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Biomedical subjects

F Leclerc

Publications and source records attributed to F Leclerc.

At least 55 records · Page 3Linked to original sources

Are there specific haemostatic abnormalities in children surviving septic shock with purpura and having skin necrosis or limb ischaemia that need skin grafts or limb amputations?

UNLABELLED: More than 10% of children surviving septic shock with purpura have skin necrosis or limb ischaemia (SNLI.). Among 44 children consecutively admitted to our pediatric intensive care unit, 35 (80%) survived, 6 of them (17%) developed SNLI (defined as the need of a surgical procedure). Two timed haemostasis measurements included the determination of coagulation factors, protein C (PC), protein S (PS), C4b binding protein (C4bBP), antithrombin (AT), and plasminogen activator inhibitor 1 (PAI-1). Two severity scores and CRP levels were determined at admission. Children with SNLI and without SNLI were compared. On admission, severity scores, and AT, PC, PS, C4bBP levels were similar in both groups with and without SNLI. Prothrombin time (23% vs 34%; P < 0.01), factor VII+X (20% vs 31%; P = 0.05) and factor VII (0% vs 19%; P < 0.01) were lower in the group with SNLI. The 2nd sample showed no difference between the two groups. Kinetics of haemostatic abnormalities were no different between the two groups. CONCLUSION: In this series, the only difference between the two groups was lower factor VII levels in children with skin necrosis or limb ischaemia. This suggests the benefit of tissue factor pathway inhibitor administration as an adjunctive therapy to prevent skin necrosis or limb ischaemia. Further studies including more children are needed to determine the potential effects of treatments such as protein C, antithrombin, and plasminogen activator inhibitor antibody administration, and to advocate tissue factor pathway inhibitor in preventing skin necrosis or limb ischaemia.

Adolescent↗

[Pneumothorax revealing cystic adenomatoid malformation of the lung in a 13 year old child].

CASE REPORT: A 13 year old boy had a seven day history of chest pain and dyspnea. His right hemithorax was immobile with abolished breathing sounds. Initial chest X-ray revealed a right tension pneumothorax. A chest tube was inserted and the right lung re-expanded. However, despite two intrapleural injections of tetracyclin, the pneumothorax reappeared. Lung CT scan showed an intraparechymal cyst in the posterior part of the right upper lobe. Lobectomy was performed and histological study confirmed the diagnosis of type I cystic adenomatoid malformation of the lung. Two months after surgery, clinical and radiological examinations were normal. CONCLUSION: Spontaneous pneumothorax, as the initial manifestation of cystic adenomatoid malformation of the lung, is rare (three cases reported in children beyond the neonatal period, and two in adults). CT scan features correlate well with the pathologic features. Because of the risk of recurrent pulmonary infections and malignancy change, removal of the cystic lesions is advisable.

Adolescent↗

[Impact of vaccination against Haemophilus influenzae on the incidence of invasive infections from Haemophilus influenzae type B in the Nord-Pas-de-Calais region].

BACKGROUND: In industrialized countries where immunization against Haemophilus influenzae b (Hib) is largely used, the incidence of invasive Hib infections has dramatically decreased. The aim of this study was to analyse the impact of immunization against Hib on the incidence of invasive Hib infections in the Nord-Pas-de-Calais area in France. PATIENTS AND METHODS: This retrospective multicenter study enrolled 11 of the 18 hospitals in the Nord-Pas-de-Calais area, comparing two periods: 1991-1993 (before immunization), and 1994-1996 (during immunization). All children less than 60 months of age and having an invasive Hib infection were included. The Pasteur-Mérieux Company was asked to provide the number of vaccines sold in the Nord-Pas-de-Calais area during the study period. RESULTS: The number of vaccines sold in 1992 was 56,208; this reached 189,173 in 1996, corresponding to an immunization ratio higher than 90%. One hundred and two children representing 155 invasive Hib infections were studied. The annual incidence was 42 during the first period (meningitis: 18.6; septicemia: 14.6; epiglottitis: 5.6), and nine (meningitis: 5; septicemia: 2.6; epiglottitis: 0.3) during the second period, that is a 78% decrease. CONCLUSION: These results confirm previous data in the literature by demonstrating that immunization in the Nord-Pas-de-Calais area has dramatically decreased the incidence of invasive Hib infections.

