[Apparent life-threatening events and sudden unexpected death in infancy: Two different entities]. / Malaise et mort inattendue du nourrisson : deux entités différentes.

Most infant apparent life-threatening events (ALTEs) are minor with spontaneously favorable prognosis. Frequent etiologies are gastroesophageal reflux, obstructive apneas, respiratory infections, and breath-holding spells. Some rare but potentially serious causes must be discussed. Diagnosis is usually guided by careful questioning of the parents and repeated clinical examinations. A few complementary examinations are systematically needed and their performance is increased if they are oriented by clinical aspects. Hospitalization is usual for monitoring, further etiological investigation, and management of parental anxiety. ALTE and sudden unexpected death in infancy (SUDI) etiologies are often different. SUDI is called sudden unexplained death in infancy if it remains unexplained after investigation including autopsy. The annual incidence in France fell sharply after prevention campaigns in the 1990s, and now is about 400 SUDI, including 250 unexplained SUDI. The main guidelines of prevention are back sleeping, cessation of smoking during and after pregnancy, securing the bed and bedding, prevention of hyperthermia, and avoidance of dangerous factors of bed sharing. In the future, infants with particular vulnerabilities may be identified. The Haute Autorité de santé (French National Authority for Health) has published guidelines to support SUDI, standardize procedures, and improve our understanding of the causes of death.

[Viral epidemiology and clinical severity during the peak of the influenza A(H1N1) variant epidemic in febrile respiratory diseases of children]. / Epidémiologie virale et sévérité clinique pendant le pic d'épidémie grippale A(H1N1) variant dans les atteintes respiratoires fébriles de l'enfant.

UNLABELLED: In 2009, a new emerging flu virus, A(H1N1), was identified. Its true medical impact on children's health remains widely debated. AIM: To define the prevalence of respiratory disease in children hospitalized with fever during the influenza A(H1N1) epidemic and to determine the clinical, paraclinical, and outcome characteristics according to the viruses identified. MATERIAL AND METHODS: Children hospitalized for a febrile respiratory disease were included in this prospective cohort study conducted at Bordeaux University's Children's Hospital (France) during the influenza epidemic from 2009/11/23 to 2009/12/20. RESULTS: Seventy-three children were included in the study. Viruses were identified by PCR in 52% (38/73) of cases, including 23% (17/73) A(H1N1) virus and 29% (21/73) other viruses, 22% (16/73) of which were syncytial respiratory viruses. There was only one case of co-infection between A(H1N1) virus and another virus from the para-influenza virus or adenovirus or bocavirus pool. No significant difference regarding age, sex, or risk factors in the different viral groups was noted. Regarding the A(H1N1) virus, the most frequent symptoms were deterioration of the overall health status, cough, ENT disease, and rapid breathing, with significantly less increased breathing effort and auscultatory abnormality albeit with more seizures. There was no significant difference between groups regarding laboratory data. Management and outcome were similar. CONCLUSION: The prevalence of A(H1N1) virus during the 2009 epidemic in Aquitaine was low among febrile hospitalized children with breathing symptoms. Clinical and paraclinical signs were non-specific. The tolerance and prognosis of influenza A(H1N1) infection in children was satisfactory.

Paediatric community-acquired septic shock: results from the REPEM network study.

UNLABELLED: INTRODUCTION AND PURPOSE OF THE STUDY: With this study we aimed to describe a "true world" picture of severe paediatric 'community-acquired' septic shock and establish the feasibility of a future prospective trial on early goal-directed therapy in children. During a 6-month to 1-year retrospective screening period in 16 emergency departments (ED) in 12 different countries, all children with severe sepsis and signs of decreased perfusion were included. RESULTS: A 270,461 paediatric ED consultations were screened, and 176 cases were identified. Significant comorbidity was present in 35.8 % of these cases. Intensive care admission was deemed necessary in 65.7 %, mechanical ventilation in 25.9 % and vasoactive medications in 42.9 %. The median amount of fluid given in the first 6 h was 30 ml/kg. The overall mortality in this sample was 4.5 %. Only 1.2 % of the survivors showed a substantial decrease in Paediatric Overall Performance Category (POPC). 'Severe' outcome (death or a decrease ≥2 in POPC) was significantly related (p < 0.01) to: any desaturation below 90 %, the amount of fluid given in the first 6 h, the need for and length of mechanical ventilation or vasoactive support, the use of dobutamine and a higher lactate or lower base excess but not to any variables of predisposition, infection or host response (as in the PIRO (Predisposition, Infection, Response, Organ dysfunction) concept). CONCLUSION: The outcome in our sample was very good. Many children received treatment early in their disease course, so avoiding subsequent intensive care. While certain variables predispose children to become septic and shocked, in our sample, only measures of organ dysfunction and concomitant treatment proved to be significantly related with outcome. We argue why future studies should rather be large multinational prospective observational trials and not necessarily randomised controlled trials.

