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Cardiopulmonary resuscitation (CPR) is essential for the survival of cardiac arrest patients, but it can cause severe traumatic complications. In the catheterization laboratory, various physical constraints complicate the appropriate performance of CPR. However, we are not aware of reports of CPR complications in this setting. Here, we report a case of coronary artery perforation (CAP) caused by manual CPR in the catheterization laboratory. The patient, a 68-year-old woman, initially underwent successful percutaneous coronary intervention (PCI) for unstable angina. Back in the ward, the patient experienced acute stent thrombosis, which resulted in cardiac arrest, and another PCI was performed under ongoing manual CPR. Although revascularization was successful, sudden CAP occurred, leading to cardiac tamponade. Despite extensive treatment efforts, the patient died 18 hours later.Initially, the compression site of CPR was on the midline of the sternum; however, the compression site shifted to the left, to just above the left anterior descending artery, by the time that CAP was detected via angiography. This corresponded to the area where rib fractures were observed upon computed tomography, suggesting the possibility of traumatic CAP due to manual CPR. The physical constraints in the catheterization laboratory can lead to an inappropriate CPR technique and severe traumatic complications.
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Reanimação Cardiopulmonar , Vasos Coronários , Intervenção Coronária Percutânea , Humanos , Idoso , Feminino , Reanimação Cardiopulmonar/efeitos adversos , Reanimação Cardiopulmonar/métodos , Vasos Coronários/lesões , Vasos Coronários/diagnóstico por imagem , Intervenção Coronária Percutânea/efeitos adversos , Evolução Fatal , Parada Cardíaca/etiologia , Parada Cardíaca/terapia , Angiografia Coronária , Cateterismo Cardíaco/efeitos adversos , Cateterismo Cardíaco/métodos , Angina Instável/terapia , Angina Instável/etiologia , Tamponamento Cardíaco/etiologiaRESUMO
Contact dermatitis is a severe complication of cardiac-device implantation that may be observed in patients with metal allergies. Some studies have suggested that wrapping cardiac devices with expanded polytetrafluoroethylene (ePTFE) sheets is effective in preventing contact dermatitis. Most of these studies involved pacemakers, whereas those on implantable cardioverter-defibrillators (ICDs) are rare. Herein, we report a method for the successful implantation of an ICD wrapped with an ePTFE sheet in a patient with metal allergy. The metal part of the ICD generator was tightly wrapped with an ePTFE sheet, which was sewn with ePTFE sutures approximating the edges of the generator. After the wrapping procedure, the patient entered the operating room, and the generator and an ePTFE-coated dual-coil shock lead were implanted via a standard procedure. The shock impedance in the coil-to-can vector was high immediately after the implantation, but it reduced to less than half of its initial value over a period of two weeks post-surgery. The patient did not develop any new skin problems during the 20-month follow-up. This is a method for successfully preventing contact dermatitis; however, attention to the associated high risk of infection is required. Learning objective: Wrapping an implantable cardioverter-defibrillator with an expanded polytetrafluoroethylene sheet was effective in preventing contact dermatitis after implantation. The shock impedance in the coil-to-can vector was high immediately after implantation but reduced to approximately half of its initial value with time.
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Atrial fibrillation (AF) is a common cardiac arrhythmia resulting in increased risk of stroke. Despite highly heritable etiology, our understanding of the genetic architecture of AF remains incomplete. Here we performed a genome-wide association study in the Japanese population comprising 9,826 cases among 150,272 individuals and identified East Asian-specific rare variants associated with AF. A cross-ancestry meta-analysis of >1 million individuals, including 77,690 cases, identified 35 new susceptibility loci. Transcriptome-wide association analysis identified IL6R as a putative causal gene, suggesting the involvement of immune responses. Integrative analysis with ChIP-seq data and functional assessment using human induced pluripotent stem cell-derived cardiomyocytes demonstrated ERRg as having a key role in the transcriptional regulation of AF-associated genes. A polygenic risk score derived from the cross-ancestry meta-analysis predicted increased risks of cardiovascular and stroke mortalities and segregated individuals with cardioembolic stroke in undiagnosed AF patients. Our results provide new biological and clinical insights into AF genetics and suggest their potential for clinical applications.
