RESUMO
Improving access to athletic trainers and increasing diversity in the profession have been major goals of the Strategic Alliance, with a particular interest in the secondary school setting. Within many marginalized communities, individuals are often faced with a lack of resources, high rates of poverty, and limited access to health care. This social and economic climate often extends to inequitable athletic training services and patterns of disparate health. Widely used and recognized strategies to cultivate diversity and address health inequities include community-engaged partnerships; however, these approaches are not well implemented across the athletic training discipline. Successful community-engaged partnerships link communities and universities, and they are rooted in intentionality to address intermediate and long-term health equity outcomes. Athletic training professionals and scholars frequently encounter gaps in resources and process-oriented methods to participate in community-engaged efforts that could include a roadmap or pathway to follow. To bridge this gap, our aims were 2-fold: (1) to disseminate a roadmap for building sustainable community-engaged partnerships in athletic training with the intent of promoting diversity, equity, inclusion, and social justice across athletic training education, research, and professional service and (2) to demonstrate how the roadmap can be implemented using a community-based athletic training education camp as an example. Implementation of the athletic training camp using the roadmap took place at secondary schools where community-engaged partnerships have been established throughout a geographic region known as the Alabama Black Belt, a region burdened with poor health outcomes, limited athletic trainer presence, and lower quality of life, exacerbated by racial and socioeconomic inequalities. Implementing this roadmap as a strategy to build sustainable community-engaged partnerships offers an innovative, interactive, and effective approach to addressing community needs by exposing secondary school students to the athletic training profession, advancing equitable athletic training research practices, and upholding and promoting the principles of diversity, equity, inclusion, and social justice in athletic training education.
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Educação Física e Treinamento , Humanos , Educação Física e Treinamento/métodos , Diversidade Cultural , Esportes , Justiça Social , Instituições Acadêmicas , Participação da ComunidadeRESUMO
Increased demand for recycling plastic has prompted concerns regarding potential introduction of hazardous chemicals into recycled goods. We present a broad screening of chemicals in 21 plastic flake and pellet samples from Canadian recycling companies. From target analysis, the organophosphorus ester flame retardants and plasticizers exhibited the highest detection frequencies (DFs) (5-100%) and concentrations (
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Retardadores de Chama , Plásticos , Plásticos/análise , Retardadores de Chama/análise , Canadá , Compostos Orgânicos , Substâncias Perigosas/análise , Cálcio/análiseRESUMO
CLINICAL SCENARIO: Sport-related concussions (SRCs) are a prevalent and problematic injury occurring among adolescents participating in sports. Health-related quality of life (HRQoL) has been shown to be affected in a portion of adolescents recovering from SRCs, though the exact nature of the relationship has yet to be firmly established for this age group through the duration and completion of recovery. HRQoL can be a nebulous construct but is often described as multifaceted and demonstrates effects of an illness, injury, or condition on one's overall well-being, encompassing satisfaction and comfortability of physical, psychosocial, sleep, and cognitive attributes. CLINICAL QUESTION: How do adolescents diagnosed with sport-related concussion perceive changes in health-related quality of life domain measures throughout recovery? SUMMARY OF KEY FINDINGS: Four studies met the inclusion criteria, including 1 longitudinal prospective case series and 3 longitudinal prospective cohort studies. The literature indicated that adolescents who sustained an SRC reported an initial immediate decrease in overall HRQoL as well as domains including cognitive, physical, school, and sleep. This initial decrease was particularly notable in those with delayed recovery or those diagnosed with post-concussion syndrome. Despite the initial decrease, all participants of varying SRC recovery duration reportedly returned to healthy, normative levels of HRQoL upon recovery. CLINICAL BOTTOM LINE: Adolescents reportedly experience initial decreases in various HRQoL domains immediately after SRC but appear to rebound to a healthy status upon recovery regardless of recovery duration. STRENGTH OF RECOMMENDATION: Results of the review of 4 longitudinal studies established level B evidence.
