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1.
PLoS One ; 14(11): e0225716, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31774875

RESUMO

OBJECTIVE: To evaluate the capacity of multivariable prediction of preeclampsia during pregnancy, based on detailed routinely collected early pregnancy data in nulliparous women. DESIGN AND SETTING: A population-based cohort study of 62 562 pregnancies of nulliparous women with deliveries 2008-13 in the Stockholm-Gotland Counties in Sweden. METHODS: Maternal social, reproductive and medical history and medical examinations (including mean arterial pressure, proteinuria, hemoglobin and capillary glucose levels) routinely collected at the first visit in antenatal care, constitute the predictive variables. Predictive models for preeclampsia were created by three methods; logistic regression models using 1) pre-specified variables (similar to the Fetal Medicine Foundation model including maternal factors and mean arterial pressure), 2) backward selection starting from the full suite of variables, and 3) a Random forest model using the same candidate variables. The performance of the British National Institute for Health and Care Excellence (NICE) binary risk classification guidelines for preeclampsia was also evaluated. The outcome measures were diagnosis of preeclampsia with delivery <34, <37, and ≥37 weeks' gestation. RESULTS: A total of 2 773 (4.4%) nulliparous women subsequently developed preeclampsia. The pre-specified variables model was superior the other two models, regarding prediction of preeclampsia with delivery <34 and <37 weeks, both with areas under the curve of 0.68, and sensitivity of 30.6% (95% CI 24.5-37.2) and 29.2% (95% CI 25.2-33.4) at a 10% false positive rate, respectively. The performance of these customizable multivariable models at the chosen false positive rate, was significantly better than the binary NICE-guidelines for preeclampsia with delivery <37 and ≥37 weeks' gestation. CONCLUSION: Multivariable models in early pregnancy had a modest performance, although providing advantages over the NICE-guidelines, in predicting preeclampsia in nulliparous women. Use of a machine learning algorithm (Random forest) did not result in superior prediction.

3.
Am J Physiol Regul Integr Comp Physiol ; 316(5): R666-R677, 2019 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-30892909

RESUMO

The type 2 diabetes epidemic makes it important to find insulin-independent ways to improve glucose homeostasis. This study examines the mechanisms activated by a dual ß2-/ß3-adrenoceptor agonist, BRL37344, to increase glucose uptake in skeletal muscle and its effects on glucose homeostasis in vivo. We measured the effect of BRL37344 on glucose uptake, glucose transporter 4 (GLUT4) translocation, cAMP levels, ß2-adrenoceptor desensitization, ß-arrestin recruitment, Akt, AMPK, and mammalian target of rapamycin (mTOR) phosphorylation using L6 skeletal muscle cells as a model. We further tested the ability of BRL37344 to modulate skeletal muscle glucose metabolism in animal models (glucose tolerance tests and in vivo and ex vivo skeletal muscle glucose uptake). In L6 cells, BRL37344 increased GLUT4 translocation and glucose uptake only by activation of ß2-adrenoceptors, with a similar potency and efficacy to that of the nonselective ß-adrenoceptor agonist isoprenaline, despite being a partial agonist with respect to cAMP generation. GLUT4 translocation occurred independently of Akt and AMPK phosphorylation but was dependent on mTORC2. Furthermore, in contrast to isoprenaline, BRL37344 did not promote agonist-mediated desensitization and failed to recruit ß-arrestin1/2 to the ß2-adrenoceptor. In conclusion, BRL37344 improved glucose tolerance and increased glucose uptake into skeletal muscle in vivo and ex vivo through a ß2-adrenoceptor-mediated mechanism independently of Akt. BRL37344 was a partial agonist with respect to cAMP, but a full agonist for glucose uptake, and importantly did not cause classical receptor desensitization or internalization of the receptor.


Assuntos
Agonistas de Receptores Adrenérgicos beta 2/farmacologia , Etanolaminas/farmacologia , Transportador de Glucose Tipo 4/metabolismo , Glucose/metabolismo , Músculo Esquelético/efeitos dos fármacos , Mioblastos Esqueléticos/efeitos dos fármacos , Receptores Adrenérgicos beta 2/efeitos dos fármacos , Animais , Linhagem Celular , AMP Cíclico/metabolismo , Feminino , Transportador de Glucose Tipo 4/genética , Humanos , Cinética , Alvo Mecanístico do Complexo 2 de Rapamicina/metabolismo , Camundongos Knockout , Músculo Esquelético/citologia , Músculo Esquelético/metabolismo , Mioblastos Esqueléticos/metabolismo , Transporte Proteico , Ratos , Receptores Adrenérgicos beta 2/metabolismo , Receptores Adrenérgicos beta 3/genética , Receptores Adrenérgicos beta 3/metabolismo , Transdução de Sinais
4.
Acta Obstet Gynecol Scand ; 98(8): 988-996, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30767210

