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1.
Am J Physiol Heart Circ Physiol ; 320(5): H1851-H1861, 2021 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-33710927

RESUMO

High altitude-related excessive erythrocytosis (EE) is associated with increased cardiovascular risk. The experimental aim of this study was to determine the effects of microvesicles isolated from Andean highlanders with EE on endothelial cell inflammation, oxidative stress, apoptosis, and nitric oxide (NO) production. Twenty-six male residents of Cerro de Pasco, Peru (4,340 m), were studied: 12 highlanders without EE (age: 40 ± 4 yr; BMI: 26.4 ± 1.7; Hb: 17.4 ± 0.5 g/dL, Spo2: 86.9 ± 1.0%) and 14 highlanders with EE (43 ± 4 yr; 26.2 ± 0.9; 24.4 ± 0.4 g/dL; 79.7 ± 1.6%). Microvesicles were isolated, enumerated, and collected from plasma by flow cytometry. Human umbilical vein endothelial cells were cultured and treated with microvesicles from highlanders without and with EE. Microvesicles from highlanders with EE induced significantly higher release of interleukin (IL)-6 (89.8 ± 2.7 vs. 77.1 ± 1.9 pg/mL) and IL-8 (62.0 ± 2.7 vs. 53.3 ± 2.2 pg/mL) compared with microvesicles from healthy highlanders. Although intracellular expression of total NF-κB p65 (65.3 ± 6.0 vs. 74.9 ± 7.8.9 AU) was not significantly affected in cells treated with microvesicles from highlanders without versus with EE, microvesicles from highlanders with EE resulted in an ∼25% higher (P < 0.05) expression of p-NF-κB p65 (173.6 ± 14.3 vs. 132.8 ± 12.2 AU). Cell reactive oxygen species production was significantly higher (76.4.7 ± 5.4 vs. 56.7 ± 1.7% of control) and endothelial nitric oxide synthase (p-eNOS) activation (231.3 ± 15.5 vs. 286.6 ± 23.0 AU) and NO production (8.3 ± 0.6 vs. 10.7 ± 0.7 µM/L) were significantly lower in cells treated with microvesicles from highlanders with versus without EE. Cell apoptotic susceptibility was not significantly affected by EE-related microvesicles. Circulating microvesicles from Andean highlanders with EE increased endothelial cell inflammation and oxidative stress and reduced NO production.NEW & NOTEWORTHY In this study, we determined the effects of microvesicles isolated from Andean highlanders with excessive erythrocytosis (EE) on endothelial cell inflammation, oxidative stress, apoptosis, and NO production. Microvesicles from highlanders with EE induced a dysfunctional response from endothelial cells characterized by increased cytokine release and expression of active nuclear factor-κB and reduced nitric oxide production. Andean highlanders with EE exhibit dysfunctional circulating extracellular microvesicles that induce a proinflammatory, proatherogenic endothelial phenotype.


Assuntos
Aclimatação , Altitude , Micropartículas Derivadas de Células/metabolismo , Células Endoteliais da Veia Umbilical Humana/metabolismo , Policitemia/sangue , Adulto , Apoptose , Estudos de Casos e Controles , Micropartículas Derivadas de Células/patologia , Células Cultivadas , Células Endoteliais da Veia Umbilical Humana/patologia , Humanos , Mediadores da Inflamação/metabolismo , Interleucina-6/metabolismo , Interleucina-8/metabolismo , Masculino , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , Estresse Oxidativo , Peru , Fenótipo , Policitemia/patologia , Policitemia/fisiopatologia , Espécies Reativas de Oxigênio/metabolismo , Fator de Transcrição RelA/metabolismo
2.
J Vis Exp ; (160)2020 06 17.
Artigo em Inglês | MEDLINE | ID: mdl-32628164

RESUMO

Twin anemia polycythemia sequence (TAPS) occurs in 5% of monochorionic twins and is characterized by large inter-twin hemoglobin differences. The postnatal diagnostic criteria for TAPS are based on hematologic parameters and placental characteristics. Placental examination after birth shows that color of the maternal side between placental territories of the anemic and polycythemic twins is remarkably different. The color difference in TAPS placentas is higher compared to monochorionic placentas with acute peripartum feto-fetal transfusion; thus, this is used as an additional diagnostic criterion for TAPS. Software such as ImageJ enables the computer-based measurement of color intensity in TAPS placentas. However, a detailed method for the calculation of color differences between anemic and polycythemic components of TAPS placentas has not yet been described. The protocol presented here provides a step-by-step method for analyzing color differences in the maternal side of TAPS placentas using ImageJ software.


Assuntos
Anemia/fisiopatologia , Pigmentação , Placenta/fisiologia , Policitemia/fisiopatologia , Gêmeos , Cor , Feminino , Hemoglobinas/metabolismo , Humanos , Processamento de Imagem Assistida por Computador , Gravidez
3.
Med. clín (Ed. impr.) ; 154(1): 16-19, ene. 2020. graf, tab
Artigo em Espanhol | IBECS | ID: ibc-188679

