Cardiovascular function in children following bone marrow transplant: a cross-sectional study.

Sixty-three patients who had undergone a BMT at age < or = 18 years were evaluated cross-sectionally to determine cardiac function as well as the long-term prevalence, types, severity, and risk factors of cardiac abnormalities. Patients were > or = 1 year post-BMT and were evaluated by history, resting ECG, echocardiography (ECHO), exercise treadmill test, chest X-ray, pulmonary function tests and review of past cardiac studies. Patients were assigned a New York Heart Association (NYHA) class based on an activity and cardiac symptoms questionnaire. Pretransplant preparative regimens included high-dose cyclophosphamide (CY) and total body/lymphoid irradiation (n = 38), CY in combination with other chemotherapy (n = 22), and other drug combinations (n = 3). Forty patients (63.5%) had received prior anthracyclines (median 307 mg/m2). Patients' ages ranged from 1.9 to 32 years (median 10.9 years) with median follow-up of 3.3 years (range 1-16.3 years). Twenty-six patients (41.3%) had a cardiac abnormality detected at follow-up. In 21 patients the abnormal finding had not been present at the pre-BMT evaluation. Ten patients (16.4%) had resting ECG abnormalities. Left ventricular ejection fraction (LVEF) by ECHO was mildly decreased to 50-54% in three patients and markedly decreased to 40% in one patient. Only one patient (1.7%) developed a mildly abnormal shortening fraction of 27%. All patients with ECHO abnormalities were asymptomatic. Twenty-three of 31 patients > or = 9 years of age (74%) who underwent a treadmill exercise test had a borderline or abnormal response to exercise. There was no correlation between demographic factors, previous therapy, preparative regimen or length of follow-up with the post-BMT ECG, ECHO and treadmill abnormalities. Overall, eight patients (12.7%) were symptomatic and NYHA class II or III, and all had abnormal exercise tests. The presence of symptoms and NYHA class were predictors for oxygen consumption during exercise (P = 0.03 and 0.02, respectively) and tended to predict overall treadmill results also. Late cardiac abnormalities do occur following BMT in childhood and thus, there is a clear need for continued, serial long-term cardiac evaluation in transplant survivors. Evaluations should include exercise stress testing to detect inadequate cardiac output as well as oxygen consumption during exercise.

Echocardiographic-guided internal jugular venous cannulation in children with heart disease.

OBJECTIVE: To determine if cannulation of the internal jugular vein (IJV) with echocardiographic guidance increases the success and decreases the complications of the procedure when performed in children with heart disease. DESIGN: Twenty-five consecutive pediatric patients with heart disease who underwent IJV cannulation with echocardiographic guidance between September 1986 and March 1992. SETTING: University hospital referral center serving a four-state area. PATIENTS AND OTHER PARTICIPANTS: Ambulatory patients were admitted for this procedure and then discharged at its completion; others included hospitalized patients. All patients were between the ages of 6 weeks and 21.8 years. All patients underwent IJV cannulation performed by a member of the Pediatric Cardiology Division at the University of Minnesota, Minneapolis. All patients either underwent heart transplant, and IJV access was obtained to perform an endomyocardial biopsy or had congenital heart disease, and the IJV was cannulated to perform a heart catheterization. Written consent was obtained either from the patient, if 18 years of age or older, or a parent or legal guardian. INTERVENTION: Cannulation of the IJV using echocardiographic guidance. MAIN OUTCOME MEASURES: Would IJV cannulation with echocardiographic guidance improve safety and diminish complications of the procedure when performed in pediatric patients with heart disease? We compared the results of our evaluation with published results in which echocardiographic guidance was not used. RESULTS: Cannulation of the IJV with echocardiographic guidance was performed successfully on 138 occasions in 25 pediatric patients. There were no lasting complications and no deaths using this method of venous access. CONCLUSIONS: As in the adult population, IJV cannulation with the assistance of echocardiography increases the success of the procedure and decreases the number of complications. Furthermore, echocardiographic guidance allows for repeated IJV cannulation in pediatric patients, regardless of age.

Repair of multiple mycotic aortic aneurysms in a newborn.

Thoracoabdominal aortic and common and internal iliac artery mycotic aneurysms resulted from an umbilical arterial catheter in a 3 1/2-week-old boy. He underwent staged repair including an 8-mm Gore-tax tube graft, primary repair of the common iliac artery aneurysm, and resection of the internal iliac aneurysm. His operative and postoperative course was uneventful. He was asymptomatic at 17 months' follow-up, with equal blood pressure in the upper and lower extremities. Magnetic resonance imaging showed no stenoses or recurrent aneurysms at the anastomotic sites of the Gore-tex tube graft. Blood supply to his left leg came from collaterals, principally a large crossing vessel from the right iliac artery. This case represents the first successful aortic replacement in a 5 week old with extensive involvement of the thoracoabdominal aorta and its branch vessels.

