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BACKGROUND: Although non-segmental vitiligo is commonly considered an autoimmune disease, the possible differences between non-segmental vitiligo patients with and without autoimmune signals have not been clearly established. OBJECTIVE: To perform a comparison of non-segmental vitiligo patients with autoimmune signals (AIS) vs. those without autoimmune signals (NAIS) in regards to clinical characteristics and toxic/drug exposure. METHODS: 112 vitiligo patients were selected for a sex and age matched (1 : 1) case control study at an university based dermatology outpatient hospital specialized in pigmentary disorders. Medical assessment was performed by dermatologists using the modified Vitiligo European Task Force form and serological and clinical signs of autoimmunity were evaluated. RESULTS: Disease duration, age of onset, patient history of cardiovascular disease, past smoking history, use of drugs, and consummation of goitrogenic foods were all significantly increased in the AIS group using McNemar's test for matched pairs. In our conditional regression model, the simultaneous presence of disease duration, use of prescription drugs, and consummation of goitrogenic foods were the best predictors of AIS vitiligo patients. CONCLUSION: The evaluation of non-segmental vitiligo patients according to the presence vs. the absence of autoimmune signals allows us to correlate patients exhibiting autoimmune phenomenon with certain clinical characteristics, namely long disease duration, use of prescription drugs, and consumption of goitrogenic substances. In the presence of the aforementioned clinical profile, we suggest an evaluation of autoimmune signals.
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Vitiligo/imunologia , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Vitiligo/induzido quimicamente , Vitiligo/patologiaRESUMO
BACKGROUND: Current studies have treated a limited portion of the subjective aspects of vitiligo patients and have yet to elucidate possible psychological differences between those with autoimmune markers (AIM) with respect to those without autoimmune markers (NAIM). OBJECTIVE: To perform an age and gender-matched 1:1 case-control study through a comparison of non-segmental vitiligo patients with autoimmune features vs. those without autoimmune features in regards to psychiatric features, psychosomatic aspects and social parameters. METHODS: A total of 112 non-segmental vitiligo patients have been examined at the Florence University dermatology outpatient service (2nd dermatology unit). Vitiligo with an autoimmune background was defined by the presence of autoimmune antibodies and/or autoimmune diseases. Psychiatric screening was performed by dermatologists using the modified Middlesex Healthcare Questionnaire (MHQ); psychosomatic aspects and social impact were analysed with a standardized, Florentine questionnaire. RESULTS: Upon performing a conditional regression model, age, phobia and obsession were significantly predictive of the presence of AIM and a low total MHQ score was significantly predictive of NAIM in vitiligo patients. With univariate analysis, we found significant differences in: identifiable stress related to the onset of vitiligo, vitiligo triggered by stress, and modified interpersonal relationships related to vitiligo, which were associated with the subgroup containing autoimmunity markers. CONCLUSIONS: We found a higher prevalence of age, obsession and phobia among vitiligo patients AIM as compared to vitiligo patients NAIM. Thus, in the presence of demonstrated autoimmunity, screening for particular psychiatric aspects may be useful in the clinical practice of vitiligo.
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Biomarcadores/metabolismo , Comportamento Obsessivo , Transtornos Fóbicos , Vitiligo/metabolismo , Adolescente , Adulto , Idoso , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários , Vitiligo/complicações , Vitiligo/psicologia , Adulto JovemRESUMO
Suicides are preventable tragedies, if risk factors are tracked and mitigated. We had previously developed a new quantitative suicidality risk assessment instrument (Convergent Functional Information for Suicidality, CFI-S), which is in essence a simple polyphenic risk score, and deployed it in a busy urban hospital Emergency Department, in a naturalistic cohort of consecutive patients. We report a four years follow-up of that population (n = 482). Overall, the single administration of the CFI-S was significantly predictive of suicidality over the ensuing 4 years (occurrence- ROC AUC 80%, severity- Pearson correlation 0.44, imminence-Cox regression Hazard Ratio 1.33). The best predictive single phenes (phenotypic items) were feeling useless (not needed), a past history of suicidality, and social isolation. We next used machine learning approaches to enhance the predictive ability of CFI-S. We divided the population into a discovery cohort (n = 255) and testing cohort (n = 227), and developed a deep neural network algorithm that showed increased accuracy for predicting risk of future suicidality (increasing the ROC AUC from 80 to 90%), as well as a similarity network classifier for visualizing patient's risk. We propose that the widespread use of CFI-S for screening purposes, with or without machine learning enhancements, can boost suicidality prevention efforts. This study also identified as top risk factors for suicidality addressable social determinants. Supplementary Information: The online version contains supplementary material available at 10.1007/s44192-022-00016-z.