RESUMO

La eritrocitaféresis terapéutica (ET) es una estrategia más eficiente que la flebotomía en la reducción del hematocrito en las eritrocitosis primarias y secundarias. Objetivo: Analizar la tasa de respuesta y seguridad de la ET en policitemia vera (PV) y eritrocitosis secundaria (ES). Pacientes y método: Revisión retrospectiva de los pacientes con PV o ES tratados con ET, ante el fracaso a flebotomías o con comorbilidades que impedían cambios importantes de volemia. Resultados: Se realizaron 127 sesiones de ET (48 PV y 79 ES) en 20 pacientes (12 ES y 8 PV). La respuesta se obtuvo en el 87,5% de PV y en el 50% de ES. La tasa de complicaciones fue del 7,08%. Conclusiones: A pesar del tamaño de nuestra muestra y la heterogeneidad clínica de nuestra serie, podemos postular que la ET reduce de manera segura los valores de hematocrito en menor tiempo que la flebotomía, especialmente en pacientes con PV y en casos seleccionados de ES en quienes se prevé intolerancia hemodinámica a la flebotomía o en quienes falla este método


Therapeutic erythrocytapheresis (TE) is a more efficient strategy compared to phlebotomy to deplete levels of haematocrit in primary and secondary erythrocytosis. Objective: To analyse response rate and safety profile of TE in polycythemia vera (PV) and secondary erythrocytosis (SE). Patients and method: Retrospective review of all patients with PV or SE treated with TE, due to phlebotomy failure, or comorbidities that prevented changes of blood volumen. Results: 217 TE sessions (48 PV and 79 SE) corresponding to 20 patients (12 ES and 8 PV). Response were achieved in 87.5% of PV patients and in 50% of SE patients. Adverse effects related to TE performance occurred in 7.08%. Conclusion: Despite our small sample size and the heterogeneous nature of the patients included, we can postulate that TE is a secure strategy that can achieve haematocrit depletion in a shorter time than phlebotomy, specifically in PV patients and in selected cases of SE with expected haemodynamic intolerance to phlebotomies or in patients who fail to respond to phlebotomies


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Citaferese/métodos , Policitemia/terapia , Policitemia Vera/terapia , Citaferese/estatística & dados numéricos , Policitemia/fisiopatologia , Policitemia Vera/fisiopatologia , Estudos Retrospectivos , Falha de Tratamento , Flebotomia/métodos
4.
Am J Physiol Heart Circ Physiol ; 317(5): H991-H1001, 2019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-31441692

RESUMO

Excessive erythrocytosis [EE; hemoglobin concentration (Hb) ≥ 21 g/dL in adult men] is a maladaptive high-altitude pathology associated with increased cardiovascular risk and reduced reactive hyperemia flow-mediated dilation (FMD); however, whether a similar impairment occurs in response to more commonly encountered sustained increases in shear stress [sustained stimulus (SS)-FMD] over a range of overlapping stimuli is unknown. We characterized SS-FMD in response to handgrip exercise in Andeans with and without EE in Cerro de Pasco, Peru (4,330 m). Andean highlanders with EE (n = 17, Hb = 23.2 ± 1.2 g/dL) and without EE (n = 23, Hb = 18.7 ± 1.9 g/dL) performed 3 min of rhythmic handgrip exercise at 20, 35, and 50% of maximum voluntary contraction (MVC). Duplex ultrasound was used to continuously record blood velocity and diameter in the brachial artery, and blood viscosity was measured to accurately calculate shear stress. Although baseline shear stress did not differ, Andeans with EE had 22% lower shear stress than Andeans without at 50% MVC (P = 0.004). At 35 and 50% MVC, SS-FMD was 2.1 ± 2.0 and 2.8 ± 2.7% in Andeans with EE compared with 4.1 ± 3.4 and 7.5 ± 4.5% in those without (P = 0.048 and P < 0.001). The stimulus-response slope (∆shear stress vs. ∆diameter) was lower in Andeans with EE compared with Andeans without (P = 0.028). This slope was inversely related to Hb in Andeans with EE (r2 = 0.396, P = 0.007). A reduced SS-FMD in response to small muscle mass exercise in Andeans with EE indicates a generalized reduction in endothelial sensitivity to shear stress, which may contribute to increased cardiovascular risk in this population.NEW & NOTEWORTHY High-altitude excessive erythrocytosis (EE; hemoglobin concentration ≥ 21 g/dL) is a maladaptation to chronic hypoxia exposure and is associated with increased cardiovascular risk. We examined flow-mediated dilation (FMD) in response to sustained elevations in shear stress achieved using progressive handgrip exercise [sustained stimulus (SS)-FMD] in Andean highlanders with and without EE at 4,330 m. Andeans with EE demonstrated lower SS-FMD compared with those without. Heightened hemoglobin concentration was related to lower SS-FMD in Andeans with EE.


Assuntos
Aclimatação , Doença da Altitude/fisiopatologia , Altitude , Artéria Braquial/fisiopatologia , Policitemia/fisiopatologia , Vasodilatação , Adulto , Doença da Altitude/sangue , Doença da Altitude/diagnóstico por imagem , Biomarcadores/sangue , Velocidade do Fluxo Sanguíneo , Viscosidade Sanguínea , Artéria Braquial/diagnóstico por imagem , Estudos de Casos e Controles , Força da Mão , Hemoglobinas/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Contração Muscular , Peru , Policitemia/sangue , Policitemia/diagnóstico , Fluxo Sanguíneo Regional , Estresse Mecânico , Fatores de Tempo , Ultrassonografia Doppler Dupla
5.
Hypertension ; 73(6): 1327-1335, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31006327

