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Biomedical subjects

M L Murphy

Publications and source records attributed to M L Murphy.

At least 19 recordsLinked to original sources
PubMed1991

Cardiac toxicity 4 to 20 years after completing anthracycline therapy.

OBJECTIVE: --To assess the cardiac status of long-term survivors of pediatric malignancies who received chemotherapy, including anthracyclines. DESIGN AND METHOD: -Patients were evaluated by echocardiogram from 4 to 20 years (median, 7 years) after completion of anthracyclines, with prospective and retrospective analysis. PATIENTS: --The consecutive sample of 201 patients had received a total anthracycline dose of 200 to 1275 mg/m2 (median, 450 mg/m2), and 51 patients had mediastinal radiotherapy. MAIN OUTCOME MEASURES: --The overall incidence and severity of abnormal systolic cardiac function were determined for the entire cohort. Risk factors of total anthracycline dose, mediastinal radiotherapy, age during treatment, and length of follow-up were examined. RESULTS: --Twenty-three percent (47/201) of the cohort had abnormal cardiac function on noninvasive testing at long-term follow-up. Correlation between total cumulative dose, length of follow-up, and mediastinal irradiation with incidence of abnormalities was significant. Fifty-six patients were followed up for 10 years or more (median, 12 years), with a median anthracycline dose of 495 mg/m2. Thirty-eight percent (21/56) of these patients, compared with 18% (26/145) of patients evaluated after less than 10 years, had abnormal findings. Sixty-three percent of patients followed up for 10 years or more after receiving 500 mg/m2 or more of anthracyclines had abnormal findings. Nine of 201 patients had late symptoms, including cardiac failure and dysrhythmia, and three patients died suddenly. Microscopic examination of the myocardium on biopsy and autopsy revealed fibrosis. CONCLUSION: --The 23% incidence of late cardiac abnormalities warrants continued evaluation of patients after anthracyclines to guide patient care and the design of future chemotherapeutic protocols.

Adolescent↗
PubMed1991

Acute and sustained release of the atrial natriuretic factor prohormone N-terminus with acute myocardial infarction.

This investigation was designed to determine if acute ischemic cardiac injury causes the release of the 98 amino acid (aa) N-terminus of the 126 aa atrial natriuretic factor prohormone (pro ANF). Seventeen patients with acute myocardial infarction, but without clinical evidence of congestive heart failure, had their circulating concentrations of the whole N-terminus (ie, pro ANF 1-98), the midportion of the N-terminus of the ANF prohormone (consisting of aa 31-67; pro ANF 31-67) and creatine phosphokinase (CPK) monitored daily for 14 days. All seventeen patients had elevated plasma pro ANF 1-98 and pro ANF 31-67 concentrations at the time of presentation. Maximal increase on day three post-infarction correlated with the size of infarction estimated by the maximal CPK (r = 0.675; p less than 0.05) but did not correlate with the amount of left ventricular dysfunction. Another three patients with acute myocardial infarction were treated with tissue plasminogen activator (tPA). The measured pro ANF 1-98 and pro ANF 31-67 levels in these patients were within our normal range and significantly lower (p less than 0.001) than seen in patients with acute myocardial infarction not given thrombolytic therapy. Six patients with unstable angina, likewise, had normal circulating pro ANFs 1-98 and 31-67 concentrations during prolonged episodes of chest pain. These data suggest that myocardial necrosis but not ischemia triggers the release of the entire 126 aa prohormone.

Adult↗
PubMed1991

Outpatient fluid-air exchange for severe postvitrectomy diabetic vitreous hemorrhage. Long-term results and complications.

