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Biomedical subjects

B J O'Neill

Publications and source records attributed to B J O'Neill.

At least 19 recordsLinked to original sources

The effect of thyroid hormone therapy on angiographic coronary artery disease progression.

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.

Aged

Angiotensin-converting enzyme inhibition with quinapril improves endothelial vasomotor dysfunction in patients with coronary artery disease. The TREND (Trial on Reversing ENdothelial Dysfunction) Study.

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.

Acetylcholine

Spontaneous pericardial tamponade during PTCA.

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.

Angioplasty, Balloon, Coronary

Does the speed of balloon deflation affect the complication rate of coronary angioplasty?

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.

Aged

Comparison of fixed-wire and over-the-wire balloon dilatation systems for percutaneous transluminal coronary angioplasty.

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)

Aged

Coronary artery fistula as a complication of percutaneous transluminal coronary angioplasty.

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.

Angina Pectoris

Frequency of angiographic detection and quantitative assessment of coronary arterial disease one and three years after cardiac transplantation.

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)

Blood Pressure

Results of operative therapy in the permanent form of junctional reciprocating tachycardia.

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)

Adolescent

A cluster of cases of lymphoma in an underground colliery.

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.

Age Factors

Functional analysis of reverse transcription by a frameshift pol mutant of murine leukemia virus.

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.

DNA, Viral

Ross River virus activity along the south coast of New South Wales.

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.

Adult

Progressive multifocal leucoencephalopathy: CT and pathological features.

A case is presented of a 58-year-old woman with treated lymphocytic lymphoma in histologically proven complete remission who developed progressive multifocal leucoencephalopathy (PML) which extended over several weeks until she died from hypostatic pneumonia. The characteristic abnormal findings in this disease are presented together with the features on computerized tomography (CT scan). Attention is drawn to the usefulness of CT scanning in the diagnosis of this disease.

Female

Mutant of B-tropic murine leukemia virus synthesizing an altered polymerase molecule.

A nonconditional mutant of B-tropic murine leukemia virus (MuLV), defective in polymerase, has been isolated by cloning chronically infected cells. The cell clone containing the mutant produced virus particles which were noninfectious. However, superinfection of the cells by replication-competent XC-negative viruses resulted in the rescue of virus capable of forming plaques in a modified XC test, termed the "complementation plaque assay" (A. Rein and R. H. Bassin, J. Virol. 28:656-660, 1978). Analysis of the noninfectious virions produced without superinfection demonstrated that they contained only 2 to 5% of the wild-type level of reverse transcriptase activity. Purification of this activity indicated that it was associated with a smaller molecule than that produced by wild-type virus. Cells producing the mutant virions did not contain the gag-pol precursor, Pr180gag-pol; however the cells contained proteins of 147K and 114K daltons precipitable with anti-pol serum. All of the normal structural proteins as well as 70S genomic RNA could be detected in the mutant particles. An interference test indicated that a functional ecotropic glycoprotein was synthesized by the mutant. These results indicate that the mutant has a unique defect in the pol gene.

Animals

The effect of oestradiol valerate therapy on coagulation factors and lipid and oestrogen levels in oöphorectomised women.

The effect of oestradiol valerate on levels of blood cholesterol, triglycerides, free oestradiol and coagulation factors, as well as on urinary oestrogens and free cortisol was measured in 10 oöphorectomised women. Despite the very high urinary oestrogen levles obtained, there was no significant change found in the other parameters during and after treatment. These findings are discussed, as is the significance of the metabolism of both endogenously produced and orally administered oestrogens in the menopausal woman.

Adult