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L Addonizio

Publications and source records attributed to L Addonizio.

11 recordsLinked to original sources
PubMed2001

Heart transplant in a factor VIII-deficient patient with a high-titre inhibitor: perioperative management using high-dose continuous infusion factor VIII and recombinant factor VIIa.

Four years prior to transplantation, a 14-year-old boy with severe haemophilia A and a high-responding factor VIII (FVIII) inhibitor developed an anteroseptal myocardial infarct while receiving high doses of an activated prothrombin complex concentrate (PCC). Cardiac transplantation was required for survival because of the ensuing cardiomyopathy. At surgery, the patient's inhibitor titre was 1.8 Bethesda units (BU). High-dose bolus therapy, followed by a continuous infusion of FVIII provided excellent operative and initial postoperative haemostasis without additional blood-product support. Once anamnaesis developed on day 6 postoperatively, recombinant factor VIIa (rFVIIa) therapy was initiated. Haemostasis remained excellent, except for the transient increase in chest-tube bleeding that was noted on day 7. epsilon-Aminocaproic acid was added and haemostasis was re-established. On day 15, rFVIIa was replaced with alternate day infusions of prothrombin complex concentrates (PCCs). On day 21 following the transplant, the patient was discharged, remaining on daily FVIII immune tolerance and thrice-weekly PCC prophylaxis. He remains well 24 months after transplant with an inhibitor titre of 39 BU. This paper describes the second case of cardiac transplantation complicated by haemophilia and an inhibitor, and discusses preoperative planning and operative and postsurgical haemostasis management.

Adolescent↗
PubMed1999

Nitric oxide modulates mitochondrial respiration in failing human heart.

Background-Our objective for this study was to investigate whether nitric oxide (NO) modulates tissue respiration in the failing human myocardium. Methods and Results-Left ventricular free wall and right ventricular tissue samples were taken from 14 failing explanted human hearts at the time of transplantation. Tissue oxygen consumption was measured with a Clark-type oxygen electrode in an airtight stirred bath containing Krebs solution buffered with HEPES at 37 degrees C (pH 7.4). Rate of decrease in oxygen concentration was expressed as a percentage of the baseline, and results of the highest dose are indicated. Bradykinin (10(-4) mol/L, -21+/-5%), amlodipine (10(-5) mol/L, -14+/-5%), the ACE inhibitor ramiprilat (10(-4) mol/L, -21+/-2%), and the neutral endopeptidase inhibitor thiorphan (10(-4) mol/L, -16+/-5%) all caused concentration-dependent decreases in tissue oxygen consumption. Responses to bradykinin (-2+/-6%), amlodipine (-2+/-4%), ramiprilat (-5+/-6%), and thiorphan (-4+/-7%) were significantly attenuated after NO synthase blockade with N-nitro-L-arginine methyl ester (10(-4) mol/L; all P<0.05). NO-releasing compounds S-nitroso-N-acetyl-penicillamine (10(-4) mol/L, -34+/-5%) and nitroglycerin (10(-4) mol/L, -21+/-5%), also decreased tissue oxygen consumption in a concentration-dependent manner. However, the reduction in tissue oxygen consumption in response to S-nitroso-N-acetyl-penicillamine (-35+/-7%) or nitroglycerin (-16+/-5%) was not significantly affected by N-nitro-L-arginine methyl ester. Conclusions-These results indicate that the modulation of oxygen consumption by both endogenous and exogenous NO is preserved in the failing human myocardium and that the inhibition of kinin degradation plays an important role in the regulation of mitochondrial respiration.

Amlodipine↗
PubMed1999

Synergy of amlodipine and angiotensin-converting enzyme inhibitors in regulating myocardial oxygen consumption in normal canine and failing human hearts.