An alternative treatment to repeat vitrectomy in postvitrectomy diabetic vitreous hemorrhage (PDVH) is outpatient fluid-air exchange, but the long-term visual results of this procedure are not known. Between January 1986 and April 1989, a pars plana air-pump technique was used to perform outpatient fluid-air exchange in 20 eyes of 17 patients (17 phakic eyes) within 8 weeks of onset of PDVH. A mean follow-up interval of 78 weeks was obtained. Preoperative vitreous hemorrhage was severe enough to obscure all fundus detail (17 eyes) or produce erythroclastic glaucoma (three eyes). Initial visual acuity was hand motions or light perception in 19 eyes and improved to a median visual acuity of 20/300 soon after resolution of the intraocular air bubble. Early complications included postoperative fibrin formation (one eye) and early postoperative intraocular pressure elevation (two eyes). Recurrent vitreous hemorrhage required repeated fluid-air exchanges in seven eyes. Long-term complications included worsening of posterior subcapsular cataract (10 of 17 phakic eyes, 59%), for which cataract extraction was required in five eyes (29%). Fluid-air exchange appeared to exacerbate cataract formation, justifying a period of observation for PDVH. However, it appeared to be a low-risk alternative to repeat vitrectomy, allowing rapid visual recovery from severe PDVH.

Adult↗
PubMed1991

Ten-year incidence of myocardial infarction and prognosis after infarction. Department of Veterans Affairs Cooperative Study of Coronary Artery Bypass Surgery.

BACKGROUND: The 10-year incidence of myocardial infarction (fatal and nonfatal) and the prognosis after infarction were evaluated in 686 patients with stable angina who were randomly assigned to medical or surgical treatment in the Veterans Administration Cooperative Study of Coronary Artery Bypass Surgery. METHODS AND RESULTS: Myocardial infarction was defined by either new Q wave findings or clinical symptoms compatible with myocardial infarction accompanied by serum enzyme elevations with or without electrocardiographic findings. Treatment comparisons were made according to original treatment assignment; 35% of the medical cohort had bypass surgery during the 10-year follow-up period. The overall cumulative infarction rate was somewhat higher in patients assigned to surgery (36%) than in medical patients (31%) (p = 0.13) due to perioperative infarctions (13%) and an accelerated infarction rate after the fifth year of follow-up (average, 2.4%/yr in the surgical group versus 1.4%/yr in the medical group). The 10-year cumulative incidence of death or myocardial infarction was also higher in surgical (54%) than in medical (49%) patients (p = 0.20). According to the Cox model, the estimated risk of death after infarction was 59% lower in surgical than in medical patients (p less than 0.0001). The reduction in postinfarction mortality with surgery was most striking in the first month after the event: 99% in the first month (p less than 0.0001) and 49% subsequently (p less than 0.0001). The estimated risk of death in the absence of infarction was nearly identical regardless of treatment (p = 0.75). Exclusion of perioperative infarctions did not alter the findings. CONCLUSIONS: Although surgery does not reduce the incidence of myocardial infarction overall, it does reduce the risk of mortality after infarction, particularly in the first 30 days after the event (fatal infarctions).

Angina Pectoris↗
PubMed1990

Reperfusion injury in ischemic myocardium: protective effect of controlled reperfusion.

Restoration of coronary artery flow following a period of ischemia often results in further ultrastructural damage to cardiac fibers, a phenomenon known as reperfusion injury. We have compared the ultrastructural effects of uncontrolled reperfusion in vivo of ischemic pig myocardium with the ultrastructural effects of reperfusion controlled at flow rates comparable to preischemia levels. Myocardial ischemia was produced for 60 minutes in 9 pigs by means of a reversible coronary artery occlusion, after which coronary artery flow was restored for 120 minutes. This restoration of flow was complete in four pigs (resulting in uncontrolled reperfusion) and partial in five pigs, with constant monitoring and adjustment of flow to maintain rates near preischemia values (controlled reperfusion). Myocardial samples from the ischemic, reperfused region were examined by electron microscopy. Ischemic damage to nuclei, mitochondria, and myofibrils and ischemic depletion of glycogen were graded independently and blindly by two investigators using a simple, nonparametric three-point scale. Ischemic damage was greater in pigs receiving uncontrolled reperfusion than in animals receiving controlled reperfusion, and these differences were significant for ischemic effects on nuclei (p less than 0.01), glycogen (p less than 0.02), and myofibrils (p less than 0.05) but not for ischemic effects on mitochondria (p = 0.095). We conclude that uncontrolled, hyperemic flow during reperfusion of ischemic myocardium is responsible, in part, for the phenomenon of reperfusion injury.

Animals↗
PubMed1990

Microvasculature sparing with controlled reperfusion of ischemic myocardium.