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BACKGROUND: The immunofiltration D-dimer assay could allow point-of-care testing for pulmonary embolism (PE). A study was undertaken to compare a clinician-performed qualitative D-dimer assay with the automated quantitative D-dimer test. METHODS: A prospective observational study was conducted from January to October 2005 at an urban academic emergency department (ED). 1193 patients of mean (SD) age 47 (16) years (66% female) were enrolled. The study protocol combined pretest probability estimation, D-dimer testing by both a qualitative immunochromatographic assay (Simplify) performed at the point of care by 192 different clinicians and a quantitative D-dimer test performed in a CLIA-certified laboratory. The criterion standard was image-proven PE or deep venous thrombosis within 45 days after enrollment. To test interobserver agreement for the qualitative assay, two blinded observers independently read 841 Simplify cartridges. RESULTS: Of 1193 patients enrolled, 45 were PE+ (3.8%, 95% CI 2.8% to 5.0%). Qualitative results were available for 1169 (98%) and quantitative results were available for 1136 (95%). Comparison of the qualitative and quantitative D-dimer tests gave the following results: sensitivity 91% (95% CI 78% to 98%) vs 93% (95% CI 80% to 98%); specificity 57% (95% CI 54% to 60%) vs 57% (95% CI 54% to 60%); likelihood ratio negative 0.16 (95% CI 0.06 to 0.37) vs 0.13 (95% CI 0.05 to 0.35). The weighted Cohen's kappa for interpretation of the qualitative assay was 0.69 (95% CI 0.63 to 0.76). CONCLUSIONS: In this very low-risk ED population, a qualitative D-dimer assay performed at the point of care had similar diagnostic accuracy to the quantitative D-dimer test. Interobserver agreement for the qualitative test was good.
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Serviço Hospitalar de Emergência , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Sistemas Automatizados de Assistência Junto ao Leito , Embolia Pulmonar/sangue , Algoritmos , Angiografia , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , North Carolina/epidemiologia , Prevalência , Estudos Prospectivos , Embolia Pulmonar/diagnóstico por imagem , Embolia Pulmonar/epidemiologia , Sensibilidade e EspecificidadeRESUMO
BACKGROUND: Diagnosing pulmonary embolism in suspected patients is notoriously difficult as signs and symptoms are non-specific. Different diagnostic strategies have been developed, usually combining clinical probability assessment with D-dimer testing. However, their predictive performance differs across different healthcare settings, patient subgroups, and clinical presentation, which are currently not accounted for in the available diagnostic approaches. METHODS: This is a protocol for a large diagnostic individual patient data meta-analysis (IPDMA) of currently available diagnostic studies in the field of pulmonary embolism. We searched MEDLINE (search date January 1, 1995, till August 25, 2016) to retrieve all primary diagnostic studies that had evaluated diagnostic strategies for pulmonary embolism. Two authors independently screened titles, abstracts, and subsequently full-text articles for eligibility from 3145 individual studies. A total of 40 studies were deemed eligible for inclusion into our IPDMA set, and principal investigators from these studies were invited to participate in a meeting at the 2017 conference from the International Society on Thrombosis and Haemostasis. All authors agreed on data sharing and participation into this project. The process of data collection of available datasets as well as potential identification of additional new datasets based upon personal contacts and an updated search will be finalized early 2018. The aim is to evaluate diagnostic strategies across three research domains: (i) the optimal diagnostic approach for different healthcare settings, (ii) influence of comorbidity on the predictive performance of each diagnostic strategy, and (iii) optimize and tailor the efficiency and safety of ruling out PE across a broad spectrum of patients with a new, patient-tailored clinical decision model that combines clinical items with quantitative D-dimer testing. DISCUSSION: This pre-planned individual patient data meta-analysis aims to contribute in resolving remaining diagnostic challenges of time-efficient diagnosis of pulmonary embolism by tailoring available diagnostic strategies for different healthcare settings and comorbidity. SYSTEMATIC REVIEW REGISTRATION: Prospero trial registration: ID 89366.
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OBJECTIVE: To estimate the frequency of contrast nephropathy after computed tomography angiography (CTA) to rule out pulmonary embolism (PE) in the emergency department (ED) setting. METHODS: We prospectively followed patients undergoing CTA for PE, while in the ED, for 45 days. Patients who refused follow-up or were receiving hemodialysis were excluded. Severe renal failure was defined as an increase in creatinine > or = 3.0 mg dL(-1) or a need for hemodialysis within the follow-up period. Patients were also followed for laboratory-defined contrast nephropathy, defined as an increase in creatinine of > 0.5 mg dL(-1) or > 25%, within seven days following CTA. RESULTS: A total of 1224 patients were followed, and 354 [29%, 95% confidence interval (CI): 26-32%] patients had paired (preCTA and post-CTA) creatinine measurements. None developed renal failure (0/1224; 0%, CI: 0-0.3%). 44 patients developed laboratory-defined contrast nephropathy, corresponding to an overall frequency of 4% (44/1224; CI: 3-5%) and 12% (44/354; 95% CI: 9-16%) among those with paired creatinine measurements. CONCLUSIONS: Following CTA for PE, the incidence of severe renal failure was very low, but the incidence of laboratory-defined contrast nephropathy (4% overall and 12% of those with paired measurements) was higher than expected.
