Search

Pneumonia caused by Streptococcus pneumoniaeis a leading cause of death worldwide. A growing body of evidence indicates that the successful treatment of bacterial infections results from synergy between antibiotic-mediated direct antibacterial activity and the host's immune defenses. However, the mechanisms underlying the protective immune responses induced by amoxicillin, a β-lactam antibiotic used as the first-line treatment of S. pneumoniaeinfections, have not been characterized. A better understanding of amoxicillin's effects on host-pathogen interactions might facilitate the development of other treatment options. Given the crucial role of neutrophils in the control of S. pneumoniaeinfections, we decided to investigate amoxicillin's impact on neutrophil development in a mouse model of pneumococcal superinfection. A single therapeutic dose of amoxicillin almost completely eradicated the bacteria and prevented local and systemic inflammatory responses. Interestingly, in this context, amoxicillin treatment did not impair the emergency granulopoiesis triggered in the bone marrow by S. pneumoniae. Importantly, treatment of pneumonia with amoxicillin was associated with a greater mature neutrophil count in the bone marrow; these neutrophils had specific transcriptomic and proteomic profiles. Furthermore, amoxicillin-conditioned, mature neutrophils in the bone marrow had a less activated phenotype and might be rapidly mobilized in peripheral tissues in response to systemic inflammation. Thus, by revealing a novel effect of amoxicillin on the development and functions of bone marrow neutrophils during S. pneumoniaepneumonia, our findings provide new insights into the impact of amoxicillin treatment on host immune responses.Amoxicillin treatment of Streptococcus pneumoniaeinfection influenced emergency granulopoiesis in the bone marrow and led to the generation of mature neutrophils with distinct antimicrobial functions and migratory capabilities.

Les données épidémiologiques concernant le chemsex sont difficiles à appréhender car les données sont diverses et éparses. Dans cette situation, il nous a semblé intéressant d’essayer d’identifier les cas d’intoxications dans un contexte de chemsex traités dans notre laboratoire (toxicologie biologique et médico-légale) au cours des 3 dernières années.

Purpose: The authors revisit the literature on the use of expatriates and specifically Boyacigiller (1990) and examine whether OW Bunker, a Danish bunker oil trader, filled positions at its foreign units with traders transferred from its other units (expatriates). The authors test the generalizability and robustness of past findings on this topic by using a different dependent variable, sample, and methodology. Design/methodology/approach: By searching the traders' LinkedIn profiles and consulting secondary sources, the authors obtain data on current and previous positions and work location and type of customer handled (global or local). Using qualitative comparative analysis (QCA), the authors analyze 236 hiring decisions made between 1983 and 2014. Findings: The authors find that OW transferred expatriates, principally home-country nationals, to handle global customers in its large foreign subsidiaries located in high-income countries. In another clear pattern, expatriates were used to start new foreign subsidiaries. These results generally confirm those of Boyacigiller. However, and contrary to her findings, none of our scenarios for internal transfers feature expatriates being sent to culturally and institutionally distant subsidiaries unless it is to serve global customers, casting doubt on the idea that a major reason for using expatriates is to remedy a local shortage of skills or to handle political risk. Originality/value: The authors test the generalizability of Boyacigiller’s (1990) findings and confirm a large part of it. They extend her study by demonstrating that MNEs deploy expatriates not only to distant countries but also to close ones.

Les opioïdes comprennent un large éventail de molécules d’indications variées : antalgiques, traitements de substitution aux opiacés, antidote de l’overdose. La pharmacologie des opioïdes est parfois compliquée par des susceptibilités individuelles d’ordre génétique. Des polymorphismes génétiques affectant les gènes qui codent pour des protéines impliquées dans la pharmacocinétique ou la pharmacodynamie des opioïdes sont parfois à-même d’expliquer, au moins partiellement, des situations cliniques délétères et inattendues. L’objectif est de présenter les éléments pharmacogénétiques pouvant participer à expliquer les variabilités interindividuelles de réponse clinique à la prise d’opioïdes.

In the last decades, tranexamic acid (TXA) has emerged as an essential tool in blood loss management in obstetrics. TXA prophylaxis for postpartum haemorrhage (PPH) has been studied in double-blind, placebo-controlled, randomized clinical trials (RCTs). Given the small observed preventive effect, the systematic use of TXA for vaginal and/or caesarean deliveries remains controversial. The result of a pharmacokinetic modelling suggests that relative to intravenous administration, intramuscular administration may be an equally effective alternative route for preventing PPH and may enable access to this drug in low-resource countries. Prophylaxis is currently studied in high-risk populations, such as women with prepartum anaemia or placenta previa.

