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1.
Int Urogynecol J ; 31(11): 2345-2351, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32785748

RESUMO

INTRODUCTION AND HYPOTHESIS: It is assumed changes occur to the biomechanics and viscoelastic response of the levator ani muscle during pregnancy; however, there is limited evidence of this. This study used instrumentation and clinical measures to determine the stiffness and active force capacity of levator ani muscle during pregnancy and post-partum, investigated any associations with delivery outcomes, and explored the biomechanical properties associated with symptoms of pelvic floor dysfunction. METHODS: This was a prospective observational study, with nulliparous women with a singleton low-risk pregnancy. Data were collected at two stages during pregnancy and post-partum. Measurements included the Australian Pelvic Floor Questionnaire, palpation of active force, and elastometry measurements. Post-partum, 3D/4D ultrasound measurements were included. Repeated measures ANOVAs, pairwise comparisons, Pearson correlation coefficients, and Student's t-tests were used as appropriate. RESULTS: Fifty-nine women took part in the study. Active force was significantly different over the pregnancy and post-partum, measured with instrumentation (p = 0.002) and palpation (p = 0.006 right, p = 0.029 left). There was no significant change in muscle stiffness during pregnancy. Post-partum muscle stiffness was significantly different between women who gave birth vaginally vs. caesarean section (p = 0.002). Post-partum there were differences in levator hiatal area, symptoms of bladder dysfunction, prolapse symptoms, and sexual dysfunction symptoms. CONCLUSIONS: Active force of the levator ani muscle was significantly reduced during pregnancy and in the post-partum period, while muscle stiffness reduced only in those who had vaginal deliveries.


Assuntos
Cesárea , Diafragma da Pelve , Austrália , Feminino , Humanos , Parto , Diafragma da Pelve/diagnóstico por imagem , Período Pós-Parto , Gravidez , Ultrassonografia
2.
Neurourol Urodyn ; 39(1): 279-285, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31663159

RESUMO

AIM: Physiotherapists typically use digital palpation to determine residual tension in a muscle, referred to as muscle stiffness or tone. These assessments are subjective, and little is known about their accuracy or repeatability. Despite this, it is standard practice to base clinical treatment on these findings. The aim of this study was to assess physiotherapists' ability to assign a seven-point palpation scale to quantitative stiffness values generated by a novel device. METHODS: Prospective observational study involving 125 musculoskeletal and pelvic floor physiotherapists. A novel device was developed that replicates the haptic feedback that clinicians assess as muscle stiffness. Measurements of displacement, force, and stiffness were recorded. RESULTS: There was wide overlap between each scale category assigned to the stiffness values, from low stiffness at -3 (119 [106, 132] N/m) to moderate stiffness at 0 (462 [435,489] N/m); to high stiffness at +3 (897 [881,913] N/m). Consistency in applying the scale was poor, and the probability of a similar value of stiffness being assigned to the same scale category by different participants was low. CONCLUSIONS: While palpation is used globally by physiotherapists as a readily available and low-cost method of assessing muscle stiffness, these results indicate that it should be used with caution in diagnosing and defining patient care. Clinical assessment of muscle stiffness requires a validated and reliable palpation scale if this metric is to be used to diagnose pathology and develop treatment protocols. Training in this scale should then be recommended to improve reliability in patient assessment.


Assuntos
Contração Muscular/fisiologia , Palpação , Diafragma da Pelve/fisiologia , Adulto , Feminino , Humanos , Estudos Prospectivos , Reprodutibilidade dos Testes
3.
Crit Rev Toxicol ; 48(1): 52-108, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-28816105

RESUMO

Thiazolidinedione (TZD) drugs used in the treatment of type 2 diabetes mellitus (T2DM) have proven effective in improving insulin sensitivity, hyperglycemia, and lipid metabolism. Though well tolerated by some patients, their mechanism of action as ligands of peroxisome proliferator-activated receptors (PPARs) results in the activation of several pathways in addition to those responsible for glycemic control and lipid homeostasis. These pathways, which include those related to inflammation, bone formation, and cell proliferation, may lead to adverse health outcomes. As treatment with TZDs has been associated with adverse hepatic, cardiovascular, osteological, and carcinogenic events in some studies, the role of TZDs in the treatment of T2DM continues to be debated. At the same time, new therapeutic roles for TZDs are being investigated, with new forms and isoforms currently in the pre-clinical phase for use in the prevention and treatment of some cancers, inflammatory diseases, and other conditions. The aims of this review are to provide an overview of the mechanism(s) of action of TZDs, a review of their safety for use in the treatment of T2DM, and a perspective on their current and future therapeutic roles.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Tiazolidinedionas/farmacologia , Tiazolidinedionas/uso terapêutico , Animais , Proliferação de Células/efeitos dos fármacos , Feminino , Humanos , Inflamação/tratamento farmacológico , Masculino , Neoplasias/tratamento farmacológico , Neoplasias/prevenção & controle , Osteogênese/efeitos dos fármacos , Tiazolidinedionas/efeitos adversos
4.
Physiother Can ; 69(2): 104-112, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28539690