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Angiografia , Meios de Contraste/efeitos adversos , Serviço Hospitalar de Emergência , Iopamidol/efeitos adversos , Embolia Pulmonar/diagnóstico por imagem , Insuficiência Renal/induzido quimicamente , Tomografia Computadorizada por Raios X , Angiografia/métodos , Doença da Artéria Coronariana/complicações , Creatinina/sangue , Feminino , Seguimentos , Humanos , Incidência , Testes de Função Renal , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Embolia Pulmonar/sangue , Insuficiência Renal/sangue , Insuficiência Renal/epidemiologia , Medição de Risco , Fatores de Risco , Índice de Gravidade de Doença , Fatores de Tempo , Tomografia Computadorizada por Raios X/métodos , Estados UnidosRESUMO
OBJECTIVES: This study was undertaken to examine in-situ heart function and metabolism during insulin treatment of verapamil-induced cardiogenic shock in awake canines. METHODS: Twenty mongrel canines were instrumented to monitor myocardial substrate uptakes (glucose, lactate, free fatty acids, oxygen [MVO2]), as well as ventricular (LV) end-systolic elastance (Emax), LV efficiency (LV minute work/MVO2), and Tau. Shock was induced by graded intraportal verapamil infusion followed by randomized assignment to one of 4 treatment groups: saline control (3.0 ml/kg/min, n = 5), epinephrine (5 micrograms/kg/min, n = 5), glucagon (10 micrograms/kg/min, n = 5) or insulin (1000 mU/min, n = 5) with dextrose to clamp arterial [glucose] +/- 10% of basal concentrations. RESULTS: Insulin treatment significantly increased Emax (34 +/- 3 vs. 17 +/- 3 mmHg/mm, saline control), and shortened Tau (9 +/- 3 ms) compared to saline control (42 +/- 5 ms), epinephrine (20 +/- 4 ms) and glucagon (35 +/- 8 ms). With insulin treatment, mechanical efficiency increased to 20,097 +/- 2070 vs. 12,424 +/- 1615 mmHg.mm/ml/O2/100 g in controls. Simultaneously, insulin increased myocardial lactate uptake (35 +/- 2 vs. 17 +/- 4 mumol/min/100 g. saline control), but did not increase glucose uptake. Epinephrine and glucagon decreased mechanical efficiency compared to saline controls, coincident with increased myocardial fatty acid consumption, but without increasing lactate uptake. One dog died early with glucagon treatment before the first death in the saline-treated group. CONCLUSIONS: Insulin improves systolic and diastolic heart function during aerobic shock and accelerates in-vivo myocardial lactate oxidation.
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Insulina/uso terapêutico , Miocárdio/metabolismo , Choque Cardiogênico/tratamento farmacológico , Função Ventricular Esquerda/efeitos dos fármacos , Animais , Bloqueadores dos Canais de Cálcio , Cães , Epinefrina/uso terapêutico , Ácidos Graxos não Esterificados/metabolismo , Feminino , Glucagon/uso terapêutico , Glucose/metabolismo , Glucose/uso terapêutico , Glicerol/metabolismo , Insulina/sangue , Ácido Láctico/metabolismo , Masculino , Distribuição Aleatória , Choque Cardiogênico/induzido quimicamente , Choque Cardiogênico/metabolismo , Choque Cardiogênico/fisiopatologia , Triglicerídeos/metabolismo , Vasoconstritores/uso terapêutico , VerapamilRESUMO
Six patients with seasonal affective disorder showed marked improvement in depressive symptoms after following three different 2-hour schedules of bright artificial light, and they relapsed when the light was withdrawn.
