Biomedical subjects
Publications and source records attributed to B J O'Neill.
The Perma-Flow graft used in bypass surgery achieves more complete revascularization when paucity of native conduits exists. We report a coronary artery to superior vena cava fistula as a complication of this graft, leading to severe right heart failure. The fistula was successfully occluded percutaneously, improving the patient's clinical situation.
BACKGROUND: Cigarette smoking is a major risk factor for developing coronary artery disease and is associated with increased coronary morbidity and mortality in patients with established atherosclerosis. This report describes the influence of smoking on coronary endothelial function in normotensive patients with coronary artery disease, but without left ventricular dysfunction, severe hypercholesterolemia, or insulin-dependent diabetes mellitus. METHODS: Placebo-treated patients (n = 54) from a larger study assessing coronary endothelial function were classified at baseline as smokers or nonsmokers for this subgroup analysis. Patients underwent coronary angiography at baseline and again after 6-month follow-up. RESULTS: At baseline, there was a trend for a greater decrease in target segment diameter (n = 54) in smokers compared with nonsmokers (-17.2 +/- 5.3% vs. -8.0 +/- 2.5%, acetylcholine 10(-4) mol/l). All measured coronary artery segments (n = 202) showed similar responses (-7.3 +/- 2.7% vs. -3.8 +/- 1.3%, acetylcholine 10(-4) mmol/l, for smokers vs. nonsmokers, respectively). After 6 months, smokers showed an even greater vasoconstrictor response to acetylcholine whereas nonsmokers did not (-21.7 +/- 5.3% vs. -8.3 +/- 2.5%, acetylcholine 10(-4) mmol/l). The vasodilatory response to nitroglycerin was similar in smokers and nonsmokers. CONCLUSIONS: In current smokers, a marked decline in endothelium-dependent vasomotor response was observed over a 6-month period.
OBJECTIVE: In the presence of low serum folate, mutant 5,20-methylenetetrahydrofolate reductase (MTHFR + [A223V/C677T]) in the homozygous state (+/+), may predispose to higher plasma homocysteine (tHct) levels and coronary artery disease (CAD). To determine the impact of this relationship on predisposition to early-onset CAD, we examined the prevalence of the mutation and plasma tHct in patients with early-onset CAD and compared them to patients manifesting CAD later in life. METHODS: Three hundred patients with history of acute myocardial infarction or angina pectoris and angiographically documented CAD were studied. Patients consisted of two groups: group 1 (G1 = 150 patients) presenting with these findings under age 50; while group 2 (G2 = 150) presented for the first time over age 65 years. Prevalence of the MTHFR+ mutation was assessed by molecular analysis, and plasma tHct and folate were measured. An association of the +/+ genotype with early onset CAD could lead to its higher prevalence in the younger age group. RESULTS: There was no significant difference in the frequency of the (+/+) genotype between the two groups (G1: 11.3% vs. G2: 11.3%). However, patients with the (+/+) genotype in both groups had higher tHct when plasma folate was below the mean value (G1: p < 0.0001 while G2: p < 0.01). CONCLUSION: The mutant MTHFR genotype was not found to be a determining factor in early-onset CAD. Higher tHct values were obtained in the older age group, which is expected because other studies have shown that tHct levels increase with age. A significant relation was shown between MTHFR genotype and low folate status yielding high tHct levels in those with the (+/+) genotype. As this relation was seen in both groups, although to a lesser extent in the older G2, it does not explain the underlying cause of early-onset CAD.
