LEOPARD syndrome.

LEOPARD syndrome (LS) is a rare hereditary disorder, characterised mainly by skin, facial and cardiac abnormalities. We report on the case of a six-year-old Djiboutian with typical features of LS. Multiple cardiovascular problems are described, including pulmonary infundibular, valvular and supra-valvular stenosis. A favourable course was observed after successful cardiac surgery. This is the first reported case of LS from the horn of Africa.

[Endothelial vasoactive factors: predictive markers of the results of the Fontan intervention?]. / Facteurs vasoactifs endothéliaux: marqueurs prédictifs du résultat de l'intervention de Fontan?

UNLABELLED: We retrospectively analyzed the pulmonary biopsies of a Fontan intervention in order to identify predictive markers of its result. The pulmonary biopsies of 17 patients who benefited from the Fontan intervention and 6 controls were studied. The histomorphometric measurements and endothelial expression of vasoactive factors (NO synthase, endothelin-1) and angiogenic factors (VEGF) were analyzed with immunohistochemistry at the level of intra-acini pulmonary arterioles. Eight patients presented a good surgical result (group 1). Distal arterioles presented a thin and regular wall: the NO synthase, endothelin and VEGF expression was low. Nine patients presented a failure of the Fontan operation (group 2). The distal arterioles were slightly musculated (p<0.01 vs. group 1 and group control). The endothelin-1 expression was comparable to that observed in group 1. Conversely, the NO synthase and VEGF expressions were significantly increased in that group (<0.001 vs. group 1 and group control). CONCLUSION: In case of Fontan operation failure, the histological modifications are subtle with a muscular extension of the distal pulmonary arterioles wall. Conversely, a marked increase of NO synthase and VEGF expression is observed which can witness of an endothelial dysfunction. This study could be able to define predictive factors of the evolution and refine the selection of patients candidate for a Fontan operation.

Bi-directional cavopulmonary shunt: is accessory pulsatile flow, good or bad?

OBJECTIVE: Evaluation of the effect and long-term outcome of accessory pulsatile blood flow versus classical bi-directional cavopulmonary connection (BCPC). METHODS: Retrospective review of the medical and surgical records. RESULTS: Two-hundred and five patients (119 boys, 86 girls) underwent BCPC from 1990 to 1996. Accessory pulsatile flow was present in 68%, flow being maintained through the pulmonary trunc in 46%, systemic-to-pulmonary artery shunt in 13% and mixed in 7%, or patent ductus arteriosus in 2%. Patients with accessory pulsatile flow had lower hospital mortality (3% versus 5%), while mean pulmonary artery pressure (14.1 versus 12.6 mmHg P = 0.050) and increase of oxygen saturation (12.4 versus 8.7, P = 0.034) were significantly higher. The period of artificial ventilation (1.9 day) and ICU stay (6 days) did not differ for both groups. Late mortality was higher following accessory pulsatile flow (6% versus 1%). At late follow-up patients with accessory pulsatile flow had significantly higher oxygen saturation (mean 85 +/- 4%, versus 79 +/- 4%; P < or = 0.005). If subsequent completion of Fontan is considered the optimal palliation and subsequent systemic to pulmonary artery shunt, arteriovenous fistula and transplantation is considered a failure, patients with accessory pulsatile flow had significantly more and earlier completion of the Fontan procedure (mean 1.7 +/- 2.4 years, versus 2.7 +/- 4.4 years; P = 0.008). Survival is not influenced by age at bi-directional cavopulmonary shunt surgery, left or right functional ventricular anatomy or previous palliative surgery. One patient with accessory pulsatile flow developed systemic-to-pulmonary collateral's eventually requiring lobectomy. CONCLUSION: Despite two different initial palliative techniques the outcome was not significantly different. Accessory pulsatile blood flow appeared not to be a contra-indication for a completion Fontan procedure. Moreover, the data suggest that after accessory pulsatile flow can safely be performed, at late follow-up oxygen saturation is higher, while, significantly more and earlier completion of Fontan occurred. Age at bi-directional cavopulmonary shunt, basic left or right ventricular anatomy or previous palliative surgery did not influence survival.

