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1.
Paediatr Anaesth ; 31(2): 116-122, 2021 02.
Article de Anglais | MEDLINE | ID: mdl-33151606

RÉSUMÉ

Scientific presentations, usually given with slide presentation software such as PowerPoint™, are the most common method for disseminating knowledge to students and peers. Unfortunately, many are boring, text-heavy, and bullet point-riddled data dumps, with animations or cartoons that obscure or distract rather than clarify the message. These presentations, which we have all sat through and/or delivered, are often so dull that they are referred to as "death by PowerPoint™." In this paper, the authors intend to impart basic techniques for organizing and communicating information in the most effective, engaging, and actionable ways possible. We focus on three processes: generating ideas and outlining a talk, creating visually appealing uncluttered slides, and delivering an inspiring, practice-changing presentation. We also discuss considerations for a virtual presentation. We believe that even experienced speakers could benefit from reflecting on these recommendations and editing their slide presentations for clarity and simplicity.


Sujet(s)
Logiciel , Humains
2.
Pediatr Crit Care Med ; 19(4): e180-e188, 2018 Apr.
Article de Anglais | MEDLINE | ID: mdl-29377867

RÉSUMÉ

OBJECTIVES: Duplicative institutional review board/research ethics committee review for multicenter studies may impose administrative burdens and inefficiencies affecting study implementation and quality. Understanding variability in site-specific institutional review board/research ethics committee assessment and barriers to using a single review committee (an increasingly proposed solution) can inform a more efficient process. We provide needed data about the regulatory oversight process for the Sepsis PRevalence, OUtcomes, and Therapies multicenter point prevalence study. DESIGN: Survey. SETTING: Sites invited to participate in Sepsis PRevalence, OUtcomes, and Therapies. SUBJECTS: Investigators at sites that expressed interest and/or participated in Sepsis PRevalence, OUtcomes, and Therapies. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Using an electronic survey, we collected data about 1) logistics of protocol submission, 2) institutional review board/research ethics committee requested modifications, and 3) use of a single institutional review board (for U.S. sites). We collected surveys from 104 of 167 sites (62%). Of the 97 sites that submitted the protocol for institutional review board/research ethics committee review, 34% conducted full board review, 54% expedited review, and 4% considered the study exempt. Time to institutional review board/research ethics committee approval required a median of 34 (range 3-186) days, which took longer at sites that required protocol modifications (median [interquartile range] 50 d [35-131 d] vs 32 d [14-54 d)]; p = 0.02). Enrollment was delayed at eight sites due to prolonged (> 50 d) time to approval. Of 49 U.S. sites, 43% considered using a single institutional review board, but only 18% utilized this option. Time to final approval for U.S. sites using the single institutional review board was 62 days (interquartile range, 34-70 d) compared with 34 days (interquartile range, 15-54 d) for nonsingle institutional review board sites (p = 0.16). CONCLUSIONS: Variability in regulatory oversight was evident for this minimal-risk observational research study, most notably in the category of type of review conducted. Duplicative review prolonged time to protocol approval at some sites. Use of a single institutional review board for U.S. sites was rare and did not improve efficiency of protocol approval. Suggestions for minimizing these challenges are provided.


Sujet(s)
Évaluation éthique , Comités d'éthique de la recherche/statistiques et données numériques , Sepsie/épidémiologie , Humains , Prévalence , Études prospectives , Plan de recherche/statistiques et données numériques , Sepsie/thérapie , Enquêtes et questionnaires , Facteurs temps
3.
JMIR Res Protoc ; 5(3): e159, 2016 Aug 02.
Article de Anglais | MEDLINE | ID: mdl-27485934