RESUMO

Excessive erythrocytosis (EE; hemoglobin concentration [Hb] ≥21 g/dL in adult males) is associated with increased cardiovascular risk in highlander Andeans. We sought to quantify shear stress and assess endothelial function via flow-mediated dilation (FMD) in male Andeans with and without EE. We hypothesized that FMD would be impaired in Andeans with EE after accounting for shear stress and that FMD would improve after isovolemic hemodilution. Brachial artery shear stress and FMD were assessed in 23 male Andeans without EE (age: 40±15 years [mean±SD]; Hb<21 g/dL) and 19 male Andeans with EE (age: 43±14 years; Hb≥21 g/dL) in Cerro de Pasco, Peru (4330 m). Shear stress was quantified from Duplex ultrasound measures of shear rate and blood viscosity. In a subset of participants (n=8), FMD was performed before and after isovolemic hemodilution with blood volume replaced by an equal volume of human serum albumin. Blood viscosity and Hb were 48% and 23% higher (both P<0.001) and FMD was 28% lower after adjusting for the shear stress stimulus ( P=0.013) in Andeans with EE compared to those without. FMD was inversely correlated with blood viscosity ( r2=0.303; P<0.001) and Hb ( r2=0.230; P=0.001). Isovolemic hemodilution decreased blood viscosity by 30±10% and Hb by 14±5% (both P<0.001) and improved shear stress stimulus-adjusted FMD from 2.7±1.9% to 4.3±1.9% ( P=0.022). Hyperviscosity, high Hb, or both, actively contribute to acutely reversible impairments in FMD in EE, suggesting that this plays a pathogenic role in the increased cardiovascular risk.


Assuntos
Altitude , Viscosidade Sanguínea/fisiologia , Artéria Braquial/fisiopatologia , Hemoglobinas/metabolismo , Policitemia/sangue , Fluxo Sanguíneo Regional/fisiologia , Vasodilatação/fisiologia , Adulto , Artéria Braquial/diagnóstico por imagem , Endotélio Vascular/fisiopatologia , Humanos , Masculino , Policitemia/etiologia , Policitemia/fisiopatologia , Fatores de Risco , Ultrassonografia Doppler
6.
Sultan Qaboos Univ Med J ; 19(4): e345-e351, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31897318

RESUMO

Objectives: Cyanotic congenital heart disease (CCHD) predisposes patients to iron deficiency due to compensatory secondary erythrocytosis. This study aimed to determine the serum iron status and prevalence of iron deficiency among children with cyanotic congenital heart disease attending the Paediatric Cardiology outpatient clinic of Lagos State University Teaching Hospital, Lagos, Nigeria. Methods: This cross-sectional case-control study took place between May and October 2015 at the Lagos State University Teaching Hospital. A total of 75 children with cyanotic congenital heart disease and 75 apparently healthy age-, gender- and socioeconomically-matched controls were analysed to determine serum iron status and the prevalence of iron deficiency as defined by the World Health Organization criteria. Results: The mean age of the children was 47.5 ± 2.9 months (range: 6-144 months old). Iron deficiency was significantly more frequent among CCHD patients compared to control subjects (9.3% versus 0%; P = 0.006). While latent iron deficiency was more prevalent among children in the control group compared to those with CCHD, this difference was not statistically significant (13.3% versus 9.3%; P = 0.303). No cases of iron deficiency anaemia were observed in the studied sample. Conclusion: Neither the children in the control group nor those with CCHD had iron deficiency anaemia. However, iron deficiency was significantly more prevalent among children with CCHD in Lagos. Periodic serum iron status screening is therefore recommended for this population.


Assuntos
Anemia Ferropriva/complicações , Cianose/fisiopatologia , Cardiopatias Congênitas/fisiopatologia , Policitemia/fisiopatologia , Anemia Ferropriva/epidemiologia , Anemia Ferropriva/fisiopatologia , Estudos de Casos e Controles , Criança , Pré-Escolar , Estudos Transversais , Cianose/sangue , Cianose/epidemiologia , Índices de Eritrócitos , Feminino , Cardiopatias Congênitas/sangue , Cardiopatias Congênitas/complicações , Hemoglobinas/análise , Humanos , Lactente , Ferro/sangue , Masculino , Nigéria/epidemiologia , Policitemia/sangue , Policitemia/etiologia , Prevalência
7.
Fetal Diagn Ther ; 45(1): 13-20, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-29332067

RESUMO

OBJECTIVES: To evaluate the incidence of residual anastomoses (RA) after laser therapy for twin-twin transfusion syndrome (TTS) and investigate risk factors for incomplete laser surgery. MATERIAL AND METHODS: All available TTS placentas treated with laser at our center between 2002 and 2016 were injected with color dye to assess the presence of RA. We evaluated the incidence of RA over the past 15 years by dividing the cohort into three time periods, and studied the association with risk factors and neonatal outcome. RESULTS: Overall, RA were detected in 21.0% (78/371) of placentas. The incidence of RA decreased from 38.8% (26/67) in the initial period to 11.7% (16/137) in the most recent period (p < 0.001). On multivariate analysis, several risk factors were independently associated with the risk of RA, including Solomon laser technique (odds ratio [OR] 0.17, 95% CI 0.09-0.33) and estimation of surgical success (OR 19.28, 95% CI 8.17-45.49). Premature delivery and neonatal morbidity occurred more often in TTS cases with RA. CONCLUSIONS: The incidence of RA after laser therapy for TTS decreased significantly in the past 15 years and is now below 15% due to the use of the Solomon technique.


