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Biomedical subjects

R E Shaddy

Publications and source records attributed to R E Shaddy.

At least 55 records · Page 3Linked to original sources
PubMed1996

Outcome of cardiac transplantation in children. Survival in a contemporary multi-institutional experience. Pediatric Heart Transplant Study.

BACKGROUND: Meaningful analysis of survival and risk factors for death in children who undergo heart transplantation is problematic because of the small number of heart transplantations performed at individual institutions. METHODS AND RESULTS: To more accurately examine survival and risk factors for death in children undergoing heart transplantation, we analyzed 191 patients between 1 and 18 years old who received transplants at 22 centers in the Pediatric Heart Transplant Study between January 1, 1993, and December 31, 1994. Cardiac diagnosis was congenital heart disease in 74 patients (39%), dilated cardiomyopathy in 73 (38%), and other in 44 (23%). Actuarial survival was 93% at 1 month, 82% at 1 year, and 81% at 2 years after transplantation. The major causes of death (n = 31) were rejection (29% of deaths), early graft failure (19%), infection (16%), sudden death (13%), and other causes (23%). By multivariate analysis, risk factors for death were assist devices (P = .02), nonidentical ABO blood types (P = .05), and younger age (P = .10). CONCLUSIONS: Contemporary survival for pediatric heart transplant recipients > or = 1 year old is comparable to survival after adult heart transplantation. Risk factors for death are the need for assist devices, nonidentical ABO blood types, and younger age. Rejection is the most common cause of death after pediatric heart transplantation.

Adolescent↗
PubMed1996

Prospective analysis of HLA immunogenicity of cryopreserved valved allografts used in pediatric heart surgery.

BACKGROUND: The HLA immunogenicity of cryopreserved valved allografts used in the surgical repair of congenital heart defects is unknown. METHODS AND RESULTS: To determine the immunogenicity of these allografts, we measured prospectively the frequency of panel-reactive HLA class I alloantibodies (PRA) before, 1 month after, and 3 months after allograft implantation in 9 children (age, 5.4 +/- 2.1 years) and after open-heart surgery without allograft implantation in 11 age-matched control children (age, 4.0 +/- 1.5 years). PRA was determined against an HLA-select frozen T-lymphocyte panel using the antiglobulin cytotoxicity technique. After allograft implantation, PRA increased from 3.2 +/- 2.7% before surgery to 63.3 +/- 12% at 25 +/- 2 days after surgery and 99.7 +/- 0.3% at 3.4 +/- 0.3 months after surgery. The use of dithiothreitol to remove IgM alloantibodies resulted in a modest decrease in PRA at 1 month (33.2 +/- 13%) but no change at 3 months (93.0 +/- 3.4%), suggesting the initial humoral response is an IgM alloantibody that switches almost exclusively to IgG by 3 months. Control patients showed no increase in PRA over time: 1.6 +/- 1% before surgery, 3.2 +/- 1% at 28 +/- 5 days after surgery, and 1.7 +/- 1% at 2.7 +/- 0.3 months after surgery. CONCLUSIONS: Cryopreserved valved allografts in children induce a marked HLA alloantibody response that increases to broad panel reactivity within 3 months after surgery. This HLA sensitization has potential not only for causing deleterious effects on allograft function but also for limiting the future opportunity of heart transplantation in patients who receive cryopreserved valved allografts.

Adolescent↗
PubMed1996

Immunohistochemical analysis of platelet-derived growth factor and basic fibroblast growth factor in cardiac biopsy and autopsy specimens of heart transplant patients.