Présenter et discuter un cas d’intoxication domestique familiale au mercure métallique diagnostiqué par la biologie, faute d’informations environnementales lors de la recherche étiologique initiale, et pour lequel un suivi des concentrations sanguines et urinaires de mercure a pu être réalisé.

La réponse clinique aux médicaments est souvent variable d’un individu à l’autre à posologie comparable. Des facteurs génétiques affectant la pharmacocinétique, et notamment le métabolisme des xénobiotiques expliquent en partie ces réponses différentes. Nous rapportons l’intérêt du dosage des métabolites des médicaments et l’intérêt de la pharmacogénétique dans la pratique médicale courante à travers la description de deux cas impliquant des polymorphismes de gènes codant des CYP450.

ABSTRACTBackgroundKlebsiella pneumoniae(hereafter, Kp) is a major public health threat responsible for high levels of multidrug resistant (MDR) human infections. Besides, Kp also causes severe infections in the community, especially in Asia and Africa. Although most Kp infections are caused by endogenous intestinal carriage, little is known about the prevalence and microbiological characteristics of Kp in asymptomatic human carriage, and attached risk factors including environmental sources exposure.MethodsHere, 911 pregnant women from communities in Madagascar, Cambodia, and Senegal were screened for gut colonization by Kp. Characteristics of Kp strains (antimicrobial susceptibility, genomic diversity, virulence, and resistance genes) were defined, and associated risk factors were investigated.ResultsKp carriage rate was 55.9%, and Kp populations were highly heterogeneous (6 phylogroups, 325 sequence types, Simpson index 99.6%). One third of Kp isolates had acquired antimicrobial resistance genes. MDR-Kp (11.7% to 39.7%) and extended spectrum beta-lactamase (ESBL)-producing Kp (0.7% to 14.7%) varied among countries. Isolates with virulence genes were detected (14.5%). Environmental exposure factors including food, animal contacts, or hospitalization of household members were associated with carriage of Kp, antimicrobial resistance and hypervirulence. However, risk factors were country-specific and Kp subpopulation-specific.ConclusionThis large-scale multicenter study uncovers the huge diversity of Kp in human gut carriage, demonstrates that antimicrobial resistance is widespread in communities of three low-income countries, and underlines the challenges posed by Kp colonization to the control of antimicrobial resistance.

Variability in genes involved in drug pharmacokinetics or drug response can be responsible for suboptimal treatment efficacy or predispose to adverse drug reactions. In addition to common genetic variations, large-scale sequencing studies have uncovered multiple rare genetic variants predicted to cause functional alterations in genes encoding proteins implicated in drug metabolism, transport and response. To understand the functional importance of rare genetic variants in DPYD, a pharmacogene whose alterations can cause severe toxicity in patients exposed to fluoropyrimidine-based regimens, massively parallel sequencing of the exonic regions and flanking splice junctions of the DPYDgene was performed in a series of nearly 3000 patients categorized according to pre-emptive DPD enzyme activity using the dihydrouracil/uracil ([UH2]/[U]) plasma ratio as a surrogate marker of DPD activity. Our results underscore the importance of integrating next-generation sequencing-based pharmacogenomic interpretation into clinical decision making to minimize fluoropyrimidine-based chemotherapy toxicity without altering treatment efficacy.

•Dalbavancin has shown good results in patients with diabetes-related foot osteomyelitis.•Dalbavancin tolerance profile is satisfactory.•Dalbavancin is a good option in case of tolerance issues with previous treatments.•Dalbavancin may ease discharge from hospital.