Assuntos
Traumatismos em Atletas , Concussão Encefálica , Síndrome Pós-Concussão , Humanos , Adolescente , Traumatismos em Atletas/psicologia , Qualidade de Vida/psicologia , Estudos Prospectivos , Concussão Encefálica/diagnóstico , Síndrome Pós-Concussão/psicologiaRESUMO
While the uptake of palliative care in the United States is steadily improving, there continues to be a gap in which many patients are not offered care that explicitly elicits and respects their personal wishes. This is due in part to a mismatch of supply and demand; the number of seriously ill individuals far exceeds the workload capacities of palliative care specialty providers. We conducted a field trial of an intervention designed to promote the identification of seriously ill patients appropriate for a discussion of their goals of care and to advance the role of nonpalliative care clinicians by enhancing their knowledge of and comfort with primary palliative care skills. At 3 large Midwestern academic medical centers, a palliative care physician or nurse clinician embedded with a selected nonpalliative care service line or unit on a regularly scheduled basis for up to 6 months. Using agreed-upon criteria, patients were identified as being appropriate for a goals of care conversation; conversations with those patients and/or their families were then conducted with the palliative care specialist providing education, coaching, and mentoring to the nonpalliative care clinician, when possible. All of the sites increased the presence of palliative care within the selected service line or unit, and the nonpalliative care clinicians reported increased comfort and skill at conducting goals of care conversations. This intervention is a first step toward increasing patients' access to palliative care to alleviate distress and to more consistently deliver care that honors patient and family preferences.
Assuntos
Comunicação , Administração Hospitalar , Capacitação em Serviço/organização & administração , Cuidados Paliativos/organização & administração , Planejamento de Assistência ao Paciente/organização & administração , Centros Médicos Acadêmicos , Humanos , Relações Médico-Paciente , Estados UnidosRESUMO
After decades of use of polybrominated diphenyl ethers (PBDEs) as flame retardants, a large reservoir of these toxins has accumulated in ecosystems worldwide. The present study used an innovative approach to examine whether the fully brominated PBDE decabromodiphenyl ether (decaBDE) degrades to more toxic congeners in aquatic environments. The authors incubated intact sediment microcosms with high-purity [(13)C]decaBDE in a remote boreal lake to assess its debromination under ambient conditions. Although the addition of [(13)C]decaBDE increased total PBDE concentrations in sediment more than 10-fold, the relative amount of [(13)C]decaBDE in sediment did not change significantly over a 1-mo incubation. However, observation of small quantities of lower-brominated [(13)C]BDEs lent support to the hypothesis that decaBDE is slowly debrominated. The authors observed a significant increase in octaBDEs and nonaBDEs in profundal, but not littoral, sediment over 30 d. A second experiment in which sediment was incubated under different light and oxygen regimes yielded a surprising result-oxygen significantly stimulated the formation of octaBDEs and nonaBDEs. The authors also conducted a large-scale in situ enclosure experiment in which they followed the fate of experimentally added decaBDE in sediment over 26 mo, but that study yielded little evidence of decaBDE debromination. Overall, the authors suggest that the debromination of decaBDE occurs very slowly, if at all, in natural sediment of boreal lakes, in contrast to the rapid degradation kinetics reported by most laboratory-based studies, which are usually conducted by dissolving decaBDE in organic solvents. The findings reinforce the need for field studies on contaminant fate to inform environmental policy decisions.
Assuntos
Retardadores de Chama/análise , Sedimentos Geológicos/química , Éteres Difenil Halogenados/análise , Lagos/química , Poluentes Químicos da Água/análise , Canadá , Cromatografia Gasosa , Poluentes Químicos da Água/químicaRESUMO
Per- and polyfluorinated alkyl substances (PFASs) enter Arctic lakes through long-range atmospheric transport and local contamination, but their behavior in aquatic food webs at high latitudes is poorly understood. This study compared the concentrations of perfluorocarboxylates, perfluorosulfonates, and fluorotelomer sulfonates (FTS) in biotic and abiotic samples from six high Arctic lakes near Resolute Bay, Nunavut, Canada. Two of these lakes are known to be locally contaminated by a small airport and Arctic char (Salvelinus alpinus) from these lakes had over 100 times higher total [PFAS] when compared to fish from neighboring lakes. Perfluorononanoate (PFOA) and perfluorooctanesulfonate (PFOS) dominated in char, benthic chironomids (their main prey), and sediments, while pelagic zooplankton and water were dominated by lower chain acids and perfluorodecanesulfonate (PFDS). This study also provides the first measures of perfluoroethylcyclohexanesulfonate (PFECHS) and FTS compounds in water, sediment, juvenile char, and benthic invertebrates from lakes in the high Arctic. Negative relationships between [PFAS] and δ(15)N values (indicative of trophic position) within these food webs indicated no biomagnification. Overall, these results suggest that habitat use and local sources of contamination, but not trophic level, are important determinants of [PFAS] in biota from freshwater food webs in the Canadian Arctic.
