Valganciclovir in adult solid organ transplant recipients: pharmacokinetic and pharmacodynamic characteristics and clinical interpretation of plasma concentration measurements.

Valganciclovir and ganciclovir are widely used for the prevention of cytomegalovirus (CMV) infection in solid organ transplant recipients, with a major impact on patients' morbidity and mortality. Oral valganciclovir, the ester prodrug of ganciclovir, has been developed to enhance the oral bioavailability of ganciclovir. It crosses the gastrointestinal barrier through peptide transporters and is then hydrolysed into ganciclovir. This review aims to describe the current knowledge of the pharmacokinetic and pharmacodynamic characteristics of this agent, and to address the issue of therapeutic drug monitoring. Based on currently available literature, ganciclovir pharmacokinetics in adult solid organ transplant recipients receiving oral valganciclovir are characterized by bioavailability of 66 +/- 10% (mean +/- SD), a maximum plasma concentration of 3.1 +/- 0.8 mg/L after a dose of 450 mg and of 6.6 +/- 1.9 mg/L after a dose of 900 mg, a time to reach the maximum plasma concentration of 3.0 +/- 1.0 hours, area under the plasma concentration-time curve values of 29.1 +/- 5.3 mg.h/L and 51.9 +/- 18.3 mg.h/L (after 450 mg and 900 mg, respectively), apparent clearance of 12.4 +/- 3.8 L/h, an elimination half-life of 5.3 +/- 1.5 hours and an apparent terminal volume of distribution of 101 +/- 36 L. The apparent clearance is highly correlated with renal function, hence the dosage needs to be adjusted in proportion to the glomerular filtration rate. Unexplained interpatient variability is limited (18% in apparent clearance and 28% in the apparent central volume of distribution). There is no indication of erratic or limited absorption in given subgroups of patients; however, this may be of concern in patients with severe malabsorption. The in vitro pharmacodynamics of ganciclovir reveal a mean concentration producing 50% inhibition (IC(50)) among CMV clinical strains of 0.7 mg/L (range 0.2-1.9 mg/L). Systemic exposure of ganciclovir appears to be moderately correlated with clinical antiviral activity and haematotoxicity during CMV prophylaxis in high-risk transplant recipients. Low ganciclovir plasma concentrations have been associated with treatment failure and high concentrations with haematotoxicity and neurotoxicity, but no formal therapeutic or toxic ranges have been validated. The pharmacokinetic parameters of ganciclovir after valganciclovir administration (bioavailability, apparent clearance and volume of distribution) are fairly predictable in adult transplant patients, with little interpatient variability beyond the effect of renal function and bodyweight. Thus ganciclovir exposure can probably be controlled with sufficient accuracy by thorough valganciclovir dosage adjustment according to patient characteristics. In addition, the therapeutic margin of ganciclovir is loosely defined. The usefulness of systematic therapeutic drug monitoring in adult transplant patients therefore appears questionable; however, studies are still needed to extend knowledge to particular subgroups of patients or dosage regimens.

Allergy to betalactam antibiotics in children: results of a 20-year study based on clinical history, skin and challenge tests.

