The impact of tacrolimus as rescue therapy in children using a double immunosuppressive regimen after heart transplantation.

BACKGROUND: Organ transplant recipients with refractory rejection or intolerance to the prescribed immunosuppressant may respond to rescue therapy with tacrolimus. We sought to evaluate the clinical outcomes of children undergoing heart transplantation who required conversion from a cyclosporine-based, steroid-free therapy to a tacrolimus-based regimen. METHODS: We performed a prospective, observational, cohort study of 28 children who underwent conversion from cyclosporine-based, steroid-free therapy to a tacrolimus-based therapy for refractory or late rejection or intolerance to cyclosporine. RESULTS: There was complete resolution of refractory rejection episodes and adverse side effects in all patients. The incidence rate (×100) of rejection episodes before and after conversion was 7.98 and 2.11, respectively (P ≤ .0001). There was a 25% mortality rate in patients using tacrolimus after a mean period of 60 months after conversion. CONCLUSION: Tacrolimus is effective as rescue therapy for refractory rejection and is a therapeutic option for pediatric patients.

Choreoathetosis after cardiac surgery with hypothermia and extracorporeal circulation.

Eleven children, 4-48 months old, with congenital cyanotic heart defects developed choreoathetoid movements 2-12 days after cardiac surgery with hypothermia and extracorporeal circulation (ECC). The abnormal movements mainly involved the limbs, facial musculature, and tongue, leading to a severe dysphagia. The symptoms had an acute onset, after a period of apparent neurologic normality, and had a variable outcome. Of the nine children that survive, three had abnormal movements when last seen (41 days to 12 months of follow-up). The other six children had a complete regression of the choreoathetoid movements 1-4 weeks after onset. No specific finding was observed in the CT scans, cerebrospinal fluid examination, or EEG that could be related to the abnormal movements. Symptomatic therapy with haloperidol with or without benzodiazepines led to symptomatic improvement in six children, although there was no evidence that this treatment modified the evolution of the disease. The authors conclude that the choreoathetoid syndrome after cardiac surgery with deep hypothermia and ECC is an ill-defined entity requiring additional study to better understand its pathogenesis so that preventive measures can be taken to avoid a condition that can lead to permanent and incapacitating neurologic sequelae.

[Neonate and infant heart transplantation]. / Transplante cardíaco neonatal e infantil.

PURPOSE: Heart transplantation has offered children with complex congenital heart diseases and severe cardiomyopathies a chance for survival. The present article was written to show the three year experience of this procedure at the Instituto do Coração-HCFMUSP. METHODS: The methodology used was based on heart transplant indication criteria, inclusion criteria for donors, postoperative management, immunosuppression and prophylaxis as well as treatment of potential complications. RESULTS: From November 1992 to November 1995, 11 children, aged 12 days old to six years (mean 2.5 years) underwent transplantation. Sixty percent of recipients were male; weight ranged from 3.5 to 17.8 kg (mean 10.3 kg). The mean age of donors was 4.4 years (a range of three weeks to ten years), 80% male, weight ranging from 3.8 to 20 kg (median 14.3 kg). The survival rate was 91% and the remaining 10 children are doing well. The most important complications were systemic hypertension, acute rejection and infection. The number of rejections and infections per patient were 3.5 and 4.7 episodes, respectively. The follow-up was between one month to three years (average 16 months). CONCLUSION: In this experience, heart transplantation has given an additional opportunity for children with complex congenital heart diseases and cardiomyopathies, with a survival rate of 91% in three years.

[Anomalous origin of the left coronary artery. Concomitant correction with valvar replacement for mitral insufficiency]. / Origem anômala de artéria coronária esquerda. Correção concomitante à substituição valvar por insuficiência mitral.

A four year-old boy with an anomalous origin of the left coronary artery (LCA) directly from the right pulmonary artery was reported. He had been underwent to mitral valve replacement by a St Judes no. 29, due to severe mitral insufficiency, secondary to an extensive myocardial infarction including the anterior and posterior papilary muscles, beside the implantation of the LCA in the aorta. Instead of this favorable outcome, it's emphasized the need for earlier recognition to avoid risk sequelae.

Left ventricular apical approach for the surgical treatment of congenital mitral stenosis.

From June 1987 to October 1991, 12 patients with congenital mitral valve stenosis underwent surgical correction. Their ages ranged from 2 to 74 months. Nine patients were less than 22 months of age. Five patients were in New York Heart Association functional class IV, and seven patients were in class III. In nine, parachute-type mitral stenosis was clearly definite. In three, a complex congenital valvular and subvalvular stenosis was found. Associated anomalies were present in every patient; five had undergone previous operations. Correction of the mitral stenosis was done through an apical left ventriculotomy. The removal of the mitral obstruction starts from below; the papillary muscle was split and the chordae were divided or fenestrated. The commissurotomies were performed from the ventricular aspect of the mitral valve. Associated anomalies were corrected simultaneously. The operative mortality rate was zero. There was one late death, which was unrelated to cardiovascular status. The echocardiographic serial postoperative studies (up to 52 months) showed no significant residual mitral stenosis and normal global and regional function of the left ventricle in all but one patient.

