Berlin heart ventricular assist device as a long-term bridge to transplantation in a Fontan patient with failing single ventricle.

The use of VADs as a BTT in children with heart failure has increased due to enhanced device design and reliability, leading to improved survival, functional capacity, and quality of life. However, the use of VADs in patients with Fontan physiology as a BTT is rare with few case reports. Here, we describe a case of implantation of the Berlin VAD as a BTT for 179 days, one of the longest reported periods of mechanical support, in a child with failing single ventricle.

Treatment of mice with anti-CD3 mAb induces endothelial vascular cell adhesion molecule-1 expression.

In vivo treatment of mice with anti-CD3 mAb causes polyclonal T cell activation and cytokine release. Since several cytokines are known to alter expression of MHC molecules and adhesion molecules on endothelia, we hypothesized that anti-CD3 mAb treatment should result in activation of vascular endothelia. In previous studies, we established that vascular endothelial cells in murine heterotopic cardiac grafts can develop at least 2 stable inflammatory phenotypes: cardiac allograft endothelia characteristically develop reactivity with MECA-32 mAb (undefined endothelial epitope) and M/K-2 mAb (murine vascular cell adhesion molecule-1 [VCAM-1]), whereas cardiac isografts develop reactivity with MECA-32, but not M/K-2 mAb. We now report that a single treatment of cardiac isograft recipients with the anti-CD3 mAb 145-2C11 caused expression of VCAM-1 on all cardiac isograft endothelia, including the microvascular endothelia. In contrast, expression of endothelial VCAM-1 in the native heart of the isograft recipient was limited to patchy areas of larger arteries. This patchy, arterial pattern of VCAM-1 expression was observed in lung, liver, kidney, and thymus of all mice treated with 145-2C11, whether or not they were implanted with a cardiac isograft, and was dissociated from expression of MECA-32 mAb reactivity. Hence, treatment of mice with anti-CD3 mAb causes systemic endothelial activation (VCAM-1 expression), and endothelial cells of recently implanted cardiac isografts appear to be hypersensitive to induction of VCAM-1 by anti-CD3 mAb treatment. Further studies showed that (1) treatment with 145-2C11 F(ab)'2 fragments did not induce endothelial activation, (2) intravenous pretreatment with pentoxifylline eliminated all endothelial effects of 145-2C11 treatment, (3) induction of endothelial activation by 145-2C11 mAb always paralleled the expression of adverse physiologic symptoms, and (4) mice exhibit strain-specific differences in endothelial responses to 145-2C11 treatment. We propose that anti-CD3 mAb treatment causes simultaneous activation of circulating T cells and systemic vascular endothelial cells which may facilitate systemic lymphocyte-endothelial interactions, and may explain the rapid disappearance of T cells from the circulation that is associated with anti-CD3 treatment in mouse and man.

Treatment with anti-vascular cell adhesion molecule 1 monoclonal antibody induces long-term murine cardiac allograft acceptance.

Daily in vivo treatment of murine H-2d --> H-2b cardiac allograft recipients with 400 micrograms/day i.p. of M/K-2, a mAb to the endothelial adhesion molecule VCAM-1, resulted in prolongation of graft survival. The surviving allografts showed little of the histologic changes observed in acutely rejecting control allografts. When antibody treatment was discontinued after 20 days, grafts continued to function for at least 40 more days. This was approximately 30 days after mAb was no longer detectable by ELISA in the circulation, or by immunoperoxidase staining at the graft site. The most notable feature of grafts that survived 60 days was the presence of mild interstitial fibrosis. Endothelial reactivity was minimal with the mAbs MECA-32 and M/K-2, which have been used in previous studies to visualize the extensive endothelial inflammation that develops during untreated acute rejection. There was a mild cellular infiltrate containing T cells, but few macrophages. However, infiltrating T cells appeared to be inactive in that IL-2R+ cells were immunohistologically undetectable and mRNA for IL-2, IL-4, or IFN-gamma was undetectable by polymerase chain reaction. In general, the immunologic conditions in these long-term grafts differed from those seen in normal cardiac tissue, cardiac isografts, or cardiac allografts. These data demonstrate that M/K-2 mAb can suppress cardiac allograft rejection and induce long-term graft acceptance. This graft survival appears to be associated with the development of a unique state of immunity at the graft site.