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Transtorno Depressivo/terapia , Fototerapia/métodos , Estações do Ano , Adulto , Alaska , Ritmo Circadiano , Transtorno Depressivo/etiologia , Transtorno Depressivo/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Escalas de Graduação PsiquiátricaRESUMO
Overuse of the d-dimer to screen for possible pulmonary embolism (PE) can have negative consequences. This study derives and tests clinical criteria to justify not ordering a d-dimer. The test threshold was estimated at 1.8% using the method of Pauker and Kassirer. The PE rule-out criteria were derived from logistic regression analysis with stepwise backward elimination of 21 variables collected on 3148 emergency department patients evaluated for PE at 10 US hospitals. Eight variables were included in a block rule: Age < 50 years, pulse < 100 bpm, SaO(2) > 94%, no unilateral leg swelling, no hemoptysis, no recent trauma or surgery, no prior PE or DVT, no hormone use. The rule was then prospectively tested in a low-risk group (1427 patients from two hospitals initially tested for PE with a d-dimer) and a very low-risk group (convenience sample of 382 patients with chief complaint of dyspnea, PE not suspected). The prevalence of PE was 8% (95% confidence interval: 7-9%) in the low-risk group and 2% (1-4%) in the very low-risk group on longitudinal follow-up. Application of the rule in the low-risk and very low-risk populations yielded sensitivities of 96% and 100% and specificities of 27% and 15%, respectively. The prevalence of PE in those who met the rule criteria was 1.4% (0.5-3.0%) and 0% (0-6.2%), respectively. The derived eight-factor block rule reduced the pretest probability below the test threshold for d-dimer in two validation populations, but the rule's utility was limited by low specificity.
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Medicina de Emergência/métodos , Produtos de Degradação da Fibrina e do Fibrinogênio/biossíntese , Embolia Pulmonar/sangue , Embolia Pulmonar/diagnóstico , Adulto , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Oxigênio/metabolismo , Prevalência , Projetos de Pesquisa , RiscoRESUMO
Recent reports suggest that physicians in non-ambulatory settings can use indirect CT venography (CTV) of the lower extremities immediately following spiral CT angiography (CTA) of the chest to identify patients with a negative CTA who have thromboembolic disease identified on CTV. We sought to determine the frequency of isolated deep venous thrombosis (DVT) discovered on CTV in emergency department (ED) patients with complaints suggestive of pulmonary embolism (PE) yet having a negative CTA. This study was conducted in a suburban and urban ED where patients with symptoms suspicious for PE were primarily evaluated with CTA and CTV. A total of 800 patients were studied, including 360 from the suburban ED and 440 from the urban ED. 88 (11%) patients were diagnosed with thromboembolic disease by CTA, or CTV, or both. Seventy-three patients had a CTA of the chest that was positive for PE, 42 (5.2%) of whom had evidence of both PE on CTA and DVT on CTV. Fifteen patients (2%, 95% CI = 1-3%) had a negative CTA and were subsequently found to have isolated DVT on CTV, all of whom received anticoagulation therapy. These data suggest that indirect CT venography of immediately following CT angiography of the chest significantly increased the frequency of diagnosed thromboembolic disease requiring anticoagulation in ED patients with suspected PE.
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Angiografia/métodos , Serviços Médicos de Emergência/métodos , Flebografia/métodos , Radiografia Torácica/métodos , Tromboembolia/diagnóstico por imagem , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Embolia Pulmonar/diagnóstico por imagem , Radiografia Torácica/normas , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodos , Tomografia Computadorizada por Raios X/normas , Estados UnidosRESUMO
We have demonstrated previously that dichloroacetate (DCA) treatment in rodents ameliorates, via activation of the pyruvate dehydrogenase complex, the cardiovascular depression observed after hemorrhagic shock. To explore the mechanism of this effect, we administered DCA in a large animal model of hemorrhagic shock. Mongrel hounds were anesthetized with 1.5% isoflurane and were measured for hemodynamics, myocardial contractility, and myocardial substrate utilization. They were hemorrhaged to a mean arterial pressure of 35 mm Hg for 90 min or until arterial lactate levels reached 7.0 mM (1137 +/- 47 mL or 49 +/- 2% total blood volume). Animals were chosen at random to receive DCA dissolved in water or an equal volume of saline at the onset of resuscitation. Two-thirds of the shed blood volume was returned immediately after giving an equivalent volume of saline. Two hours after the onset of resuscitation, mean arterial pressure was not different between DCA and control groups (79 +/- 3 vs. 82 +/- 3 mm Hg, respectively). Arterial lactate levels were significantly reduced by DCA (0.5 +/- 0.06 vs. 2.0 +/- 0.2 mM). However, DCA treatment was associated with a decreased stroke volume index (0.56 +/- 0.06 vs. 0.82 +/- 0.08 mL/kg/beat) and a decreased myocardial efficiency (19 vs. 41 L x mm Hg/mL/100 g tissue). During resuscitation by DCA, myocardial lactate consumption was reduced (21.4 +/- 3.7 vs. 70.7 +/- 16.3 micromole/min/100 g tissue) despite a three-fold increase in myocardial pyruvate dehydrogenase activity, while free fatty acid levels actually began to rise. Although increased lactate oxidation should be beneficial during resuscitation, we propose that DCA treatment led to a deprivation of myocardial lactate supply, which reduced net myocardial lactate oxidation, thus compromising myocardial function during resuscitation from hemorrhagic shock.