L’administration d’aminosides peut provoquer une néphrotoxicité ou une ototoxicité, contrôlables par un suivi thérapeutique pharmacologique. Néanmoins, une prédisposition génétique liée à des variants du gène mitochondrial MT-RNR1, peut favoriser la survenue d’une ototoxicité dès les premières administrations. Des recommandations d’analyse pharmacogénétique ont été proposées récemment par le Clinical Pharmacogenetics Implementation Consortium(CPIC). Le Réseau francophone de pharmacogénétique (RNPGx) propose une revue bibliographique de cette prédisposition génétique, ainsi que des recommandations professionnelles. Le gène MT-RNR1 code pour l’ARNr 12S mitochondrial, qui constitue la petite sous-unité du ribosome mitochondrial. Trois variants de ce gène sont associés à une ototoxicité des aminosides : les variants m.1555A>G et m.1494C>T disposent d’un niveau de preuve « élevé », alors que le variant m.1095T>C dispose lui d’un niveau de preuve « modéré ». La recherche de ces variants peut être réalisée en laboratoire si l’administration d’aminosides peut être différée après l’obtention du résultat. En revanche, si le traitement revêt un caractère d’urgence, il n’existe actuellement pas de test rapide disponible en France, alors qu’un test « point-of-care » est autorisé en Grande-Bretagne. Le RNPGx considère (1) comme « indispensable » la recherche des variants m.1555A>G, m.1494C>T et « conseillée » celle de m.1095T>C avant l’administration d’un aminoside (si compatible avec le contexte médical). À noter que le niveau d’hétéroplasmie détecté ne modifie pas la recommandation ; (2) l’analyse pharmacogénétique n’est actuellement pas envisageable pour une administration d’aminosides à court terme, en l’absence de solution analytique disponible (test rapide à évaluer en France) ; (3) la réalisation d’une analyse rétrospective en cas d’ototoxicité des aminosides est « recommandée » ; (4) l’analyse des apparentés est « recommandée ». Le RNPGx propose ainsi une revue actualisée du couple gène – médicament, MT-RNR1-aminosides, pouvant servir de base à une adaptation des pratiques concernant l’analyse pharmacogénétique liée au traitement par aminosides.

Le chemsex est pratiqué essentiellement par des hommes ayant des relations avec les hommes, mais également dans les milieux hétérosexuels libertins. Par ces prises de substances, les pratiquants de chemsex recherchent une augmentation et une prolongation du désir, du plaisir, des sensations et des performances. Les effets recherchés sont donc en premier lieu des effets stimulants (et/ou hallucinogènes) à l’origine d’effets euphorisants et déshinibiteurs, qui sont obtenus par la prise de GHB/GBL, dérivés des cathinones (3-MMC, …), cocaïne, méthamphétamine, MDMA, et parfois kétamine ou des dérivés. Ces consommations de drogues s’accompagnent souvent de prises de médicaments qui favorisent l’érection : inhibiteurs de la phosphodiestérase de type 5 et poppers. Parce que les données épidémiologiques concernant le chemsex sont difficiles à appréhender car les données sont diverses et éparses, il nous a semblé intéressant d’essayer d’identifier les cas d’intoxications dans un contexte de chemsex dont les analyses ont été traitées dans notre laboratoire (toxicologie biologique et médicolégale) au cours des 3 dernières années.

Les fluoropyrimidines restent les molécules anticancéreuses les plus prescrites dans le traitement des tumeurs solides. Elles induisent des toxicités sévères chez 10–40 % des patients et des toxicités létales chez 0,2–0,8 % des patients. Une abondante littérature a établi le lien entre un déficit enzymatique en dihydropyrimidine déshydrogénase (DPD, enzyme qui dégrade le 5-FU) et la survenue d’une toxicité sévère sous fluoropyrimidine. Si les déficits complets en DPD sont rares (0,1–0,5 %), les déficits partiels sont retrouvés chez 3–15 % des patients. La recherche du déficit en DPD peut être réalisée par phénotypage (mesure directe ou indirecte de l’activité enzymatique) ou par génotypage (recherche des principaux polymorphismes fonctionnels du gène DPYD). Actuellement, il n’existe pas d’obligation réglementaire pour le dépistage du déficit en DPD avant l’administration de fluoropyrimidines. Sur la base des niveaux de preuve issus de la littérature, et des pratiques actuelles, le Groupe de Pharmacologie Clinique Oncologique (GPCO)-UNICANCER et le Réseau National de Pharmacogénétique hospitalière (RNPGx) recommandent : (1) de rechercher un déficit en DPD avant la mise en route de tout traitement à base de 5-FU ou capécitabine ; (2) de réaliser ce dépistage par phénotypage en dosant en première intention l’uracile plasmatique (U) (éventuellement complété par le rapport dihydrouracil/U) et en y associant le génotypage des variants *2A, *13, p.D949V et HapB3 ; (3) de réduire si nécessaire la posologie en fonction du statut DPD dès la première cure et d’envisager une augmentation de dose aux cures suivantes en fonction de la tolérance. Actuellement en France, 17 laboratoires hospitaliers réalisent en routine la recherche du déficit en DPD.

Acetaminophen (paracetamol) voluntary (or not) intoxications are a major cause of life-threatening liver damage. Most of available assays on the market show an upper range measurement level that is close to thresholds considered as toxic levels. Therefore, high concentration samples must be further diluted in to accurately measure paracetamol levels.

Décrire un cas d’intoxication pédiatrique au tramadol chez un enfant porteur d’un génotype particulier du CYP2D6.

