULTS: Total cholesterol (6.9 +/- 0.3 vs. 4.6 +/- 0.1 mmol/l, P < 0.0001), low density lipoprotein (4.9 +/- 0.4 vs. 2.7 +/- 0.1 mmol/l, P < 0.001) and triglyceride (1.3 +/- 0.2 vs. 0.8 +/- 0.1 mmol/l, P = 0.005) levels were higher in the hypercholesterolemic group. Basal FBF and resistance were similar in the two groups. Hypercholesterolemia impaired the peak FBF response to ACh (11.1 +/- 1.9 vs. 17.6 +/- 2.2 ml/100 ml/min, P = 0.03), and reduced the peak response to sodium nitroprusside (6.0 +/- 0.4 vs. 8.1 +/- 0.6 ml/100 ml/min, P < 0.01). However, hypercholesterolemia did not affect peak hyperemic FBF (13.1 +/- 1.0 vs. 13.2 +/- 1.0 ml/100 ml/min, P = 1.0) or the FBF volume repayment during the 1 or 5 min after exercise. Resting FBF was reduced by L-NMMA to a similar degree (by 33% vs. 40%, P = 0.17) in both groups. Although L-NMMA reduced peak hyperemic FBF (by 16% vs. 17%, P = 0.93) and the volume repaid after exercise in both groups, there were no differences between the two groups. CONCLUSIONS: Exercise-induced metabolic vasodilation is in part dependent on NO release. Hypercholesterolemia impairs NO-mediated vasodilation, but is not associated with a reduction in exercise-induced hyperemia. This may indicate that multiple compensatory mechanisms are operative in skeletal muscle metabolic vasodilation.

Acetylcholine↗