Organ donation by Maastricht-III pediatric patients: Recommendations of the Groupe Francophone de Réanimation et Urgences Pédiatriques (GFRUP) and Association des Anesthésistes Réanimateurs Pédiatriques d'Expression Française (ADARPEF). Part II: Specific organizational and technical considerations.

A panel of pediatric experts met to develop recommendations on the technical requirements specific to pediatric controlled donation after planned withdrawal of life-sustaining therapies (Maastricht category III). The panel recommends following the withdrawal of life-sustaining therapies protocol usually applied in each unit, which may or may not include immediate extubation. The organ retrieval process should be halted if death does not occur within 3 h of life-support discontinuation. Circulatory arrest is defined as loss of pulsatile arterial pressure and should be followed by a 5-min no-touch observation period. Death is declared based on a list of clinical criteria assessed by two senior physicians. The no-flow time should be no longer than 30, 45, and 90 min for the liver, kidneys, and lungs, respectively. At present, the panel does not recommend pediatric heart donation after death by circulatory arrest. The mean arterial pressure cutoff that defines the start of the functional warm ischemia (FWI) phase is 45 mmHg in patients older than 5 years and/or weighing more than 20 kg. The panel recommends normothermic regional perfusion in these patients. The FWI phase should not exceed 30 and 45 min for retrieving the pancreas and liver, respectively. There is no time limit to the FWI phase for the lungs and kidneys. The panel recommends routine sharing of experience with Maastricht-III donation among all healthcare institutions involved in order to ensure optimal outcome assessment and continuous discussion on the potential difficulties, notably those related to the management of normothermic regional perfusion in small children.

Organ donation by Maastricht-III pediatric patients: Recommendations of the Groupe Francophone de Réanimation et Urgences Pédiatriques (GFRUP) and Association des Anesthésistes Réanimateurs Pédiatriques d'Expression Française (ADARPEF) Part I: Ethical considerations and family care.

The French Transplant Health Authority (Agence de la Biomédecine) has broadened its organ- and tissue-donation criteria to include pediatric patients whose death is defined by circulatory criteria and after the planned withdrawal of life-sustaining therapies (WLST) (Maastricht category III). A panel of pediatric experts convened to translate data in the international literature into recommendations for organ and tissue donation in this patient subgroup. The panel estimated that, among children aged 5 years or over with severe irreversible neurological injury (due to primary neurological injury or post-anoxic brain injury) and no progression to brain death, the number of potential donors, although small, deserves attention. The experts emphasized the importance of adhering strictly to the collegial procedure for deciding to withdraw life support. Once this decision is made, the available data should be used to evaluate whether the patient might be a potential donor, before suggesting organ donation to the parents. This suggestion should be reserved for parents who have unequivocally manifested their acceptance of WLST. The discussion with the parents should include both the pediatric intensive care unit (PICU) team under the responsibility of a senior physician and the hospital organ- and tissue-procurement team. All recommendations about family care during the end of life of a child in the PICU must be followed. The course and potential challenges of organ donation in Maastricht-III pediatric patients must be anticipated. The panel of experts recommended strict compliance with French recommendations (by the Groupe Francophone de Réanimation et Urgences Pédiatriques) about WLST and providing deep and continuous sedation until circulatory arrest. The experts identified the PICU as the best place to implement life-support discontinuation and emphasized the importance of returning the body to the PICU after organ donation. French law prohibits the transfer of these patients from one hospital to another. A description of the expert-panel recommendations regarding the organization and techniques appropriate for children who die after controlled circulatory arrest (Maastricht III) is published simultaneously in the current issue of this journal..

Tree-ring reconstruction of snow avalanche activity: Does avalanche path selection matter?