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Acidose Láctica/fisiopatologia , Ácido Dicloroacético/toxicidade , Metabolismo Energético/efeitos dos fármacos , Hemodinâmica/efeitos dos fármacos , Ácido Láctico/metabolismo , Miocárdio/metabolismo , Choque Hemorrágico/fisiopatologia , Acidose Láctica/etiologia , Animais , Ácido Dicloroacético/farmacologia , Ácido Dicloroacético/uso terapêutico , Cães , Avaliação Pré-Clínica de Medicamentos , Ativação Enzimática/efeitos dos fármacos , Ácidos Graxos/metabolismo , Hidratação/efeitos adversos , Soluções Isotônicas/uso terapêutico , Ácido Láctico/toxicidade , Complexo Piruvato Desidrogenase/metabolismo , Ressuscitação , Lactato de Ringer , Choque Hemorrágico/sangue , Choque Hemorrágico/complicaçõesRESUMO
Resuscitation with crystalloid and packed red blood cells has for the most part replaced the use of plasma and whole blood in the initial treatment of hemorrhagic shock. The effects of such changes on cardiovascular function following hemorrhagic shock remain largely unexplored. We examined cardiovascular function in anesthetized canines subjected to severe hemorrhagic shock. Mongrel canines of either gender were anesthetized with isoflurane and instrumented for measurement of arterial pressure, cardiac output, coronary flow, and left ventricular pressure and volume for the determination of end systolic elastance (Ees). Following a 30-min stabilization period, blood was rapidly removed to induce fixed pressure (mean arterial pressure = 35 mmHg) hemorrhagic shock for 90 min or until an arterial lactate of 7.0 mM was achieved. Animals were then resuscitated with 2/3 of the shed volume as lactated Ringer's and an equal volume of either whole blood (WB, n = 8) or packed red blood cells (PRBC, n = 10) resuspended in lactated Ringer's (LR) solution to replace expressed plasma volume. PRBC resuscitated dogs showed lower values of mean arterial pressure, cardiac output, rates of ventricular contraction and relaxation and myocardial work. Increasing the maintenance infusion rate of LR (10 mL/kg/h) following PRBC infusion normalized mean arterial pressure, but not other indices of cardiovascular function. Thus, WB, but not PRBC resuscitation restores normal myocardial function during resuscitation from severe hemorrhagic shock.
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Transfusão de Sangue , Transfusão de Eritrócitos , Hemodinâmica , Ressuscitação , Choque Hemorrágico/terapia , Animais , Débito Cardíaco , Baixo Débito Cardíaco/prevenção & controle , Soluções Cristaloides , Cães , Estudos de Avaliação como Assunto , Feminino , Soluções Isotônicas/uso terapêutico , Lactatos/sangue , Masculino , Substitutos do Plasma/uso terapêutico , Lactato de Ringer , Choque Hemorrágico/fisiopatologia , Função Ventricular EsquerdaRESUMO
This study was undertaken to examine the role of lactate on cardiac function and metabolism after severe acute hemorrhagic shock. Anesthetized, nonheparinized rats were bled to a mean arterial pressure of 25-30 mm Hg for 1 h; controls were not bled. Their hearts were removed, and cardiac work and efficiency (work/oxygen consumption) were measured in the isolated working heart mode for 60 min. The hearts were perfused with one of five substrate combinations: 1) glucose (11 mM), 2) glucose + 0.4 mM palmitate, 3) glucose + 0.4 mM palmitate + 8.0 mM lactate, 4) glucose + 1.2 mM palmitate, or 5) glucose + 1.2 mM palmitate + 8.0 mM lactate. After perfusion, hearts were freeze-clamped, and tissue contents of free coenzyme-A (CoA), acetyl CoA, and succinyl CoA were measured, as was myocardial pyruvate dehydrogenase (PDH) activity. The addition of 8.0 mM lactate significantly improved cardiac work in shocked hearts perfused with 0.4 mM palmitate and increased cardiac efficiency in the presence of either 0.4 mM or 1.2 mM palmitate. Compared to control hearts, shocked hearts exhibited a 20-30% decrease in PDH activity. Shocked hearts perfused with lactate demonstrated no increase in acetyl CoA content but did have a significant increase in tissue succinyl CoA compared to control hearts perfused with lactate or shocked hearts perfused without lactate. In the heart recovering from severe hemorrhagic shock, lactate improves cardiac efficiency in the presence of free fatty acids, possibly by a anaplerosis of the tricarboxylic acid cycle.