Assuntos
Anastomose Arteriovenosa/cirurgia , Doenças em Gêmeos/cirurgia , Transfusão Feto-Fetal/cirurgia , Fetoscopia/efeitos adversos , Fotocoagulação a Laser/efeitos adversos , Placenta/irrigação sanguínea , Placenta/cirurgia , Circulação Placentária , Complicações Pós-Operatórias/epidemiologia , Anastomose Arteriovenosa/fisiopatologia , Doenças em Gêmeos/diagnóstico , Doenças em Gêmeos/epidemiologia , Doenças em Gêmeos/fisiopatologia , Feminino , Transfusão Feto-Fetal/diagnóstico , Transfusão Feto-Fetal/epidemiologia , Transfusão Feto-Fetal/fisiopatologia , Humanos , Incidência , Masculino , Países Baixos/epidemiologia , Policitemia/epidemiologia , Policitemia/fisiopatologia , Complicações Pós-Operatórias/diagnóstico por imagem , Complicações Pós-Operatórias/fisiopatologia , Gravidez , Recidiva , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
8.
Ultrasound Obstet Gynecol ; 53(6): 794-797, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30207009

RESUMO

OBJECTIVES: To evaluate the relationship between the fetal intertwin difference in middle cerebral artery peak systolic velocity (MCA-PSV) and intertwin difference in hemoglobin (Hb) concentration at birth in monochorionic diamniotic (MCDA) twin pregnancies in order to assess its potential role in the prediction of twin anemia-polycythemia sequence (TAPS). METHODS: This was a retrospective cohort study of MCDA twin pregnancies delivered between January 2012 and January 2018. All pregnancies with measurements of MCA-PSV within 7 days prior to delivery and in which neonatal Hb concentration was available were included. The correlation between fetal intertwin difference in MCA-PSV, expressed in multiples of the median (MoM), and neonatal intertwin difference in Hb concentration was investigated. Receiver-operating characteristics (ROC) curve analysis was used to assess the performance of fetal intertwin difference in MCA-PSV for predicting intertwin difference in Hb > 90th centile at birth. RESULTS: A total of 154 out of 256 MC twin pregnancies fulfilled the inclusion criteria. Fetal intertwin difference in MCA-PSV MoM correlated positively with neonatal intertwin difference in Hb concentration (r = 0.79; P < 0.001). The 90th centile for intertwin difference in Hb was 7.25 g/dL. There were 15 (9.7%) cases with a Hb difference ≥ 7.25 g/dL at birth. ROC curve analysis showed a high accuracy of fetal intertwin MCA-PSV MoM difference for the prediction of neonatal intertwin Hb difference ≥ 7.25 g/dL at birth (area under the ROC curve, 0.976 (95% CI, 0.935-0.993); P = 0.012). The optimal cut-off for intertwin MCA-PSV MoM difference was 0.373, with a sensitivity of 93.3% (95% CI, 68.1-99.8%) and a specificity of 95.7% (95% CI, 90.8-98.4%). The positive predictive value was 70% (95% CI, 45.7-88.1%) and the negative predictive value was 99.3% (95% CI, 95.9-100%). CONCLUSION: Our findings show that fetal intertwin MCA-PSV MoM difference is a good predictor of neonatal intertwin Hb concentration difference > 90th centile and potentially of TAPS. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.


Assuntos
Anemia/fisiopatologia , Policitemia/fisiopatologia , Gêmeos Monozigóticos , Ultrassonografia Pré-Natal , Adolescente , Adulto , Anemia/congênito , Anemia/diagnóstico , Anemia/diagnóstico por imagem , Velocidade do Fluxo Sanguíneo , Estudos de Coortes , Feminino , Humanos , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Policitemia/congênito , Policitemia/diagnóstico , Policitemia/diagnóstico por imagem , Gravidez , Fluxo Pulsátil , Estudos Retrospectivos , Sensibilidade e Especificidade , Sístole , Adulto Jovem
9.
Fetal Diagn Ther ; 45(1): 28-35, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-29533957

RESUMO

Monochorionic twin pregnancies are at risk of unique complications due to placental sharing and vascular connections between placental territories assigned for each twin. Twin anemia-polycythemia sequence (TAPS) is an infrequent but potentially dangerous complication of abnormal placental vascular connections. TAPS occurs due to very-small-caliber (< 1 mm) abnormal placental vascular connections which lead to chronic anemia in the donor twin and polycythemia in the recipient twin. TAPS may occur spontaneously or following fetoscopic laser photocoagulation of communicating placental vessels for twin-twin transfusion syndrome. One of the hallmarks of TAPS is the absence of polyhydramnios and oligohydramnios. The postnatal diagnosis is based on significant hemoglobin discrepancy between the twins. Middle cerebral artery peak systolic velocity Doppler ultrasound allows for the prenatal diagnosis of TAPS. The optimal prenatal treatment and intervention timing has not been established. Here, we report 3 spontaneous TAPS cases diagnosed and managed in the prenatal period with a combination of in utero blood transfusion for the anemic twin (donor) and in utero partial exchange transfusion for the polycythemic twin (recipient). These cases contribute to the limited outcome data of this underutilized method for the management of TAPS.