Reperfusion of ischemic myocardium may result in further ultrastructural damage to cardiac fibers, a phenomenon known as reperfusion injury. We have recently shown that controlled reperfusion, with maintenance of reperfusion flow rates near preischemia levels, prevents much of this reperfusion damage. This observation suggests that mechanical damage to the myocardial microvasculature is important in the pathogenesis of reperfusion injury. In this study, we have used electron microscopy to examine the microcirculation of ischemic, reperfused pig myocardium under conditions of uncontrolled and controlled reperfusion. Animals receiving uncontrolled reperfusion (reperfusion flow 3-4 times preischemia levels) showed ultrastructural damage to myocardial capillaries after 1 hour of ischemia and 2 hours of reperfusion. This damage was manifested as depletion of endothelial cell pinocytotic vesicles, plugging of capillaries by erythrocytes, leukocytes, and fibrin-containing microthrombi, and perivascular microhemorrhages. None of these changes were found in animals receiving controlled coronary artery reperfusion. We conclude that mechanical damage to the myocardial microvasculature is important in the pathogenesis of reperfusion injury and that such damage is obviated under conditions of controlled coronary artery flow during reperfusion.

Animals↗
PubMed1990

Reperfusion injury in ischemic myocardium: effects of nifedipine and verapamil.

Coronary reperfusion following myocardial ischemia may result in further damage to injured myocytes, as judged by their ultrastructural appearance. Calcium entry into myocytes has been implicated in this effect, and calcium channel-blocking agents have been used in attempts to prevent or limit such damage. In this study, we produced myocardial ischemia in pigs by means of reversible coronary artery occlusion. The pigs were infused with either nifedipine or verapamil (both clinically employed calcium channel-blocking agents) prior to and during coronary reperfusion. During reperfusion, nifedipine produced a lowering of mean arterial pressure, while mean arterial pressure was constant in verapamil-treated pigs and rose in pigs not receiving drugs. Myocardial samples from the ischemic, reperfused region were examined by electron microscopy. Ischemic damage to nuclei, mitochondria, and myofibrils and glycogen depletion were independently graded on a three-point scale by two investigators. For each of the organelles studied, ischemic damage was significantly less for nifedipine-treated animals than for controls. Ischemic damage in verapamil-treated pigs was not different from that seen in control animals, except for a slight improvement in myofibrillar appearance. We conclude that nifedipine, administered prior to and during reperfusion of myocardium, protects against reperfusion injury. The mechanism of this protective effect may be attributable, in part, to afterload reduction and, in part, to inhibition of transmembrane calcium flux in cardiac fibers.

Animals↗
PubMed1989

Acute and sustained release of atrial natriuretic factor with acute myocardial infarction.

The present investigation was designed to determine if acute ischemic cardiac injury causes the release of atrial natriuretic factor (ANF). Seventeen patients with acute myocardial infarction but without clinical evidence of congestive heart failure had their circulating concentration of ANF and creatine phosphokinase monitored daily for 14 days. All 17 patients had an elevated plasma ANF concentration at time of presentation. Maximal increase in ANF was on day 2 and 3 post-infarction. This maximal increase correlated with the size of infarction estimated by the maximal creatine phosphokinase concentration (r = 0.475; p less than 0.05), but did not correlate with the amount of left ventricular dysfunction. ANF began to decrease by day 4 post-infarction and was normal at 10 days post-infarction in 14 of the 17 (82%) patients. At 12 days post-infarction, all 17 patients had normal ANF levels. Another three patients with acute myocardial infarction were treated with tissue plasminogen activator (tPA). The measured ANF levels in these patients were within our normal range and were significantly lower (p less than 0.001) than those seen in patients with acute myocardial infarction not given thrombolytic therapy. Six patients with unstable angina likewise had normal circulating ANF concentrations during prolonged episodes of chest pain. These levels were also significantly lower (p less than 0.001) than the 17 patients with acute infarcts not given tPA. The distinct pattern of release of ANF may be useful as an adjunct to serum cardiac enzymes in determining if a myocardial infarction has occurred.

Adult↗
PubMed1989

Controlled versus hyperemic flow during reperfusion of jeopardized ischemic myocardium.

