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Biomedical subjects

W D Edwards

Publications and source records attributed to W D Edwards.

At least 217 records · Page 12Linked to original sources

The relationship between atrial granularity and circulating atrial natriuretic peptide in hamsters with congestive heart failure.

The BIO 14.6 strain of hamster is a model of familial cardiomyopathy complicated by congestive heart failure, sodium retention, and edema. In previous studies, bioassay techniques have demonstrated that the cardiac content of atrial natriuretic peptide (ANP) is reduced in these animals. On the basis of this observation, the syndrome of congestive heart failure has been hypothesized to be due to a deficiency in ANP. The current study was designed to correlate the cardiac content of ANP (determined by immunohistochemical techniques) with plasma circulating ANP (determined by radioimmunoassay). alpha-ANP antibodies were used for both determinations. The content of ANP in the atria was based on the degree of immunoreactive staining present (1 = lowest; 5 = highest), as graded by two observers. The mean granularity score of the cardiomyopathic hamsters was decreased (2.1 +/- 0.3) in comparison with that of age- and sex-matched control animals (3.5 +/- 0.5; P less than 0.05). In contrast, circulating immunoreactive ANP was higher in the hamsters with congestive heart failure than in the control animals--185.5 +/- 27.2 pg/ml versus 77.7 +/- 10.8 pg/ml (P less than 0.005). This study demonstrates that an inverse relationship exists between ANP content in the atria and circulating ANP. Furthermore, this study suggests that these hamsters with congestive heart failure are not deficient in ANP; rather, secretion of ANP is stimulated and storage of the peptide, represented by atrial granularity, is reduced.

Animals↗

Thromboembolic splenic infarction.

Splenic infarction occurs as a consequence of systemic thromboembolization in association with several cardiovascular disorders. We describe a case of splenic infarction in a patient who had paroxysmal atrial fibrillation after aortic valve replacement. In an autopsy series of 96 consecutive cases of splenic infarction, only 10% had been suspected clinically even though the splenic infarctions had contributed substantially to morbidity and mortality in 44% of the cases. Thromboembolic causes were responsible for the splenic infarcts in 67% of the cases, and concomitant infarcts in other organ systems were found in 62%. Embolization of atheromatous debris from the aorta, thrombotic elements from the left ventricle (in dilated cardiomyopathy and acute myocardial infarction), and vegetations from infected valves are the most common settings in which thromboembolic splenic infarcts are noted. The clinical picture associated with splenic infarction is typically nonspecific; manifestations may include fever, tachycardia, and left-upper-quadrant tenderness. Computed tomographic scanning and, to a lesser degree, ultrasonography are the imaging techniques of choice for diagnosing splenic infarction.

Aortic Valve Stenosis↗

Myocardial ischemia in patients with pulmonary atresia and intact ventricular septum.

Children who die after operation for pulmonary atresia and intact ventricular septum may have myocardial ischemia. The relation between histologic evidence of myocardial ischemic injury and the presence of a right ventricle to coronary artery fistula, coronary artery dysplasia and operation in 17 autopsy specimens was assessed. Age at death ranged from 1 day to 16 years (median, 11 days). Of the 17 hearts, 6 (35%) had right ventricle to coronary artery fistulas, 5 of which had coronary artery dysplasia. In three cases, there was segmental or complete absence of a coronary artery. Ischemia was present in four of these six hearts, two of which had right ventricular outflow reconstruction. Six of the 11 hearts without right ventricle to coronary artery fistulas also had myocardial ischemia. Of these six cases, four had right ventricular outflow reconstruction and two had shunt operations. Death occurred from 1 to 8 days (mean 3) after operation. Hearts with pulmonary atresia and intact ventricular septum may have myocardial ischemia with or without either right ventricle to coronary artery fistulas or coronary artery dysplasia. Myocardial ischemia may occur after right ventricular outflow reconstruction or shunt operations. Thus, myocardial ischemia occurs commonly in patients with pulmonary atresia and intact ventricular septum and is not always related to coronary abnormalities or operation.

Adolescent↗

Incidence and distribution of left ventricular false tendons: an autopsy study of 483 normal human hearts.

The incidence and distribution of left ventricular false tendons were studied in a series of 483 autopsy specimens of human hearts from subjects evenly distributed by sex and age. False tendons were observed in 265 specimens (55%), and their incidence was greater in hearts from male than from female subjects (61 versus 49%; p less than 0.01). Neither the incidence nor the location of false tendons varied appreciably with age. Of the 265 specimens containing false tendons, 100 (38%) exhibited 2 or more, such that the total number of false tendons identified was 414. Of these 414, 272 (66%) were located between the posteromedial papillary muscle and the ventricular septum, 49 (12%) between the two papillary muscles, 47 (11%) between the anterolateral papillary muscle and the ventricular septum, 38 (9%) between the free wall and the septum and 3 (less than 1%) between two aspects of the free wall; 5 (1%) had three or more points of insertion and formed weblike structures. False tendons are common anatomic variants of the normal human left ventricle which may be detected by two-dimensional echocardiography and should not be misinterpreted as pathologic structures such as flail mitral chordae tendineae or mural thrombi.