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Fibrilação Atrial , Células-Tronco Pluripotentes Induzidas , Acidente Vascular Cerebral , Humanos , Fibrilação Atrial/genética , Biologia , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla/métodos , Polimorfismo de Nucleotídeo Único/genética , Acidente Vascular Cerebral/genética , Genoma HumanoRESUMO
BACKGROUND: In recent years, there has been considerable research on the use of artificial intelligence to estimate age and disease status from medical images. However, age estimation from chest X-ray (CXR) images has not been well studied and the clinical significance of estimated age has not been fully determined. METHODS: To address this, we trained a deep neural network (DNN) model using more than 100,000 CXRs to estimate the patients' age solely from CXRs. We applied our DNN to CXRs of 1562 consecutive hospitalized heart failure patients, and 3586 patients admitted to the intensive care unit with cardiovascular disease. RESULTS: The DNN's estimated age (X-ray age) showed a strong significant correlation with chronological age on the hold-out test data and independent test data. Elevated X-ray age is associated with worse clinical outcomes (heart failure readmission and all-cause death) for heart failure. Additionally, elevated X-ray age was associated with a worse prognosis in 3586 patients admitted to the intensive care unit with cardiovascular disease. CONCLUSIONS: Our results suggest that X-ray age can serve as a useful indicator of cardiovascular abnormalities, which will help clinicians to predict, prevent and manage cardiovascular diseases.
Chest X-ray is one of the most widely used medical imaging tests worldwide to diagnose and manage heart and lung diseases. In this study, we developed a computer-based tool to predict patients' age from chest X-rays. The tool precisely estimated patients' age from chest X-rays. Furthermore, in patients with heart failure and those admitted to the intensive care unit for cardiovascular disease, elevated X-ray age estimated by our tool was associated with poor clinical outcomes, including readmission for heart failure or death from any cause. With further testing, our tool may help clinicians to predict outcomes in patients with heart disease based on a simple chest X-ray.
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Background: In patients undergoing catheter ablation (CA) for atrial fibrillation (AF), the use of uninterrupted direct oral anticoagulants (DOACs) is the current protocol. This study evaluated bleeding complications following the uninterrupted use of 4 DOACs in patients undergoing CA for AF without any change in the dosing regimen. Moreover, we assessed differences between once- and twice-daily DOAC dosing in patients undergoing CA for AF who continued on DOACs without any change in the dosing regimen. MethodsâandâResults: This study was a retrospective single-center cohort study of consecutive patients. All patients continued DOACs without interruption or changes to the dosing schedule, even in the case of morning procedures. The primary endpoint was the incidence of major bleeding events within the first 30 days after CA. In all, 710 consecutive patients were included in the study. Bleeding complications were less frequent in the uninterrupted twice- than once-daily DOACs group. However, the incidence of cardiac tamponade across all DOACs was low (0.98%; 7/710), suggesting that uninterrupted DOACs without changes to the dosing regimen may be an acceptable strategy. The rate of total bleeding events, including minor bleeding (12/710; 1.6%), was also satisfactory. Conclusions: Uninterrupted DOACs without any change in dosing regimen for patients undergoing CA for AF is acceptable. Bleeding complications may be less frequent in patients receiving DOACs twice rather than once daily.
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Background: Axitinib is a tyrosine kinase inhibitor (TKI) that inhibits vascular endothelial growth factor receptor signaling and is approved for second-line treatment of advanced renal cell carcinoma (RCC). Although the occurrence of hypertension with axitinib use has been documented, it is unclear whether a first-line TKI regimen can significantly affect the development of hypertension when axitinib is used as second-line therapy. MethodsâandâResults: In this single-center retrospective study, advanced RCC patients treated with axitinib after first-line chemotherapy were divided into 2 groups according to the use of TKIs as part of first-line treatment before the initiation of axitinib. Clinical outcomes were compared between patients who were treated with (TKI(+); n=11) or without (TKI(-); n=11) a TKI. Although 63.6% of all patients had hypertension at baseline, axitinib-induced hypertension developed in 81.8% of patients, and 36.4% of patients experienced Grade 3 hypertension. After initiation of axitinib, both systolic and diastolic blood pressures and the hypertension grade were significantly elevated both in the TKI(+) and TKI(-) groups, and the number of antihypertensive drugs was significantly increased among all patients. Conclusions: This study suggests the need for proper monitoring and management of blood pressure in RCC patients treated with axitinib, regardless of a prior regimen with or without TKIs.