Controlled versus uncontrolled reperfusion of ischemic myocardium after experimental coronary artery occlusion was studied to determine the effect on regional ventricular wall motion and associated biochemical alterations. Fourteen pigs underwent coronary artery occlusion for 1 hour followed by 2 hours of reperfusion. In seven animals uncontrolled reperfusion was achieved by complete release of the arterial occlusion resulting in hyperemic flow. In seven other animals coronary flow during reperfusion was controlled at baseline levels eliminating hyperemic flow. Our results show that controlled reperfusion lessens end-diastolic wall thickness, reduces myocardial calcium deposition, increases the rate of mitochondrial oxidative phosphorylation, and preserves cellular high-energy phosphate stores in the ischemic-reperfused myocardium when compared to the uncontrolled reperfusion state. These data suggest that the magnitude of flow at an early stage of reperfusion is one of the important determinants in the outcome of ischemic myocardium.

Adenosine Triphosphate↗
PubMed1989

Chronic cor pulmonale.

Chronic cor pulmonale is defined as right heart hypertrophy and/or chronic right heart failure. There are many etiologies, but the common cause is increased right heart work from pulmonary hypertension. Etiology can be conveniently discussed by assuming two prototypes, the asphyxial or hypoxic type and the vascular obliterative type. A common cause of the asphyxial type is chronic obstructive pulmonary disease, and the obliterative type is represented by chronic pulmonary thromboembolic disease or primary pulmonary hypertension. Pathology is discussed, emphasizing the cardiac manifestations of chronic cor pulmonale including data of specific cardiac chamber size. An overview of hemodynamics is given, and the use and limitation of electrocardiography and chest x-rays are discussed. The exciting potential use of echocardiography for the serial non-invasive measurement of anatomical and pathophysiological features is outlined, along with the value of a careful physical examination and the proper utilization of laboratory tests in the diagnosis of chronic cor pulmonale. In the patient with the asphyxial type, the treatment of pulmonary infectious exacerbations, the role of corticosteroids, digoxin, diuretics, phlebotomy, bronchodilators (theophylline, beta adrenergic agonists, and anticholinergics), and long-term oxygen therapy is noted. The controversy surrounding the use of vasodilators and calcium blockers in these patients is discussed. Treatment aspects of the vascular obliterative type, including the role of vasodilators, calcium blockers, prostacyclin, anticoagulants, and overall strategy are discussed. A brief note is mentioned of the promising role of surgical therapy in chronic thromboembolic disease causing chronic cor pulmonale.

Adult↗
PubMed1989

Reperfusion injury in ischemic myocardium: protective effects of ruthenium red and of nitroprusside.

Coronary reperfusion following myocardial ischemia may result in further damage to injured myocytes, as judged by their ultrastructural appearance. Ruthenium red is an inorganic dye with calcium flux-inhibiting properties which protects ischemic myocardium against reperfusion damage, as judged by biochemical indices of mitochondrial function. In this study, we produced myocardial ischemia in pigs by means of reversible coronary artery occlusion. The pigs were infused with either ruthenium red or nitroprusside (an after-load reducing agent with no known calcium flux-inhibiting properties) prior to and during coronary reperfusion. During reperfusion, both ruthenium red and nitroprusside produced similar lowering of mean arterial pressure, while mean arterial pressure rose in pigs not receiving these drugs. Myocardial samples from the ischemic reperfused region were examined by electron microscopy. Ischemic damage to nuclei, mitochondria, and myofibrils and glycogen depletion were graded independently on a three-point scale by two investigators. For each of the organelles studied, ischemic damage was significantly less for treated animals than for controls. This protective effect was similar for both ruthenium red-treated animals and nitroprusside-treated animals. These results suggest that the protective effects of ruthenium red treatment are attributable to its afterload reducing properties rather than to inhibition of transmembrane calcium flux in cardiac fibers.

Animals↗
PubMed1988

The relationship between hypertrophy and dilatation in the postmortem heart.