RESUMO

Purpose: The authors investigated the reliability of myotonometry-measured muscle tone in the thenar and perineal muscles. Methods: Participants were women aged 18-50 years who were asymptomatic for thumb and pelvic floor dysfunction (interrater study n=20; intrarater study n=43) or who were symptomatic for vulvodynia (interrater study n=14; intrarater study n=32). Mechanical properties (stiffness, frequency, decrement, relaxation time, and creep) of the muscles were measured using a myotonometer (MyotonPRO) while the muscles were in a relaxed state. Measures were performed twice by two assessors. Intra- and interrater reliability were determined using intra-class correlation coefficients (ICCs) and absolute reliability using the standard error of measurement and a minimum detectable change. Results: The primary property of interest, muscle stiffness, showed very good interrater (ICC 0.85-0.86) and intrarater (ICC 0.82-0.88) reliability in the thenar eminence. In the perineal muscles, reliability results ranged from good to very good for interrater (ICC 0.70-0.86) and intrarater (ICC 0.80-0.91) reliability for muscle stiffness. Absolute reliability was confirmed, with all measures showing minimal variance. Conclusions: Muscle stiffness of the smaller muscles of the body can be reliably measured using the MyotonPRO. The device could be used as a reference standard in the development of a digital palpation scale that would facilitate accurate diagnosis of muscle tone.


Objectif : étudier la fiabilité de la raideur musculaire mesurée par myotonométrie dans les muscles de l'éminence thénar et du périnée. Méthodologie : Les participantes étaient des femmes âgées de 18 à 50 ans ne présentant aucun symptôme de dysfonctionnement du pouce ni du plancher pelvien (étude interévaluateur n=20; étude intra-évaluateur n=43) ou présentant des symptômes de vulvodynie (étude interévaluateur n=14; étude intra-évaluateur n=32). Les propriétés mécaniques (raideur, fréquence, décrément, temps de relaxation et fluage) des muscles au repos ont été mesurées à l'aide d'un myotonomètre (MyotonPRO). Les mesures ont été prises deux fois par deux évaluateurs. La fiabilité intra-évaluateur et interévaluateur a été déterminée à l'aide des coefficients de corrélation intraclasse (CCI) et la fiabilité absolue à l'aide de l'écart type de mesure et du changement minimal détectable. Résultats : la propriété d'intérêt principal, la raideur musculaire, a montré une très bonne fiabilité interévaluateur (CCI 0,85-0,86) et intra-évaluateur (CCI 0,82-0,88) pour l'éminence thénar. Concernant les muscles du périnée, les résultats de fiabilité variaient de bons à très bons pour la fiabilité interévaluateur (CCI 0,70-0,86) et intra-évaluateur (CCI 0,80-0,91) pour la raideur musculaire. La fiabilité absolue a été confirmée, toutes les mesures montrant une variabilité minimale. Conclusions : la raideur musculaire des plus petits muscles du corps peut être mesurée de manière fiable à l'aide du MyotonPRO. L'appareil pourrait être utilisé comme norme de référence dans la conception d'une échelle numérique de palpation qui faciliterait le diagnostic exact du tonus musculaire.

5.
A A Case Rep ; 7(3): 60-2, 2016 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-27258181

RESUMO

In 2010, our department instituted a nonclinical, administrative rotation in operating room management for anesthesiology residents. Subsequently, we mandated the rotation for all senior anesthesiology residents in 2013. In 2014, under the auspices of the American Society of Anesthesiologists, we developed a web-based module covering the basics of finance, accounting, and operating room management. A multiple-choice test was given to residents at the beginning and end of the rotation, and we compared the mean scores between residents who took the traditional course and residents who took the web-based module. We found no significant difference between the groups of residents, suggesting that the web-based module is as effective as traditional didactics.