To cite this article: Ponvert C, Perrin Y, Bados-Albiero A, Le Bourgeois M, Karila C, Delacourt C, Scheinmann P, De Blic J. Allergy to betalactam antibiotics in children: results of a 20-year study based on clinical history, skin and challenge tests. Pediatr Allergy Immunol 2011; 22: 411-418. ABSTRACT: Studies based on skin and challenge tests have shown that 12-60% of children with suspected betalactam hypersensitivity were allergic to betalactams. Responses in skin and challenge tests were studied in 1865 children with suspected betalactam allergy (i) to confirm or rule out the suspected diagnosis; (ii) to evaluate diagnostic value of immediate and non-immediate responses in skin and challenge tests; (iii) to determine frequency of betalactam allergy in those children, and (iv) to determine potential risk factors for betalactam allergy. The work-up was completed in 1431 children, of whom 227 (15.9%) were diagnosed allergic to betalactams. Betalactam hypersensitivity was diagnosed in 50 of the 162 (30.9%) children reporting immediate reactions and in 177 of the 1087 (16.7%) children reporting non-immediate reactions (p < 0.001). The likelihood of betalactam hypersensitivity was also significantly higher in children reporting anaphylaxis, serum sickness-like reactions, and (potentially) severe skin reactions such as acute generalized exanthematic pustulosis, Stevens-Johnson syndrome, and drug reaction with systemic symptoms than in other children (p < 0.001). Skin tests diagnosed 86% of immediate and 31.6% of non-immediate sensitizations. Cross-reactivity and/or cosensitization among betalactams was diagnosed in 76% and 14.7% of the children with immediate and non-immediate hypersensitivity, respectively. The number of children diagnosed allergic to betalactams decreased with time between the reaction and the work-up, probably because the majority of children with severe and worrying reactions were referred for allergological work-up more promptly than the other children. Sex, age, and atopy were not risk factors for betalactam hypersensitivity. In conclusion, we confirm in numerous children that (i) only a few children with suspected betalactam hypersensitivity are allergic to betalactams; (ii) the likelihood of betalactam allergy increases with earliness and/or severity of the reactions; (iii) although non-immediate-reading skin tests (intradermal and patch tests) may diagnose non-immediate sensitizations in children with non-immediate reactions to betalactams (maculopapular rashes and potentially severe skin reactions especially), the diagnostic value of non-immediate-reading skin tests is far lower than the diagnostic value of immediate-reading skin tests, most non-immediate sensitizations to betalactams being diagnosed by means of challenge tests; (iv) cross-reactivity and/or cosensitizations among betalactams are much more frequent in children reporting immediate and/or anaphylactic reactions than in the other children; (v) age, sex and personal atopy are not significant risk factors for betalactam hypersensitivity; and (vi) the number of children with diagnosed allergy to betalactams (of the immediate-type hypersensitivity especially) decreases with time between the reaction and allergological work-up. Finally, based on our experience, we also propose a practical diagnostic approach in children with suspected betalactam hypersensitivity.

Iowa Flood Mitigation Board Annual Report, 2013

The Iowa Flood Mitigation Program is created within Code of Iowa, Chapter 418. The Program seeks to provide funds for flood mitigation projects that otherwise would not be funded. The Flood Mitigation Board is responsible for the implementation Code of Iowa Chapter 418. The membership of the Board is comprised of four voting public members appointed by the Governor, five voting members representing state agencies, and four non-voting ex-officio members of the legislature.

Ethics and adolescent care: an international perspective.

PURPOSE OF REVIEW: This update reviews the concepts underlying ethical issues in various contexts and countries, highlighting the evolution in the use of the core values underpinning the field and practice of bioethics as applied to healthcare. RECENT FINDINGS: It stresses the specific position of the adolescent as being a unique individual searching for autonomy and, most of the time, being competent to make decisions regarding the adolescent's own health. It briefly outlines the principles of a 'deliberative' approach in which the practitioner, while keeping in mind the legal context of the country where the practitioner is working, assesses to what extent the adolescent can be considered as competent, and then discusses with the adolescent the medical and psychosocial aspects of the various actions to be taken in a situation, as well as the basic ethical values linked with each of the various options available. The deliberation can involve relevant stakeholders, provided the issues concerning confidentiality have been fully discussed with the adolescent. SUMMARY: This process forces the practitioner, the adolescent patient and those who care for the adolescent patient to look outside their usual frameworks and make a decision that is in the best interest of the young person, and is informed by various ethical values.

