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1.
Surg Clin North Am ; 99(6): 1063-1082, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31676048

RESUMO

The roles of flexible endoscopy in the setting of inflammatory bowel disease include diagnosis, surveillance, and determining response to treatment and monitoring for the development of recurrence, dysplasia, or malignancy. Advanced techniques, such as chromoendoscopy and narrow band imaging, can be useful adjuncts when performing endoscopy in patients with inflammatory bowel disease. There are several roles for therapeutic endoscopy in the setting of inflammatory bowel disease, including endoscopic balloon dilation and endoscopic stricturotomy.


Assuntos
Colonoscopia/métodos , Neoplasias Colorretais/diagnóstico , Progressão da Doença , Doenças Inflamatórias Intestinais/diagnóstico , Doenças Inflamatórias Intestinais/terapia , Biópsia por Agulha , Neoplasias Colorretais/patologia , Feminino , Humanos , Imuno-Histoquímica , Doenças Inflamatórias Intestinais/patologia , Mucosa Intestinal/patologia , Masculino , Imagem de Banda Estreita/métodos , Sensibilidade e Especificidade , Índice de Gravidade de Doença
2.
Artigo em Chinês | MEDLINE | ID: mdl-31623037

RESUMO

Objective:By retrospectively analyzing the results of ultrasound guided coarse needle biopsy(CNB) of thyroid nodules based on large samples, so as to evaluate its diagnostic value as first-line diagnostic tool for thyroid nodules. Method:From October 2015 to November 2017, a total of 508 nodules were studied from 474 patients who underwent CNB in general surgery department of tianjin first central hospital. The nondiagnostic rate, inconclusive rate, unnecessary surgery rate and complication rate of thyroid nodules diagnosed by CNB were calculated. The accuracy, sensitivity, specificity, positive predictive value and negative predictive value of CNB in thyroid cancer diagnosis were analyzed. The correlation between inconclusive diagnostic results and ultrasonic findings like echogenicity, composition, margin, calcification type, blood supply and nodule size was analyzed. Result:The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of CNB diagnosis were 97.27%, 99.17%, 99.07%, 99.45% and 99.36%, respectively. However, the nondiagnostic rate, the inconclusive rate, the conclusive rate and the unnecessary surgery rate of thyroid nodules diagnosed by CNB were 2.95%, 7.09%, 92.92% and 1.86%, respectively. Conclusion:Ultrasound guided coarse needle biopsy might be safe and reliable for the diagnosis of thyroid nodules, with relatively stable diagnostic effect. It is not only of high diagnostic value but also can significantly reduce diagnostic surgery. Therefore, CNB could be the preferred examinational method for nodules with suspicious ultrasonic findings.


Assuntos
Biópsia por Agulha , Neoplasias da Glândula Tireoide/diagnóstico , Nódulo da Glândula Tireoide/diagnóstico , Biópsia com Agulha de Grande Calibre , Humanos , Estudos Retrospectivos , Sensibilidade e Especificidade , Ultrassonografia de Intervenção
4.
Klin Lab Diagn ; 64(9): 565-570, 2019.
Artigo em Russo | MEDLINE | ID: mdl-31610110

RESUMO

To analyze the method HBV covalent-closed circular DNA quantitative determination in liver puncture biopsies and evaluate its significance in identifying HBsAg-negative viral hepatitis B. In this work, samples of liver tissue biopsy material were used from 128 patients living in St. Petersburg, in various regions of the Russian Federation, as well as in the Republic of Uzbekistan. For quantitative analysis of HBV covalently closed circular DNA in a biopsy material a method was developed based on real-time PCR using TaqMan probes for the target fragment and for the endogenous reference gene, based on the detecting ccc HBV DNA method of Pollicino T. et al. When quantifying ccc DNA HBV in liver tissue of 18 moderately HBV activity with HBV DNA PCR positive results patients and 16 inactive HBsAg carriers, the ccc DNA HBV content was significantly different between groups (p<0.034) and in terms 1 copy of the ß-globin gene among moderate activity HBV patients amounted to 1.71±1.32 copies/cell, and for inactive HBsAg carriers 0.15±0.14 copies/cell. In the group of patients with severe liver fibrosis and cirrhosis, the amount of ccc DNA HBV in liver tissue in patients with HBV averaged 2.5±0.4 copies/cell, in patients with HBV + D on average 0.7±0.25 copies/cell, in patients with HCV + HBV co-infection 0.45±0.07 copies/cell, in patients with a preliminary diagnosis of chronic hepatitis C hepatitis, on average 0.12±0.04 copies/cell, in patients with cryptogenic hepatitis 0.2± 0.05 copies/cell. A significant difference was shown between the group of patients with chronic hepatitis B with marked fibrosis and cirrhosis of the liver with other patients groups, except for the group of 18 moderate activity chronic hepatitis B patients. The values of Student's t-test when compared with other groups were respectively: for patients with a HCV preliminary diagnosis t=5,92 p<0,05 f = 19, patients with cryptogenic hepatitis t=5,71 p<0,05 f = 18, with «inactive HBsAg carriage¼ t=5,55 p<0,05 f = 29, with HCV + HBV co-infection t=5,05 p<0,05 f = 15 and HBV + D co-infection t=3,82 p<0,05 f = 17. The covalently closed circular DNA HBV quantitative assessment method in liver puncture biopsies allows identifying HBsAgnegative chronic viral hepatitis B forms and also reflects the virus replication activity, which, in turn, makes it possible to assume further disease progression and evaluate the antiviral therapy effectiveness.