Assuntos
Anestesiologia/educação , Competência Clínica , Internet , Internato e Residência/métodos , Sistemas de Informação em Salas Cirúrgicas , Salas Cirúrgicas/métodos , Agendamento de Consultas , Humanos , Sistemas de Informação em Salas Cirúrgicas/normas , Salas Cirúrgicas/normas
6.
Int Urogynecol J ; 26(12): 1735-50, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26072126

RESUMO

INTRODUCTION AND HYPOTHESIS: We performed a review of the literature reporting on the effects of pelvic floor muscle training (PFMT) on female sexual function (SF). METHODS: Pubmed (from 1946 to December 2014), Ovid Medline (from 1946 to December 2014), CINAHL (from 1937 to December 2014), PsycINFO (from 1805 to December 2014), Scopus and Cochrane Central Register of Controlled Trials were searched by two independent reviewers. Randomised controlled trials (RCTs) investigating the impact of PFMT on women's SF published in English were included. Methodological quality was scored using the PEDro scale. Data were analysed qualitatively and interpreted. RESULTS: A total of 1341 women were included in the eight RCTs covered by this review. The studies were published between 1997 and 2014. Methodological scores were between 4 and 7. The sample included derived from heterogeneous populations of women. In only one study was SF the primary outcome measure. Pelvic floor dysfunction was an inclusion criterion in the majority of studies. Most studies reported a significant improvement in SF score after PFMT between control and intervention groups. CONCLUSIONS: Although most studies indicated an improvement of at least one sexual variable in women with pelvic floor dysfunction, and one study demonstrated an improvement in SF in postpartum women selected independently of their continence status, the results need to be interpreted with caution. High-quality RCTs specifically designed to investigate the impact of PFMT on women's SF are required.


Assuntos
Terapia por Exercício , Diafragma da Pelve , Comportamento Sexual , Feminino , Humanos
7.
Inflamm Bowel Dis ; 19(10): 2091-7, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23899539

RESUMO

BACKGROUND: Ocular disease is known widely to occur in a subset of patients experiencing inflammatory bowel diseases. Although this extraintestinal manifestation has been recognized for a number of years, the pathogenetic mechanisms responsible for this distant organ inflammatory response are unknown. METHODS: In the current study, we used a T-cell transfer model of chronic colitis in mice in which we quantified colonic inflammation, ocular function (electroretinography), ocular blood flow (intravital microscopy of the retina), intraocular pressure, and retinal hypoxia. RESULTS: Ocular function in colitic mice was significantly impaired, with decreases in retinal b-wave amplitudes and oscillatory potentials. Moreover, retinal a waves and oscillatory potentials were delayed. Retinal blood flow was significantly reduced in the colitic mice, and this decrease in perfusion coupled with significant decreases in hematocrit would decrease oxygen delivery to the eye. Accordingly, mice with severe colitis showed increased levels of immunostaining for the hypoxia-dependent probe pimonidazole. Finally, intraocular pressures were found to be reduced in the colitic mice. CONCLUSIONS: Ocular disease occurs in a mouse model of chronic colitis, with retinal dysfunction seeming to be related to insufficient perfusion and oxygen delivery.


Assuntos
Colite/complicações , Modelos Animais de Doenças , Oftalmopatias/etiologia , Trato Gastrointestinal/patologia , Proteínas de Homeodomínio/fisiologia , Inflamação/complicações , Interleucina-10/fisiologia , Animais , Doença Crônica , Colite/metabolismo , Colite/patologia , Eletrorretinografia , Oftalmopatias/metabolismo , Oftalmopatias/patologia , Trato Gastrointestinal/metabolismo , Hipóxia , Inflamação/metabolismo , Inflamação/patologia , Pressão Intraocular , Camundongos , Camundongos Endogâmicos C57BL , Retina/metabolismo , Retina/patologia , Linfócitos T/imunologia , Linfócitos T/patologia
8.
Inflamm Bowel Dis ; 19(6): 1260-5, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23567781

RESUMO

BACKGROUND: Approximately one-half of patients with inflammatory bowel disease (IBD) suffer from anemia, with the most prevalent cause being iron deficiency. Accompanying the anemia are increases in erythropoietin, a plasma protein that can initiate the feedback production of new red blood cells. Anemia also occurs in animal models that are used to investigate the mechanisms of IBD; however, the extent to which iron deficiency produces the anemia in these animal models is unknown. Also unknown in the different animal models of IBD is whether the anemia upregulates the production of erythropoietin or, alternatively, whether a decrease in erythropoietin contributes to the induction of anemia. METHODS: Two mouse models of colitis were used in this study: (1) acute 6-day ingestion of dextran sodium sulfate and (2) T-cell transfer into lymphopenic recipient mice. Measurements included indices of colitis severity, hematocrit, blood hemoglobin, plasma erythropoietin, serum iron concentration, plasma iron-binding capacities, transferrin saturation, and tissue iron concentrations. RESULTS: Both models of colitis induced significant decreases in hematocrit, blood hemoglobin, and transferrin saturation, with the spleen and liver showing a decrease in iron content in the T-cell transfer model. Additionally, both models of colitis demonstrated significant increases in plasma erythropoietin and plasma iron-binding capacities. CONCLUSIONS: The measurements of iron, whether in acute (dextran sodium sulfate) or chronic (T-cell transfer) models of colitis, were generally consistent with iron-deficient anemia, with large increases in erythropoietin indicative of tissue hypoxia. These changes in animal models of colitis are similar to those found in human IBD.


