Anomalous left coronary artery from the pulmonary artery: significance of associated intracardiac defects.

Two patients with anomalous origin of the left main coronary artery from the pulmonary artery had an associated defect (one, critical pulmonary stenosis; the other, ventricular septal defect). They presented with signs and symptoms of the associated defect and the coronary anomaly was unrecognized. Both cases at autopsy lacked the usual large right coronary artery seen with this anomaly. The pathophysiologic features of the combined defects are described, their differences from the isolated anomaly are noted and their relation to surgery is discussed.

Ventriculocoronary connections in hypoplastic right heart syndrome: autopsy serial section study of six cases.

Myocardial sinusoids communicating with the coronary systems occur in pulmonary atresia with intact ventricular septum. To test the hypothesis that the extent of ventriculocoronary connections correlates with the degree of right ventricular outflow obstruction as evidenced by clinical, angiographic and gross anatomic findings, a serial section study of six human autopsy hearts representing a spectrum of hypoplastic right heart was undertaken. Slides were evaluated for the presence and extent of ventriculocoronary connections, associated developmental abnormalities and secondary changes in the ventricular walls. Whereas extensive blind-ended deep sinusoids were a feature of all five cases with unrelieved obstruction, ventriculocoronary connections were identified in three. Changes that suggested ongoing remodeling provide new evidence for the postnatal temporal evolution of these anomalous communications. The regional distribution of myofiber disarray in hypoplastic right heart supports the concept that vascularization parallels myocardial organization in the developing human heart.

Low renin in young mothers and their children following hypertension in pregnancy.

Young women who became pregnant as adolescents and developed hypertension during their first pregnancies had higher blood pressures than women who had remained normotensive throughout pregnancy. These young mothers served as subjects for a study to evaluate the relationship between different levels of "normal" blood pressure and renin-aldosterone. Overall, plasma renin activity (PRA), but not plasma aldosterone, was inversely related to systolic blood pressure both before (r = -0.28; p less than 0.003) and after (r = -0.24, p less than 1.01) treadmill exercise. Unrelated to blood pressure, PRA was also lower in blacks and in women using oral contraceptive agents (p less than 0.01). Of women with a history of hypertension in pregnancy, 30% (9 of 30) had low PRA after exercise. Low renin was associated with higher blood pressures. At the time of a second exercise test 3 years later, these women still showed elevated arterial pressure and low renin. PRA was also suppressed in the children of mothers with low renin, and there were significant correlations between maternal and child PRA (r = +0.55; p less than 0.003) and between maternal and child aldosterone (r = +0.60; p less than 0.001). In conclusion, low renin may be an appropriate response to higher arterial pressures, and within families may be a marker of "pre-hypertension."

Low renin-aldosterone in "prehypertensive" young adults.

PRA is suppressed in approximately 25% of patients with essential hypertension. To determine if renin suppression precedes the onset of hypertension, PRA and plasma aldosterone were measured before and after treadmill exercise in 129 young adults with relatively high, intermediate, or relatively low blood pressures sustained over 5 yr. PRA and aldosterone responses to exercise were lower (P less than 0.01) in the high blood pressure group. In contrast, plasma renin substrate was lower (P less than 0.01) in the low blood pressure group. Unrelated to blood pressure, PRA, but not aldosterone, was lower in black than in white subjects both before and after exercise. In conclusion, renin suppression precedes the onset of hypertension and may be an appropriate response to higher levels of arterial pressure.

Correlates of adolescent blood pressure at five-year follow-up.

In 1973, standardized measurements of blood pressure (BP), height, and weight were obtained on all adolescents attending high school in a rural Kentucky county. In 1978, a 5-year follow-up BP study was undertaken of all adolescents who were 14-15 years old at the time of the initial survey (n = 310), and of selected 16-19 year olds who were in the high, intermediate, and low ranges of the initial sex-specific BP distributions (n = 198). Follow-up measurements included height, weight, and BP on all subjects and, in addition, overnight sodium (Na) excretion, serum cholesterol, glucose, triglyceride, and uric acid concentrations on the older group. Our findings indicate that BP in young adults is related to BP in adoleslcence, change in relative weight since adoleslcence, and current relative weight. Relative rank order of initial BP levels were maintained over the 5-year period in both the younger and older groups. Additional cardiovascular disease risk factors were found to cluster in young adults with high BP, and clustering of risk factors may, in part, be related to high relative weight.