Assuntos
DNA Circular/análise , DNA Viral/análise , Hepatite B Crônica/diagnóstico , Biópsia por Agulha , Antígenos de Superfície da Hepatite B , Vírus da Hepatite B , Humanos , Fígado , Federação Russa
5.
Bone Joint J ; 101-B(10): 1313-1320, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31564158

RESUMO

AIMS: The aim of this study was to report the outcomes of patients who underwent definitive surgery for secondary chondrosarcomas arising from osteochondromas. PATIENTS AND METHODS: A total of 51 patients with secondary chondrosarcomas occurring from osteochondromas were reviewed. Median age was 36 years (interquartile range (IQR) 15 to 82). Median follow-up was 6.9 years (IQR 2.8 to 10.6). The pelvis was the most commonly affected site (59%). Histological grades were grade I in 35 (69%), grade II in 13 (25%), and grade III in three patients (6%). RESULTS: Preoperative biopsy histology correctly predicted the final histological grade in 27% of patients. The ten-year disease-specific survival (DSS) for all patients was 89.4%. Local recurrence occurred in 15 patients (29%), more commonly in pelvic tumours (37%) compared with limb tumours (19%). Four patients with pelvic tumours died from progression of local recurrence. No patient with limb tumours died of disease. Wide/radical margin was associated with improved local recurrence-free survival (p = 0.032) and local recurrence was associated with worse DSS (p = 0.005). CONCLUSION: We recommend that a secondary chondrosarcoma arising from osteochondroma of the pelvis is resected with wide/radical resection margins. The balance between the morbidity of surgery and risk of local recurrence needs to be considered in patients with limb secondary chondrosarcomas. Cite this article: Bone Joint J 2019;101-B:1313-1320.


Assuntos
Neoplasias Ósseas/patologia , Condrossarcoma/secundário , Recidiva Local de Neoplasia/mortalidade , Osteocondroma/patologia , Adulto , Biópsia por Agulha , Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/mortalidade , Neoplasias Ósseas/cirurgia , Condrossarcoma/diagnóstico por imagem , Condrossarcoma/mortalidade , Condrossarcoma/cirurgia , Estudos de Coortes , Intervalo Livre de Doença , Extremidades/patologia , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Imagem por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia , Estadiamento de Neoplasias , Osteocondroma/diagnóstico por imagem , Osteocondroma/mortalidade , Osteocondroma/cirurgia , Ossos Pélvicos/patologia , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Medição de Risco , Análise de Sobrevida , Resultado do Tratamento
6.
Zhonghua Zhong Liu Za Zhi ; 41(10): 792-795, 2019 Oct 23.
Artigo em Chinês | MEDLINE | ID: mdl-31648504

RESUMO

Objective: To evaluate the role of endobronchial ultrasound guided transbronchial needle aspiration (EBUS-TBNA) in lymph node staging and resectability assessment of patients with non-small cell lung cancer (NSCLC). Methods: The clinical data of 154 patients with NSCLC who underwent EBUS-TBNA from March 2015 to December 2018 were collected. All accessible mediastinal and hilar lymph nodes were systematically explored and punctured using EBUS-TBNA. EBUS-TBNA and CT were used for preoperative staging and resectability evaluation. Results: The sensitivity, specificity and accuracy of EBUS-TBNA were 94.2%, 100.0% and 96.0%, respectively, while those of CT were 89.9%, 31.8% and 72.0%, respectively. The differences were statistically significant (P<0.05). The sensitivity, specificity and accuracy of EBUS-TBNA in lymph nodes with short diameter less than 15 mm were 92.4%, 100.0% and 96.0%, respectively, while those of CT were 80.7%, 34.8% and 60.1%, respectively, with statistical differences (P<0.05). The staging of 62 patients was changed, 27 cases were up-regulated and 35 cases were down-regulated. Among them, 32 cases had been changed to resectable. The evaluating resectability of EBUS-TBNA showed excellent consistency with that of pathological results (Kappa=0.95). The sensitivity and specificity were 100.0% and 97.2%, respectively. Conclusion: EBUS-TBNA can systemically evaluate the metastatic status of NSCLC patients and improve the accuracy of preoperative lymph node staging and resectability assessment.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/patologia , Linfonodos/cirurgia , Metástase Linfática/patologia , Biópsia por Agulha , Broncoscopia , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Endossonografia , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/cirurgia , Linfonodos/patologia , Metástase Linfática/diagnóstico por imagem , Estadiamento de Neoplasias
7.
Medicine (Baltimore) ; 98(40): e17183, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31577708