[Spontaneous regression of a false aneurysm of the ascending aorta following surgery for dissection]. / Régression spontanée d'un faux anévrisme de l'aorte ascendante consécutif à une chirurgie pour dissection.

We report the case of a 50-year-old man admitted to hospital for a type A aortic dissection. After conventional surgical repair, he was asymptomatic and underwent computed tomography imaging at 15 days, 3 and 6 months. The first CT scan showed a small perigraft circulating false aneurysm which totally disappeared on the last exam. This case emphasizes the potential role of CT scan in the follow-up of patient after aortic surgery and the likely favorable outcome of some false aneurysm.

Pharmacokinetic-pharmacodynamic relationships between pirarubicin exposure and hematotoxicity: clinical application using only one blood sample.

The objective of the present study was to evaluate the relationship between the pharmacokinetic parameters of pirarubicin and of its metabolite doxorubicin measured in plasma and whole blood, and the hematologic toxicity of this drug, in order to evaluate the predictability of changes in white blood cells (WBC) by single measurement of drug concentrations. This pharmacokinetic-pharmacodynamic relationship was studied in a total of 45 patients with different tumor types treated by combined chemotherapy containing pirarubicin, administered as short infusion (10+/-2 min) at doses ranging from 50 to 90 mg. In 45 courses performed in 24 patients, we established the relationship between the half-product of pirarubicin level in whole blood at the end of the infusion and the duration of this infusion, which represents an estimate of the area under the time x concentration curve (AUC(PIRA,wb,ei) = C(PIRA,wb,ei) x duration of infusion/2), the age of the patients and the relative fall in WBC counts. These results allowed us to establish a predictive formula in order to anticipate the number of WBC that the patient will obtain about 12 days after treatment, at the nadir of the counting. WBCnadir = 0.032404 x Age + 2.005 + WBCinitial x e(-0.009316 x AUC(PIRA,wb,ei) + 4.202265), WBC being expressed as x 10(3) cells/microl and AUC(PIRA,wb,ei) in ng/ml x h. In a second step, the validation of the prediction was carried out in 43 courses from 21 patients treated in the same conditions, for which WBC(predicted nadir) was compared by linear regression to WBCcounted. We obtained a highly significant correlation: r = 0.656; p<0.0001). Therefore, we show in this paper that the hematological toxicity, especially the WBC nadir count, can be predicted from single-sample blood HPLC analysis. This rapid and easy prediction of leukopenia can help the clinician in anticipating important hematological toxicities and in deciding to start early prophylactic treatment with hematopoietic growth factors.

Abdominal aortic aneurysm in a child with tuberous sclerosis.

Tuberous sclerosis is known to be associated with neurologic, renal and cardiac lesions. We report a case involving a child with tuberous sclerosis who developed infrarenal abdominal aortic aneurysm. Surgical therapy was successful. Although aortic aneurysm is uncommon in children with tuberous sclerosis, routine screening is necessary due to the high risk of death by rupture. Surgical treatment must be performed immediately.

[Chemical stability of pirarubicin in its use for continuous infusion]. / Stabilité chimique de la pirarubicine en vue de son utilisation en perfusion continue.

The aim of this study was to examine the chemical stability of pirarubicin in conditions close to ambulatory continuous infusions (infusor). The analyses were performed using an HPLC method in two infusion fluids (G5% and water), in different conditions of conservation (light and obscurity) and at different temperatures (+35 degrees C and +4 degrees C). The results demonstrated that light did not increase the chemical degradation of pirarubicin in doxorubicin which occurred more rapidly in G5% than in water. On the other hand, the temperature was a comparably major influence (> than 80% of deterioration in 7 days). In conclusion, the use of pirarubicin in continuous infusion (5 days infusors) is currently impossible without leading to a fast and important outcome of doxorubicin, which present different therapeutic activity and different toxicity.