RESUMO

INTRODUCTION: The impact of placenta previa on pregnancy, delivery and infant outcomes has been extensively studied. However, less is known about the possible association of placental location other than previa with pregnancy outcomes. The aim of this study was to investigate if placental location other than previa is associated with adverse pregnancy, delivery and infant outcomes. MATERIAL AND METHODS: This is a population-based cohort study, with data from the regional population-based Stockholm-Gotland Obstetric Cohort, Sweden, from 2008 to 2014. The study population included 74 087 nulliparous women with singleton pregnancies resulting in live-born infants, with information about placental location from the second-trimester ultrasound screening. The association between placental location (fundal, lateral, anterior or posterior) and pregnancy outcomes was estimated using logistic regression analysis. Odds ratios (OR) with 95% confidence intervals (95% CI) were calculated, and adjustments were made for maternal age, height, country of birth, smoking in early pregnancy, sex of the infant and in vitro fertilization. Main outcome measures were pregnancy, delivery and infant outcomes. RESULTS: Compared with posterior placental location, fundal and lateral placental locations were associated with a number of adverse pregnancy outcomes, the most important being: very preterm birth (<32 weeks of gestation) (adjusted OR [aOR] 1.78, 95% CI 1.18-2.63 and aOR 2.12, 95% CI 1.39-2.25, respectively), moderate preterm birth (32-36 weeks of gestation) (aOR 1.23, 95% CI 1.001-1.51 and aOR 1.62, 95% CI 1.32-2.00, respectively), small-for-gestational-age birth (aOR 1.67, 95% CI 1.34-2.07 and aOR 1.77, 95% CI 1.39-2.25, respectively) and manual removal of the placenta in vaginal births (aOR 3.27, 95% CI 2.68-3.99 and aOR 3.27, 95% CI 2.60-4.10, respectively). Additionally, lateral placental location was associated with preeclampsia (aOR 1.30, 95% CI 1.03-1.65) and severe postpartum hemorrhage (aOR 1.42, 95% CI 1.27-1.82). CONCLUSIONS: Compared with posterior placental location, fundal and lateral placental locations are associated with a number of adverse pregnancy, delivery and infant outcomes.

5.
J Perinatol ; 38(9): 1144-1150, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29915374

RESUMO

OBJECTIVE: To investigate whether maternal overweight and obesity increased the risk of fetal acidosis measured in umbilical cord arterial blood after delivery. STUDY DESIGN: Population-based cohort study of 84,785 term (≥37 weeks) infants. Logistic regression was used to estimate risks of fetal acidosis in umbilical cord arterial blood. Fetal acidosis was defined as pH <7.10 or as pH <1st percentile on a normal reference curve. RESULT: Risks of fetal acidosis increased, regardless of definition, with maternal overweight and obesity severity. Compared to normal weight (BMI 18.5-<25), the odds ratios (95% confidence interval) for pH <7.10 were 1.35 (1.23-1.47) for overweight (BMI 25-<30), 1.46 (1.27-1.69) for mild obesity (BMI 30-<35), and 1.75 (1.42-2.15) for severe obesity (BMI ≥35). The association for obesity was attenuated in analyses restricted to non-instrumental vaginal deliveries. CONCLUSION: Maternal overweight and obesity increased the risk of fetal acidosis. More complicated deliveries in obese women may partially explain this association.


Assuntos
Acidose/epidemiologia , Trabalho de Parto , Obesidade Mórbida/complicações , Sobrepeso/complicações , Complicações na Gravidez/epidemiologia , Acidose/sangue , Adolescente , Adulto , Índice de Massa Corporal , Estudos de Coortes , Feminino , Sangue Fetal/química , Idade Gestacional , Humanos , Concentração de Íons de Hidrogênio , Recém-Nascido , Modelos Logísticos , Masculino , Gravidez , Complicações na Gravidez/sangue , Fatores de Risco , Suécia/epidemiologia , Adulto Jovem
6.
J Med Case Rep ; 12(1): 96, 2018 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-29655368

RESUMO

BACKGROUND: Hernias of the posterior rectus sheath are very rare abdominal wall hernias with only a handful of cases reported in the literature to date. As an uncommon disease, it is important to recognize and report this case in order to enhance scientific knowledge of this disease. CASE PRESENTATION: This case report presents a spontaneous posterior rectus sheath herniation in a 79-year-old white man with previous abdominal surgery for appendicitis. His herniation was discovered incidentally during an examination for his chief complaints of lower abdominal pain and diarrhea which were later diagnosed as Salmonella-related gastroenteritis. A computed tomography scan of his abdomen and pelvis showed abdominal wall hernia with loops of small bowel extending into his rectus abdominis muscle. In this case, it was decided to leave the situation alone for now due to no evidence of bowel obstruction and the low risk of this hernia getting strangulated, which otherwise would have warranted urgent surgery. CONCLUSIONS: This report adds to the limited stock of available literature on this unusual issue and strengthens the evidence base on the best approach to support informed clinical decision making. The significant clinical implication of such case reports is increased identification rate of rare clinical conditions which otherwise often go unnoticed.