Subcellular localization and antiviral activity of carminic acid/poly r(A-U) combinations.

Carminic acid (CAR) enhances the antiviral activity of poly r(A-U) twelve-fold without increasing interferon induction, inactivating the vesicular stomatitis virus or inducing host cell cytotoxicity. Phase contrast photomicrographs of human foreskin fibroblasts (HSF) incubated with CAR alone, poly r(A-U) alone or with a CAR/poly r(A-U) combination illustrate that the CAR/poly r(A-U) combinations display altered subcellular distribution with the CAR being localized in the nucleoli and chromatin. Phase contrast and fluorescence photomicrographs of adriamycin (ADR)-treated and ADR/poly r(A-U)-treated HSF cells corroborate these findings. These results suggest that modulation of one or more nucleolar processes may be responsible for the enhanced antiviral activity.

Transcatheter closure of congenital coronary arterial fistula with a detachable balloon.

Coronary arterial fistulae are rare congenital cardiac defects that typically are treated by surgery. A case of transcatheter closure of a left anterior descending coronary artery to right ventricular fistula with a detachable balloon is described in a 16-month-old child. The fistula was easily occluded without complication. Follow-up 1.5 years later revealed normal ventricular function and no recurrence of the fistula. Detachable balloon occlusion of coronary arterial fistula is feasible in patients as young as 4 months.

Results of a right ventricular outflow patch for pulmonary atresia with intact ventricular septum.

BACKGROUND: Although overall outcome has improved, pulmonary atresia with intact septum remains a difficult surgical and clinical problem. To determine whether an early right ventricular outflow patch will result in biventricular repair for this lesion, we reviewed the long-term follow-up (5.8 +/- 0.8 years) of 19 newborns who underwent repair between 1979 and 1990. METHODS AND RESULTS: An early right ventricular outflow patch was placed in 15 of 19 newborns; in the remaining four, this was preceded by an aortopulmonary shunt. Prostaglandin E1 infusion postoperatively eliminated the need for shunt in 14 of 15. Coronary sinusoids were ligated in three newborns. Based on right ventricular morphology, the newborns were divided into two groups: group 1 (tripartite, n = 9) and group 2 (bipartite and monopartite, n = 10). Before surgery, group 1 had significantly larger right ventricular volumes (23.6 +/- 3.7 versus 5.2 +/- 1.1 ml/m2, p < 0.002). Five-year survival was 79% for the entire series. Four infants, all group 2, died within 12 months of their initial surgery. Fourteen of 15 survivors (nine group 1 and five group 2) currently are acyanotic and New York Heart Association functional class I. A biventricular repair was achieved in 12 of 15, and three other children are awaiting evaluation. All 15 survivors had significant right ventricular and tricuspid annulus growth. CONCLUSIONS: Our data suggest that early placement of a right ventricular outflow patch in infants with pulmonary atresia and intact ventricular septum, regardless of right ventricular anatomy, results in an excellent chance for biventricular repair.

Enhanced antiviral activity and altered subcellular distribution of magnesium/poly r(A-U) combinations.

When Mg2+ or ethidium bromide (EB) were combined with poly r(A-U) at a ligand/ribonucleotide ratio of 1/4, the antiviral activity of the Mg2+ and EB increased 136-fold and 154-fold. Eriochrome Blue SE was employed to visualize the subcellular distribution of Mg2+ following co-incubation of Human Foreskin Fibroblasts (HSF) with Mg2+ alone or with the Mg2+/poly r(A-U) combination. Phase contrast micrographs of these Mg(2+)-treated HSF cells as well as phase contrast and fluorescence micrographs of EB-treated or EB/poly r(A-U)-treated HSF cells illustrated that the Mg2+ (or EB)/poly r(A-U) combinations display altered subcellular distribution with the Mg2+ and EB being localized in the nucleoli and chromatin of the HSF cells. These results suggest that modulation of nuclear processes may be responsible for the enhanced antiviral activity.

Diagnostic and therapeutic advances in pediatric cardiology (2).