Adolescent↗

Regression in thromboembolic type of primary pulmonary hypertension during 2 1/2 years of antithrombotic therapy.

Primary pulmonary hypertension carries a poor prognosis, with a 5 year survival rate of less than 25%. However, a previous study of more than 100 patients with tissue-proved primary pulmonary hypertension suggested that antithrombotic therapy may have a beneficial effect on survival, especially in patients with the thromboembolic type of primary pulmonary hypertension. This report describes a 54 year old white man with primary pulmonary hypertension of the thromboembolic type (proved by right upper lobe lung biopsy) who, after long-term antithrombotic therapy, showed resolution of symptoms of dyspnea and fatigue, regression of electrocardiographic signs of right ventricular hypertrophy and regression of elevated pulmonary artery pressure. Base-line cardiac catheterization in January 1982 revealed elevated pulmonary artery pressure (104/37 mm Hg) and pulmonary vascular resistance (14.6 units/m2) that did not decrease with 100% oxygen or intravenous hydralazine (12 mg). The patient was treated with warfarin and dipyridamole, 100 mg four times daily. The most recent cardiac catheterization in January 1984 revealed a pulmonary artery pressure of 50/15 mm Hg and a pulmonary vascular resistance of 8.7 units/m2. It is believed that this is the first report of regression of the symptoms and signs of biopsy-proved primary pulmonary hypertension. In view of the lack of a response to vasodilators in 1982, it is suggested that antithrombotic therapy is partially responsible for the improvement of this patient.

Cardiac Catheterization↗

Penetrating atherosclerotic ulcers of the thoracic aorta: natural history and clinicopathologic correlations.

Clinically, penetrating atheromatous ulceration of the aortic wall may be confused with either symptomatic thoracic aneurysm or classic spontaneous aortic dissection. Aortography and computed tomographic (CT) scanning of the thoracic aorta provide specific diagnostic information which permits one to distinguish this lesion from atherosclerotic aneurysm and classic dissection. Hallmarks of findings on aortography and CT scan include the presence of the ulcer and an intramural hematoma. Since the findings may be disarmingly subtle, the potentially progressive and serious nature of this condition may remain unappreciated. Recognition of the penetrating atheromatous ulcer and distinguishing it from aortic dissection arising just distal to the origin of the left subclavian artery is mandatory. Resection of only a conservative segment of the proximal descending aorta suffices for classic dissection in the upper descending thoracic aorta, but the penetrating aortic ulcer requires graft replacement in the area of the ulcer and intramural hematoma.

Aged↗

Molecular basis for anticancer drug amplification: interaction of phleomycin amplifiers with DNA.

The interaction of two phleomycin amplifiers, N,N-dimethyl-2-[[4'-(thien-2''-yl)pyrimidin-2'-yl]thio]ethylamine (1S, high activity) and N-[2''-(dimethylamino)ethyl]-4-(thien-2'-yl)pyrimidin-2-amine (1N, low activity) with DNA has been evaluated. The visible absorption bands of both compounds shift to longer wavelengths, and both exhibit hypochromicity on titration with DNA. The effects for 1S at low concentration are significantly greater than for 1N. 1S increases the DNA Tm by 2.5 degrees C while 1N causes only a 1.0 degree C increase under the same conditions. Spectrophotometric binding analysis of the interaction of 1S and 1N with calf thymus DNA indicates that 1S binds over 4 times more strongly to this DNA than 1N. Both compounds increase DNA viscosity, cause downfield shifts in DNA 31P NMR spectra, and shift the DNA imino base pair protons upfield, conclusively demonstrating that they bind to DNA by intercalation. Signals for the aromatic protons of 1S and 1N are shifted upfield on addition of DNA as expected for intercalation. The shifts for all aromatic protons are similar on 1S and on 1N, indicating that both the pyrimidine and thiophene are inserted between the DNA base pairs in the complex. NOE experiments demonstrate that the compounds are in the s-cis conformation both free in solution and in the DNA intercalation complex. Semiempirical INDO/S calculations indicate greater polarization of the pi-electron system of 1S than 1N. This greater polarization may account for the stronger interaction of 1S with DNA base pairs than 1N. The interaction of these compounds with DNA is strongly correlated with their biological amplification activity.