Biventricular repair for aortic atresia or hypoplasia and ventricular septal defect.

OBJECTIVE: Aortic valve atresia or hypoplasia can present with a ventricular septal defect and a normal mitral valve and left ventricle. These patients may be suitable for biventricular repair, although the optimal initial management strategy remains unknown. METHODS: From January 1991 through March 1999, 20 patients with aortic atresia or hypoplasia and ventricular septal defect underwent operation with the intent to achieve biventricular repair. Aortic atresia was present in 7 patients, and aortic valve hypoplasia was present in 13 patients. Among those patients with aortic hypoplasia, Z-scores of the aortic valve anulus ranged from -8.8 to -2.7. Associated anomalies included interrupted aortic arch (n = 12 patients), coarctation (n = 6 patients), aortopulmonary window (n = 1 patient), and heterotaxia (n = 1 patient). Nine patients were staged with an initial Norwood procedure followed by biventricular repair in 8 patients. One patient awaits biventricular repair after a Norwood procedure. The conditions of 11 patients were corrected with a single procedure. RESULTS: Among the 9 patients who underwent staged repair, there were no deaths after the Norwood procedure and 1 death after biventricular repair. For the 11 patients who underwent a primary biventricular repair, there was 1 early death and 2 late deaths from noncardiac causes. Follow-up ranged from 1 to 85 months (mean, 28 months). Actuarial survival for the entire group was 78% +/- 10% at 5 years and was not significantly different between staged repair (89%) and primary biventricular repair (73%). CONCLUSIONS: Both primary and staged biventricular repair for patients with aortic atresia or hypoplasia and ventricular septal defect may be performed with good late survival. Refinements in technique of conduit insertion and arch reconstruction have resulted in primary biventricular repair becoming our preferred approach.

Prevention of acute murine cardiac allograft rejection: anti-CD4 or anti-vascular cell adhesion molecule one monoclonal antibodies block acute rejection but permit persistent graft-reactive alloimmunity and chronic tissue remodelling.

We treated C57BL/6 mouse recipients of DBA/2 cardiac allografts with anti-CD4 monoclonal antibodies (mAb) or anti-vascular cell adhesion molecule 1 mAb to promote long-term allograft survival and subjected both the recipient animals and the long-surviving allografts to a battery of histologic and immunologic tests. The results were similar regardless of the mAb used for antirejection therapy. At all tested times after transplantation, the allografts displayed histologic evidence of ongoing microvascular endothelial activation and interstitial leukocytic infiltration. Reverse transcription polymerase chain reaction analyses revealed continuous intragraft expression of messenger RNA for interleukin 1, interleukin 2, interleukin 4, interleukin 6, tumor necrosis factor, interferon gamma, and transforming growth factor beta. All grafts had histologic evidence of ongoing vascular and parenchymal tissue remodeling, including interstitial fibrosis and vascular neointimal hyperplasia. The graft recipients retained limiting dilution analysis--detectable, donor-reactive cytolytic T lymphocyte, and helper T lymphocyte in their spleens and produced high liters of donor-reactive alloantibodies. Variable amounts of allogeneic microchimerism were detectable in some, but not all of the long-surviving graft recipients. In general, these observations indicate that (1) a similar immune status is achieved in long-surviving allografts and their recipients when either anti-CD4 mAb or anti-vascular cell adhesion molecule-1 mAb was used for antirejection therapy, in spite of the major differences in lineage and distribution of cells targeted by these two mAbs, (2) this immune status is characterized by continuous, long-term inflammatory and immune processes very similar to those observed during acute allograft rejection, and (3) in spite of these processes the allografts continue to function, although they invariably develop a chronic rejection-like histopathologic condition that may ultimately limit graft function. In this regard, the recipients of long-surviving allografts do not seem to be tolerant of their graft alloantigens.

