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Biomedical subjects

C O'Sullivan

Publications and source records attributed to C O'Sullivan.

At least 19 recordsLinked to original sources
PubMed1996

Heart rhythms, ventricular arrhythmias, and death in chronic heart failure.

BACKGROUND: The aim of this study was to evaluate whether abnormalities in heart rate variability (HRV) could act as markers of ventricular tachycardia and prognosis in patients with advanced, chronic heart failure. Fifty patients with chronic heart failure (45 men; mean age, 59 +/- 9 years; New York Heart Association [NYHA] class II-III; left ventricular ejection fraction [LVEF], 19 +/- 9% and peak oxygen consumption, 16.6 +/- 5.4 mL/kg/min) caused by idiopathic dilated cardiomyopathy (n = 12) and ischemic heart disease (n = 38) were included in the study. Heart rate variability measures derived from 24-hour electrocardiographic (ECG) monitoring (Marquette 8500 recorder, Marquette Electronics, Milwaukee, WI) were calculated in the time domain and frequency domain. METHODS AND RESULTS: Twenty-five patients (50%) revealed episodes of ventricular tachycardia on 24-hour ECG monitoring (1-143 episodes). The presence of ventricular tachycardia was associated with lower LVEF but there was no difference in NYHA class and peak oxygen consumption between patients with and without ventricular tachycardia (LVEF, 16 vs 22%, P = .01; NYHA class, 2.6 vs 2.4; peak oxygen consumption, 16.5 vs 16.8 mL/kg/min, not significant). Patients with ventricular tachycardia exhibited markedly lower HRV measures. Multiple regression analysis was used to test HRV parameters as potential predictors of ventricular tachycardia. Among them, high-frequency power was the only independent predictor of the presence of ventricular tachycardia, and this predictive correlation was independent of LVEF and mean R-R interval duration. During a follow-up period of 24 +/- 18 months, 12 patients (24%) died. No difference was found in age, etiology, NYHA class, peak oxygen consumption, or occurrence of ventricular tachycardia, but a lower LVEF (15 +/- 6 vs 21 +/- 9%, P = .046) was observed in those who died compared with those who survived. Certain estimates of HRV were in contrast, lower in those who subsequently died: standard deviation of all normal R-R intervals (61 +/- 30 vs 101 +/- 33 ms), standard deviation of 5-minute mean R-R intervals (55 +/- 27 vs 92 +/- 31 ms), mean of all 5-minute standard deviations of R-R intervals (22 +/- 12 vs 37 +/- 11 ms), and the low-frequency (3.2 +/- 1.8 vs 4.8 +/- 0.9 ln ms2) and high-frequency (3.0 +/- 1.1 vs 3.8 +/- 0.8 ln ms2) components of the HRV spectrum (all differences, P < .01). In univariate Cox analysis, all of these HRV measures were independent predictors of death. Kaplan-Meier survival analysis revealed that the standard deviations of all normal R-R intervals and of 5-minute mean R-R intervals dichotomized at median values (99 and 90.5 ms, respectively) were the best predictors of mortality. CONCLUSIONS: In patients with moderate to severe chronic heart failure, depressed indices of HRV on 24-hour ambulatory ECG monitoring could be related to higher risk of ventricular tachycardia and death, suggesting that analysis of HRV could be usefully applied to risk stratification in chronic heart failure patients.

Arrhythmias, Cardiac↗
PubMed1996

Effect of acute alterations in afterload on left ventricular function in patients with combined coronary artery and peripheral vascular disease.