Confusion may exist at the time of postmortem examination as to whether the diseased heart is dilated, hypertrophied, or both. Ventricular dilatation and ventricular hypertrophy were therefore evaluated by cardiac partition techniques in 441 subjects at autopsy to determine their relationship. Specific weight and surface area of each ventricle were obtained and patients were divided into categories of disease. Wall thickness measurements, a parameter routinely used in the ordinary autopsy, were found to be unreliable in defining hypertrophy. Ventricular surface area (an index of dilatation) was highly correlated with ventricular weight in most disease categories. Exceptions were cardiomyopathy and aortic stenosis, in which hypertrophy predominated. We conclude from these data that dilatation and hypertrophy occur proportionately in the postmortem heart in most disease categories except in cardiomyopathy and aortic stenosis. These findings clarify the relationship of dilatation and hypertrophy at the time of autopsy in most cases. Therefore, uncertainty as to whether cardiac dilatation or hypertrophy is present or which predominates is usually related to the inability to assess these states critically at the time of autopsy when the ordinary pathological methods are used.

Cardiomegaly↗
PubMed1988

Sustained therapeutic efficacy and safety of oral propafenone for treatment of chronic ventricular arrhythmias: a 2-year experience.

Thirty-two men with chronic ventricular arrhythmias responded to propafenone, a new potent antiarrhythmic agent, in short-term trials with 85% or greater reduction of total ventricular premature complexes (VPCs) per hour, 95% or greater reduction of ventricular couplets (VCs) per hour, and 100% abolition of ventricular tachycardia (VT) beats per 24 hours. These patients were continued on long-term propafenone therapy to assess sustained therapeutic efficacy and safety. Thirty patients completed 1 year and 26 patients completed 2 years of testing with this agent; one patient died of sudden death and another died of a noncardiac cause. Although there were significantly fewer patient responders at 1 and 2 years, the majority of patients (greater than 79%) continued to respond optimally to propafenone. Side effects were minor and included bitter taste, dizziness, congestive heart failure, fatigue, and significant prolongation of the PR and QRS intervals. Propafenone has sustained antiarrhythmic efficacy after 2 years without serious toxicity.

Aged↗
PubMed1988

Evaluation of biochemical functions and ventricular performance in regional ischemic-reperfused myocardium by afterload reduction: differential effects of calcium blocking and non-calcium blocking vasodilators.

The effects of afterload reduction with and without calcium blockade on reperfusion injury were studied in the pig. Reversible occlusion of the left anterior descending coronary artery was performed for 60 minutes followed by 120 minutes of reperfusion. For 15 minutes prior to and throughout reperfusion, treatment was administered with a calcium blocker (nifedipine or verapamil), a metallic organic dye and Ca2+ antagonist (ruthenium red), a vasodilator (nitroprusside), or saline. Biochemical functions, i.e., mitochondrial oxidative phosphorylation, myocardial ATP and Ca2+ content, and sarcoplasmic reticulum Ca2+ uptake were determined. Regional left ventricular wall motion was measured echocardiographically. Nifedipine and ruthenium red improved biochemical indices of ischemic myocardium in part by reducing afterload and thereby reducing oxygen demand and in part by reducing calcium entry into cells and mitochondria. Verapamil in the doses used failed to reduce afterload and demonstrated no salutary effect on biochemical parameters in ischemic myocardium. Nitroprusside reduced afterload, improved mitochondrial ATP production and increased percent wall thickening. Our findings suggest that afterload reduction with and without calcium blockade during the early reperfusion phase improves ischemic myocardium. These changes are predominantly biochemical in nature.

Adenosine Triphosphate↗
PubMed1987

Altered dental root development in long-term survivors of pediatric acute lymphoblastic leukemia. A review of 17 cases.

Seventeen patients treated for acute lymphoblastic leukemia by combination chemotherapy before their reaching 10 years of age were studied for altered dental root development of their premolar teeth. Five of the 17 patients showed subjective radiographic evidence of marked shortening of the premolar dental roots; 13 had thinning of the roots. A quantitative analysis was developed and verified, which disclosed a 63.33% to 84.38% reduction of premolar root length when compared with the mean of the historical controls. With recent significant increases in long-term survival rates of children with malignancies, altered dental development becomes an important factor to follow years after chemotherapy is discontinued. The findings of these chemotherapy-associated dental development changes impacts on the patient's quality of life and also can serve as a research tool to assess permanent effects of chemotherapy on normal tissue growth and development.

Adolescent↗