Bleomycin↗

Quantification of regional platelet and calcium deposition on pericardial tissue valve prostheses in calves and effect of hydroxyethylene diphosphonate.

Mitral valves were replaced with 25 mm bovine pericardial tissue valve prostheses (Ionescu-Shiley) in 45 calves (23 controls and 22 treated daily with hydroxyethylene diphosphonate). Before being killed 1, 14, 30, and 90 days later, the calves received In-labeled autologous platelets intravenously. Regional variations in platelet deposition were measured by a new technique. Thrombus was noted early on the flexion zone of the valve; with time it increased on the free edge and central zone. Platelet deposition was initially high on the flexion zone, attachment zone, sewing ring, and perivalvular tissue but decreased with time. Hydroxyethylene diphosphonate treatment tended to decrease platelet deposition in all zones. Calcium content was high in thrombus and increased in all zones with time, in both groups, but the deposition was less in the group treated with hydroxyethylene diphosphonate. Collagenous tissue and adherent thrombus appear to provide nucleation sites for calcification.

Animals↗

Sudden death in an adolescent four years after recovery from mucocutaneous lymph node syndrome (Kawasaki disease).

A case is presented of sudden death during physical activity in a 15-year-old boy with clinically inactive mucocutaneous lymph node syndrome (Kawasaki disease). At autopsy, the coronary arteries were involved by multiple aneurysms and obstructive thrombi, and the left ventricular myocardium was extensively scarred. Although Kawasaki disease most commonly occurs in infants and young children, it may be a cause of sudden death in adolescents.

Adolescent↗

Pathogenesis of cocaine-induced ischemic heart disease. Autopsy findings in a 21-year-old man.

A 21-year-old man with a five-year history of recreational intravenous cocaine abuse developed chest pain within one minute and cardiopulmonary arrest within one hour following an injection. He died and, on autopsy, was found to have severe coronary obstructive lesions, as a result of chronic intimal proliferation, and acute platelet thrombosis. Secondary chronic and acute myocardial ischemic lesions also were observed. Cocaine-induced coronary artery spasm may have occurred and produced focal endothelial injury and platelet aggregation; this pathogenetic mechanism may have accounted for both the chronic and the acute coronary obstructive lesions. In addition, lymphocytic myocarditis was present and may have been related to the long-term cocaine abuse.

Adult↗

Aortic dissection with fistula to right atrium. Noninvasive diagnosis by two-dimensional and Doppler echocardiography with successful repair. Case report and review of the literature.

Aortic dissection with rupture into the right atrium is rare, and a high index of suspicion is required for its clinical recognition. The diagnosis should be considered in a patient with chest pain or dyspnea who at presentation has a widened pulse pressure, a continuous murmur, and evidence of right ventricular volume overload, especially when there is a history of a previous cardiac operation. Two-dimensional and Doppler echocardiography can establish the diagnosis and permit early surgical repair of the dissection and fistula.

Aged↗

Infective endocarditis. Olmsted County, Minnesota, 1950 through 1981.

Strict criteria were used to identify all definite, probable, and possible cases of endocarditis in residents of Olmsted County, Minnesota, from 1950 through 1981. The mean annual age- and sex-adjusted incidence rates per 100,000 person-years were 3.8 for total cases and 3.2 for definite and probable cases only. Total rates were 4.3 for 1950 through 1959, 3.3 for 1960 through 1969, and 3.9 for 1970 through 1981. Rheumatic heart disease was the underlying disorder in 26% of cases, with a shift noted during 1970 through 1981 to involvement of prosthetic rather than natural valves in these patients. Mitral valve prolapse was identified in 17% of cases. No source of infection could be identified in 41% of cases, including half of those cases with rheumatic or congenital heart disease. In cases diagnosed prior to autopsy, the 60-day fatality fell from 46% during 1950 through 1959 to 22% and 26% during 1960 through 1969 and 1970 through 1981, respectively.

Adolescent↗

Straddling atrioventricular valve: two-dimensional echocardiographic diagnosis, classification and surgical implications.

The usefulness of subclassifying the anatomic variations of straddling and overriding atrioventricular (AV) valve by 2-dimensional echocardiographic observation were evaluated. Chordae straddling into a contralateral ventricle were subdivided into type A (chordae inserting into the contralateral ventricle near the crest of the ventricular septum), type B (chordae inserting along the contralateral ventricular septum) and type C (chordae inserting into the free wall or papillary muscles of the contralateral ventricle). Overriding AV valve anulus was described as minor (less than 50% of the anulus committed to the contralateral ventricle), major (about 50% of the anulus committed to each ventricle), and double-inlet ventricle (greater than 50% of both AV valves committed to a single ventricular chamber). In 52 patients straddling AV valve was diagnosed by echocardiography and confirmed by direct examination at surgery or autopsy. In 60 of 66 straddling AV valves (91%), the diagnosis and the degree of straddling (type A, B or C) were correctly identified by 2-D echocardiography. Major associated cardiac defects included double-outlet right ventricle (31%), complete transposition (23%), corrected transposition (19%), double-inlet ventricle (19%) and other complex defects (8%). Twenty-two patients (42%) had right-sided straddling, 21 (40%) had left-sided straddling and 9 (17%) had straddling of both AV valves. In 41% of the patients, straddling AV valve had a major impact on the type of surgery or the surgical outcome. Of these valves, 52% were type C (severe), 26% type B and 22% type A straddling.(ABSTRACT TRUNCATED AT 250 WORDS)

