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1.
BMC Surg ; 18(1): 7, 2018 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-29386002

RESUMO

BACKGROUND: Liver resection for intrahepatic cholangiocarcinoma (ICC) with invasion of the inferior vena cava (IVC) and hepatic veins (HV) is a challenging procedure. CASE PRESENTATION: We report a case of a 63-year-old woman with a 6-cm, centrally located liver mass. Her biochemistry results were normal except for a Ca19-9 level of 1199 U/ml. The liver biopsy was consistent with ICC and 60% macrosteatosis. Abdominal CT scans revealed a large central mass invading the left HV, middle HV and right HV, infringing on their junction with the vena cava. An operation was planned using a 3-dimensional (3D) computer simulation model using dedicated software. We also describe a novel veno-portal-venous extracorporeal membrane oxygenation (VPV-ECMO) support with in-situ hypothermic perfusion (IHP) during this procedure. We aimed to perform an extended left hepatectomy and reconstruct 3 right HV orifices with an interposition jump graft to the IVC with total vascular exclusion (TVE) and IHP A supplemental video describing the preoperative planning, the operative procedure with the postoperative follow-up in detail is presented. After the patient was discharged, she developed a hepatic venous outflow obstruction 3 months postoperatively, which was effectively managed with hepatic venous stenting by interventional radiology. She is currently symptom free and without tumour recurrence at the 1-year follow-up. CONCLUSIONS: This report demonstrates that extended left hepatectomy for IHC with IHP and VPV-ECMO is safe and feasible under the supervision of a highly experienced team.


Assuntos
Neoplasias dos Ductos Biliares/cirurgia , Colangiocarcinoma/cirurgia , Oxigenação por Membrana Extracorpórea , Hepatectomia/métodos , Veias Hepáticas/cirurgia , Hipotermia Induzida , Neoplasias dos Ductos Biliares/diagnóstico por imagem , Colangiocarcinoma/diagnóstico por imagem , Colangiocarcinoma/patologia , Simulação por Computador , Feminino , Veias Hepáticas/diagnóstico por imagem , Veias Hepáticas/patologia , Humanos , Imagem Tridimensional , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Vasculares , Veia Cava Inferior/patologia , Veia Cava Inferior/cirurgia
2.
J Vasc Surg Venous Lymphat Disord ; 6(1): 57-65, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29248109

RESUMO

BACKGROUND: The role of cutaneous microvascular dysfunction is well known in the development of chronic venous disease. However, the effects of venous obstruction on microcirculation have not been well investigated. The aim of this study was to assess cutaneous microvascular function in patients with iliocaval venous obstruction (ICVO) before and after venous stent placement. METHODS: Endothelium-dependent and endothelium-independent vasodilator responses to iontophoretic administration of incremental doses of acetylcholine (ACh) and sodium nitroprusside (SNP) were evaluated using a laser Doppler scanner in the perimalleolar region in the supine and sitting positions in patients with ICVO (n = 11) and in healthy control subjects (n = 15). Cutaneous microvascular function, the Venous Clinical Severity Score (VCSS), and the Clinical, Etiology, Anatomy, and Pathophysiology (CEAP) clinical class were re-evaluated 3 months after stent placement in patients with ICVO. RESULTS: The vasodilatory responses to ACh and SNP in the cutaneous microcirculation were lower in patients with ICVO than in healthy subjects in the sitting position (P < .05). Recanalization and stent placement were successful in all patients in the evaluation of VCSS and clinical class, and a significant decrease was determined in the signs and symptoms of the venous disease (P < .01). Stent placement resulted in a significant increase in vasodilation response to both ACh and SNP in the supine position and no improvement in the sitting position in patients with ICVO. CONCLUSIONS: ICVO impairs endothelium-dependent and endothelium-independent vasodilation in the perimalleolar region. Iliocaval venous stent placement may recover microvascular dysfunction at different levels.