OBJECTIVE: To assess the effect of acute alterations in afterload by aortoiliac clamping, during peripheral vascular surgery, on left ventricular function. DESIGN: Prospective examination of the left ventricular long axis and transmitral Doppler flow preoperatively and intraoperatively; before aortic clamping, during clamping and 5 min, 15 min, and 5 days after unclamping. SETTING: A tertiary referral centre for cardiac and vascular disease equipped with invasive and non-invasive facilities. PATIENTS: 20 patients (11 men; mean (SD) age 61 (8) years) with significant aortoiliac disease and documented coronary artery disease and 21 normal controls of similar age. RESULTS: Preoperatively: long axis function was abnormal compared with that in normal controls. In systole total long axis excursion and peak shortening rate were reduced, onset of shortening delayed, and there was pre-ejection lengthening (P < 0.001). In diastole there was abnormal shortening during isovolumic relaxation, delaying the onset of long axis lengthening (P < 0.001). Peak lengthening rate was also reduced and A wave excursion increased (P < 0.001). Transmitral Doppler showed increased A wave velocity and reduced peak E/A diastolic flow velocities ratio (P < 0.001). Intraoperatively: preclamping results did not differ from those before operation. With clamping the extent of systolic and diastolic abnormalities promptly increased as to a lesser extent did those of transmitral flow velocity, although heart rate and blood pressure did not change significantly. Total long axis excursion and A wave amplitude were more reduced by aortic than iliac clamping, whereas the onset of lengthening was more delayed and the lengthening velocity more reduced with iliac clamping. Some 5 min after unclamping systolic long axis function had already returned towards normal; total excursion increased, as did the peak shortening rate, and the onset of shortening became less delayed (P < 0.001). In diastole the delayed onset of lengthening regressed, its lengthening velocity increased, and A wave excursion fell (P < 0.001). Early diastolic transmitral flow velocity also increased. This improvement in systolic and diastolic long axis function had progressed 15 min after unclamping but showed no further change at 5 days. At 5 days after operation, however, systolic and diastolic measurements had improved compared with those preoperatively. CONCLUSION: Resting left ventricular long axis function is abnormal in patients with combined coronary artery disease and peripheral vascular disease. It is unaffected by anaesthesia but deteriorates with aortic or iliac clamping, although blood pressure remains unchanged. It promptly improves with unclamping after successful peripheral arterial reconstruction. Thus, even in apparently stable coronary artery disease, resting subendocardial function is labile, showing pronounced alterations with changing after-load, even when arterial pressure itself does not change.

Blood Pressure↗
PubMed1996

ACE inhibitors unmask incoordinate diastolic wall motion in restrictive left ventricular disease.

OBJECTIVE: To assess the effect of ACE-inhibition on left ventricular filling and wall motion in patients with a clinical diagnosis of heart failure. DESIGN: Prospective examination of left ventricular systolic and diastolic function using M mode echocardiography and pulsed and continuous wave Doppler before and three weeks after starting an ACE inhibitor. SETTING: A tertiary referral centre for cardiac disease equipped with non-invasive facilities. SUBJECTS: 30 outpatients with a clinical diagnosis of heart failure in whom treatment with an ACE inhibitor was started; age 61 (SD 11) years; 27 male; 3 female; 21 healthy controls of similar age. RESULTS: Left ventricular cavity was dilated both at end systole and end diastole, and fractional shortening reduced. Although mean isovolumetric relaxation time (IVRT) and transmitral E (early) to A (late) filling velocity (E/A) ratio were not different from normal, a value of 1.0 on the normal frequency plot of the E/A ratio divided the patients bimodally into two groups: 20 patients (group A) with E/A ratio > 1.0 and 10 patients (group B) < 1.0. In group A patients, IVRT was short as was transmitral E wave deceleration time compared to normal (P < 0.001), fulfilling the criteria of restrictive left ventricular physiology. Left ventricular wall motion during IVRT was coordinate and left ventricular end diastolic pressure was raised on the apex-cardiogram (P < 0.001). In group B, E wave deceleration time was longer, relaxation incoordinate, and apexcardiogram normal. With an ACE inhibitor: in group A, left ventricular dimensions fell at end diastole (P < 0.05) and end systole (P < 0.01) but fractional shortening did not change; long axis total excursion (P < 0.01) and peak rate of shortening (P < 0.05) both increased; IVRT increased (P < 0.001) with the appearance of markedly incoordinate wall motion, minor axis lengthening, and long axis shortening (P < 0.001 for both); A wave amplitude also consistently increased (P < 0.001); finally, transmitral E wave velocity fell and A wave velocity increased. ACE inhibition did not alter any of the left ventricular minor and long axis or transmitral Doppler variables in patients in group B. CONCLUSIONS: Patients with a clinical diagnosis of heart failure differ in their presentation and response to ACE inhibition according to baseline haemodynamics. In restrictive left ventricular physiology, ACE inhibition reduces cavity size and prolongs IVRT, compatible with a fall in left atrial pressure. At the same time, ventricular relaxation becomes very delayed and incoordinate, greatly reducing early diastolic left ventricular filling velocity. Thus ACE inhibition unmasks major diastolic abnormalities in patients with restrictive left ventricular disease.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1995

Association of reduced PR-AC interval with ventricular early potentials in dilated cardiomyopathy.