RÉSUMÉ

BACKGROUND: Evidence increasingly indicates that childhood obesity prevention efforts should begin as early as infancy. However, few interventions meet the needs of families whose infants are at increased obesity risk due to factors including income and maternal body mass index (BMI). Social media peer groups may offer a promising new way to provide these families with the knowledge, strategies, and support they need to adopt obesity prevention behaviors. OBJECTIVE: The aim of this study is to develop and pilot test a Facebook-based peer group intervention for mothers, designed to prevent pediatric obesity and promote health beginning in infancy. METHODS: We conducted in-depth semi-structured interviews with 29 mothers of infants and focus groups with 30 pediatric clinicians, to inform the development of a theory-based intervention. We then conducted a single-group pilot trial with 8 mothers to assess its feasibility and acceptability. All participants were recruited offline at pediatric primary care practices. Participants in the pilot trial joined a private Facebook group, moderated by a psychologist, with a weekly video-based curriculum, and also had the option to meet at a face-to-face event. Within the Facebook group, mothers were encouraged to chat, ask questions, and share photos and videos of themselves and babies practicing healthy behaviors. Consistent with the literature on obesity prevention, the curriculum addressed infant feeding, sleep, activity, and maternal well-being. Feasibility was assessed using the frequency and content of group participation by mothers, and acceptability was measured using online surveys and phone interviews. RESULTS: Based on preferences of mothers interviewed (mean BMI 35 kg/m(2), all Medicaid-insured, mean age 27, all Black), we designed the intervention to include frequent posts with new information, videos showing parents of infants demonstrating healthy behaviors, and an optional face-to-face meeting. We developed a privacy and safety plan that met the needs of participants as well as the requirements of the local institutional review board (IRB), which included use of a "secret" group and frequent screening of participant posts. Clinicians, 97% (29/30) women and 87% (26/30) pediatricians, preferred no direct involvement in the intervention, but were supportive of their patients' participation. In our 8-week, single group pilot trial, all participants (mean BMI 35 kg/m(2), all Medicaid-insured, mean age 28, all Black) viewed every weekly video post, and interacted frequently, with a weekly average of 4.4 posts/comments from each participant. All participant posts were related to parenting topics. Participants initiated conversations about behaviors related to healthy infant growth including solid food introduction, feeding volume, and managing stress. All 8 pilot group participants reported that they found the group helpful and would recommend it to others. CONCLUSIONS: Our methodology was feasible and acceptable to low-income mothers of infants at high risk of obesity, and could be adapted to implement peer groups through social media for underserved populations in varied settings. CLINICALTRIAL: ClinicalTrials.gov NCT01977105; https://clinicaltrials.gov/ct2/show/NCT01977105 (Archived by WebCite at http://www.webcitation.org/6iMFfOBat).

4.
J Gerontol Soc Work ; 58(6): 572-89, 2015.
Article de Anglais | MEDLINE | ID: mdl-26016650

RÉSUMÉ

We examine the 10-year follow-up effects on retirement saving of an individual development account (IDA) program using data from a randomized experiment that ran from 1998 to 2003 in Tulsa, Oklahoma. The IDA program included financial education, encouragement to save, and matching funds for several qualified uses of the saving, including contributions to retirement accounts. The results indicate that as of 2009, 6 years after the program ended, the IDA program had no impact on the propensity to hold a retirement account, the account balance, or the sufficiency of retirement balances to meet retirement expenses.


Sujet(s)
Services bancaires aux particuliers , Éducation du patient comme sujet , Pensions , Pauvreté , Retraite/économie , Sujet âgé , Éducation/méthodes , États financiers/statistiques et données numériques , Humains , Oklahoma , Éducation du patient comme sujet/méthodes , Éducation du patient comme sujet/organisation et administration , Pauvreté/économie , Pauvreté/statistiques et données numériques , Mise au point de programmes , Répartition aléatoire
5.
Pediatrics ; 134(5): 1006-12, 2014 Nov.
Article de Anglais | MEDLINE | ID: mdl-25287456

RÉSUMÉ

It is difficult to do scientifically rigorous research on treatments that must be administered urgently or emergently. Therefore, such treatments are often provided without a strong evidence base. Research would be facilitated if it were permissible to waive the requirement for parental consent. However, that raises a different set of concerns. Federal regulations allow waiver of the requirement for consent but only if studies meet certain conditions. Institutional review boards must decide whether those conditions are met. Sometimes, reasonable people disagree. We present and analyze a protocol for which investigators request a waiver of consent.


