[Can we explain the sudden infant death syndrome? About a series of 80 cases with an autopsy in Rennes University Hospital, France in the period 1994-2007]. / Peut-on expliquer la mort inattendue du nourrisson? Réflexions à partir d'une série de 80 cas autopsiés au CHU de Rennes entre 1994 et 2007.

Sudden infant death syndrome (SIDS) is a huge hardship for parents, but also for health professionals. In 2007, 210 cases occurred in France, corresponding to a crude rate of 31.8 for 100,000 births. Between 1994 and 2007, 140 children of less than 2 years old were examined in the reference centre for SIDS in Rennes, France. We included in our study the children who were aged more than 28 days at death date, did not have a known lethal disease and were autopsied. A total of 80 children fulfilled those criteria. Post-mortem investigation included an autopsy, clinical and paraclinical exams (blood test, radiography, CT-scan...), and investigation of the circumstances of the death. Most of the cases were boys and were 2- to 5-month old. Ventral decubitus and gastrointestinal symptoms were often present. Autopsy gave elements about the causes of death in 23 cases and the other exams performed frequently showed an infectious viral context. Thanks to prevention and information campaigns about childcare done in the 1990s, SIDS incidence has largely decreased in France, but it is still too frequent. In our opinion, advice needs to be given again and again, especially concerning safe sleep practices, in order to increase adherence to these recommendations. Moreover, research should be continued to better understand this unexplained syndrome.

[Gliomatosis peritonei, an unusual abdominal carcinomatosis: report of two cases]. / La gliomatose péritonéale: un aspect inhabituel de carcinomatose: à propos de deux cas.

We report on 2 cases of ovarian teratoma associated with gliomatosis peritonei in 2 young girls aged 9 and 14 years. Gliomatosis peritonei is an unusual miliary-like peritoneal carcinomatosis of glial tissue. In our experience, follow-up was important to detect abdominal recurrence of glial implants, which had to be removed by iterative surgery. We report a 14-year follow-up and an unusual pleural metastatic disease.

[Value of transient elastography in noninvasive assessment in children's hepatic fibrosis]. / Intérêt de l'élastométrie impulsionnelle dans l'évaluation non invasive du stade de fibrose hépatique chez l'enfant.

AIM: Transient elastography (FibroScan) is a novel, noninvasive, rapid bedside method to assess liver fibrosis by measuring liver stiffness. This study aimed to determine the feasibility and reliability of liver stiffness measurement in children with liver diseases. PATIENTS AND METHODS: Liver stiffness measurements were carried out on 72 children, from 4 to 18 years of age, with potential hepatic fibrosis disease. The clinical, biological, ultrasonographic, and endoscopic parameters were noted to identify children with portal hypertension syndrome. The APRI (ASAT-to-platelet ratio index) test was calculated according to the standard formula. An APRI test score higher than 1.5 indicates significant hepatic fibrosis. METAVIR scoring from 14 liver biopsies was compared to the liver stiffness using the Kappa statistic. RESULTS: Twenty-eight patients had viral hepatitis, 20 cystic fibrosis, 16 chronic liver cholestasis, 5 autoimmune hepatitis, and 3 patients had liver fibrosis with uncertain etiology. FibroScan measurements were available in all children. There was good agreement between FibroScan and pathological studies (weighted kappa=0.814). Only 9 children had portal hypertension syndrome with an average measurement of liver stiffness significantly higher than children without portal hypertension (26.5kPa vs 6.4kPa; p<0.01). The APRI test for 6 out of 9 patients scored higher than 1.5. CONCLUSION: These results indicate that liver stiffness measurement is feasible in children and seems to be related to liver fibrosis. Larger prospective studies are needed to validate this FibroScan method.

Macrophage activation syndrome: an autopsy case of sudden death.