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Genotype-by-environment (G × E) interactions are important for understanding genotype-phenotype relationships. To date, various statistical models have been proposed to account for G × E effects, especially in genomic selection (GS) studies. Generally, GS does not focus on the detection of each quantitative trait locus (QTL), while the genome-wide association study (GWAS) was designed for QTL detection. G × E modeling methods in GS can be included as covariates in GWAS using unified linear mixed models (LMMs). However, the efficacy of G × E modeling methods in GS studies has not been evaluated for GWAS. In this study, we performed a comprehensive comparison of LMMs that integrate the G × E modeling methods to detect both QTL and QTL-by-environment (Q × E) interaction effects. Model efficacy was evaluated using simulation experiments. For the fixed effect terms representing Q × E effects, simultaneous scoring of specific and nonspecific environmental effects was recommended because of the higher recall and improved genomic inflation factor value. For random effects, it was necessary to account for both G × E and genotype-by-trial (G × T) effects to control genomic inflation factor value. Thus, the recommended LMM includes fixed QTL effect terms that simultaneously score specific and nonspecific environmental effects and random effects accounting for both G × E and G × T. The LMM was applied to real tomato phenotype data obtained from two different cropping seasons. We detected not only QTLs with persistent effects across the cropping seasons but also QTLs with Q × E effects. The optimal LMM identified in this study successfully detected more QTLs with Q × E effects.
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Estudo de Associação Genômica Ampla , Locos de Características Quantitativas , Mapeamento Cromossômico , Interação Gene-Ambiente , Genótipo , FenótipoRESUMO
The technique of catheter ablation has been improved within the past few decades, especially by three-dimensional (3D) mapping system. 3D mapping system has reduced radiation exposure but ablation procedures still require fluoroscopy. Our previous study showed the safety and efficacy of catheter ablation based on intracardiac echogram combined with CARTOSOUND/CARTO3 system, however fluoroscopy use for an average of 16 min is required for this procedure. The present study was aimed to reduce radiation exposure to zero and establish a radiation free catheter ablation method with the goal of utilizing it in routine clinical practice. We conducted single center, retrospective study during 2019 April to 2020 February. Consecutive 76 patients were enrolled. In the first 18 cases, the previously reported procedure (CARTOSOUND/CARTO3 method) was used. The remaining 58 cases were transitioned to fluoroless catheter ablation. The procedure time, success rates and complication rates were analyzed. Not only AF patients but atrial flutter (AFL), paroxysmal supraventricular tachycardia (PSVT) and ventricular arrhythmia patients were included. Catheter positioning, catheter visualization and collecting the geometry of each camber of the heart were conducted by using contact force and ICE based geometry on CARTO system without either prior computed tomography (CT) or magnetic resonance image (MRI). In fluoroless group, all catheter ablations were successfully performed without lead aprons. No complications occurred in either group. There were no significant differences in procedure time in any type of procedure (Total procedure time Fluoro-group; 149 ± 51 min vs. Fluoroless-group; 162 ± 43 min, N.S.), (PSVT 170 ± 53 min vs. 162 ± 29 min, N.S.), (AFL 110 ± 70 min vs. 123 ± 43 min, N.S.), (AF 162 ± 43 min vs. 163 ± 32 min, N.S.). The total radiation time was reduced to zero in fluoroless group. Catheter ablation with ICE and 3D mapping system guide without fluoroscopy could be safely performed with a high success rate, without any prior CT/MRI 3D images. Radiation was reduced completely for patients and staff, negating the need for protective wear for operators.
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Ablação por Cateter/métodos , Ecocardiografia Tridimensional/métodos , Cardiopatias/cirurgia , Ultrassonografia de Intervenção/métodos , Procedimentos Cirúrgicos Cardíacos/métodos , Feminino , Fluoroscopia , Cardiopatias/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
To elucidate the genetics of coronary artery disease (CAD) in the Japanese population, we conducted a large-scale genome-wide association study of 168,228 individuals of Japanese ancestry (25,892 cases and 142,336 controls) with genotype imputation using a newly developed reference panel of Japanese haplotypes including 1,781 CAD cases and 2,636 controls. We detected eight new susceptibility loci and Japanese-specific rare variants contributing to disease severity and increased cardiovascular mortality. We then conducted a trans-ancestry meta-analysis and discovered 35 additional new loci. Using the meta-analysis results, we derived a polygenic risk score (PRS) for CAD, which outperformed those derived from either Japanese or European genome-wide association studies. The PRS prioritized risk factors among various clinical parameters and segregated individuals with increased risk of long-term cardiovascular mortality. Our data improve the clinical characterization of CAD genetics and suggest the utility of trans-ancestry meta-analysis for PRS derivation in non-European populations.