Sujet(s)
Services des urgences médicales/éthique , Nouveau-né , Consentement parental/éthique , Essais contrôlés randomisés comme sujet/éthique , Services des urgences médicales/méthodes , Humains , Consentement libre et éclairé/éthique , Essais contrôlés randomisés comme sujet/méthodes
9.
Paediatr Anaesth ; 23(7): 655-64, 2013 Jul.
Article de Anglais | MEDLINE | ID: mdl-23679061

RÉSUMÉ

Dr. John J. 'Jack' Downes (1930-), the anesthesiologist-in-chief at The Children's Hospital of Philadelphia (1972-1996), has made numerous contributions to pediatric anesthesia and critical care medicine through a broad spectrum of research on chronic respiratory failure, status asthmaticus, postoperative risks of apnea in premature infants, and home-assisted mechanical ventilation. However, his defining moment was in January 1967, when The Children's Hospital of Philadelphia inaugurated its pediatric intensive care unit--the first of its kind in North America. During his tenure, he and his colleagues trained an entire generation of pediatric anesthesiologists and intensivists and set a standard of care and professionalism that continues to the present day. Based on an interview with Dr. Downes, this article reviews a career that advanced pediatric anesthesia and critical care medicine and describes the development of that first pediatric intensive care unit at The Children's Hospital of Philadelphia.


Sujet(s)
Anesthésiologie/histoire , Soins de réanimation/histoire , Hôpitaux pédiatriques/histoire , Pédiatrie/histoire , Enfant , Histoire du 20ème siècle , Humains , Philadelphie
10.
JAMA Pediatr ; 167(7): 603-5, 2013 Jul.
Article de Anglais | MEDLINE | ID: mdl-23700102
12.
Anesth Analg ; 109(3): 727-36, 2009 Sep.
Article de Anglais | MEDLINE | ID: mdl-19690239

RÉSUMÉ

BACKGROUND: The safety of 2-h preoperative clear liquid fasts has not been established for overweight/obese pediatric day surgical patients. Healthy children and obese adults who fasted 2 h have small residual gastric fluid volumes (GFVs), which are thought to reflect low pulmonary aspiration risk. We sought to measure the prevalence of overweight/obesity in our day surgery population. We hypothesized that neither body mass index (BMI) percentile nor fasting duration would significantly affect GFV or gastric fluid pH. In children who were allowed clear liquids up until 2 h before surgery, we hypothesized that overweight/obese subjects would not have increased GFV over lean/normal subjects and that emesis/pulmonary aspiration events would be rare. METHODS: Demographics, medical history, height, and weight were recorded for 1000 consecutive day surgery patients aged 2-12 yr. In addition, 1000 day surgery patients (age 2-12 yr) undergoing general endotracheal anesthesia were enrolled. After tracheal intubation, a 14-18F orogastric tube was inserted and gastric contents evacuated. Medications, fasting interval, GFV, pH, and emetic episodes were documented. Age- and gender-specific Center for Disease Control and Prevention growth charts (2000) were used to determine ideal body weight (IBW = 50th percentile) and to classify patients as lean/normal (BMI 25th-75th percentile), overweight (BMI > or = 85th to <95th percentile), or obese (BMI > or = 95th percentile). RESULTS: Of all day surgery patients, 14.0% were overweight and 13.3% were obese. Obese children had lower GFV per total body weight (P < 0.001). When corrected for IBW, however, volumes GFV(IBW) were identical across all BMI categories (mean 0.96 mL/kg, sd 0.71; median 0.86 mL/kg, IQR 0.96). Preoperative acetaminophen and midazolam contributed to increased GFV(IBW) (P = 0.025 and P = 0.001). Lower GFV(IBW) was associated with ASA physical status III (P = 0.024), male gender (P = 0.012), gastroesophageal reflux disease (P = 0.049), and proton pump inhibitor administration (P = 0.018). GFV(IBW) did not correlate with fasting duration or age. Decreased gastric fluid acidity was associated with younger age (P = 0.005), increased BMI percentile (P = 0.036), and African American race (P = 0.033). Emesis on induction occurred in eight patients (50% of whom were obese, P = 0.052, and 75% of whom had obstructive sleep apnea, P = 0.061). Emesis was associated with increased ASA physical status (P = 0.006) but not with fasting duration. There were no pulmonary aspiration events. CONCLUSIONS: Twenty-seven percent of pediatric day surgery patients are overweight/obese. These children may be allowed clear liquids 2 h before surgery as GFV(IBW) averages 1 mL/kg regardless of BMI and fasting interval. Rare emetic episodes were not associated with shortened fasting intervals in this population.