RESUMO

This study aimed to compare the quality of histological endometrial samples collected through Pipelle aspiration and hysteroscopic biopsies to assess the agreement between these 2 biopsies in the histological diagnosis of malignancy and to compare the costs of both biopsies.This was a cross-sectional study. Forty-five women were biopsied, first using Pipelle and immediately after using hysteroscopy. The material collected was sent for analysis, and hysteroscopy was considered the gold standard. The results were divided into the following 3 categories: normal (atrophic, proliferative, and secretory endometrium); polyps; and malignancies. We report the agreement between Pipelle and hysteroscopy in the diagnosis of malignancy and compare their costs.The study showed that while analyzing endometrial malignancies, Pipelle sampling had 100% sensitivity and specificity. In the detection of polyps, Pipelle sampling showed 26.1% sensitivity, 88.9% specificity, 75% positive predictive value, 48.5% negative predictive value, and 53.7% accuracy. Agreement with hysteroscopy in the diagnosis of malignancy was 100%. The Pipelle device costs 27 times less than hysteroscopic biopsy for health insurance companies. This cost is 13.7 times lower in the Brazilian Unified Health System.Endometrial biopsies using the Pipelle have a high accuracy for endometrial cancer and a low accuracy for polyps. We detected 100% agreement between the reports of Pipelle and hysteroscopy with regard to malignancy. Pipelle is the most cost-effective method of endometrial biopsy.


Assuntos
Biópsia por Agulha/métodos , Neoplasias do Endométrio/patologia , Endométrio/patologia , Histeroscopia/métodos , Adulto , Idoso , Biópsia por Agulha/economia , Biópsia por Agulha/normas , Brasil , Estudos Transversais , Feminino , Humanos , Histeroscopia/economia , Histeroscopia/normas , Menopausa/fisiologia , Pessoa de Meia-Idade , Pólipos , Sensibilidade e Especificidade
8.
Int Heart J ; 60(5): 1211-1218, 2019 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-31484857

RESUMO

Extra- and/or intracorporeal renal replacement therapy can improve the cardiorenal hemodynamics in patients with advanced heart failure (HF) refractory to medical therapy and renal failure. Here, we report the case of a 51-year-old woman with inotrope-dependent end-stage HF and chronic renal failure due to anthracycline-induced cardiomyopathy, in whom the induction of hemodiafiltration and subsequent chronic peritoneal dialysis (PD) provided a dramatic improvement of her cardiac hemodynamics from restrictive to almost normal physiology assessed by echocardiography and cardiac catheterization. The patient returned to office work with New York Heart Association functional class I-II symptoms for at least 3 years with continuous ambulatory PD after hospital discharge.


Assuntos
Síndrome Cardiorrenal/terapia , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/diagnóstico por imagem , Falência Renal Crônica/complicações , Falência Renal Crônica/terapia , Diálise Peritoneal/métodos , Antraciclinas/efeitos adversos , Antraciclinas/uso terapêutico , Biópsia por Agulha , Síndrome Cardiorrenal/diagnóstico por imagem , Doença Crônica , Progressão da Doença , Ecocardiografia Doppler/métodos , Eletrocardiografia/métodos , Feminino , Insuficiência Cardíaca/terapia , Hemodiafiltração/métodos , Hemodinâmica/fisiologia , Humanos , Imuno-Histoquímica , Falência Renal Crônica/diagnóstico , Pessoa de Meia-Idade , Prognóstico , Retorno ao Trabalho , Resultado do Tratamento
9.
Int Heart J ; 60(5): 1168-1175, 2019 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-31484876

RESUMO

The aims of the present study were to investigate the effects of angiotensin receptor neprilysin inhibitors (ARNi) on the susceptibility of ventricular arrhythmias (VAs) in rats with myocardial infarction (MI) and to explore the related mechanisms.A total of 32 adult male Sprague-Dawley rats were divided into 3 groups: a control group, MI group, and MI+ARNi group. MI was generated by ligation of the left anterior descending coronary artery. ARNi was given at 68 mg/kg/day for 4 weeks after MI surgery. At 4 weeks after MI, electrical programmed stimulation (EPS) was performed in all groups for the evaluation of VAs, and echocardiography was used to evaluate cardiac function. Indicators of sympathetic neural remodeling and cardiac remodeling were detected to further explore the related mechanisms.Four weeks after MI, rats in the ARNi group exhibited low susceptibility of VAs in comparison with that in the MI group, which was coincident with the attenuation of sympathetic nerve remodeling, amelioration of cardiac fibrosis, and regulation of Cx43 expression.ARNi is effective in reducing VAs in rats with ischemic cardiomyopathy, which is associated with attenuating sympathetic nerve remodeling and myocardial fibrosis.