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Doença da Artéria Coronariana/genética , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Adulto , Idoso , Alelos , Colestanotriol 26-Mono-Oxigenase/genética , Mapeamento Cromossômico , Doença da Artéria Coronariana/mortalidade , Pleiotropia Genética , Genótipo , Humanos , Japão , Pessoa de Meia-Idade , Linhagem , Fatores de RiscoRESUMO
BACKGROUND: Genome-wide association studies provided many biological insights into coronary artery disease (CAD), but these studies were mainly performed in Europeans. Genome-wide association studies in diverse populations have the potential to advance our understanding of CAD. METHODS: We conducted 2 genome-wide association studies for CAD in the Japanese population, which included 12 494 cases and 28 879 controls and 2808 cases and 7261 controls, respectively. Then, we performed transethnic meta-analysis using the results of the coronary artery disease genome-wide replication and meta-analysis plus the coronary artery disease 1000 Genomes meta-analysis with UK Biobank. We then explored the pathophysiological significance of these novel loci and examined the differences in CAD-susceptibility loci between Japanese and Europeans. RESULTS: We identified 3 new loci on chromosome 1q21 (CTSS), 10q26 (WDR11-FGFR2), and 11q22 (RDX-FDX1). Quantitative trait locus analyses suggested the association of CTSS and RDX-FDX1 with atherosclerotic immune cells. Tissue/cell type enrichment analysis showed the involvement of arteries, adrenal glands, and fat tissues in the development of CAD. We next compared the odds ratios of lead variants for myocardial infarction at 76 genome-wide significant loci in the transethnic meta-analysis and a moderate correlation between Japanese and Europeans, where 8 loci showed a difference. Finally, we performed tissue/cell type enrichment analysis using East Asian-frequent and European-frequent variants according to the risk allele frequencies and identified significant enrichment of adrenal glands in the East Asian-frequent group while the enrichment of arteries and fat tissues was found in the European-frequent group. These findings indicate biological differences in CAD susceptibility between Japanese and Europeans. CONCLUSIONS: We identified 3 new loci for CAD and highlighted the genetic differences between the Japanese and European populations. Moreover, our transethnic analyses showed both shared and unique genetic architectures between the Japanese and Europeans. While most of the underlying genetic bases for CAD are shared, further analyses in diverse populations will be needed to elucidate variations fully.
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Povo Asiático , Cromossomos Humanos/genética , Doença da Artéria Coronariana , Loci Gênicos , População Branca , Povo Asiático/etnologia , Povo Asiático/genética , Doença da Artéria Coronariana/etnologia , Doença da Artéria Coronariana/genética , Feminino , Estudo de Associação Genômica Ampla , Humanos , Japão/etnologia , Masculino , Metanálise como Assunto , Reino Unido/etnologia , População Branca/etnologia , População Branca/genéticaRESUMO
A core collection of eggplant (Solanum melongena L.) was developed based on a dataset of genome-wide 831 SNP and 50 SSR genotypes analyzed in 893 accessions of eggplant genetic resources collected in the NARO Genebank using the Core Hunter II program. The 893 accessions were collected worldwide, mainly Asia. Genetic variation and population structure among the 893 eggplant accessions were characterized. The genetic diversity of the Asian accessions, especially the South Asian and Southeast Asian accessions, forming the center of diversity in eggplant, was higher than that of the other regions. The resulting core collection, World Eggplant Core (WEC) collection consisted of 100 accessions basically collected from the high genetic diversity countries. Based on the results of the cluster and STRUCTURE analyses with SNP genotypes, the WEC collection was divided into four clusters (S1-S4). Each cluster corresponds to a geographical group as below, S1; the European, American and African countries, S2; the East Asian countries, S3; the Southeast Asian countries, S4; the South Asian and Southeast Asian countries. The genotype and phenotype data of the WEC collection are available from the VegMarks database (https://vegmarks.nivot.affrc.go.jp/resource/), and seed samples are available from the NARO Genebank (https://www.gene.affrc.go.jp/databases-core_collections.php).