Assuntos
Anemia/etiologia , Colite/complicações , Sulfato de Dextrana/toxicidade , Modelos Animais de Doenças , Eritropoetina/sangue , Ferro/metabolismo , Linfócitos T/transplante , Doença Aguda , Anemia/metabolismo , Animais , Doença Crônica , Colite/metabolismo , Proteínas de Homeodomínio/fisiologia , Humanos , Interleucina-10/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout
9.
J Clin Anesth ; 25(3): 181-7, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23523976

RESUMO

STUDY OBJECTIVE: To test the hypothesis that emotional intelligence, as measured by a BarOn Emotional Quotient Inventory (EQ-i), the 125-item version personal inventory (EQ-i:125), correlates with resident performance. DESIGN: Survey (personal inventory) instrument. SETTING: Five U.S. academic anesthesiology residency programs. PARTICIPANTS: Postgraduate year (PGY) 2, 3, and 4 residents enrolled in university-based anesthesiology residency programs. MEASUREMENTS: Residents confidentially completed the BarOn EQ-i:125 personal inventory. The deidentified resident evaluations were sent to the principal investigator of a separate data collection study for data analysis. Data collected from the inventory were correlated with daily evaluations of the residents by residency program faculty. Results of the individual BarOn EQ-i:125 and daily faculty evaluations of the residents were compiled and analyzed. MAIN RESULTS: Univariate correlation analysis and multivariate canonical analysis showed that some aspects of the BarOn EQ-i:125 were significantly correlated with, and likely to be predictors of, resident performance. CONCLUSIONS: Emotional intelligence, as measured by the BarOn EQ-i personal inventory, has considerable promise as an independent indicator of performance as an anesthesiology resident.


Assuntos
Anestesiologia/educação , Competência Clínica , Inteligência Emocional , Internato e Residência/normas , Estudantes de Medicina/psicologia , Adulto , Educação de Pós-Graduação em Medicina/organização & administração , Feminino , Humanos , Relações Interpessoais , Masculino , Seleção de Pessoal/métodos , Médicos/psicologia , Psicometria , Autoimagem , Estados Unidos
10.
Inflamm Bowel Dis ; 18(12): 2360-70, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22488891

RESUMO

INTRODUCTION: We have previously demonstrated that adoptive transfer of naïve CD4(+) T cells devoid of lymphocyte function-associated antigen-1-deficient (LFA-1; CD11a/CD18) into recombination activating gene-1 (RAG-1) deficient (RAG(-/-) ) mice fails to induce chronic colitis whereas transfer of wild type (WT) T-cells induces unrelenting and chronic disease. METHODS: The objectives of this study were to assess the role of lymphocyte function-associated antigen-1 (LFA-1) in enteric antigen (EAg)-induced activation of T cells in vitro and in vivo and to define the importance of this integrin in promoting trafficking of T cells to the mesenteric lymph nodes (MLNs) and colon. RESULTS: We found that EAg-pulsed dendritic cells (DCs) induced proliferation of LFA-1-deficient (CD11a(-/-) ) CD4(+) T cells that was very similar to that induced using WT T cells, suggesting that LFA-1 is not required for activation/proliferation of T cells in vitro. Coculture of WT or CD11a(-/-) T cells with EAg-pulsed DCs induced the generation of similar amounts of interferon-gamma, interleukin (IL)-4, and IL-10, whereas IL-17A production was reduced ≈ 2-fold in cocultures with CD11a(-/-) T cells. Short-term (20-22 hours) trafficking studies demonstrated that while both WT and CD11a(-/-) T cells migrated equally well into the spleen, liver, lungs, small intestine, cecum, and colon, trafficking of CD11a(-/-) T cells to the MLNs was reduced by 50% when compared to WT T cells. When the observation period was extended to 3-7 days posttransfer, we observed ≈ 2-3-fold more WT T cells within the MLNs and colon than CD11a(-/-) T cells, whereas T-cell proliferation (as measured by CFSE dilution) was comparable in both populations. CONCLUSIONS: Taken together, our data suggest that LFA-1 is not required for EAg-induced activation of CD4(+) T cells in vitro or in vivo but is required for trafficking of T cells to the MLNs and homing of colitogenic effector cells to the colon where they initiate chronic gut inflammation.


