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Biomedical subjects

J K French

Publications and source records attributed to J K French.

At least 55 records · Page 3Linked to original sources
PubMed1998

The roles for coronary surgery and angioplasty in the management of patients with stable angina: evidence and decision making.

Evidence from the randomized studies of coronary surgery suggests that patients who benefit from surgery in terms of improved survival are those with left main stem stenosis, triple vessel coronary artery disease, impaired left ventricular function or higher angina class. Patients currently undergoing surgery are in general older, with more severe angina, more comorbidity and more extensive coronary disease as compared with the population randomized in the earlier studies. Angioplasty has been shown to improve symptoms and to reduce the need for surgery in certain patients. Recent changes in procedural techniques and adjunctive therapies have reduced the number of acute complications and the rate of restenosis. However, recent evidence suggests that some patients with mild angina (< class 2) or good exercise tolerance may not benefit as much from angioplasty as other patients with more severe angina.

Angina Pectoris↗
PubMed1997

Randomized, double-blind comparison of hirulog versus heparin in patients receiving streptokinase and aspirin for acute myocardial infarction (HERO). Hirulog Early Reperfusion/Occlusion (HERO) Trial Investigators.

BACKGROUND: Thrombolytic therapy improves survival after myocardial infarction through reperfusion of the infarct-related artery. Thrombin generated during thrombolytic administration may reduce the efficacy of thrombolysis. A direct thrombin inhibitor may improve early patency rates. METHODS AND RESULTS: Four hundred twelve patients presenting within 12 hours with ST-segment elevation were given aspirin and streptokinase and randomized in a double-blind manner to receive up to 60 hours of either heparin (5000 U bolus followed by 1000 to 1200 U/h), low-dose hirulog (0.125 mg/kg bolus followed by 0.25 mg x kg(-1) x h(-1) for 12 hours then 0.125 mg x kg(-1) x h(-1)), or high-dose hirulog (0.25 mg/kg bolus followed by 0.5 mg x kg(-1) x h(-1) for 12 hours then 0.25 mg x kg(-1) x h(-1)). The primary outcome was Thrombolysis In Myocardial Infarction trial (TIMI) grade 3 flow of the infarct-related artery at 90 to 120 minutes. TIMI 3 flow was 35% (95% CI, 28% to 44%) with heparin, 46% (95% CI, 38% to 55%) with low-dose hirulog, and 48% (95% CI, 40% to 57%) with high-dose hirulog (heparin versus hirulog, P=.023; heparin versus high-dose hirulog, P=.03). At 48 hours, reocclusion had occurred in 7% of heparin, 5% of low-dose hirulog, and 1% of high-dose hirulog patients (P=NS). By 35 days, death, cardiogenic shock, or reinfarction had occurred in 25 heparin (17.9%), 19 low-dose hirulog (14%), and 17 high-dose hirulog patients (12.5%) (P=NS). Two strokes occurred with heparin, none with low-dose hirulog, and two with high-dose hirulog. Major bleeding (40% from the groin site) occurred in 28% of heparin, 14% of low-dose hirulog, and 19% of high-dose hirulog patients (heparin versus low-dose hirulog, P<.01). CONCLUSIONS: Hirulog was more effective than heparin in producing early patency in patients treated with aspirin and streptokinase without increasing the risk of major bleeding. Direct thrombin inhibition may improve clinical outcome.

Analysis of Variance↗
PubMed1997

Defective antigen-induced lymphocyte proliferation in the X-linked hyper-IgM syndrome.

We examined T-cell proliferation in five patients with X-linked hyper-IgM syndrome (XHIM), using a panel of antigens and lectins. All patients had impaired antigen-induced proliferation, whereas their lectin responses were normal. Thus, in addition to severely depressed antibody responses, patients with XHIM have a defect in antigen-specific T-cell proliferation, which may explain their susceptibility to pathogens such as Pneumocystis carinii.

Antigens↗
PubMed1997

Coronary revascularisation in young adults.