Rapporter l’expérience du laboratoire du CHU de Lille dans la mise en œuvre en 24/24 d’un screening toxicologique par spectrométrie de masse haute résolution (CL-SMHR), et illustrer les capacités d’adaptation de cet outil aux nécessités cliniques.

Objectives: Ethyl-β-D-6-glucuronide (EtG) is a minor phase-II metabolite of ethanol. The aim of this work was to develop and validate a gas chromatography negative chemical ionization tandem mass spectrometry (GC-NCI-MS/MS) method to measure EtG levels in human urine and serum with both high sensitivity and specificity. Methods: EtG was extracted and purified from 1 mL urine or 0.5 mL serum by solid-phase extraction (SPE) using Mixed-mode Anion-eXchange (Oasis®MAX) extraction cartridges, followed by derivatization with pentafluoropropionic anhydride (PFPA). The analysis was performed in the multiple reaction monitoring (MRM) mode using the transitions m/z 496→163 (for EtG quantification), m/z 347→163 and m/z 496→119 (for identification), and m/z 501→163 for the internal standard EtG-D5. The validation procedure was performed according to the guidelines of the French Society of Analytical Toxicology (SFTA) and the French Committee of Accreditation (COFRAC; LAB GTA 04). Results: Calibration curves were linear in the concentration range of 10 to 10 000 ng/mL and 5 to 1 000 ng/mL in urine and serum, respectively, with a coefficient of correlation (r) above 0.996. The LOD and LOQ values were 5 and 10 ng/mL, respectively, for both matrices. The intra- and inter-day precision (relative standard deviation RSD%) and relative bias were less than 20%. Conclusion: To our knowledge, this is the first report of the application of a GC-MS/MS method for EtG measurement in urine and serum. The LOQ achieved appears to be better than those reported in the literature using other validated analytical techniques. This method could be used routinely for EtG measurement in various clinical and forensic contexts.

Background Food technology transfer to rural households, based on local ingredients, is a relevant and sustainable strategy to ensure better nutrition of young children.Objective To develop an improved mush based on local ingredients and evaluate the potential for transferring its technology to rural housewives.Methods We developed a flour-based food using Alicom software and performed laboratory trials to evaluate its actual nutritional quality. Then we recruited housewives from each of the 27 project villages and trained them in flour production and mush preparation twice daily, 6 days a week, for 26 weeks. Mush was sampled during the training session and at weeks 4, 12, and 22 and evaluated for actual flow distance and dry matter content, which served to estimate energy density and iron and zinc contents.Results The laboratory trials reported average energy densities of 103 kcal/100 g, iron contents of 2.6 mg/100 kcal, and zinc contents of 1.2 mg/100 kcal. The average (±SD) energy densities of the mush samples obtained during the training session and at weeks 4, 12, and 22 were 103.0 ± 5.6,103.3 ± 5.2,107.9 ± 11.5, and 101.3 ± 8.7 kcal/100 g, respectively. The average iron contents were 2.3 ± 0.5,2.3 ± 0.5,2.6 ± 0.3, and 1.8± 0.8 mg/ 100 kcal, respectively, and the average zinc contents were 1.6± 0.1, 1.6± 0.1,1.7 ± 0.1, and 1.6± 0.2 mg/100 kcal.Conclusions Developing a suitable complementary food from local ingredients and educating households in nutrition and use of local products are feasible. Such education should come with measures aimed at improving the accessibility of some ingredients to ensure feasibility and sustainability.

This study aims to investigate the liability of foreignness, or the additional difficulties of foreign companies compared to their local competitors. Past studies have found fair amount of empirical evidences for the liability of foreignness. The present study attempts to take one step further by addressing two questions: what are the sources of such disadvantages and what are the solutions sought by the companies? To do this, we conducted a field study exploring the on-going dynamics of foreign multinationals. Specifically, we collected primary data through interviews with Dutch and Korean managers of Korean multinational companies. Through the interviews, we found evidence for the existence of such disadvantages. We identified four sources of the liability of foreignness - cross-border transfer, interaction with the local government, local discrimination, and interaction within the multinational - and two ways in which these companies actively reduced their exposure to the problem - localization and unfamiliarity reduction. This study should be useful to both practitioners and theorists in international business with an interest in disadvantages connected to the foreign status of a company.