In the current context of anthropogenic global warming, one of the purposes of dendrogeomorphic analyses is to provide long and continuous chronologies of mass movements, so as to detect potential trends or shift related to increasing temperatures. However, on documented slopes, the comparison between historical archives and tree-ring records suggests that dendrogeomorphic reconstructions systematically underestimate the natural activity of the process under investigation. In the specific case of snow avalanches, underestimation generally amounts to 50% and the main causes generally given for this difference are related to the magnitude of past events. In this study, we hypothesize that the morphometric characteristics of avalanche paths and their forest cover could have significant impacts on the length and reliability of tree-ring reconstructions. In order to test this hypothesis, we selected four adjacent, albeit differently structured, avalanche paths from the Queyras massif (French Alps), with the aim to compare their potential for a continuous reconstruction of past avalanche activity. On the most active avalanche paths characterized by high-altitude release areas (covered only by shrubby vegetation), tree-ring reconstructions do not exceed one century in length, with recurrence intervals of high magnitude events >25 years. By contrast, on forested couloirs where lower slopes and forest coverage up to the release areas limits the intensity of events, the frequency of reconstructed snow avalanches is 2.5 times higher, the reconstructions span longer periods and the convergence rate with historical archives attest to the reliability of the dendrogeomorphic approach. These results suggest that a careful selection of couloirs is essential and that priority should be given to forested sites as (i) they allow for exhaustive and (ii) reliable reconstructions over (iii) long periods of time.

Climate-growth relationships in a Larix decidua Mill. network in the French Alps.

A better understanding of the respective role of key climatic variables on tree growth is crucial for an accurate assessment of how ongoing global changes may affect both dynamics and distribution of forest tree species in the future. The aim of this study was (i) to explore growth patterns of European larch (Larix decidua Mill.) through a network of tree-ring chronologies developed for the French Alps and (ii) to identify the main climatic drivers explaining radial growth. Climate-growth relationships were coupled with a hierarchical analysis. This relationship revealed significant variability expressed spatially by the existence of five clusters, initially discriminated by an elevational contrast related to (i) a negative correlation between summer temperatures and larch growth at lower elevations and (ii) a stronger response of low-elevation larch stands to winter precipitation. In the high-elevation clusters, tree growth depends on previous autumn and current summer temperatures and water supply in July. The differentiation, that portrays a strong geographical coherence, is mainly related to the latitudinal gradient; (i) the northwestern stands are mostly sensitive to high temperatures in summer; (ii) the growth of the southernmost clusters is equally driven by temperatures during autumn, winter, and summers; (iii) the populations of a cluster located in a transitional zone of the inner French Alps, subject to both Mediterranean and Continental influences, exhibit negative correlations to late winter and early spring precipitation. This significant spatial heterogeneity of climate-tree ring relationships in L. decidua clearly underlines the high plasticity of the species to adapt its growth to local climate conditions.

Dietary N-acetyl-L-cysteine modulates benzo[a]pyrene-induced skin tumors in cancer-prone p53 haploinsufficient Tg.AC (v-Ha-ras) mice.

Epidemiologic studies support the protective role of dietary antioxidants in preventing cancer. However, emerging evidence from clinical trials and laboratory data suggest that in some cases individual antioxidant supplements may actually exacerbate carcinogenesis. Our goal was to explore these paradoxical activities in a rodent model that possesses genotypic characteristics of human cancers. We selected the p53 haploinsufficient Tg.AC (v-Ha-ras) mouse as a model, because it contains an activated, carcinogeninducible ras oncogene and an inactivated p53 tumor suppressor gene, which are frequent genetic alterations in human cancers. These mice develop chemically induced benign and malignant skin tumors rapidly which can easily be quantified. Mice were fed basal diets with or without 3% N-acetyl-L-cysteine (NAC), a well-recognized antioxidant, prior to, during and after topical application of the carcinogen benzo[a]pyrene (64 microg/mouse) applied twice per week for 7 weeks. Tumor incidence exceeded 90% for both groups, and NAC did not reduce tumor latency. Mice fed NAC displayed a 43% reduction (P < 0.05) in tumor multiplicity and delayed the appearance of lesions (P < 0.05). Dietary NAC also significantly (P < 0.05) improved group survival by 5 weeks. Total tumor yields were reduced in both dietary groups but malignant spindle cell tumors (SCT) increased by 25% in NAC-fed mice. The v-Ha-ras oncogene and p53 protein products were clearly co-expressed in both benign and malignant lesions from both dietary groups. In summary, dietary supplementation with NAC was chemopreventive, but the marginal increase in SCT suggests a paradoxical effect.