OBJECTIVE: To evaluate the long-term outcome of coronary artery bypass surgery (CABG) in patients < 40 years old and to determine factors predictive of adverse outcomes. METHODS: Retrospective review of data on 220 patients who underwent isolated CABG at Green Lane Hospital, New Zealand from 1970 to 1992. RESULTS: The actuarial survival after surgery was 91, 74 and 50% at 5, 10 and 15 years, respectively. Recurrence of ischaemic symptoms occurred at a median time of 72 months, and only 20% of patients remained asymptomatic 10 years after CABG. Univariate analysis of potentially adverse surgical factors showed that patients who had prolonged bypass time (> or = 100 min, P < 0.007) had increased late mortality. There were two distinct operative eras with respect to the use of IMA conduits (4% pre 1985, 87% post 1984) The relationship between IMA conduits use and survival was significant on time independent analysis (P < 0.02), but was not using the log-rank test. Preoperative clinical characteristics associated with increased late mortality were impaired left ventricular function (end-systolic volume (ESV) > or = 80 ml, P = 0.008; ejection fraction < 40%, P = 0.0005), and lack of aspirin use either pre- or post-operatively (P < 0.0001). Multivariate analysis indicated that reduced ejection fraction (P = 0.04) and prolonged bypass time (P = 0.05) was associated with an increased risk of late death. Aspirin therapy (P = 0.001) was associated with decreased late mortality. Cumulative events rate of reintervention and mortality was reduced in female patients (P = 0.0009). At review, 45% of patients had total cholesterol > 6.5 mmol/l. CONCLUSION: To avoid the early recurrence of symptoms, the need for reintervention and late mortality, young patients should receive IMA conduits, cardioplegia as myocardial protection, aspirin and therapy to modify/ameliorate their risk factors including dyslipidaemia, diabetes and left ventricular dysfunction.

Actuarial Analysis↗
PubMed1996

Prospective evaluation of eligibility for thrombolytic therapy in acute myocardial infarction.

OBJECTIVES: To determine the proportion of patients presenting with acute myocardial infarction who are eligible for thrombolytic therapy. DESIGN: Cohort follow up study. SETTING: The four coronary care units in Auckland, New Zealand. SUBJECTS: All 3014 patients presenting to the units with suspected myocardial infarction in 1993. MAIN OUTCOME MEASURES: Eligibility for reperfusion with thrombolytic therapy (presentation within 12 hours of the onset of ischaemic chest pain with ST elevation > or = 2 mm in leads V1-V3, ST elevation > or = 1 mm in any other two contiguous leads, or new left bundle branch block); proportions of (a) patients eligible for reperfusion and (b) patients with contraindications to thrombolysis; death (including causes); definite myocardial infarction. RESULTS: 948 patients had definite myocardial infarction, 124 probable myocardial infarction, and nine ST elevation but no infarction; 1274 patients had unstable angina and 659 chest pain of other causes. Of patients with definite or probable myocardial infarction, 576 (53.3%) were eligible for reperfusion, 39 had definite contraindications to thrombolysis (risk of bleeding). Hence 49.7% of patients (537/1081) were eligible for thrombolysis and 43.5% (470) received this treatment. Hospital mortality among patients eligible for reperfusion was 11.7% (55/470 cases) among those who received thrombolysis and 17.0% (18/106) among those who did not. CONCLUSIONS: On current criteria about half of patients admitted to coronary care units with definite or probable myocardial infarction are eligible for thrombolytic therapy. Few eligible patients have definite contraindications to thrombolytic therapy. Mortality for all community admissions for myocardial infarction remains high.

Age Factors↗
PubMed1995

Late outcome after coronary artery bypass graft surgery in patients < 40 years old.