Assuntos
Anastomose Arteriovenosa/fisiopatologia , Transfusão de Sangue Intrauterina , Transfusão Total , Transfusão Feto-Fetal/terapia , Placenta/irrigação sanguínea , Policitemia/terapia , Gêmeos Monozigóticos , Adulto , Anastomose Arteriovenosa/diagnóstico por imagem , Feminino , Transfusão Feto-Fetal/diagnóstico por imagem , Transfusão Feto-Fetal/fisiopatologia , Humanos , Recém-Nascido , Nascimento Vivo , Circulação Placentária , Policitemia/diagnóstico por imagem , Policitemia/fisiopatologia , Gravidez , Resultado do Tratamento , Ultrassonografia Doppler , Ultrassonografia Pré-Natal/métodos
10.
Mil Med ; 184(5-6): e486-e488, 2019 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-30423154

RESUMO

High-affinity hemoglobinopathies are a rare clinical entity that commonly presents as an isolated erythrocytosis in asymptomatic individuals. We report such a case involving an 18-year-old active duty military trainee who presented to the hematology clinic after an isolated erythrocytosis was incidentally discovered during a flight physical. The patient was asymptomatic but did report a family history of erythrocytosis in his mother and maternal grandmother which intermittently required venesection. Initial history and physical exam were unremarkable. P50 RBC Oxygen Dissociation showed a left-shifted oxygen dissociation curve, although hemoglobin electrophoresis did not reveal an abnormal hemoglobin variant. A ß-globin variant was identified via mass spectrometry and sequencing that was consistent with the rare high-oxygen affinity hemoglobin variant designated hemoglobin San Diego. This patient was medically cleared to return to training without limitations and counseled regarding the potential significance of being a carrier of this rare hemoglobin variant. This case represents the first observation of hemoglobin San Diego in the U.S. military population.


Assuntos
Policitemia/congênito , Adolescente , Humanos , Achados Incidentais , Masculino , Militares , Exame Físico , Policitemia/diagnóstico , Policitemia/fisiopatologia
11.
Ultrasound Obstet Gynecol ; 53(6): 788-793, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30125414

RESUMO

OBJECTIVES: To investigate the diagnostic accuracy of delta middle cerebral artery peak systolic velocity (MCA-PSV) > 0.5 multiples of the median (MoM) and compare its predictive value with that of the current MCA-PSV cut-off values of > 1.5 MoM in the donor and < 1.0 MoM in the recipient, for the diagnosis of twin anemia-polycythemia sequence (TAPS) in monochorionic twin pregnancy. METHODS: This was a retrospective consecutive cohort study comprising all uncomplicated monochorionic twin pregnancies and twin pregnancies with a postnatal diagnosis of TAPS managed between 2003 and 2017 in the Dutch national referral center for fetal therapy. Cases with incomplete MCA-PSV Doppler measurements 1 week prior to delivery or with incomplete hemoglobin measurements within 1 day after birth were excluded. The postnatal diagnosis of TAPS was based on an intertwin hemoglobin difference > 8 g/dL and at least one of the following: reticulocyte count ratio > 1.7 or presence of minuscule anastomoses on the placental surface. We compared the predictive accuracy of the current diagnostic method using MCA-PSV cut-off values of > 1.5 MoM in the donor and < 1.0 MoM in the recipient with that of a new method based on intertwin difference in MCA-PSV > 0.5 MoM for prediction of TAPS. RESULTS: In total, 45 uncomplicated and 35 TAPS monochorionic twin pregnancies were analyzed. The sensitivity and specificity of the cut-off MCA-PSV values (donor > 1.5 MoM, recipient < 1.0 MoM) to predict TAPS was 46% (95% CI, 30-62%) and 100% (95% CI, 92-100%), respectively; positive predictive value was 100% (95% CI, 81-100%) and negative predictive value 70% (95% CI, 58-80%). Delta MCA-PSV showed a sensitivity of 83% (95% CI, 67-92%) and a specificity of 100% (95% CI, 92-100%); the positive and negative predictive values were 100% (95% CI, 88-100%) and 88% (95% CI, 77-94%), respectively. Of the 35 cases with TAPS diagnosed postnatally, 13 twin pairs showed a delta MCA-PSV > 0.5 MoM but did not fulfill the cut-off MCA-PSV criteria. Of these 13 TAPS twins, nine donors and four recipients had normal MCA-PSV values. There was a high correlation between delta MCA-PSV and intertwin difference in hemoglobin level (R = 0.725, P < 0.01). CONCLUSION: Delta MCA-PSV > 0.5 MoM has a greater diagnostic accuracy for predicting TAPS compared to the current MCA-PSV cut-off criteria. We therefore propose a new antenatal classification system for TAPS. In monochorionic twin pregnancies with delta MCA-PSV > 0.5 MoM on Doppler ultrasound, but normal MCA-PSV values in the donor or recipient, obstetricians should be aware of the therapeutic implications and neonatal morbidities associated with TAPS. © 2018 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.


Assuntos
Anemia/diagnóstico , Artéria Cerebral Média/fisiopatologia , Policitemia/diagnóstico , Gêmeos Monozigóticos , Ultrassonografia Pré-Natal , Anemia/congênito , Anemia/diagnóstico por imagem , Anemia/fisiopatologia , Velocidade do Fluxo Sanguíneo , Estudos de Coortes , Feminino , Humanos , Recém-Nascido , Masculino , Artéria Cerebral Média/diagnóstico por imagem , Policitemia/congênito , Policitemia/diagnóstico por imagem , Policitemia/fisiopatologia , Gravidez , Fluxo Pulsátil , Estudos Retrospectivos , Sensibilidade e Especificidade , Sístole
12.
J Med Case Rep ; 12(1): 381, 2018 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-30587223

RESUMO

BACKGROUND: Hypernatremia is a very common electrolyte disorder and is frequently encountered in out-patient as well as in-hospital settings. We describe an adult who was found to have unexplained relative polycythemia and episodic hypernatremia. A diagnosis of idiopathic hypodipsic-hypernatremia syndrome was made and the patient was managed with a water-drinking schedule. CASE PRESENTATION: A 24-year-old South African-Indian man was found to have polycythemia in association with episodes of hypernatremia. Investigations indicated that he had relative polycythemia. He experienced no thirst at a time when his serum sodium concentration was found to be 151 mmol/L. Further testing indicated that his renal response to arginine vasopressin was intact and magnetic resonance imaging of his brain revealed no hypothalamic lesions. A diagnosis of idiopathic hypodipsic-hypernatremia syndrome was made and he was managed with a water-drinking schedule that corrected his hypernatremia. CONCLUSION: Hypodipsia should always be considered when a patient without physical or cognitive disability presents with unexplained episodic hypernatremia or with relative polycythemia.