Assuntos
Colite/etiologia , Antígeno-1 Associado à Função Linfocitária/fisiologia , Linfócitos T/fisiologia , Animais , Movimento Celular/imunologia , Movimento Celular/fisiologia , Colite/imunologia , Citocinas/imunologia , Citocinas/fisiologia , Células Dendríticas/imunologia , Células Dendríticas/fisiologia , Linfonodos/citologia , Linfonodos/imunologia , Ativação Linfocitária/imunologia , Ativação Linfocitária/fisiologia , Antígeno-1 Associado à Função Linfocitária/imunologia , Mesentério/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Linfócitos T/imunologia
11.
Pathophysiology ; 18(4): 305-11, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21680162

RESUMO

The mechanisms by which microvascular alterations contribute to the pathogenesis of the inflammatory bowel diseases (IBDs; Crohn's disease, ulcerative colitis) have not been clearly delineated. The purpose of the current study was to characterize the inflammatory events, microvascular alterations, and blood cell changes that occur in a mouse model of IBD. In this model, CD4(+) T-lymphocytes obtained from interleukin-10-deficient mice were injected intraperitoneally into lymphopenic, recombinase-activating gene-1 deficient (RAG(-/-)) mice. Two groups of control mice were also included: RAG(-/-) mice and C57BL/6 mice that were injected with phosphate-buffered saline but did not receive the T-cells. Four weeks later, the RAG(-/-) mice that had received the T-cell transfer showed significant signs of colonic inflammation, but without significant decreases in either body weight or mean arterial blood pressure. T-cell transfer increased the volume % of circulating platelets, while decreasing the number of circulating red blood cells. Additionally, the T-cell transfer tended to increase the circulating numbers of both lymphocytes and neutrophils when compared to unmanipulated RAG(-/-) mice. First-order colonic arterioles and venules tended to dilate in the colitic mice; however, the dilation was considerably more substantial with higher numbers of circulating leukocytes. The possibility that circulating inflammatory cells initiate the microvascular alterations in colitis warrants further investigation.

12.
J Toxicol Environ Health A ; 74(6): 364-79, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21271437

RESUMO

Adverse effects of methylmercury (MeHg) exposure during amphibian metamorphosis remain to be fully characterized. Most previous investigations determined effects of short-term exposure to elevated dose rates, without information on mercury (Hg) depuration and degradation pathways. Since metamorphosis is primarily controlled by thyroid hormones (TH), alterations in this process suggest a disruption of the TH endocrine axis. The aim of this research was to (1) characterize patterns of MeHg accumulation and depuration in tadpoles and (2) examine effects of MeHg accumulation on metamorphosis and the TH axis. Silurana tropicalis tadpoles were exposed to environmental levels of dietary MeHg until metamorphic climax. Whole-body MeHg and total Hg (THg) levels were measured, as well as the number of metamorphs, rate of metamorphosis, body size, and whole-body triiodothyronine (T3) levels at metamorphosis. Tadpoles exposed to a higher level of MeHg exhibited increased mortality and size, and reduced metamorphosis. At lower levels of MeHg, body burdens increased rapidly and eventually reached a plateau, whereas no plateau was reached at a higher level of MeHg exposure. T3 levels were not affected. Data indicate that at low and medium levels of exposure, depuration of MeHg may prevent toxicity in tadpoles. However, depuration mechanisms may be insufficient at high doses, producing disruption of metamorphosis and death. Although there were no marked effects of MeHg on whole-body T3 levels, further investigation of other components of the TH axis is warranted.


Assuntos
Ração Animal , Compostos de Metilmercúrio/toxicidade , Poluentes Químicos da Água/toxicidade , Xenopus/crescimento & desenvolvimento , Animais , Tamanho Corporal/efeitos dos fármacos , Relação Dose-Resposta a Droga , Larva/efeitos dos fármacos , Larva/crescimento & desenvolvimento , Larva/metabolismo , Metamorfose Biológica/efeitos dos fármacos , Compostos de Metilmercúrio/administração & dosagem , Fatores de Tempo , Tri-Iodotironina/análise , Tri-Iodotironina/metabolismo , Poluentes Químicos da Água/administração & dosagem , Xenopus/embriologia
13.
Inflamm Bowel Dis ; 17(3): 742-6, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-20878754