It is shown how mesh‐centered finite differences can be obtained from unconventional mixed‐hybrid nodal finite elements. The classical Raviart‐Thomas schemes of index k(RTk) are based on interpolation parameters that are cell and/or edge moments. For the unconventional form (URTk), they become point values at Gaussian points. In particular, the scheme URT1 is fully described. © 2006 Wiley Periodicals, Inc. Numer Methods Partial Differential Eq 2006

In this paper we sketch a theory of the motives of alliances and joint ventures, deduce the reasons for their instability, and discuss the structural factors that affect their performance. We argue that the alliance literature, by focusing on knowledge internalization, has given short shrift to the empirically more important motive of knowledge access, a strategy we call ‘cooperative specialization’. Cooperative specialization allows firms to pool their competencies with those of their partner and to specialize in what they do best, but it also exposes them to opportunism. We discuss how such opportunism can be checked by proper structural design. The main issue is how to reward partners for their contribution to the alliance, and two main contractual forms are possible, ex anteand residual-sharing contracts, a category which includes equity joint ventures. Focusing on the latter, we investigate how various structural solutions can be used to align the interests of the joint venture partners.

In-hospital mortality from lower respiratory tract infections (LTRI) is unacceptably high in developing countries where LTRI are still a leading cause of death.

Using complementary theories derived from the foreign-entry mode and alliance literatures and two databases on Japanese/US alliances and investments, this study examines the prevalence — a combination of formation and termination — of the full range of investment and cross-border linkage alternatives available to firms. We find that some combinations among the administrative forms, the knowledge flow intent between the partners, and industry-related technology and risk factors were more prevalent than others. Specifically, there were three prevalent combinations consistent with the notions of production efficiency, transaction cost efficiency and learning/adaptation: (1) wholly owned subsidiaries in low R&D-intense industries with the intent of unidirectional knowledge flow; (2) joint ventures in medium R&D-intense industries with reciprocal knowledge flows; and (3) technical agreements with reciprocal knowledge flows in high-tech industries.

Study objectiveComparison of children's nutritional status in refugee populations with that of local host populations, one year after outbreak refugee crisis in the North Kivu region of Democratic Republic of Congo.DesignCross sectional surveys.SettingTemporary and other settlements, in the town of Goma and surrounding rural areas.SubjectsAnthropometric indicators of nutritional status and presence or absence of oedema were measured among 5121 children aged 6 to 59 months recruited by cluster sampling with probability proportional to size, between June and August 1995.ResultsChildren in all locations demonstrated a typical pattern of growth deficit relative to international reference. Prevalence of acute malnutrition (wt/ht < -2 Z score) was higher among children in the rural non-refugee populations (3.8 and 5.8%) than among those in the urban non-refugee populations (1.4%) or in the refugee population living in temporary settlements (1.7%). Presence of oedema was scarcely noticed in camps (0.4%) while it was a common observation at least in the most remote rural areas (10.1%). As compared with baseline data collected in 1989, there is evidence that nutritional status was worsening in rural non-refugee populations.ConclusionsChildren living in the main town or in the refugee camps benefited the most from nutritional relief while those in the rural non-refugee areas were ignored. This is a worrying case of inequity in nutritional relief.

Depuis 2019, le laboratoire de toxicologie du CHU de Lille met en œuvre en 24/24 un criblage toxicologique par spectrométrie de masse haute résolution (CL-SMHR) pour répondre aux demandes de recherche large de xénobiotiques en urgence (urgentistes et réanimateurs du CHU et des hôpitaux périphériques). Cette méthode analytique repose sur une étape d’extraction en ligne (colonne OASIS HLB) avant une séparation chromatographique en 15minutes (colonne ACQUITY HSS C18). L’acquisition et le retraitement des données est réalisée par un Xevo G2 Q-TOF en et l’identification est réalisée à l’aide d’une bibliothèque de plus de 1600 substances incluant plus de 650 NPS et métabolites (RichevalC. Thèse de Doctorat, Université de Lille, Septembre 2018). Nous rapportons la transformation ponctuelle de cette méthode de criblage en une méthode de dosage adaptée à un suivi toxicocinétique en temps réel d’une intoxication par amlodipine et aténolol.

Les intoxications pédiatriques peuvent survenir dans un contexte accidentel, parfois en lien avec une négligence, voire un contexte de maltraitance, entraînant d’éventuelles conséquences médico-légales ou médico-sociales. Dans leur prise en charge, les frontières médicales et médico-légales sont proches et le dialogue clinico-biologique indispensable. Nous l’illustrons par un cas d’intoxication éthylique aiguë pédiatrique.

La dépendance au tramadol (TR), antalgique morphinomimétique le plus prescrit en France, est une réalité inquiétante : obtention illégale en augmentation (enquête OPPIDUM 2018) et implication la plus fréquente dans les décès, directs ou indirects (par ex. par noyade), par antalgiques : 49/119 décès de l’enquête DTA 2018. Nous rapportons ici un type particulier de décès : celui d’un nourrisson (Mort Inattendue du Nourrisson ou MIN) en lien avec l’addiction au TR d’un parent en période de confinement lié à la pandémie de COVID-19.

