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Biomedical subjects

C Rambaud

Publications and source records attributed to C Rambaud.

At least 19 recordsLinked to original sources

[Pediatric autopsy and informed parental consent].

AIM: In French legal terminology, the definition of autopsy is "organs'withholding". This phrase is ambiguous, meaning both removing the organs for their macroscopic exam and their retention for subsequent histology. The autopsy of a child requires an informed consent from both parents. The issue is that the pathologist who performs the autopsy is not the one who delivers the information and gets the parents' consent: therefore, he does not know what they were told and what they actually agreed upon. MATERIALS AND METHODS: A questionnaire was sent to 3 groups of paediatricians (N=891) to approach their knowledge regarding autopsy. RESULTS: Among 362 paediatricians who answered the questionnaire, 57.2% never attended an autopsy and procedures were badly known. They did not know whether or not organs, were systematically sampled especially brain. Regarding the possibility of conservation of organs, a majority thought that one should not solely answer to parents'queries (63.8%) but rather that one should point out every possibility, without giving the ins and outs (60.8%). The majority favoured organs retention and use for research. CONCLUSION: We make 3 suggestions: to register autopsy in the Natioanal Securite Sociale nomenclature, to establish information and consent forms for organs'removal, retention and disposal, and to offer parents the possibility of an interview with the pathologist before and/or after the autopsy, in association with the paediatrician.

Autopsy↗

[Sudden death of a two-year-old boy with influenza A virus infection: study of an autopsy case].

UNLABELLED: Influenza A virus infections are common in childhood and infancy and are often underdiagnosed while serious or lethal forms are rare. CASE-REPORT: We describe a case of sudden death in a two-year-old boy. Pathologic findings at autopsy were consistent with Myxovirus influenzae A virus infection and the virus was isolated by post mortem PCR. CONCLUSION: In the case of sudden death in infants, especially if pathologic findings are compatible with a viral infection, PCR may allow identification of the causative virus.

Autopsy↗

A model of pulmonary adenocarcinoma in transgenic mice expressing the simian virus 40 T antigen driven by the rat Calbindin-D9K (CaBP9K) promoter.

Lung cancer is the most frequent cause of cancer deaths. Its origin and development remain poorly understood, partly because of the lack of pertinent animal models. This study produced transgenic mice expressing the simian virus (SV) 40 T antigen (Tag) driven by a 1011 base-pair DNA fragment of the rat Calbindin-D9K (CaBP9K) promoter. All transgenic animals developed multifocal pulmonary tumours with pathological and ultrastructural features consistent with adenocarcinomas. Using immunohistochemistry, northern blot or western blot, tumours were found to express the transcription factor TTF-1, as well as specific markers of the peripheral airway Clara cells (CC10) and alveolar type II cells (surfactant proteins A, B, C, and D). This model, with its similarities to human adenocarcinoma, should be useful not only for addressing the mechanisms underlying the development and progression of lung cancer, but also for testing new therapeutic approaches.

Adenocarcinoma↗

Fetal magnetic resonance imaging (MRI) of ischemic brain injury.

The aim of the present study was to demonstrate the usefulness of fetal magnetic resonance imaging (MRI) in ischemic brain injury. We report seven cases of fetal brain ischemia prenatally suspected on ultrasound (US) and confirmed by fetal MRI. Sonographic abnormalities included ventricular dilatation (n=3), microcephaly (n=1), twin pregnancy with in utero death of a twin and suspected cerebral lesion in the surviving co-twin (n=3). MRI was performed with a 1.0 T unit using half-Fourier acquisition single-shot turbo spin-echo (HASTE) sequences between 28 and 35 weeks of gestation. US and MRI images were compared with pathologic findings or postnatal imaging. MRI diagnosed hydranencephaly (n=1), porencephaly (n=2), multicystic encephalomalacia (n=2), unilateral capsular ischemia (n=1), corpus callosum and cerebral atrophy (n=1). In comparison with US, visualization of fetal brain anomalies was superior with MRI. The present cases demonstrate that MRI is a valuable complementary means of investigation when a brain pathology is discovered or suspected during prenatal US.

Brain↗

Late-onset cystic periventricular leukomalacia in premature infants: a threat until term.