Assuntos
Ingestão de Líquidos , Hipernatremia/diagnóstico , Condutos Olfatórios/fisiopatologia , Policitemia/diagnóstico , Prolapso Retal/patologia , Água , Colonoscopia , Hidratação , Humanos , Hipernatremia/fisiopatologia , Hipernatremia/terapia , Masculino , Policitemia/fisiopatologia , Policitemia/terapia , Síndrome , Sede , Resultado do Tratamento , Água/administração & dosagem , Adulto Jovem
13.
Hum Genomics ; 12(1): 37, 2018 07 27.
Artigo em Inglês | MEDLINE | ID: mdl-30053909

RESUMO

BACKGROUND: High-altitude polycythemia (HAPC) is a chronic high-altitude disease that can lead to an increase in the production of red blood cells in the people who live in the plateau, a hypoxia environment, for a long time. The most frequent symptoms of HAPC include headache, dizziness, breathlessness, sleep disorders, and dilation of veins. Although chronic hypoxia is the main cause of HAPC, the fundamental pathophysiologic process and related molecular mechanisms responsible for its development remain largely unclear yet. AIM/METHODS: This study aimed to explore the related hereditary factors of HAPC in the Chinese Han and Tibetan populations. A total of 140 patients (70 Han and 70 Tibetan) with HAPC and 60 healthy control subjects (30 Han and 30 Tibetan) were recruited for a case-control association study. To explore the genetic basis of HAPC, we investigated the association between HAPC and both phosphatidylinositol-4,5-bisphosphonate 3-kinase, catalytic subunit delta gene (PIK3CD) and collagen type IV α3 chain gene (COL4A3) in Chinese Han and Tibetan populations. RESULTS/CONCLUSION: Using the unconditional logistic regression analysis and the false discovery rate (FDR) calculation, we found that eight SNPs in PIK3CD and one SNP in COL4A3 were associated with HAPC in the Tibetan population. However, in the Han population, we did not find any significant association. Our study suggested that polymorphisms in the PIK3CD and COL4A3 were correlated with susceptibility to HAPC in the Tibetan population.


Assuntos
Doença da Altitude/genética , Autoantígenos/genética , Classe I de Fosfatidilinositol 3-Quinases/genética , Colágeno Tipo IV/genética , Policitemia/genética , Adulto , Altitude , Doença da Altitude/complicações , Doença da Altitude/fisiopatologia , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Policitemia/complicações , Policitemia/fisiopatologia , Polimorfismo de Nucleotídeo Único/genética , Tibet
14.
High Alt Med Biol ; 19(3): 221-231, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29782186

RESUMO

Corante, Noemí, Cecilia Anza-Ramírez, Rómulo Figueroa-Mujíca, José Luis Macarlupú, Gustavo Vizcardo-Galindo, Grzegorz Bilo, Gianfranco Parati, Jorge L. Gamboa, Fabiola León-Velarde, and Francisco C. Villafuerte. Excessive erythrocytosis and cardiovascular risk in Andean highlanders. High Alt Med Biol. 19:221-231, 2018.-Cardiovascular diseases are the main cause of death worldwide. Life under high-altitude (HA) hypoxic conditions is believed to provide highlanders with a natural protection against cardiovascular and metabolic diseases compared with sea-level inhabitants. However, some HA dwellers become intolerant to chronic hypoxia and develop a progressive incapacitating syndrome known as chronic mountain sickness (CMS), characterized by excessive erythrocytosis (EE; Hb ≥21 g/dL in men, Hb ≥19 g/dL in women). Evidence from HA studies suggests that, in addition to CMS typical signs and symptoms, these highlanders may also suffer from metabolic and cardiovascular disorders. Thus, we hypothesize that this syndrome is also associated to the loss of the cardiometabolic protection observed in healthy highlanders (HH), and therefore to a higher cardiovascular risk (CVR). The aim of the present work was to evaluate the association between EE and CVR calculated using the Framingham General CVR Score and between EE and CVR factors in male highlanders. This cross-sectional study included 342 males from Cerro de Pasco, Peru at 4340 m (HH = 209, CMS = 133). Associations were assessed by multiple logistic regressions adjusted for potential confounders (BMI, pulse oxygen saturation and age). The adjusted models show that the odds of high CVR (>20%) in highlanders with EE was 3.63 times the odds in HH (CI 95%:1.22-10.78; p = 0.020), and that EE is associated to hypertension, elevated fasting serum glucose, insulin resistance, and elevated fasting serum triglycerides. Our results suggest that individuals who suffer from EE are at increased risk of developing cardiovascular events compared with their healthy counterparts.