The practice of pediatric cardiology has undergone remarkable changes over the past decade. Cardiac structural abnormalities may frequently be diagnosed with echocardiography alone, and treatment for many of these structural problems may be corrected during cardiac catheterization. Arrhythmia diagnosis and management have made similar progress, such that diagnosis of arrhythmia mechanisms and catheter ablative therapy may be performed during a single procedure, sparing the young patient a lifetime of antiarrhythmic drug therapy. Cardiac transplantation is now included among the treatment options for some patients with severe congenital or acquired cardiac abnormalities unresponsive to standard therapy. In this paper, we provide a brief description of current applications of recent advances in the practice of pediatric cardiology.

Potentiation of the antiviral activity of poly r(A-U) by xanthene dyes.

Ten xanthene dyes (XAN) are evaluated for their ability to potentiate the antiviral activity of poly r(A-U) using a human foreskin fibroblast-vesicular stomatitis virus bioassay in which the XAN is combined with 0.2 mM poly r(A-U) to produce a XAN/ribonucleotide ratio of 1/4. Four of the ten XANs tested in this study, rhodamine 123, rhodamine B, rhodamine 6G and sulforhodamine B, enhance the antiviral activity of poly r(A-U) 8- to 15-fold. The interferon-inducing activity of the four active XAN/poly r(A-U) combinations is equal to the sum of the activities of their constituents. These four XANs appear to potentiate the antiviral activity of the poly r(A-U) without superinduction of interferon. The direct viral inactivation study demonstrates that the XANs, poly r(A-U) and the XAN/poly r(A-U) combinations do not inactivate the VSV at concentrations near the 50% effective dose.

A useful projection for demonstrating the bifurcation of the pulmonary artery.

The demonstration of the pulmonary bifurcation is important in order to exclude pulmonary branch stenoses. The origin of the right and left pulmonary arteries can be demonstrated in the anteroposterior plane if cranial angulation is used. Depending on the course of the left pulmonary artery, the origin of the left pulmonary artery may not be seen in spite of the maximal cranial angulation. On the lateral plane without tube angulation the origin left pulmonary artery is commonly superimposed on the origin of the right pulmonary artery. If maximum caudal angulation is added to the steep left anterior oblique view, not only the left, but also the origin of the right pulmonary artery can be seen.

In vitro antiviral activity of poly (A-U) and ellipticines.

The role of N2-methyl-9-hydroxy-ellipticine (NMHE) and N2,N6-dimethyl-9-hydroxy-ellipticine (DMHE) in modulating the antiviral activity of poly (A-U) was examined using a human foreskin fibroblast-vesicular stomatitis virus (HSF-VSV) bioassay in which the concentration of poly (A-U) was fixed at 0.05 mM or 0.2 mM while the NMHE or DMHE concentration was varied to produce variable NMHE (or DMHE)/ribonucleotide ratios ranging from 1:16 to 2:1. Poly (A-U), NMHE and DMHE tested individually were not efficacious antiviral agents. When the poly (A-U) was combined with the NMHE or DMHE, the antiviral activity of the poly (A-U) was potentiated 16- to 20-fold a NMHE (or DMHE)/ribonucleotide ratios in the region of 1/4. Poly (A-U), NMHE and DMHE induce beta-IFN. The interferon-inducing activity of the NMHE (or DMHE)/poly (A-U) combination was equal to the sum of the interferon-inducing activity of the poly (A-U) alone and the NMHE (or DMHE) alone. The direct viral inactivation study demonstrated that NMHE, DMHE, poly (A-U) and the NMHE (or DMHE)/poly (A-U) combinations did not inactivate VSV at concentrations near the 50% viral inhibitory dose. Photomicrographs of HSF cells incubated with NMHE alone or with a NMHE/poly (A-U) combination suggest that poly (A-U) affects the subcellular distribution of the NMHE by steering the NMHE to the nucleolus. These observations suggest that modulation of a nuclear process may be responsible for the enhanced antiviral activity.

Polyribonucleotide-anthraquinone interactions: in vitro antiviral activity studies.

Twelve anthraquinones (AQ) were evaluated for their ability to potentiate the antiviral activity of poly r(A-U) using a human foreskin fibroblast-vesicular stomatitis virus bioassay in which the AQ was combined with 0.2 mM poly r(A-U) to produce an AQ/ribonucleotide ratio of 1/4. Poly r(A-U) and the AQ alone were not effective antiviral agents. Five of the twelve AQs tested, mitoxantrone, adriamycin, ametantrone, carminic acid and daunomycin, enhanced the antiviral activity of poly r(A-U) 9- to 13-fold. The interferon-inducing activity of the five active AQ/poly r(A-U) combinations was equal to the sum of the interferon-inducing activities of their constituents. These five AQs appear to potentiate the antiviral activity of poly r(A-U) without superinduction of interferon.