The purposes of this study are (1) to describe a "late-onset" form of cystic periventricular leukomalacia eventually appearing in premature infants whose neurological assessments were normal in the first month of life; (2) to retrospectively evaluate its incidence among a large population of premature infants; (3) to suggest that a few unexpected complications of prematurity may trigger the development of white matter damage, even several weeks after birth. Retrospective study in a population of 1452 surviving infants after 5 days born before 33 weeks. We identified 10 cases of late-onset cystic periventricular leukomalacia appearing beyond the first 5 weeks of life. In 8 cases, an intercurrent event associated with a systemic inflammatory response preceded the appearance of cysts: necrotizing enterocolitis (n = 5), septicemia (n = 2 cases), strangulated inguinal hernia in one infant. Neurological surveillance should be repeated until discharge in very preterm infants, especially after the occurrence of an intercurrent complication coming along with a systemic inflammatory response.

Age of Onset↗

Jeune syndrome and liver disease: report of three cases treated with ursodeoxycholic acid.

Three children with Jeune syndrome (asphyxiating thoracic dystrophy) had clinical and laboratory evidence of liver disease. In two patients the disease evolved to biliary cirrhosis, whereas in the third it was recognized when extensive fibrosis was developing. In the three patients, treatment with ursodeoxycholic acid appeared to control the progression of the hepatic dysfunction.

Alanine Transaminase↗

Microbiology in sudden infant death syndrome (SIDS) and other childhood deaths.

The usefulness of post-mortem microbiology in the assessment of sudden unexpected deaths in infants and children has been debated by many pathologists. In our centre, microbiological investigations have been part of the post-mortem protocol for investigation of sudden deaths in infants and children for the past 12 years. The objective of this study was to review the microbiological findings for infants and children examined by our unit during the past 4 years in relation to gross and histological findings of the autopsy and the medical and social histories of the children. We reviewed 57 consecutive sudden deaths in infants and children examined by our Referral Centre between November 1994 and October 1998. These 57 sudden deaths were aged from 1 day to 4 years and 9 months including 40 cases of sudden infant death syndrome (SIDS) and 17 non-SIDS deaths. Results of the microbiological investigations of tissues and body fluids were assessed during the case review with reference to histological shock signs, severe gastric aspiration, and signs of acute thymic involution. Bacteria alone or in association with viruses were identified in 45/57 (79%) cases including 34/40 (85%) SIDS. The most frequent bacterial isolate was Escherichia coli (27), and the virus identified most frequently was enterovirus (8). C-reactive protein was increased in 10 out of the 42 cases tested including 8/32 (25%) SIDS. Significant gastric content aspiration was found in 17/57 (29.8%) including 13/40 (32.5%) SIDS. Histological signs of shock were present in 33/55 (60%) cases including 22/39 SIDS (56.4%). The microbiological findings were positive for 27/33 (81.8%). We conclude that post-mortem microbiology is essential in sudden death investigation. The conclusion that a death is unexplained if no microbiology was done is not valid, even if in some cases it may be difficult to know precisely in what way the pathogen contributed to the death.

Autopsy↗

Detection of pyrogenic toxins of Staphylococcus aureus in sudden infant death syndrome.

It has been suggested that pyrogenic toxins of Staphylococcus aureus are involved in the series of events leading to some cases of sudden infant death syndrome (SIDS). The objectives of the study were to screen tissues from SIDS infants for pyrogenic toxins and to compare incidence of identification of these toxins among these infants from different countries. An enzyme-linked immunosorbent assay (ELISA) and a flow cytometry method were used to screen body fluids and frozen or formalin-fixed tissues for pyrogenic toxins of S. aureus, toxic shock syndrome toxin 1 (TSST), staphylococcal enterotoxins A (SEA), B (SEB), and C1 (SEC). Toxins were identified in tissues of 33/62 (53%) SIDS infants from three different countries: Scotland (10/ 19, 56%); France (7/13, 55%); Australia (16/30, 53%). In the Australian series, toxins were identified in only 3/19 (16%) non-SIDS deaths (chi2 = 5.42, P < 0.02). The flow cytometry method was useful for toxin detection in both frozen and fixed tissues, but ELISA was suitable only for frozen tissues or those fixed for less than 12 months. Identification of pyrogenic toxins in > 50% of SIDS infants from three different countries indicated further investigation into the role the toxins play in cot deaths might result in development of additional measures to reduce further the incidence of these infant deaths.

Bacterial Toxins↗

Blind protected specimen brush and bronchoalveolar lavage in ventilated children.