BACKGROUND: Randomized trials confirm the long-term efficacy of coronary artery bypass graft surgery (CABG), although there are no randomized data in patients < 40 years old. Because these patients have been reported to have an early recurrence of symptoms, the long-term postoperative outcome was examined. METHODS AND RESULTS: The long-term outcome of patients (n = 221) < 40 years old undergoing CABG at Green Lane Hospital, New Zealand, from 1970 to 1992 was determined. The 30-day mortality rate was 1.8% for initial and 9.5% for redo CABG. The median times to angina or myocardial infarction (recurrent ischemic event), further intervention, and death were 6.0, 9.6, and 14.2 years, respectively. Factors associated with increased late mortality on univariate analysis included end-systolic volume (ESV) > or = 80 mL (P = .004; 10-year mortality 19% versus 39% ESV > or = 80 mL), no internal mammary conduit (P = .01), no lipid-modifying therapy (P = .005), and no postoperative aspirin use (P = .0002); the latter was also associated with increased recurrent ischemic events (P = .04) or increased reintervention (P = .02). On stepwise logistic regression analysis, factors associated with increased late mortality were increasing ESV (P = .004), no internal mammary artery conduit (P = .009), diabetes (P = .04), and no postoperative aspirin (P = .02); the latter was also associated with increased recurrent ischemic events (P = .02). Hypercholesterolemia (> or = 6.5 mmol/L) was present in 65% of patients at presentation and 45% at follow-up. CONCLUSIONS: To attempt to prevent recurrent ischemia or late death, patients < 40 years old who require CABG should receive internal mammary conduits, aspirin, lipid-modifying therapy, therapy to inhibit ventricular dilatation, and strict diabetes management.

Actuarial Analysis↗
PubMed1995

Frequent reocclusion of patent infarct-related arteries between 4 weeks and 1 year: effects of antiplatelet therapy.

OBJECTIVES: This study assessed the effect of the combination of aspirin and dipyridamole on patency of the infarct-related artery between 4 weeks and 1 year after myocardial infarction. BACKGROUND: Patency of the infarct-related artery is an important determinant of prognosis after myocardial infarction. The incidence of late reocclusion and the effects of antiplatelet therapy are unknown. METHODS: To investigate the importance of antiplatelet therapy for the prevention of late reocclusion, 215 patients who had a patent infarct-related artery 4 weeks after myocardial infarction were randomized in a double-blind manner to receive either a combination of 25 mg of aspirin and 200 mg of dipyridamole twice daily or placebo. One hundred fifty-four patients underwent further coronary arteriography 1 year later. RESULTS: At 1 year, 38 (25%) of 154 patients had reocclusion of the infarct-related artery; 18 (23%) of 79 patients receiving aspirin and dipyridamole had late reocclusion versus 20 (27%) of 75 who received placebo (p = NS). The rate of reocclusion was related to the severity of the residual coronary artery stenosis at 4 weeks (< 50% stenosis 9.2%; 50% to 69% stenosis 11.6%; 70% to 89% stenosis 30.4%; > or = 90% stenosis 70%, p < 0.01). The majority of reocclusions were silent, and only 17 (45%) of 38 were clinically associated with further infarction. There were no differences for a hierarchic end point of cardiac death, myocardial infarction or revascularization (14.8% aspirin and dipyridamole vs. 17.8% placebo). CONCLUSIONS: Late reocclusion of the patent infarct-related artery is a frequent event, occurring in 25% of patients. Antiplatelet therapy with the combination of aspirin and dipyridamole does not alter the overall rate of late reocclusion. Other strategies are required to reduce late reocclusion.

Aspirin↗
PubMed1995

Left ventricular function following thrombolytic therapy for myocardial infarction.

1. The aim of this study was to evaluate the utility of measurement of left ventricular function in assessing the efficacy of thrombolytic agents. 2. All published studies were reviewed. 3. The major effect of the introduction of thrombolytic therapy on mortality after myocardial infarction has been a dramatic decrease in the number of patients dying from cardiac failure. In the thrombolytic era, left ventricular function has remained the most important prognostic factor after recovery from acute myocardial infarction. There are three trials with the statistical power to evaluate left ventricular function, where both left ventricular function and survival were improved compared to placebo or control treatment. The recent Global Utility of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO) Trial supports these findings, with left ventricular function being strongly correlated with mortality reduction. Left ventricular function, measured at 90 min either as ejection fraction, end-systolic volume or infarct zone contractility, closely correlated with 30 day mortality, P < 0.01. 4. Left ventricular function remains an important factor in the evaluation of the efficacy of different thrombolytic and adjuvant regimens.

Humans↗
PubMed1995

Effects of streptokinase in patients presenting within 6 hours of prolonged chest pain with ST segment depression.