Biologia e exigências térmicas do ácaro-vermelho (Tetranychus ludeni Zacher) em folhas de algodoeiro

O objetivo deste trabalho foi estudar a biologia e as exigências térmicas de Tetranychus ludeni Zacher (Acari: Tetranychidae) em folhas de algodoeiro (Gossypium hirsutum L. r. latifolium (Hutch)). Foram utilizadas câmaras climatizadas, ajustadas nas temperaturas de 20, 23, 25, 28 e 30ºC, umidade relativa de 70% e fotófase de 12 horas. Os períodos de desenvolvimento de ovo a adulto variaram de 20,77 (20ºC) a 8,50 dias (30ºC), em fêmeas, e de 18,83 (20ºC) a 7,75 dias (30ºC), em machos. As temperaturasbase, estimadas pelo método da intersecção de X, para os períodos de desenvolvimento de ovoadulto, foram de 14,05ºC para fêmeas e 13,91ºC para machos, enquanto os valores da constante térmica estimados de acordo com a lei de Réamur foram de 138,34 grausdia, para fêmeas e 130,91 grausdia, para machos. Na temperatura de 30ºC foram observados os maiores valores de razão intrínseca de crescimento (0,418), número de ovos de fêmeas/dia (3,47), fecundidade (61,29) e taxa líquida de reprodução (48,00) e o menor valor para o tempo médio de uma geração (9,27).

Produtos agrícolas e florestais como alimento suplementar de tambaqui em policultivo com jaraqui

O objetivo deste trabalho foi avaliar o desempenho de tambaqui (Colossoma macropomum), em policultivo com jaraqui (Semaprochilodus insignis), alimentado com produtos agrícolas e florestais como suplemento. Dois viveiros, medindo 644 m² (Viveiro A, consorciado com suínos) e 1.075 m² (Viveiro B, não-consorciado), foram utilizados com 0,5 tambaqui/m² e 0,1 jaraqui/m². Após 371 dias, os tambaquis apresentaram crescimento de 18,6±4,5 g para 997,1±195,08 g no Viveiro A e de 81,4±18,8 g para 519,9±191,7 g no Viveiro B. O manejo alimentar do Viveiro A pode ser uma alternativa sustentável de produção de tambaqui em substituição às rações comerciais.

Summary of Early Triassic carbon isotope records

Much attention has been given to the negative d13C anomaly nearly coincident with the Permian-Triassic boundary. New data indicate a stepwise decline in d13C initiating before the Latest Permian extinction event followed by highly variable d13C values during the remaining Early Triassic. d13C values appear much less erratic as global metazoan diversity increased in the Middle Triassic. Given the previously unappreciated magnitude of isotopic change and the number of large d13C excursions that occurred during the Early Triassic, catastrophic mechanisms like methane release/bolide impact become less attractive to explain the Early Triassic carbon isotopic record as a whole.

Anciens catalogues de la Bibliothèque du Roi et de différentes collections qui sont venues l'accroître aux XVIIe, XVIIIe et XIXe siècles. Catalogues de divers fonds orientaux.

