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AIMS: Familial hypercholesterolemia (FH) is a genetic disorder characterized by elevated low-density lipoprotein cholesterol (LDL-C) levels, which increases the risk of premature coronary artery disease. Early detection and treatment are vital, especially in children. To improve FH diagnosis in children, the Japan Atherosclerosis Society (JAS) released new guidelines in July 2022. This study assessed and compared the sensitivity and specificity of the clinical diagnostic criteria from the JAS pediatric FH guidelines of 2017 and 2022. METHODS: From September 2020 to March 2023, 69 children with elevated plasma LDL-C levels (≥ 140 mg/dL) were included in a pediatric FH screening project in Kagawa. The children were evaluated using genetic testing alongside the clinical diagnostic criteria from the JAS pediatric FH guidelines of 2017 and 2022. RESULTS: Using the JAS pediatric FH 2017 criteria, eight children were diagnosed as FH-positive and 61 children as FH-negative. The JAS pediatric FH 2022 criteria identified 15 children with definite FH, 31 with probable FH, and 23 with possible FH. Genetic testing detected FH pathogenic variants in 24 children. The sensitivity and specificity for the JAS pediatric FH 2017 criteria were 0.292 and 0.978, respectively. For the JAS pediatric FH 2022 criteria, the sensitivity was 0.542 for definite FH with a specificity of 0.956, and 0.917 for probable FH with a specificity of 0.467. CONCLUSION: The clinical diagnostic criteria of the JAS pediatric FH 2022 guidelines demonstrated improved diagnostic efficiency compared with those of 2017, as evidenced by the increased sensitivity while preserving specificity.
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Hiperlipoproteinemia Tipo II , Humanos , Hiperlipoproteinemia Tipo II/diagnóstico , Hiperlipoproteinemia Tipo II/genética , Criança , Feminino , Masculino , Japão/epidemiologia , Testes Genéticos/métodos , Testes Genéticos/normas , Adolescente , LDL-Colesterol/sangue , Guias de Prática Clínica como Assunto , Pré-Escolar , Aterosclerose/diagnóstico , Aterosclerose/sangue , Sensibilidade e Especificidade , Sociedades MédicasRESUMO
Fabry disease is an X-linked hereditary disorder caused by deficient α-galactosidase A (GLA) activity. Patients with Fabry disease are often treated with enzyme replacement therapy (ERT). However, ERT often induces the formation of neutralizing antidrug antibodies (ADAs), which may impair the therapeutic efficacy. Here, we report the case of a 32-year-old man with Fabry disease and resultant neutralizing ADAs who was treated by switching from agalsidase-α to agalsidase-ß. We monitored biomarkers, such as plasma globotriaosylsphingosine (lyso-Gb3), urinary globotriaosylceramide (Gb3), urinary mulberry bodies, renal and cardiac parameters, and disease severity during the treatment period. Although plasma lyso-Gb3 and urinary Gb3 levels quickly decreased within two months after the initiation of ERT with agalsidase-α, they gradually increased thereafter. The urinary mulberry bodies continued to appear. Both the ADA titer and serum mediated GLA inhibition rates started to increase after two months. Moreover, 3.5 years after ERT, the vacuolated podocyte area in the renal biopsy decreased slightly from 23.1 to 18.9%. However, plasma lyso-Gb3 levels increased, and urinary Gb3, mulberry body levels, and ADA titers remained high. Therefore, we switched to agalsidase-ß which reduced, but did not normalize, plasma lyso-Gb3 levels and stabilized renal and cardiac parameters. Disease severity was attenuated. However, urinary Gb3 and mulberry body levels did not decrease noticeably in the presence of high ADA titers. The kidneys take up a small amount of the administered recombinant enzyme, and the clearance of Gb3 that has accumulated in the kidney may be limited despite the switching from agalsidase-α to agalsidase-ß.