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Polímeros de Fluorcarboneto/química , Cadeia Alimentar , Hidrocarbonetos Fluorados/química , Lagos , Animais , Regiões Árticas , Canadá , Monitoramento Ambiental , Peixes , Invertebrados , Nunavut , Poluentes Químicos da Água/análise , ZooplânctonRESUMO
Autologous human induced pluripotent stem cells (hiPSCs) should allow cellular therapeutics without an associated immune response. This concept has been controversial since the original report that syngeneic mouse iPSCs elicited an immune response after transplantation. However, an investigative analysis of any potential acute immune responses in hiPSCs and their derivatives has yet to be conducted. In the present study, we used correlative gene expression analysis of two putative mouse "immunogenicity" genes, ZG16 and HORMAD1, to assay their human homologous expression levels in human pluripotent stem cells and their derivatives. We found that ZG16 expression is heterogeneous across multiple human embryonic stem cell and hiPSC-derived cell types. Additionally, ectopic expression of ZG16 in antigen-presenting cells is insufficient to trigger a detectable response in a peripheral blood mononuclear cell coculture assay. Neither of the previous immunogenicity-associated genes in the mouse currently appears to be relevant in a human context.
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Células-Tronco Embrionárias/imunologia , Perfilação da Expressão Gênica , Regulação da Expressão Gênica/imunologia , Células-Tronco Pluripotentes/imunologia , Animais , Linhagem Celular , Células-Tronco Embrionárias/citologia , Humanos , Lectinas/imunologia , Proteínas de Membrana/imunologia , Camundongos , Células-Tronco Pluripotentes/citologia , Especificidade da EspécieRESUMO
Temporal, biological, and environmental factors affecting accumulation of perfluoroalkyl substances (PFASs) are poorly understood in comparison with legacy lipid-soluble persistent organic pollutants. Temporal and biological comparisons of PFAS concentrations were made in great skuas (Stercorarius skua), a marine apex predator. Concentrations of 16 PFASs were quantified, including C4-C10 perfluorosulfonates (PFSAs), perfluorooctanesulfonamide (PFOSA), and C5-C14 perfluorocarboxylates (PFCAs). Concentrations of PFASs (ng/g wet wt) were significantly higher in eggs collected in Shetland in 2008 compared with 1980 for most compounds. However, the magnitude of the differences was small, with a mean increase of 3 ng/g. Levels of PFASs in great skuas were low compared with those of other seabirds in similar ecological niches; and in contrast to other contaminants measured in the same eggs, concentrations of PFASs did not correlate with trophic level. Concentrations of PFASs in adult plasma were significantly higher in males than in females for most PFASs. This suggests that maternal transfer through egg laying may be a significant mode of elimination of PFASs in female great skuas. The low concentrations of PFASs in eggs and plasma compared with other halogenated organic contaminants and other species suggest that great skuas do not bioaccumulate PFASs to the same extent as some other seabirds.
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Charadriiformes/metabolismo , Poluentes Ambientais/metabolismo , Fluorocarbonos/metabolismo , Óvulo/metabolismo , Animais , Monitoramento Ambiental , Feminino , Masculino , Sulfonamidas/metabolismoRESUMO
Although most asymptomatic patients with aortic stenosis (AS) have an excellent prognosis with observation only, some patients with severely stenotic aortic valves in the absence of symptoms may benefit from early intervention. In this article, we will review the literature on the use of varied imaging modalities, clinical factors, and biomarker testing to risk stratify such patients. Additionally, we will review the role of medical therapy to modify the course in AS.