Assuntos
Procedimentos Endovasculares/instrumentação , Veia Ilíaca , Microcirculação , Pele/irrigação sanguínea , Stents , Vasodilatação , Veia Cava Inferior , Insuficiência Venosa/terapia , Trombose Venosa/terapia , Administração Cutânea , Adulto , Estudos de Casos e Controles , Angiografia por Tomografia Computadorizada , Endotélio Vascular/fisiopatologia , Procedimentos Endovasculares/efeitos adversos , Feminino , Humanos , Veia Ilíaca/diagnóstico por imagem , Veia Ilíaca/fisiopatologia , Iontoforese , Masculino , Microcirculação/efeitos dos fármacos , Pessoa de Meia-Idade , Posicionamento do Paciente , Flebografia/métodos , Estudos Prospectivos , Fluxo Sanguíneo Regional , Decúbito Dorsal , Fatores de Tempo , Resultado do Tratamento , Ultrassonografia Doppler Dupla , Grau de Desobstrução Vascular , Vasodilatação/efeitos dos fármacos , Vasodilatadores/administração & dosagem , Veia Cava Inferior/diagnóstico por imagem , Veia Cava Inferior/fisiopatologia , Insuficiência Venosa/diagnóstico por imagem , Insuficiência Venosa/fisiopatologia , Trombose Venosa/diagnóstico por imagem , Trombose Venosa/fisiopatologia
4.
Turk J Pediatr ; 59(6): 619-624, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-30035392

RESUMO

Çetinkaya A, Taskiran E, Soyer T, Simsek-Kiper PÖ, Utine GE, Tunçbilek G, Boduroglu K, Alikasifoglu M. Dermal fibroblast transcriptome indicates contribution of WNT signaling pathways in the pathogenesis of Apert syndrome. Turk J Pediatr 2017; 59: 619-624. Cranial sutures are unossified connective tissue structures between the cranial bones, which allow expansion of these bones during development. Premature ossification of these structures is called craniosynostosis. Apert syndrome is a well-defined genetic syndrome, which is characterized by craniosynostosis and arises as a result of two missense mutations in Fibroblast Growth Factor Receptor, type 2 gene (FGFR2). In this study, differentially expressed genes in dermal fibroblasts from individuals with Apert syndrome and controls were investigated to identify important pathways in the pathogenesis of Apert syndrome. For this purpose, primary skin fibroblast cultures obtained from 3 individuals with Apert syndrome and 3 controls without craniosynostosis were compared by transcriptome microarray, GeneChip Human Genome U133 Plus 2.0. As a result, 181 genes were shown to be differentially expressed between experimental groups. Among these, 10 genes, which significantly differ in Apert syndrome fibroblasts compared to controls, were shown to be involved in a common interaction network and have common Gene ontology (GO) biological processes terms. COL11A1, COMP, CPXM2, ITGA8, MGF and TNC are differentially expressed genes that have GO terms associated with extracellular matrix (ECM) organization, while FRZB, SFRP2 and WNT2 are involved in WNT signaling pathway. Reorganization of ECM and changes in WNT signaling pathway show that Apert syndrome primary fibroblast cultures may have an increased potential for bone differentiation. The results of this study support craniosynostosis in Apert syndrome may be the result of fast and early differentiation of connective tissue along the sutures.

5.
Eur J Med Genet ; 59(11): 604-606, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27638328

RESUMO

Al-Awadi-Raas-Rothschild syndrome (AARRS) is a rare autosomal recessive disorder which consists of severe malformations of the upper and lower limbs, abnormal genitalia and underdeveloped pelvis. Here, we present a fetus with severe limbs defects, including bilateral humeroradial synostosis, bilateral oligodactyly in hands, underdeveloped pelvis, short femora and tibiae, absence of fibulae, severely small feet, and absence of uterus. An autosomal recessively inherited novel mutation in WNT7A found in the fetus, c.304C > T, affects an evolutionarily well-conserved amino acid, causing the p.(R102W) missense change at protein level. The findings presented in this fetus are compatible with diagnosis of AARRS, expanding the mutational spectrum of limb malformations arising from defects in WNT7A.