We studied 31 patients with dilated cardiomyopathy, correlating mitral valve cusp motion with the continuous wave Doppler signal of mitral regurgitation and the signal averaged electrocardiogram (ECG). Sixteen patients had a B point (early partial closure) on the mitral echogram and 15 did not. Fifteen normal cases were used as controls. The duration of ventricular early potentials (< 40 microV) was measured on the signal averaged ECG of the QRS complex. The PR interval was increased in patients with a B point (190 (33) ms vs. 145 (16) ms in normal, P < 0.01) and PR-AC interval was reduced (25 (71) ms vs. 65 (11) ms in normal, P < 0.05). The B point itself was effectively synchronous with the onset of low velocity early systolic mitral regurgitation, and followed the Q wave of the succeeding beat by 20 ms or less. Early low velocity on mitral regurgitation was not present in patients without a B point. The duration of early potentials was greatly increased in patients with a B point (43 (26) ms) compared both to those without (17 (20) ms, P < 0.01) and to normals (12 (7) ms, P < 0.01) and their duration correlated with B-C interval (r = 0.6, P < 0.02). We conclude that a B point on the mitral echogram in patients with left ventricular disease is due to early systolic low velocity mitral regurgitation which itself results from an abnormal pattern of left ventricular activation, probably bilateral bundle branch block. Once established, this low velocity jet delays complete mitral valve closure.

Adult↗
PubMed1995

Abnormal ventricular long-axis function in systemic sclerosis.

STUDY OBJECTIVE: To assess possible effects of systemic sclerosis on ventricular function. DESIGN: Retrospective analysis of patients referred for echocardiographic examination to assess ventricular function. SETTING: Tertiary referral center for cardiac and chest diseases equipped with invasive and noninvasive facilities. PATIENTS: Thirty-four patients with clinical diagnosis of systemic sclerosis, aged 49 +/- 12 years; 24 had pulmonary fibrosis and 10 did not. There were 21 normal controls of similar age. MEASUREMENTS: Two-dimensional guided M-mode echocardiographic recordings of the left ventricular minor and long axis at the left and septal sites and right ventricle were obtained. Transmitral and transtricuspid Doppler flow velocities were also obtained with ECG and phonocardiogram. RESULTS: In 24 patients with pulmonary fibrosis, long-axis excursion was reduced 2.1 +/- 0.5 vs 2.7 +/- 0.4 cm/s as was peak rate of shortening and lengthening, 8.5 +/- 3.3 vs 10.8 +/- 2.4 cm/s and 7.5 +/- 2.5 vs 12 +/- 3.6 cm/s, respectively (p < 0.001), at the right side compared with 10 patients without. The onset of right long-axis shortening and lengthening was delayed with respect to the Q wave of the ECG and P2 of the phonocardiogram (p < 0.001 in both vs controls). The onset of tricuspid forward flow from the second heart sound was also delayed in the two groups, 110 +/- 15 ms and 100 +/- 20 ms vs 80 +/- 15 ms, respectively (p < 0.001). Right ventricular late diastolic filling velocities were increased 35 +/- 15 and 35 +/- 12 cm/s vs 20 +/- 10 cm/s in both groups (p < 0.01), and hence E:A ratio reduced 1.25 +/- 0.5 and 1.4 +/- 0.3 vs 1.9 +/- 0.4, respectively (p < 0.001). Pulmonary flow acceleration time was reduced only in patients with pulmonary fibrosis, 105 +/- 30 ms vs 125 +/- 30 ms (p < 0.001). At the left side, total long-axis excursion was reduced only in patients with pulmonary fibrosis (p < 0.01), while peak shortening and lengthening rates were reduced in both groups (p < 0.05). The onset of shortening from the Q wave and lengthening from the second heart sound were both delayed in the two groups with the latter greatly delayed in patients with pulmonary fibrosis (p < 0.05). CONCLUSIONS: Right and left ventricular long-axis function is frequently abnormal in patients with systemic sclerosis. Abnormalities are more profound in patients with CT evidence of pulmonary fibrosis than in those without. We suggest that these disturbances are due to myocardial fibrosis which, from the anatomic distribution of longitudinally directed fibers, is likely to have been subendocardial.

Blood Flow Velocity↗
PubMed1994

Spinal cord tumors in children: long-term results of combined surgical and radiation treatment.