Assuntos
Hérnia Ventral/diagnóstico , Reto do Abdome , Dor Abdominal/etiologia , Idoso , Tratamento Conservador , Hérnia Ventral/complicações , Humanos , Achados Incidentais , Intestino Delgado/diagnóstico por imagem , Masculino , Reto do Abdome/diagnóstico por imagem , Tomografia Computadorizada por Raios X
7.
Biochem Pharmacol ; 148: 27-40, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29175420

RESUMO

The capacity of G protein-coupled receptors to modulate mechanistic target of rapamycin (mTOR) activity is a newly emerging paradigm with the potential to link cell surface receptors with cell survival. Cardiomyocyte viability is linked to signalling pathways involving Akt and mTOR, as well as increased glucose uptake and utilization. Our aim was to determine whether the α1A-adrenoceptor (AR) couples to these protective pathways, and increased glucose uptake. We characterised α1A-AR signalling in CHO-K1 cells co-expressing the human α1A-AR and GLUT4 (CHOα1AGLUT4myc) and in neonatal rat ventricular cardiomyocytes (NRVM), and measured glucose uptake, intracellular Ca2+ mobilization, and phosphorylation of mTOR, Akt, 5' adenosine monophosphate-activated kinase (AMPK) and S6 ribosomal protein (S6rp). In both systems, noradrenaline and the α1A-AR selective agonist A61603 stimulated glucose uptake by parallel pathways involving mTOR and AMPK, whereas another α1-AR agonist oxymetazoline increased glucose uptake predominantly by mTOR. All agonists promoted phosphorylation of mTOR at Ser2448 and Ser2481, indicating activation of both mTORC1 and mTORC2, but did not increase Akt phosphorylation. In CHOα1AGLUT4myc cells, siRNA directed against rictor but not raptor suppressed α1A-AR mediated glucose uptake. We have thus identified mTORC2 as a key component in glucose uptake stimulated by α1A-AR agonists. Our findings identify a novel link between the α1A-AR, mTORC2 and glucose uptake, that have been implicated separately in cardiomyocyte survival. Our studies provide an improved framework for examining the utility of α1A-AR selective agonists as tools in the treatment of cardiac dysfunction.


Assuntos
Glucose/metabolismo , Miócitos Cardíacos/metabolismo , Receptores Adrenérgicos alfa 1/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Animais , Células CHO , Calcimicina , Cálcio , Cricetinae , Cricetulus , Regulação da Expressão Gênica/efeitos dos fármacos , Transportador de Glucose Tipo 4/genética , Transportador de Glucose Tipo 4/metabolismo , Norepinefrina , Fosforilação , Prazosina/metabolismo , Prazosina/farmacologia , Ratos , Transdução de Sinais , Serina-Treonina Quinases TOR/genética
8.
BMJ Case Rep ; 20172017 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-28716872

RESUMO

Femoral hernias can be difficult to diagnose and are at high risk of strangulation. This report is of a rare case of an irreducible femoral hernia containing caecum and appendix presenting as an emergency. To the authors' knowledge, there have only been three cases reported, the first described by Duari. This case was incorrectly diagnosed preoperatively as an inguinal hernia, so the CT diagnosis of femoral hernias is reviewed, in particular demonstrating the radiological use of the femoral vein compression sign.


Assuntos
Veia Femoral/patologia , Fêmur/patologia , Hérnia Femoral/diagnóstico , Doenças Vasculares/diagnóstico , Erros de Diagnóstico , Veia Femoral/diagnóstico por imagem , Fêmur/diagnóstico por imagem , Hérnia Femoral/complicações , Hérnia Femoral/diagnóstico por imagem , Hérnia Femoral/patologia , Hérnia Inguinal/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios X , Doenças Vasculares/diagnóstico por imagem , Doenças Vasculares/etiologia
9.
Mol Metab ; 6(6): 611-619, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28580291