The production of endogenous nitric oxide, which regulates myocardial oxygen consumption, is decreased in heart failure. As with angiotensin-converting enzyme (ACE) inhibitors, amlodipine, a calcium antagonist, increases kinin-mediated nitric oxide production in coronary microvessels. We investigated the possibility of synergy between ACE inhibitors and amlodipine in regulating myocardial oxygen consumption. Left ventricular myocardium was isolated from 6 healthy dog hearts and 5 human hearts with end-stage heart failure at the time of orthotopic heart transplantation. Myocardial oxygen consumption was measured before and after administration of bradykinin, S-nitroso N-acetyl penicillamine (SNAP, a nitric oxide donor), ramiprilat (an ACE inhibitor), amlodipine, and the combination of a sub-threshold dose of ramiprilat (10(-8) md/L) + amlodipine. These experiments were repeated with L-nitro-arginine methyl ester (L-NAME, an inhibitor of nitric oxide synthesis), dichloroisocoumarin (an inhibitor of kinin synthesis), and HOE 140 (a B2 kinin-receptor antagonist). Baseline myocardial oxygen consumption in canine hearts was 182 +/- 21 nmol/g/min. Bradykinin and SNAP caused dose-dependent reductions in myocardial oxygen consumption (p <0.05). Ramiprilat and amlodipine caused a 10 +/- 3.2% and 11 +/- 0.8% reduction in myocardial oxygen consumption, respectively, when used alone (p <0.05). In the presence of a subthreshold dose of ramiprilat, amlodipine caused a larger (15 +/- 1.7%) reduction in myocardial oxygen consumption compared with either drug used alone (p <0.05). In human hearts, baseline myocardial oxygen consumption was 248 +/- 57 nmol/g/min. Amlodipine caused a larger reduction in myocardial oxygen consumption when used with ramiprilat (22 +/- 3.2%) as compared with amlodipine alone (15 +/- 2.6%). The effect of both drugs was attenuated by L-NAME, dichloroisocoumarin, and HOE 140 (p <0.05). In conclusion, ACE inhibitors and amlodipine act synergistically to regulate myocardial oxygen consumption by modulating kinin-mediated nitric oxide release, and this combination of drugs may be useful in the treatment of heart failure.

Adolescent↗
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↗
PubMed1995

Molecular genetic analysis demonstrates that multiple posttransplantation lymphoproliferative disorders occurring in one anatomic site in a single patient represent distinct primary lymphoid neoplasms.

BACKGROUND: Posttransplantation lymphoproliferative disorders (PT-LPDs) are a clinicopathologically heterogeneous group of lymphoid proliferations of varied clonal composition, the majority of which are associated with Epstein-Barr virus (EBV) infection. The clonal content and clonal relatedness of 24 separate PT-LPD lesions occurring synchronously in one organ in a single patient were investigated. METHODS: Twenty-four separate PT-LPD lesions from the colon and mesentery of a 15-year-old male, developing 4 months after cardiac transplantation, were studied for clonality based on immunoglobulin heavy chain (IgH) gene rearrangements for the presence, clonality, and type of EBV infection and for the presence of c-myc, ras, and p53 gene alterations. Southern blot hybridization, polymerase chain reaction, and single strand conformation polymorphism assays were employed. RESULTS: All 24 lesions were histologically similar (polymorphic B-cell lymphomas) but exhibited varied clonality and were clonally distinct with respect to both IgH gene rearrangements and EBV infection. All lesions were infected with EBV type A. Structural alterations of oncogenes or tumor suppressor genes were not identified. CONCLUSIONS: Separate PT-LPD lesions occurring synchronously in a single organ or patient may be clonally distinct, suggesting that they represent multiple distinct primary lymphoid proliferations rather than metastatic disease as in conventional malignant lymphomas. This may explain partially the rapid development in some patients of a large PT-LPD tumor burden that may regress rapidly after reduction of immunosuppression.

Adolescent↗
PubMed1995

Cholelithiasis in pediatric cardiac transplant patients on cyclosporine.