Assuntos
Estenose da Valva Aórtica , Estenose da Valva Aórtica/terapia , Ecocardiografia , Tolerância ao Exercício , Humanos , Imageamento por Ressonância Magnética , Tomografia Computadorizada por Raios XRESUMO
The biomagnification behavior of perfluorinated carboxylates (PFCAs) and perfluorinated sulfonates (PFSAs) was studied in terrestrial food webs consisting of lichen and plants, caribou, and wolves from two remote northern areas in Canada. Six PFCAs with eight to thirteen carbons and perfluorooctane sulfonate (PFOS) were regularly detected in all species. Lowest concentrations were found for vegetation (0.02-0.26 ng/g wet weight (ww) sum (Σ) PFCAs and 0.002-0.038 ng/g ww PFOS). Wolf liver showed highest concentrations (10-18 ng/g ww ΣPFCAs and 1.4-1.7 ng/g ww PFOS) followed by caribou liver (6-10 ng/g ww ΣPFCAs and 0.7-2.2 ng/g ww PFOS). Biomagnification factors were highly tissue and substance specific. Therefore, individual whole body concentrations were calculated and used for biomagnification and trophic magnification assessment. Trophic magnification factors (TMF) were highest for PFCAs with nine to eleven carbons (TMF = 2.2-2.9) as well as PFOS (TMF = 2.3-2.6) and all but perfluorooctanoate were significantly biomagnified. The relationship of PFCA and PFSA TMFs with the chain length in the terrestrial food chain was similar to previous studies for Arctic marine mammal food web, but the absolute values of TMFs were around two times lower for this study than in the marine environment. This study demonstrates that challenges remain for applying the TMF approach to studies of biomagnification of PFCAs and PFSAs, especially for terrestrial animals.
Assuntos
Fluorocarbonos/metabolismo , Cadeia Alimentar , Líquens/metabolismo , Rena/metabolismo , Lobos/metabolismo , Ácidos Alcanossulfônicos/metabolismo , AnimaisAssuntos
Arritmias Cardíacas/fisiopatologia , Eletrocardiografia , Sistema de Condução Cardíaco/fisiopatologia , Potenciais de Ação , Arritmias Cardíacas/diagnóstico , Arritmias Cardíacas/epidemiologia , Arritmias Cardíacas/etiologia , Humanos , Cinética , Valor Preditivo dos Testes , Prognóstico , Reprodutibilidade dos Testes , Fatores de RiscoRESUMO
INTRODUCTION: Primary mitochondrial cytopathies include more than 40 different identified diseases that have varied genetic features. The common factor among these diseases is that the mitochondria are unable to effectively complete oxidative phosphorylation to generate energy. One in 5000 children per year in the United Sates are born with mitochondrial disease. The term primary mitochondrial disease refers specifically to mitochondrial dysfunction caused by genetic mutations directly impacting the composition and function of the respiratory chain. These defects impair mitochondrial oxidative phosphorylation, the process by which oxidation of the end products of metabolism in the electron transport chain is coupled to phosphorylation of adenosine diphosphate to produce energy in the form of adenosine triphosphate. The effects of mitochondrial disease can be quite varied, and the severity of the defect may be great or small. We sought to find the common otolaryngologic manifestations of this disease, to enable better treatment of the patients. We report on 41 pediatric cases of mitochondrial cytopathy diagnosed from 2001 to 2006 at our Center for Child Neurology (Cleveland, OH). We performed a retrospective review after obtaining institutional review board approval. Patients who had otologic manifestations including recurrent otitis media and hearing loss comprise 14.6%. Patients who were noted to have obstructive sleep apnea requiring adenotonsillectomy comprise 9.8%. Patients who had dysphagia comprise 22%; however, all of these patients were noted to have some developmental delay and seizures. It was also noted that there was a 17% incidence of gastroesophageal reflux, and 36.6% incidence of seizures in our patient population. In conclusion, mitochondrial cytopathies exhibit extreme clinical variability. This variability greatly increases the burden for affected families and impairs our ability to understand the pathogenesis of these disorders. In otolaryngologic examination, children appear to have recurrent otitis, dysphagia, and sleep apnea, at a much higher incidence than the general pediatric population. A comprehensive management approach to these patients including pediatric neurology, genetics, speech pathology, otolaryngology, and audiology is essential to their care.