RESUMO

OBJECTIVE: Today, the presence and activity of brown adipose tissue (BAT) in adult humans is generally equated with the induced accumulation of [2-18F]2-fluoro-2-deoxy-d-glucose ([18F]FDG) in adipose tissues, as investigated by positron emission tomography (PET) scanning. In reality, PET-FDG is currently the only method available for in vivo quantification of BAT activity in adult humans. The underlying assumption is that the glucose uptake reflects the thermogenic activity of the tissue. METHODS: To examine this basic assumption, we here followed [18F]FDG uptake by PET and by tissue [3H]-2-deoxy-d-glucose uptake in wildtype and UCP1(-/-) mice, i.e. in mice that do or do not possess the unique thermogenic and calorie-consuming ability of BAT. RESULTS: Unexpectedly, we found that ß3-adrenergically induced (by CL-316,243) glucose uptake was UCP1-independent. Thus, whereas PET-FDG scans adequately reflect glucose uptake, this acute glucose uptake is not secondary to thermogenesis but is governed by an independent cellular signalling, here demonstrated to be mediated via the previously described KU-0063794-sensitive mTOR pathway. CONCLUSIONS: Thus, PET-FDG scans do not exclusively reveal active BAT deposits but rather any tissue possessing an adrenergically-mediated glucose uptake pathway. In contrast, we found that the marked glucose uptake-ameliorating effect of prolonged ß3-adrenergic treatment was UCP1 dependent. Thus, therapeutically, UCP1 activity is required for any anti-diabetic effect of BAT activation.


Assuntos
Tecido Adiposo Marrom/metabolismo , Agonistas de Receptores Adrenérgicos beta 3/farmacologia , Fluordesoxiglucose F18/farmacocinética , Serina-Treonina Quinases TOR/metabolismo , Proteína Desacopladora 1/metabolismo , Tecido Adiposo Marrom/efeitos dos fármacos , Animais , Camundongos , Camundongos Endogâmicos C57BL , Proteína Desacopladora 1/genética
10.
BMC Pregnancy Childbirth ; 17(1): 72, 2017 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-28222704

RESUMO

BACKGROUND: We sought to investigate the impact of the duration of second stage of labor on risk of severe perineal lacerations (third and fourth degree). METHODS: This population based cohort study was conducted in the Stockholm/Gotland region, Sweden, 2008-2014. Study population included 52 211 primiparous women undergoing vaginal delivery with cephalic presentation at term. Unconditional logistic regression analysis was used to calculate crude and adjusted odds ratios (OR), using 95% confidence intervals (CI). Main exposure was duration of second stage of labor, and main outcome was risks of severe perineal lacerations (third and fourth degree). RESULTS: Risk of severe perineal lacerations increased with duration of second stage of labor. Compared with a second stage of labor of 1 h or less, women with a second stage of more than 2 h had an increased risk (aOR 1.42; 95% CI 1.28-1.58). Compared with non-instrumental vaginal deliveries, the risk was elevated among instrumental vaginal deliveries (aOR 2.24; 95% CI 2.07-2.42). The risk of perineal laceration increased with duration of second stage of labor until less than 3 h in both instrumental and non-instrumental vaginal deliveries, but after 3 h, the ORs did not further increase. After adjustments for potential confounders, macrosomia (birth weight > 4 500 g) and occiput posterior fetal position were risk factors of severe perineal lacerations. CONCLUSIONS: The risk of severe perineal laceration increases with duration until the third hour of second stage of labor. Instrumental delivery is the most significant risk factor for severe lacerations, followed by duration of second stage of labor, fetal size and occiput posterior fetal position.


Assuntos
Parto Obstétrico/efeitos adversos , Episiotomia/efeitos adversos , Lacerações/epidemiologia , Complicações do Trabalho de Parto/epidemiologia , Forceps Obstétrico/efeitos adversos , Períneo/lesões , Vigilância da População , Adulto , Episiotomia/instrumentação , Feminino , Humanos , Recém-Nascido , Lacerações/etiologia , Masculino , Complicações do Trabalho de Parto/etiologia , Razão de Chances , Gravidez , Estudos Retrospectivos , Fatores de Risco , Suécia/epidemiologia , Adulto Jovem
11.
ANZ J Surg ; 87(7-8): 587-590, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26573997