RESUMO

BACKGROUND: Hypoxia has been reported to be associated with the colonic inflammation observed in a chemically induced mouse model of self-limiting colitis, suggesting that low tissue oxygen tension may play a role in the pathophysiology of inflammatory tissue injury. However, no studies have been reported evaluating whether tissue hypoxia is associated with chronic gut inflammation. Therefore, the objective of the present study was to determine whether hypoxia is produced within the colon during the development of chronic gut inflammation. METHODS: Adoptive transfer of CD4(+) T cells obtained from interleukin-10-deficient (IL-10(-/-)) mice into lymphopenic recombinase-activating gene-1-deficient (RAG(-/-)) mice induces chronic colonic inflammation, with the inflammation ranging from mild to severe as determined by blinded histological analyses. Colonic blood flow, hematocrit, and vascular density were determined using standard protocols, whereas tissue hypoxia was determined using the oxygen-dependent probe pimonidazole. RESULTS: Adoptive transfer of IL-10(-/-) CD4(+) T cells into RAG(-/-) recipients induced chronic colonic inflammation that ranged from mild to severe at 8 weeks following T-cell transfer. The colitis was characterized by bowel wall thickening, goblet cell dropout, and inflammatory infiltrate. Surprisingly, we found that animals exhibiting mild colonic inflammation had increased hypoxia and decreased systemic hematocrit, whereas mice with severe colitis exhibited levels of hypoxia and hematocrit similar to healthy controls. In addition, we observed that the extent of hypoxia correlated inversely with hematocrit and vascular density. CONCLUSIONS: Changes in hematocrit, vascular density, and inflammatory state appear to influence the extent of tissue oxygenation in the T-cell-mediated model of chronic gut inflammation.


Assuntos
Linfócitos T CD4-Positivos/transplante , Colite/metabolismo , Modelos Animais de Doenças , Hipóxia/metabolismo , Mucosa Intestinal/metabolismo , Transferência Adotiva , Animais , Doença Crônica , Colite/patologia , Proteínas de Homeodomínio/fisiologia , Interleucina-10/fisiologia , Mucosa Intestinal/patologia , Camundongos
14.
Inflamm Bowel Dis ; 17(1): 268-78, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-20812332

RESUMO

BACKGROUND: It is well known that enteric bacterial antigens drive the development of chronic colitis in a variety of different mouse models of the inflammatory bowel diseases (IBD). The objective of this study was to evaluate the role of gut-associated lymphoid tissue (GALT; Peyer's patches, isolated lymphoid follicles), mesenteric lymph nodes (MLNs) and spleen in the pathogenesis of chronic colitis in mice. METHODS: Surgical as well as genetic approaches were used to generate lymphopenic mice devoid of one or more of these lymphoid tissues. For the first series of studies, we subjected recombinase activating gene-1-deficient mice (RAG(-/-) ) to sham surgery (Sham), mesenteric lymphadenectomy (MLNx), splenectomy (Splx) or both (MLNx/Splx). In a second series of studies we intercrossed lymphotoxinß-deficient (LTß(-/-) ) mice with RAG(-/-) animals to generate LTß(-/-) x RAG(-/-) offspring that were anticipated to contain functional MLNs but be devoid of GALT and most peripheral lymph nodes. Flow purified naïve (CD4(+) CD45RB(high) ) T-cells were adoptively transferred into the different groups of RAG(-/-) recipients to induce chronic colitis. RESULTS: We found that at 3-5 wks following T-cell transfer, all four of the surgically-manipulated RAG(-/-) groups (Sham, MLNx, Splx and MLNx/Splx) developed chronic colitis that was similar in onset and severity. Flow cytometric analysis revealed no differences among the different groups with respect to surface expression of different gut-homing markers nor were there any differences noted in IFN-γ and IL-17 generation by mononuclear cells isolated among these surgically-manipulated mice. Although we anticipated that LTß(-/-) x RAG(-/-) mice would contain functional MLNs but be devoid of GALT and peripheral lymph nodes (PLNs), we found that LTß(-/-) x RAG(-/-) mice were in fact devoid of MLNs as well as GALT and PLNs. Adoptive transfer of CD45RB(high) T-cells into LTß(-/-) x RAG(-/-) mice or their littermate controls (LTß(+/+) x RAG(-/-) ) induced rapid and severe colitis in both groups. CONCLUSIONS: Taken together, our data demonstrate that: a) neither the GALT, MLNs nor PLNs are required for induction of chronic gut inflammation in this model of IBD and b) T-and/or B-cells may be required for the development of MLNs in LTß(-/-) mice.


Assuntos
Colite/etiologia , Proteínas de Homeodomínio/fisiologia , Tecido Linfoide , Linfotoxina-beta/fisiologia , Nódulos Linfáticos Agregados , Animais , Doença Crônica , Feminino , Interleucina-17/imunologia , Linfonodos/imunologia , Linfonodos/patologia , Masculino , Camundongos , Camundongos Knockout , Baço/imunologia , Baço/patologia , Linfócitos T/imunologia , Células Th1/imunologia
15.
Anesth Analg ; 111(4): 1004-10, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20705788