Lung beta-adrenoceptors in pulmonary hypertension. A study of biopsy specimens in children with congenital heart disease.

Characteristics of beta-adrenoceptors were analyzed using radioligand-binding techniques with 3H-dihydroalprenolol in lung specimens from 11 children with pulmonary hypertension (median age, three years) undergoing surgical repair of congenital heart defects and four pediatric control subjects (median age, five years) undergoing thoracotomy for removal of neoplasms or cysts. Scatchard analysis of 3H-DHA binding to lung membranes showed similar values of the dissociation constant in both groups (Kd = 0.72 +/- 0.22 nM in patients vs 1.22 +/- 0.22 nM in controls; p = NS). The receptor density was significantly increased in patients in comparison with controls, with respective values of 164 +/- 19 and 95 +/- 13 fmol/mg of protein (p less than 0.025), and correlated directly with mean pulmonary arterial pressure (r = 0.82; p less than 0.0005). No significant relationship was observed between receptor number and pulmonary arterial medial thickness. Thus, the increase in receptor density in these patients may be related to adaptative changes in cells other than vascular smooth muscle.

Application of cardiac monitoring to surgical patients.

Not all surgical patients need the utmost in sophisticated cardiac monitoring. For those who do, however, there is a considerable gain in morbidity and mortality reduction. In this paper, we outline the place of cardiac monitoring in the spectrum of cardiac disease and present cases illustrating its usefulness in both preoperative and postoperative settings. The significant capacity of cardiac monitoring to determine very poor risks for major surgery candidates is also determined.

A technique for correction of truncus arteriosus types I and II without extracardiac conduits.

A new corrective operation for truncus arteriosus without the use of an extracardiac conduit was performed in seven patients with truncus type I (six patients) or type II (one patient) aged from 2 to 9 months. The common truncus arteriosus was septated with a patch into aortic and pulmonary segments and the ventricular septal defect was closed through a ventriculotomy. A direct anastomosis between the pulmonary arteries and the right ventricle was performed, the anterior wall being constructed with a patch with a monocusp valve. There was one death in the immediate postoperative period. In the surviving six patients the postoperative right ventricular/left ventricular peak systolic pressure ratio was less than 0.51 in five and 0.60 in one with a residual ventricular septal defect. All are in functional class I between 1 and 14 months after the operation. On the basis of these results, we propose this technique for patients with truncus type I or II in the first year of life.

Activation of 2',5'-oligoadenylate synthetase and B-2 microglobulin in cancer patients treated with partially pure gamma interferon: dependence of biological effect on administration route.

Partially pure immune (gamma) interferon (IFN-gamma) was administered to patients intramuscularly (IM), by rapid IV bolus, and by 6-h continuous infusion as part of a phase I clinical trial. The activity of 2',5'-oligoadenylate synthetase (2,5 A) in peripheral blood cells and the concentration of beta-2 microglobulin (B-2M) in serum were monitored as indicators of interferon biological activity in vivo. Five patients received IFN-gamma by the IM route in doses ranging from 6.5 X 10(5) to 9.6 X 10(6) antiviral units daily. There was little induction either of serum B-2M or of 2,5A in peripheral blood cells. Eight patients received IFN-gamma by rapid (5 min) IV bolus infusion in doses ranging from 6.5 X 10(5) to 54 X 10(6) antiviral units daily. As with IM administration, there was little significant induction of 2,5A synthetase, but the concentration of B-2M was increased above pretherapy values in most patients. Eleven patients received IFN-gamma by 6-h infusion daily for 10 days at a dosage of 27 X 10(6) units/day. In contrast to IM and IV bolus administration, 6-h infusion of IFN-gamma resulted in significant induction of both B-2M serum concentration and of 2,5A activity in all patients. The induction of 2,5A was highest on days 2 and 4 of therapy and decreased to pretherapy values by day 7. During the second 10-day course of the infusion study 2,5A activity was not induced until day 7 of therapy, and it decreased rapidly thereafter. These studies show clearly that consistent biological activity such as B-2M activation and specific intracellular biochemical events such as 2,5A induction may be optimally obtained by the administration of IFN-gamma by continuous IV infusion.

Monitorização hemodinâmica no pós-operatório de crianças submetidas a correção de cardiopatia congênita / Hemodynamic monitoring in postoperative period of children subjected to correction of congenital heart diseases

Propõe-se um método de monitorização hemodinâmica que compreende a avaliação do debito cardíaco, pressões atriais, pressão arterial, frequência cardíaca, temperatura corporal e volume urinário. Esta monitorização mais ampla foi utilizada em 12 crianças com media de idade 24 meses (desvio padrão 17 meses). As principais indicações foram: idade e peso reduzidos, necessidade de drogas inotrópicas ao sair de circulação extracorpórea, complexidade da cardiopatia e da correção cirúrgica, e insuficiência cardíaca ou respiratória antes da operação. São analisados os resultados terapêuticos, através de curva de função ventricular e particularidades na evolução hemodinâmica no pós-operatório em gráficos separados. O debito cardíaco foi obtido por termodiluição e são discutidos aspectos relacionados com o método utilizado em sua determinação. O procedimento revelou-se seguro e reprodutível, fornecendo subsídios importantes para decisões terapêuticas