OBJECTIVE: To determine whether nonbronchoscopic protected specimen brush (PSB) and bronchoalveolar lavage (BAL) are contributive for diagnosing ventilator-associated pneumonia in mechanically ventilated children. DESIGN: Prospective study. SETTING: Fifteen-bed pediatric intensive care unit in a university hospital. PATIENTS: A total of 103 mechanically ventilated children, ranging in age from 7 days to 8.8 yrs, most with a high clinical suspicion for bacterial pneumonia. INTERVENTIONS: All the children underwent nonbronchoscopic PSB and BAL. Nonbronchoscopic PSB was performed with a plugged double-sheathed brush and BAL with a double-lumen plugged catheter. Endotracheal secretions and blood cultures were also collected. Open-lung biopsy was performed for any child who died within 7 days after the inclusion in the study, according to the parental consent. MEASUREMENTS AND MAIN RESULTS: The PSB specimens were submitted for bacteriologic quantitative culture (positive threshold, 10(3) colony-forming units [cfu]/mL). The BAL samples were processed for microscopic quantification of the polymorphonuclear cells containing intracellular bacteria (positive threshold, 1%) and quantitative culture (positive threshold, 10(4) cfu/mL). According to diagnostic categories based on clinical, biological, radiologic, and pathologic criteria, 29 children had bacterial pneumonia and 64 did not Ten children were classified as having an uncertain status. Of the 29 children with bacterial pneumonia, 26 (90%) met one of the following three criteria: a) PSB specimen culture, > or =10(3) cfu/mL; b) intracellular bacteria in cells retrieved by BAL, > or =1%; and c) BAL fluid culture, > or =10(4) cfu/mL. In contrast, 56 (88%) of the 64 patients without pneumonia did not. CONCLUSION: The results of this study indicate the following: a) nonbronchoscopic PSB and BAL were feasible in a large population of mechanically ventilated children; b) nonbronchoscopic techniques were contributive for diagnosing ventilator-associated pneumonia in children; and c) a combined diagnostic approach, using nonbronchoscopic PSB and BAL, was superior to using either test alone.

Bacteria↗

Vitamin A decreases the incidence and severity of nitrofen-induced congenital diaphragmatic hernia in rats.

Congenital diaphragmatic hernia (CDH) is a major cause of refractory respiratory failure in the newborn. Pulmonary hypoplasia often limits survival. Vitamin A (Vit A) is an important signal for lung growth. We hypothesized that antenatal treatment with Vit A would stimulate lung growth and decrease mortality in experimental CDH induced in rats by ingestion of the herbicide nitrofen (2, 4-dichlorophenyl-p-nitrophenyl ether). Nitrofen was administered to pregnant rats on day 12 of gestation (term 22 days). Rats were assigned to five groups: three groups received one dose of oral antenatal Vit A (15,000 IU) before (day 10), concomitant with (day 12), or after (day 14) nitrofen administration; one group received only nitrofen; and a control group received vehicle (olive oil). The incidence of CDH was markedly lower in all groups receiving Vit A (day 10, 44%; day 12, 20%; and day 14, 40%) compared with the nitrofen-treated group (84%; P < 0.05). The 72-h survival was higher in all 3 Vit A-treated groups (day 10, 40%; day 12, 58%; and day 14, 70%) compared with the nitrofen-treated group (16%; P < 0.05). Lung-to-body weight ratio and radial saccular count were significantly increased by Vit A. Antenatal treatment with Vit A lowers the incidence and severity of experimental CDH and increases lung growth and maturation.

Animals↗

Autoradiographic distribution of brainstem substance P binding sites in humans: ontogenic study and relation to sudden infant death syndrome (SIDS).

The precise distribution of substance P (SP) binding sites in the human brainstem was investigated in normal cases (3 fetuses and 24 new-borns) and in 9 cases of Sudden Infant Death Syndrome (SIDS) by in vitro quantitative autoradiography. We discussed the widely but uneven distribution of SP binding sites as regards to the role of SP in brainstem cardio-respiratory ontogenic control and its possible involvement in SIDS.

Autoradiography↗

Segregation of the G8993 mutant mitochondrial DNA through generations and embryonic tissues in a family at risk of Leigh syndrome.

We identified the T8993G mitochondrial mutation in a female infant who died of Leigh syndrome. The proportion of mutant mitochondrial DNA increased to near homoplasmy in three generations of the pedigree. A similarly high proportion of mutant mitochondrial DNA was found in the chorionic villi and in fetal tissues from a pregnancy interrupted because of the risk of Leigh syndrome. This study supports the concept that prenatal diagnosis can be used for Leigh syndrome with the T8993G mitochondrial DNA mutation.

Abortion, Therapeutic↗

Prenatal diagnosis of neural tube defect before 12 weeks' gestation: direct and indirect ultrasonographic semeiology.