The purposes of this study were to examine 250 heart biopsy specimens and 20 autopsy specimens from heart transplant patients for the presence and localization of platelet-derived growth factor (PDGF)and basic fibroblast growth factor (bFGF) and to correlate these findings with the histologic features of rejection and the autopsy findings of graft coronary vasculopathy and global ischemia. Positive specimen staining was significantly more prevalent for PDGF (78% of specimens) than for bFGF (54% of specimens) (p< 0.001). PDGF was distributed more in an interstitial (53%) than a vascular (28%) pattern and was associated with macrophages, whereas bFGF was distributed more in a vascular (50%) than an interstitial (12%) pattern. The prevalence of PDGF (but not bFGF) staining was significantly greater in biopsy specimens with at least grade 2 vascular rejection changes (81%) than in those without vascular rejection changes (58%) (p<0.001). In autopsy specimens, PDGF staining was present in the hearts of all 5 patients (100%) who died of graft failure from coronary vasculopathy and was present in all 11 hearts (100%) with global ischemic changes, but in only 4 of 9 (44%) of the hearts without global ischemia (p<0.01). PDGF staining was absent in nontransplanted heart specimens, whereas bFGF staining in nontransplanted heart specimen was similar to that in transplanted hearts. We conclude that PDGF is increased in transplanted hearts, is distributed more in an interstitial pattern, and is associated with macrophages. Furthermore, PDGF staining is increased in transplanted hearts with evidence of vascular rejection, coronary vasculopathy, or global ischemia.

Adolescent↗
PubMed1996

Murine and pediatric myocardial growth factor mRNA expression using reverse transcription-polymerase chain reaction.

We utilized reverse transcription-polymerase chain reaction (RT-PCR) to examine the myocardial mRNA expression of growth factors in mice and children. Total cellular RNA was extracted from these tissues using acidified-phenol guanidinium thiocyanate. Optimal oligonucleotide primer pairs for RT-PCR were selected with the aid of the computer program Oligo 4.0. RT-PCR analysis of total cellular RNA demonstrated the measurable presence of the mRNA for the following growth factors in the myocardium of both mice and children: acidic fibroblast growth factor (aFGF), basic FGF (bFGF), insulin-like growth factor (IGF)-1, IGF-2, platelet-derived growth factor (PDGF)-A chain, PDGF-B chain, transforming growth factor (TGF)beta-1, TGFbeta-2, and TGFbeta-3. The amplified cDNA message for the growth factors and beta-actin migrated as a discrete band at the expected base pair number on agarose gels stained with the intercalating fluorescent dye ethidium bromide. Densitometry of the photographic negatives of these gels permitted the rapid and semiquantitative comparison of these factors. These data demonstrate the feasibility and reproducibility of utilizing RT-PCR for the specific detection and semiquantitation of mRNA expression of myocardial aFGF, bFGF, PDGF-A chain, PDGF-B chain, lGF-1, lGF-2, TGFbeta-1, TGFbeta-2, and TGFbeta-3 in mice and children.

Animals↗
PubMed1996

Growth factor expression and effects of amrinone in monocrotaline-induced pulmonary hypertension in rats.

Platelet-derived growth factor (PDGF) and basic fibroblast growth factor (bFGF) have been implicated in myointimal proliferative arteriopathy, a lesion seen in monocrotaline-induced pulmonary hypertension (MIPH). The purpose of this study was to examine the expression of PDGF and bFGF in the lungs of rats given monocrotaline and to examine the effects of amrinone on the hearts and lungs of these rats. Twenty-four 26-day-old rats were randomized to receive either monocrotaline (approximately 3.6 mg/kg/d) or no monocrotaline and concomitantly to receive either amrinone (100 mg/kg/d) or no amrinone for 21 days. Lungs were examined for immunohistochemical evidence of PDGF and bFGF, and hearts were examined for effects of pulmonary hypertension and amrinone. Immunohistochemical staining of lungs showed no evidence of PDGF except in bronchioles. bFGF staining was similar between groups (no monocrotaline 25%, monocrotaline 27%, monocrotaline and amrinone 22%), and the staining was confined to the arterial walls. Rats given monocrotaline showed significantly greater right ventricular (RV) weight (0.13 +/- 0.02 g versus 0.23 +/- 0.04 g [mean +/- SD], P < 0.001), right ventricular/left ventricular (RV/LV) weight ratio (0.29 +/- 0.06 versus 0.59 +/- 0.1, P < 0.001), and lung/body weight ratio (0.006 +/- 0.001 versus 0.01 +/- 0.003, P < 0.05) than controls. Rats given monocrotaline and amrinone were not significantly different from rats given only monocrotaline with regard to RV weight, RV/LV weight ratio, or lung/body weight ratio. We conclude that the vasculopathy seen in MIPH is not associated with the presence of PDGF or bFGF, suggesting that other growth factors may mediate this process. The course of MIPH is not altered by amrinone.