Assuntos
Conexina 43/metabolismo , Infarto do Miocárdio/tratamento farmacológico , Neprilisina/farmacologia , Taquicardia Ventricular/tratamento farmacológico , Remodelação Ventricular/efeitos dos fármacos , Animais , Biópsia por Agulha , China , Modelos Animais de Doenças , Ecocardiografia/métodos , Imuno-Histoquímica , Masculino , Contração Miocárdica/efeitos dos fármacos , Infarto do Miocárdio/diagnóstico por imagem , Infarto do Miocárdio/patologia , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Fatores de Risco , Taxa de Sobrevida , Sistema Nervoso Simpático/efeitos dos fármacos , Taquicardia Ventricular/diagnóstico por imagem
10.
Hypertension ; 74(5): 1113-1123, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31542966

RESUMO

Chronic kidney disease (CKD) universally associates with renal microvascular rarefaction and inflammation, but whether a link exists between these 2 processes is unclear. We designed a therapeutic construct of VEGF (vascular endothelial growth factor) fused to an ELP (elastin-like polypeptide) carrier and show that it improves renal function in experimental renovascular disease. We test the hypothesis that ELP-VEGF therapy will improve CKD, and that recovery will be driven by decreasing microvascular rarefaction partly via modulation of macrophage phenotype and inflammation. CKD was induced in 14 pigs, which were observed for 14 weeks. At 6 weeks, renal blood flow and filtration were quantified using multidetector computed tomography, and then pigs received single intrarenal ELP-VEGF or placebo (n=7 each). Renal function was quantified again 4 and 8 weeks later. Pigs were euthanized and renal microvascular density, angiogenic and inflammatory markers, fibrosis, macrophage infiltration, and phenotype were quantified. Loss of renal hemodynamics in CKD was progressively recovered by ELP-VEGF therapy, accompanied by improved renal microvascular density, fibrosis, and expression of inflammatory mediators. Although renal macrophage infiltration was similar in both CKD groups, ELP-VEGF therapy distinctly shifted their phenotype from proinflammatory M1 to VEGF-expressing M2. Our study unravels potential mechanisms and feasibility of a new strategy to offset progression of CKD using drug-delivery technologies. The results indicate that renal recovery after ELP-VEGF therapy was largely driven by modulation of renal macrophages toward VEGF-expressing M2 phenotype, restoring VEGF signaling and sustaining improvement of renal function and microvascular integrity in CKD.


Assuntos
Elastina/farmacologia , Macrófagos/efeitos dos fármacos , Circulação Renal/efeitos dos fármacos , Insuficiência Renal Crônica/tratamento farmacológico , Fator A de Crescimento do Endotélio Vascular/farmacologia , Animais , Biópsia por Agulha , Células Cultivadas , Modelos Animais de Doenças , Portadores de Fármacos , Imuno-Histoquímica , Injeções Intralesionais , Testes de Função Renal , Macrófagos/citologia , Microcirculação/efeitos dos fármacos , Tomografia Computadorizada Multidetectores/métodos , Distribuição Aleatória , Recuperação de Função Fisiológica , Insuficiência Renal Crônica/diagnóstico por imagem , Insuficiência Renal Crônica/patologia , Sensibilidade e Especificidade , Sus scrofa , Coleta de Tecidos e Órgãos , Resultado do Tratamento
11.
Medicine (Baltimore) ; 98(31): e16461, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31374007

RESUMO

Ultrasonography (USG)-guided fine needle aspiration (FNA) is widely used for diagnosis of lymph node (LN) metastasis in papillary thyroid cancer (PTC). However, FNA cytology sometimes shows inconclusive results. Recently, the measurement of thyroglobulin (Tg) in FNA washout fluid (aspirate-Tg) has been widely adopted, but there are some difficulties in the preparation of the sample and standardization of the procedure. Here, we examined serum Tg after FNA as a new predictive marker for LN metastasis of PTC. We performed USG-guided FNA cytology and examined aspirate-Tg in PTC patients showing suspicious metastatic LNs during follow-up. We measured baseline serum thyroid stimulating hormone (TSH), Tg, and Tg antibody levels before FNA, and serum Tg level within an hour after FNA. We defined aspirate-Tg level above 0.9 ng/mL as positive, and a 30% increase in serum Tg level after FNA compared to the baseline as elevation of serum Tg. Twenty-two patients were included in our study. Nine patients (40.9%) showed elevation of Tg level after FNA, and the mean value of Tg elevation was 24.8 ±â€Š48.0 ng/mL. Among these 9 patients, 8 were diagnosed with PTC and 1 patient showed cellular atypia on cytopathology. All these patients showed positive aspirate-Tg. Thirteen patients (59.1%) did not show elevation of Tg level after FNA. Among these patients, 2 had PTC, 2 had cellular atypia, and 9 yielded negative results for malignancy on cytopathology. Elevation of serum Tg level after FNA might have a diagnostic role for predicting LN metastasis of PTC.


