French national diagnostic and care protocol for Kawasaki disease.

Kawasaki disease (KD) is an acute vasculitis with a particular tropism for the coronary arteries. KD mainly affects male children between 6 months and 5 years of age. The diagnosis is clinical, based on the international American Heart Association criteria. It should be systematically considered in children with a fever, either of 5 days or more, or of 3 days if all other criteria are present. It is important to note that most children present with marked irritability and may have digestive signs. Although the biological inflammatory response is not specific, it is of great value for the diagnosis. Because of the difficulty of recognising incomplete or atypical forms of KD, and the need for urgent treatment, the child should be referred to a paediatric hospital as soon as the diagnosis is suspected. In the event of signs of heart failure (pallor, tachycardia, polypnea, sweating, hepatomegaly, unstable blood pressure), medical transfer to an intensive care unit (ICU) is essential. The standard treatment is an infusion of IVIG combined with aspirin (before 10 days of fever, and for a minimum of 6 weeks), which reduces the risk of coronary aneurysms. In case of coronary involvement, antiplatelet therapy can be maintained for life. In case of a giant aneurysm, anticoagulant treatment is added to the antiplatelet agent. The prognosis of KD is generally good and most children recover without sequelae. The prognosis in children with initial coronary involvement depends on the progression of the cardiac anomalies, which are monitored during careful specialised cardiological follow-up.

Markers of a recent bocavirus infection in children with Kawasaki disease: "a year prospective study".

BACKGROUND: Retrospective studies and case-reports have suggested the possible role of various viruses in the pathogenesis of the Kawasaki disease. OBJECTIVES: To determine prospectively the incidence of Kawasaki diseases associated with a recent bocavirus infection in the course of a year. STUDY DESIGN: Thirty-two children with Kawasaki disease were enrolled in a 13 months prospective study to assess the frequency of human bocavirus type 1 infections. Seasonal shedding of virus, markers of recent infection such as viraemia, viral load, and serum interferon alpha were analyzed. RESULTS: Three of 32 (9%) children had HBoV-DNA in the serum suggesting a recent infection. HBoV-DNA was detected in naso-pharyngeal aspiration of 7/32 (21.8%) children with Kawasaki Disease and six of them (18%) had an increased viral load. No common respiratory viruses were isolated from the 32 patients with the exception of one adenovirus. The seven bocaviruses were identified during the winter-spring season. In addition, 4 of 7 of Kawasaki disease patients shedding bocavirus had detectable interferon alpha in the blood, indicating a possible active or recent viral infection. CONCLUSIONS: This study shows that a recent bocavirus infection is concomitant with the onset of some cases of Kawasaki disease. Bocavirus may be a cofactor in the pathogenesis of this disease as previously reported for other infectious agents.

Prenatal diagnosis of isolated total anomalous pulmonary venous connection: a series of 10 cases.

OBJECTIVES: To report on a series of 10 fetuses with prenatally diagnosed isolated total anomalous pulmonary venous connection (TAPVC), focusing on echocardiographic features leading to diagnosis, assess accuracy of prenatal diagnosis and describe postnatal outcome. METHODS: In this review of our experience of prenatal diagnosis of isolated TAPVC, we analyzed retrospectively medical records and fetal echocardiography findings in all cases with prenatal diagnosis of isolated TAPVC delivered between 1 January 2001 and 1 October 2011 at a tertiary referral center, paying special attention to echocardiographic signs that led to referral. RESULTS: During the study period, 95 infants with isolated TAPVC were seen at the center. Initially, expert fetal echocardiography identified 14 fetuses with isolated TAPVC. Prenatal diagnosis was made at a mean gestational age of 31 (range, 25-37) weeks. Ten true-positive cases of TAPVC were confirmed after birth. The remaining four were considered false-positive cases: two had normal heart with left superior vena cava to coronary sinus, one had partial anomalous venous connection and one was lost to follow-up. Of the 85 diagnosed postnatally with TAPVC, only one had been seen prenatally by an expert cardiac sonographer. Echocardiographic signs leading to referral were related to pulmonary venous connection in half of the cases. Other suspected defects which led to referral were ostium prium atrial defect (n = 3), left-right asymmetry (n = 1), abnormal mitral valve (n = 1) and hepatic vascular malformation (n = 1). All infants with TAPVC underwent surgery. There was one postoperative death and nine survivors, with a mean follow-up of 31 (range, 2-104) months. CONCLUSION: Fetal diagnosis of isolated TAPVC is challenging even for experts. Echocardiographic anomalies may appear late in gestation. New tools should be proposed to identify abnormal venous drainage at the screening level.