Enhancement of the antiviral activity of poly r(A-U) by ametantrone and mitoxantrone.

The role of ametantrone (HAQ) and mitoxantrone (DHAQ) in modulating the antiviral and interferon-inducing activities of poly r(A-U) was examined using the human foreskin fibroblast-vesicular stomatitis virus (HSF-VSV) bioassay system in which the concentration of poly r(A-U) was fixed at 0.05 mM or 0.2 mM while the HAQ or DHAQ concentration was varied to produce variable HAQ (or DHAQ)/ribonucleotide ratios ranging from 1:16 to 2:1. HAQ, DHAQ and poly r(A-U) tested individually were not efficacious antiviral agents. When poly r(A-U) was combined with the ametantrone or mitoxantrone the antiviral activity was potentiated 10-fold at HAQ (or DHAQ)/ribonucleotide ratios in the region of 1/4 to 1/6. The interferon-inducing activity of the HAQ (or DHAQ)/poly r(A-U) combinations were equal to the sum of the interferon-inducing activity of the poly r(A-U) and the HAQ (or DHAQ). These results indicate that the HAQ and DHAQ potentiate the antiviral activity of the poly r(A-U) without the superinduction of interferon. The direct viral inactivation study demonstrated that HAQ, DHAQ, poly r(A-U) and the HAQ (or DHAQ)/poly r(A-U) combinations did not inactivate the VSV at concentrations near the viral 50% inhibitory dose.

Factors influencing the structure and shape of stenotic and regurgitant jets: an in vitro investigation using Doppler color flow mapping and optical flow visualization.

To evaluate factors influencing the structure and shape of stenotic and regurgitant jets, Doppler color flow mapping and optical flow visualization studies were performed with use of a syringe model with a constant rate of ejection to simulate jets of valvular regurgitation and a pulsatile flow model of the right heart chambers to simulate jets of mild, moderate and severe valvular pulmonary stenosis. Ink-(0 to 40%) glycerol-water jets (viscosity 1 to 3.5 centiPoise) were produced by injecting the fluid at a constant rate into a 10 gallon rectangular reservoir of the same still fluid through 1.4 and 3.4 mm needles. The Doppler color flow scanners imaged the laminar jet length within 3 mm of actual jet length (2 to 6 cm) and the jet width within 2 to 3 mm of the actual jet width. Jet flows with Reynolds numbers ranging from 230 to 1,200 injected into still fluid yielded jet length/width ratios that decreased with increasing Reynolds numbers and leveled off to a length/width ratio of 5-6:1 at a Reynolds number near 600. When the fluid reservoir was swirled to better mimic the effect of flow entering the same cardiac chamber from a second source, the jets showed diminution of the jet length/width ratio and a clearly defined zone of turbulence. Studies of the pulsatile flow model were performed at cardiac outputs of 1 to 6 liters/min for the normal and each stenotic valve. Mild stenosis had an orifice area of 2.8 cm2, moderate stenosis an area of 1.0 cm2 and severe stenosis an area of 0.5 cm2. Laminar jet length represented the length of the total jet, which had a symmetric width and was measured from the valve opening to a region where the jet exhibited a spray effect. Laminar jet lengths (0.2 to 1.1 cm) were imaged by Doppler color flow mapping and optical visualization only in the moderate and severely stenotic valves and only at flows less than or equal to 3 liters/min (mean Reynolds numbers less than or equal to 3,470). Beyond this flow rate the jets exhibited a spray effect. Laminar jet length/width ratio approached unity with an increased amount of valvular stenosis and higher flow volumes (cardiac output). Proximal aliasing was present in each valve studied. the length of aliasing (0 to 3.2 cm) proximal to the valve was longer with increased flow rates and increased amounts of stenosis.(ABSTRACT TRUNCATED AT 400 WORDS)

Elucidation of the natural history of ventricular septal defects by serial Doppler color flow mapping studies.