Sujet(s)
Jeûne , Suc gastrique/métabolisme , Obésité/complications , Surpoids/complications , Inhalation bronchique/prévention et contrôle , Procédures de chirurgie opératoire/méthodes , Anesthésie générale/normes , Indice de masse corporelle , Enfant , Enfant d'âge préscolaire , Femelle , Contenus gastro-intestinaux/composition chimique , Recommandations comme sujet , Humains , Mâle , Procédures de chirurgie opératoire/normes
13.
J Mol Microbiol Biotechnol ; 16(3-4): 236-9, 2009.
Article de Anglais | MEDLINE | ID: mdl-17890844

RÉSUMÉ

In Corynebacterium glutamicum, the transcriptional regulator RamB negatively controls the expression of genes involved in acetate metabolism. Here we show that during growth in media containing glucose and in complex medium without glucose RamB activates expression of the aceE gene, encoding the E1p subunit of the pyruvate dehydrogenase complex. Thus, RamB functions both as repressor and as activator in C. glutamicum.


Sujet(s)
Protéines bactériennes/génétique , Protéines bactériennes/métabolisme , Corynebacterium glutamicum/enzymologie , Régulation de l'expression des gènes bactériens , Pyruvate dehydrogenase (lipoamide)/génétique , Pyruvate dehydrogenase (lipoamide)/métabolisme , Acétates/métabolisme , Séquence nucléotidique , Corynebacterium glutamicum/génétique , Corynebacterium glutamicum/croissance et développement , Corynebacterium glutamicum/métabolisme , Données de séquences moléculaires
14.
J Thorac Cardiovasc Surg ; 136(5): 1229-36, 2008 Nov.
Article de Anglais | MEDLINE | ID: mdl-19026808

RÉSUMÉ

OBJECTIVE: The hospital course for pediatric coarctation repair has not been described. We had 4 aims: (1) to determine the influence of age, anatomy, and type of repair on aortic crossclamp time, (2) to determine the impact of age or aortic crossclamp time on postoperative morbidity, (3) to describe current antihypertensive strategies, and (4) to describe antihypertensive medications at hospital discharge. METHODS: Data were obtained from a prospective randomized multicenter esmolol safety and efficacy trial. The study included patients who were scheduled for a coarctation repair receiving esmolol as their first-line antihypertensive medication in the operating room (n = 118; weight > or = 2.5 kg and age < 6 years). RESULTS: (1) Patient age and type of coarctation did not affect the aortic crossclamp time. (2) Younger age, but not aortic crossclamp time, was associated with a significantly longer time to extubation and longer hospital length of stay. (3) A combination of esmolol and sodium nitroprusside (Nipride, Roche, Basel, Switzerland) provided excellent early blood pressure control. (4) At discharge, 64% of patients were receiving antihypertensive medications. Older patients were more likely to be discharged with antihypertensive medication (91% of patients aged 2-6 years, P < .0002). CONCLUSION: The study describes a multi-institutional approach to the repair of isolated coarctation in infants and children. Patients repaired by end-to-end anastomosis had shorter aortic crossclamp time, younger patients had longer hospital length of stay, a majority of patients had sodium nitroprusside (Nipride) added to esmolol for early blood pressure control, and older patients were more likely to be discharged with antihypertensive medication.


Sujet(s)
Antagonistes bêta-adrénergiques/usage thérapeutique , Antihypertenseurs/usage thérapeutique , Coarctation aortique/chirurgie , Propanolamines/usage thérapeutique , Thoracotomie , Antagonistes bêta-adrénergiques/administration et posologie , Facteurs âges , Antihypertenseurs/administration et posologie , Enfant , Enfant d'âge préscolaire , Femelle , Humains , Nourrisson , Nouveau-né , Durée du séjour , Mâle , Nitroprussiate/administration et posologie , Propanolamines/administration et posologie , Études prospectives
15.
J Thorac Cardiovasc Surg ; 136(2): 321-8, 2008 Aug.
Article de Anglais | MEDLINE | ID: mdl-18692637