Chordae Tendineae↗

Catheter-induced lesions of the right side of the heart. A one-year prospective study of 141 autopsies.

We examined prospectively for one year the hearts from 141 consecutive autopsy cases in which a central catheter was present at the time of death. Three deaths were attributable to catheter use, two to perforation. Furthermore, mural thrombi were present in 33 (33%) of 99 patients with pulmonary arterial catheters and in 12 (29%) of 42 patients with central venous catheters. The incidence of pulmonary emboli or bacteremia was no greater in patients with thrombi than in those without. The use of central catheters may thus be complicated by perforation or the development of mural thrombi. Although the thrombi may embolize or may become infected, the incidence and clinical significance appear to be low. The incidence of catheter-related deaths in our autopsy population does not necessarily reflect the incidence in a population of living patients.

Adolescent↗

Histologic abnormalities of the left ventricle in a patient with arrhythmogenic right ventricular dysplasia.

Right ventricular histologic abnormalities have been described in association with arrhythmogenic right ventricular dysplasia, but the cause of the disease is unknown. Identical abnormalities were noted in endomyocardial biopsy specimens from the right and left ventricles of a 20-year-old male patient with the clinical syndrome of arrhythmogenic right ventricular dysplasia. Left ventricular function was normal at rest and during bicycle exercise. Eighteen months previously, he had shown clinical and serologic evidence of mycoplasmal myocarditis. Arrhythmogenic right ventricular dysplasia may represent predominant involvement of the right ventricle in a generalized cardiomyopathic process, possibly as a consequence of healed myocarditis.

Adult↗

Current problems in establishing quantitative histopathologic criteria for the diagnosis of lymphocytic myocarditis by endomyocardial biopsy.

Both the clinical and the biopsy diagnoses of myocarditis are prone to false-positive and false-negative interpretations. False-positive clinical diagnoses probably most commonly result from a failure to recognize other disorders, such as cardiomyopathy and myocardial infarction, that may mimic myocarditis. False-negative clinical diagnoses may occur in patients with myocarditis in whom the signs and symptoms are atypical, absent, or misinterpreted. The two most common errors made by pathologists that produce false-positive tissue diagnoses appear to be a failure to recognize the number of lymphocytes that occupy the normal myocardial interstitium and a misinterpretation of noninflammatory interstitial cells as lymphocytes. Sampling error may be the most usual cause of false-negative tissue diagnoses. Since myocarditis is characterized by leukocytic and reparative responses, the most important features to evaluate in endomyocardial biopsy tissues are the type, distribution, and extent of the inflammatory infiltrate and the presence and extent of interstitial and endocardial fibrosis. Although no single histopathologic criterion is both sensitive and specific for myocarditis, it appears that quantitative evidence of an interstitial leukocytic infiltrate is currently the best available hallmark for myocarditis in biopsy specimens. It is suggested that a mean lymphocyte count greater than 5.0/high-power (X 400) microscopic field be considered indicative of lymphocytic myocarditis and that a mean count less than this be interpreted as myocarditis only if discrete clusters of lymphocytes are identified, since differentiation of low-grade diffuse infiltrates from expected normal lymphocytic populations is problematic at levels less than 5.0.

Biopsy↗

Surgical pathology of combined aortic stenosis and insufficiency: a study of 213 cases.

The gross surgical pathologic features of the aortic valve were reviewed in 213 patients who had had clinically combined aortic stenosis and insufficiency and aortic valve replacement at our institution during the years 1965, 1970, 1975, and 1980. The three most common causes were postinflammatory disease (69%) and calcification of congenitally bicuspid (19%) and unicommissural (6%) aortic valves. Other causes included infective endocarditis (2%) and congenitally quadricuspid or malformed tricuspid aortic valves (1% each); the cause was indeterminate in 1%. In the postinflammatory and bicuspid states, calcification tended to be more extensive in men than in women. The relative incidence of postinflammatory disease in our study did not change appreciably from 1965 to 1980, despite the steadily decreasing incidence of acute rheumatic fever reported in western countries.

Adult↗