Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 3.981
Filtrar
1.
Gene ; 715: 144027, 2019 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-31374327

RESUMO

OBJECTIVES: To explore the clinical and molecular characteristics of a Chinese Zhuang minority patient with leukocyte adhesion deficiency type-1 (LAD-1) and glucose-6-phosphate dehydrogenase deficiency (G6PDD). METHODS: Routine clinical and physical examinations were performed, and patient data was collected and analyzed. Protein expression levels of Itgb2 and glucose-6-phosphate dehydrogenase (G6pd) proteins were assessed by flow cytometry and the glucose-6-phosphate (G6P) substrate method, respectively. Whole exome sequencing was performed to investigate genetic variations of the patient and his parents. RESULTS: The patient had fester disease and delayed separation of the umbilical cord at birth. Staphylococcus was detected in the fluid secretion of the auditory meatus of the patient. He exhibited a recurrent cheek scab, swollen hand, and swollen gum. Hematological examination indicated dramatic elevation of leukocytes including lymphocytes, monocytes, neutrophils and eosinophils. A novel homozygous mutation was detected in the ITGB2 gene of the patient, which was determined to be a two nucleotide deletion at the site of c.1537-1538 (c.1537-1538delGT), causing a frameshift of 24 amino acids from p.513 and inducing a stop codon (p.V513Lfs*24). A base substitution mutation was identified at c.1466 (c.1466G>T) of G6PD on chromosome X of the patient, which resulted in an amino acid change from arginine to leucine at p.489 (p.R489L). The patient also showed deficient lymphocyte expression of CD18 (2.99%) and significant downregulation of the G6pd protein. CONCLUSIONS: The patient was diagnosed with G6PDD and moderate LAD-1. The combination of LAD-1 and G6PDD in this case may have been due to the high incidence of genetic disease in this minority ethnic population. Analyzing existing LAD-1 and G6PDD cases from different populations can facilitate disease diagnosis and treatment. Particularly, reporting pathogenic mutations of LAD-1 and G6PDD will be crucial for genetic testing and prenatal diagnosis in an effort to decrease the incidence of these diseases.


Assuntos
Antígenos CD18/genética , Deficiência de Glucosefosfato Desidrogenase/genética , Homozigoto , Síndrome da Aderência Leucocítica Deficitária/genética , Mutação de Sentido Incorreto , Substituição de Aminoácidos , Grupo com Ancestrais do Continente Asiático , Antígenos CD18/metabolismo , Deficiência de Glucosefosfato Desidrogenase/patologia , Humanos , Lactente , Síndrome da Aderência Leucocítica Deficitária/metabolismo , Síndrome da Aderência Leucocítica Deficitária/patologia , Leucócitos/metabolismo , Leucócitos/patologia , Masculino
2.
J Clin Pathol ; 72(11): 755-761, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31256009

RESUMO

AIMS: Morphological differentiation among different blast cell lineages is a difficult task and there is a lack of automated analysers able to recognise these abnormal cells. This study aims to develop a machine learning approach to predict the diagnosis of acute leukaemia using peripheral blood (PB) images. METHODS: A set of 442 smears was analysed from 206 patients. It was split into a training set with 75% of these smears and a testing set with the remaining 25%. Colour clustering and mathematical morphology were used to segment cell images, which allowed the extraction of 2,867 geometric, colour and texture features. Several classification techniques were studied to obtain the most accurate classification method. Afterwards, the classifier was assessed with the images of the testing set. The final strategy was to predict the patient's diagnosis using the PB smear, and the final assessment was done with the cell images of the smears of the testing set. RESULTS: The highest classification accuracy was achieved with the selection of 700 features with linear discriminant analysis. The overall classification accuracy for the six groups of cell types was 85.8%, while the overall classification accuracy for individual smears was 94% as compared with the true confirmed diagnosis. CONCLUSIONS: The proposed method achieves a high diagnostic precision in the recognition of different types of blast cells among other mononuclear cells circulating in blood. It is the first encouraging step towards the idea of being a diagnostic support tool in the future.