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Metabolismo Energético/efeitos dos fármacos , Coração/efeitos dos fármacos , Ácido Láctico/farmacologia , Miocárdio/metabolismo , Choque Hemorrágico/fisiopatologia , Acetilcoenzima A/metabolismo , Acil Coenzima A/metabolismo , Animais , Débito Cardíaco/efeitos dos fármacos , Ciclo do Ácido Cítrico/efeitos dos fármacos , Ativação Enzimática/efeitos dos fármacos , Glucose/metabolismo , Glucose/farmacologia , Testes de Função Cardíaca , Ácido Láctico/sangue , Ácido Láctico/uso terapêutico , Consumo de Oxigênio/efeitos dos fármacos , Ácido Palmítico/metabolismo , Ácido Palmítico/farmacologia , Perfusão , Complexo Piruvato Desidrogenase/efeitos dos fármacos , Ratos , Choque Hemorrágico/sangue , Choque Hemorrágico/complicaçõesRESUMO
OBJECTIVE: Test whether brief deep hemorrhagic hypotension or prolonged moderate hemorrhagic hypotension impairs intrinsic heart function. METHODS: Pentobarbital-anesthetized, non-anticoagulated rats were cannulated via the carotid artery. This study focuses on three main groups: 1) hemorrhage to a mean arterial blood pressure (MAP)=25 mm Hg for 1 h (1 h severe shock), 2) hemorrhage to MAP=40 mm Hg for 3 h (3 h moderate shock), 3) no hemorrhage (control). Hearts were either freeze-clamped in-situ for tissue analysis (n=6 per group) or were removed to study in vitro cardiac function and efficiency using a working heart perfusion (n=12 per group, glucose (11 mM)/palmitate (0.4 mM), 3% BSA buffer). Following perfusion, hearts were freeze-clamped and analyzed for free CoA, acetyl-, succinyl-, and malonyl-CoA, ATP content and for TNF-alpha content. RESULTS: Isolated working hearts obtained following 1 h of severe shock generated 20% less hydraulic work than hearts obtained from control rats or rats subjected to 3 h of moderate shock. The cardiac efficiency (work/O2 consumption) was also significantly reduced with 1 h severe shock (0.76 +/- 0.07 after 15 min perfusion) versus control (0.96 +/- 0.06) or 3 h prolonged shock (1.10 +/- 0.09). Myocardial Co-A ester, ATP and TNF-alpha concentrations were not different between control and shocked hearts, although TNF-alpha concentrations increased significantly in all hearts during ex vivo perfusion. CONCLUSIONS: Depth of hypotension is more important than duration in causing intrinsic cardiac dysfunction. This post-hemorrhagic cardiac dysfunction is not a result of substrate limitation to the heart, nor myocardial TNF-alpha accumulation, but is more likely a result of impaired transfer of energy from molecular oxygen into external cardiac work.
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Coração/fisiopatologia , Choque Hemorrágico/fisiopatologia , Trifosfato de Adenosina/metabolismo , Animais , Coenzima A/metabolismo , Ésteres/metabolismo , Coração/efeitos dos fármacos , Testes de Função Cardíaca , Hipnóticos e Sedativos/farmacologia , Hipotensão/fisiopatologia , Masculino , Pentobarbital/farmacologia , Ratos , Ratos Sprague-Dawley , Choque Hemorrágico/metabolismo , Fator de Necrose Tumoral alfa/metabolismoRESUMO
This study tested the hypothesis that removal of fatty acids as a fuel source would improve cardiac efficiency at the expense of reduced cardiac contractile function in the isolated working heart after hemorrhage-retransfusion. Non-heparinized male Sprague-Dawley rats were anesthetized with ketamine-xylazine and were hemorrhaged to a mean arterial blood pressure of 40 mmHg for 1 h. Two-thirds volume of shed blood was reinfused together with 0.9% NaCl in a volume equal to 2.3 times the shed blood volume, followed by continuous infusion of 0.9% NaCl at 10 mL/kg per h for 3 h. Hearts were removed and perfused in closed, recirculating working mode for 60 min to measure hydraulic work and cardiac efficiency. Rates of glycolysis and glucose oxidation were assessed with [5-3H/U-14C] glucose (11 mM) in the absence or presence of 0.4 mM palmitate. Compared to baseline measurements, hemorrhage-retransfusion significantly reduced arterial blood glucose (228+/-7 versus 118+/-12 mg/dL) and non-esterified fatty acid concentrations (0.36+/-0.01 versus 0.30+/-0.02 mM), while elevating blood lactate (0.8+/-0.1 versus 2.5+/-0.4 mM). Perfusion of sham hearts with glucose-only did not alter cardiac work compared to shams perfused with glucose plus palmitate. However, shocked hearts perfused with glucose-only demonstrated a significant reduction in cardiac work compared to shocked hearts perfused with glucose plus palmitate and compared to sham hearts perfused with glucose only (P < 0.05, repeated measures ANOVA). Shocked hearts perfused with glucose plus palmitate showed no reduction in cardiac work compared to shams. Shocked hearts perfused with glucose-only had increased glucose oxidation rates compared to shams perfused with glucose plus palmitate. In sham hearts perfused with glucose-only, myocardial glycogen and triacylglycerol contents were significantly reduced compared to hearts freeze-clamped in situ. These endogenous fuels were not decreased in shocked hearts. These data indicate that hemorrhagic shock renders the heart unable to mobilize endogenous fuels, and suggest that withdrawal of fatty acid oxidation will impair myocardial energy metabolism during resuscitation.