In a context of viral gastroenteritis, we report an unusual case of sudden death in an 8-year-old child. The only macroscopic abnormality observed in the autopsy was a diffuse mesenteric adenitis. Organ samples were taken for histopathological examination and a diffuse lymphocytic infiltration was observed. A sinusoidal histiocytic hyperplasia was found in the lymph nodes. Microscopic examination of the lungs and the lymph nodes revealed haemophagocytic lesions (lymphocytes within the cytoplasm of histiocytic macrophages). Immunohistochemical studies demonstrated that the histiocytes were CD68+ PS100- CD1A-. Following this microscopic examination macrophage activation or haemophagocytic syndrome was diagnosed. The syndrome is a distinct clinical entity characterised by fever, pancytopaenia, splenomegaly, and haemophagocytosis in the bone marrow, liver and lymph nodes. It is a clinical entity that is very difficult to diagnose due to the lack of specific clinical signs. It is generally a complication of an infectious process, an aggravation of an auto-immune disease or a complication of a neoplastic process. The physiopathology involves a disregulation of T lymphocytes and particularly T helper lymphocytes. To make this diagnosis the anatomopathological examination must be performed by an experienced practitioner. The presence of a lymphocyte infiltrate of macrophagic histiocytes in myeloid organs and especially positive CD68+ immune markers are the anatomopathological proofs of diagnosis. The autopsy examination must be carefully performed and include systematic sample harvesting for anatomopathological examination. The results of all these examinations taken together allow the diagnosis of haemophagocytic syndrome to be finally made.

Fluorescent in situ hybridization (FISH) on paraffin-embedded placental tissues as an adjunct for understanding the etiology of early spontaneous abortion.

OBJECTIVES: An investigation of first-trimester spontaneous abortions (SAs) for those cases in which karyotype is not available was designed to test the efficiency of fluorescence in situ hybridization (FISH) on paraffin-embedded tissues combined with pathological examination for understanding the etiology of SAs. METHODS: Pathological examination of 202 placental tissues from SAs was performed. FISH analysis was then carried out on paraffin-embedded tissue sections from the same abortion products with probes specific for chromosomes 13, 16, 18, 21, X, Y. RESULTS: FISH could be achieved in 196 cases (97%). After pathological analysis alone, the etiology of SAs was evoked in 40 cases. The suspected diagnosis was confirmed by FISH in 26 cases (13.2%). After combined pathological and FISH analysis, the etiology of SAs was identified in 83 from the 196 cases (42.3%) with the probe set used. CONCLUSION: The present study demonstrates the value of FISH on paraffin-embedded tissues as an adjunct for understanding the etiology of SAs for those cases in which karyotype is not available. Combination of pathological and FISH analysis increases the yield of diagnosis by a factor of 3.2. The results also demonstrate that predictions of the karyotype from pathological examination should be avoided.

[Hemorrhagic colitis in exclusively breast-fed infants]. / Colite hémorragique chez les nourrissons en allaitement maternel exclusif.

INTRODUCTION: Authors report clinical, biological and endoscopic data of six children aged less 3 months with bloody stools while they were exclusively breast-fed. RESULTS: Two girls and four boys aged 1 to 2 months presented with isolated but recurrent rectal bleeding. All were explored by fiberoptic rectosigmoidoscopy between 1 and 3,2 months. Macroscopic aspects were congestion (6 cases), petechial and ecchymotic (4 cases), with normal mucosal areas (5 cases). Histopathology showed eosinophilic infiltrates in all 5 children with rectal biopsy. Evolution was satisfactory after cow's milk protein exclusion in maternal diet for five children and after weaning in 1. All children were weaned with protein hydrolysate. Cow's milk protein were later introduced without adverse reactions at 6 to 23 months. CONCLUSION: Food allergy can be considered in proctocolitis including exclusive breast-fed children. Evolution after maternal diet is, as usual, simple.

The detection of Tel-TrkC chimeric transcripts is more specific than TrkC immunoreactivity for the diagnosis of congenital fibrosarcoma.