Assuntos
Amenorreia/genética , Ectromelia/genética , Extremidades/fisiopatologia , Ossos Pélvicos/anormalidades , Útero/anormalidades , Proteínas Wnt/genética , Amenorreia/fisiopatologia , Ectromelia/fisiopatologia , Feminino , Feto/fisiopatologia , Humanos , Mutação de Sentido Incorreto , Ossos Pélvicos/fisiopatologia , Polidactilia/genética , Polidactilia/fisiopatologia , Gravidez , Sinostose/genética , Sinostose/fisiopatologia , Útero/fisiopatologia
6.
Am J Hum Genet ; 99(2): 299-317, 2016 08 04.
Artigo em Inglês | MEDLINE | ID: mdl-27476657

RESUMO

Vascular malformations are non-neoplastic expansions of blood vessels that arise due to errors during angiogenesis. They are a heterogeneous group of sporadic or inherited vascular disorders characterized by localized lesions of arteriovenous, capillary, or lymphatic origin. Vascular malformations that occur inside bone tissue are rare. Herein, we report loss-of-function mutations in ELMO2 (which translates extracellular signals into cellular movements) that are causative for autosomal-recessive intraosseous vascular malformation (VMOS) in five different families. Individuals with VMOS suffer from life-threatening progressive expansion of the jaw, craniofacial, and other intramembranous bones caused by malformed blood vessels that lack a mature vascular smooth muscle layer. Analysis of primary fibroblasts from an affected individual showed that absence of ELMO2 correlated with a significant downregulation of binding partner DOCK1, resulting in deficient RAC1-dependent cell migration. Unexpectedly, elmo2-knockout zebrafish appeared phenotypically normal, suggesting that there might be human-specific ELMO2 requirements in bone vasculature homeostasis or genetic compensation by related genes. Comparative phylogenetic analysis indicated that elmo2 originated upon the appearance of intramembranous bones and the jaw in ancestral vertebrates, implying that elmo2 might have been involved in the evolution of these novel traits. The present findings highlight the necessity of ELMO2 for maintaining vascular integrity, specifically in intramembranous bones.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Osso e Ossos/irrigação sanguínea , Proteínas do Citoesqueleto/genética , Mutação/genética , Transdução de Sinais/genética , Malformações Vasculares/genética , Proteínas rac1 de Ligação ao GTP/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/deficiência , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Adulto , Alelos , Animais , Movimento Celular , Proteínas do Citoesqueleto/deficiência , Proteínas do Citoesqueleto/metabolismo , Evolução Molecular , Feminino , Homozigoto , Humanos , Masculino , Fenótipo , Filogenia , Especificidade da Espécie , Malformações Vasculares/metabolismo , Malformações Vasculares/patologia , Peixe-Zebra/genética , Peixe-Zebra/fisiologia , Proteínas rac de Ligação ao GTP/genética
7.
Psychiatry Investig ; 13(4): 427-33, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27482244

RESUMO

OBJECTIVE: ObjectiveaaWe evaluated the distribution of alpha-2A adrenergic receptor (ADRA2A) and catechol-o-methyltransferase (COMT) single nucleotide polymorphisms (SNPs) among ADHD subtypes and other homogeneous patient populations including treatment-resistant cases and patients with high symptom severity. METHODS: Methodsaa121 ADHD patients aged 6-18 years were included in the study. Diagnosis and subtypes designation were confirmed using the Kiddie Schedule for Affective Disorders and Schizophrenia (K-SADS) and symptoms were evaluated using the Conners' Parent (CPRS) and Teacher Rating Scales (CTRS). The response to methylphenidate was assessed objectively using the Clinical Global Impression-Severity Scale (CGI-S) and Global Assessment of Functioning Scale (GAS) as well as the Continuous Performance (CPT) and Trail Making tests (TMT-A, B). Patients were genotyped for ADRA2A (rs1800544) and COMT (rs4680) SNPs by PCR/RFLP and compared to a gender-matched control group. RESULTS: Although there was no association of COMT (rs4680) SNP with symptoms or diagnosis, the ADRA2A polymorphism, low socioeconomic status (SES), and comorbid psychiatric diagnosis were all associated with poor response to methylphenidate in logistic regression analysis. CONCLUSION: Clinicians may consider adjuvant strategies when these negative factors are present to increase the success of tailored ADHD treatments in the future.