Amrinone↗
PubMed1996

Aortic valve repair and replacement after balloon aortic valvuloplasty in children.

BACKGROUND: Little is known about the incidence, indications, and results of surgical repair or replacement of the aortic valve after balloon aortic valvuloplasty (BAV) for congenital aortic stenosis in children. This study was designed to evaluate patterns of failure requiring operation after BAV for congenital aortic stenosis and to review our experience with successful repair, rather than replacement, of selected aortic valves after BAV. METHODS: From March 1986 to June 1995, 60 patients with congenital aortic stenosis aged 1 day to 27 years (mean +/- standard deviation, 7.3 +/- 6 years) underwent BAV. Twenty-three patients (38%) required operation a mean of 44 +/- 37 months (range, 1 to 110 months) after BAV, because of severe aortic insufficiency in 13 patients and recurrent or residual aortic stenosis in 10 patients. Severe aortic insufficiency was invariably due to avulsion of a cusp from the annulus, with resulting cusp prolapse and insufficiency. Operative intervention consisted of valve replacement in 14 patients and valve repair in 9 patients. Repair techniques included reattachment of an avulsed cusp to the aortic annulus, relief of commissural fusion, and debridement of thickened cusps. RESULTS: Actuarial freedom from surgical intervention after BAV was 88% +/- 4% at 1 year, 70% +/- 6% at 5 years, and 51% +/- 12% at 9 years. The need for aortic valve operation was unrelated to age at the time of BAV, indication for operation (aortic insufficiency versus aortic stenosis), age of operation, or preoperative gradient. All patients survived aortic valve operation; there was one late death at an average follow-up of 27 +/- 20 months (range, 2 to 61 months) after aortic valve operation. Stenosis was well relieved in all patients undergoing valve replacement. The 9 valve repair patients have been followed for 22 +/- 14 months (range, 1 to 47 months). Echocardiographic follow-up of the valve repair patients revealed a mean residual aortic stenosis peak instantaneous gradient of 32 mm Hg and mild aortic insufficiency or less in all patients. CONCLUSIONS: Aortic valve operation is required in 5% to 7% of patients yearly after BAV. The need for operation appears to be unrelated to age at the time of BAV; aortic insufficiency predominates over aortic stenosis as an indication for operative intervention. Valve repair can be applied in some patients after BAV with good intermediate-term results and may delay the need for aortic valve replacement.

Adolescent↗
PubMed1996

Etiology and outcome of outpatient fevers in pediatric heart transplant patients.

We reviewed 74 outpatient febrile episodes in 22 pediatric heart transplant patients in order to determine etiologies, rates of serious and nonserious illness, and factors predictive of serious disease. Twenty-two febrile episodes (30%) resulted in hospital admission. Only three variables were predictive of serious illness: longer duration of fever, shorter time since transplant, and lower febrile episode number. We conclude that at least 70% of outpatient febrile episodes are nonserious and can be managed safely in an outpatient setting. The duration of fever may be predictive of serious disease but is not useful at initial presentation.

Adolescent↗
PubMed1995

Abnormal Doppler pulmonary venous flow patterns in children after repaired total anomalous pulmonary venous connection.