The Ross/Konno procedure in neonates and infants: intermediate-term survival and autograft function.

BACKGROUND: The Ross procedure has been increasingly applied to neonates and infants. Addition of a modified Konno-type enlargement of the aortic annulus allows the application of this procedure to neonates and infants with significant annular hypoplasia. The potential for growth and the proven durability make the autograft an ideal aortic valve replacement. METHODS: Between March 1993 and December 2000, 10 patients under 1 year of age underwent a Ross/Konno procedure at our institution (range, 2 to 349 days; median 16). All patients had severe to critical aortic stenosis. All patients required aortic annulus enlargement for size mismatch between the aortic and pulmonary valves. RESULTS: There were no deaths at a median follow-up of 48 months (range, 1 to 74 months). All patients had none to mild aortic stenosis on Doppler echocardiography. Eight patients had a 0 to 1+ aortic insufficiency, 1 patient had a 2+ aortic insufficiency, and 1 patient had a 3+ aortic insufficiency. Aortic annular dilatation was not observed. Aortic sinus dilatation occurred initially (mean change in z-value: 0 to 12 months, +2.1) and then stabilized (mean change in z-value: 12 to > 36 months, +0.6). No patient required additional procedures for aortic valve disease. Two patients required three pulmonary allograft replacements. CONCLUSIONS: The Ross procedure with a modified Konno-type enlargement of the aortic annulus is an excellent approach to aortic valve disease in the neonate and infant. The procedure can be accomplished with low morbidity and mortality, and low rates of reoperation. The pulmonary autograft demonstrates durability without developing aortic stenosis, aortic insufficiency, or progressive dilatation. Enlargement of the aortic annulus parallels somatic growth.

Primary repair of aortic arch obstruction with ventricular septal defect in preterm and low birth weight infants.

OBJECTIVE: Previous reports have suggested that prematurity and low birth weight are risk factors for definitive surgical intervention in congenital cardiac malformations. The following data review our experience with primary repair of the complex malformation of aortic arch obstruction with ventricular septal defect (VSD) in this patient population. METHODS: Since 1988, 21 consecutive preterm (

Pediatric bronchioloalveolar carcinoma: a favorable pediatric malignancy?

Primary pulmonary tumors are infrequent in children. Bronchioloalveolar carcinoma has been documented rarely in the pediatric population. Before this report, there have been only three cases of bronchioloalveolar carcinoma in patients less than 16 years of age. Our two cases represent two of the youngest cases (ages 6 and 15 years) reported with bronchioloalveolar carcinoma. They illustrate many of the typical findings of this disease including clinical presentation, diagnostic difficulty, and better prognosis compared with other pulmonary malignancies. This neoplasm appears to have a favorable outcome in childhood.

Anesthetic management for resection of cor triatriatum during the second trimester of pregnancy.

Hemodynamic changes during pregnancy can result in cardiovascular decompensation in women with pre-existing cardiac diseases. Despite optimized medical treatment, some patients with severe structural cardiac abnormalities may need surgical intervention during pregnancy. We describe a woman who presented at 20 weeks of gestation with acute heart failure due to cor triatriatum, a rare form of congenital heart disease. This condition is characterized by a perforated fibromuscular membrane dividing the left atrium into two chambers. The clinical presentation varies from asymptomatic to acute heart failure depending on the size of the fenestrations in the membrane and the presence of associated cardiac malformations. In our patient, two severely restrictive orifices in a membrane within the left atrium, moderate to severe pulmonary hypertension and good biventricular function were demonstrated by transthoracic echocardiography. Without surgical resection, the increased blood volume and cardiac output associated with pregnancy could have resulted in cardiovascular decompensation. She underwent urgent corrective open heart surgery with cardiopulmonary bypass. Perioperative anesthetic management included prevention of tachycardia, atrial dysrhythmias and pulmonary hypertension, close monitoring for and prompt treatment of maternal hypotension, maintaining euvolemia and good cardiac contractility and avoiding hemodilution and hypothermia. These approaches, together with minimizing bypass time, resulted in successful maternal and fetal outcome.