Bacteremia↗

[Indications of bronchial endoscopy in suspected tracheo-bronchial foreign body in children].

The diagnosis and early extraction of a respiratory foreign body (FB) in a child requires a rapid bronchoscopy. Thus, the possibility of a foreign body requires an endoscopy even in the absence of clinical or radiological signs. While the sensitivity of "the foreign body syndrome" is important (79-85%) its specificity is low (21-46%) which results in numerous endoscopies which do not show FB. This justifies the promotion of flexible fibroscopy, under a simple local anaesthesia of the upper airways and some sedation, each time that the foreign body is not obvious. That is when there is an absence of a radio-opaque foreign body (2-20% of cases) or an absence of associated unilateral diminution in breath sounds or ipsilateral obstructive emphysema (a positive predicted value of 94%, 95% confidence interval: 71-100%). The complications of flexible fibroscopy are rare but still justify its performance in an environment where there is resuscitation equipment and the possibility of rapidly performing a rigid bronchoscopy. Rigid bronchoscopy, which requires a general anaesthesia, remains the best technique to remove a foreign body in a child. It is also indicated initially in cases of respiratory distress where there is a fear of a foreign body in the trachea. The extraction of the CE by flexible fibroscopy under general anaesthesia has been reported in children but it is more difficult and more risky.

Algorithms↗

Modeling RNA-ligand interactions: the Rev-binding element RNA-aminoglycoside complex.

An approach to the modeling of ligand-RNA complexes has been developed by combining three-dimensional structure-activity relationship (3D-SAR) computations with a docking protocol. The ability of 3D-SAR to predict bound conformations of flexible ligands was first assessed by attempting to reconstruct the known, bound conformations of phenyloxazolines complexed with human rhinovirus 14 (HRV14) RNA. Subsequently, the same 3D-SAR analysis was applied to the identification of bound conformations of aminoglycosides which associate with the Rev-binding element (RBE) RNA. Bound conformations were identified by parsing ligand conformational data sets with pharmacophores determined by the 3D-SAR analysis. These "bioactive" structures were docked to the receptor RNA, and optimization of the complex was undertaken by extensive searching of ligand conformational space coupled with molecular dynamics computations. The similarity between the bound conformations of the ligand from the 3D-SAR analysis and those found in the docking protocol suggests that this methodology is valid for the prediction of bound ligand conformations and the modeling of the structure of the ligand-RNA complexes.

Aminoglycosides↗

Measurement of respiratory mechanics in paediatric intensive care: in vitro assessment of a pulmonary function device.

OBJECTIVE: To evaluate a recently developed and manufactured device for monitoring respiratory parameters in mechanically ventilated children. DESIGN: In vitro study using a lung model. SETTING: University paediatric intensive care unit. MATERIAL AND INTERVENTIONS: Evaluation of the accuracy of volume and pressure measurements, of the determination of respiratory system compliance (10 to 30 ml/cmH2O) and of resistance (20 and 50 cmH2O/l per s) by the inflation technique (volume- and pressure-controlled mode of ventilation); assessment of interobserver agreement for compliance (10, 15 ml/cmH2O) and resistance (20, 50 cmH2O/l per s) determinations (ANOVA, intraclass correlation coefficient). MEASUREMENTS AND RESULTS: The accuracy of volume measurements (No.1 Fleisch pneumotachograph) was < or = 5 % of true volumes up to 11 (Flow: 30 l/min) even after the introduction of an endotracheal tube. The accuracy of pressure measurements up to 70 cmH2O was < or = 2.5% of the true values. Coefficients of variation of volume and pressure measurements were < 2%. The accuracy of compliance and resistance determinations was, respectively, < or = 17 and 25% of the true values. No significant observer effect was found on compliance and resistance determinations. Indeed, mean differences in compliance and resistance determinations by pairs of observers were < 1%. Intraclass correlation coefficients were > 0.98. CONCLUSIONS: The measuring error of volume, pressure, compliance and resistance determined using this monitoring system seems acceptable for monitoring purpose. Moreover, use of this system by members of the medical team can be recommended since results obtained by observers, even untrained ones, were similar. In vivo evaluation is now needed.