Two-dimensional echocardiography has provided information to aid in the diagnosis and management of infants with ventricular septal defect, but its inability to resolve very small ventricular septal defects and problems with defining ventricular septal defect orifice size (because of overlying muscle or tricuspid tissue) have made it unsuitable as a standard for defining the natural history of ventricular septal defect. In this study, 114 serial two-dimensional Doppler color flow mapping studies were performed to define ventricular septal defect anatomy, location and color flow diameter as an indicator of shunt size in 66 patients (over a 40 month period). Twenty-five patients first studied at 6 months of age (mean age at most recent study 15.9 months) had congestive heart failure and 41 (mean age 45 months) did not. In the congestive heart failure group, there were 24 perimembranous and 1 muscular ventricular septal defect and aneurysm formation was present in 17. Mean (+/- SD) color flow diameter was 8.2 +/- 1.9 mm and color flow diameter/aortic root diameter ratio was 0.63. In the 30 patients who underwent cardiac catheterization, color flow diameter bore a close relation to angiographic diameter (r = 0.96) and pulmonary/systemic flow ratio (Qp/Qs) (r = 0.88). In the patients with congestive heart failure, 4 of the 25 ventricular septal defects, all with aneurysm present or positioned adjacent to the tricuspid valve, became smaller but none closed. Of the 41 patients without congestive heart failure, 21 had a perimembranous defect (15 with aneurysm), 18 had a muscular ventricular septal defect and 2 had a supracristal ventricular septal defect.(ABSTRACT TRUNCATED AT 250 WORDS)

Potentiation of the antiviral activity of poly r(A-U) by riboflavin, FAD and FMN.

The role of riboflavin (RFN), FAD or FMN in modulating the antiviral activity of poly r(A-U) was examined by the human foreskin fibroblast-vesicular stomatitis virus bioassay in which the concentrations of poly r(A-U) was fixed at 0.1 mM or 0.2 mM while the riboflavin, FAD or FMN concentration was varied to produce variable RFN (or FAD or FMN)/ribonucleotide ratios ranging from 1/16 to 2/1. Riboflavin, FAD and FMN tested individually did not exhibit any antiviral activity, while poly r(A-U) alone exhibited antiviral activity. When poly r(A-U) was combined with riboflavin, FAD or FMN, the antiviral activity was potentiated seven- to twelve-fold at RFN (or FAD or FMN)/ribonucleotide ratios in the region of 1/4.

Evaluation of coronary artery anatomy in patients with tetralogy of Fallot by two-dimensional echocardiography.

A major coronary artery crossing the right ventricular outflow tract in patients with tetralogy of Fallot interferes with a transannular patch, and preoperative detection of this artery is important. We evaluated the ability of two-dimensional echocardiography to define noninvasively the coronary artery anatomy in 37 consecutive patients (age range, 1 day to 18 years; mean age, 40.9 months). The origin and distribution of the right anterior descending and circumflex coronary arteries, as well as any anteriorly coursing vessel, were examined from parasternal views. Complete studies were obtained in 29 (78%) of the 37 patients. Coronary artery anatomy was determined to be normal by echocardiography in 20 (69%) of the 29 patients. An anterior vessel across the right ventricular outflow tract was detected in the remaining nine patients. Six patients had an anterior descending artery from the left main coronary artery (paired anterior descending arteries in three patients, a right anterior descending artery from the left main coronary artery in two patients, and a right coronary-to-pulmonary artery fistula in one patient). Three patients had no anterior descending artery from the left main coronary artery (anterior descending artery from the right main coronary artery in two patients, and anterior descending and circumflex arteries from the right main coronary artery in one patient). Angiography, surgery, or autopsy confirmed the diagnoses in all but the final patient in whom the anterior descending artery arose from the right main coronary artery as observed at surgery, but the circumflex artery was not seen. Accurate evaluation of coronary artery anatomy is possible by echocardiography in the majority of patients with tetralogy of Fallot. Noninvasive identification of a major coronary artery coursing anteriorly can influence the timing of cardiac catheterization and surgery and the need for angiography.

Enhancement of the antiviral and interferon-inducing activities of poly r(A-U) by carminic acid.

Experiments have been designed to systematically examine the effects of carminic acid (CAR) on the antiviral/interferon-inducing activity of poly r(A-U), using the human foreskin fibroblast-vesicular stomatitis virus bioassay system. Modulation of the antiviral/interferon-inducing activity of poly r(A-U) by carminic acid was examined at fixed poly r(A-U) concentrations of 0.05 mM or 0.2 mM while varying the carminic acid concentrations to produce variable CAR/ribonucleotide ratios ranging from 1:16 to 2:1. Carminic acid and poly r(A-U) were tested individually at the concentrations employed in the CAR/poly r(A-U) combinations. Neither the carminic acid alone nor poly r(A-U) alone were effective antiviral agents/interferon inducers. The antiviral/interferon-inducing activity of poly r(A-U) was potentiated twelve-fold at CAR/ribonucleotide ratios in the region of 1/6 to 1/4. These results suggest a synergism between the poly r(A-U) and the carminic acid at the concentrations employed in this study.