« Notices sur quelques manuscrits arabes, par M. Woepke (fol. 1) ; — Notices sur quelques mss. sanscrits, par M. Fauriel (fol. 6) ; — Notices sur quelques mss. sanscrits (fol. 40) ; — Notices sur quelques mss. sanscrits en caractère bengali, par M. Loiseleur Deslongchamps (fol. 58) ; — Notices sur quelques mss. arabes, par M. Hassler (fol. 94) ; — Notices sur quelques mss. arabes, par M. Reinaud (fol. 99) ; — Catalogue des mss. orientaux de l'ancienne maison de la Sorbonne, par M. Reinaud (fol. 126) ; — Catalogue des mss. orientaux de l'ancien couvent de l'Oratoire, par M. Reinaud (fol. 136) ; — Catalogue des mss. orientaux des différentes bibliothèques publiques de Paris (fol. 146) ; — Liste des livres et des mss. orientaux venus d'Alger et adressés à la Bibliothèque royale, le 30 nov. 1832 (fol. 152) ; — Note de quelques mss. orientaux appartenant à M. Wahl (fol. 156) ; — Mss. orientaux provenant de feu M. Schultz (fol. 157 et 159) ; — Mss., papiers et autres objets provenant de feu M. Schultz (fol. 163) ; — Collection Asselin (fol. 165 et 270) ; — Lettres et pièces relatives au fonds Asselin (fol. 263) ; — Mss. arabes, persans, samskrits et hindous tanys, cédés à la Bibliothèque du Roi par M. de Polier (fol. 291 et 293) ; — Évaluation de 47 mss. arabes, persans, maures, bengalis, etc., provenant de feu Ouessant, interprète de la Compagnie de Pondichéry (fol. 295) ; — Mss. arabes, turcs et persans de M. Ducaurroy (fol. 298) ; — Collection des mss. orientaux appartenant à la succession de feu M. le baron Rousseau, consul général à Tripoly de Barbarie (fol. 303) ; — Liste des mss. tamouls cédés à la Bibliothèque du Roi par M. Ducler (fol. 309) ; — Liste des mss. tamouls donnés à la Bibliothèque du Roi par M. Reydelet (fol. 311) ; — Mss, arabes et berbères de M. Delaporte père, 4848 (fol. 314) ; — État sommaire de quelques mss. réputés venir de feu M. Huet,... trouvés dans la maison Kerboeuf (fol. 323) ; — Mss. orientaux distraits du fonds Renaudot (fol. 324) ; — Mss. arabes rapportés d'Égypte par le citoyen Raiye (fol. 325) ; — Cinq volumes arabes mss. offerts à la Bibliothèque royale par S. A. R. Mgr le duc de Nemours (fol. 326) ; — Liste des livres qu'on a envoyés à Mrs de la Compagnie, en tamoul, 14 déc. 1729 (fol. 327) ; — Catalogue des mss. indiens de la Bibliothèque du Roi (fol. 328) ; — « Mémoire concernant l'acquisition des mss. persiens qu'il conviendroit de faire aux Indes pour la Bibliothèque du Roy » (fol. 362) ; — Mémoire de livres à rechercher dans le Levant pour la Bibliothèque du Roy (fol. 366) ; — État des mss. à rechercher à Constantinople pour la Bibliothèque impériale (fol. 384) ; — Catalogue des mss. orientaux appartenant à M. R. Johnson, 1806 (fol. 386) ; — Liste des mss. orientaux de la bibliothèque de sir Thomas Phillipps à Middlehill, 1829 (fol. 396) ; — Indication des mss. arabes les plus importants de la bibliothèque d'Alger (fol. 398) ; — Liste des livres et mss. venus d'Alger (fol. 402) ; — Liste des bibliothèques turques de Constantinople, 1854 (fol. 404) ; — Bibliothèque du sultan Ahmet III, au vieux sérail : catalogue des livres d'histoire, 1854 (fol. 408) ; — Note des mss. orientaux extraits de la bibliothèque de Vienne, que le conservatoire de la Bibliothèque impériale juge entièrement inutiles (fol. 416) ; — Notice par Ascari de l'ancien ms. syriaque 13 (fol. 418) ; — Manuscrits persans historiques de l'Indoustan, et livres en langue samscretam, apportés à la Bibliothèque du Roi en 1778 » (fol. 420).

Vitamina E no desempenho, características de carcaça e qualidade do presunto cozido de suínos

O objetivo deste trabalho foi avaliar o efeito da vitamina E sobre o desempenho, características de carcaça e qualidade do presunto. Noventa e seis suínos foram submetidos aos seguintes tratamentos: controle, 100, 200 e 400 mg de vitamina E por kg de ração, fornecidas a partir de 116 dias antes do abate. Após o abate, as carcaças foram avaliadas, resfriadas, desossadas e o pernil foi removido para fabricação de presunto cozido. Análises dos teores de vitamina E e ácido tiobarbitúrico (TBARS) foram realizadas em amostras de pernil e de presunto. A média do ganho de peso foi 789,81 g por dia, do consumo 2.418 g por dia e da conversão alimentar 3,06. Os animais apresentaram 113,57 kg de peso vivo; 85,90 kg de peso de carcaça; 75,62% de rendimento de carcaça; 61,28 mm de profundidade de lombo; 23,16 mm de espessura de toucinho e 49,28% de carne magra. Amostras de presunto com suplementação de vitamina E apresentaram de 0,61 a 1,19 mg kg-1 de TBARS, contra 1,77 a 3,91 mg kg-1 de TBARS do controle. Dietas com 200 mg vitamina E por kg de ração reduziram os níveis de oxidação em 70% no presunto cozido e diminuíram a espessura de toucinho.