Pedicled pericardium for repair of right ventricular outflow tract and pulmonary arterial stenoses in tetralogy of Fallot: a six-year experience.

From June 1988 through June 1994, 20 children with symptomatic tetralogy of Fallot, associated with hypoplastic or stenotic pulmonary arteries in 19 cases, were operated on in our institution. Mean age at operation was 49.5 +/- 43 months (ranging from 10 months to 12.5 years). Mean weight was 13.5 +/- 6.5 kg (range 6.2 to 30 kg) and mean body surface area was 0.6 +/- 0.2 m2. Mean preoperative hematocrit value was 47.6% +/- 11.1%, and mean preoperative arterial oxygen saturation ratio was 75.7 +/- 9.5. Six patients (30%) had prior systemic-pulmonary arterial shunts. Pulmonary arterial stenoses were congenital or iatrogenic (or both) and were located principally on the left pulmonary artery (63%), on the pulmonary bifurcation (15%), or separately on the left and right pulmonary arteries (21%). In all children the pulmonary arterial tree was repaired with the patient's own pedicled pericardium. Mean follow-up is 36 +/- 25.2 months (range 1 to 71 months). Hospital mortality rate was 0%. There was one late death, and two children were lost to long-term follow-up. No child required reoperation. Seventeen children returned for evaluation, consisting of physical examination, electrocardiogram, chest roentgenogram, and Doppler echocardiogram, and 11 underwent late catheterization or magnetic resonance imaging of the chest to evaluate the pulmonary arterial repair. All children were in New York Heart Association class I or II. Right ventricular function was normal by echocardiography in 100% with a mean right ventricular systolic pressure of 39.37 +/- 8.4 mm Hg. Mild to moderate pulmonary regurgitation was present in the majority of patients. The results of pulmonary arterial repair were good in 100%. There was no residual stenosis, and we observed uniform enlargement of the repaired pulmonary arteries over a 5-month to 6-year follow-up period. These results are of particular interest inasmuch as other materials previously used for repair of pulmonary arteries do not grow and may even shrink, resulting in residual stenosis.

Ten-year experience with surgical treatment of partial atrioventricular septal defect: risk factors in the early postoperative period.

Partial atrioventricular septal defects are electively repaired with good results. However, recent reports suggest that such repair is potentially a high-risk surgical procedure. Our aim was to determine the risk factors of adverse outcome early after surgical treatment of atrioventricular septal defects in our hospital. A retrospective study was done in 100 consecutive patients from 2 months to 50.6 years old (median 3.6 years) who underwent surgical correction between January 1984 and December 1993. An intermediate form of the lesion was noted in 31% of cases. Congestive heart failure occurred in 50% of cases. Preoperative left atrioventricular valve incompetence (moderate to severe) was present in 63% of patients. Severe abnormalities of left subvalvular apparatus were noted in 28% of patients. The cleft of the left atrioventricular valve was closed in 76% of cases. The study was done to determine risk factors associated with hospital mortality (13%), postoperative residual left atrioventricular valve incompetence (23%), and early reoperation (14%) within the first 30 postoperative days. Univariate analysis showed that age at the date of operation and cleft closure were not related to an early adverse outcome. A stepwise logistic regression with variables selected by univariate analysis identified infections and severe abnormalities of left subvalvular apparatus as predictive factors of early death (odds ratio, 28.07 and 6.18, respectively), preoperative left atrioventricular valve regurgitation as a predictive factor of residual postoperative left atrioventricular valve regurgitation (odds ratio, 5.34), and severe abnormalities of left subvalvular apparatus as a predictive factor of early reoperation (odds ratio, 5.27). These results emphasize the importance of the severity of the morphologic features of the left subvalvular apparatus, the occurrence of early postoperative infections, and the presence of residual left atrioventricular valve regurgitation as risk factors in the early period after surgical correction of partial atrioventricular septal defects.

"Classic" repair of congenitally corrected transposition and ventricular septal defect.