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Coração/efeitos dos fármacos , Coração/fisiologia , Ácido Palmítico/farmacologia , Choque Hemorrágico/fisiopatologia , Animais , Pressão Sanguínea/efeitos dos fármacos , Glucose/metabolismo , Glicogênio/metabolismo , Glicólise , Testes de Função Cardíaca , Concentração de Íons de Hidrogênio , Masculino , Perfusão , Ratos , Ratos Sprague-Dawley , Ressuscitação , Choque Hemorrágico/mortalidade , Choque Hemorrágico/terapia , Taxa de Sobrevida , Triglicerídeos/metabolismoRESUMO
BACKGROUND: Massive pulmonary embolism (PE) that causes severe pulmonary hypertension can produce specific ECG abnormalities. We hypothesized that an ECG scoring system would vary in proportion to the severity of pulmonary hypertension and would help to distinguish patients with massive PE from patients with smaller PE and those without PE. METHODS: A 21-point ECG scoring system was derived (relative weights in parentheses): sinus tachycardia (2), incomplete right bundle branch block (2), complete right bundle branch block (3), T-wave inversion in leads V(1) through V(4) (0 to 12), S wave in lead I (0), Q wave in lead III (1), inverted T in lead III (1), and entire S(1)Q(3)T(3) complex (2). ECGs obtained within 48 h prior to pulmonary arteriography were located for 60 patients (26 positive for PE, 34 negative for PE) and for 25 patients with fatal PE. RESULTS: Interobserver agreement (11 readers) for ECG score was good (Spearman r = 0.74). The ECG score showed significant positive relationship to systolic pulmonary arterial pressure (sPAP) in patients with PE (r = 0.387, p < 0.001), whereas no significant relationship was seen in patients without PE (r = - 0.08, p = 0.122). When patients were grouped by severity of pulmonary hypertension (low, moderate, severe), only patients with severe pulmonary hypertension from PE had a significantly higher ECG score (mean, 5.8 +/- 4.9). At a cutoff of 10 points, the ECG score was 23.5% (95% confidence interval [CI], 16 to 31%) sensitive and 97.7% (95% CI, 96 to 99%) specific for the recognition of severe pulmonary hypertension (sPAP > 50 mm Hg) secondary to PE. In 25 patients with fatal PE, the ECG score was 9.5 +/- 5.2. CONCLUSIONS: The derived ECG score increases with severity of pulmonary hypertension from PE, and a score > or = 10 is highly suggestive of severe pulmonary hypertension from PE.
Assuntos
Eletrocardiografia , Coração/fisiopatologia , Hipertensão Pulmonar/etiologia , Embolia Pulmonar/fisiopatologia , Pressão Sanguínea , Humanos , Hipertensão Pulmonar/diagnóstico , Variações Dependentes do Observador , Embolia Pulmonar/complicaçõesRESUMO
BACKGROUND: Pulmonary embolism (PE) produces ventilation/perfusion mismatch that may be manifested in various variables of the volume-based capnogram (VBC). We hypothesized that a neural network (NN) system could detect changes in VBC variables that reflect the presence of a PE. METHODS: A commercial VBC system was used to record multiple respiratory variables from consecutive expiratory breaths. Data from 12 subjects (n = 6 PE+ and n = 6 PE-) were used as input to a fully connected back-propagating NN for model development. The derived model was tested in a prospective, observational study at an urban teaching hospital. Volumetric capnograms were then collected on 53 test subjects: 30 subjects with PE confirmed by pulmonary angiography or diagnostic scintillation lung scan, and 23 subjects without PE based on pulmonary angiography. The derived NN model was applied to VBC data from the test population. RESULTS: Seventeen VBC variables were used by the derived NN model to generate a numeric probability of PE. When the derived NN model was applied to VBC data from the 53 test subjects, PE was detected with a sensitivity of 100% (95% CI = 89% to 100%) and a specificity of 48% (95% CI = 27% to 69%). The likelihood ratio positive [LR(+)] for the VBC-NN test was 1.82 and the LR (-) was 0.1. CONCLUSION: This study demonstrates the feasibility of developing a rapid, noninvasive breath test for diagnosing PE using volumetric capnography and NN analysis.