RESUMO

BACKGROUND: The diagnosis of acute appendicitis is made using clinical findings and investigations. Recent studies have suggested that serum bilirubin, a cheap and simple biochemical test, is a positive predictor in the diagnosis of appendiceal perforation and may be more specific than C-reactive protein (CRP) and white cell count (WCC). The aim of this study was to investigate the utility of the serum bilirubin level in patients with suspected acute but non-perforative appendicitis. METHODS: A retrospective chart review of 213 patients who presented with suspected appendicitis in a 6-month period to Nambour General Hospital was performed. Serum bilirubin, WCC and CRP were recorded and analysed as to their utility in relation to the final diagnosis. RESULTS: A total of 196 patients underwent an appendicectomy and 41 of these were negative. The specificity of hyperbilirubinaemia for appendicitis overall was 0.83 with a positive predictive value (PPV) of 0.86, compared with CRP (specificity 0.40, PPV 0.75) and WCC (specificity 0.67, PPV 0.85). The area under the receiver operating characteristic curve for bilirubin was 0.6289 compared to 0.6171 for CRP and 0.7219 for WCC. A subgroup analysis of those with complicated appendicitis demonstrated a PPV for bilirubin of 0.66 compared to 0.58 for WCC and 0.34 for CRP in agreement with the literature. Subgroup analysis of hyperbilirubinaemia in simple appendicitis demonstrated a PPV of 0.81 compared to CRP (0.71) and WCC (0.82). CONCLUSION: Bilirubin had a higher specificity than CRP and WCC overall in patients with appendicitis. Hyperbilirubinaemia had a high PPV in patients with simple appendicitis.


Assuntos
Apendicite/sangue , Apendicite/diagnóstico , Bilirrubina/sangue , Apendicite/complicações , Humanos , Hiperbilirrubinemia/etiologia , Estudos Retrospectivos
12.
Ann Vasc Surg ; 38: 316.e13-316.e16, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27522969

RESUMO

Injuries to the popliteal artery during total knee arthroplasty (TKA) are rare. We present a case of a 72-year-old man with popliteal artery thrombosis and a pseudoaneurysm presenting immediately after TKA. First-line management of acute limb ischemia is currently transitioning from open surgery to endovascular strategies such as catheter-directed thrombolysis or mechanical thrombectomy. Due to the rarity of acute limb ischemia and pseudoaneurysms after TKA, endovascular management is only reported in a few case studies. This case is distinctive by having both popliteal artery thrombosis and a pseudoaneurysm which were successfully managed entirely endovascular using AngioJet thrombolysis and a flexible covered stent. This case contributes to the evidence supporting endovascular management of this rare complication of TKA.


Assuntos
Falso Aneurisma/terapia , Angioplastia com Balão , Arteriopatias Oclusivas/terapia , Artroplastia do Joelho/efeitos adversos , Artéria Poplítea/lesões , Trombose/terapia , Lesões do Sistema Vascular/terapia , Idoso , Falso Aneurisma/diagnóstico por imagem , Falso Aneurisma/etiologia , Angioplastia com Balão/instrumentação , Arteriopatias Oclusivas/diagnóstico por imagem , Arteriopatias Oclusivas/etiologia , Humanos , Masculino , Artéria Poplítea/diagnóstico por imagem , Stents , Terapia Trombolítica , Trombose/diagnóstico por imagem , Trombose/etiologia , Resultado do Tratamento , Lesões do Sistema Vascular/diagnóstico por imagem , Lesões do Sistema Vascular/etiologia
13.
Ann Vasc Surg ; 38: 315.e15-315.e17, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27522977

RESUMO

Venous aneurysms are a rare pathology that was first reported in the literature in 1968. Popliteal venous aneurysms (PVAs) are the most common lower limb venous aneurysm and have significant consequences including deep vein thrombosis, pulmonary embolus (PE), and death. A 52-year-old woman presented with chest pain and shortness of breath. A computed tomography (CT) angiography demonstrated bilateral pulmonary emboli, and she was commenced on rivaroxaban. History revealed no significant risk factors, and a thrombophilia screen was negative. However, an aneurysmal popliteal vein as seen on an ultrasound scan that was further clarified with CT venography. She underwent an uncomplicated open tangential resection and lateral venorrhaphy. The diagnosis of PVA is usually made incidentally during investigations for pulmonary embolism or chronic venous insufficiency. Surgery is indicated in all symptomatic patients with PE as anticoagulation alone is inadequate in these patients. Surgery is also recommended in patients with asymptomatic saccular aneurysms or large (>20 mm) fusiform aneurysms. The current mainstay of treatment for PVAs is open surgical management.


Assuntos
Aneurisma/complicações , Veia Poplítea , Embolia Pulmonar/etiologia , Aneurisma/diagnóstico por imagem , Aneurisma/terapia , Anticoagulantes/uso terapêutico , Angiografia por Tomografia Computadorizada , Feminino , Humanos , Pessoa de Meia-Idade , Flebografia/métodos , Veia Poplítea/diagnóstico por imagem , Veia Poplítea/cirurgia , Embolia Pulmonar/diagnóstico por imagem , Embolia Pulmonar/terapia , Fatores de Risco , Rivaroxabana/uso terapêutico , Resultado do Tratamento , Procedimentos Cirúrgicos Vasculares
14.
Ann Vasc Surg ; 36: 296.e9-296.e12, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27427351