Airway Resistance↗

[Exhale nitric oxide (NO) and respiratory function measured with body plethysmography in children].

BACKGROUND: Exhaled nitric oxide (NO) may be a marker of airway inflammation. Previous studies in adults have shown that the level of NO in exhaled air is influenced by several factors (breath holding, exercise, etc), or by several disease (asthma, congestive heart failure, diseases of the upper respiratory tract, cystic fibrosis, etc). However, few studies have been performed in children less than 3 years of age. The aim of this study was to determine endogenous NO levels in children with various diseases during lung volume measurements. PATIENTS AND METHODS: Fifty-two children aged 18.3 +/- 9.5 months were studied. The population was divided in two groups, according to the underlying disease: a group of 39 children with cystic fibrosis (n = 7), bronchopulmonary dysplasia (n = 17), asthma (n = 7) or recurrent respiratory tract infections (n = 8) and a second group of 13 children without respiratory disease. Lung function was measured by whole body plethysmography and several respiratory parameters were calculated (functional residual capacity [FRC], compliance and resistances of the respiratory system, trapped volume). NO production was measured on a chemiluminescence analyzer from mixed exhaled air collected into a bag, over a period of 5 minutes. RESULTS: NO production was related to disease: exhaled NO levels were three times higher in bronchopulmonary dysplasia and cystic fibrosis, compared to NO levels in children without respiratory disease. They were higher in asthma. They were not altered in recurrent respiratory tract infections. No correlation was found between respiratory parameters and NO production. However, exhaled NO levels were correlated to trapped volume, which defined dynamic part of pulmonary hyperinflation. CONCLUSION: Levels of endogenous NO in infants were similar to those measured in adults with and without inflammatory respiratory disease. Lung distention influenced exhaled NO production.

Biomarkers↗

[Acute rhabdomyolysis in the child].

Rhabdomyolysis results from muscular fibre lysis with release of cellular contents (myoglobin, enzymes, electrolytes) into the plasma. Traumatic (crush syndrome) and non-traumatic rhabdomyolysis have been mostly reported in adults. Traumatic rhabdomyolysis are mostly due to ischemic and reperfusion injuries. Non-traumatic rhabdomyolysis include several factors: muscular compression (comas), cytotoxic injury (infections and poisonings), ischemia (shock, cardiorespiratory arrest) or excessive muscular activity (seizures, strenuous exercise). The main etiologies reported in children are: anoxic-ischemic encephalopathy (including sudden infant death and life threatening events); electrolyte disorders; severe hyperthermia; poisonings; hereditary myopathies. Non-traumatic rhabdomyolysis must be suspected in these circumstances, requiring blood creatinine phosphokinase measurements. Indeed, clinical signs are inconstant and non-specific, and functional signs are difficult to appreciate in children. During the initial phase, the main risk is arrhythmias secondary to hyperkalemia. The two main complications are the compartmental syndrome leading to irreversible vasculo-nervous injuries and acute renal failure. Treatment of traumatic and non-traumatic rhabdomyolysis includes correction of hyperkalemia, active fluid loading in order to prevent acute renal failure and alkalinisation. Prognosis of rhabdomyolysis relates to the aetiology and the presence of acute renal failure.

Acute Kidney Injury↗

[Long-term follow-up of children with esophageal caustic stenosis].

BACKGROUND: Long term follow-up of children with esophageal caustic stenosis is not well known. The aim of the present study was to describe functional, organic and psychological, as well as social consequences. PATIENTS AND METHODS: Thirty-four children with a mean age of 3 years and 7 months +/- 3 years and 2 months (ranges: 1 month-14 years and 3 months) were included in a longitudinal study. Various parameters have been studied: treatment, functional symptoms, nutritional status (weight/height, body composition) and psychological and social consequences. chi 2 and Mann-Whitney tests were used for statistical analysis. RESULTS: Twenty-one patients have been treated by mechanical dilatations whereas surgery was performed in 12 children; the mean number of dilatations per child was higher in patients treated by dilatations (21 +/- 17 vs 14 +/- 16; P < 0.05). The frequency of dysphagia was not different in patients with colon interposition or not (69% vs 53%; P = 0.1). Nutritional status was not affected by the presence of esophageal caustic stenosis. Psychological and social consequences were characterized by scholastic difficulties, anxiety and severe depression. One case of suicide was observed. CONCLUSION: Children with caustic stenosis should be followed for a long period of time. A multidisciplinary approach is necessary, taking into account medical, social and psychological consequences.