Plasma renin activity, reactivity, concentration and substrate following hypertension during pregnancy. Effect of oral contraceptive agents.

Plasma renin activity is suppressed in approximately 25% of patients with essential hypertension, and the rate of in vitro angiotensin I production after addition of exogenous renin (renin reactivity) is increased in plasma of hypertensive patients. We have recently observed that blood pressure (116 +/- 1.5/68 +/- 1.7 mm Hg) of young women who had hypertension during a first pregnancy 3--6 years earlier (n = 63) was higher (p less than 0.005) than blood pressure (109 +/- 1.4/61 +/- 1.7 mm Hg) of women who remained normotensive during pregnancy (n = 52). To determine if alterations of the renin-angiotensin axis observed in patients with established hypertension also occur in young adults with relatively high blood pressure, plasma renin activity (PRA), plasma renin concentration (PRC), plasma renin substrate (PRS) and plasma renin reactivity (PRR) were compared in these two groups of subjects. Overall, PRA and PRC were inversely related to systolic blood pressure (p less than 0.02). Excluding women on oral contraceptive agents, the PRA response to standardized treadmill exercise was suppressed (less than 1.0 ng/ml/hr) in 19% of women with a history of hypertension during pregnancy and in no women who remained normotensive throughout a previous pregnancy; PRR did not differ (p greater than 0.8) in the two groups of young mothers (27.1 ng/ml/30 min +/- 1.2 SE VS 26.2 ng/ml/30 min +/- 0.9 SE). Thus, renin suppression, but not increased PRR, precedes the onset of hypertension. Oral contraceptive usage was associated with higher systolic blood pressures, increased PRS, and low PRC. Highest blood pressures and lowest PRA occurred in women with a history of hypertension during pregnancy who were taking oral contraceptive agents at the time of study.

Parental genetic contribution to mode of presentation in Pompe disease.

Echocardiograms were performed on parents of five infants with Pompe disease (glycogen storage disease, type II). Three of the infants had presented with congestive cardiomyopathy and two with dynamic muscular subaortic stenosis. No heart murmurs were audible in any of the parents of the five infants. The parents of the three infants without left ventricular outflow tract obstruction had normal echocardiographic results, whereas one parent of each of the infants with left ventricular outflow obstruction had asymmetric septal hypertrophy. The association between left ventricular outflow obstruction and parental asymmetric septal hypertrophy suggests that both septal hypertrophy and glycogen storage disease were inherited by these two infants.

Echocardiographic mitral valve deformity in the mucopolysaccharidoses.

Previously reported echocardiographic abnormalities in patients with mucopolysaccaridosis and the Hunter-Hurler phenotype have stressed the similarity to calcific mitral stenosis despite the fact that mitral stenosis is a relatively uncommon manifestation of this disease. The purpose of this report is to describe the echocardiographic abnormalities in five patients with the Hunter-Hurler phenotype who had no clinical evidence of mitral stenosis. All had abnormal thickening of the mitral valve leaflets and one had echoes suggestive of calcification of the mitral annulus. All patients had normal electrocardiograms and roentgenographic cardiothoracic ratios, and two patients had no cardiac murmur. The high frequency of valvular deformity in this disease and the sensitivity of echocardiography in detecting these deformities suggest that echocardiography should be performed in the evaluation of patients with mucopolysaccharidosis. When echocardiographic evidence of valvular deformity is obtained, consideration should be given to bacterial endocarditis prophylaxis.

Effect of respiration on the echocardiogram in children with cystic fibrosis.

Respiration-related cyclic variation was noted in echocardiographic measurements of right and left ventricular end-diastolic dimension. D-E amplitude of the anterior mitral leaflet, and mitral valve E-F slope in 26 children with cystic fibrosis. The observed echographic changes seem to be an exaggeration of the normal physiologic variation seen with respiration. In children with advanced respiratory disease, airway obstruction, rather than cor pulmonale, may be responsible for this exaggeration.