Assuntos
Capnografia/métodos , Redes Neurais de Computação , Embolia Pulmonar/diagnóstico , Angiografia , Feminino , Hospitais de Ensino , Humanos , Pulmão/diagnóstico por imagem , Pulmão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Estudos Prospectivos , Artéria Pulmonar/diagnóstico por imagem , Embolia Pulmonar/metabolismo , Embolia Pulmonar/fisiopatologia , Cintilografia , Sensibilidade e Especificidade , Volume de Ventilação Pulmonar , População Urbana , Relação Ventilação-PerfusãoRESUMO
Cardiac dysfunction has been documented in vivo after acute massive pulmonary embolism (AMPE). The present study tests whether intrinsic ventricular dysfunction occurs in rat hearts isolated after AMPE. AMPE was induced in spontaneously breathing ketamine-xylazine-anesthetized rats by thrombus infusion until mean arterial blood pressure (MAP) was approximately 40% of basal measurement. A hypotensive control group underwent controlled blood withdrawal to produce MAP approximately 40% of basal levels. Shams underwent identical surgical and anesthesia preparation but without pulmonary embolization. Hearts were perfused in isovolumetric mode, and simultaneous right ventricular (RV) and left ventricular (LV) pressures were measured. AMPE caused arterial hypotension with hypoxemia (PO(2) = 50 +/- 14 Torr), acidemia (pH = 7.26 +/- 0.11), and high lactate concentration (6.9 +/- 1.7 mM). Starling curves from both ventricles demonstrated that AMPE significantly reduced ex vivo systolic contractile function in the RV (P = 0.031) and LV (P = 0.008) compared with both the hypotensive control and sham hearts. AMPE did not alter coronary flow or compliance in either ventricle. Soluble tumor necrosis factor-alpha decreased in the RV (P = 0.043) and LV (P = 0.005) tissue. These data support the hypothesis that AMPE produces intrinsic biventricular dysfunction and suggest that arterial hypotension is not the principal mechanism of this dysfunction.
Assuntos
Coração/fisiopatologia , Embolia Pulmonar/fisiopatologia , Disfunção Ventricular/fisiopatologia , Animais , Pressão Sanguínea , Dióxido de Carbono/sangue , Hipotensão/etiologia , Hipotensão/fisiopatologia , Técnicas In Vitro , Masculino , Contração Miocárdica , Oxigênio/sangue , Pressão Parcial , Embolia Pulmonar/complicações , Ratos , Ratos Sprague-Dawley , Sístole , Fatores de Tempo , Disfunção Ventricular/etiologia , Função Ventricular Esquerda , Função Ventricular DireitaRESUMO
Fibronectin, a large-molecular-weight glycoprotein present on cell surfaces and in human plasma, promotes cell adhesion and may modulate reticuloendothelial clearance of particulate debris and bacteria. Amniotic fluid is known to contain a heavily glycosylated variety of fibronectin, and cells derived from amniotic fluid synthesize and secrete fibronectin in tissue culture. The purpose of this study was to determine the relationship between the concentration of fibronectin in amniotic fluid and gestational age. Amniotic fluid samples, obtained from 54 women whose pregnancies ranged in gestation from 15-40 weeks, demonstrated a significant decrease in fibronectin levels with increasing duration of pregnancy (r = -0.70). Diminished concentrations of amniotic fluid fibronectin in the latter stages of pregnancy may represent either decreasing synthesis by amniocytes or a dilutional effect from fetal urine.
Assuntos
Líquido Amniótico/análise , Fibronectinas/análise , Idade Gestacional , Feminino , Humanos , GravidezRESUMO
BACKGROUND: the objective was to determine clinical characteristics that can quickly distinguish sudden death from massive pulmonary embolism (MPE) from other causes of sudden death. METHODS AND RESULTS: all medical examiner reports from Charlotte, NC from 1992 to 1999 (n=4926) were hand-searched for cases of sudden death which met the inclusion criteria: non-traumatic death, age 18-65 years, transported to an emergency department (ED), and autopsy performed. Supplemental data from ED and prehospital records were retrieved to complete documentation. Data were analyzed by univariate odds ratios (OR) followed by chi-square (chi(2)) recursive partitioning for decision tree construction. Three hundred eighty four cases met inclusion criteria; MPE was the second most frequent cause of cardiac arrest in this cohort (37/384, 9.6%). The mean age of subjects with MPE (40.2+/-11.1 years) was significantly lower compared with non-PE subjects (46.5+/-9.9 years). Pulseless electrical activity was observed as the initial arrest rhythm (primary PEA) in 52/384 (13.5%) subjects. Out of 52 subjects with primary PEA, 28 (53%) died from MPE. Odds ratio data indicated significant association of MPE with female gender, arrest witnessed by medical providers, presence of primary PEA, and return of spontaneous circulation. The most accurate decision rule to recognize MPE consisted of witnessed arrest+primary PEA. This rule generated sensitivity=67.6% and specificity=94.5% and yielded a posttest probability of MPE of 57%. CONCLUSIONS: outpatients with witnessed cardiac arrest and primary PEA carry a high probability of MPE.