Doppler echocardiography was used to evaluate pulmonary venous flow patterns in 16 children with repaired total anomalous pulmonary venous connection and in 16 age-matched normal controls. Using right upper pulmonary venous pulsed Doppler tracings, peak velocities and velocity time integrals were determined for ventricular systole, ventricular diastole, and atrial systole. Mitral inflow indexes and cardiac outputs were obtained. Patients with repaired total anomalous pulmonary venous connection and controls were similar in weight, heart rate, mitral inflow indexes, and cardiac output. In normal children, peak velocities were greater during ventricular diastole than systole, but velocity time integrals were greater during ventricular systole than diastole. Compared with normals, repaired patients had unobstructed flow patterns with increased peak velocities during ventricular diastole (0.92 +/- 0.35 vs 0.62 +/- 0.12 m/s) and atrial systole (0.27 +/- 0.12 vs 0.17 +/- 0.04 m/s). Velocity time integrals of repaired patients were increased during atrial systole (0.02 +/- 0.01 vs 0.01 +/- 0.03 m) but decreased during ventricular systole (0.08 +/- 0.03 vs 0.12 +/- 0.03 m). Systolic-to-diastolic ratios were decreased in repaired patients for peak velocity (0.56 +/- 0.20 vs 0.79 +/- 0.12) and velocity time integral (0.6 +/- 0.18 vs 1.48 +/- 0.35). Thus, pulmonary venous flow in normal children is greater during ventricular systole than during ventricular diastole. Repaired patients show a shift in forward flow from ventricular systole to diastole, with greater reversed flow during atrial systole.

Case-Control Studies↗
PubMed1995

Epoetin alfa therapy in infants awaiting heart transplantation.

OBJECTIVE: To determine the safety and efficacy of epoetin alfa therapy in infants awaiting heart transplantation to minimize the need for blood transfusions. DESIGN: Prospective case series analysis. SETTING: Pediatric tertiary care center. PATIENTS: Eleven term infants (4 to 54 days old) awaiting heart transplantation. INTERVENTION: Infants received 16 courses of daily epoetin therapy and four subsequent courses of alternate-day epoetin therapy. RESULTS: Daily epoetin therapy was instituted at 23.6 +/- 4.5 days of age, and the duration of treatment was 13.8 +/- 3.9 days (mean +/- SEM). During daily epoetin therapy, the hematocrit increased from 0.42 +/- 0.015 to 0.50 +/- 0.019 (P < .001), and the reticulocyte count increased from 58 +/- 9 x 10(-3) to 105 +/- 16 X 10(-3) (P < .05). There were no significant changes in leukocyte count (13.4 +/- 1.0 X 10(9)/L vs 15.1 +/- 0.9 X 10(9)/L), platelet count (402 +/- 43 X 10(9)/L vs 387 +/- 39 X 10(9)/L), or creatinine (53 +/- 9 mumol/L [0.6 +/- 0.1 mg/dL] vs 53 +/- 9 mumol/L [0.6 +/- 0.1 mg/dL]) (not significant). Four patients received blood transfusions during daily epoetin therapy, but the amount of blood administered to patients was significantly less (0.9 +/- 0.5 mL/kg per day) than the phlebotomy losses (1.8 +/- 0.4 mL/kg per day) (P < .01). During alternate-day epoetin therapy, the hematocrit decreased from 0.53 +/- 0.014 to 0.43 +/- 0.019 (P < .05). CONCLUSIONS: Daily epoetin therapy appears to be effective in maintaining stable hematocrit in infants awaiting heart transplantation, who generally require multiple transfusions secondary to iatrogenic blood losses.

Anemia↗
PubMed1995

Effects of cytomegalovirus infection on growth factor production in endothelial cells and fibroblasts.

To determine whether cytomegalovirus (CMV) infection alters growth factor production from endothelial cells (EC) or fibroblasts, we infected human umbilical vein EC with CMV VHL/E, a strain of CMV with affinity for human EC, and we infected human foreskin fibroblasts with CMV AD169. CMV caused cytopathic effect and positive CMV staining by immunofluorescence within 5 d, effects not seen in cells infected with UV-irradiated CMV or in uninfected (control) cells. The supernatants from the EC were assayed for platelet-derived growth factor (PDGF)-like protein using a radioreceptor inhibition assay, and EC and fibroblasts were assayed for basic fibroblast growth factor (bFGF) by Western blot analysis. There were no significant differences in PDGF production between groups of EC: CMV-infected EC, 13.5 +/- 2.6; UV-irradiated infected EC, 12.1 +/- 3.6; control EC, 12.9 +/- 1.7 fmol/10(6) EC (mean +/- SD, n = 10, p = NS). There were also no significant differences in bFGF production between CMV-infected EC, UV-irradiated infected EC, and control EC as evidenced by similar intensity of migration of bFGF as a single band at approximately 18 kD (n = 5). In contrast, CMV infection of fibroblasts induced a shift in production of bFGF to higher molecular weight forms migrating at 24 and 26 kD molecular mass. alpha-Interferon failed to alter bFGF production. We conclude that CMV VHL/E infection of EC does not directly alter PDGF or bFGF production from EC. However, CMV infection of cultured human fibroblasts qualitatively alters bFGF by inducing a shift to higher molecular weight forms.