OBJECTIVE: To determine the impact of mutations in the HFE gene (human leukocyte antigen H) on predisposition to coronary artery disease (CAD) in patients not diagnosed with hereditary hemochromatosis. BACKGROUND: Elevated iron stores can predispose to acute myocardial infarction. Two mutations (C282Y and H63D) in the novel major histocompatibility complex (MHC) class 1 gene HFE were found in most patients with hereditary hemochromatosis causing high iron stores. The effect of these mutations on predisposition to CAD has not been investigated previously. METHODS: Three hundred patients with a history of myocardial infarction or angina pectoris and angiographically documented CAD were studied. Patients were divided into two groups: group 1 (150 patients), manifesting early onset CAD and presenting with these findings under age 50 years; and group 2 (150 patients), presenting for the first time over age 65 years. Prevalence of the C282Y and H63D mutations was assessed by molecular analysis, and plasma ferritin was measured immunochemically. RESULTS: There was no difference in the prevalence of homozygous, heterozygous or compound heterozygous (C282Y/H63D) states between the groups. Males in group 1 had higher plasma ferritin than those in group 2 (234 +/- 174 micrograms/L versus 136 +/- 103 micrograms/L, P < 0.0001), but this was not significantly different in females (75 +/- 54 micrograms/L versus 92 +/- 73 micrograms/L, P = 0.26). Ferritin remained higher in group 1 than in group 2 males after exclusion of mutation carriers (195 +/- 121 micrograms/L versus 109 +/- 76 micrograms/L, respectively, P < 0.0001), but did not change in females. CONCLUSIONS: Higher iron stores were found in males with early onset CAD. This association was not related to the C282Y or H63D mutation in HFE. It is suggested that association of the MHC locus with delayed onset CAD is probably unrelated to HFE in these patients, and that HFE mutations are not a major risk factor in the development of high iron stores in early onset CAD.
In autumn 1996, shortly after the platelet glycoprotein (GP) IIb/IIIa inhibitor abciximab was approved for clinical use by the Health Protection Branch of Health Canada, seven interventional cardiologists met in a roundtable forum to review the use of abciximab in percutaneous transluminal coronary angioplasty (PTCA). While a compelling body of data was presented that argued strongly for adjunctive abciximab in conventional balloon angioplasty, the participants found in difficult to extrapolate the findings to contemporary interventional practice dominated by stent implantation. This uncertainty stemmed from the lack of clinical trials of abciximab during the stent era. Concerns were also raised that the unrestricted use of two expensive therapeutic modalities (stent implantation and GP IIb/IIIa inhibition) would place severe strains on catheterization laboratory budgets. The general consensus was that, pending the availability of further data, abciximab should probably be reserved for selected at-risk patients. This article summarized the roundtable discussions to provide cardiologists' perspectives on the use of abciximab in interventional practice. An overview of platelet physiology and the rationale for GP IIb/IIIa receptor inhibition; a summary of the results of recent randomized clinical trials that assessed the efficacy of abciximab in PTCA; an account of how stents became the most prevalent technique used in coronary intervention; a summary of the available data evaluating abciximab in conjunction with stent implantation; and a synopsis of the conference discussions are included.
Patients with diabetic amyotrophy may have an inflammatory vasculopathy and may obtain reversal of neurological deficits with immunosuppression. We present a patient with NIDDM, subacute onset of painful asymmetric polyradiculopathy, and unilateral enhancement of lumbar nerve roots on MRI. Clinical improvement and resolution of nerve root enhancement occurred with immunosuppression. We suggest, therefore, that nerve biopsy and gadolinum-enhanced lumbosacral MRI be performed in all patients presenting with diabetic amyotrophy. If nerve root enhancement is present or if nerve biopsy shows perivascular infiltrates, we recommend a trial of immunosuppression.