Assuntos
Interpretação de Imagem Assistida por Computador/métodos , Leucemia/patologia , Leucócitos/patologia , Aprendizado de Máquina , Reconhecimento Automatizado de Padrão/métodos , Coloração e Rotulagem/métodos , Doença Aguda , Coleta de Amostras Sanguíneas , Linhagem da Célula , Diagnóstico Diferencial , Humanos , Leucemia/sangue , Leucemia/classificação , Valor Preditivo dos Testes , Reprodutibilidade dos Testes
3.
Ann Hematol ; 98(8): 1933-1936, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31201513

RESUMO

Ruxolitinib is the only commercially available JAK1/2 inhibitor approved for the treatment of myelofibrosis-related splenomegaly and symptoms. During treatment, as rare conditions, leukocytosis and/or thrombocytosis could develop and the management of these situations is not well established. We report here 53 myelofibrosis patients that received a combination of hydroxyurea and ruxolitinib because of uncontrolled myeloproliferation. Both drugs were administered outside clinical trials. At 48 weeks, a significant reduction in leucocyte and platelet counts was observed (p = 0.02 and p = 0.04, respectively). Additionally, the spleen volume decreased from a median value of 10 cm below the left costal margin (range, 0-10) to 6 cm (range, 0-15). The rate of spleen response increased from 14% at the start of the combination to 45% after 48 weeks. The safety profile of the combination was consistent with that observed with ruxolitinib single agent. These data require further confirmation in large cohorts of patients prospectively assessed.


Assuntos
Plaquetas/efeitos dos fármacos , Hidroxiureia/uso terapêutico , Leucócitos/efeitos dos fármacos , Mielofibrose Primária/tratamento farmacológico , Pirazóis/uso terapêutico , Esplenomegalia/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Plaquetas/patologia , Contagem de Células , Proliferação de Células/efeitos dos fármacos , Esquema de Medicação , Quimioterapia Combinada , Feminino , Humanos , Leucócitos/patologia , Masculino , Pessoa de Meia-Idade , Segurança do Paciente , Mielofibrose Primária/complicações , Mielofibrose Primária/mortalidade , Mielofibrose Primária/patologia , Estudos Retrospectivos , Esplenomegalia/complicações , Esplenomegalia/mortalidade , Esplenomegalia/patologia , Análise de Sobrevida , Resultado do Tratamento
4.
Methods Mol Biol ; 1979: 305-315, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31028646

RESUMO

Flow cytometry is one of the most suitable techniques for analyzing and classifying different cell suspensions derived from blood or others compartments. The characterization of all different cellular subtypes is made with different antibodies that detect surface or intracytoplasmic antigens. Here we describe the technique to thoroughly characterize immune cells from tumor infiltrates and proceed to isolation using single-cell sorting.


Assuntos
Citometria de Fluxo/métodos , Leucócitos/imunologia , Neoplasias/imunologia , Análise de Célula Única/métodos , Animais , Antígenos CD/análise , Antígenos CD/imunologia , Humanos , Leucócitos/patologia , Linfócitos/imunologia , Linfócitos/patologia , Camundongos , Monócitos/imunologia , Monócitos/patologia , Neoplasias/patologia , Ratos , Coloração e Rotulagem/métodos
5.
Ann Biol Clin (Paris) ; 77(2): 174-178, 2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-30998198

RESUMO

Nowadays, laboratories have more efficient haematology analyzers. These analyzers have to be used in the most efficient and the most adapted way according to the internal organisation of laboratories and prescribers' expectations. The aim of this study was to evaluate the performance of the blast flag on ADVIA 2120/2120i, and to suggest what to do, depending on the flag intensity, to identify positive samples the most surely and the most rapidly as possible. MATERIALS AND METHODS: Seven hospital laboratories were included in this prospective study, 148 144 samples of hospital patients were tested during this 4 months study. RESULTS: Sensitivity and specificity of the blast flag are respectively 89,04% and 98,97%. A good correlation between the flag level and the blast count on blood smear is noticed. CONCLUSION: This study could be helpful for laboratories using ADVIA 2120/2120i, to adapt their procedures, depending on the level of the flag provided by the analyser.