Adolescent↗

No resuscitation orders and withdrawal of therapy in French paediatric intensive care units. Groupe Francophone de Réanimation et d'Urgences Pédiatriques.

OBJECTIVE: To determine the incidence of different modes of death in French paediatric intensive care units and to compare patients' characteristics, including a severity of illness score (Paediatric Risk of Mortality: PRISM score) and prior health status (Paediatric Overall Performance Category scale), according to the mode of death. DESIGN: A 4-month prospective cohort study. SETTING: Nine French multidisciplinary paediatric intensive care units. PATIENTS: All patients who died in PICUs, except premature babies. MAIN RESULTS: Among 712 admissions, 13% patients died. Brain death was declared in 20%, failure of cardiopulmonary resuscitation occurred in 26%, do-not-resuscitate status was identified in 27%, and withdrawal of supportive therapy was noted in 27%. The PRISM score and the baseline Paediatric Overall Performance Category were not different between the four groups. Brain-dead patients were older than those in whom a do-not-resuscitate order and withdrawal of therapy were made (median age 81 vs 7 and 4 months). CONCLUSIONS: Decisions to limit or to withdraw supportive care were made for a majority of patients dying in French paediatric intensive care units. Chronic health evaluation and severity of illness index are not sufficient to describe dead-patient populations.

Brain Death↗

Structural rules and conformational compensations in the tRNA L-form.

The mitochondrial tRNAs (mtRNA) of five distinct, secondary structure types have been identified in the tRNA sequence compilation, and the three-dimensional modeling for representative sequences of these types has been carried out using a new criterion for the lengths of the helical domains and connector regions in a full-sized tRNA conformation. This criterion has been derived from the analysis of the known structures of cytosolic tRNAs and states that in the tRNA structure nucleotide 59 of the T-loop should stack onto Domain 1. To ensure this, Domain 1 must have 12 layers of stacked nucleotides, and in the case of a deletion of a base-pair in the T-stem, an additional 13th layer is required. Although a number of mitochondrial tRNAs harbored deficiencies in this criterion and, therefore, could not be modeled directly, this disability could be corrected and modeling accomplished by invoking structural compensations derived from one of two unusual aspects of these tRNAs. One class of these tRNAs contained an unpaired nucleotide in their anticodon stem, and their three-dimensional structure was successfully modeled when the unpaired nucleotide was intercalated into the helical domain of the stem. The second class contained more than the required number of nucleotides connecting the tRNA helical domains; the conformational flexibility of these nucleotides allowed them to take the place of the absent layers. The conformational compensation that we report rationalizes disparate features of these tRNAs and suggests that the stacking of nucleotide 59 on Domain 1 is an essential feature of the three-dimensional L-form of tRNA.

Base Composition↗

On the origin of protein synthesis factors: a gene duplication/fusion model.

Sequence similarity has given rise to the proposal that IF-2, EF-G, and EF-Tu are related through a common ancestor. We evaluate this proposition and whether the relationship can be extended to other factors of protein synthesis. Analysis of amino acid sequence similarity gives statistical support for an evolutionary affiliation among IF-1, IF-2, IF-3, EF-Tu, EF-Ts, and EF-G and suggests further that this association is a result of gene duplication/fusion events. In support of this mechanism, the three-dimensional structures of IF-3, EF-Tu, and EF-G display a predictable domain structure and overall conformational similarity. The model that we propose consists of three consecutives duplication/fusion events which would have taken place before the divergence of the three superkingdoms: eubacteria, archaea, and eukaryotes. The root of this protein superfamily tree would be an ancestor of the modern IF-1 gene sequence. The repeated fundamental motif of this protein superfamily is a small RNA binding domain composed of two alpha-helices packed along side of an antiparallel beta-sheet.

Amino Acid Sequence↗