[Kawasaki disease: what you need to know]. / Maladie de Kawasaki : ce qu'il faut savoir.

Kawasaki disease (KD) is an acute systemic vasculitis syndrome occurring mostly in children younger than 5 years of age. Especially young infants (<1 year) have an increased risk of coronary artery lesions (CAL). Whereas the etiology of KD is still unknown, progress in treatment during its acute phase has decreased the incidence of CAL from 25-30% to 3-5%. In "atypical KD", the clinical picture is dominated by an unusual symptom as seizure, bloody diarrhea, compressive cervical adenopathy, nephrotic syndrome or hyponatremia. To make a diagnosis in case of "incomplete KD", the supplementary criteria (clinical and biological) suggested by the American Heart Association can be helpful. Once the diagnosis established, the treatment of choice is the intravenous administration of immunoglobulin associated to aspirin at anti-inflammatory dose. However, some patients remain feverish within 36 hours following the end of immunoglobulin administration. This treatment resistance seems increasing in some regions of the globe and can touch up 20% of patients. The unsatisfactory answer to the initial treatment is associated to a higher risk of CAL. Predictive criteria of resistance have been identified and allow to strengthen the medical treatment with a second administration of immunoglobulins. Moreover, methylprednisolone pulse therapy and tumor necrosis factor-alpha blockade (infliximab) appear to be interesting therapeutic options in the future. At last, other treatments have not been the object of controlled studies yet but are alternatives in refractory forms e.g. cytotoxic agents (cyclosporine A, cyclophosphamide, methotrexate), plasmapheresis, plasma exchange or abciximab, especially in patients with aneurysms. Sclerotic vascular changes are often observed in post-Kawasaki disease patients, including those without coronary lesions during the acute phase. Indeed, endothelial dysfunction and risk factors for the development of atherosclerosis, such as dyslipidemia, decreased vascular elasticity, increased C-reactive protein, oxidative stress, and inflammatory cytokines, are known to be present in the late phase of KD. However, it is not clearly established that the survivors of KD carry a higher risk of coronary disease. The epidemiological studies of the next decade should give clearer answers as far as these patients henceforth achieved the age of the atherosclerosis. In conclusion, the diagnosis of KD imposes a strict supervision by a pediatric cardiologist initially. The follow-up is organized according to the existence or non-existence of coronary artery lesions. Late complications as stenosis or coronary thrombosis can occur but remain rare. Thus, it is necessary to be reassuring with the parents, especially for those whose children had no or regressive CAL, while recommending a prevention of the cardiovascular risk factors in the adulthood.

[Vitamin K antagonist overdose induced blindness in an infant: an argument for a therapeutic educational program]. / Cécité secondaire à un surdosage en antivitamine K chez l'enfant : un argument pour l'éducation thérapeutique.

INTRODUCTION: Vitamin K antagonist (VKA) treatment is associated with significant risks and requires strict monitoring by measuring the international normalized ratio (INR), either by conventional methods or by self-measurement under medical supervision. We present a case of blindness occurring secondary to a moderate head injury, in a pediatric setting with no VKA therapeutic education. CASE REPORT: A 7-year-old child with a single ventricle had been operated on for a total cavopulmonary shunt at the age of 5 years. He took VKA therapy with an INR target between 2 and 3. After a head trauma, he had a frontal hematoma. His parents did not request a medical exam and did not check his INR. Six days after the injury, the INR was 2.23. The parents went to the emergency ward because the child had bilateral orbital hematoma. At admission, the INR was 5.6. The orbital hematoma was surgically evacuated in the emergency setting. Unilateral blindness occurred and remains a sequelae of the overdose. COMMENTS AND CONCLUSION: VKA treatment requires close supervision to prevent overdose, whose complications such as internal bleeding can have terrible consequences such as the case of blindness reported herein. This case report is a strong argument in favor of an educational program for children with VKA treatment.

[Neonatal atrial tachycardia: suggestive clinical sign of Costello syndrome]. / La tachycardie atriale néonatale : association non fortuite avec le syndrome de Costello. À propos de 2 cas.

Costello syndrome is a rare association of symptoms caused by de novo germline mutations of the HRAS oncogene interfering in the RAS/mitogen-activated protein kinase (MAPK) signal transduction pathway. Mutations in this pathway are also responsible for Noonan syndrome and the related cardiofaciocutaneous syndrome (CFC) as well as LEOPARD syndrome. The 4 syndromes share phenotypic resemblances concerning patients' morphology but also regarding associated cardiac disease, namely hypertrophic cardiomyopathy, pulmonary stenosis, and atrial septal defect. The electrocardiogram often shows an upper deviation of the QRS axis. Arrhythmias are rare but, if present, are particularly typical of CS. We describe herein two newborn infants with Costello syndrome revealed by atrial tachycardia associated with characteristic morphological and cardiac features of syndromes related to mutations in the RAS/MAPK pathway.