Transepidermal water loss and resting energy expenditure in preterm infants.

Skin water loss of preterm infants, nursed naked in incubators under thermoneutral conditions, was assessed by a method based on the measurement of water vapor pressure gradient close to the skin surface. The corresponding skin evaporative heat loss was calculated using an energy equivalent of 0.58 kcal/g water vaporised. During the first 5 weeks of life, 128 sets of measurements were made on 56 infants whose gestational age ranged from 28 to 37 weeks. In the first week of life, infants of less than 30 weeks of gestation had substantially higher transepidermal water loss (TEWL) and skin evaporative heat loss (skin EHL) (41.5 +/- 11.5 g/kg X day TEWL; 24.1 +/- 6.5 kcal/kg X day skin EHL) than infants of 34 weeks and greater (11.1 +/- 4.1 g/kg X day; 6.4 +/- 2.4 kcal/kg X day). Infants of 30-33 weeks of gestation had intermediate values (22.4 +/- 7.6 g/kg X day; 13 +/- 4.4 kcal/kg X day). From the third week of life on, TEWL was similar for all preterm infants, i.e. 14.2 +/- 2.6 to 12.7 +/- 1.9 g/kg X day and corresponds to skin EHL of 8.2 +/- 1.5 to 7.4 +/- 1.1 kcal/kg X day. There was a significant inverse relationship between gestational age and TEWL and also between postnatal age and TEWL. In an additional group of 7 preterm infants (30-34 weeks of gestation, mean postnatal age of 21 +/- 9 days) transepidermal water loss and energy expenditure were measured simultaneously. The skin evaporative heat loss (8.8 +/- 2.5 kcal/kg X day) accounted for 17 +/- 5% of energy expenditure (53.3 +/- 4.1 kcal/kg X day). This study emphasizes that in infants of less than 30 weeks of gestation, the transepidermal water loss is of great importance and makes a major contribution to water and heat balances.

Iowa Flood Mitigation Board Annual Report, 2014

The Iowa Flood Mitigation Program is created within Code of Iowa, Chapter 418. The Program seeks to provide funds for flood mitigation projects that otherwise would not be funded. The Flood Mitigation Board is responsible for the implementation Code of Iowa Chapter 418. The membership of the Board is comprised of four voting public members appointed by the Governor, five voting members representing state agencies, and four non-voting ex-officio members of the legislature.

Biocontrole da queima-das-bainhas e do nematoide-das-galhas e promoção de crescimento de plantas de arroz por rizobactérias

O objetivo deste trabalho foi avaliar a compatibilidade entre rizobactérias biocontroladoras pré-selecionadas e o efeito de suas combinações sobre a queima-das-bainhas (Rhizoctonia solani), a meloidoginose (Meloidogyne graminicola) e a promoção de crescimento de plantas de arroz. A compatibilidade foi determinada pela antibiose. O efeito das combinações de isolados foi avaliado por microbiolização de sementes de arroz, cultivar El Paso L144, com suspensões das rizobactérias DFs185 (Pseudomonas synxantha), DFs223 (P. fluorescens), DFs306 (ainda não identificada), DFs416 e DFs418 (Bacillus sp.). Essas rizobactérias foram usadas isoladamente ou combinadas em arranjos de dois, três e quatro isolados. O isolado DFs223 não foi combinado com nenhum outro por ser incompatível com os demais isolados. Cinco combinações de rizobactérias (DFs185/418, DFs306/416, DFs306/418, DFs416/418, DFs185/306/418) e o isolado DFs306 destacaram-se por reduzir a reprodução de M. graminicola e promover o crescimento das plantas. A combinação DFs185/306 apresentou os melhores resultados quanto ao controle de R. solani e à promoção de crescimento. A combinação DFs306/416 proporcionou os melhores resultados para o controle das duas doenças.