BACKGROUND: The effects of streptokinase on the occurrence of a combined clinical outcome in patients presenting with recent chest pain and ST depression were investigated in view of the role of thrombus in the pathogenesis of acute ischaemic syndromes. METHODS: 112 patients aged < or = 75 years presenting within 6 h of the last episode of ischaemic chest pain of least 20 min duration with > or = 1 mm ST depression were randomised in a double blind manner to receive either streptokinase 1.5 million units over 30 min (n = 57) or placebo (n = 55). The primary end point was the combination of death, frequency of myocardial infarction (defined as peak creatine kinase > 600 U/ml), need for angiography because of uncontrollable ischaemia, and an exercise test within 35 days showing > or = 1 mm ST depression at < or = 6 min. The secondary end points were safety, frequency of chest pain, readmission with myocardial infarction or unstable angina, or need for revascularisation between 35 days and 1 year. The severity of ST depression on presentation was analysed with respect to clinical outcome. RESULTS: The frequency of the combined hierarchical end point of death, myocardial infarction, early angiography, and a positive exercise test was 82% (47 of 57 patients) with streptokinase and 75% (41 of 55 patients) with placebo. There were four deaths, two in each group. 27 patients (47%) receiving streptokinase and 22 (40%) receiving placebo developed myocardial infarction. 11 patients (eight streptokinase and three placebo) required coronary arteriography and subsequent revascularisation because of angina uncontrolled by medical treatment. 44 patients (22 in each group) had a positive exercise test. There were three further cardiac deaths (one streptokinase, two placebo), and three noncardiac deaths within 1 year. A conservative approach to intervention was adopted and over a period of 1 year 29 patients (26%) (13 streptokinase and 16 placebo) underwent revascularisation procedures. Three patients (two streptokinase and one placebo) required transfusion. ST depression > or = 3 mm had 90% specificity but only 60% positive predictive value for myocardial infarction at presentation (P = 0.008, stepwise logistic regression). ST depression > or = 2 mm was predictive of death, late development of myocardial infarction, or a need for angiography (P = 0.02). CONCLUSION: Patients presenting with ischaemic chest pain and ST depression frequently develop myocardial infarction. Severe ST depression is predictive of an adverse outcome. The 35 day (3.6% cardiac and total) and 1 year mortality (8.9% total, 6.3% cardiac) are low with conservative management and expeditious revascularisation. Streptokinase treatment within 6 h of the last episode of pain does not seem to be beneficial.

Aged↗
PubMed1993

Association of angiographically detected coronary artery disease with low levels of high-density lipoprotein cholesterol and systemic hypertension.

The prevalence of risk factors for atherosclerosis in 488 consecutive patients undergoing cardiac catheterization for the investigation of chest pain was compared with that in 868 subjects from a population sample. The presence and severity of angiographic coronary artery disease (CAD) (defined as mean diameter stenosis > 50%), total and high-density lipoprotein (HDL) cholesterol, triglycerides, history of systemic hypertension, smoking, diabetes mellitus, family history and drug therapy were assessed. Low HDL cholesterol (< 0.9 mmol/liter [35 mg/dl]) was more prevalent in patients with CAD than in the population sample in both men (44% [95% confidence interval 38 to 48] vs 21% [12 to 28]; p < 0.01) and women (12% [9 to 15] vs 1% [0 to 3]; p < 0.01). There were no differences in total cholesterol levels between these 2 groups. Total:HDL cholesterol ratios were significantly greater in patients with CAD. History of systemic hypertension was more prevalent in both men and women with CAD than in the population sample (47% [37 to 57] vs 20% [16 to 25] for men, and 31% [26 to 36] vs 21% [17 to 26] for women; p < 0.01). The prevalence of other risk factors was not significantly different between the 2 groups. In patients with CAD, the severity of disease was inversely correlated with levels of HDL cholesterol in both men and women (p < 0.01), and positively correlated with total cholesterol in men aged < 55 years (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Cholesterol↗
PubMed1992

Molecular cloning and characterization of grancalcin, a novel EF-hand calcium-binding protein abundant in neutrophils and monocytes.