[Clinical features and outcome of 2009 H1N1 influenza in the pediatric setting. Multicenter prospective study in the ED]. / Présentation clinique et évolution d'une population pédiatrique atteinte de la grippe A (H1N1)v. Enquête multicentrique prospective aux urgences pédiatriques.

STUDY OBJECTIVE: The clinical manifestations and outcome of infants and children with confirmed 2009 H1N1 influenza in emergency departments is described. METHODS: We conducted a prospective multicenter case series involving children with symptoms of influenza-like illness in whom 2009 H1N1 influenza was diagnosed on reverse-transcriptase polymerase chain reaction assay on a nasopharyngeal swab or nasal aspirates and who were admitted to the ED of four university pediatric hospitals. The following data were collected: age, gender, preexisting chronic conditions (PECs) associated with a high risk for influenza-related complications, clinical symptoms, outcome, antiviral treatment, and complications. We recorded length of cough and fever during a phone-call on day 8. RESULTS: Between 1st October and 31st December 2009, 466 children were included. Their median age was 4 years (range, 1 day to 17 years). The median time to consultation was 24h. Of these 466 infants and children, 55 were aged less than three months and 153 had one or more PECs. Asthma was the most frequent condition. Children at risk and children without risk did not differ for complications (28% vs 31%, P>0.05). Respiratory complications (17%) and decompensations of preexisting disease were the most frequent. Infants aged less than three months did not have more complications than infants without PECs. At-risk infants and children were more frequently hospitalized (P<0.02) and the duration of the pediatric ward stay was longer (P<0.02). This was true only for children aged less than three months. Of the hospitalized children, 17 (9%) were admitted to an ICU. Duration of fever (3.8 days) and duration of cough (6.3 days) did not differ according to whether or not children received oseltamivir. CONCLUSION: Infants younger than three months of age are not a group at risk for influenza-related complications. Oseltamivir did not reduce duration of symptoms in this population.

Emerging evidence of the impact of kidney disease on drug metabolism and transport.

Several lines of emerging evidence indicate that kidney disease differentially affects uptake and efflux transporters and metabolic enzymes in the liver and gastrointestinal (GI) tract, and uremic toxins have been implicated as the cause. In patients with kidney disease, even drugs that are eliminated by nonrenal transport and metabolism could lead to important unintended consequences if they are administered without dose adjustment for reduced renal function. This is particularly so in the case of drugs with narrow therapeutic windows and may translate into clinically significant variations in exposure and response.

[Quality of training and professional outcomes of medical students in pediatric residency programs: survey of graduating classes between 1990 and 2000, in the western interregion]. / Qualité de la formation et devenir professionnel des étudiants du diplôme d'études spéciales de pédiatrie: enquête auprès des promotions 1990 à 2000 de l'interrégion ouest.

OBJECTIVES: Little information is available to incoming students in pediatrics residency programs on the experiences of past residents. The objective of this study was to investigate the pediatrics training programs and determine the professional outcomes of graduating residents between 1990 and 2000 in the Western Interregion. POPULATION AND METHODS: Questionnaires were distributed to the 187 medical students enrolled in pediatrics residency programs between 1990 and 2000 in the six university hospital centers of the Western Interregion. The questions concerned the details of training, the modes of residency positions, and current professional and personal situations. One hundred and sixty-five (88%) individuals responded. RESULTS: Seventy-seven percent of the practicing pediatricians stated that the training they had received during residency was adapted to their current practice. This percentage was higher for hospital staff physicians (82%) than for the physicians in private practice (50%) or those with salaried positions outside the hospital system (58%). One hundred and twenty-four had either completed post-residency training (97) or were doing so (27) at the time of the survey. All but one were professionally active, three quarters of them in hospitals and, of these, most were in the hospitals where they had trained. Eighty-six percent of the practicing pediatricians said they were satisfied with their professional work and 73% said they were satisfied with their personal lives. CONCLUSION: These results support the current reflection on reforming the residency training program in pediatrics, especially with regard to its prolongation and the diversification of the training options to take into account the individual student's professional orientation.

Novel nevirapine-like inhibitors with improved activity against NNRTI-resistant HIV: 8-heteroarylthiomethyldipyridodiazepinone derivatives.

A series of 8-heteroarylthiomethyldipyridodiazepinone derivatives were prepared and evaluated for their antiviral profile against wild type virus and the important K103N/Y181C mutant as an indicator for broad activity. 2,6-Dimethylpyridine derivative 16 was found to have a good pharmacokinetic profile in spite of poor metabolic stability in rat liver microsomes.

A new coding region polymorphism of human IgLC2.