Pediatric Legionnaires' disease: diagnosis by direct immunofluorescent staining of sputum.

Legionnaires' disease occurred in a 3-year-old boy with Down's syndrome. His illness was characterized by bilateral pneumonia, high fever, and response to erythromycin. The diagnosis was made by demonstrating Legionella pneumophila, serogroup 1, in sputum with a direct fluorescent antibody stain. L pneumophila antigen was detected in urine by an enzyme-linked immunospecific assay. The diagnosis was confirmed by a more than fourfold rise in serum antibody titer. Although Legionnaires' disease appears to be uncommon in children, it should be included in the differential diagnosis of pneumonia in the immunocompromised child.

Iodine-123-HIPDM lung imaging in pulmonary vein-banded pulmonary hypertension.

To evaluate the use of N,N,N'-trimethyl-N,-[2-hydroxy-3-methyl-5 iodobenzyl-1, 3 propanediamine iodine-123 (HIPDM) in lung imagings for the diagnosis of individual pulmonary vein stenosis, 14 single-pulmonary vein-banded rats underwent lung imaging. After i.v. injection of 250-300 microCi [123I]HIPDM lung images were recorded at 2 min by a gamma camera interfaced with a PDP computer. Banded lung demonstrated higher [123I]HIPDM radioactivity than that of nonbanded lungs. The activity ratio of banded-to-nonbanded lungs ranged from 4.0 to 1.22 (average 1.62). Technetium-99m-macroaggregated albumin (MAA) lung images showed decreased perfusion in banded lung, and normal perfusion in the nonbanded lung. Postmortem microscopic changes in pulmonary arteries and veins were compatible with the elevated pulmonary artery and venous pressure in vein-banded lung. Whether the high uptake of [123I]HIPDM in banded lungs relates to endothelial receptors for HIPDM is unknown. Nevertheless, the finding of high lung uptake in banded lung in [123I]HIPDM lung imaging may be potentially used to diagnose individual pulmonary vein stenosis.

False diagnosis of subpulmonary obstruction by echocardiography in d-transposition of the great arteries.

Twenty-one consecutive children (aged 3 to 14 months) with d-transposition of the great arteries were evaluated with standard M mode echocardiography at the time of hospital admission for routine preoperative cardiac catheterization. At catheterization, 6 of the 21 were found to have a systolic pressure gradient between the body of the left ventricle and the main pulmonary artery. Echocardiographic systolic anterior mitral valve motion was noted in nine patients, including five who did not have a left ventricular to pulmonary arterial systolic pressure gradient. Diastolic approximation of the anterior mitral leaflet to the septum was noted in 14 (9 without a gradient), pulmonary valve flutter was also present in 14 (9 without a gradient) and there was premature systolic pulmonary valve closure in 6 (3 without a gradient). Echographic left heart dimensions were not different in patients with a left ventricular outflow pressure gradient than in those without, but patients wit systolic anterior mitral valve motion and diastolic approximation of the mitral leaflet to the septum did have smaller left ventricular and pulmonary root dimensions than did those without these echocardiographic findings. Echocardiographic findings that have been described as suggesting left ventricular outflow obstruction in patients with d-transposition of the great arteries appear to be more related to size and configuration of the left ventricle than to the presence or absence of obstruction.

Right ventricular outflow muscle in tetralogy of Fallot: Histologic and immunohistochemical monoclonal antibody analysis.