Assuntos
Altitude , Pressão Sanguínea , Doenças Cardiovasculares/epidemiologia , Policitemia/epidemiologia , Adolescente , Adulto , Idoso , Glicemia/metabolismo , Doenças Cardiovasculares/fisiopatologia , Estudos Transversais , Humanos , Hipertensão/epidemiologia , Hipertensão/fisiopatologia , Resistência à Insulina , Masculino , Pessoa de Meia-Idade , Peru/epidemiologia , Policitemia/fisiopatologia , Fatores de Risco , Triglicerídeos/sangue , Adulto Jovem
16.
Ultrasound Obstet Gynecol ; 52(3): 373-377, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28557152

RESUMO

OBJECTIVE: To quantify sonographic placental echogenicity in twin anemia-polycythemia sequence (TAPS) and to correlate it with middle cerebral artery peak systolic velocity (MCA-PSV) measurements. METHODS: We performed a retrospective search for consecutive TAPS cases between 16 and 36 weeks of gestation (MCA-PSV > 1.5 multiples of the median (MoM) in the anemic donor and < 1.0 MoM in the polycythemic recipient) in our database of monochorionic twin gestations from January 2007 until December 2016. In cases for which ultrasound images showing the donor's and the recipient's part of the placenta were available, echogenicity for both twins was quantified by image processing. MCA-PSV Doppler values of both fetuses were correlated to their respective placental echogenicity. Placental thickness of both twins was also measured. RESULTS: Of 756 cases with MCA-PSV measurements identified from the database, 36 (4.8%) had TAPS; of these, 23 had TAPS combined with twin-twin transfusion syndrome and 13 showed isolated TAPS. Placental echogenicity could be quantified in 28 pregnancies. Mean ± SD placental echogenicity of donor twins was significantly higher than that of recipients (138.7 ± 22.8 vs 77.9 ± 37.0; P < 0.0001). Furthermore, a significant positive correlation was found between placental echogenicity and MCA-PSV MoM (R = 0.67, P < 0.0001). Mean placental thickness of donor twins (n = 20) was significantly higher than that of recipients (49.3 mm ± 13.4 vs 25.4 mm ± 10.1; P < 0.0001). CONCLUSIONS: Echogenicity of the placental share in recipient and donor twins with TAPS correlates with MCA-PSV values. Quantification of sonographic placental echogenicity may help to determine the severity of TAPS in monochorionic twins. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.


Assuntos
Transfusão Feto-Fetal/diagnóstico por imagem , Artéria Cerebral Média/diagnóstico por imagem , Policitemia/diagnóstico por imagem , Feminino , Transfusão Feto-Fetal/complicações , Transfusão Feto-Fetal/fisiopatologia , Humanos , Artéria Cerebral Média/fisiopatologia , Placenta/diagnóstico por imagem , Placenta/patologia , Policitemia/etiologia , Policitemia/fisiopatologia , Gravidez , Estudos Retrospectivos , Índice de Gravidade de Doença , Ultrassonografia Pré-Natal
17.
Comput Methods Programs Biomed ; 154: 109-122, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29249336

RESUMO

BACKGROUND AND OBJECTIVE: In this study, the interaction of pulsatile blood flow with the viscoelastic walls of the axisymmetric artery is numerically investigated for different severities of stenosis. The geometry of artery is modeled by an axisymmetric cylindrical tube with a symmetric stenosis in a two-dimensional case. The effects of stenosis severity on the axial velocity profile, pressure distribution, streamlines, wall shear stress, and wall radial displacement for the viscoelastic artery are also compared to the elastics artery. Furthermore, the effects of atherosclerosis and polycythemia diseases on the hemodynamics and the mechanical behavior of arterial walls are investigated. METHODS: The pulsatile flow of non-Newtonian blood is simulated inside the viscoelastic artery using the COMSOL Multiphysics software (version 5) and by employing the fluid-structure interaction (FSI) method and the arbitrary Lagrangian-Eulerian (ALE) method. Moreover, finite element method (FEM) is used to solve the governing equations on the unstructured grids. For modeling the non-Newtonian blood fluid and the viscoelastic arterial wall, the modified Casson model, and generalized Maxwell model are used, respectively. RESULTS: According to the results, with stenosis severity increasing from 25% to 75% at the time of maximum volumetric flow rate, the maximum value of axial velocity and its gradient increase 7.9 and 19.6 times, and the maximum wall shear stress of viscoelastic wall increases 24.2 times in the constriction zone. With the progression of the atherosclerosis disease (fivefold growth of arterial elastic modulus), the wall radial displacement of viscoelastic arterial walls decreases nearly 40%. CONCLUSIONS: In this study, axial velocity profile, pressure distribution, streamlines, wall radial displacement, and wall shear stress were examined for different percentages of stenosis (25%, 50%, and 75%). The atherosclerosis disease was investigated by the fivefold growth of viscoelastic arterial elastic modulus and polycythemia disease was examined by the 21-fold increase in the yield stress of the blood fluid. Furthermore, the comparison of results between the elastic and viscoelastic arterial walls shows that the wall radial displacement for viscoelastic artery is lower than that for the elastic artery as much as 21.7% for the severe stenosis of 75%.