RESUMO

BACKGROUND: Dexmedetomidine, a specific α(2) agonist, has an analgesic-sparing effect and reduces emergence agitation. We compared an intraoperative dexmedetomidine infusion with bolus fentanyl to reduce perioperative opioid use and decrease emergence agitation in children with obstructive sleep apnea syndrome undergoing adenotonsillectomy (T&A). METHODS: One hundred twenty-two patients with obstructive sleep apnea syndrome undergoing T&A, ages 2 to 10 years, completed this prospective, randomized, U.S. Food and Drug Administration-approved study. After mask induction with sevoflurane, group D received IV dexmedetomidine 2 µg · kg(-1) over 10 minutes, followed by 0.7 µg · kg(-1) · h(-1), and group F received IV fentanyl bolus 1 µg · kg(-1). Anesthesia was maintained with sevoflurane, oxygen, and nitrous oxide. Fentanyl 0.5 to 1 µg · kg(-1) was given to subjects in both groups for an increase in heart rate or systolic blood pressure 30% above preincision values that continued for 5 minutes. Observers in the postanesthesia care unit (PACU) were blinded to treatment groups. Pain was evaluated using the objective pain score in the PACU on arrival, at 5 minutes, at 15 minutes, then every 15 minutes for 120 minutes. Emergence agitation was evaluated at the same intervals by 2 scales: the Pediatric Anesthesia Emergence Delirium scale and a 5-point scale described by Cole. Morphine (0.05 to 0.1 mg · kg(-1)) was given for pain (score >4) or severe agitation (score 4 or 5) lasting more than 5 minutes. RESULTS: In group D, 9.8% patients needed intraoperative rescue fentanyl in comparison with 36% in group F (P = 0.001). Mean systolic blood pressure and heart rate were significantly lower in group D (P < 0.05). Minimum alveolar concentration values were significantly different between the 2 groups (P = 0.015). The median objective pain score was 3 for group D and 5 for group F (P = 0.001). In group D, 10 (16.3%) patients required rescue morphine, in comparison with 29 (47.5%) in group F (P = 0.002). The frequency of severe emergence agitation on arrival in the PACU was 18% in group D and 45.9% in group F (P = 0.004); at 5 minutes and at 15 minutes, it was lower in group D (P = 0.028). The duration of agitation on the Cole scale was statistically lower in group D (P = 0.004). In group D, 18% of patients and 40.9% in group F had an episode of Spo(2) below 95% (P = 0.01). CONCLUSIONS: An intraoperative infusion of dexmedetomidine combined with inhalation anesthetics provided satisfactory intraoperative conditions for T&A without adverse hemodynamic effects. Postoperative opioid requirements were significantly reduced, and the incidence and duration of severe emergence agitation was lower with fewer patients having desaturation episodes.


Assuntos
Adenoidectomia , Período de Recuperação da Anestesia , Dexmedetomidina/administração & dosagem , Agitação Psicomotora/prevenção & controle , Apneia Obstrutiva do Sono/cirurgia , Tonsilectomia , Adenoidectomia/efeitos adversos , Analgesia/métodos , Analgésicos não Narcóticos/administração & dosagem , Criança , Pré-Escolar , Feminino , Fentanila/administração & dosagem , Humanos , Infusões Intravenosas , Masculino , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Estudos Prospectivos , Agitação Psicomotora/etiologia , Apneia Obstrutiva do Sono/tratamento farmacológico , Tonsilectomia/efeitos adversos
16.
Am J Physiol Gastrointest Liver Physiol ; 296(2): G135-46, 2009 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19033538

RESUMO

The inflammatory bowel diseases (Crohn's disease; ulcerative colitis) are idiopathic chronic inflammatory disorders of the intestine and/or colon. A major advancement in our understanding of the pathogenesis of these diseases has been the development of mouse models of chronic gut inflammation. One model that has been instrumental in delineating the immunological mechanisms responsible for the induction as well as regulation of intestinal inflammation is the T cell transfer model of chronic colitis. This paper presents a detailed protocol describing the methods used to induce chronic colitis in mice. Special attention is given to the immunological concepts that explain disease pathogenesis in this model, considerations and potential pitfalls in using this model, and finally different "tricks" that we have learned over the past 12 years that have allowed us to develop a more simplified version of this model of experimental IBD.


Assuntos
Transferência Adotiva , Linfócitos T CD4-Positivos/transplante , Colite/imunologia , Colo/imunologia , Modelos Animais de Doenças , Doenças Inflamatórias Intestinais/imunologia , Animais , Antígeno CD11a/genética , Antígeno CD11a/metabolismo , Linfócitos T CD4-Positivos/imunologia , Separação Celular , Células Cultivadas , Doença Crônica , Colite/patologia , Colo/patologia , Progressão da Doença , Citometria de Fluxo , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Doenças Inflamatórias Intestinais/patologia , Interleucina-10/genética , Interleucina-10/metabolismo , Antígenos Comuns de Leucócito/análise , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Índice de Gravidade de Doença , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/transplante , Fatores de Tempo
17.
Pediatr Clin North Am ; 55(5): 1099-111, xi, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-18929054

RESUMO

This article reviews the general health care guidelines pertaining to pediatric patients with Down syndrome and presents, in a systems-based approach, an update of the current evidence behind these guidelines. To ensure the best possible long-term outcome for these patients, clinicians should provide routine well-child examinations and immunizations while maintaining a high index of suspicion for comorbid conditions more common in Down syndrome. The primary care provider should be prepared to provide information on community resources, to coordinate care with subspecialists, and to refer to early intervention services as soon as the diagnosis is made.