OBJECTIVE: To study the effect of adequacy of thyroid hormone replacement therapy on coronary atherosclerosis. DESIGN: Retrospective cohort study of elderly hypothyroid patients with coexisting coronary artery disease. The association between the adequacy of thyroid replacement and the progression of angiographic coronary artery disease was investigated. Fisher's exact test was used for statistical analysis. SETTING: Coronary angiographies were performed at the Cardiac Catheterization Laboratory of the Victoria General Hospital, Halifax, Nova Scotia, the only tertiary referral centre for Nova Scotia and Prince Edward Island. Information about the past and current thyroid status of the subjects was collected from their family physicians. PATIENTS: Of 4103 patients admitted for coronary angiography during 1992 and 1993, 25 were on thyroid replacement therapy to treat hypothyroidism. Ten patients who underwent more than one coronary arteriography were selected (seven females and three males, mean age 65 +/- 10 years). RESULTS: Of five patients inadequately treated for hypothyroidism, all demonstrated angiographic evidence of coronary atherosclerosis progression. However, five of seven who were treated adequately did not show atherosclerosis progression (P = 0.02, OR = 0.72, 95% CI 1.36 to infinity). Decreasing or maintaining the dose of L-thyroxine at 100 micrograms or less resulted in coronary atherosclerosis progression in six of six patients, whereas five of six patients taking fixed or increasing doses of L-thyroxine 150 micrograms or higher were spared from disease progression (P = 0.015, OR = 0.41, 95% CI 2.4 to infinity). CONCLUSIONS: Angiographic coronary artery disease progression may be prevented by adequate thyroid replacement in hypothyroidism. With the help of modern, sensitive thyroid stimulating hormone assays higher doses of L-thyroxine may be safer and more effective in the atherosclerosis management of this patient population. Thyroid hormones can protect against atherosclerosis, presumably due to their metabolic affects on plaque progression.
BACKGROUND: Angiotensin-converting enzyme (ACE) inhibitors may exert some of their benefits in the therapy of hypertension, congestive heart failure, and acute myocardial infarction by their improvement of endothelial dysfunction. TREND (Trial on Reversing ENdothelial Dysfunction) investigated whether quinapril might improve endothelial dysfunction in normotensive patients with coronary artery disease and no heart failure, cardiomyopathy, or major lipid abnormalities so that confounding variables that affect endothelial dysfunction could be minimized. METHODS AND RESULTS: Using a double-blind, randomized, placebo-controlled design, we measured the effects of quinapril (40 mg daily) on coronary artery diameter responses to acetylcholine using quantitative coronary angiography. The primary response variable was the net change in the acetylcholine-provoked constriction of target segments between the baseline (prerandomization) and 6-month follow-up angiograms. The constrictive responses to acetylcholine were comparable in the placebo (n = 54) and quinapril (n = 51) groups at baseline. After 6 months, only the quinapril group showed significant net improvement in response to incremental concentrations of acetylcholine (4.5 +/- 3.0% [mean +/- SEM] versus -0.1 +/- 2.8% at 10(-6) mol/L and 12.1 +/- 3.0% versus -0.8 +/- 2.9% at 10(-4) mol/L, quinapril versus placebo, respectively; overall P = .002). CONCLUSIONS: TREND shows that ACE inhibition with quinapril improved endothelial dysfunction in patients who were normotensive and who did not have severe hyperlipidemia or evidence of heart failure. These benefits of ACE inhibition are likely due to attenuation of the contractile effects and superoxide-generating effects of angiotensin II and to enhancement of endothelial cell release of nitric oxide secondary to diminished breakdown of bradykinin.
A case of acute hemorrhagic pericardial tamponade complicating a successful percutaneous transluminal coronary angioplasty (PTCA) is described, in the setting of rheumatoid arthritis (with no evidence of prior or concomitant pericarditis), large doses of intravenous heparin administration and a relatively high activated clotting time. There was no evidence of coronary artery rupture and there was no recent use of other anticoagulants or thrombolytic agents. Successful treatment comprised emergency pericardial drainage and intravenous protamine sulphate. The authors believe this to be the first reported case of acute hemorrhagic pericardial tamponade due solely to heparin administration. The possibility of acute hemorrhage of a rheumatoid nodule was considered but subsequent magnetic resonance imaging scan with contrast gadolinium was normal.
Two hundred consecutive coronary arteries in 157 patients undergoing angioplasty were randomized to fast or slow balloon deflation. Angioplasty was successful in 188 cases (101 with slow and 87 with fast deflation). There was no significant difference between the 2 groups with regard to the total number of dissections, although there was a greater number in the slow deflation group, and no difference in the number of minor dissections (National Heart, Lung, and Blood Institute types A and B). There was a significantly greater number of more severe dissections (types C to F) in the slow deflation group (20 vs 5; p = 0.013). It is proposed that the greater number of severe dissections is due to either increased turbulence or movement of the partially deflated balloon during slow deflation. Thus, slow balloon deflation during coronary angioplasty is associated with a higher complication rate than is conventional rapid deflation.