RESUMO

INTRODUCTION: Visceral artery aneurysms (VAAs) are an uncommon vascular pathology with an incidence estimated at 0.01-2%. The likely etiology of VAAs is uncertain, which includes atherosclerosis, trauma, and inflammation. VAAs are often asymptomatic until rupture which causes life-threatening hemorrhage and are associated with a high mortality. Gastric artery aneurysms (GAA) form a very small proportion of VAAs (<4%). CASE DESCRIPTION: This is a case series of 3 patients who presented to the Nambour Hospital with a ruptured left gastric aneurysm. They each presented with acute abdominal pain and hemodynamic instability with imaging revealing a ruptured left gastric artery aneurysm and hemoperitoneum. Patients 1 and 2 received open surgical repair in the first instance, while Patient 3 was managed endovascularly initially and proceeded to open repair due to ongoing hemorrhage. DISCUSSION: Management of ruptured VAAs can be by either open surgical or endovascular means. The advantages of open exploration in the emergency setting include the ability to directly inspect the gastric wall and other viscera and to evacuate hematoma. Additionally, it does not require the use of an angiographic suite. We feel that open repair remains an important means of managing a ruptured GAA, particularly in the shocked patient.


Assuntos
Aneurisma Roto/cirurgia , Artérias/cirurgia , Hemorragia Gastrointestinal/cirurgia , Estômago/irrigação sanguínea , Procedimentos Cirúrgicos Vasculares , Dor Abdominal/etiologia , Dor Aguda/etiologia , Idoso , Aneurisma Roto/complicações , Aneurisma Roto/diagnóstico por imagem , Aneurisma Roto/fisiopatologia , Artérias/diagnóstico por imagem , Artérias/fisiopatologia , Angiografia por Tomografia Computadorizada , Emergências , Feminino , Hemorragia Gastrointestinal/diagnóstico por imagem , Hemorragia Gastrointestinal/fisiopatologia , Hemodinâmica , Hemoperitônio/etiologia , Humanos , Ligadura , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
15.
PLoS One ; 10(10): e0140422, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26465918

RESUMO

BACKGROUND: The use of low-molecular-weight heparins (LMWHs) during pregnancy is increasing. In vitro studies and small clinical studies support the hypothesis that LMWH treatment during pregnancy may reduce duration of labor. The aim of this study was to investigate if use of LMWH is associated with a reduced risk of diagnosis of prolonged labor, after taking maternal, fetal and other delivery characteristics into account. METHODS AND FINDINGS: A population-based cohort study from the Swedish Medical Birth Register from April 2006 through December 2011. We identified 514 875 term (≥37 weeks) deliveries of live singleton infants in cephalic presentation with spontaneous or induced onsets of labor. The Birth Register was linked to the Prescribed Drug Register to retrieve information on dispensed LMWH during pregnancy and to the Patient Register for information on underlying diagnosis for use of LMWH. Diagnosis of prolonged labor in the Birth Register was retrieved from diagnosis at discharge from the delivery hospital. The risk of diagnosis of prolonged labor in relation to treatment with LMWH was assessed using logistic regression analysis to estimate unadjusted and adjusted odds ratios. A total of 5 275 (1.0%) of the pregnant women used LMWH. The absolute risk of diagnosis of prolonged labor for nulliparous women was 19.9% among women using LMWH in third trimester, and 21.2% in women without use of LMWH. For parous women the corresponding absolute risks were 4.3% and 4.7%, respectively. Compared to nulliparous women without use of LMWH, nulliparous women with LMWH during third trimester had an odds ratio (OR) of 0.92 (95% CI 0.81-1.05, p-value: 0.051) for diagnosis of prolonged labor in unadjusted analyses and after adjustments for maternal characteristics, gestational age and epidural analgesia the OR was 1.00 (95% CI 0.87-1.15, p-value: 0.673). Parous women treated with LMWH in third trimester presented the same pattern, unadjusted OR for diagnosis of prolonged labor was 0.92 (95% CI 0.76-1.12, p-value: 0.418) and after adjustments OR was 0.99 (95% CI 0.80-1.22, p-value: 0.892). One limitation with the study was that information on prolonged labor was based on discharge diagnoses from the delivery hospital according to the International Classification of Diseases (ICD). CONCLUSIONS: Treatment with LMWH during pregnancy is not associated with a risk of diagnosis of prolonged labor after adjustments for maternal, fetal and delivery characteristics.