The t(12;15)(p13;q25) translocation, a recurrent chromosomal abnormality of congenital fibrosarcoma, leads to the expression of a Tel-TrkC fusion transcript. To determine whether detection of the chimeric protein may be helpful for the diagnosis of congenital fibrosarcoma, immunohistochemistry was performed with an anti-TrkC antibody on 26 spindle cell tumours of newborn or young children (n=19) or adults (n=7). Four out of five congenital fibrosarcomas showed TrkC immunoreactivity with cytoplasmic paranuclear staining. However, TrkC immunoreactivity was not restricted to congenital fibrosarcoma and was observed in infantile myofibromatosis, congenital haemangiopericytoma, desmoid tumour, nodular fasciitis, fibrous hamartoma, inflammatory myofibroblastic tumour, and adult fibrosarcoma. RT-PCR analysis was performed on nine cases, including four congenital fibrosarcomas, for which frozen material was available. Tel-TrkC transcripts were detected by RT-PCR in the four congenital fibrosarcomas analysed, but not in the five other spindle cell tumours. Furthermore, several Tel-TrkC transcripts encoding for kinase isoforms of the Tel-TrkC protein were detected in congenital fibrosarcoma and may be involved in oncogenesis. The reciprocal TrkC-Tel transcript was detected in only one congenital fibrosarcoma. While the detection of a Tel-TrkC fusion transcript is a recurrent feature of congenital fibrosarcoma, TrkC immunoreactivity does not appear specific for the diagnosis of fibromatous paediatric tumours.

Ex vivo and in situ PLGA microspheres uptake by pig ileal Peyer's patch segment.

We investigated the ability of pig ileal Peyer's patch segments to transport intestinal poly (D,L-lactide-co-glycolide) microspheres (PLGA MS) from intestinal lumen across the mucosae using in situ and ex vivo segments with confocal laser scanning microscopy (CLSM) and transmission electronic microscopy (TEM). From a global aspect, CLSM suggested that PLGA MS were translocated by M cells labelled with a FITC-conjugated anti-cytokeratin peptide 18, and transported through the follicle-associated epithelium (FAE) in the dome area in both types of experiments. At the ultrastructural level, TEM showed the traffic of PLGA MS throughout M cells, their transport into the basolateral invaginations of the M cells and their subsequent migration into the dome area and the follicular area in contact with macrophages and lymphatic vessels. Although in situ experiments allowed following the migration of PLGA MS until mesenteric lymph nodes, an ex vivo model could be used as a useful tool to study the targeting ability of PLGA MS formulations to the gut-associated lymphoid tissue (GALT).

Histological demonstration of haemosiderin deposits in lungs and liver from victims of chronic physical child abuse.

In the context of chronic physical child abuse, two entities have been described based on macroscopical and radiological criteria: the battered baby syndrome and the shaken baby syndrome. However, in some autopsy cases, clinico-radiological information may not be available. In these cases, histological examinations are necessary to look for sequelae of repeated haemorrhages, particularly in organs likely to have suffered traumatisms such as the lungs, or in organs belonging to the mononucleated macrophage resorption system, such as the liver and the spleen. We examined a series of 15 young children who died from proven chronic child abuse and compared them with 15 sex and age-matched control subjects who died from natural causes with no history of child abuse. Using Perl's stain for iron, we identified haemosiderin deposits in pulmonary, hepatic and splenic samples and the deposits were evaluated qualitatively and quantitatively. Haemosiderin deposits were significantly (P < 0.001) more abundant in the lungs and liver of the chronic abuse victims than in those of the control subjects. However, they were not significantly more abundant in the spleens of child abuse victims than in controls. We conclude that haemosiderin deposits in lungs and liver could be proposed as a marker for chronic physical child abuse. This study stresses the importance of systematic histological examination to look for pulmonary and hepatic haemosiderin deposits in cases in which chronic child abuse is suspected.

Induction of Fos protein expression in spinal cord neurons of tumour-bearing rats.

The absence of discernible abnormal symptoms such as pain, often leading to delayed diagnosis in cancer patients, may be indicative of a dysregulation in sensory transmission between the tumour and the central nervous system. We explored expression of Fos protein in spinal cord neurons in rats, during the development of the MAT-LyLu prostatic adenocarcinoma grafted on the hind limb. The tumour triggered the densest Fos labelling in the L3-L5 lumbar segments, ipsilateral to the grafted limb. The labelling, detected at day 5, increased until day 10 and dropped off thereafter. The ventral horn (except lamina IX) was the most densely labelled region. Histological examination of the grafted limbs demonstrated that no inflammatory reaction accompanied the tumour growth. Rats exhibited no behavioural alterations either spontaneous or induced by handling. These results demonstrate that signals are sent to the central nervous system by the peripheral tumour. Considering both the behavioural and histological observations, it is unlikely that spinal activity reflects a painful state. The nature of these signals, inefficient to trigger the appropriate reaction of the organism against the tumour, remain to be determined with regard to the pharmacologically active compounds synthesized and released by the tumour cells.