There is controversy concerning the relative safety and efficacy of the 2 currently available percutaneous transluminal coronary angioplasty dilatation systems--fixed-wire (FW) and over-the-wire (OW). A randomized, prospective trial comparing the 2 systems was performed to examine this controversy. Of 1,513 patients undergoing percutaneous transluminal coronary angioplasty at 3 centers between June 1990 and October 1991, 602 (40%) fulfilled the eligibility criteria for the study. There were 643 lesions, of which 327 were randomized to FW and 316 to OW systems. There was no difference in the success rate between FW (92%) and OW (94%) systems. Inability to cross with a wire was infrequent with either system (FW: 1.8%; and OW: 1.6%). Inability to cross with a balloon when the wire crossed the lesion did not occur. An FW system was successful in 6 cases (1.9%) in which the OW system had been unsuccessful, whereas an OW system succeeded in 14 (4.3%) after the FW system had been unsuccessful (p = NS). Time to cross stenoses was 200 +/- 21 and 233 +/- 22 seconds, procedural time was 21 +/- 1.3 and 21 +/- 1.0 minutes, fluoroscopy time was 6.7 +/- 0.4 and 7.1 +/- 0.4 minutes, contrast used was 89.0 +/- 4.2 and 84.0 +/- 3.5 ml, and number of cine runs was 5.9 +/- 3.0 and 6.3 +/- 3.4 in the FW and OW systems, respectively. Complications were infrequent with either system (FW: 10.4%; and OW: 9.5%). Acute closure occurred in 1.8 and 2.2% of cases in the FW and OW systems, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
A patient underwent successful percutaneous transluminal coronary angioplasty (PTCA) of the left anterior descending and the right coronary arteries for worsening angina and was discharged without any apparent complication. Repeat cardiac catheterization, done four weeks later for recurrent angina, showed a coronary artery fistula to the right ventricle at the site of moderately severe subintimal dissection. The patient was managed conservatively. At cardiac catheterization 18 months after the PTCA procedure, there was no evidence of the fistula.
The reported high incidence of coronary atherosclerosis in many transplant series led us to critically review our experience in 83 patients who have had selective coronary angiography at greater than or equal to 1 years after transplantation. Angiograms were reviewed for evidence of coronary vascular disease, and quantitative analysis of multiple coronary artery segments was performed in serial films. Qualitative analysis revealed only 3 of 83 patients with any angiographic abnormality at follow-up, 1 with minimal luminal irregularities in the right coronary artery at 1 year, a second with a 50% diameter stenosis of the proximal left anterior descending artery and minimal irregularity of the proximal circumflex artery at 1 year and a third patient who developed a new 30% diameter eccentric proximal right coronary artery stenosis at 3-year follow-up. The cumulative incidence of graft vascular disease assessed angiographically was therefore 2% at 1 year and 4% at 3 years. Quantitative analysis, however, showed a significant decrease in coronary artery luminal diameter over time. The mean left main coronary artery diameter decreased from 5.4 +/- 0.9 mm at 1 year to 4.7 +/- 0.8 mm at 3 years (p = 0.0007).(ABSTRACT TRUNCATED AT 250 WORDS)
To assess the results of operative therapy for permanent junctional reciprocating tachycardia, a type of incessant tachycardia, the clinical and electrophysiologic data of 8 such patients referred for management of tachycardia were reviewed. The duration of incessant tachycardia was 14 +/- 10 years (range 2 to 30). The heart rate at rest during tachycardia ranged from 120 to 150 beats/min. Four of 8 patients had cardiomegaly or depressed ejection fraction (16 +/- 10%, range 5 to 27) at presentation and, of these, 2 had symptoms of congestive heart failure. Exertional dyspnea despite normal left ventricular function was noted in 1 patient, 2 had chronic palpitations and 3 were asymptomatic. Electrophysiologic data confirmed the presence of a posteroseptal pathway with atrioventricular node-like properties conducting slowly in the retrograde direction only. Seven patients underwent successful surgical ablation of the accessory pathway. Hypothermic cardiopulmonary bypass was used in 2 and a closed heart technique without cardiopulmonary bypass in the other 5. Three of 4 patients with reduced left ventricular function showed an improvement in