The authors report a series of 31 children under 17 years of age with primary spinal cord tumors who underwent radiation treatment following decompression laminectomy with or without tumor resection between 1959 and 1990. The tumors consisted of 15 astrocytomas, 11 ependymomas, one mixed glioma, one gangliolioma, and three of unknown histology. Ten- and 20-year survival rates and 10- and 20-year relapse-free survival rates for the 28 patients with known histology were 80% and 53%, and 73% and 67%, respectively. Eleven patients (35%) had no resection, 14 (45%) had a partial resection, and six (19%) had a grossly complete resection. Eight patients (26%) are dead: five due to recurrent tumor, two due to a second malignant tumor, and one due to intercurrent disease. primary tumor relapse or progression occurred in nine patients (29%), four of whom were salvaged. A second malignant tumor developed in four patients (13%), two of whom died. Local control of the tumor was finally achieved in 26 cases (84%), despite either grossly incomplete or no resection in 25 of these cases (81%). These statistics suggest that radiation treatment without resection may achieve long-term control in children with astrocytoma or ependymoma of the spinal cord.

Adolescent↗
PubMed1994

Adenovirus-mediated gene transfer for cystic fibrosis: quantitative evaluation of repeated in vivo vector administration to the lung.

Adenoviral vectors have an important role as in vivo gene delivery vehicles in developing human gene therapy for the fatal pulmonary component of cystic fibrosis. In this study we evaluated the immune responses to wild-type adenovirus and replication-deficient, first generation adenoviral (Av1) vectors in the cotton rat (Sigmodon hispidus) and then quantitatively evaluated the efficiency of gene delivery and expression of single and repeated in vivo administration of Av1 vectors to the respiratory tract. Av1 vector reporter gene expression was quantitatively evaluated by employing a luciferase expression vector (Av1Luc1) and measuring luciferase activity in whole lung tissue homogenates by routine luminometry. Gene transfer and expression in naive animals (e.g. first Av1 vector dose) was efficient. A repeat dose also resulted in successful gene transfer and expression, although at a significantly reduced level (p < 0.01) compared with naive animals. This reduction inversely correlated with serum human adenovirus neutralizing antibody (HANA) titers. Importantly, increasing doses of Av1Cf2, an Av1 vector expressing the human CFTR cDNA, resulted in a graded HANA response consistent with a lack of in vivo replication. These observations have significant implications for repeated administration of adenoviral vectors to the lungs of individuals with cystic fibrosis.

Adenoviruses, Human↗
PubMed1993

Secretion of epidermal growth factor by macrophages associated with breast carcinoma.

By means of a cytokine release assay we have shown that in cell populations derived from primary breast carcinoma, epidermal growth factor (EGF) is secreted by cells with the characteristic morphological and immunophenotypic profile of activated macrophages (positive for CD68, CD16, CD25). EGF secretion was observed in 11 (31%) of 35 primary tumours. Secretion of EGF by normal or malignant epithelial cells was not observed. We found no association between EGF secretion by the primary tumour and recognised clinical indices of prognosis.

Adult↗
PubMed1993

Differential pulse voltammetric determination of 7-hydroxycoumarin in human urine.

The electrochemical behaviour of 7-OH-coumarin at the bare glassy carbon electrode has been studied using differential pulse voltammetry, and based on anodic detection of this metabolite at 0.66 V (vs SCE) using DC amperometry, a method has been developed for the determination of 7-OH-coumarin levels in urine samples, and a pharmacokinetic profile established.

Electrodes↗
PubMed1993

Development of an antibody-based amperometric biosensor to study the reaction of 7-hydroxycoumarin with its specific antibody.

An amperometric biosensor, based on an anti-7-hydroxycoumarin (7-OH-coumarin) antibody immobilized at the surface of a glassy carbon electrode, and contained behind a cellulose dialysis membrane, is described. The electrochemical behaviour of this metabolite at the bare glassy carbon electrode was found to be well defined by using differential-pulse voltammetry, and a 90% decrease in peak height was observed on binding of the antibody to the antigen, which occurs at the electroactive site of 7-OH-coumarin. The kinetics of the antibody-antigen reaction was investigated and a first-order reaction was observed with k = 0.0329 mA min-1. This system provides a novel method for studying antibody specificity and the kinetics of such antibody-antigen interactions.

Antibodies↗
PubMed1993

Shortened left ventricular filling time in dilated cardiomyopathy: additional effects on heart rate variability?