The lateral tunnel Fontan procedure for hypoplastic left heart syndrome: results of 100 consecutive patients.

The Fontan procedure for hypoplastic left heart syndrome (HLHS) is well established. Multiple surgical techniques including extracardiac conduits and autologous tissue connections have been developed. We reviewed the results of 100 consecutive patients undergoing the lateral tunnel modification of the Fontan procedure at the University of Michigan. A cross-sectional retrospective study was performed for 100 consecutive patients identified in the University of Michigan Congenital Heart Surgery database with the diagnosis of HLHS. All patients had undergone a lateral tunnel Fontan procedure between June 2000 and August 2004. The medical record was reviewed to assess patient, procedural, and morphologic determinants of outcome. Hospital survival was 97% and intermediate-term survival was 96% with a median follow-up time of 34 months. Preoperative mean pulmonary artery pressure, right ventricular end diastolic pressure, aortic cross-clamp time, and tricuspid valve regurgitation were not associated with late right ventricular function or survival. Three patients required takedown of the lateral tunnel Fontan in the early postoperative period. A positive association was found between protein-losing enteropathy and prolonged (>2 weeks) postoperative pleural drainage (p = 0.035). No patient required cardiac transplantation or late intervention on the Fontan pathway. At the time of follow-up, 100% of patients were New York Heart Association class I or II and 90% were in normal sinus rhythm. The lateral tunnel Fontan procedure for HLHS can be performed with acceptable early and intermediate-term risk. There was a low prevalence of late rhythm disturbances and other complications. Protein-losing enteropathy and prolonged pleural drainage were associated.

Bell's palsy.

Idiopathic facial (Bell's) palsy is an affliction commonly seen and managed by the family physician. Although the prognosis is generally good, steroids and cromolyn sodium have each been advocated to enhance full recovery. Surgical exploration of the nerve is indicated when the diagnosis is unclear. Various measures may be necessary to protect the eye.

Advances in congenital heart surgery.

Congenital heart surgery is a young and constantly evolving field. Since the first patent ductus arteriosus ligation by Robert Gross of Boston in 1938, a greater understanding of the anatomy and pathophysiology of congenital heart disease, improved diagnostics, and the advent of cardiopulmonary bypass and deep hypothermic circulatory arrest have allowed the open repair of many lesions. Further advances in preoperative, intraoperative, and postoperative patient management have resulted in greatly improved survivals for even the most complex congenital defects. By looking forward through continual technical innovation and back with the critical evaluation of established techniques, we continue to advance the care of the patient with congenital heart disease.

Amplatzer closure of atrial septal defect and da Vinci robot-assisted repair of vascular ring.

Technology for minimally invasive approaches to congenital heart disease is a rapidly evolving field. This case report reviews a novel approach to combining two of the newer technologies available to treat a pediatric patient with an atrial septal defect (ASD) and a vascular ring. This report is the first to describe the use of the da Vinci surgical system to assist in a thoracoscopic procedure for a pediatric patient. The da Vinci assisted division of the vascular ring, joined with an Amplatzer closure of the ASD, demonstrates how maximum benefit can be obtained for patients by combining emerging technologies.

Diversity of isolates of penicillinase-producing Neisseria gonorrhoeae (PPNG) in Honolulu, Hawaii: 1982-1991.