Assuntos
Alarmes Clínicos , Leucócitos/citologia , Coleta de Amostras Sanguíneas/normas , Alarmes Clínicos/normas , França , Testes Hematológicos/métodos , Testes Hematológicos/normas , Humanos , Laboratórios/normas , Ensaio de Proficiência Laboratorial , Contagem de Leucócitos , Leucócitos/patologia , Limite de Detecção , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
6.
PLoS One ; 14(3): e0213549, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30870488

RESUMO

BACKGROUND: Urinary Calprotectin, a mediator of the innate immune system, has been identified as a biomarker in bladder cancer. Our aim was to investigate the association between sterile leukocyturia and urinary Calprotectin in low-grade and high-grade bladder cancer. MATERIALS AND METHODS: We performed a prospective cross-sectional study including 52 patients with bladder cancer and 40 healthy controls. Definition of sterile leukocyturia was > 5.0 leukocytes per visual field in absence of bacteriuria. RESULTS: The rate of sterile leukocyturia in low-grade (60.0%) and high-grade (62.0%) bladder cancer was comparable (p = 0.87). However, the median absolute urinary leukocyte count in patients with sterile leukocyturia was significantly higher in high-grade than in low-grade bladder cancer (p < 0.01). Spearman correlation revealed a significant correlation between urinary Calprotectin and leucocyte concentration (R = 0.4, p < 0.001). Median urinary Calprotectin concentration was 4.5 times higher in bladder cancer patients with than in patients without sterile leukocyturia (p = 0.03). Subgroup analysis revealed a significant difference in urinary Calprotectin regarding the presence of sterile leukocyturia in high-grade patients (596.8 [91.8-1655.5] vs. 90.4 [28.0-202.3] ng ml-1, p = 0.02). Multivariate analysis identified the leukocyte concentration to be the only significant impact factor for urinary Calprotectin (OR 3.2, 95% CI 2.5-3.8, p = 0.001). Immunohistochemistry showed Calprotectin positive neutrophils and tumour cells in high-grade bladder cancer with sterile leukocyturia. CONCLUSIONS: Urinary Calprotectin cannot be regarded as a specific tumour marker for bladder cancer, but rather as a surrogate parameter for tumour inflammation.


Assuntos
Biomarcadores Tumorais/urina , Complexo Antígeno L1 Leucocitário/urina , Leucócitos/metabolismo , Neoplasias da Bexiga Urinária/urina , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Humanos , Leucócitos/patologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Neoplasias da Bexiga Urinária/patologia
7.
Zhonghua Bing Li Xue Za Zhi ; 48(3): 220-224, 2019 Mar 08.
Artigo em Chinês | MEDLINE | ID: mdl-30831649

RESUMO

Objective: To investigate the clinicpathological and molecular features of Erdheim-Chester disease (ECD) as well langerhans cell histiocytosis (LCH). Methods: The clinical, histopathological, molecular findings, immunophenotype, treatment and prognosis in 4 cases of ECD combined LCH were evaluated from February 2015 to September 2018 with review of the relevant literature. Results: 2 cases were male, and 2 were female, aged from 7-55 years. Microscopically, there were two different areas, in the first area, the lesions were composed of foamy histiocytes, spindle-shaped fibroblasts, scattered multinucleated giant cells. Lymphocytes, plasma cells, and giant cells were also found. In the other, the lesions were composed of histiocytes with obvious nuclear groove, associated with a variable number of eosinophils, lymphocytes and plasma cells. Immunephenotype, In the second area, histiocytes were positive for CD1a (4/4), S-100 (4/4),CD207/Langerin (4/4), cyclin D1(4/4), and in the two different area, the histiocytes were positive for CD68, CD163, Braf. Ki-67 positive index 1%-10% BRAF V600E gene mutation was detected in three cases. Conclusion: ECD combined LCH was a very rare histiocytosis tumor and its correct diagnosis relies on histopathologic features, immunohistochemical staining, and BRAF V600E gene detection.


Assuntos
Doença de Erdheim-Chester/patologia , Histiocitose de Células de Langerhans/patologia , Adolescente , Adulto , Criança , Diagnóstico Diferencial , Feminino , Fibroblastos/patologia , Células Gigantes/patologia , Histiócitos/patologia , Humanos , Imunofenotipagem , Leucócitos/patologia , Masculino , Pessoa de Meia-Idade
8.
Cells ; 8(3)2019 03 20.
Artigo em Inglês | MEDLINE | ID: mdl-30897778

RESUMO

The function of proteasomes in extracellular space is still largely unknown. The extracellular proteasome-osteopontin circuit has recently been hypothesized to be part of the inflammatory machinery regulating relapse/remission phase alternation in multiple sclerosis. However, it is still unclear what dynamics there are between the different elements of the circuit, what the role of proteasome isoforms is, and whether these inflammatory circuit dynamics are associated with the clinical severity of multiple sclerosis. To shed light on these aspects of this novel inflammatory circuit, we integrated in vitro proteasome isoform data, cell chemotaxis cell culture data, and clinical data of multiple sclerosis cohorts in a coherent computational inference framework. Thereby, we modeled extracellular osteopontin-proteasome circuit dynamics during relapse/remission alternation in multiple sclerosis. Applying this computational framework to a longitudinal study on single multiple sclerosis patients suggests a complex interaction between extracellular proteasome isoforms and osteopontin with potential clinical implications.