Assuntos
Biópsia por Agulha/efeitos adversos , Tireoglobulina/análise , Câncer Papilífero da Tireoide/cirurgia , Adulto , Idoso , Biópsia por Agulha/métodos , Feminino , Humanos , Linfonodos/lesões , Linfonodos/metabolismo , Metástase Linfática/patologia , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Valor Preditivo dos Testes , Estudos Retrospectivos , Tireoglobulina/sangue , Câncer Papilífero da Tireoide/complicações , Ultrassonografia/métodos
12.
Nihon Shokakibyo Gakkai Zasshi ; 116(8): 685-689, 2019.
Artigo em Japonês | MEDLINE | ID: mdl-31406074

RESUMO

Here, we report the case of an 82-year-old woman with sclerosing mesenteritis diagnosed using needle biopsy under the guidance of computed tomography (CT) and ultrasound (US). The patient manifested appetite loss, weight loss, and epigastric pain. CT of the abdomen and pelvis revealed increased density of the mesentery adjacent to the small bowel along with enlarged lymph nodes. Hence, we suspected sclerosing mesenteritis but also considered malignancies, such as lymphoma. We then performed CT- and US-guided needle biopsy with coaxial technique. We inserted an introducer needle by verifying its location using CT and extracted multiple specimens using a finer needle that passed through the introducer without incident. The collected specimens were adequate and histological diagnosis revealed sclerosing mesenteritis. We treated the patient with corticosteroids, and her symptoms and radiographic findings improved. Thus, the coaxial technique was a useful and minimally invasive tool for the diagnosis of sclerosing mesenteritis.


Assuntos
Paniculite Peritoneal/diagnóstico por imagem , Idoso de 80 Anos ou mais , Biópsia por Agulha , Feminino , Humanos , Mesentério , Tomografia Computadorizada por Raios X , Ultrassonografia
13.
Hypertension ; 74(3): 546-554, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31303108

RESUMO

Radiofrequency renal denervation is under investigation for treatment of hypertension with variable success. We developed preclinical models to examine the dependence of ablation biomarkers on renal denervation treatment parameters and anatomic variables. One hundred twenty-nine porcine renal arteries were denervated with an irrigated radiofrequency catheter with multiple helically arrayed electrodes. Nerve effects and ablation geometries at 7 days were characterized histomorphometrically and correlated with associated renal norepinephrine levels. Norepinephrine exhibited a threshold dependence on the percentage of affected nerves across the range of treatment durations (30-60 s) and power set points (6-20 W). For 15 W/30 s treatments, norepinephrine reduction and percentage of affected nerves tracked with number of electrode treatments, confirming additive effects of helically staggered ablations. Threshold effects were only attained when ≥4 electrodes were powered. Histomorphometry and computational modeling both illustrated that radiofrequency treatments directed at large neighboring veins resulted in subaverage ablation areas and, therefore, contributed suboptimally to efficacy. Account for measured nerve distribution patterns and the annular geometry of the artery revealed that, regardless of treatment variables, total ablation area and circumferential coverage were the prime determinants of renal denervation efficacy, with increased efficacy at smaller diameters.


Assuntos
Ablação por Cateter/métodos , Hipertensão/cirurgia , Rim/inervação , Norepinefrina/sangue , Artéria Renal/cirurgia , Simpatectomia/métodos , Animais , Biópsia por Agulha , Modelos Animais de Doenças , Eletrodos , Feminino , Humanos , Hipertensão/fisiopatologia , Imuno-Histoquímica , Masculino , Distribuição Aleatória , Valores de Referência , Suínos , Resultado do Tratamento
14.
Hypertension ; 74(3): 581-589, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31327269

RESUMO

Demethylation of the forkhead box P3 (FOXP3) corresponds with stability of FOXP3 expression and immunosuppressive function of regulatory T cells (Tregs). Previous studies have demonstrated that reduction in Tregs is associated with acute coronary syndrome (ACS). The aim of this study was to establish the relationship between methylation level of FOXP3-TSDR (Treg-specific demethylated region) and clinical outcomes of ACS. We first evaluated the prognostic significance of methylation levels of FOXP3-TSDR in patients with ACS (n=171). Then, we explored the possible mechanism of methylation levels of FOXP3-TSDR on clinical outcomes of ACS in vivo. We analyzed methylation of FOXP3-TSDR, percentage of Tregs in total peripheral blood, and atherosclerotic lesions in aortic root in ApoE-/- mice (n=48; 6 groups). During the follow-up of 4.5±0.8 years, survival free of major adverse cardiovascular events was the lowest in the highest tertile of FOXP3-TSDR methylation (log-rank P=0.004). Multivariate analysis showed that FOXP3-TSDR methylation was independently and positively related to major adverse cardiovascular events (adjusted hazard ratio, 2.13; 95% CI, 1.21-3.75; P=0.009). We observed a duration-dependent increase in the methylation levels of FOXP3-TSDR in mice fed with Western diet at a period of 0, 3, 6, 9, 12, and 15 weeks. Elevated methylation levels of FOXP3-TSDR were significantly correlated of severity of atherosclerosis. We further found that FOXP3-TSDR methylation was inversely related to the percentages of Treg TGF-ß (transforming growth factor-ß) and IL (interleukin)-10 levels. Our results indicate that elevated methylation levels of FOXP3-TSDR are associated with increased risk for adverse outcomes in patients with ACS.