A new allelic form of the human IgLC2 gene is described. The marker involves a T to C substitution in the C lambda 2 constant region gene, a silent substitution at amino acid coding position 178 (YAASSYLSL) and two substitutions in the 3'-flanking region. Analysis of IgLC2 alleles in a total of 60 individuals has indicated a frequency of 0.32 for the new allele, which has been designated IgLC2*B2. The *B1 and *B2 alleles encode T and C, respectively, at nucleotide position 212 in the IgLC2 coding region. Both the *B1 and *B2 alleles are found in individuals homozygous for the single-copy RFLP allele of IgLC2/IgLC3 (8 kb EcoRI). Knowledge of alleles of this marker will be important for studies on the expression of the IgLC2 and IgLC3 isotypes in normal and autoimmune lymphocyte populations, as the coding regions of the two isotypes differ only at this position. The marker will also be useful in further studies of linkage with other IgLV and IgLC markers and to establish possible correlations with susceptibility to autoimmune disorders.

Fractional quantum hall effect in infinite-layer systems.

Stacked two dimensional electron systems in transverse magnetic fields exhibit three dimensional fractional quantum Hall phases. We analyze the simplest such phases and find novel bulk properties, e.g. , irrational braiding. These phases host "one and a half" dimensional surface phases in which motion in one direction is chiral. We offer a general analysis of conduction in the latter by combining sum rule and renormalization group arguments, and find that when interlayer tunneling is marginal or irrelevant they are chiral semimetals that conduct only at T > 0 or with disorder.

Synthesis and antiviral activity of monobactams inhibiting the human cytomegalovirus protease.

A series of monobactam inhibitors of HCMV (N(o)) protease bearing a heterocycle linked by a methylene group at C-4 is described. Inhibitors containing a heterocycle such as a 2-furyl, 2-thiophenyl, 4-methyl-2-tetrazole and 2-benzothiazole were found to be active in a plaque reduction assay. Furthermore, 2-benzothiazole derivatives were shown to inhibit the HCMV protease activity inside cells by using a cell transfection assay, indicating that their antiviral activity in the plaque reduction assay could be attributed to protease inhibition.

beta-Lactam derivatives as inhibitors of human cytomegalovirus protease.

The development of novel monobactam inhibitors of HCMV protease incorporating a carbon side chain at C-4 and a urea function at N-1 is described. Substitution with small groups at the C-3 position of the beta-lactam ring gave an increase in enzymatic activity and in stability; however, a lack of selectivity against other serine proteases was noted. The use of both tri- and tetrasubstituted urea functionalities gave effective inhibitors of HCMV protease. Benzyl substitution of the urea moiety was beneficial, especially when strong electron-withdrawing groups where attached at the para position. Modest antiviral activity was found in a plaque reduction assay.

Potent beta-lactam inhibitors of human cytomegalovirus protease.

A series of novel monobactam inhibitors of human cytomegalovirus (HCMV) protease has been described that possess a heterocyclic thiomethyl side chain at C-4. Changes to the heterocycle did not significantly change the inhibitory activity of these compounds in an enzymatic assay, although improvements in solubility and cell culture activity were noted. A number of permutations between C-4 substitutions and N-1 derivatives led to the identification of several beta-lactams with antiviral activity in a plaque reduction assay. N-methyl thiotetrazole-containing compounds were found to be the most potent inhibitors in the enzymatic assay.

The zinc iodide-osmium tetroxide staining-fixative of Maillet. Nature of the precipitate studied by x-ray microanalysis and detection of Ca2+-affinity subcellular sites in a tonic smooth muscle.

A mechanism of osmium reduction during zinc iodide-osmium tetroxide (ZIO) fixation is proposed. X-ray powder microanalyses of ZIO precipitates formed both in the presence or absence of tissues are identical with those of CuOsO4 and CuRuO4. Therefore, and based on indexation methods, ZnOsO4 was found to be the formula of the ZIO mixture reduction; this zinc osmate has an orthorhombic crystalline lattice. In smooth muscle preparations, ZIO electron dense deposits are localized in both cisternae of the sarcoplasmic reticulum and in mitochondria after a short fixation time. According to the microanalysis results, the zinc osmate has been associated to Ca2+ high affinity sites since Zn2+ is either replacing Ca2+ and/or displacing it by having a higher affinity for Ca2+ binding sites. Consequently, the ZIO mixture might be useful in revealing some Ca2+ storage sites in cells. This hypothesis was tested in ABRM preparations by selectively depleting sites which are known to bind Ca2+. In this case, the sarcoplasmic reticulum only retains the staining deposits after a short ZIO fixation. It is likely that OsO4 alone, used as fixative in cytology might be due to the formation of metallic osmates (e.g., divalent osmates like CaOsO4). In addition, of course, reduction of osmium during tissue fixation is accompanied by oxidation of double bonds of lipoproteic complexes or unsaturated lipids, and oxidation of sulfhydryl groups and amino groups.