[Neurological complications revealing infectious endocarditis: 2 case reports]. / Complications neurologiques révélatrices d'une endocardite infectieuse : à propos de 2 cas.

Neurological signs are reported in less than 20% of infectious endocarditis (IE) cases. The most frequent complications include cerebral infarction, intracerebral hemorrhage, meningitis, and mycotic aneurysm. We describe two patients, one with congenital heart disease and the other with normal heart, who presented neurological manifestations and fever leading to an IE diagnosis. Neurological complications may be the first symptom of infectious endocarditis and are a major factor associated with increased morbidity and mortality. Early diagnosis and early treatment will minimize cardiac and neurological morbidities.

[Prognosis of atrioventricular canal in euploid foetus without abnormality of atrial situs]. / Pronostic des canaux atrioventriculaires chez les foetus euploïdes sans anomalie du situs atrial.

Atrioventricular septal defects are commonly diagnosed during fetal life. Postnatal prognosis of atrioventricular septal defects associated with trisomy 21 and with heterotaxia sequences are relatively well known. However, predicting postnatal outcome in fetus with atrioventricular septal defects and normal chromosome and normal atrial situs remains a challenge. In a series of 141 fetal atrioventricular septal defects, we analyzed 80 fetuses with normal karyotype. Twenty-seven had an abnormal atrial situs. One fetus was lost for follow-up. Finally, 52 fetuses were included in the study. Termination of pregnancy was performed in 18 cases (34%). Six fetuses died in utero (18% of ongoing pregnancies). Twenty eight infants were born alive, 2 of them were lost for follow-up right after birth and 3 live born infants died postanatally (11%). Postoperative mortality was 3/15 (20%). Complete repair was proceed for 13 infants, palliative repair for 2; and 8 infants didn't have surgery at the end of follow-up because of partial or intermediate atrioventricular septal defect. The only factor significantly associated with poor outcome was the small size of the left ventricle. Isolated atrioventricular septal defects are of poor cardiac prognosis particularly when associated with left heart obstructions.

[Molecular aspects of congenital heart diseases]. / Bases moléculaires des cardiopathies congénitales humaines.

Significant advances in the understanding of the molecular and genetic basis of congenital heart disease have emerged from gene inactivation studies in mice and from human genetic investigations. The identification of genes for heart defects have led to a clinical approach of these malformations in children and their families. These progresses have been made with the help of molecular biology as well as with the analysis of mouse models. Paediatric cardiologists have improved their efficiency in defining cardiac phenotypes but the genetic heterogeneity has made the molecular approach of a given defect difficult. In this review, we summarize different genetic causes for congenital heart disease and we highlight relevant genetic data for cardiac development in animal models.

[Left heart defects and genetics]. / Malformations obstructives du coeur gauche et génétique.

The obstructive cardiac defects of the left heart are an heterogeneous group of malformations. These past years their molecular bases have been partially understood. The associated chromosomal anomalies are mainly represented by the Turner syndrome, the microdeletion of the chromosome 11q and the 7q23 deletion in Williams syndrome. In isolated obstructive left heart diseases, new insights into their genetic bases have been made because the dominant inheritance has been demonstrated and the notion of a phenotypic continuum between bicuspid aortic valve and the complete form of hypoplastic left heart has been proposed. Finally, mutations in genes involved in heart development, namely NKX2.5 and NOTCH1, have been identified in these defects and support the former hypotheses. The low penetrance and the variable expression of these known mutations did not completely solved prenatal genetic counselling.

Late coronary complications after arterial switch operation for transposition of great arteries. Clinical and therapeutic implications.

The arterial switch operation is the procedure of choice for correction of transposition of the great arteries. Although offering excellent long term results, this procedure is burdened by the risk of acute and subacute coronary occlusion. No guide-lines exist for the management of acute or chronic ischemia in this setting. We briefly review the literature and present the results of our institution.

[Intra-uterine inseminations with hyperstimulation in male infertility]. / Inséminations intra-utérines avec hyperstimulation dans les indications masculines.

Our aim is to evaluate the efficacity of intrauterine insemination in male infertility after controlled ovarian hyperstimulation. 96 cycles were carried out. 16 pregnancies were achieved, the pregnancy rate per cycle is 16.7% (43.3% per couple) and 12.5% ongoing pregnancies. Six cycles were proposed and the higher cumulative probability of pregnancy is obtained at the 4th cycle. The best pregnancy rate per cycle is obtained with 5.10(6) to 10.10(6) inseminated. The success rate is not associated with the number of sperm abnormalities in our study.