Assuntos
Anticoagulantes/efeitos adversos , Heparina de Baixo Peso Molecular/efeitos adversos , Complicações do Trabalho de Parto/etiologia , Adulto , Estudos de Coortes , Feminino , Humanos , Complicações do Trabalho de Parto/epidemiologia , Gravidez
16.
Eur J Epidemiol ; 30(11): 1209-15, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26008749

RESUMO

There is no consensus on the effects of a prolonged second stage of labor on neonatal outcomes. In this large Swedish population-based cohort study, our objective was to investigate prolonged second stage and risk of low Apgar score at 5 min. All nulliparous women (n = 32,796) delivering a live born singleton infant in cephalic presentation at ≥37 completed weeks after spontaneous onset of labor between 2008 and 2012 in the counties of Stockholm and Gotland were included. Data were obtained from computerized records. Exposure was time from fully retracted cervix until delivery. Logistic regression analyses were used to estimate crude and adjusted odds ratios (ORs) with 95% confidence intervals (CIs). Adjustments were made for maternal age, height, BMI, smoking, sex, gestational age, sex-specific birth weight for gestational age and head circumference. Epidural analgesia was included in a second model. The primary outcome measure was Apgar score at 5 min <7 and <4. We found that the overall rates of 5 min Apgar score <7 and <4 were 7.0 and 1.3 per 1000 births, respectively. Compared to women with <1 h from retracted cervix to birth, adjusted ORs of Apgar score <7 at 5 min generally increased with length of second stage of labor: 1 to <2 h: OR 1.78 (95% CI 1.19-2.66); 2 to <3 h: OR 1.66 (1.05-2.62); 3 to <4 h: OR 2.08 (1.29-3.35); and ≥4 h: OR 2.71 (1.67-4.40). We conclude that prolonged second stage of labor is associated with an increased risk of low 5 min Apgar score.


Assuntos
Índice de Apgar , Parto Obstétrico/estatística & dados numéricos , Segunda Fase do Trabalho de Parto/fisiologia , Adulto , Asfixia Neonatal/epidemiologia , Asfixia Neonatal/etiologia , Distocia/epidemiologia , Distocia/etiologia , Feminino , Humanos , Recém-Nascido , Idade Materna , Complicações do Trabalho de Parto/epidemiologia , Complicações do Trabalho de Parto/etiologia , Ocitócicos/administração & dosagem , Ocitocina/administração & dosagem , Paridade , Vigilância da População , Gravidez , Resultado da Gravidez , Fatores de Risco , Suécia , Adulto Jovem
17.
J Cell Biol ; 207(3): 365-74, 2014 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-25385184

RESUMO

Brown adipose tissue is the primary site for thermogenesis and can consume, in addition to free fatty acids, a very high amount of glucose from the blood, which can both acutely and chronically affect glucose homeostasis. Here, we show that mechanistic target of rapamycin (mTOR) complex 2 has a novel role in ß3-adrenoceptor-stimulated glucose uptake in brown adipose tissue. We show that ß3-adrenoceptors stimulate glucose uptake in brown adipose tissue via a signaling pathway that is comprised of two different parts: one part dependent on cAMP-mediated increases in GLUT1 transcription and de novo synthesis of GLUT1 and another part dependent on mTOR complex 2-stimulated translocation of newly synthesized GLUT1 to the plasma membrane, leading to increased glucose uptake. Both parts are essential for ß3-adrenoceptor-stimulated glucose uptake. Importantly, the effect of ß3-adrenoceptor on mTOR complex 2 is independent of the classical insulin-phosphoinositide 3-kinase-Akt pathway, highlighting a novel mechanism of mTOR complex 2 activation.


Assuntos
Adipócitos Marrons/metabolismo , Transportador de Glucose Tipo 1/metabolismo , Glucose/metabolismo , Complexos Multiproteicos/fisiologia , Serina-Treonina Quinases TOR/fisiologia , Agonistas de Receptores Adrenérgicos beta 3/farmacologia , Animais , Células Cultivadas , Feminino , Humanos , Insulina/farmacologia , Insulina/fisiologia , Isoproterenol/farmacologia , Masculino , Alvo Mecanístico do Complexo 2 de Rapamicina , Camundongos , Morfolinas/farmacologia , Células-Tronco Multipotentes/metabolismo , Fosforilação , Cultura Primária de Células , Processamento de Proteína Pós-Traducional , Transporte Proteico , Pirimidinas/farmacologia , Receptores Adrenérgicos beta 3/metabolismo , Sirolimo/farmacologia , Serina-Treonina Quinases TOR/antagonistas & inibidores , Serina-Treonina Quinases TOR/metabolismo
18.
Diabetes ; 63(12): 4115-29, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25008179