Assuntos
Perda Auditiva/etiologia , Doenças Mitocondriais/complicações , Infecções Respiratórias/etiologia , Apneia Obstrutiva do Sono/etiologia , Adolescente , Criança , Pré-Escolar , Feminino , Perda Auditiva/genética , Perda Auditiva/metabolismo , Humanos , Masculino , Doenças Mitocondriais/diagnóstico , Doenças Mitocondriais/genética , Doenças Mitocondriais/metabolismo , Fosforilação Oxidativa , Infecções Respiratórias/genética , Infecções Respiratórias/metabolismo , Estudos Retrospectivos , Convulsões/genética , Convulsões/metabolismo , Apneia Obstrutiva do Sono/genética , Apneia Obstrutiva do Sono/metabolismoRESUMO
PURPOSE: Test a practice-based intervention to foster involvement of a relative or friend for the reduction of cardiovascular risk in patients with type 2 diabetes. METHODS: We enrolled in a randomized controlled trial 199 patients and 108 support persons (SPs) from 18 practices within a practice-based research network. All patient participants had type 2 diabetes with suboptimal blood pressure control and were prepared to designate a SP. A subset of the patients also had dyslipidemia. All study visits were conducted at the practice sites where staff took standardized blood pressure measurements and collected blood samples. All patients completed one education session and received newsletters aimed at improving key health behaviors. Intervention group patients included their chosen SP in the education session and the SPs received newsletters. RESULTS: After 9 to 12 months, the intervention had no significant effect on systolic blood pressure, HbA1C, health-related quality of life, patient satisfaction, medication adherence, or perceived health competence. Power was insufficient to detect an effect on low-density lipoprotein cholesterol. Baseline cardiovascular risk values were not very high, with mean systolic blood pressure at 140 mm Hg; mean HbA1C at 7.6%; and mean low-density lipoprotein at 137 mg/dL. Patient health care satisfaction was high. CONCLUSION: This practice-based intervention to foster social support for chronic care management among diabetics had no significant impact on the targeted outcomes.
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Assistência Ambulatorial/métodos , Doenças Cardiovasculares/prevenção & controle , Diabetes Mellitus Tipo 2/complicações , Educação de Pacientes como Assunto , Apoio Social , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Feminino , Humanos , Kentucky/epidemiologia , Masculino , Pessoa de Meia-Idade , Satisfação do Paciente , Fatores de RiscoRESUMO
INTRODUCTION: Hepatic dysfunction is an important determinant of the clearance of tacrolimus; however, the impact of reduced hepatic mass in living donor liver transplant (LDLT) patients on the drug exposure and clearance of tacrolimus is not known. AIM.: The aim of the present study is to compare the dosage, concentration and pharmacokinetics parameters of tacrolimus between LDLT and deceased donor liver transplant (DDLT) recipients. PATIENTS AND METHODS: Daily doses used and trough concentrations measured were compared in 12 LDLT and 12 DDLT patients. Multiple blood samples were taken over one dosing interval after oral tacrolimus administration, and pharmacokinetics differences were compared. RESULTS: The mean tacrolimus dosage in first 14 postoperative days was (0.06 mg/kg/day) for LDLT and (0.09 mg/kg/day) for DDLT (P=0.0001). Despite the lower doses used, mean trough concentration was significantly greater in LDLT as compared with DDLT (8.8+/-2.5 ng/mL vs. 6.79+/-1.5 ng/mL, respectively, P=0.013). On the day of the pharmacokinetic study, minimum Concentration (Cmin), 12-hr postdose concentration (Clast), and average concentration (Cavg) were significantly greater in LDLT as compared with DDLT (LDLT: 6.6+/-2.4 ng/mL, 7.2+/-1.8 ng/mL, 8.9+/-3.0 ng/mL; DDLT: 4.3+/-1.0 ng/mL, 4.9+/-1.6 ng/mL, 5.9+/-1.4 ng/mL, P=0.02, 0.04, and 0.02, respectively). Dose normalized AUC was 37.7% greater and clearance, 47.5% lower in LDLT as compared with DDLT. CONCLUSION: Although not statistically significant, the dose normalized AUC was 37.7% greater and clearance 47.5% lower in LDLT as compared with DDLT. An initial tacrolimus dose reduction of about 30-40% may be prudent in LDLT compared with DDLT recipients.