RÉSUMÉ

OBJECTIVES: Blood pressure control is important after repair of coarctation of the aorta. We report the first prospective multi-institutional trial addressing the safety and efficacy of esmolol after repair of coarctation of the aorta in infants and children. METHODS: The primary objective of this phase IIIb, multicenter, double-blind, randomized, dose-ranging trial was the efficacy of esmolol to control hypertension. Candidates included subjects younger than 6 years and weighing 2.5 kg or more who underwent surgical intervention for coarctation of the aorta and required therapy for systemic hypertension. One hundred sixteen subjects received esmolol: 36 received a low dose (125 microg/kg), 43 received a medium dose (250 microg/kg), and 37 received a high dose (500 microg/kg). The primary outcomes were the change in systolic blood pressure and the need for additional antihypertensive rescue medication 5 minutes after the initiation of esmolol. RESULTS: All dose groups showed a significant decrease from baseline in systolic blood pressure (-9.6 +/- 16.3 mm Hg, P < .001). There were no differences in systolic blood pressure response at 5 minutes between dose groups (high, medium, or low) or age groups. The need for rescue medication at 5 minutes was not different between dose groups. All dose groups showed similar incidences of adverse events. There were no serious adverse events. DISCUSSION: Esmolol can be administered safely to patients younger than 6 years after repair of coarctation of the aorta. In the dose range of 125 to 500 microg/kg, esmolol significantly decreased systolic blood pressure.


Sujet(s)
Antagonistes bêta-adrénergiques/administration et posologie , Antihypertenseurs/administration et posologie , Coarctation aortique/chirurgie , Pression sanguine/effets des médicaments et des substances chimiques , Hypertension artérielle/traitement médicamenteux , Complications postopératoires , Propanolamines/administration et posologie , Antagonistes bêta-adrénergiques/effets indésirables , Antagonistes bêta-adrénergiques/pharmacocinétique , Antihypertenseurs/effets indésirables , Antihypertenseurs/pharmacocinétique , Coarctation aortique/physiopathologie , Relation dose-effet des médicaments , Méthode en double aveugle , Femelle , Humains , Hypertension artérielle/étiologie , Nourrisson , Nouveau-né , Mâle , Propanolamines/effets indésirables , Propanolamines/pharmacocinétique
16.
Appl Microbiol Biotechnol ; 79(3): 471-9, 2008 Jun.
Article de Anglais | MEDLINE | ID: mdl-18379776

RÉSUMÉ

We recently engineered the wild type of Corynebacterium glutamicum for the growth-decoupled production of L: -valine from glucose by inactivation of the pyruvate dehydrogenase complex and additional overexpression of the ilvBNCE genes, encoding the L-valine biosynthetic enzymes acetohydroxyacid synthase, isomeroreductase, and transaminase B. Based on the first generation of pyruvate-dehydrogenase-complex-deficient C. glutamicum strains, a second generation of high-yield L-valine producers was constructed by successive deletion of the genes encoding pyruvate:quinone oxidoreductase, phosphoglucose isomerase, and pyruvate carboxylase and overexpression of ilvBNCE. In fed-batch fermentations at high cell densities, the newly constructed strains produced up to 410 mM (48 g/l) L-valine, showed a maximum yield of 0.75 to 0.86 mol/mol (0.49 to 0.56 g/g) of glucose in the production phase and, in contrast to the first generation strains, excreted neither pyruvate nor any other by-product tested.


Sujet(s)
Corynebacterium glutamicum/métabolisme , Génie génétique , Valine/métabolisme , Protéines bactériennes/génétique , Protéines bactériennes/métabolisme , Biomasse , Voies de biosynthèse , Corynebacterium glutamicum/enzymologie , Corynebacterium glutamicum/génétique , Fermentation , Expression des gènes , Ketol-acid reductoisomerase/génétique , Ketol-acid reductoisomerase/métabolisme , Oxidoreductases/génétique , Oxidoreductases/métabolisme , Complexe du pyruvate déshydrogénase/génétique , Complexe du pyruvate déshydrogénase/métabolisme , Transaminases/génétique , Transaminases/métabolisme
17.
Appl Microbiol Biotechnol ; 76(3): 615-23, 2007 Sep.
Article de Anglais | MEDLINE | ID: mdl-17333167