Assuntos
Anticorpos Neutralizantes , Biomarcadores , Terapia de Reposição de Enzimas , Doença de Fabry , Isoenzimas , Esfingolipídeos , Triexosilceramidas , alfa-Galactosidase , Humanos , Doença de Fabry/tratamento farmacológico , Doença de Fabry/diagnóstico , Masculino , Adulto , alfa-Galactosidase/uso terapêutico , alfa-Galactosidase/administração & dosagem , alfa-Galactosidase/imunologia , Biomarcadores/sangue , Terapia de Reposição de Enzimas/métodos , Isoenzimas/uso terapêutico , Isoenzimas/administração & dosagem , Anticorpos Neutralizantes/sangue , Triexosilceramidas/urina , Esfingolipídeos/sangue , Glicolipídeos , Rim/patologia , Índice de Gravidade de Doença , Resultado do Tratamento , Proteínas RecombinantesRESUMO
AIM: Familial hypercholesterolemia (FH) is an underdiagnosed autosomal dominant genetic disorder characterized by high levels of plasma low-density lipoprotein cholesterol (LDL-C) from birth. This study aimed to assess the genetic identification of FH in children with high LDL-C levels who are identified in a universal pediatric FH screening in Kagawa, Japan. METHOD: In 2018 and 2019, 15,665 children aged 9 or 10 years underwent the universal lipid screening as part of the annual health checkups for the prevention of lifestyle-related diseases in the Kagawa prefecture. After excluding secondary hyper-LDL cholesterolemia at the local medical institutions, 67 children with LDL-C levels of ≥ 140 mg/dL underwent genetic testing to detect FH causative mutations at four designated hospitals. RESULTS: The LDL-C levels of 140 and 180 mg/dL in 15,665 children corresponded to the 96.3 and 99.7 percentile values, respectively. Among 67 children who underwent genetic testing, 41 had FH causative mutations (36 in the LDL-receptor, 4 in proprotein convertase subtilisin/kexin type 9, and 1 in apolipoprotein B). The area under the curve of receiver operating characteristic curve predicting the presence of FH causative mutation by LDL-C level was 0.705, and FH causative mutations were found in all children with LDL-C levels of ≥ 250 mg/dL. CONCLUSION: FH causative mutations were confirmed in almost 60% of the referred children, who were identified through the combination of the lipid universal screening as a part of the health checkup system and the exclusion of secondary hyper-LDL cholesterolemia at the local medical institutions.
Assuntos
Hiperlipoproteinemia Tipo II , Apolipoproteínas B/genética , Criança , LDL-Colesterol , Humanos , Hiperlipoproteinemia Tipo II/diagnóstico , Hiperlipoproteinemia Tipo II/epidemiologia , Hiperlipoproteinemia Tipo II/genética , Japão/epidemiologia , Mutação , Pró-Proteína Convertase 9/genéticaRESUMO
Loop-mediated isothermal amplification (LAMP) rapidly amplifies DNA under isothermal conditions. The aim of this study was to detect Candida albicans and compare the positivity rate in the LAMP reaction with that of conventional methods for oral exfoliative cytology (EC) samples. Sixty-eight EC samples from 53 patients were subjected to LAMP analysis. These patients had been clinically diagnosed with leukoplakia, squamous cell carcinoma, oral lichen planus (OLP), stomatitis, oral candidiasis, and other malignancies. LAMP reactions were defined as positive when the sample turbidity exceeded 0.1 (arbitrary unit). Periodic acid-Schiff (PAS) staining and microbial culture were also performed to detect Candida species in EC samples. The LAMP reaction detected C. albicans in 42.6% of EC samples. Candida species were detected in 32.4% of the same samples by culturing and in 29.4% of samples by PAS staining. C. albicans DNA was detected most frequently in samples from OLP patients. We conclude that, in comparison to conventional methods for detection of C. albicans, the LAMP method is highly sensitive and time-saving, and does not require expensive equipment or diagnostic technology. It may therefore be useful for on-site screening of C. albicans at dental clinics.