Assuntos
Transplante de Fígado/imunologia , Tacrolimo/farmacocinética , Tacrolimo/uso terapêutico , Adulto , Área Sob a Curva , Nitrogênio da Ureia Sanguínea , Cadáver , Creatinina/sangue , Feminino , Humanos , Imunossupressores/farmacocinética , Imunossupressores/uso terapêutico , Hepatopatias/cirurgia , Doadores Vivos , Masculino , Pessoa de Meia-Idade , Doadores de TecidosRESUMO
The widespread environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) has been linked to developmental neurotoxicity associated with abnormal cerebellar maturation in both humans and rodents. TCDD mediates toxicity via binding to the aryl hydrocarbon receptor (AhR), a transcription factor that regulates the expression of xenobiotic metabolizing enzymes and growth regulatory molecules. Our previous studies demonstrated that cerebellar granule neuron precursor cells (GNPs) express transcriptionally active AhR during critical developmental periods. TCDD exposure also impaired GNP proliferation and survival in vitro. Therefore, this study tested the hypothesis that TCDD exposure disrupts cerebellar development by interfering with GNP differentiation. In vivo experiments indicated that TCDD exposure on postnatal day (PND) 6 resulted in increased expression of a mitotic marker and increased thickness of the external granule layer (EGL) on PND10. Expression of the early differentiation marker TAG-1 was also more pronounced in postmitotic, premigratory granule neurons of the EGL, and increased apoptosis of GNPs was observed. On PND21, expression of the late GNP differentiation marker GABA(A alpha 6) receptor (GABAR(A alpha 6)) and total estimated cell numbers were both reduced following exposure on PND6. Studies in unexposed adult AhR(-/-) mice revealed lower GABAR(A alpha 6) levels and DNA content. In vitro studies showed elevated expression of the early differentiation marker p27/Kip1 and the GABAR(A alpha 6) in GNPs following TCDD exposure, and the expression patterns of proteins related to granule cell neurite outgrowth, beta III-tubulin and polysialic acid neural cell adhesion molecule, were consistent with enhanced neuroblast differentiation. Together, our data suggest that TCDD disrupts a normal physiological role of AhR, resulting in compromised GNP maturation and neuroblast survival, which impacts final cell number in the cerebellum.
Assuntos
Cerebelo/efeitos dos fármacos , Grânulos Citoplasmáticos/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Dibenzodioxinas Policloradas/toxicidade , Animais , Diferenciação Celular , Cerebelo/citologia , Cerebelo/metabolismo , Grânulos Citoplasmáticos/metabolismo , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Neurônios/metabolismo , Receptores de GABA-A/metabolismo , Ácido gama-Aminobutírico/metabolismoRESUMO
OBJECTIVE: To assess the effects of nonsteroidal anti-inflammatory drugs (NSAIDs) on bleeding for pediatric adenotonsillectomy in a retrospective study, based on the common practices at 2 different tertiary care facilities. DESIGN: A retrospective study. SETTING: Two different tertiary care facilities. PATIENTS: Children up to 16 years of age, who underwent elective adenotonsillectomy or tonsillectomy, were included in the study. All indications for adenotonsillectomy, and all surgical techniques were included. Children with a bleeding tendency, and those with contraindications to the use of NSAIDs (eg, because of allergy), were excluded from the study. INTERVENTIONS: Nonsteroidal anti-inflammatory drugs. MAIN OUTCOME MEASURE: Postoperative bleeding in patients. RESULTS: A total of 1160 patients were selected who met the criteria: 673 patients underwent an adenotonsillectomy or tonsillectomy and did not receive any preoperative and postoperative ibuprofen, and 487 patients underwent routine adenotonsillectomy or tonsillectomy and were given postoperative ibuprofen. We noted a 0.7% postoperative bleeding rate in patients who were not allowed to take ibuprofen perioperatively. There was a 1.0% postoperative bleeding rate in patients who were allowed to take ibuprofen perioperatively (P = .75). CONCLUSION: Ibuprofen is not a contraindication to adenotonsillectomy or tonsillectomy and should be used in the control of postoperative pain if it is indicated in the patient.