8.
Turk J Med Sci ; 46(2): 489-94, 2016 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-27511516

RESUMO

BACKGROUND/AIM: Neural tube defects (NTDs) are common congenital malformations that develop as a result of interactions between several genes and environmental factors. Many factors have been investigated in order to understand the etiology of NTDs, and many studies have identified folate intake as a common contributing factor. The exact etiology of the disease is still unknown. MATERIALS AND METHODS: In this study, we compared serum folate, vitamin B12, and homocysteine levels, along with common thrombophilia-related genetic variations, including factor V Leiden, factor II g.20210G>A, MTHFR c.677C>T, and MTHFR c.1298A>C, in 35 pregnant women with fetal NTDs and 38 pregnant women with healthy fetuses. RESULTS: A significant difference in serum vitamin B12 level and factor V Leiden frequency was detected between the two groups. On the other hand, serum folate, homocysteine levels, and factor II g.20210G>A, MTHFR c.677C>T, and MTHFR c.1298A>C were not significantly different in the NTD group compared to the controls. CONCLUSION: These results indicate that vitamin B12 supplementation along with folate may help in lowering NTD frequency. In addition, this is the first study that provides evidence for a possible relationship between increased NTD risk and factor V Leiden.


Assuntos
Defeitos do Tubo Neural , Feminino , Ácido Fólico , Genótipo , Homocisteína , Humanos , Metilenotetra-Hidrofolato Redutase (NADPH2) , Mutação , Gravidez , Protrombina , Vitamina B 12
9.
J Child Neurol ; 31(7): 913-7, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-26809768

RESUMO

Mowat-Wilson syndrome is a multiple congenital anomaly and intellectual disability syndrome characterized by a unique face and various other structural and functional anomalies. The condition is caused by de novo heterozygous mutations or deletions in ZEB2 gene located at 2q22. ZEB2 encodes Sip1 protein, which acts during central nervous system development as an important transcription factor. Herein, we report on 3 novel mutations in 6 patients with the syndrome, with an overview of corresponding clinical findings. Growth retardation and Hirschsprung disease were less common in the present cohort. One patient with a novel mutation p.Y489X had no associated anomalies except the characteristic facial and neurobehavioral phenotype. Reporting new patients with novel mutations would contribute to better delineation of the syndrome and would help clinicians establish formal diagnostic criteria and genotype-phenotype correlations.


Assuntos
Doença de Hirschsprung/diagnóstico , Doença de Hirschsprung/genética , Deficiência Intelectual/diagnóstico , Deficiência Intelectual/genética , Microcefalia/diagnóstico , Microcefalia/genética , Mutação , Homeobox 2 de Ligação a E-box com Dedos de Zinco/genética , Criança , Pré-Escolar , Estudos de Coortes , Diagnóstico Diferencial , Face/anormalidades , Facies , Feminino , Estudos de Associação Genética , Doença de Hirschsprung/fisiopatologia , Humanos , Deficiência Intelectual/fisiopatologia , Masculino , Microcefalia/fisiopatologia , Fenótipo
10.
Artigo em Inglês | MEDLINE | ID: mdl-25868129