Day-case anaesthesia requires rapidly eliminated anaesthetics which are relatively expensive. This multinational, multicentre European study assessed the relative costs of propofol or sevoflurane anaesthesia in 211 patients. Anaesthesia was induced and maintained with propofol in group 1, with propofol and sevoflurane in group 2, and with sevoflurane in group 3. Drug and delivery costs were calculated in US$. Induction of anaesthesia was fastest in groups 1 and 2, although spontaneous ventilation resumed earliest in group 3. Emergence times and times at which patients were fit for discharge were similar in all groups. Group 2 had the lowest costs based on actual drug use (mean $14.2 (SEM 0.8) vs $18.7 (0.8) and $17.3 (0.8) in groups 1 and 3, respectively). Anaesthetic drug wastage and disposable costs were highest in group 1 and lowest in group 3. Consequently, total costs were highest in group 1 ($31.9 (0.9)) compared with groups 2 ($19.7 (0.9)) and 3 ($18.8 (0.9)). Although we observed increased nausea and vomiting in groups 2 and 3 and reduced patient satisfaction in group 3, these differences should be balanced against the greater cost of propofol anaesthesia.

The efficacy of dobutamine and dopamine in association with calcium chloride to improve the hemodynamic state at the end of cardiopulmonary bypass (CPB) has been investigated in 34 patients after isolated aortic valve replacement. The heart rate, cardiac index, left ventricular dp/dt maximum (LV dp/dt max), systemic arterial blood pressure, mean central venous pressure (MCVP), stroke volume index (SVI), left ventricular stroke work index (LVSWI), and systemic vascular resistance (SVR) were measured in standardized conditions 3 minutes after the end of CPB, 2 minutes after calcium chloride (Ca 0.6 g / m2body surface area [BSA]) infused intravenously over 30 seconds, and finally 5 and 10 minutes after the start of either a dobutamine (17 patients) or a dopamine (17 patients) infusion (200 μg/min/m2BSA). Calcium infusion was followed by a substantial improvement in the cardiovascular state, principally cardiac index (+ 10%, p < 0.01), LV dp/dt max (+42%, p < 0.001), and LVSWI (+ 16%, p < 0.001). No significant variations were observed in heart rate and SVR. Further increases in cardiac performance were obtained after dobutamine and dopamine infusions: cardiac index, +34% with dobutamine (p <0.001), +11% with dopamine (p <0.05); LV dp/dt max, +48% with dobutamine (p < 0.001), +51% with dopamine (p < 0.001); LVSWI, +48% with dobutamine (p < 0.05), +32% with dopamine (p < 0.05); heart rate, +19% with dobutamine (p <0.01), +9% with dopamine (p < 0.001); SVR, + 14% with dopamine (p < 0.05), −3% with dobutamine (NS). In conclusion, the additional effects of the calcium-dobutamine association were more marked than those of the calcium-dopamine association at the end of CPB.

AbstractA nodal algorithm for the solution of the multigroup diffusion equations in hexagonal arrays is analyzed. Basically, the method consists of dividing each hexagon into four quarters and mapping the hexagon quarters onto squares. The resulting boundary value problem on a quadrangular domain is solved in primal weak formulation. Nodal finite element methods like the Raviart-Thomas RTk schemes provide accurate analytical expansions of the solution in the hexagons. Transverse integration cannot be performed on the equations in the quadrangular domain as simply as it is usually done on squares because these equations have essentially variable coefficients. However, by considering an auxiliary problem with constant coefficients (on the same quadrangular domain) and by using a “preconditioning” approach, transverse integration can be performed as for rectangular geometry. A description of the algorithm is given for a one-group diffusion equation. Numerical results are presentedfor a simple model problem with a known analytical solution and for keffevaluations ofsome benchmark problems proposed in the literature. For the analytical problem, the results indicate that the theoretical convergence Orders of RTk schemes (k = 0,1) are obtained, yielding accurate solutions at the expense of a few preconditioning iterations.

To determine whether significant historical differences distinguish the near-miss for Sudden Infant Death from the infants who died of SIDS, we analysed the histories and clinical data from two groups of infants seen in our University Hospital and from collaborative research group. The data were obtained with the use of a standardised questionnaire and consultation of all available medical data.

To determine the prevalence of enteroaggregative Escherichia coli(EAggEC) in African diarrheal children in Lwiro, Congo, to characterize EAggEC isolates by possible genotypic and phenotypic markers, and to evaluate the EAggEC probe pCVD432 in identifying EAggEC.