Probing the importance of spacial and conformational domains in captopril analogs for angiotensin converting enzyme activity.

A new synthesis of 4,5-methano-L-prolines and the enzymatic activity of the corresponding N-(3-mercapto-2-R-methyl-propionyl) analogs as inhibitors of angiotensin converting enzyme are described.

Role of interferon-gamma in contact hypersensitivity assessed in interferon-gamma receptor-deficient mice.

The role of interferon-gamma (IFN gamma) in contact hypersensitivity induced by the haptens, oxazolone and 2,4,6-trinitrochlorobenzene (TNCB), was investigated in mice with a targeted disruption of the IFN gamma receptor (IFN gamma-R-/-). The 24-h ear-swelling response to oxazolone or TNCB in sensitized animals was not significantly reduced by the disruption of IFN gamma signalling. Dermal mononuclear infiltrates (MN) and epidermal microabscesses, however, were clearly diminished in the mutant mice. The hapten-induced upregulation of intercellular-adhesion molecule-1 (ICAM-1) and major histocompatibility complex (MHC) class I in IFN gamma-R-/- mice was smaller when compared to wild-type mice. It is concluded that oxazolone- and TNCB-induced contact hypersensitivity is partially dependent on a functional IFN gamma system. While the cutaneous oedema is IFN gamma-independent, the mononuclear cell infiltration and epidermal microabscess formation are at least partly IFN gamma-dependent. Therefore, reduced cellular infiltrates are likely due to a reduced upregulation of ICAM-1 and class I antigen expression in IFN gamma-R-/- mice.

Quantitation of the interaction of the immunosuppressant deoxyspergualin and analogs with Hsc70 and Hsp90.

Deoxyspergualin (DSG), a spermidinyl, alpha-hydroxyglycyl, 7-guanidinoheptanoyl peptidomimetic, shows immunosuppressive activity. In confirmation of a recent report that immobilized methoxyDSG selectively retains the heat shock protein Hsc70, we report here quantitative binding of DSG and analogs to both Hsc70 and the 90-kDa heat shock protein Hsp90. We have utilized affinity capillary electrophoresis to obtain Kd values for DSG and analogs, and stimulation of the ATPase activity of Hsc70 to obtain Km values for DSG, that are comparable and corroborative. Kd values are 4 microM for DSG binding to Hsc70 and 5 microM for DSG binding to Hsp90. Two active analogs, methoxy- and glycylDSG, bind with similar affinities. Glyoxylylspermidine and des(aminopropyl)DSG, two inactive metabolites, have much reduced affinity for Hsc70 and Hsp90. These data validate binding of these novel immunosuppressant agents to these molecular chaperones, at concentrations in the range of pharmacologically active doses, and indicate that further characterization of Hsc70 and/or Hsp90 as potential targets for DSG is warranted.

Evaluation of a rapid latex test for direct detection of Streptococcus agalactiae in various obstetrical and gynaecological disorders.

Cervical samples collected during speculum examination in 413 women were tested for the presence of Streptococcus agalactiae by Gram staining, a new latex agglutination test and standard cultures. The results of each method are reported in correlation with the clinical circumstances of isolation. Gram stain and the latex agglutination test had a sensitivity of 30% and 78%, and a specificity of 89% and 98% respectively compared with culture. The sensitivity of the latex agglutination test was higher in cases of premature rupture of membranes (90%), presumed chorioamnionitis (86%), presumed post-partum endometritis (86%) and presumed salpingitis (87%). This latex agglutination test appears to be useful for identifying patients who are heavily colonized with Streptococcus agalactiae and are at a high risk of infection.