From June 1984 to June 1993, symptomatic chlolethiasis was observed in six (6.7%) of 90 cases of pediatric heart or heart-lung transplants at the author's institution. The incidence of cholelithiasis for all children under 16 years of age is estimated to be less than 1%. Previously, information on cholelithiasis in pediatric transplant patients on cyclosporine therapy had been limited. Studies concerning the incidence of gallstones in adult kidney and cardiac transplant patients have shown that there is an increase associated with cyclosporine, possibly related to elevated levels and hepatoxicity. Five patients underwent uneventful cholecystectomy. There was only one death, which occurred after emergency cholecysostomy tube placement for biliary sepsis. If indicated, biliary tract surgery can be performed safely in cardiac transplant patients. The authors report on their experience with symptomatic cholelithiasis in pediatric cardiac transplant patients and review the current literature on the hepatotoxic effects of cyclosporine.

Adolescent↗
PubMed1995

Head and neck infections in pediatric cardiac transplant patients.

A retrospective chart review was undertaken at Columbia Presbyterian Medical Center to assess the incidence, etiology and management of head and neck infections in pediatric cardiac transplant patients on immunosuppression. From June 1984 to February 1992, 59 cardiac transplants were performed on 57 pediatric patients. Standard immunosuppressive therapy was used. Thirteen of these patients died within three months of transplant and were not included. Of the 44 patient charts reviewed, 82 head and neck infections were documented in 27 patients (61%). There were 26 episodes of sinusitis, 27 episodes of otitis media and 20 episodes of tonsillitis/pharyngitis. Unusual middle-ear pathogens seen included Morganella morgagni and Pseudomonas aeruginosa. These preliminary data suggest that children on immunosuppression for cardiac transplant may be at risk for head and neck infections from unusual or unsuspected organisms, and tympanocentesis plays an important role in diagnosis and treatment. A prospective study is planned to gain further data.

Adolescent↗
PubMedDate not supplied

The psychosocial impact of pediatric heart transplantation.

Children with terminal heart disease experience a dramatic improvement in functional status after heart transplantation but may be at increased risk for problems in psychosocial adaptation. Selected psychosocial outcomes were assessed in 49 pediatric heart transplant recipients and their families from five heart transplantation centers. Heart transplant recipients did not appear significantly different from their peers on self-report measures of self-concept and anxiety, but they showed significantly less social competence and more behavior problems than a normative population. Behavior problems observed were most frequently suggestive of depression and were significantly associated with greater family stress and diminished family resources for managing stress. The study findings further suggest that the heart transplant recipients' ability to verbalize or ventilate their feelings and concerns to others seems to facilitate psychosocial adaptation. Assessment of stress, resources, and coping is imperative to enable health professionals to promote the psychosocial adaptation of pediatric heart transplant recipients and their families.

Adaptation, Psychological↗
PubMedDate not supplied

Pediatric retransplantation.

Previous studies have attempted to outline the efficacy of heart retransplantation in adults. A limited number of these retransplantation procedures have been performed in children; however, no study to date has evaluated the risk of heart retransplantation in this specific patient population. We conducted a retrospective review of 17 pediatric (non-neonatal) heart transplant recipients who subsequently underwent heart retransplantation. Thirteen male and four female patients underwent retransplantation at four different institutions between 1974 and 1992. Patient age at the time of primary transplantation ranged from 2 to 19 years (mean, 12.5 years) and from 3 to 30 years (mean, 16 years) at retransplantation. The time interval between transplantation procedures ranged from 2 days to 15.6 years and was not predictive of patient outcome. Follow-up after retransplantation ranged from 1 day to 11 years (mean, 2.8 years). All patients were New York Heart Association class 3 or class 4 at the time of retransplantation. After retransplantation all survivors were New York Heart Association class 1. No patient had mechanical device implantation or extracorporeal membrane oxygenation bridge-to-transplantation at primary transplantation or retransplantation. The indication for retransplantation was transplant coronary artery disease (TxCAD) in seven patients (41.2%), acute rejection in four (23.5%), chronic rejection in one (5.8%), chronic rejection associated with TxCAD in four (23.5%), and intraoperative donor organ failure in one (5.8%). No significant difference occurred in linearized rates of rejection or infection or in actuarial freedom from rejection or infection when secondary grafts were compared with primary grafts in patients undergoing retransplantation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