Assuntos
Arteriosclerose/fisiopatologia , Vasos Sanguíneos/fisiopatologia , Constrição Patológica/fisiopatologia , Vasos Coronários/fisiopatologia , Módulo de Elasticidade , Modelos Cardiovasculares , Policitemia/fisiopatologia , Fluxo Pulsátil , Viscosidade , Arteriosclerose/patologia , Vasos Sanguíneos/patologia , Simulação por Computador , Constrição Patológica/patologia , Vasos Coronários/patologia , Análise de Elementos Finitos , Humanos , Policitemia/patologia , Software , Estresse Mecânico
18.
Intern Med ; 56(13): 1705-1710, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28674362

RESUMO

Less than 5% of patients with polycythemia vera (PV) show JAK2 exon 12 mutations. Although PV patients with JAK2 exon 12 mutations are known to develop post-PV myelofibrosis (MF) as well as PV with JAK2V617F, the role of JAK inhibitors in post-PV MF patients with JAK2 exon 12 mutations remains unknown. We describe how treatment with a JAK1/2 inhibitor, ruxolitinib, led to the rapid amelioration of marrow fibrosis, erythrocytosis and thrombocytopenia in a 77-year-old man with post-PV MF who carried a JAK2 exon 12 mutation (JAK2H538QK539L). This case suggests that ruxolitinib is a treatment option for post-PV MF in patients with thrombocytopenia or JAK2 exon 12 mutations.


Assuntos
Janus Quinase 2/genética , Policitemia Vera/tratamento farmacológico , Policitemia Vera/genética , Pirazóis/uso terapêutico , Idoso de 80 Anos ou mais , Éxons , Humanos , Janus Quinase 2/antagonistas & inibidores , Masculino , Mutação , Policitemia/genética , Policitemia/fisiopatologia , Mielofibrose Primária/genética , Mielofibrose Primária/fisiopatologia , Pirazóis/farmacologia , Trombocitopenia/genética , Trombocitopenia/fisiopatologia
19.
Physiol Rep ; 5(7)2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28400504

RESUMO

Oxygen-dependent regulation of the erythropoietin gene is mediated by the hypoxia-inducible factor (HIF) family of transcription factors. When oxygen is plentiful, HIF undergoes hydroxylation by a family of oxygen-dependent prolyl hydroxylase domain (PHD) proteins, promoting its association with the von Hippel-Lindau (VHL) ubiquitin E3 ligase and subsequent proteosomal degradation. When oxygen is scarce, the PHD enzymes are inactivated, leading to HIF accumulation and upregulation not only of erythropoietin expression, but also the expression of hundreds of other genes, including those coordinating cardiovascular and ventilatory adaptation to hypoxia. Nevertheless, despite the identification of over 50 mutations in the PHD-HIF-VHL pathway in patients with previously unexplained congenital erythrocytosis, there are very few reports of associated cardiopulmonary abnormalities. We now report exaggerated pulmonary vascular and ventilatory responses to acute hypoxia in a 35-year-old man with erythrocytosis secondary to heterozygous mutation in PHD2, the most abundant of the PHD isoforms. We compare this phenotype with that reported in patients with the archetypal disorder of cellular oxygen sensing, Chuvash polycythemia, and discuss the possible clinical implications of our findings, particularly in the light of the emerging role for small molecule PHD inhibitors in clinical practice.


Assuntos
Pressão Sanguínea/fisiologia , Volume Expiratório Forçado/fisiologia , Frequência Cardíaca/fisiologia , Prolina Dioxigenases do Fator Induzível por Hipóxia/genética , Fenótipo , Policitemia/genética , Adulto , Débito Cardíaco/fisiologia , Ecocardiografia Doppler , Humanos , Hipóxia/fisiopatologia , Masculino , Mutação , Policitemia/fisiopatologia , Espirometria
20.
Hepatology ; 65(1): 134-151, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27774607

RESUMO

Erythrocytosis is a common paraneoplastic syndrome associated with hepatocellular carcinoma. Although increased erythropoietin (EPO) is found in these patients, the clinical significance and molecular mechanisms underlying this observation are unclear. We demonstrate an inverse relationship between EPO production and overall prognosis in our cohort of 664 patients as well as in data from The Cancer Genome Atlas. In the subset of hepatocellular carcinoma patients with erythrocytosis, we identified somatic mutations of mitochondrial DNA, resulting in impairment of respiratory metabolism, which sequentially led to depletion of α-ketoglutarate, stabilization of hypoxia inducible factor-α, and expression of target genes such as EPO. Cell lines and patient-derived xenograft models were used to demonstrate that EPO promoted cancer stem cell self-renewal and expansion in an autocrine/paracrine manner through enhanced Janus kinase/signal transducer and activator of transcription signaling both in vitro and in vivo. Furthermore, to explore the therapeutic targeting of EPO-induced tumor changes, we found that blocking EPO signaling with soluble EPO receptor extracellular domain Fc fusion protein could inhibit tumor growth both in vitro and in vivo. CONCLUSION: These findings suggest clinical and therapeutic implications for erythrocytosis in hepatocellular carcinoma. There is an underlying link between mitochondrial function and hypoxia inducible factor alpha signaling, revealing a mechanism of erythrocytosis in a subset of hepatocellular carcinoma patients who may benefit from treatment involving EPO signaling interference. (Hepatology 2017;65:134-151).


Assuntos
Carcinoma Hepatocelular/complicações , Carcinoma Hepatocelular/genética , DNA Mitocondrial/genética , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/genética , Mutação , Síndromes Paraneoplásicas/etiologia , Policitemia/etiologia , Carcinoma Hepatocelular/fisiopatologia , Hipóxia Celular , Feminino , Humanos , Neoplasias Hepáticas/fisiopatologia , Masculino , Doenças Mitocondriais/genética , Policitemia/fisiopatologia , Prognóstico
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