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Candida albicans/isolamento & purificação , Doenças da Boca/microbiologia , Boca/microbiologia , Candida albicans/genética , Feminino , Genes Fúngicos , Humanos , Masculino , Pessoa de Meia-Idade , Técnicas de Amplificação de Ácido NucleicoRESUMO
Secretory leukocyte protease inhibitor (SLPI) is a serine protease inhibitor whose expression level is positively correlated with tumor aggressiveness and metastatic potential. However, the mechanism underlying SLPI-induced enhancement of malignant phenotype is not completely understood. The malignancy of cancer cells is highly dependent on cell migration activity. Our previous study revealed that gingival carcinoma Ca9-22 cells, but not colorectal adenocarcinoma HT-29 cells, expressed SLPI. Therefore, we investigated the migration activity of these two cell types to understand the nature of SLPI-mediated tumor aggressiveness and metastatic potential. In vitro wound healing assay indicated that HT-29 cells and SLPI-deleted Ca9-22 cells showed lower migration activity than wild-type Ca9-22 cells, suggesting that SLPI-induced cell migration plays an important role in tumor aggressiveness and metastatic potential. In addition, our gene expression profiling study based on microarray data for the three cell types identified a number of candidates, including LCP1 and GLI, that could be key molecules in the mechanism of SLPI-induced cell migration.
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Adenocarcinoma/genética , Movimento Celular/fisiologia , Neoplasias Colorretais/genética , Perfilação da Expressão Gênica , Neoplasias Gengivais/genética , Inibidor Secretado de Peptidases Leucocitárias/fisiologia , Adenocarcinoma/patologia , Neoplasias Colorretais/patologia , Neoplasias Gengivais/patologia , Células HT29 , Humanos , Metástase Neoplásica , Inibidor Secretado de Peptidases Leucocitárias/genéticaRESUMO
BACKGROUND: Natriuretic peptides have been proposed as biomarkers of cardiovascular disease, especially heart failure. Brain natriuretic peptide (BNP) has also been shown to be upregulated at the transcriptional and translational levels by pro-inflammatory cytokines in cardiac myocytes. Although we often measure plasma BNP levels in cancer patients, it remains unknown whether cancer-related inflammation affects the plasma BNP levels. We investigated the relationship between the BNP and human cancers. METHODS: We retrospectively studied 2,923 patients in whom the plasma BNP levels and serum C-reactive protein (CRP) were measured and echocardiography was performed. Patients with clinically evident heart failure (NYHA II or higher), heart disease requiring medical treatment or surgery, renal dysfunction, and inflammatory disease were excluded. There were 234 patients in the final analysis. Blood sampling was performed before surgery and chemotherapy. In addition, we evaluated the relationship between the inflammation and plasma BNP levels in mouse models of colon cancer. RESULTS: Of the 234 patients, 80 were diagnosed with cancer. Both the plasma BNP and serum CRP levels were significantly higher in cancer patients than those without. There were no significant differences in the echocardiographic parameters. There was a significant positive correlation between the plasma BNP and serum CRP levels in cancer patients (r = 0.360, P<0.01) but not in those without. In cancer patients, only the CRP correlated with the BNP independent of the age, creatinine level, hypertension, and body mass index. In addition, in nude mice with subcutaneous colon cancer, the plasma BNP level was elevated compared with that in non-cancer mice, and there was a significant relationship between the plasma BNP and serum levels of the inflammatory markers. CONCLUSIONS: In cancer patients, as well as colon cancer model mice, the plasma BNP levels were elevated, possibly due to cancer-related inflammation. The effect of cancer on the BNP levels should be considered when using BNP as an indicator of heart failure in cancer patients.
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Peptídeo Natriurético Encefálico/sangue , Neoplasias/sangue , Animais , Índice de Massa Corporal , Proteína C-Reativa/metabolismo , Creatinina/sangue , Modelos Animais de Doenças , Feminino , Humanos , Camundongos , Neoplasias/tratamento farmacológico , Neoplasias/cirurgia , Análise de Regressão , Estudos RetrospectivosRESUMO
There have been a number of recent reports on the occurrence of autoimmune conditions after autologous hematopoietic stem cell transplantation. We describe a rare case of Evans syndrome (ES) that developed in a 16-year-old patient >1 year after autologous peripheral blood stem cell transplantation for recurrent Hodgkin lymphoma. ES is a rare and frequently refractory condition. No therapy for the condition has been established, and it can often be fatal. In the present case, i.v. cyclosporine A injection was significantly effective against the ES, which has not recurred.