Assuntos
Adenoidectomia , Anti-Inflamatórios não Esteroides/efeitos adversos , Hemorragia Pós-Operatória/induzido quimicamente , Tonsilectomia , Anti-Inflamatórios não Esteroides/administração & dosagem , Distribuição de Qui-Quadrado , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Dor Pós-Operatória/prevenção & controle , Estudos RetrospectivosRESUMO
The bioavailability of mycophenolic acid (MPA) after oral administration of mycophenolate mofetil (MMF) has been reported to be more than 90% in healthy volunteers, and in kidney and thoracic organ transplant patients. Such information is limited in liver transplant (LTx) patients. The present study compares the pharmacokinetics of MPA after intravenous (IV) and oral administrations of MMF in LTx recipients. Pharmacokinetic parameters were calculated using WinNonlin software. A total of 12 deceased donor LTx patients initially received IV MMF and were switched to oral MMF after 2-7 days (mean, 3.3 +/- 1.7) when oral feeds were started. Multiple blood samples were drawn immediately prior to and after IV or oral MMF and the plasma concentration of MPA was measured. The mean peak plasma concentrations and the area under the plasma concentration vs. time curve (AUC) were significantly higher after IV MMF compared to oral MMF (peak plasma concentrations of 10.7 +/- 2.1 microg/mL for IV vs. 4.5 +/- 2.8 microg/mL for oral; P = 0.0001; and AUC of 28.9 +/- 7.1 microg . hr/mL for IV vs. 12.8 +/- 4.2 microg . hr/mL for oral; P = 0.0001). The oral bioavailability of MPA was 48.5 +/- 18.7%. The systemic clearance, half-life, and steady state volume of distribution of MPA were 26.9 +/- 6 L/hour, 5.5 hours, and 85 liters, respectively. The terminal disposition half-life was not significantly different between the 2 routes of administration. In conclusion, during the early postoperative period, LTx recipients have MPA exposure with oral MMF of less than half that of IV MMF. Use of IV MMF immediately post-LTx may provide an immunological advantage.
Assuntos
Rejeição de Enxerto/prevenção & controle , Imunossupressores/farmacocinética , Transplante de Fígado/efeitos adversos , Ácido Micofenólico/análogos & derivados , Administração Oral , Adulto , Disponibilidade Biológica , Feminino , Humanos , Imunossupressores/administração & dosagem , Injeções Intravenosas , Masculino , Pessoa de Meia-Idade , Ácido Micofenólico/administração & dosagem , Ácido Micofenólico/farmacocinética , Período Pós-Operatório , Estudos ProspectivosRESUMO
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a potent teratogen that produces neurobehavioral abnormalities associated with both cognitive and locomotor systems, yet the precise regional and cellular targets of developmental neurotoxicity remain largely unknown. Most, if not all, TCDD-induced pathology is mediated via binding to the aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor that belongs to the basic helix-loop-helix/Per-Arnt-Sim (bHLH/PAS) superfamily. Upon ligand binding, AhR translocates to the nucleus, dimerizes with the AhR nuclear translocator protein (Arnt), and regulates transcription by interaction with dioxin-response elements (DREs) in target genes, most notably specific cytochrome P450 (CYP) family members. To assess whether developing cerebellar granule neuroblasts are potential direct targets for TCDD toxicity, AhR expression and transcriptional activity were examined. AhR and Arnt proteins were present in mouse cerebellum from birth throughout postnatal development. AhR protein levels peaked between postnatal day (PND) 3-10, a critical period for granule neuroblast growth and maturation. Transcriptionally active AhR was detected in immature cerebellar granule cells in a transgenic dioxin-responsive lacZ mouse model after acute TCDD exposure. AhR and Arnt were also expressed in cerebellar granule neuroblast cultures. AhR localized to the nucleus in granule cells 15 min after TCDD treatment. TCCD elicited time-dependent and concentration-dependent increases in CYP1A1 and 1B1 mRNA and protein levels. Moreover, TCDD treatment reduced both thymidine incorporation and granule neuroblast survival in a concentration-dependent manner. These data suggest that (1) granule neuroblasts are direct targets for developmental AhR-mediated TCDD neurotoxicity and (2) TCDD exposure may disrupt granule cell neurogenesis.