RESUMO

We assessed DNA damage in patients with metabolic syndrome (MetS) by performing comet and micronucleus (MN) assays on peripheral blood lymphocyte cultures from study participants. 52 MetS patients and 35 age-matched healthy controls were evaluated for abdominal obesity, body-mass index (BMI), blood pressure, serum triglycerides, HbA1c, HDL-C, and fasting blood glucose levels. In addition, malondialdehyde (MDA) levels and activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were determined. Serum levels of triglycerides, HbA1c, fasting blood glucose and waist circumference, systolic blood pressure, diastolic blood pressure, and BMI of the subjects in the MetS group were significantly higher than those of the control group (for each, p<0.001). However, the mean level of HDL-C in the MetS group was lower than in the control group (p<0.001). In the study, the length of comet tails was significantly higher in the MetS patients (10.23±1.98, range 5.72-15.08) than in the controls (3.12±1.73, range 0.6-7.1) (p<0.001). MN frequency was also significantly increased in MetS patients (3.68±1.27 per 1000 cells) compared to that of the control group (1.81±0.84 per 1000 cells) (p<0.001). Micronucleated cell frequency and comet-tail length in subjects showed positive correlations with waist circumference, BMI, and plasma triglyceride levels (p<0.01) and negative correlations with HDL-C levels (p<0.01). Among the oxidative stress factors, MDA levels were significantly higher in MetS patients than in the controls. However, SOD and GSH-Px enzyme activities were significantly lower in the MetS group than in the controls. These findings suggest that patients with MetS have increased DNA damage and oxidative stress.


Assuntos
Dano ao DNA , Linfócitos/metabolismo , Síndrome Metabólica/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Glicemia/metabolismo , Pressão Sanguínea , Índice de Massa Corporal , HDL-Colesterol/sangue , Ensaio Cometa , Feminino , Glutationa Peroxidase/sangue , Hemoglobina A Glicada/metabolismo , Humanos , Masculino , Malondialdeído/sangue , Síndrome Metabólica/sangue , Síndrome Metabólica/patologia , Síndrome Metabólica/fisiopatologia , Testes para Micronúcleos , Pessoa de Meia-Idade , Obesidade Abdominal , Superóxido Dismutase/sangue , Triglicerídeos/sangue , Adulto Jovem
11.
Eur J Paediatr Neurol ; 18(3): 327-37, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24508361

RESUMO

Intellectual disability (ID) has a prevalence of 3% and is classified according to its severity. An underlying etiology cannot be determined in 75-80% in mild ID, and in 20-50% of severe ID. After it has been shown that copy number variations involving short DNA segments may cause ID, genome-wide SNP microarrays are being used as a tool for detecting submicroscopic copy number changes and uniparental disomy. This study was performed to investigate the presence of copy number changes in patients with ID of unidentified etiology. Affymetrix(®) 6.0 SNP microarray platform was used for analysis of 100 patients and their healthy parents, and data were evaluated using various databases and literature. Etiological diagnoses were made in 12 patients (12%). Homozygous deletion in NRXN1 gene and duplication in IL1RAPL1 gene were detected for the first time. Two separate patients had deletions in FOXP2 and UBE2A genes, respectively, for which only few patients have recently been reported. Interstitial and subtelomeric copy number changes were described in 6 patients, in whom routine cytogenetic tools revealed normal results. In one patient uniparental disomy type of Angelman syndrome was diagnosed. SNP microarrays constitute a screening test able to detect very small genomic changes, with a high etiological yield even in patients already evaluated using traditional cytogenetic tools, offer analysis for uniparental disomy and homozygosity, and thereby are helpful in finding novel disease-causing genes: for these reasons they should be considered as a first-tier genetic screening test in the evaluation of patients with ID and autism.