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Anemia Hemolítica Autoimune/etiologia , Doença de Hodgkin/cirurgia , Recidiva Local de Neoplasia/cirurgia , Transplante de Células-Tronco de Sangue Periférico/efeitos adversos , Trombocitopenia/etiologia , Adolescente , Anemia Hemolítica Autoimune/diagnóstico , Biópsia por Agulha , Células da Medula Óssea/patologia , Feminino , Humanos , Imageamento por Ressonância Magnética , Trombocitopenia/diagnósticoRESUMO
Secretory leukocyte protease inhibitor (SLPI) is a serine protease inhibitor that diminishes tissue destruction during inflammation. A recent report revealed high levels of SLPI expression in the oral carcinoma cell. In addition, overexpression of SLPI up-regulates metastasis in lung carcinoma cells. On the other hand, matrix metalloproteinases (MMPs) are proteinases that participate in extracellular matrix degradation. SLPI and MMPs are involved as accelerators of the tumor invasion process; however, their exact roles are not fully understood. Understanding the mechanism of tumor invasion requires models that take the effect of microenvironmental factors into account. In one such in vitro model, different carcinoma cells have been shown to invade myoma tissue in highly distinct patterns. We have used this myoma model, as it provides a more natural stroma-like environment, to investigate the role of SLPI in tumor invasion. Our results indicate that the model provides a relevant matrix for tumor invasion studies, and that SLPI is important for the invasion of oral carcinoma Ca9-22 cells in conjunction with MMPs. Furthermore, using bioinformatics analysis, we have identified candidates as key molecules involved in SLPI-mediated tumor invasion.
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Movimento Celular , Perfilação da Expressão Gênica , Leiomioma/enzimologia , Neoplasias Bucais/enzimologia , Inibidor Secretado de Peptidases Leucocitárias/metabolismo , Neoplasias Uterinas/enzimologia , Linhagem Celular Tumoral , Técnicas de Cocultura , Biologia Computacional , Bases de Dados Genéticas , Feminino , Perfilação da Expressão Gênica/métodos , Regulação Enzimológica da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Leiomioma/patologia , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Neoplasias Bucais/genética , Neoplasias Bucais/patologia , Invasividade Neoplásica , Análise de Sequência com Séries de Oligonucleotídeos , Inibidor Secretado de Peptidases Leucocitárias/genética , Transdução de Sinais , Fatores de Tempo , Técnicas de Cultura de Tecidos , Transfecção , Microambiente Tumoral , Neoplasias Uterinas/patologiaRESUMO
An 8-year-old Japanese girl was admitted with an ovarian yolk sac tumor. Regarding birth history, the patient had been delivered by cesarean section at 25 weeks of gestation with a birthweight of 711g. She had required neonatal intensive care including oxygenation, various medications, and tests. After surgery and chemotherapy, there was no recurrence for 2 years, at the time of writing. Yolk sac tumor, which is a malignant germ cell tumor, is rare in children. Although the cause and risk factors are unclear, it has been reported that malignant germ cell tumors in childhood have been associated with pathophysiology at birth. Given that premature infants are more likely to survive due to advances in perinatal care, it is expected that such cases will increase in the near future. We suggest that children born prematurely require careful follow up.