BACKGROUND: This study examined the results of "classic" repair of congenitally corrected transposition of the great arteries and ventricular septal defect. METHODS: From 1974 to 1994, 52 patients underwent a classic complete repair of lesions associated with congenitally corrected transposition. They were divided into two groups: ventricular septal defect plus left ventricular outflow tract obstruction (group I, 37 patients) and isolated ventricular septal defect (group II, 15 patients). Tricuspid plasty or replacement was performed primarily in 1 patient of group I (3%) and in 8 patients of group II (53%). RESULTS: The overall operative mortality was 15% (8/52 patients), and the incidence of postoperative atrioventricular block was 27% (14/52 patients). Eight patients died secondarily, 5 of heart failure. Survival rates were 83% +/- 6% at 1 year and 55% +/- 14% at 10 years for group I and 86% +/- 9% at 1 year and 71% +/- 12% at 10 years for group II (not significant). Redo tricuspid plasty or replacement was performed in 12 patients. CONCLUSIONS: Results of classic complete repair of lesions associated with congenitally corrected transposition are not satisfactory in our experience because (1) the operative mortality and the incidences of tricuspid valve replacement and atrioventricular block are high and (2) secondary heart failure is frequent. However, a retrospective review of morphologic findings shows that "anatomic" complete repairs would not have been feasible in 6 of our patients.

Donor-recipient size matching in pediatric heart transplantation: a word of caution about small grafts.

BACKGROUND: The increased shortage of donor organs led centers to extend the conventional donor criteria, particularly regarding donor-recipient size mismatching. Little information is available in the pediatric age group. METHODS: Between December 1987 and May 1994, 73 pediatric orthotopic heart transplantations were performed. Indications for heart transplantation included congenital heart defect (29 patients), cardiomyopathy (40 patients), valvular disease (1 patient), and retransplantation (3 patients). Patients ranged in age from 9 days to 18 years (mean: 5.7 +/- 5 years). The following factors were evaluated: cardiomyopathy, congenital heart disease, age, pretransplantation pulmonary hypertension, previous sternotomy, status at transplantation, donor to recipient weight ratio, graft ischemic time, degree of donor inotropic support, ABO compatibility, gender mismatch. RESULTS: The overall mortality rate before discharge (7 days to 4.5 months) was 27.4%. Donor heart failure occurred in 31.5%. Donor heart failure and early mortality were strongly correlated (p = 0.0002). Risk factors for donor heart failure were pretransplantation pulmonary hypertension (p = 0.024), donor/recipient ratio (p = 0.033), and major donor inotropic support (p = 0.034). Donor heart failure rate was 50% in donor/recipient ratio less than 1, 33% in donor/recipient ratio between 1 and 1.6, and 7% in donor/recipient ratio more than 1.6. Donor/recipient ratio less than 1 was the only significant risk of postoperative death by univariate (p = 0.0045) and multivariate (p < 0.01) analysis. CONCLUSIONS: Donor heart failure remains the main cause of early mortality in pediatric heart transplantation. The use of oversized donor may be beneficial, particularly in patients with pretransplantation pulmonary hypertension. The use of undersized donor grafts should be strongly discouraged.

A limited sampling strategy for the study of pirarubicin pharmacokinetics in humans.

Pirarubicin (4'-O-tetrahydropyranyldoxorubicin, THP-Adriamycin) is a new anthracycline antibiotic that has recently been developed because its reduced cardiac toxicity is associated with an antitumour efficacy similar to that of doxorubicin. Pirarubicin is characterised by strong haematological toxicity, which has been shown to be correlated with pharmacokinetic parameters, especially the area under the time-concentration curve. To obtain routine pharmacokinetic evaluations of pirarubicin for dose monitoring we developed a limited sampling strategy relying on three blood samples taken at the end of the infusion and at 12 and 24 h post-infusion. The characteristics of interindividual variability were assessed on the first courses of treatment performed in 18 patients; the model was then validated on 10 independent first courses of treatment performed in 10 other patients. The main pharmacokinetic parameters (half-lives, total volume of distribution, total plasma clearance) were estimated in the test group by maximum-likelihood estimation using all samples and by Bayesian estimation using three samples. The concordance between the two estimates was correct (the bias and precision for clearance were 2.3% and 12.1%, respectively), which shows that this limited sampling strategy can be used in routine drug monitoring.