To evaluate progressive muscular right ventricular outflow tract (RVOT) obstruction in tetralogy of Fallot (TOF), we hypothesized that this tissue would demonstrate more prominent selected immunohistochemical markers of myogenous cell differentiation, growth factor/receptor, and extracellular matrix. Sections of formalin-fixed, paraffin-embedded myectomy tissue obtained from RVOT at the time of surgical correction of TOF (n = 32; ages = 3 months through 13 years) were compared with age-matched tissue from the RVOT of normal control hearts (n = 12) obtained at autopsy after non-cardiac death. Examining by light microscopy slides stained with a combination of hematoxylin and eosin and elastic trichrome revealed cardiomyocyte (CM) hypertrophy, extensive myofiber disarray, trabeculation, multinucleation (more than two nuclei per myocyte), fibrosis, and thick-walled coronary arteries within the myocardium of TOF tissue. The endocardium from TOF specimens was thickened and hypercellular with prominent fibrosis and elastosis. Mitosis was not observed. At the interface between the endocardium and myocardium, the TOF specimens demonstrated myocyte dispolarity (orientation of CMs perpendicular to the endocardial surface), vascularization, and fibrosis. Immunohistochemical studies were performed using monoclonal antibodies to vimentin, desmin, muscle-specific actin (MSA), epidermal growth factor (EGF), epidermal growth factor receptor (EGFR), and laminin. Compared to the tissue from controls, TOF tissue showed a pattern of upregulated expression of epitopes within the endocardium and adjacent subendocardial myocardium. Decoration for MSA, vimentin, desmin, and EGFR highlighted the zonal nature of this tissue hyperactivity. Laminin prominently outlined endocardial cells, subendocardial CMs, and interface vessels in TOF tissue compared to the remainder of the myocardium and tissue from controls. Overall, changes in TOF were age-related, with older patients showing less zonal myocardial reactivity. These findings provide evidence for an ongoing, complex remodeling of the RVOT muscle in TOF.

Cytolytic response to HIV in patients with HIV disease treated with extracorporeal photochemotherapy: preliminary study.

Extracorporeal photochemotherapy (photopheresis), an immunomodulatory therapy that targets circulating T helper lymphocytes, has been applied to the management of human immunodeficiency virus (HIV) disease. Any therapy that exerts its actions on CD4+ T cells has the potential of exacerbating HIV infection. Therefore, it was necessary to observe immune function during treatment. Because cytotoxic T lymphocytes (CTL) and natural-killer cells are thought to play an important role in the response against HIV infection, we examined the effect of photopheresis on HIV cytolytic activity. The study group consisted of seven patients with late-stage HIV disease who had not received any previous treatment for HIV infection. Patients were treated exclusively with photopheresis on two consecutive days each month for 14-32 months (average, 25 months). Peripheral lymphocytes, collected at various points during treatment, were used as effectors in a 51Cr release assay. Epstein-Barr virus (EBV)-transformed autologous B cell lines transfected with recombinant vaccinia vectors that expressed the HIV env (gp120, gp41) and gag (p24) proteins were used as target cells. All seven patients demonstrated relatively constant levels of cytolysis (>10% above controls) during treatment in the context of stable CD4+ T cell counts and a stable clinical status. These results suggest that extracorporeal photochemotherapy did not impair the cytolytic response to HIV infection and may have enhanced it in some patients.

Supravalvular aortic stenosis. Clinical and pathologic observations in six patients.

Supravalvular aortic stenosis with a mean pressure gradient of 101 mm Hg was encountered in six patients aged 1 1/2 to 12 years. Three patients had Williams syndrome. In two other patients the stenosis was familial. The angiographic/anatomic subtype of deformity was hourglass in four patients, diffuse in one, and membranous in one. Four patients are alive following successful surgical repair; the other two died without surgery. Microscopically, disorganized medial elements with fibrotic intima sometimes containing lacunae were observed in five cases; the one other had valvelike tissue only. Ultrastructurally, thick irregular elastic fibers, abundant swirling collagen, hypertrophied smooth-muscle cells, and scant ground substance characterized the medial tissue defect. Although hemodynamics during intrauterine development may predispose to localization of the stenosis to the supra-aortic valvar region, the cause for the mural dysplasia remains uncertain.

"Meandering" pulmonary veins: report of a case in an asymptomatic 12-year-old girl.

We report a case of a healthy, asymptomatic 12-year-old girl in whom anomalous pulmonary venous connection to the left atrium occurred as an isolated congenital anomaly. This condition, termed "meandering" pulmonary veins, is closely related to scimitar syndrome and is usually associated with hypogenesis of the right lung and dextropositioning of the heart. To our knowledge, ours is only the second reported case of meandering pulmonary veins occurring as an isolated anomaly.