[Value of karyotype in psychiatry: the 3-D syndrome (dysthymia-dysgonosomia-deterioration). First clinical, cytogenetic, anatomical correlation]. / Intérêt du caryotype en psychiatrie: le syndrome 3-D (dysthymie-dysgonosomie-détérioration). Première confrontation clinique, cytogénétique et anatomique.

The systematic study of the karyotype in Adult Psychiatry reveals among the group of periodical psychoses the existence of the 3-D Syndrome, marked by long clinical cycles, a course towards a dementia, the presence of a X-dysgonosomy with mosaicism, a relative and better clinical response with the use of lithium than with the use of tricyclic antidepressants. These characteristics discriminate the 3-D syndrome from the periodical manic depressive psychosis, which neither includes the course towards a dementia nor does it include until now identified cellular abnormalities. From the anatomical point of view the brain is quasi-normal, when the ultimate phase is a dementia. The 3-D Syndrome seems to be linked with a phenomenon of chromosomal instability. The caryotype takes a part among the usual biological tests in psychiatry.

[Value of a meiotic study of male sterility]. / Intérêt d'une étude méiotique dans les stérilités masculines.

Both in men where the somatic karyotype is abnormal as well as in cases where it is normal, it is worth while studying meiosis in the male. The picture of meiosis has been studied in the main from testicular biopsies and also partly from spermatic line cells found in sperm. Studying the haploid portion of the male pronucleus using the hamster test reflects the process of meiosis. In this way it has been possible to individualise different pathological entities such as asynapsis or desynapsis, alterations in synaptic complexes, the presence of several nucleoli or micronucleoli in the pachytene stage, hyper or hypo polidies, the presence of univalents and the breakdown of bivalents, oligochiasmatasis, chain or ring pictures or early desynapsis of the sexual vesicle in the diacinesis and in the first metaphase stage. Aneuploidies have been found in the second metaphase stage or when carrying out chromosome analysis on the male pronucleus. The abnormalities in the number of chromosomes which are found with the formula 47,XXY, may be due to faults in spermatogenesis, but in the case of the double Y in 47,XYY the extra Y will rarely be found during meiotic divisions. The Robertsonian translocations causing abnormalities in structure are due to the formation of trivalents whereas reciprocal translocations give rise to the idea of quadrivalent pictures mainly associated with faults in spermatogenesis. Finally, autosomal chromosome translocations seem to have more severe meiotic repercussions, particularly in cases where the inactive autosomal X chromosome is involved. Even where a somatic karyotype is normal in a fertile subject that does not mean that there is no meiotic abnormality present, because 8-10% of the cells that were studied showed such an abnormality.

Chromosomal changes in a documented case of malignant histiocytosis: significance of polyploidy.

A case of malignant histiocytosis was studied by cytology, cytochemistry, electron microscopy, and cytogenetics. It was shown that the malignant cells expressed a fully differentiated histiocytic pattern with high macrophagic activity. This correlated with the presence of polyploid metaphases. The significance of polyploid cells in the definition of malignant histiocytosis is discussed.

[Does ultrasound have an adverse effect on the fertility of women?]. / Les ultrasons ont-ils un effet nocif sur la fécondité des femmes?

Fifty women who were subfertile received artificial insemination from donors (A.I.D.) with ultrasound monitoring of ovulation. They were compared with an identical number of women who were inseminated without ultrasound control. The series side by side showed that there was a lower fertilisation rate in those who were monitored (4.2% compared with 6.2%) per month on an average over six months as compared with those who were not monitored by ultrasound, and those who were monitored took significantly longer to become pregnant than those who were not monitored. Because of these results the authors wonder whether ultrasounds are harmful for ovulation.

[A peripheral biological marker of organicity. Chromosome mosaic anomalies in general psychiatry]. / Un marqueur biologique périphérique d'organicité. Les anomalies chromosomiales en mosaïques en psychiatrie générale.

During February 1979 to December 1982 we studied the karyotype of 706 psychiatric adult patients without making a clinical selection. We found a chromosomial mosaïc aberration in 37 cases, concerning one leukocyte mitosis for ten studied cells : so a proportion of 5.2% cases. There do not exist statistics concerning the general population's mosaïc aberrations but in the same population the proportion of the homogeneous aberrations is near 0.5%, so 10 times lower than the proportion that we observed. The largest number of aberrations found concern the gonosomes, essentially some monosomics 45,XO or some trisomics 47,3X, among women who present a maniac depressive psychosis or another type of depression.