Assuntos
Síndrome Coronariana Aguda/genética , Síndrome Coronariana Aguda/mortalidade , Causas de Morte , Metilação de DNA/genética , Fatores de Transcrição Forkhead/genética , Síndrome Coronariana Aguda/patologia , Adulto , Idoso , Biópsia por Agulha , Estudos de Coortes , Citocinas/metabolismo , Desmetilação , Citometria de Fluxo , Regulação da Expressão Gênica , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Reação em Cadeia da Polimerase/métodos , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Medição de Risco , Índice de Gravidade de Doença , Análise de Sobrevida , Linfócitos T Reguladores/metabolismo
15.
Hypertension ; 74(3): 518-525, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31327271

RESUMO

Although maternal high-fructose intake induces cardiometabolic syndrome in adult offspring, whether it induces hypertension in successive multiple generations has not yet been studied. We hypothesized that maternal high-fructose intake induces multigenerational activation of the renin-angiotensin-aldosterone system. Pregnant mice were offered 20% fructose in drinking water, of which subsequent first to fourth generation offspring were raised without being offered fructose. Blood pressure was measured via the tail-cuff method, mRNA expression was determined using the quantitative polymerase chain reaction, and fibrosis was evaluated using trichrome staining. Maternal high-fructose intake statistically significantly increased blood pressure in the first and second, but not the third and fourth, generation offspring as compared to the control group, with maximal increases in serum renin, angiotensin II, and aldosterone in the third generation offspring. It increased the mRNA expression of renin-angiotensin-aldosterone system genes as well as the expression of renin in the kidneys in the first to third generation offspring, with the exception of the vasodilatory Mas1 gene, the mRNA expression of which was the lowest in the second generation offspring. Moreover, it maximally increased fibrosis and the mRNA expression of inflammatory cytokines in the second generation offspring and increased the mRNA expression of oxidative factors in the first to third generation offspring, but maximally decreased the mRNA expression of antioxidant-encoding Sod1 in the second generation offspring. Maternal high-fructose intake induces multigenerational activation of renin-angiotensin-aldosterone system, and the results of this study implicate that it epigenetically induces cardiometabolic syndrome in multiple generations of offspring.


Assuntos
Frutose/efeitos adversos , Hipertensão/etiologia , Prenhez , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , RNA Mensageiro/genética , Sistema Renina-Angiotensina/genética , Animais , Animais Recém-Nascidos , Biópsia por Agulha , Modelos Animais de Doenças , Características da Família , Feminino , Frutose/administração & dosagem , Predisposição Genética para Doença/genética , Hipertensão/fisiopatologia , Imuno-Histoquímica , Camundongos , Gravidez , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Distribuição Aleatória , Valores de Referência , Medição de Risco
16.
Hypertension ; 74(3): 509-517, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31352823

RESUMO

We have previously shown that podocyte injury increases the glomerular filtration of liver-derived Agt (angiotensinogen) and the generation of intrarenal Ang II (angiotensin II) and that the filtered Agt is reabsorbed by proximal tubules in a manner dependent on megalin. In the present study, we aimed to study the role of megalin in the generation of renal Ang II and sodium handling during nephrotic syndrome. We generated proximal tubule-specific megalin KO (knockout) mice and crossed these animals with NEP25 mice, in which podocyte-specific injury can be induced by injection of the immunotoxin LMB2. Without podocyte injury, renal Agt staining was markedly diminished and urinary Agt increased in KO mice. However, renal Ang II was similar between KO and control mice on average: 117 (95% CI, 101-134) versus 101 (95% CI, 68-133) fmol/g tissue. We next tested the effect of megalin KO on intrarenal Ang II generation with podocyte injury. Control NEP25 mice showed markedly increased renal Agt staining and renal Ang II levels: 450 (336-565) fmol/g tissue. Megalin KO/NEP25 mice showed markedly diminished Agt reabsorption and attenuated renal Ang II: 199 (156-242) fmol/g tissue (P<0.001). Compared with control NEP25 mice, megalin KO/NEP25 mice excreted 5-fold more sodium in the urine. Western blot analysis showed that megalin KO decreased NHE3 and the cleaved α and γ forms of Epithelial Na Channel. These data indicate that Agt reabsorbed by proximal tubules via megalin in nephrotic syndrome is converted to Ang II, which may contribute to sodium retention and edema formation by activating NHE3 and Epithelial Na Channel.