RESUMO

There is an increasing worldwide epidemic of type 2 diabetes that poses major health problems. We have identified a novel physiological system that increases glucose uptake in skeletal muscle but not in white adipocytes. Activation of this system improves glucose tolerance in Goto-Kakizaki rats or mice fed a high-fat diet, which are established models for type 2 diabetes. The pathway involves activation of ß2-adrenoceptors that increase cAMP levels and activate cAMP-dependent protein kinase, which phosphorylates mammalian target of rapamycin complex 2 (mTORC2) at S2481. The active mTORC2 causes translocation of GLUT4 to the plasma membrane and glucose uptake without the involvement of Akt or AS160. Stimulation of glucose uptake into skeletal muscle after activation of the sympathetic nervous system is likely to be of high physiological relevance because mTORC2 activation was observed at the cellular, tissue, and whole-animal level in rodent and human systems. This signaling pathway provides new opportunities for the treatment of type 2 diabetes.


Assuntos
Glicemia/metabolismo , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Transportador de Glucose Tipo 4/metabolismo , Complexos Multiproteicos/metabolismo , Músculo Esquelético/metabolismo , Receptores Adrenérgicos beta 2/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Animais , Células Cultivadas , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Diabetes Mellitus Experimental/etiologia , Diabetes Mellitus Tipo 2/etiologia , Dieta Hiperlipídica/efeitos adversos , Teste de Tolerância a Glucose , Alvo Mecanístico do Complexo 2 de Rapamicina , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Fosforilação , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Ratos Sprague-Dawley , Transdução de Sinais
19.
Proteomics Clin Appl ; 6(9-10): 486-96, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22930578

RESUMO

PURPOSE: Pancreatitis is an inflammatory state of the pancreas, for which high-performing serological biomarkers are lacking. The aim of the present study was to evaluate the use of affinity proteomics for identifying potential markers of disease and stratifying pancreatitis subtypes. EXPERIMENTAL DESIGN: High-content, recombinant antibody microarrays were applied for serum protein expression profiling of 113 serum samples from patients with chronic, acute, and autoimmune pancreatitis, as well as healthy controls. The sample groups were compared using supervised classification based on support vector machine analysis. RESULTS: This discovery study showed that pancreatitis subtypes could be discriminated with high accuracy. Using unfiltered data, the individual subtypes, as well as the combined pancreatitis cohort, were distinguished from healthy controls with high AUC values (0.96-1.00). Moreover, characteristic protein patterns and AUC values in the range of 0.69-0.95 were observed for the individual pancreatitis entities when compared to each other, and to all other samples combined. CONCLUSIONS AND CLINICAL RELEVANCE: This study demonstrated the potential of the antibody microarray approach for stratification of pancreatitis. Distinct candidate multiplex serum biomarker signatures for chronic, acute, and autoimmune pancreatitis were defined, which could enhance our fundamental knowledge of the underlying molecular mechanisms, and potentially lead to improved diagnosis.


Assuntos
Pancreatite/sangue , Análise Serial de Proteínas , Proteoma/análise , Anticorpos de Cadeia Única/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Biomarcadores/sangue , Feminino , Perfilação da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Pancreatite/patologia , Proteômica , Proteínas Recombinantes/genética , Proteínas Recombinantes/imunologia , Proteínas Recombinantes/metabolismo , Estudos Retrospectivos , Anticorpos de Cadeia Única/genética , Anticorpos de Cadeia Única/metabolismo , Adulto Jovem
20.
Cancer Res ; 72(10): 2481-90, 2012 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-22589272

RESUMO

Pancreatic cancer is an aggressive disease with poor prognosis, due, in part, to the lack of disease-specific biomarkers that could afford early and accurate diagnosis. With a recombinant antibody microarray platform, targeting mainly immunoregulatory proteins, we screened sera from 148 patients with pancreatic cancer, chronic pancreatitis, autoimmune pancreatitis (AIP), and healthy controls (N). Serum biomarker signatures were derived from training cohorts and the predictive power was evaluated using independent test cohorts. The results identified serum portraits distinguishing pancreatic cancer from N [receiver operating characteristics area under the curve (AUC) of 0.95], chronic pancreatitis (0.86), and AIP (0.99). Importantly, a 25-serum biomarker signature discriminating pancreatic cancer from the combined group of N, chronic pancreatitis, and AIP was determined. This signature exhibited a high diagnostic potential (AUC of 0.88). In summary, we present the first prevalidated, multiplexed serum biomarker signature for diagnosis of pancreatic cancer that may improve diagnosis and prevention in premalignant diseases and in screening of high-risk individuals.


Assuntos
Biomarcadores Tumorais/sangue , Carcinoma Ductal Pancreático/sangue , Neoplasias Pancreáticas/sangue , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Humanos , Pessoa de Meia-Idade , Pancreatite/diagnóstico , Pancreatite Crônica/sangue
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