OBJECTIVE: To assess possible mechanical influences underlying the reduced heart rate variability in patients with dilated cardiomyopathy. DESIGN: Comparison of standard non-spectral indices of heart rate variability with echocardiographic Doppler measures of left ventricular function in patients and normal controls. PATIENTS: 20 patients with dilated cardiomyopathy and 15 normal subjects of similar ages were studied. METHODS: Standard non-spectral indices of heart rate variability were measured over 24 hours. These were correlated with left ventricular cavity size, shortening fraction, and isovolumic relaxation time measured by M mode echocardiography, and the duration of functional mitral regurgitation and left ventricular filling time assessed by continuous wave Doppler. RESULTS: Mean RR interval and estimates of short term variability (root mean square difference of successive RR intervals, proportion of adjacent RR intervals > 50 ms different, and SD indices) were not different from normal. The overall mean (SD) of the RR interval (65 (35)), and SD of five minute mean RR intervals (55 (30)), however, were reduced compared with normal values (115 (40) and 105 (45); p < 0.01 for both). Neither correlated with left ventricular cavity size or shortening fraction, but both were strongly related to left ventricular filling time (coefficient of variation, r = 0.82 and r = 0.81 respectively). Correlation persisted when the SD was corrected for RR interval (r = 0.69) although this correlation was not found in the controls. In individual patients, the difference between RR interval at the time of echo and minimum value during the 24 hours, a measure of ability to increase heart rate, also correlated closely with filling time (r = 0.92). CONCLUSION: As the duration of functional mitral regurgitation is effectively fixed, its presence can limit the time available for left ventricular filling in dilated cardiomyopathy when heart rate is high. This may become the mechanism by which maximum heart rate is set, becoming fixed to optimise cardiac output. This manifestation of dilated cardiomyopathy may be an important factor in reduction of heart rate variability in these patients.

Adult↗
PubMed1993

Microalbuminuria and coronary heart disease in non-diabetics.

Microalbuminuria (or urinary albumin excretion rates (AER) above normal limits) is associated with coronary heart disease (CHD) particularly in diabetics. To determine the sensitivity and specificity of AER for CHD in a non-diabetic population we prospectively studied 115 consecutive patients undergoing coronary angiography and 66 undergoing exercise electrocardiography (ECG). There was no relationship between AER and the severity of CHD determined by angiography (Gensini-scored). While microalbuminuria (AER > 20 micrograms/minute) was 91% specific it had low sensitivity (12%). Microalbuminuria is not a sensitive indicator of CHD in a non-diabetic population.

Aged↗
PubMed1991

Activating point mutations of the gsp oncogene in human thyroid adenomas.

The gene for the alpha polypeptide chain (alpha s) of the heterotrimeric G protein Gs can be activated to the putative oncogene gsp by specific point mutations at codons 201 and 227. Such mutations have been reported in 40% of human growth hormone-secreting pituitary adenomas and in a single autonomously functioning thyroid adenoma. We examined an archival series of 45 differentiated human thyroid tumors by polymerase chain reaction amplification and oligonucleotide hybridization to identify point mutations at each of the affected codons. Successful amplification was achieved in 38 cases, and activating mutations were identified in 5 of 13 (38%) autonomously functioning adenomas, but in none of 16 nonfunctioning adenomas, six papillary carcinomas, or three follicular carcinomas. Our results confirm that the gsp oncogene is involved in the pathogenesis of autonomously functioning tumors but do not support a role in other thyroid tumors.

Adenoma↗
PubMed1991

Abnormalities of the p53 tumour suppressor gene in human pancreatic cancer.

The tumour suppressor gene p53 has been found to be mutated or inactivated at high frequency in several common human tumours. We have examined a series of exocrine pancreatic carcinomas for over-expression of mutant forms of p53 by immunohistochemistry with a panel of specific antibodies. We found immunodetectable p53 in 13 of 22 (60%) frozen pancreatic cancers and seven of 13 pancreatic cell lines. One of the antibodies, CM1, recognises p53 in formalin-fixed, paraffin-embedded archival material and using this reagent we found immunodetectable p53 in 28 of 124 (23%) pancreatic cancers. We have successfully demonstrated the presence of point mutations by direct sequencing of genomic DNA extracted from archival tissue showing CM1 immunoreactivity. We conclude that p53 activation is an important event in human pancreatic tumorigenesis and that the CM1 antibody can detect a proportion of cases of overexpression of mutant p53 in archival pathological material.

Antibodies, Monoclonal↗