We describe the direct and indirect ultrasonographic features of a case of lumbar open spina bifida. The spinal defect was the prominent feature at 10 weeks + 5 days' gestation; however, cranial signs including narrowing of the frontal bones and flattening of the occiput were helpful at 12 weeks. This 'acorn' sign is likely to precede the 'lemon' sign, describing scalloping of the frontal bones at a later gestation. The diagnosis of spina bifida was confirmed by electrophoresis of the amniotic fluid, which showed an abnormal migration of acetylcholinesterase. Postmortem ultrasound examination of the same fetus proved useful in refining the diagnosis and also revealed the presence of the Arnold-Chiari malformation. Development of ultrasound screening in the first trimester of pregnancy should allow further evaluation of these findings. It seems reasonable to confirm such an early diagnosis by electrophoresis of the amniotic fluid as an alternative to ultrasonographic confirmation at 13-14 weeks.

Acetylcholinesterase↗

Interaction of Neisseria maningitidis with the components of the blood-brain barrier correlates with an increased expression of PilC.

A fatal untreated case of fulminant meningococcemia was examined to investigate the crossing of the blood-brain barrier (BBB) by Neisseria meningitidis. Microscopic examination showed bacteria in vivo adhering to the endothelium of both the choroid plexus and the meninges. Comparison of the isolates cultivated from the blood and the cerebrospinal fluid (CSF) revealed no antigenic variation of the pilin or the class 5 protein, whereas the expression of the PilC protein was greater in the CSF and the choroid plexus than in the blood. This was due to an increased activity of one of the pilC promotors. This higher expression of PilC correlated in vitro with greater adhesiveness to endothelial cells. A mutation in the single pilC locus of this strain abolished in vitro pilus-mediated adhesion to endothelial cells. These data suggest that PilC plays an important role in the crossing of the BBB, likely through pilus-mediated adhesion.

Bacterial Adhesion↗

Cd1a-positive cells in bronchoalveolar lavage samples from children with Langerhans cell histiocytosis.

We evaluated CD1a-positive cells in bronchoalveolar lavage samples from children with Langerhans cell histiocytosis (LCH). All children with multifocal LCH and pulmonary symptoms scored higher than 5% (30.6% +/- 7.2%), whereas those with other lung disorders scored much less than 5%. In children with multifocal LCH, bronchoalveolar lavage fluid abnormalities can precede pulmonary symptoms. During chemotherapy the CD1a-positive cell count lends to decrease.

Adolescent↗

Regional distribution of substance P binding sites in the brainstem of the human newborn.

The distribution of [3H]substance P ([3H]SP) binding sites in the brainstem of the human newborn was investigated in eleven cases (aged 1 h to 6 months) by in vitro quantitative receptor autoradiography. The binding of [3H]SP to newborn brainstem tissue was found to be saturable (for the eight cases examined, Kd and Bmax (M +/- S.E.M.) were 0.29 +/- 0.03 nM and 206 +/- 21 fmol/mg tissue, respectively). Competition studies showed unlabeled SP to be the most potent peptide for displacing [3H]SP binding from tissue sections. The desaturating effect of GTP on the specific binding of [3H]SP was also investigated, but was not found to be significant. Autoradiographic analysis showed that the neurokinin-1 (NK-1)/SP binding sites were widely but unevenly distributed, and that they varied with age. The highest densities of (NK-1)/SP binding sites were observed in the locus coeruleus, olivaris inferior nuclei, raphe magnus and obscurus nuclei, while low to moderate densities were observed in other brainstem structures. These findings support the idea that SP is involved in cardiovascular regulation, and that it may interact with the catecholaminergic and/or serotonergic system.

Autoradiography↗

Molecular identification of viruses in sudden infant death associated with myocarditis and pericarditis.

A subset of infants dying suddenly and unexpectedly have myocarditis with or without pericarditis found at autopsy. To address whether viruses known to cause infantile myocarditis and pericarditis might be present in such infants, we examined myocardium, liver and skeletal muscle for the presence of genomic sequences from adenovirus, cytomegalovirus, enterovirus and echovirus 22/23 in infants enrolled in a comprehensive evaluation protocol. We studied eight infants who died suddenly and unexpectedly with histologic evidence of myocarditis and/or pericarditis detected at postmortem examination. One infant with myocarditis and pericarditis had adenovirus genome detected in the myocardium. In an additional infant with severe pericarditis alone, enterovirus genome was detected in the liver. Although echovirus 22/23 has been associated with myopericarditis in young infants, no previous studies have used molecular methods to search for the genomic sequences of these viruses in clinical samples. No echovirus 22/23 genome was detected in the patients reported here. The significance of enterovirus and adenovirus genome in the tissues of two patients dying suddenly and unexpectedly remains speculative but raises the possibility that pathogenic viruses may cause little or no clinical symptoms and yet be contributory to sudden death in young infants.

Adenoviridae↗