BACKGROUND AND OBJECTIVES: Gonococcal infections caused by penicillinase-producing Neisseria gonorrhoeae (PPNG) isolates have increased in geographic distribution and prevalence. It was postulated that PPNG strains would become endemic in Honolulu and that, in turn, this city would serve as a reservoir for the introduction of PPNG strains into the continental United States. GOAL OF THIS STUDY: To assess the role of Honolulu as a reservoir for PPNG strains by assessing the diversity and persistence of PPNG strains between 1982 and 1991. STUDY DESIGN: A total of 432 PPNG strains were characterized by auxotype/serovar (A/S) class and plasmid content, and their distribution during the 10-year period was studied. RESULTS: Of 432 isolates, 373 (86.4%) possessed a 4.4-Mdal beta-lactamase plasmid; 39 (9.0%) possessed a 3.2-Mdal beta-lactamase plasmid; and 20 (4.6%) possessed a 3.05-Mdal beta-lactamase plasmid. A total of 53 A/S classes were identified. Asian, African, and Toronto PPNG strains belonged to 49 (92.5%), 15 (28.3%), and 11 (20.7%) A/S classes, respectively. Though all Toronto PPNG strains possessed a 24.5-Mdal conjugative plasmid, these plasmids could not be transferred by conjugation. Although some apparent microepidemics of PPNG strains were identified, most strains were isolated sporadically. CONCLUSIONS: A large number of different strains have been associated with PPNG infections in Honolulu, but there was no evidence that any strain persisted endemically during the study period. These observations have important implications for the design and assessment of community gonorrhea control strategies.

Quantitative digital angiography as an adjunct to the intraoperative placement of endovascular stents in congenital heart disease.

Clearly identifiable intraoperative landmarks render the placement of intraoperative stents difficult. Preoperative use of quantitative digital angiography helps the surgeon accurately insert endovascular stents intraoperatively. By using defined points of reference, we were able to carefully select the size and lengths of stents before the operation and precisely place these stents in the operating room. Furthermore, we have been able to redilate these stents using the same techniques at subsequent operations. Our results reflect the efficacy of this technique.

Postductal origin of the left carotid, left subclavian, and aberrant retroesophageal right innominate arteries in truncus arteriosus with interrupted aortic arch.

A neonate presented to the C.S. Mott Children's Hospital at the University of Michigan with truncus arteriosus and interrupted left aortic arch, with associated postductal origin of the left carotid, left subclavian, and aberrant retroesophageal right innominate arteries. In addition, the patient was diagnosed with DiGeorge syndrome. This unique anomaly has not been previously reported. The anatomy, pathophysiology, embryology, and successful surgical management of this anomaly are reviewed in this report.

Importance of endothelial VCAM-1 for inflammatory leukocytic infiltration in vivo.

The microvascular endothelia of rejecting DBA/2----C57B1/6 murine cardiac allografts develop reactivity with the mAb M/K-2, which recognizes the murine homologue of the human leukocyte adhesion molecule VCAM-1. This reactivity does not develop in DBA/2----DBA/2 cardiac isografts or normal DBA/2 cardiac tissues. To determine whether endothelial VCAM-1 plays a role in allograft inflammation, cardiac allograft recipients were treated with M/K-2 antibody and monitored for leukocytic graft infiltration and graft survival. Treatment of the graft recipients with 200 micrograms/day M/K-2 Ig prolonged graft survival by 5 to 6 days (statistically significant); whereas treatment with 100 micrograms M/K-2 Ig every other day after transplant did not influence graft survival. Neither treatment interfered with leukocytic infiltration, as detected histologically or by limiting dilution analysis. The high dose treatment, but not the low dose treatment, resulted in high circulating levels of M/K-2, as detected by serum ELISA, and prominent antibody deposition on the graft vascular endothelia, as demonstrated by immunohistologic analysis. These data demonstrate that VCAM-1 is uniquely expressed on the vascular endothelia of rejecting murine cardiac allografts, and that a mAb to VCAM-1 can interfere with the allograft rejection process. Although this antibody can interfere with lymphocyte-endothelial adhesion in vitro, it has little effect on leukocytic infiltration in rejecting allografts suggesting that this process does not depend exclusively on VCAM-1 expression.