A novel EF-hand Ca(2+)-binding protein we have called grancalcin has been identified and characterized. This protein is particularly abundant in neutrophils and monocytes, with relatively small amounts in lymphocytes. The cDNA for this protein has been cloned and sequenced. The sequence predicts that the protein is composed of 217 amino acids, with a molecular mass of 24,010 daltons. It contains four EF-hand calcium-binding motifs and exhibits strong homology to sorcin, one of two proteins overexpressed in multidrug-resistant cells whose function is unknown. There are potentially one phosphorylation and two glycosylation sites. The 1.65-kilobase mRNA is detected in bone marrow and is present in neutrophils, monocytes, macrophages, B and T lymphocytes, and the promyelocytic cell line HL60s. The protein displays a Ca(2+)-dependent translocation to the granules and plasma membrane of neutrophils, suggesting that it might play an effector role in the specialized functions of these cells.

Amino Acid Sequence↗
PubMed1992

The role of dipyridamole in addition to low dose aspirin in the prevention of occlusion of coronary artery bypass grafts.

One hundred and one subjects were randomised to receive either aspirin 100 mg or aspirin 100 mg + dipyridamole 300 mg daily before undergoing coronary bypass surgery. The drugs were commenced at least 36 hours before operation and patients were followed for one year. There were three perioperative deaths and 37 withdrawals, of which 14 were drug related (aspirin four, aspirin + dipyridamole ten). Cineangiocardiograms at nine weeks and one year showed vein graft patency rates of 93% and 87% for subjects treated with aspirin alone; and 90% and 89% in those who received aspirin+dipyridamole. During the follow-up period 14% of 232 coronary lesions in the aspirin treated group advanced by more than two grades compared with 15% of 315 lesions in the aspirin+dipyridamole group. The study did not establish superiority of one regimen over another in terms of graft patency or progress of lesions in native vessels. However, low dose aspirin was better tolerated than combination therapy.

Aged↗
PubMed1991

Treatment of primary hypercholesterolaemia with simvastatin. New Zealand multicentre evaluation.

OBJECTIVE: To assess the efficacy of simvastatin in a large patient cohort. DESIGN: In an open multicentre study, after a four week placebo phase, patients were treated with simvastatin for 24 weeks; a subgroup continued therapy for a further 24 weeks. Efficacy of simvastatin (a) with prolonged use over three years, and (b) in combination with bezafibrate was assessed in an open single site study. SETTING: Lipid or cardiology specialist hospital outpatient clinics. PATIENTS: For the open multicentre study, 228 patients with primary hypercholesterolaemia (total cholesterol level greater than 6.5 mmol/L) were recruited, of whom 224 met entry criteria and completed the study. Forty-seven of these patients continued therapy for one year. In the open single site study, 22 patients (with low density lipoprotein [LDL] cholesterol levels greater than 4.3 mmol/L) participated in studies of long term use (n = 9) or of combined therapy (n = 13). INTERVENTION: Therapy in the open multicentre study began with 10 mg of simvastatin per day, doubling to 20 mg after six weeks and then 40 mg after 12 weeks of therapy if total cholesterol levels persisted above 5.2 mmol/L. In the study of long term use, simvastatin (40 mg daily) was taken continuously over three years. In the study of combination therapy, bezafibrate (600 mg daily) was taken in addition to simvastatin (40 mg daily) for 10 months. MAIN OUTCOME MEASURES: Plasma lipid and lipoprotein concentrations. RESULTS: In the multicentre study, total plasma cholesterol levels were reduced by 32.8% from 9.11 +/- 1.84 (in mmol/L, mean +/- SD) to 6.12 +/- 1.25 (P less than 0.001), and LDL cholesterol levels by 41.4% from 6.90 +/- 1.92 to 4.04 +/- 0.31 (P less than 0.001). The effect of therapy was sustained in those patients continuing therapy to 48 weeks. The study of long term use found no significant attenuation of effect over three years of monotherapy. Combined simvastatin/bezafibrate therapy reduced the LDL cholesterol concentration by a further 19.9% (P less than 0.001) from levels achieved on simvastatin alone. CONCLUSIONS: Simvastatin is an effective, well tolerated lipid lowering drug, without significant attenuation of effect with prolonged use. Simvastatin plus bezafibrate appears to be a potentially useful drug combination.

Adult↗