Assuntos
Angiotensina II/metabolismo , Hipernatremia/fisiopatologia , Túbulos Renais Proximais/metabolismo , Proteína-2 Relacionada a Receptor de Lipoproteína de Baixa Densidade/metabolismo , Síndrome Nefrótica/metabolismo , Síndrome Nefrótica/patologia , Animais , Biópsia por Agulha , Edema/etiologia , Edema/fisiopatologia , Hipernatremia/metabolismo , Imuno-Histoquímica , Túbulos Renais Proximais/patologia , Masculino , Camundongos , Camundongos Knockout , Podócitos/citologia , Podócitos/metabolismo , Receptor Tipo 1 de Angiotensina/metabolismo , Sistema Renina-Angiotensina , Fatores de Risco , Sensibilidade e Especificidade , Sódio/metabolismo , Urinálise
17.
J Pediatr Orthop ; 39(7): 382-386, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31305383

RESUMO

BACKGROUND: Autologous bone marrow aspirates are utilized to treat various conditions in children. The biological value of bone marrow aspirate depends on the concentration of competent osteoblastic progenitors present in the aspirate. It has been shown in adults that increasing bone marrow aspiration volume beyond 2 mL decreases the concentration of osteoblast progenitor cells because of dilution of the sample with peripheral blood. The effect of varying bone marrow aspiration volumes on the osteoblast cell content has not been determined in children. METHODS: In total, 21 children (3 male and 18 female patients, age range 8 mo to 14 y) scheduled for pelvic osteotomy were included in the study. Three separate bone marrow aspirates of 1, 5, and 10 mL were obtained from the anterior superior iliac crest. Total number of nucleated cells was counted per aspirate and the prevalence of alkaline phosphatase-positive colony-forming units was determined per million nucleated cells. RESULTS: We measured a significant, proportional increase in the total number of nucleated bone marrow precursor cells between the 1 and 5 mL samples (mean±SD, 27±13 and 152±78 million nucleated cells, respectively; P<0.0001). When the aspiration volume doubled from 5 to 10 mL the total number of nucleated cells was 178±76 million (P=0.17). A proportional increase from 2214 alkaline phosphatase-positive colony-forming units in the 1 mL sample to 14,100 alkaline phosphatase-positive colony-forming units in the 5 mL sample was observed. However, the number of colony-forming units per aspirate decreased to 11,880 in the 10 mL sample. CONCLUSIONS: These data demonstrate that in children aspiration up to 5 mL bone marrow from the iliac crest yields a proportional increase in osteoblastic progenitor cells per aspirate. Increasing the aspiration volume beyond 5 mL results in hemodilution, rather than further selection of osteoblastic material. CLINICAL RELEVANCE: These data provide clinicians with a guideline for optimizing aspiration volume of bone marrow in children. LEVEL OF EVIDENCE: Level II-development of diagnostic criteria on basis of consecutive patients.


Assuntos
Células da Medula Óssea , Ílio/citologia , Células-Tronco , Adolescente , Fosfatase Alcalina/análise , Biópsia por Agulha , Medula Óssea , Transplante de Medula Óssea , Contagem de Células , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Osteoblastos , Sucção
18.
Breast Dis ; 38(2): 47-55, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31256114

RESUMO

INTRODUCTION: Inflammatory Breast Cancer (IBC) is a distinct and rare type of breast cancer accounting for up to 6% of all breast cancer cases in Europe. The aim of this study was to investigate diagnostic methods, treatments, and outcome after IBC in patients treated at a single institution in Denmark. METHOD: All patients treated for IBC at Aarhus University Hospital between 2000 and 2014 were identified and included in the cohort. Survival was assessed using Kaplan-Meier curves and log-rank statistics. RESULTS: A total of 89 patients were identified with a median follow up of 3.6 years. The overall survival at 5 and 10 years were 41% and 18%, respectively. The disease free survival at 5 and 10 years were 47% and 27%, respectively. Thirty-four percent had distant metastasis at time of diagnosis. Patients with ER positive tumors had a significantly better overall survival than patients with ER negative tumors (p = 0.01). CONCLUSION: Despite a more aggressive systemic and loco-regional treatment today, IBC is still a very serious disease with a high mortality.