Assuntos
Síndrome de Down/complicações , Síndrome de Down/terapia , Atenção Primária à Saúde , Adolescente , Criança , Síndrome de Down/diagnóstico , Humanos , Guias de Prática Clínica como Assunto
19.
J Anim Ecol ; 77(6): 1082-91, 2008 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-18624834

RESUMO

1. We studied chick diet in a known-age, sexed population of a long-lived seabird, the Brünnich's guillemot (Uria lomvia), over 15 years (N = 136; 1993-2007) and attached time-depth-temperature recorders to examine foraging behaviour in multiple years (N = 36; 2004-07). 2. Adults showed specialization in prey fed to offspring, described by multiple indices calculated over 15 years: 27% of diet diversity was attributable to among-individual variation (within-individual component of total niche width = 0.73); average similarity of an individual's diet to the overall diet was 65% (mean proportional similarity between individuals and population = 0.65); diet was significantly more specialized than expected for 70% of individuals (mean likelihood = 0.53). These indices suggest higher specialization than the average for an across-taxa comparison of 49 taxa. 3. Foraging behaviour varied along three axes: flight time, dive depth and dive shape. Individuals showed specialized individual foraging behaviour along each axis. These foraging strategies were reflected in the prey type delivered to their offspring and were maintained over scales of hours to years. 4. Specialization in foraging behaviour and diet was greater over short time spans (hours, days) than over long time spans (years). Regardless of sex or age, the main component of variation in foraging behaviour and chick diet was between individuals. 5. Plasma stable isotope values were similar across years, within a given individual, and variance was low relative to that expected from prey isotope values, suggesting adult diet specialized across years. Stable isotope values were similar among individuals that fed their nestlings similar prey items and there was no difference in trophic level between adults and chicks. We suggest that guillemots specialize on a single foraging strategy regardless of whether chick-provisioning and self-feeding. With little individual difference in body mass and physiology, specialization likely represents learning and memorizing optimal feeding locations and behaviours. 6. There was no difference in survival or reproductive success between specialists and generalists, suggesting these are largely equivalent strategies in terms of evolutionary fitness, presumably because different strategies were advantageous at different levels of prey abundance or predictability. The development of individual specialization may be an important precursor to diversification among seabirds.


Assuntos
Charadriiformes/fisiologia , Dieta , Comportamento Predatório , Envelhecimento , Animais , Mergulho , Voo Animal , Método de Monte Carlo , Reprodução , Fatores de Tempo
20.
Anesth Analg ; 106(6): 1837-43, 2008 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-18499619

RESUMO

BACKGROUND: Teaching and assessment of the systems-based practice competency has been problematic in hospital-based specialties such as anesthesiology. We developed a method to teach systems-based practice with collaborative team projects. The outcome was assessed with a tool that focused on group attributes. METHODS: Resident teams chose projects that focused on the health care system. Projects included economic analyses, safety initiatives, process analyses, and policy revisions. Projects were presented by groups in poster discussion sessions. The educational program was evaluated using five criteria: implementation, awareness and acceptance in the organization, utility, sustainability, and diffusion to other programs. RESULTS: The plan was implemented in 2005 and remains a required part of the resident curriculum. Key hospital and medical school leaders in our health care system participated in projects. Interdisciplinary collaboration occurred with multiple clinical departments. Nine projects performed economic analysis, 5 involved safety initiatives, 10 performed process analysis and recommended change, and 4 affected policy change in the institution. The program has been sustainable and has been effective in creating multidisciplinary institutional policy. CONCLUSIONS: We developed an innovative method to teach systems-based practice through a team-based project initiative. The projects appear to have had a positive impact on our health care organization. Our assessment tool for the project evaluated team, rather than individual, performance, which is crucial in this competency.


Assuntos
Anestesiologia/educação , Competência Clínica , Comportamento Cooperativo , Educação de Pós-Graduação em Medicina , Processos Grupais , Pesquisa sobre Serviços de Saúde , Internato e Residência , Avaliação de Processos em Cuidados de Saúde , Anestesiologia/economia , Anestesiologia/organização & administração , Conscientização , Currículo , Docentes de Medicina , Humanos , Mentores , Modelos Educacionais , Formulação de Políticas , Avaliação de Programas e Projetos de Saúde
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