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BACKGROUND: Periprocedural anticoagulation is important in catheter ablation (CA) of atrial fibrillation (AF) and there is increasing evidence that uninterrupted vitamin K antagonist (VKA) therapy is superior to interrupted anticoagulation strategies. Since the emergence of direct oral anticoagulants (DOACs), numerous studies have shown promising results for their use in uninterrupted strategies. However, further studies are needed to further deï¬ne the efï¬cacy and safety of performing AF ablation with uninterrupted factor XA inhibitors or direct thrombin inhibitors.MethodsâandâResults:We have performed CA of AF without discontinuation of either VKA or DOAC therapy since April 2014. A total of 376 patients with AF underwent CA including pulmonary vein isolation. All of the patients were divided into 2 groups (uninterrupted VKA or uninterrupted DOACs). Anticoagulation with DOACs was associated with fewer complications than uninterrupted VKA therapy (P=0.04). There were significant differences between groups in the rates of congestive heart failure, left ventricular ejection fraction, body weight, and estimated glomerular filtration rate and of the CHADS2, CHA2DS2-VASc and HAS-BLED scores. Therefore, we also analyzed the results using the propensity score-matching method. We found no significant difference in periprocedural complications between uninterrupted VKA or DOACs therapy (P=0.65). CONCLUSIONS: CA of AF without discontinuation of DOACs is not inferior to CA without discontinuation of a VKA, with regard to ischemic or hemorrhagic complications.
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Anticoagulantes/uso terapêutico , Fibrilação Atrial/terapia , Ablação por Cateter/efeitos adversos , Vitamina K/antagonistas & inibidores , Idoso , Tamponamento Cardíaco/etiologia , Ablação por Cateter/métodos , Feminino , Hemorragia/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Acidente Vascular Cerebral/etiologiaRESUMO
KEY MESSAGE: Using newly developed euchromatin-derived genomic SSR markers and a flexible Bayesian mapping method, 13 significant agricultural QTLs were identified in a segregating population derived from a four-way cross of tomato. So far, many QTL mapping studies in tomato have been performed for progeny obtained from crosses between two genetically distant parents, e.g., domesticated tomatoes and wild relatives. However, QTL information of quantitative traits related to yield (e.g., flower or fruit number, and total or average weight of fruits) in such intercross populations would be of limited use for breeding commercial tomato cultivars because individuals in the populations have specific genetic backgrounds underlying extremely different phenotypes between the parents such as large fruit in domesticated tomatoes and small fruit in wild relatives, which may not be reflective of the genetic variation in tomato breeding populations. In this study, we constructed F2 population derived from a cross between two commercial F1 cultivars in tomato to extract QTL information practical for tomato breeding. This cross corresponded to a four-way cross, because the four parental lines of the two F1 cultivars were considered to be the founders. We developed 2510 new expressed sequence tag (EST)-based (euchromatin-derived) genomic SSR markers and selected 262 markers from these new SSR markers and publicly available SSR markers to construct a linkage map. QTL analysis for ten agricultural traits of tomato was performed based on the phenotypes and marker genotypes of F2 plants using a flexible Bayesian method. As results, 13 QTL regions were detected for six traits by the Bayesian method developed in this study.
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Mapeamento Cromossômico/métodos , Repetições de Microssatélites , Locos de Características Quantitativas , Solanum lycopersicum/genética , Teorema de Bayes , Cruzamentos Genéticos , Etiquetas de Sequências Expressas , Ligação Genética , Marcadores Genéticos , Variação Genética , Genótipo , Modelos Genéticos , Fenótipo , Melhoramento VegetalRESUMO
Efficient plant breeding methods must be developed in order to increase yields and feed a growing world population, as well as to meet the demands of consumers with diverse preferences who require high-quality foods. We propose a strategy that integrates breeding simulations and phenotype prediction models using genomic information. The validity of this strategy was evaluated by the simultaneous genetic improvement of the yield and flavour of the tomato (Solanum lycopersicum), as an example. Reliable phenotype prediction models for the simulation were constructed from actual genotype and phenotype data. Our simulation predicted that selection for both yield and flavour would eventually result in morphological changes that would increase the total plant biomass and decrease the light extinction coefficient, an essential requirement for these improvements. This simulation-based genome-assisted approach to breeding will help to optimise plant breeding, not only in the tomato but also in other important agricultural crops.