Assuntos
Neoplasias Inflamatórias Mamárias/diagnóstico por imagem , Neoplasias Inflamatórias Mamárias/tratamento farmacológico , Sistema de Registros , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Biópsia por Agulha , Dinamarca/epidemiologia , Intervalo Livre de Doença , Feminino , Humanos , Neoplasias Inflamatórias Mamárias/epidemiologia , Neoplasias Inflamatórias Mamárias/secundário , Imagem por Ressonância Magnética , Mamografia , Pessoa de Meia-Idade , Metástase Neoplásica , Receptores Estrogênicos/genética , Estudos Retrospectivos , Pele/patologia , Taxa de Sobrevida
19.
Pan Afr Med J ; 32: 158, 2019.
Artigo em Francês | MEDLINE | ID: mdl-31303928

RESUMO

Renal amyloidosis is a rare complication of adult onset Still's disease. We here report three cases of renal amyloidosis in a series of 33 cases of adult onset Still's disease. The three patients enrolled had an average age of 43 years (with a range from 33 to 58 years). The diagnosis of Still's disease was retained on the basis of febrile polyarthritis (3 cases) associated with fleeting rush (1 case), biologic inflammatory syndrome in the absence of any infectious, inflammatory or neoplastic causes. All patients were treated with corticosteroids secondarily associated with methotrexate due to destructive polyarthritis (2 cases) and to a recurrence (1 case). Renal amyloidosis had occurred 4.9 years after Still's disease (with a range from 33 months to 7 years). Amyloidosis was revealed by nephrotic syndrome (3 cases) associated with renal failure (1 case). Diagnosis was based on renal puncture biopsy (3 cases) which showed AA amyloidosis (2 cases) and untyped amyloidosis (1 case). All patients received colchicine. Outcome was favorable in a female patient while in the other two patients the disease progressed to chronic renal failure. Renal amyloidosis uncommonly results from adult onset Still's disease. Once the disease gets established it can be life-threatening.


Assuntos
Amiloidose/etiologia , Síndrome Nefrótica/etiologia , Doença de Still de Início Tardio/complicações , Corticosteroides/administração & dosagem , Adulto , Amiloidose/diagnóstico , Amiloidose/tratamento farmacológico , Biópsia por Agulha , Colchicina/administração & dosagem , Progressão da Doença , Feminino , Humanos , Falência Renal Crônica/etiologia , Metotrexato/administração & dosagem , Pessoa de Meia-Idade , Insuficiência Renal/etiologia , Doença de Still de Início Tardio/diagnóstico , Doença de Still de Início Tardio/tratamento farmacológico
20.
Hypertension ; 74(2): 295-304, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31291149

RESUMO

Subendocardial damage is among the first cardiac manifestations of hypertension and is already present in asymptomatic disease states. Accordingly, markers of subendocardial impairment may facilitate early detection of cardiac damages and risk stratification under these conditions. This study aimed to investigate the impact of subendocardial damage on myocardial microstructure and function to elucidate early pathophysiologic processes and to identify corresponding diagnostic measures. Mice (n=38) were injected with isoproterenol to induce isolated subendocardial scarring or saline as corresponding control. Cardiac function and myocardial deformation were determined by high-frequency echocardiography. The cardiac stress response was assessed in a graded exercise test and during dobutamine stress echocardiography. Myocardial microstructure was studied ex vivo by 7 T diffusion tensor magnetic resonance imaging at a spatial resolution of 100×100×100 µm 3 . Results were correlated with histology and biomarker expression. Subendocardial fibrosis was accompanied by diastolic dysfunction, impaired longitudinal deformation (global peak longitudinal strain [LS]: -12.5±0.5% versus -15.6±0.5%; P<0.001) and elevated biomarker expression (ANP [atrial natriuretic peptide], Galectin-3, and ST2). Systolic function and cardiac stress response remained preserved. Diffusion tensor magnetic resonance imaging revealed a left-shift in helix angle towards lower values in isoproterenol-treated animals, which was mainly determined by subepicardial myofibers (mean helix angle: 2.2±0.8° versus 5.9±1.0°; P<0.01). Longitudinal strain and subepicardial helix angle were highly predictive for subendocardial fibrosis (sensitivity, 82%-92% and specificity, 89%-90%). The results indicate that circumscribed subendocardial damage alone can cause several hallmarks observed in cardiovascular high-risk patients. Microstructural remodeling under these conditions involves also remote regions, and corresponding changes in longitudinal strain and helix angle might serve as diagnostic markers.


Assuntos
Endocárdio/patologia , Interpretação de Imagem Assistida por Computador , Isoproterenol/efeitos adversos , Imagem Cinética por Ressonância Magnética/métodos , Disfunção Ventricular Esquerda/diagnóstico por imagem , Animais , Biópsia por Agulha , Modelos Animais de Doenças , Ecocardiografia/métodos , Endocárdio/diagnóstico por imagem , Endocárdio/lesões , Fibrose/diagnóstico por imagem , Fibrose/patologia , Alemanha , Humanos , Imuno-Histoquímica , Injeções Subcutâneas , Isoproterenol/administração & dosagem , Modelos Lineares , Camundongos , Camundongos Endogâmicos , Curva ROC , Distribuição Aleatória , Valores de Referência , Volume Sistólico/fisiologia , Análise de Sobrevida , Disfunção Ventricular Esquerda/patologia
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