ejection fraction to 34 +/- 20% (range 16 to 63) after control of dysrhythmia. Three patients had no evidence of cardiomegaly despite equivalent periods of incessant tachycardia. Another patient with normal left ventricular function despite incessant tachycardia for over 30 years underwent spontaneous remission to sinus rhythm and did not undergo surgery. These data suggest that permanent junctional reciprocating tachycardia has a variable presentation and that congestive heart failure is not an infrequent presenting symptom. The substrate is invariably an accessory atrioventricular pathway with a long conduction time and decremental properties conducting only in the retrograde direction.(ABSTRACT TRUNCATED AT 250 WORDS)
An apparent occupational outbreak of cases of non-Hodgkin's lymphoma among the employees of an underground colliery on the NSW south coast has been investigated. The employment register of the mine recorded that 1004 men had worked at the colliery from its opening in 1946 until December 31, 1986. In this period, this cohort of men had amassed 18,818 person-years. A person-years analysis of the mortality and morbidity of cancer showed a standardized incidence ratio for non-Hodgkin's lymphoma of 3.27 (95% confidence interval [CI], 1.31-6.74) and for Hodgkin's disease of 7.27 (95% CI, 1.98-18.59). All of the cases of non-Hodgkin's lymphoma were diagnosed after 1978. An excess of cases of cancer of the salivary gland also was present (standardized incidence ratio, 10.00; 95% CI, 1.21-36.10). The method of coal extraction, the geology and chemistry of the coal-seams that were mined and the general characteristics of the work-force at the colliery are similar to those at other collieries in the region. Furthermore, an exhaustive work-place environmental study at the colliery has failed to identify any plausible carcinogenic agent to which the findings of this study can be attributed. Coal-miners previously have not been shown to be at a greater risk of developing lymphoma or related malignancies, and the region in which the mine is located has lower prevalence rates of non-Hodgkin's lymphoma and Hodgkin's disease than does New South Wales as a whole.
Endogenous reverse transcription by wild-type murine leukemia virus (MuLV) was compared to that catalyzed by clone 23, a pol mutant containing a reverse transcriptase protein which lacks the carboxyl-terminal third of the molecule (J. G. Levin, S. C. Hu, A. Rein, L. I. Messer, and B. I. Gerwin (1984), J. Virol. 51, 470-478). Competition immunoassays revealed that mutant virions contain normal amounts of polymerase protein, indicating that the lack of carboxyl-terminal sequences does not alter normal processing of enzyme precursors. Although the mutant enzyme was previously shown to have the ability to copy and degrade RNA:DNA hybrids, the present study demonstrates that it is defective in functions required to generate full-length copies of viral DNA. Analysis of products of endogenous reverse transcription showed that minus-strand strong-stop DNA is formed and that mutant virions synthesize a series of minus-strand DNA intermediates up to 2.2 kb in length. Comparison of mutant and wild-type MuLV reaction products indicated that the 2.2-kb termination site of the mutant corresponds to a normal pausing region for the wild-type enzyme. Computer analysis of sequences and structure within pausing regions suggested the involvement of C-rich consensus sequences plus multibranch loop structures in the general phenomenon of enzyme-pausing during reverse transcription.
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The sera of 468 blood donors and 63 domestic animals, collected from the south coast of New South Wales, were tested for the presence of antibodies to Ross River virus. Antibodies were detected in 7% of human sera, 25% of cow sera and 65% of horse sera. Using the blood donors as 'human sentinels', seroconversions were demonstrated in two donors from the Nowra-Kiama region and from a patient in the same area; none of the three had been outside of the study area during the period of seroconversion or at the time of infection. Of the 15 seropositive horses, 6 (40%) had lived continuously since birth on the farms on which they were bled. That humans and horses were infected with Ross River and not a related alphavirus was shown by microneutralization tests against Ross River virus and the other two alpha-viruses (Getah, Sindbis) known to occur in Australia.