[Papillary fibroelastoma: a cardiac tumor rarely reported in children]. / Le fibroélastome papillaire: une tumeur cardiaque rare chez l'enfant.

Papillary fibroelastoma is a seldom reported tumour. It usually occurs in adults and develops on the aortic and mitral valves. It is not different of giant Lambl excrescences and differential diagnostic can be difficult with the myxoma. Its systematic surgical ablation is justified by the important risk of embolic complications. It has rarely been reported in children. We report a case peculiar by fortuitous diagnostic, tricuspid site, large size and occurrence in a 3-year old child.

Central nervous system malformations and early end-stage renal disease in oro-facio-digital syndrome type I: a review.

Intracerebral cysts and porencephaly or arachnoid cysts are rarely but are repeatedly reported in orofaciodigital (OFD) syndrome type 1. We report on 2 families in which OFD syndrome type 1 was observed with central nervous system (CNS) malformations and 3 sporadic cases of OFD with CNS defects, most likely representing fresh mutations for OFD 1. In one case, vermis hypoplasia was present; in another, periventricular heterotopiae were noted. We review the literature on CNS anomalies in OFD syndromes and stress the difficulties in genetic counseling and functional prognosis for children of OFD 1 female carriers prenatally diagnosed with a malformation of the brain. As for CNS malformations, renal cystic disease is an often overlooked complication specific to OFD 1. In 1 family, cystic medullary disease was noted in OFD 1 carriers, leading 1 patient to dialysis by age 35 years and the other to severe renal insufficiency by age 28 years. Longitudinal follow-up of OFD 1 carriers should be performed, and renal function should be assessed in those with cysts because the functional prognosis of this developmental anomaly may be worse than usually reported in the literature.

[Spontaneous abortion of male fetuses with incontinentia pigmenti (apropos of a family)]. / L'interruption spontanée des grossesses de foetus mâles atteints dans l'incontinentia pigmenti (a propos d'une famille).

We report a family with incontinentia pigmenti. One affected woman had seven pregnancies, seven miscarriages; a prenatal diagnosis by molecular biology was undertaken in the last four cases (two males, two females). In the last two males, a miscarriage occurred at the beginning of the second trimester with cystic hygroma in a case. In the first two males a miscarriage was observed also at the beginning of the second trimester after chorionic biopsy or amniocentesis. These two miscarriages would not be a complication of prenatal diagnosis but spontaneous abortion of an affected male. The date of the miscarriage of affected males (the beginning of the second trimester) and the role of a cystic hygroma for the diagnosis of incontinentia pigmenti in this mother of a fetus karyotyped 46,XY are discussed.

[Contribution of post mortem skull scanning for the study of sudden infant death]. / Contribution du scanner crânien post-mortem à l'étude de la mort subite du nourrisson.

BACKGROUND: Despite post-mortem examination and autopsy, many cases of sudden infant death (SID) remain unexplained. The aim of this study was to assess usefulness of CT-scan in the Sudden Infant Death Syndrome (SIDS). POPULATION: Twenty-three cases of SIDS had a post-mortem CT-scan evaluation of skull and brain. The pictures were retrospectively reviewed by several independent radiologists who were unaware of the circumstances of death and results of autopsy. RESULTS: Aspects of pneumatocele, probably due to lumbar puncture were found in 6 cases. The subarachnoid spaces appeared inexplically hyperdense, as they were not correlated to the results of lumbar puncture and autopsy. The ventricles were normal in size or density. Density of the dural sinuses (superfical and deep) was often increased, an aspect possibly artefactual, due to post-mortem thrombosis. The cerebral parenchyma was often slighty hypodense; microcalcifications due to congenital toxoplasmosis were found in one case. CONCLUSION: There was no correlation between the CT-scan imaging and the delay of death and lumbar puncture. Infants with or without subarachnoid hemorrage had the same CT scan findings. The CT-scan has a poor value when autopsy is performed; in its absence, it could be useful for diagnosing post-traumatic intracerebral hematoma.