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OBJECTIVES: The promotion of adipose tissue inflammation by lifestyle-related diseases such as obesity and diabetes accelerates atherogenesis; however, the underlying mechanisms remain incompletely understood. Nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP3) inflammasome contributes to chronic inflammation in adipose tissue. Here, we investigated the link between NLRP3 expression in subcutaneous adipose tissue (SAT) and the severity of coronary atherosclerosis. METHODS AND RESULTS: SAT was obtained from 72 patients who underwent heart device implantation and coronary angiography. Expression of NLRP3 inflammasome-related molecules (NLRP3, IL-1ß and IL-18) in SAT were evaluated by quantitative RT-PCR. Laboratory markers related to lifestyle-related diseases were measured. Patients with obesity, dyslipidemia (P < 0.05, respectively), diabetes or hyperuricemia (P < 0.01, respectively) had significantly higher expression of NLRP3. Multivariate analysis demonstrated that body mass index and serum level of uric acid were predictors of NLRP3 expression in SAT. The expression of NLRP3 in SAT correlated negatively with serum adiponectin level (r = -0.23, P < 0.05). Patients with coronary artery disease showed higher NLRP3 expression than patients without significant stenosis (P < 0.01). Furthermore, the expression of NLRP3 in SAT correlated positively with the severity of coronary atherosclerosis as determined by Gensini score (r = 0.47, P < 0.0001) or SYNTAX score (r = 0.55, P < 0.0001). Multiple regression analysis revealed that the expression of NLRP3 in SAT remains as an independent predictors for the severity of coronary atherosclerosis. CONCLUSIONS: The expression of NLRP3 in SAT, which is affected by lifestyle-related diseases, is associated with the severity of coronary atherosclerosis. Our results suggest that NLRP3 inflammasome in SAT may have a role in atherogenesis.
Assuntos
Adiponectina/sangue , Tecido Adiposo/metabolismo , Proteínas de Transporte/metabolismo , Doença da Artéria Coronariana/metabolismo , Regulação da Expressão Gênica , Tecido Adiposo/patologia , Idoso , Biomarcadores , Terapia de Ressincronização Cardíaca , Constrição Patológica/fisiopatologia , Vasos Coronários/patologia , Desfibriladores Implantáveis , Feminino , Humanos , Inflamassomos , Estilo de Vida , Macrófagos/citologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Proteína 3 que Contém Domínio de Pirina da Família NLR , Marca-Passo Artificial , Fatores de Risco , Índice de Gravidade de Doença , Gordura Subcutânea/patologia , Ácido Úrico/sangueAssuntos
Aneurisma Coronário/diagnóstico por imagem , Doenças Palpebrais/etiologia , Imunoglobulina G/sangue , Paraproteinemias/diagnóstico por imagem , Plasmócitos/patologia , Tomografia por Emissão de Pósitrons , Tomografia Computadorizada por Raios X , Idoso de 80 Anos ou mais , Anticorpos Anti-Idiotípicos/sangue , Artérias/diagnóstico por imagem , Cardiomegalia/etiologia , Aneurisma Coronário/etiologia , Doenças Palpebrais/imunologia , Doenças Palpebrais/patologia , Fluordesoxiglucose F18 , Humanos , Masculino , Paraproteinemias/sangue , Paraproteinemias/patologia , Compostos RadiofarmacêuticosRESUMO
Several studies have shown that various chemokines are more highly expressed in atherosclerotic plaques than in normal vessel walls. In the present study, we investigated the relationship between coronary atherosclerosis and noteworthy chemokines, including interferon-inducible protein of 10 kD (IP-10); monocyte chemoattractant protein 1 (MCP-1); regulated on activation, normal T-cell expressed and secreted (RANTES); and high-sensitivity C-reactive protein (hsCRP), an established marker of atherosclerotic disease. We studied 28 patients who underwent coronary angiography because of suspected coronary artery disease (CAD). CAD was defined as stenosis of more than 50% of the vessel diameter on coronary angiograms. Blood samples were obtained both from the aorta and the coronary sinus (CS) just before coronary angiography. Relative to CAD (-) patients, those who were CAD (+) tended to have higher plasma concentrations of IP-10 in the aorta, as well as significantly higher transcoronary concentration gradients of circulating IP-10. There were no significant differences between the two groups in aortic plasma concentrations or transcoronary concentration gradients of MCP-1, RANTES, and hsCRP. Furthermore, both the aortic plasma concentrations and transcoronary concentration gradients of IP-10 correlated with the Gensini score (r = 0.58 and r = 0.63, respectively, P < 0.01), while the plasma MCP-1, RANTES, and serum hsCRP concentrations did not. This study suggests that IP-10 is a good surrogate marker of coronary atherosclerosis.