An important concern in surveys of the prevalence of endemic goitre is the possibility of inaccuracy that can occur when estimating thyroid enlargement by clinical examination. We report here the results of a study from central Africa that demonstrated the importance of interobserver variation in the assessment of goitre size among experts and participants attending an international training course on iodine deficiency disorders (IDD). Agreement among raters estimated by calculation of the kappa statistic was poor on average when the five-stage goitre classification recommended by WHO was used. As expected, agreement on a single category was slightly better, especially when the category of interest was visible goitre. Our results suggest that palpation alone is not a reliable method for assessing the severity of IDD endemia. Other sources of inaccuracies are discussed and recommendations are made for better data collection on IDD in Africa and other regions.

A general formalism using piecewise continuous functions in “time” is proposed for the discretization of “initial” value problems. After some practical choices have been examined in Section 2, applications to kinetics and transport are mentioned in Section 3.

Summary The classical Ritz-Galerkin method is applied to a linear, second-order, self-adjoint boundary value problem. The coefficient functions of the operator exhibit a piecewise smooth behaviour characteristic of some “physical” situations. A trial function is constructed using a modified quintic smooth Hermite space $$\tilde H_0^{(3)} (\pi )$$ , in order to meet some desired regularity conditions for the approximate solution. A collocation technique is used to reduce the amount of computational work. Known convergence properties for the projection method are recalled which, in this particular case, are illustrated by a series of numerical experiments.

In companion papers (hereafter referred to as Part I and Part II), we described a generalized nodal finite element formalism, including practically all existing numerical schemes for solving the discrete ordinates equations in slab geometry. General discrete (or cell-edge) and continuous convergence orders as well as convergence orders for moments of the approximations were proved in several theorems given in Part I and II and they are verified here using a model problem. Finally the methods described in Part I and II are applied to some non-model problems.

A generalized nodal finite element formalism is presented, which covers virtually all known finite difference approximations to the discrete ordinates equations in slab geometry. This paper (hereafter referred to as Part II) presents the theory of the so-called "discontinuous moment methods", which include such well-known methods as the "linear discontinuous" scheme. It is the sequel of a first paper (Part I) where "continuous moment methods" were presented. Corresponding numerical results for all the schemes of both parts will be presented in a third paper (Part III).

A generalized nodal finite element formalism is presented, which covers virtually all known finite difference approximations to the discrete ordinates equations in slab geometry. This paper (Part I) presents the theory of the so-called "continuous moment methods", which include such well-known methods as the "diamond difference" and the "characteristic" schemes. In a second paper (hereafter referred to as Part II), we shall present the theory of the "discontinuous moment methods", consisting in particular of the "linear discontinuous' scheme as well as of an entire new class of schemes. Corresponding numerical results are available for all these schemes and will be presented in a third paper (Part III).

Objective: To determine the prevalence of enteroaggregative Escherichia coli(EAggEC) in African diarrheal children in Lwiro, Congo, to characterize EAggEC isolates by possible genotypic and phenotypic markers, and to evaluate the EAggEC probe pCVD432 in identifying EAggEC.

After it is shown that the classical five-point mesh-centered finite difference scheme can be derived from a low-order nodal finite element scheme by using nonstandard quadrature formulae, higher-order block mesh-centered finite difference schemes for second-order elliptic problems are derived from higher-order nodal finite elements with nonstandard quadrature formulae as before, combined to a procedure known as “transverse integration.” Numerical experiments with uniform and nonuniform meshes and different types of boundary conditions confirm the theoretical predictions, in discrete as well as continuous norms. © 1998 John Wiley & Sons, Inc. Numer Methods Partial Differential Eq 14: 439–465, 1998

We recorded adductor pollicis mechanical activity in response to low (0.1 and 2 Hz) and high (50 and 100 Hz) frequency stimulation 15 min after edrophonium 250, 500 and 1000 micrograms kg-1, given to antagonize vecuronium-induced block at 10, 25 and 50% pre-reversal twitch height. We studied 54 ASA class I and II anaesthetized (methohexitone, fentanyl, nitrous oxide) young adult patients allocated randomly to nine groups of six patients each. The greater sensitivity of train-of four (TOF) ratio and residual force after 100-Hz, 5-s tetanic stimulation (RF100) to residual deficit allowed discrimination more readily between the effects of edrophonium dose and pre-reversal twitch height (P < 0.001, two-way analysis of variance). The highest reversal scores (approximately 0.9 TOF ratio and 0.6 RF100) were obtained when edrophonium 500-1000 mg kg-1 was given at 50% twitch height (P < 0.05, Duncan's test).