Fetal ascites and oligohydramnios: prenatal diagnosis of a sialic acid storage disease (index case).

In a 20-year-old primiparous patient, a routine ultrasound scan performed at 28 weeks revealed fetal ascites, bilateral talipes, and oligohydramnios. This woman, married to possibly her first cousin, was at risk for an autosomal recessive disease, a metabolic disorder. At 29 weeks, an amniotic fluid biochemical study revealed the presence of an abnormal band of free sialic acid, leading to a diagnosis of a congenital form of sialic acid storage disease. Termination of pregnancy was performed at 30 weeks. Measurement of free sialic acid in cultured fetal skin fibroblasts confirmed the diagnosis.

[Langerhans cell granulomatosis of the orbit. Apropos of an anatomo-clinical case]. / Granulomatose à cellules de Langerhans monotissulaire de l'orbite. A propos d'une observation anatomo-clinique.

Langerhans' cell granulomatosis of the orbit was observed in a 7-year-old boy successfully treated by a simple biopsy. Recovery can be established one year after the biopsy on the basis of bone defect healing on the standard X-ray of the skull.

[Reflections on 10 years of medically induced abortions in Ille-et-Vilaine]. / Réflexions sur 10 ans d'interruptions médicales de grossesse (IMG) en Ille-et-Vilaine.

The medical files of 532 patients who underwent medically induced abortion over a 10-year period (1982-1991) in the French department of Ille-et-Vilaine were studied in order to evaluate the indications and outcomes. Among the patients, 358 resided in the department (67%). Comparatively with the number of births during the 10-year period, there was a relative increase in the number of medically induced abortions from 3.5/1000 to 5.5/1000. This parameter was taken into consideration for the interpretation of a parallel decrease in the perinatal mortality during the same period, from 5.9/1000 to 5.1/1000. There was a maternal indication in 91 cases which correspond to the former category of therapeutic induced abortions. There was a clear increase in 1991 corresponding to abortions induced because of extremely premature rupture of the membranes which were formerly allowed to continue to dead births. Foetal indications were frequent: 441 cases (83%). Exogenous causes were lower (15.6%), particularly due to the disappearance of indications resulting from maternal irradiation. For indications related to infection, the vaccination against rubella and improved prenatal diagnosis resulted in the disappearance of rubella as an indication during the last three years of the study and a clear decrease in the number of toxoplasmosis indications. There were few indications due to maternal infection by human immunodeficiency virus (4 cases). Chromosomal abnormalities were the main cause of medically induced abortion among the foetal indications (27.7%).(ABSTRACT TRUNCATED AT 250 WORDS)

[Orbital rhabdomyosarcoma in children. Apropos of 2 cases]. / Rhabdomyosarcome orbitaire de l'enfant. A propos de 2 observations.

Rhabdomyosarcoma accounts for 5% of childhood malignant tumours; in 10% it occurs in the orbit where it is the most frequent malignant tumour. Rhabdomyosarcoma is a mesenchymatous tumour with striated muscular differentiation. However, this myogenous differentiation is sometimes undiscernable on standard histological examination and requires immunohistochemical and ultrastructural studies to be shown. Treatment depends on the assessment of local extension, principally based on tomodensitometry. When the tumour is limited to the orbit, survival rate may reach 100% with todays therapeutic protocols. When the orbital walls are invaded the tumour is parameningeal and recovery can only be achieved by increasing chemotherapy at the cost of long-term side effects. Hence, this tumour must be diagnosed and treated very early. The authors report two cases of rhabdomyosarcoma dealing with the two main histological forms of the tumour and with their evolutive risks.

Renal cystic tumours in children--a diagnostic challenge.

A series of 8 cystic renal tumours is reported in seven-months to four-years-old children. The final diagnosis was cystic nephroma (multilocular cyst) in 4, cystic, partially differentiated nephroblastoma in 3 and partially cystic nephroblastoma in one. Pre-operative distinction between those three types is difficult and inadequate therapeutic approach may result from a wrong diagnosis. Progress in imaging techniques allows a better analysis of cysts and septa. If no solid part can be detected in the tumour, total nephrectomy is sufficient to obtain a favourable outcome.