3T3 Cells↗
PubMed1994

Equitable distribution in pediatric heart transplantation. Arguments in favor of a national list.

The disparity between the supply and demand for pediatric donor hearts remains the major constraint in pediatric heart transplantation. This disparity draws attention to the importance of an equitable distribution policy for pediatric hearts. An examination of the policy on pediatric heart distribution shows that although a governmental task force recommended that these organs be allocated according to a national list, the current policy, developed by the United Network of Organ Sharing, emphasizes the local distribution of pediatric hearts. The decision to allocate organs locally was based on both theoretical and practical concerns about national distribution. In analyzing these concerns, we conclude not only that a national list may be a more equitable means of distribution but also that the arguments against a national list no longer justify a policy favoring local distribution. We suggest, therefore, that the time has come to reconsider implementation of a national list for pediatric heart distribution.

Child↗
PubMed1994

Fetal cardiac bypass: improved placental function with moderately high flow rates.

Prenatal correction of certain cardiac lesions with a poor prognosis may have advantages over postnatal repair. For this to be done, safe and effective support of the fetal circulation must be devised. Studies involving fetal cardiac bypass have demonstrated progressive fetal hypoxemia, hypercapnia, and acidosis, indicating placental dysfunction. We performed fetal cardiac bypass in 18 fetal lambs (126 to 140 days' gestation) to assess the effect of flow rate on fetal oxygenation and metabolism and function of the placenta as an in vivo oxygenator. Fetal cardiac bypass was done for a 30-minute study period at normothermia in all fetuses. During the study period the fetal aorta was cross-clamped and cold cardioplegia was administered to the heart so there was no fetal cardiac contribution to systemic output. Nine fetuses underwent studies at low flow rates (109 +/- 20 mL.kg-1.min-1) and 9 at higher flow rates (324 +/- 93 mL.kg-1.min-1). At the lower flow rate, mean aortic pressure, arterial pH, and oxygen tension decreased whereas carbon dioxide tension and lactate levels increased when compared with prebypass levels. At the higher flow rate mean aortic pressure, pH, oxygen tension, carbon dioxide tension, and lactate levels remained similar to prebypass levels during the 30-minute study period. When the animals were weaned from the bypass circuit after studies at high flow rates, arterial oxygen tension and pH decreased whereas carbon dioxide tension increased to levels similar to those in the low-flow group.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Efficacy of 100 consecutive right ventricular endomyocardial biopsies in pediatric patients using the right internal jugular venous approach.

Indications for endomyocardial biopsy (EMB) in pediatric patients include cardiomyopathy and postheart transplant rejection surveillance. There have been few reports of the use of the internal jugular venous approach for right ventricular EMB in pediatric patients. In this study, we report our experience with 100 consecutive EMBs in pediatric patients using this approach. Indications for EMB were cardiomyopathy of unknown etiology in four patients, adriamycin cardiomyopathy in three patients, postheart transplant rejection surveillance in five patients, right ventricular outflow tract tumors in one patient, and sustained ventricular tachycardia in one patient. Histologic diagnoses of biopsy specimens included interstitial fibrosis, vasculopathy, hypertrophy, anthracycline cardiotoxicity, and various degrees of allograft rejection. All EMBs were performed successfully and without complications. We conclude that right ventricular EMB using the right internal jugular venous approach can be performed safely and successfully in pediatric patients as young as 2 months of age and repeatedly in patients as young as 8 years old.

Adolescent↗