Assuntos
Quimiocina CXCL10/sangue , Doença da Artéria Coronariana/sangue , Idoso , Biomarcadores/sangue , Proteína C-Reativa/metabolismo , Quimiocina CCL2/sangue , Quimiocina CCL5/metabolismo , Angiografia Coronária , Doença da Artéria Coronariana/diagnóstico por imagem , Fosfatos de Dinucleosídeos , Feminino , Humanos , Masculino , Linfócitos T/fisiologia , TionucleotídeosRESUMO
AIM: The consumption of n-3 polyunsaturated fatty acids (PUFA), including docosahexaenoic acid DHA), reduces the incidence of cardiovascular events, and reduced serum levels of n-3 PUFA may be associated with an increased risk of cardiovascular events. However, controversy remains regarding which components of PUFA are associated with the endothelial function in patients with coronary artery disease (CAD). We therefore examined the associations between the n-3 and n-6 PUFA levels and CAD. METHODS: We retrospectively reviewed 160 consecutive Japanese patients with CAD whose endothelial function was measured according to the percent change in flow-mediated dilation (FMD) and the serum levels of n-3 PUFA, including eicosapentaenoic acid (EPA) and DHA, and n-6 PUFA, including arachidonic acid (AA) and dihomo-gamma-linolenic acid (DHLA). RESULTS: A single regression analysis showed no relationships between the FMD and the serum levels of PUFA, including EPA, DHA, AA and DHLA. In contrast, a multiple regression analysis showed that the DHA level was a positive (ï¼ 0.01) and age was a negative (P ï¼ 0.001) contributor to an increased FMD; however, sex, body mass index, systolic and diastolic blood pressure, current/past smoking and the levels of HbA1c, triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, EPA, AA and DHLA did not significantly affect the outcome. CONCLUSIONS: The serum level of DHA is associated with the endothelial function evaluated according to the FMD in patients with CAD, thus suggesting that a low serum level of DHA may be a predictive biomarker for endothelial dysfunction.
Assuntos
Doença da Artéria Coronariana/fisiopatologia , Ácidos Docosa-Hexaenoicos/farmacologia , Endotélio Vascular/efeitos dos fármacos , Idoso , Endotélio Vascular/fisiopatologia , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
BACKGROUND: Recent studies have shown that intake of n-3 polyunsaturated fatty acids (PUFAs) is associated with reduced risk of cognitive impairment and coronary artery disease (CAD); however, it is currently unknown whether reduced serum n-3 PUFA is associated with cognitive impairment in patients with CAD. METHODS: We retrospectively evaluated cognitive function with the mini-mental state examination (MMSE), serum levels of PUFAs (including eicosapentaenoic acid [EPA], docosahexaenoic acid [DHA], dihomogammalinolenic acid [DGLA], and arachidonic acid [AA]), cardiovascular risk factors (hypertension, dyslipidemia, diabetes mellitus, cerebrovascular disease, and history of current/previous smoking), and parameters of cardiac function (left ventricular ejection fraction and brain natriuretic peptide levels) in 146 Japanese CAD patients. The associations between the MMSE scores and the other parameters were evaluated. RESULTS: Pearson correlation analysis showed that EPA (R = 0.25, P <0.01), EPA/AA ratio (R = 0.22, P = 0.01), and left ventricular ejection fraction (R = 0.15, P = 0.04) were positively associated with MMSE score, and that age (R = -0.20, P <0.01) and brain natriuretic peptide levels (R = -0.28, P <0.01) were inversely associated with MMSE score. Multiple regression analysis showed that age (P <0.05) was negatively associated with MMSE score, while EPA (P <0.01) and EPA/AA ratio (P <0.05) were positively associated with MMSE score; however, sex; body mass index; left ventricular ejection fraction; levels of DHA, AA, and DGLA; DHA/AA ratio; brain natriuretic peptide; and presence of hypertension, dyslipidemia, diabetes mellitus, cerebrovascular disease, and history of current/previous smoking were statistically excluded. CONCLUSIONS: Serum EPA concentration is associated with cognitive function in patients with CAD, suggesting that a low serum EPA level is a risk factor for cognitive impairment independent of cardiac function, including left ventricular ejection fraction. This correlation potentially lends further support to a role of dietary n-3 PUFAs in preventing the cognitive decline in CAD patients.