Pharmacokinetics and metabolism of pirarubicin in humans: correlation with pharmacodynamics.

The pharmacokinetic monitoring of anthracycline-containing regimens is warranted because of the important toxicity of these drugs and because pharmacokinetic-pharmacodynamic relationships have been clearly established. We studied the pharmacokinetics of the new anthracycline pirarubicin in 80 courses of treatment performed in 27 patients, using a limited sampling protocol we had previously validated. We observed (for 47 of these courses) a significant correlation between the leucocyte cell kill and the pirarubicin area under the time x concentration curve, but the most significant correlation was obtained using the plasma concentration of doxorubicin, a metabolite of pirarubicin, at the end of the infusion. On the basis of this value, it is possible to predict for pirarubicin haematological toxicity in a way that can help the clinician in identifying patients at risk for toxicity.

[Risk factors of coronary graft disease following heart transplantation in children]. / Facteurs de risque de la maladie coronaire du greffon après transplantation cardiaque de l'enfant.

Coronary disease after cardiac transplantation is a major medium and long-term complication in adult patients. In childhood, this is reputed to be rare and, therefore, the authors undertook a study to evaluate its incidence and the role of potential risk factors in this age group. The study included 30 children followed up at least one year after cardiac transplantation and investigated by at least one selective coronary angiography after the first postoperative year. Seventeen patients (57%) had a normal coronary angiography but 13 had coronary lesions (43%). The two groups were compared for age, sex, HLA groups of the donor-recipient couple, the duration of ischaemia of the transplants, cytomegalovirus serology, lipid profile, number of episodes of acute rejection that were treated, the necessity for steroid therapy for more than 3 months, and the blood pressure. The only significant differences, probably inter-related, were the number of rejections treated, greater in the group with coronary lesions (2.23 +/- 1.01 per patient) than in the group with normal coronary arteries (1.53 +/- 1.01 per patient) (p < 0.05) and the necessity of triple therapy with addition of prednisone, greater in the first group (9/13) than in the second (4/17) (p < 0.02). These results show that coronary disease after cardiac transplantation is as common and as early in children as in adults. They strongly suggest an important role of immunological factors. On the other hand, the authors' experience did not confirm the role of other potential risk factors.

Surgical treatment of multiple ventricular septal defects using a biologic glue.

The closure of multiple ventricular septal defects remains a surgical challenge. Mortality and morbidity are high. Left ventricular incision and multiple patches or stitches impair septal motion and function. We searched for a method that would cause minimal left ventricular and septal dysfunction. The use of fibrin seal for closing ventricular septal defects was considered. The method was first tested in animals so as to assess the internal resistance of the fibrin seal to stretching and fragmentation in addition to its adhesiveness and hence the absence of left-to-right embolization of the fibrin seal clot and the long-term success of the ventricular septal defect closure further to complete resorption of the ventricular septal defect clot. This experimental work was very satisfactory. Between April 1986 and September 1991, 15 children were operated on with the use of this technique. The overall hospital mortality rate was 6%. There were no reoperations for residual ventricular septal defects. All the long-term survivors (n = 13) were in excellent clinical condition with no or trivial residual shunt attested by color flow mapping investigation. This experimental and clinical experience suggests that satisfactory results can be achieved with the use of fibrin seal for the closure of multiple muscular ventricular septal defects.

Arterial switch operation: a new technique of coronary transfer.