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Cruzamento , Simulação por Computador , Genoma de Planta , Modelos Genéticos , Solanum lycopersicum/genética , Mapeamento Cromossômico , Genética Populacional , Estudo de Associação Genômica Ampla , Desequilíbrio de Ligação , Fenótipo , Locos de Características Quantitativas , Característica Quantitativa Herdável , Seleção GenéticaRESUMO
With the aim of understanding relationship between genetic and phenotypic variations in cultivated tomato, single nucleotide polymorphism (SNP) markers covering the whole genome of cultivated tomato were developed and genome-wide association studies (GWAS) were performed. The whole genomes of six tomato lines were sequenced with the ABI-5500xl SOLiD sequencer. Sequence reads covering ~13.7× of the genome for each line were obtained, and mapped onto tomato reference genomes (SL2.40) to detect ~1.5 million SNP candidates. Of the identified SNPs, 1.5% were considered to confer gene functions. In the subsequent Illumina GoldenGate assay for 1536 SNPs, 1293 SNPs were successfully genotyped, and 1248 showed polymorphisms among 663 tomato accessions. The whole-genome linkage disequilibrium (LD) analysis detected highly biased LD decays between euchromatic (58 kb) and heterochromatic regions (13.8 Mb). Subsequent GWAS identified SNPs that were significantly associated with agronomical traits, with SNP loci located near genes that were previously reported as candidates for these traits. This study demonstrates that attractive loci can be identified by performing GWAS with a large number of SNPs obtained from re-sequencing analysis.
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Genoma de Planta , Polimorfismo de Nucleotídeo Único , Solanum lycopersicum/genética , Produtos Agrícolas/genética , Loci Gênicos , Marcadores Genéticos/fisiologia , Estudo de Associação Genômica Ampla , Genótipo , Desequilíbrio de Ligação , Análise de Sequência de DNARESUMO
White rot fungus, Phanerochaete chrysosporium, and brown rot fungus, Postia placenta, grown on agar plates, were visualized by fluorescence in situ hybridization (FISH) using a peptide nucleic acid (PNA) probe. Mycelia grown on wood chips were also clearly detected by PNA-FISH following blocking treatment. To the best of our knowledge, this is the first report on the visualization of fungi in wood by FISH.
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Hibridização in Situ Fluorescente/métodos , Micélio/ultraestrutura , Sondas de Ácido Nucleico/química , Ácidos Nucleicos Peptídicos/química , Phanerochaete/ultraestrutura , Polyporales/ultraestrutura , Microscopia de Fluorescência , Micélio/crescimento & desenvolvimento , Phanerochaete/crescimento & desenvolvimento , Polyporales/crescimento & desenvolvimento , RNA Ribossômico 18S/análise , Madeira/microbiologiaRESUMO
BACKGROUND: It has been suggested that replicative senescence might be involved in the pathophysiology of age-related diseases. AIM: To study the process of senescence in trabecular meshwork (TM) cells. METHODS: Porcine TM tissues were obtained and placed in primary cultures with Dulbecco's modified Eagle's medium/Ham's F-12 medium. After 2-3 weeks, migrated and proliferated TM cells were trypsinised and cultured in serial passages, and identified with fluorescein-labelled low-density lipoprotein (DiI-Ac-LDL), a marker of TM cells. Staining for senescence-related beta-galactosidase activity was performed at population doubling level (PDL) 2, 8 and 16 at pH 6. Terminal restriction fragment (TRF) length was examined by Southern blot analysis using a (32)P-labelled telomere-specific sequence (TTAGGG)(3) at each PDL. RESULTS: DiI-Ac-LDL staining revealed that most (nearly 100%) of the cells in the culture were TM cells, which were flattened in shape and positive for senescence-related beta-galactosidase staining at PDL 16. Reduction of TRF length as a function of population doubling was also shown. CONCLUSIONS: TM cells exhibited characteristics of senescence at PDL 16 in vitro. The results demonstrated that cellular senescence may be related to the pathophysiology of primary open-angle glaucoma.