RÉSUMÉ

Intracellular precursor supply is a critical factor for amino acid productivity of Corynebacterium glutamicum. To test for the effect of improved pyruvate availability on L-lysine production, we deleted the aceE gene encoding the E1p enzyme of the pyruvate dehydrogenase complex (PDHC) in the L-lysine-producer C. glutamicum DM1729 and characterised the resulting strain DM1729-BB1 for growth and L-lysine production. Compared to the host strain, C. glutamicum DM1729-BB1 showed no PDHC activity, was acetate auxotrophic and, after complete consumption of the available carbon sources glucose and acetate, showed a more than 50% lower substrate-specific biomass yield (0.14 vs 0.33 mol C/mol C), an about fourfold higher biomass-specific L-lysine yield (5.27 vs 1.23 mmol/g cell dry weight) and a more than 40% higher substrate-specific L-lysine yield (0.13 vs 0.09 mol C/mol C). Overexpression of the pyruvate carboxylase or diaminopimelate dehydrogenase genes in C. glutamicum DM1729-BB1 resulted in a further increase in the biomass-specific L-lysine yield by 6 and 56%, respectively. In addition to L-lysine, significant amounts of pyruvate, L-alanine and L-valine were produced by C. glutamicum DM1729-BB1 and its derivatives, suggesting a surplus of precursor availability and a further potential to improve L-lysine production by engineering the L-lysine biosynthetic pathway.


Sujet(s)
Corynebacterium glutamicum/métabolisme , Lysine/biosynthèse , Complexe du pyruvate déshydrogénase/métabolisme , Séquence nucléotidique , Biotechnologie , Corynebacterium glutamicum/génétique , Corynebacterium glutamicum/croissance et développement , ADN bactérien/génétique , Fermentation , Délétion de gène , Expression des gènes , Gènes bactériens , Cinétique , Complexe du pyruvate déshydrogénase/génétique
18.
J AAPOS ; 11(3): 273-6, 2007 Jun.
Article de Anglais | MEDLINE | ID: mdl-17383912

RÉSUMÉ

INTRODUCTION: Pediatric strabismus surgery may be associated with postoperative nausea, vomiting, and emergence agitation (restlessness, thrashing, crying, moaning, disorientation). We hypothesize that emergence agitation after strabismus surgery is in part related to pain and that topical tetracaine ophthalmic drops can decrease the intensity and incidence of postoperative pain and emergence agitation. METHODS: Eighty-eight subjects aged 1 to 12 years scheduled for strabismus surgery were enrolled in a double-masked randomized control trial. The patients were randomized to one of three groups: Group A received normal saline drops before and after surgery; Group B received normal saline drops before and tetracaine 1% drops after surgery; Group C received tetracaine 1% drops before and after surgery. An observer masked to group assignment assessed each patient in the postanesthesia care unit (PACU) using both a behavior scale and a modified behavioral pain scale. RESULTS: Patients in Group A were found to be in significantly more pain than Groups B or C at 5 minutes after arrival to the PACU (p < 0.013). Using the behavior scale, a significantly greater proportion of patients in Group A were crying or crying and thrashing at 5, 15, and 30 minutes after arrival to the PACU (5 minutes, p < 0.019; 15 minutes, p < 0.041; 30 minutes, p < 0.021). There was no significant difference between groups in total PACU time, PACU vomiting, PACU morphine use, or pain at home. CONCLUSIONS: Postoperative strabismus surgery pain was improved by the use of preoperative, and pre- and postoperative, tetracaine drops. Emergence agitation was not fully evaluated by the behavioral scale, and therefore, the effect of tetracaine drops on emergence agitation was not clarified. This study suggests that tetracaine drops can lead to a less stressful early postoperative experience for the patient.