A successful outcome after arterial switch operation (ASO) for transposition of the great arteries (TGA) depends in large part on the adequacy of transfer of the coronary arteries to the neoaorta. The present paper describes a new technique of coronary transfer which was used in 43 patients: 28 neonates with TGA and intact septum (with coarctation in one), 10 neonates with TGA and ventricular septal defect (with coarctation in one), 2 children undergoing ASO after failed Senning operation and 3 patients with complex TGA. A standardized uniform technique of coronary transfer was used; this technique involved reimplantation of the two coronary ostia side by side after excision of a single button of neoaortic wall. Most coronary patterns were encountered: the usual pattern in 30, circumflex from right coronary artery in 7, inverted coronary arteries in 3, inverted circumflex and right coronary arteries in 3. There was no early coronary-related mortality or morbidity. One late death (3 months) was probably coronary-related. The overall coronary risk was 2.3% (70% confidence limits = 0.3%-7.5%). The proposed technique of coronary transfer can be used in most patients with TGA (all patients without coronary arteries running between the great arteries) and entails a low coronary risk.

Diffuse subaortic stenosis: modified Konno procedures with aortic valve preservation.

The Konno procedure provides adequate relief of diffuse subaortic stenosis but requires aortic valve replacement. This may be questionable in patients without aortic valve lesions. Eleven patients had diffuse subaortic stenosis and normal aortic orifice: tunnel subaortic stenosis (6 patients) or diffuse hypertrophic obstructive cardiomyopathy (5 patients). The mean age was 16 +/- 14 years (range: 3 months to 45 years). The mean subaortic gradient was 95 +/- 24 mmHg (range: 60 to 150 mmHg). Two patients had previously undergone resection of discrete subaortic stenosis. Modified Konno procedures were used: aortoseptal approach with aortic annulus division in 5 patients, conal enlargement without aortic annulus division in 6 patients. There was one early death (9%, 70% CL = 1%-27%) and no late deaths. Reoperation was required in two patients: one early for iatrogenic aortic regurgitation and one late for residual ventricular septal defect and mitral regurgitation. The mean follow-up was 3.8 +/- 4.2 years (range: 2 months to 10 years). The survivors were in functional class I (8/10), had a normal left ventricular function (9/10), were in sinus rhythm (10/10) and had left ventricular outflow tract gradients ranging up to 25 mmHg (mean = 6 +/- 10 mmHg). Residual surgery-related defects included ventricular septal defect (one) and aortic regurgitation (one). In patients with diffuse subaortic stenosis and normal aortic orifice, modified Konno procedures with aortic valve preservation are preferable, effective and can be safely performed in infants and children.

Anomalous left coronary artery from the pulmonary artery: results of isolated aortic reimplantation.

Thirty-one consecutive children with anomalous left coronary artery underwent direct aortic reimplantation of the anomalous artery without an associated procedure. There were five deaths (16%; 70% confidence limits, 9% to 26%), three in the hospital and two early (within 3 months). The severity of preoperative left ventricular dysfunction was the only incremental risk factor for mortality: 31% mortality rate among patients with left ventricular shortening fraction of less than 0.20 versus 0% among patients with a left ventricular shortening fraction of 0.20 or more (p = 0.03). There were no late deaths up to 6 years, a survival rate of 84% +/- 7%. Late results were studied in 23 survivors having a follow-up of longer than 12 months. Ninety-six percent were free of symptoms; left ventricular function recovered to normal in all patients; moderate to severe mitral regurgitation decreased to minimal or no regurgitation in most patients (5/7); and the reimplanted anomalous left coronary artery was patent in each patient. Based on this study, we reached five conclusions. (1) Direct aortic reimplantation is technically feasible in most patients with anomalous left coronary artery and yields a high rate of late patency. (2) Left ventricular resection is unnecessary. (3) The mitral valve should not be interfered with at the initial operation, but mitral regurgitation may persist in a few patients and necessitate later operation. (4) In patients with moderate left ventricular dysfunction, the operative risk is low and early operation indicated. (5) In patients with severe left ventricular dysfunction, the operative risk is high; heart transplantation may be suggested, but our current approach favors an immediate corrective procedure.