After it is shown that the classical five‐point mesh‐centered finite difference scheme can be derived from a low‐order nodal finite element scheme by using nonstandard quadrature formulae, higher‐order block mesh‐centered finite difference schemes for second‐order elliptic problems are derived from higher‐order nodal finite elements with nonstandard quadrature formulae as before, combined to a procedure known as “transverse integration.” Numerical experiments with uniform and nonuniform meshes and different types of boundary conditions confirm the theoretical predictions, in discrete as well as continuous norms. © 1998 John Wiley & Sons, Inc. Numer Methods Partial Differential Eq 14: 439–465, 1998

In developing countries, severe vitamin A deficiency is associated with increased child mortality. In Kivu, Zaïre, child mortality rate is approximately 50 per 1000 per year and protein calorie malnutrition is endemic. To evaluate vitamin A status in this population, we measured plasma retinol levels in 28 severely malnourished hospitalized children (plasma albumin level below 3 g/dl), and in 153 outpatients (mean plasma albumin level: 3.19 +/- 0.7 g/dl) as controls. Sixty percent of inpatients and 37 percent of out-patients had retinol levels below 10 micrograms/dl (P = 0.02) suggesting a high prevalence of severe vitamin A deficiency in this population. We found that plasma retinol levels were correlated with low retinol binding protein plasma levels (r = 0.77). We conclude that although vitamin A deficiency probably exists in this malnourished population, low retinol levels could at least partly be related to decreased levels of its carrier protein.

SummaryBiological markers were used in an attempt to predict mortality in children admitted to the hospital in Kivu, Zaire, for protein energy malnutrition. Data for 39 children who died (16.4) showed significantly lower levels of albumin (1.61 vs. 2.53 g/dl; p < 0.001), transferrin (82.1 vs. 167.7 mg/dl; p < 0.001), and transthyretin (6.49 vs. 9.87 mg/dl; p < 0.001), but not of retinol-binding protein, than for the 199 survivors. Since albumin and transferrin were correlated, a Cox model was used to see whether albumin or transferrin has a significant predictive value independent of transthyretin. The relative risk predicted by each indicator was of the same order of magnitude, ∼4. We conclude that specific biological markers help to discriminate among hospitalized subjects at risk and to identify those in need of more intensive nutritional support to prevent early death.

New methods are proposed for the numerical solution of systems of first-order differential equations. On each subinterval of a given mesh of size h, a polynomial of degree l is constructed, its parameters being determined by a multiple collocation technique. The resulting piecewise polynomial approximation is of order $ O({h^{l + 1}})$jth derivatives of the approximation on each subinterval provide approximations of order $ O({h^{l + 1 - j}})$ $ j = 1, \ldots ,l$A-stable or even strongly A-stable.

In 24 ASA I-II adults anaesthetized with thiopentone, fentanyl and nitrous oxide in oxygen, we studied neuromuscular transmission with isometric adductor pollicis monitoring. Patients received mivacurium 0.2 mg kg-1 followed by an infusion lasting at least 60 min and adjusted to maintain twitch height at 1-5%. After termination of the mivacurium infusion, when twitch height spontaneously regained 25% of its control value, the patients were allocated to two groups of 12 patients each. In group NEO patients received neostigmine 40 micrograms kg-1 and atropine 15 micrograms kg-1 and in group SPO neuromuscular transmission was allowed to recover spontaneously. Twitch height was measured every 10 s and train-of-four (TOF) (2 Hz) every 3 min. After 15 min, residual force after tetanic stimulation (50 and 100 Hz, 5-s duration (RF50HZ, RF100HZ), 1 min apart) were recorded sequentially. At 15 min, mean TOF ratio was greater in group NEO (0.94 (SEM 0.01)) than in group SPO (0.87 (0.02)) (P < 0.01). All patients in group NEO recovered to a TOF ratio greater than 0.7 after 6 min compared with 15 min in group SPO (P < 0.005). A TOF ratio greater than 0.9 was observed in all patients in group NEO compared with only six in group SPO (P < 0.025). Nevertheless, RF50HZ and RF100HZ did not differ significantly (0.92 (0.01) (group NEO), 0.91 (0.01) (group SPO) and 0.83 (0.02) (group NEO), 0.78 (0.03) (group SPO), respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Summary In this paper, we propose an algorithm to derive nodal methods corresponding to various two and three-dimensional nonconforming and mixed finite elements. We show that this algorithm can be used to obtain several classical schemes as well as some more recently developed schemes, and that it leads to a simple proof of unisolvence for these methods. Finally we use our method to obtain a three dimensional nodal scheme of BDM type.