Sujet(s)
Anesthésiques locaux/administration et posologie , Douleur postopératoire/traitement médicamenteux , Troubles psychomoteurs/traitement médicamenteux , Strabisme/chirurgie , Tétracaïne/administration et posologie , Administration par voie topique , Symptômes comportementaux , Enfant , Enfant d'âge préscolaire , Méthode en double aveugle , Femelle , Humains , Nourrisson , Mâle , Muscles oculomoteurs/chirurgie , Solutions ophtalmiques , Soins postopératoires , Soins préopératoires , Plan de recherche
19.
Appl Environ Microbiol ; 73(7): 2079-84, 2007 Apr.
Article de Anglais | MEDLINE | ID: mdl-17293513

RÉSUMÉ

Corynebacterium glutamicum was engineered for the production of L-valine from glucose by deletion of the aceE gene encoding the E1p enzyme of the pyruvate dehydrogenase complex and additional overexpression of the ilvBNCE genes encoding the L-valine biosynthetic enzymes acetohydroxyacid synthase, isomeroreductase, and transaminase B. In the absence of cellular growth, C. glutamicum DeltaaceE showed a relatively high intracellular concentration of pyruvate (25.9 mM) and produced significant amounts of pyruvate, L-alanine, and L-valine from glucose as the sole carbon source. Lactate or acetate was not formed. Plasmid-bound overexpression of ilvBNCE in C. glutamicum DeltaaceE resulted in an approximately 10-fold-lower intracellular pyruvate concentration (2.3 mM) and a shift of the extracellular product pattern from pyruvate and L-alanine towards L-valine. In fed-batch fermentations at high cell densities and an excess of glucose, C. glutamicum DeltaaceE(pJC4ilvBNCE) produced up to 210 mM L-valine with a volumetric productivity of 10.0 mM h(-1) (1.17 g l(-1) h(-1)) and a maximum yield of about 0.6 mol per mol (0.4 g per g) of glucose.


Sujet(s)
Corynebacterium glutamicum/métabolisme , Complexe du pyruvate déshydrogénase/physiologie , Valine/biosynthèse , Alanine/biosynthèse , Fermentation , Isoleucine/biosynthèse , Lysine/biosynthèse , Complexe du pyruvate déshydrogénase/génétique , Acide pyruvique/métabolisme
20.
Pediatr Cardiol ; 27(4): 420-7, 2006.
Article de Anglais | MEDLINE | ID: mdl-16835806

RÉSUMÉ

Esmolol is often used in the acute management of children with arrhythmias and/or hypertension; however, pharmacokinetic studies of the drug in children have been limited. The objective of this study was to determine the pharmacokinetics of esmolol in children with a history of supraventricular arrhythmias (SVT) who were scheduled for diagnostic electrophysiology study or a catheter ablation procedure. Subjects were stratified into two age groups: 2-11 and 12-16 years. After an episode of stimulated or spontaneous SVT, esmolol was administered intravenously as a 1,000 microg/kg bolus followed by continuous infusion at 300 microg/kg/min. Blood samples were collected before, at 5, 10 and 15 min after the loading dose, and 3, 6, 9, 12, 15 and 20 min after the end of the infusion. Plasma concentration of esmolol was quantitated by a specific LC/MS assay. Pharmacokinetic data were available for 25 subjects. Arterial esmolol concentrations were approximately five times greater than venous concentrations. Esmolol had an extremely short distribution half-life (0.6 min), a rapid terminal elimination half-life (6.9 min), and a rapid clearance (119 +/- 51 mL/min/kg) which was not related to subject age or weight. Seventeen of the subjects (63%) converted to normal sinus rhythm in an average of 2 min (range 0-5 min). The pharmacokinetics of esmolol and its efficacy in terminating SVT in children is similar to that observed in adults.


Sujet(s)
Antagonistes bêta-adrénergiques/pharmacocinétique , Propanolamines/pharmacocinétique , Tachycardie supraventriculaire/traitement médicamenteux , Adolescent , Antagonistes bêta-adrénergiques/administration et posologie , Antagonistes bêta-adrénergiques/sang , Pression sanguine/effets des médicaments et des substances chimiques , Ablation par cathéter , Enfant , Enfant d'âge préscolaire , Techniques électrophysiologiques cardiaques , Femelle , Période , Système de conduction du coeur/effets des médicaments et des substances chimiques , Système de conduction du coeur/physiopathologie , Système de conduction du coeur/chirurgie , Rythme cardiaque/effets des médicaments et des substances chimiques , Humains , Perfusions veineuses , Mâle , Propanolamines/administration et posologie , Propanolamines/sang , Tachycardie supraventriculaire/physiopathologie , Tachycardie supraventriculaire/chirurgie , Résultat thérapeutique , États-Unis
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