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Cognição/fisiologia , Doença das Coronárias/sangue , Ácido Eicosapentaenoico/sangue , Idoso , Ácido Araquidônico/sangue , Transtornos Cognitivos/sangue , Transtornos Cognitivos/prevenção & controle , Ácidos Graxos Ômega-3/sangue , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Volume SistólicoRESUMO
Dubin-Johnson syndrome (DJS) is an autosomal recessive inherited disorder characterized by conjugated hyperbilirubinemia. Neonatal-onset DJS is rare. It is caused by dysfunction of adenosine triphosphate-binding cassette, sub-family C, member 2 (ABCC2). We found a novel compound heterozygous mutation of DJS-related gene: W709R (T2145C): a missense mutation in exon 17, and R768W (C2302T), a missense mutation in exon 18. Serum diglucuronosyl bilirubin/monoglucuronosyl bilirubin ratio was high. ABCC2 may excrete diglucuronosyl bilirubin preferentially over monoglucuronosyl bilirubin.
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Icterícia Idiopática Crônica/genética , Proteínas Associadas à Resistência a Múltiplos Medicamentos/genética , Mutação , Feminino , Heterozigoto , Humanos , Recém-Nascido , Proteína 2 Associada à Farmacorresistência MúltiplaRESUMO
PURPOSE: The purpose of this study was to evaluate the physiological uptake pattern of (18)F-FDG in the left ventricular myocardium of patients under preparation for tumor FDG-PET. PATIENTS AND METHODS: We enrolled 188 patients without cardiac disease. The accumulation patterns were classified as either 'none', 'diffuse', 'focal' or 'focal on diffuse'. When a focal uptake was only observed on the basal wall, then the patterns were classified as having either a 'ring', 'over half' or 'spot' uptake. RESULTS: The frequencies of the myocardial FDG uptake patterns were as follows: none, n=52 (27.7%); diffuse, n=63 (33.5%); focal on diffuse, n=40 (21.3%) and focal, n=33 (17.6%). The age, blood glucose level, weight and dose of FDG did not differ significantly for each pattern. The focal and focal on diffuse patterns were seen in 73 patients, and 65 patients had a focal uptake only on the basal wall; ring uptake in 29 patients, over half in 20 and spot uptake in 16 patients. CONCLUSIONS: The physiological myocardial uptake showed several patterns. Focal uptake was often seen in patients with cardiac disease, but it did not always indicate an abnormal finding when the accumulation was only on the basal wall.
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Fluordesoxiglucose F18/farmacocinética , Ventrículos do Coração/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Fenômenos Fisiológicos Cardiovasculares , Feminino , Ventrículos do Coração/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons , Estudos RetrospectivosRESUMO
Congenital long QT syndrome is a genetic disorder encompassing a family of mutations that can lead to aberrant ventricular electrical activity. We report on two brothers with long QT syndrome caused by compound mutations in the KCNH2 gene inherited from parents who had no prolonged QT interval on electrocardiography. The proband had syncope, and his elder brother suffered from ventricular fibrillation. Genetic testing revealed that both brothers had multiple mutations in the KCNH2 gene, including a missense mutation of C1474T (exon 6) as well as a frameshift/nonsense mutation, resulting from the insertion of 25 nucleotides, which caused an altered amino acid sequence beginning at codon 302 and a premature termination codon (i.e., TAG) at codon 339 (exon 4). Family genetic screening found that their father had the same frameshift mutation, and their mother and sister had the same missense mutation, in the KCNH2 gene. However, these other family members were asymptomatic, with normal QT intervals on electrocardiography. These results suggest that compound mutations in the KCNH2 gene inherited independently from the parents made the phenotypes of their sons more severe.