Assuntos
Predisposição Genética para Doença/etiologia , Deficiência Intelectual/genética , Polimorfismo de Nucleotídeo Único/genética , Dissomia Uniparental/etiologia , Adolescente , Criança , Pré-Escolar , Variações do Número de Cópias de DNA/genética , Feminino , Predisposição Genética para Doença/genética , Testes Genéticos/métodos , Humanos , Masculino , Análise em Microsséries , Dissomia Uniparental/genética , Adulto Jovem
12.
J Child Neurol ; 28(7): 926-32, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23611888

RESUMO

GRID2 is a member of the ionotropic glutamate receptor family of excitatory neurotransmitter receptors. GRID2 encodes the glutamate receptor subunit delta-2, selectively expressed in cerebellar Purkinje cells. The phenotype associated with loss of GRID2 function was described only in mice until now, characterized by different degrees of cerebellar ataxia and usually relatively mild abnormalities of the cerebellum. This work describes for the first time the human phenotype associated with homozygous partial deletion of GRID2 in 3 children in one large consanguineous Turkish family. Homozygous deletion of exons 3 and 4 of GRID2 (94 153 589-94 298 037 bp) in the proband and similarly affected cousins, and heterozygous deletions in parental DNA were shown using Affymetrix® 6.0 single-nucleotide polymorphism array, confirmed by real-time polymerase chain reaction. The phenotype includes nystagmus, hypotonia with marked developmental delay in gross motor skills in early infancy followed by a static encephalopathy course with development of cerebellar ataxia, oculomotor apraxia, and pyramidal tract involvement.


Assuntos
Ataxia Cerebelar/genética , Cerebelo/patologia , Receptores de Glutamato/genética , Deleção de Sequência/genética , Atrofia/complicações , Atrofia/genética , Ataxia Cerebelar/complicações , Criança , Cromossomos Humanos Par 5/genética , Progressão da Doença , Saúde da Família , Perfilação da Expressão Gênica , Humanos , Estudos Longitudinais , Imagem por Ressonância Magnética , Masculino , Análise de Sequência com Séries de Oligonucleotídeos , Fenótipo
13.
J Cell Biochem ; 113(11): 3536-46, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22730186

RESUMO

MEFV which encodes pyrin, cause familial Mediterranean fever (FMF), the most common auto-inflammatory disease. Pyrin is believed to be a regulator of inflammation, though the nature of this regulatory activity remains to be identified. Prophylactic treatment with colchicine, a microtubule toxin, has had a remarkable effect on disease progression and outcome. It has been thought that, inhibition of microtubule polymerization is the main mechanism of action of colchicine. But, the exact cellular mechanism explaining the efficacy of colchicine in suppressing FMF attacks is still unclear. Given the ability of colchicine treatment to be considered as a differential diagnosis criteria of FMF, we hypothesized that colchicine may have a specific effect on pyrin and pyrin interacting proteins. This study showed that colchicine prevents reticulated fibrils formed by PSTPIP1 filaments and reduces ASC speck rates in transfected cells. We further noted that, colchicine down-regulates MEFV expression in THP-1 cells. We also observed that colchicine causes re-organization of actin cytoskeleton in THP-1 cells. Pyrin is an actin-binding protein that specifically localizes with polymerizing actin filaments. Thus, MEFV expression might be affected by re-organization of actin cytoskeleton. The data presented here reveal an important connection between colchicine and pyrin which might explain the remarkable efficacy of colchicine in preventing FMF attacks.


Assuntos
Citoesqueleto de Actina/efeitos dos fármacos , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Colchicina/farmacologia , Proteínas do Citoesqueleto/metabolismo , Moduladores de Tubulina/farmacologia , Citoesqueleto de Actina/genética , Citoesqueleto de Actina/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Animais , Células COS , Cercopithecus aethiops , Proteínas do Citoesqueleto/antagonistas & inibidores , Proteínas do Citoesqueleto/genética , Relação Dose-Resposta a Droga , Regulação da Expressão Gênica/efeitos dos fármacos , Genes Reporter , Proteínas de Fluorescência Verde , Células HeLa , Humanos , Microtúbulos/efeitos dos fármacos , Microtúbulos/metabolismo , Mutação , Ligação Proteica , Pirina , Transfecção
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