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Senescência Celular , Malha Trabecular/citologia , Animais , Técnicas de Cultura de Células/métodos , Proliferação de Células , Forma Celular , Lipoproteínas LDL/metabolismo , Polimorfismo de Fragmento de Restrição , Suínos , Telômero , Técnicas de Cultura de Tecidos , Malha Trabecular/metabolismo , Regulação para Cima , beta-Galactosidase/metabolismoRESUMO
CONTEXT: Pigment epithelium-derived factor (PEDF) is a strong inhibitor of angiogenesis. Eyes with diabetic retinopathy have low levels of ocular PEDF; however, the PEDF levels in the blood of diabetics have still not been determined. OBJECTIVES: Our objective was to determine the plasma levels of PEDF in diabetic patients and to determine the relationship with the stage of the diabetic retinopathy. DESIGN AND SETTING: This study was designed as a cross-sectional, institutional study. PATIENTS OR OTHER PARTICIPANTS: A total of 145 Japanese were studied; 112 had type 2 diabetes mellitus, and 33 were healthy controls. INTERVENTION: There was no intervention. MAIN OUTCOME MEASURES: The plasma level of PEDF was measured by ELISA, and the stage of diabetic retinopathy was determined by ophthalmic examinations. Clinical systemic status of diabetic patients was also examined. RESULTS: The plasma PEDF level in diabetic patients (6.68 +/- 0.54 microg/ml; mean +/- sem) was significantly higher than that in controls (4.38 +/- 0.59 microg/ml, P = 0.03), and the level was especially high in patients with proliferative diabetic retinopathy (7.78 +/- 0.98 microg/ml; n = 45; P = 0.005). The gender (P = 0.03), blood urea nitrogen (P = 0.005), and triglycerides (P = 0.04) were significant and independent determinants of plasma PEDF levels in diabetic patients. CONCLUSIONS: The PEDF level in the plasma was significantly elevated in diabetic patients, especially those with proliferative diabetic retinopathy. High levels of PEDF in the plasma may be related to the progression of diabetic retinopathy.
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Diabetes Mellitus Tipo 2/sangue , Retinopatia Diabética/sangue , Proteínas do Olho/sangue , Fatores de Crescimento Neural/sangue , Serpinas/sangue , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Diabetes Mellitus Tipo 2/complicações , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise de RegressãoRESUMO
PURPOSE: The present study was performed to clarify the long-term natural history of polypoidal choroidal vasculopathy (PCV). DESIGN: Prospective, consecutive observational case series. METHODS: Fourteen eyes of 12 consecutive patients with PCV were prospectively followed in our clinic for at least 2 years without any treatment after a first visit to the clinic between February 1996 and November 1998. All patients underwent complete ophthalmologic examination, color fundus photography, and fluorescein and indocyanine green (ICG) angiography at regular intervals. Inclusion criteria were as follows: eyes had serous and/or hemorrhagic pigment epithelium detachment (PED) and retinal detachment in the posterior pole, and ICG angiography revealed a branching vascular network with polypoidal dilations at the terminals of the network. Exclusion criteria were as follows: other diseases such as exudative age-related macular degeneration, high myopia, angioid streaks, and presumed ocular histoplasmosis syndrome, and patients who previously underwent any ocular surgery. RESULTS: Patients were followed for mean of 39.9 months (range, 24-54 months). PCV was present in 10 (83%) men and two women and in the elderly (mean age 68.1 years), usually unilateral (83%) with vascular lesions located at the macula (93%). The PCV manifested in two patterns, exudative and hemorrhagic. In the exudative pattern, serous PED and retinal detachment were predominant at the macula. The hemorrhagic pattern was characterized by hemorrhagic PED and subretinal hemorrhage at the macula. ICG angiography revealed polypoidal choroidal neovascularization that was changeable in appearance and repeatedly grew and spontaneously regressed, but the vascular network persisted. In some eyes, a collection of small aneurysmal dilations of vessels resembling a cluster of grapes appeared and all of them had marked bleeding and leakage and worse outcome. CONCLUSION: Polypoidal choroidal vasculopathy is a long persistent chronic disease and the patients had a variable course. Fifty percent of the patients had a favorable course. In the remaining half of the patients, the disorder persisted for a long time with occasional repeated bleeding and leakage, resulting in macular degeneration and visual loss. Eyes with a cluster of grapes-like polypoidal dilatations of the vessels had a high risk for severe visual loss.