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Canais de Potássio Éter-A-Go-Go/genética , Mutação da Fase de Leitura , Síndrome do QT Longo/genética , Mutação de Sentido Incorreto , Análise Mutacional de DNA , Canal de Potássio ERG1 , Eletrocardiografia , Predisposição Genética para Doença , Hereditariedade , Humanos , Síndrome do QT Longo/diagnóstico , Síndrome do QT Longo/fisiopatologia , Masculino , Linhagem , Fenótipo , Índice de Gravidade de Doença , Adulto JovemRESUMO
Increasing evidence indicates that inflammation contributes to the pathogenesis of atrial fibrillation (AF). Pentraxin 3 (PTX3) is produced abundantly in local inflammatory lesions while C-reactive protein (CRP) is produced mainly in the liver. In this study, we investigated whether a local level of PTX3 might be a sensitive marker for the local inflammation of AF. Blood from the periphery and left atrial appendage (LAA) was sampled from 23 patients with AF undergoing pulmonary vein isolation, and from 10 control subjects with Wolff-Parkinson-White syndrome. We measured peripheral and LAA plasma concentrations of CRP, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and PTX3. Plasma PTX3 concentrations in both locations were higher in patients with AF than in control subjects. PTX3 concentrations were significantly higher in the LAA than the periphery in patients with AF (3.7 ± 1.4 vs 3.3 ± 1.2 ng/ml, P < 0.01), but not in control subjects (2.4 ± 0.5 vs 2.4 ± 0.5 ng/ml, not significant). Patients and controls showed no significant differences in CRP, IL-6, or TNF-α concentrations between the periphery and LAA. Interestingly, there was a significant positive correlation between LAA plasma concentrations of PTX3 and left atrial volume (r = 0.55, P < 0.01). These data demonstrate that local PTX3 production in the left atrium might reflect the local inflammation of AF.
Assuntos
Apêndice Atrial/imunologia , Fibrilação Atrial/imunologia , Proteína C-Reativa/análise , Mediadores da Inflamação/análise , Componente Amiloide P Sérico/análise , Idoso , Fibrilação Atrial/sangue , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/cirurgia , Biomarcadores/análise , Estudos de Casos e Controles , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Imuno-Histoquímica , Mediadores da Inflamação/sangue , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Regulação para CimaRESUMO
BACKGROUND: Telmisartan has unique pleiotropic effects in addition to renin-angiotensin system (RAS)-inhibition effects. The aim of this study was to evaluate the effects of telmisartan on the coronary plaque component and local inflammatory cytokines. METHODS AND RESULTS: A total of 50 patients with hypertension were randomized to 2 groups: the telmisartan group (additional treatment with telmisartan 80mg/day, n=25) or the control group (additional treatment with other anti-hypertensive drugs except RAS blockers, n=25) for 6 months. Tissue characteristics of target coronary plaque were analyzed using integrated backscatter intravascular ultrasound (IB-IVUS) before and after treatment. Plasma levels of inflammatory cytokines sampled in the coronary sinus (CS) and peripheral vein were also measured. Significant increases in fibrous volume (51.2±10.4 to 58.3±7.7%, P=0.03) and reductions in lipid volume (38.4±12.4 to 32.8±9.7%, P=0.03) were observed on IB in the telmisartan group, while there were no significant changes in the plaque component in the control group. CS levels of inflammatory cytokines (matrix metalloproteinase [MMP]3, tumor necrosis factor-α, high-sensitivity C-reactive protein and MMP9) were lower after than before treatment in the only telmisartan group (7.7±6.1 to 5.5±4.9ng/ml, 3.1±1.9 to 2.3±2.0pg/ml, 5.6±6.0 to 2.2±2.4mg/L, 36.1±39.3 to 19.9±27.5ng/ml, P=0.02, P=0.03, P=0.04, P=0.07, respectively). CONCLUSIONS: Decreased local inflammatory response and plaque stabilization on IB imaging were observed after 6 months of telmisartan treatment. These findings might be associated with local anti-inflammatory and anti-arteriosclerotic effects of telmisartan.