Assuntos
Espaço Extracelular/metabolismo , Esclerose Múltipla/metabolismo , Osteopontina/metabolismo , Complexo de Endopeptidases do Proteassoma/metabolismo , Sistema Nervoso Central/patologia , Quimiotaxia , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Leucócitos/patologia , Modelos Biológicos , Esclerose Múltipla/imunologia , Esclerose Múltipla/patologia , Osteopontina/sangue , Isoformas de Proteínas/metabolismo , Recidiva , Indução de Remissão , Trombina/farmacologia
9.
J Neurooncol ; 143(1): 15-25, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30827009

RESUMO

PURPOSE: The aim of this study was to test the possibility of using specimens obtained by a cavitron ultrasonic surgical aspirator (CUSA) in flow and mass cytometry investigations of pediatric brain tumors. METHODS: CUSA specimens obtained from 19 pediatric patients with brain tumors were investigated. Flow and mass cytometry methods were applied to analyze the composition of material collected using the CUSA. Cell suspensions were prepared from CUSA aspirates. Then sample viability was assessed by conventional flow cytometry and subsequently stained with a panel of 31 metal-labeled antibodies. RESULTS: Viability assessment was performed using conventional flow cytometry. Viability of cells in the acquired samples was below 50% in 16 of 19 cases. A mass cytometry investigation and subsequent analysis enabled us to discriminate brain tumor cells from contaminating leukocytes, whose proportions varied across the specimens. The addition of the viability marker cisplatin directly into the mass cytometry panel gave the means to selecting viable cells only for subsequent analyses. The proportion of non-viable cells was higher among tumor cells compared leukocytes. CONCLUSIONS: When the analysis of the tumor cell immunophenotype is performed with markers for determining viability, the expression of the investigated markers can be evaluated. Suitable markers can be selected by high-throughput methods, such as mass cytometry, and those that are diagnostically relevant can be investigated using flow cytometry, which is more flexible in terms of time.


Assuntos
Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/patologia , Biomarcadores Tumorais/metabolismo , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/cirurgia , Sobrevivência Celular , Cisplatino/metabolismo , Citometria de Fluxo , Humanos , Leucócitos/metabolismo , Leucócitos/patologia , Procedimentos Neurocirúrgicos/instrumentação , Análise de Célula Única , Terapia por Ultrassom/instrumentação
10.
J Neuroinflammation ; 16(1): 59, 2019 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-30857557

RESUMO

BACKGROUND: Long-term outcome in multiple sclerosis (MS) depends on early treatment. In patients with acute optic neuritis (ON), an early inflammatory event, we investigated markers in cerebrospinal fluid (CSF), which may predict a diagnosis of MS. METHODS: Forty patients with acute ON were recruited in a prospective population-based cohort with median 29 months (range 19-41) of follow-up. Paired CSF and serum samples were taken within 14 days (range 2-38), prior to treatment. Prospectively, 16/40 patients were by a uniform algorithm diagnosed with MS (MS-ON) and 24 patients continued to manifest isolated ON (ION) during follow-up. Levels of cytokines and neurofilament light chain (NF-L) were measured at the onset of acute ON and compared to healthy controls (HC). Significance levels were corrected for multiple comparisons ("q"). The predictive value of biomarkers was determined with multivariable prediction models using nomograms. RESULTS: CSF TNF-α, IL-10, and CXCL13 levels were increased in MS-ON compared to those in ION patients (q = 0.021, 0.004, and 0.0006, respectively). MS-ON patients had increased CSF pleocytosis, IgG indices, and oligoclonal bands (OCBs) compared to ION (q = 0.0007, q = 0.0058, and q = 0.0021, respectively). CSF levels of IL-10, TNF-a, IL-17A, and CXCL13 in MS-ON patients correlated with leukocyte counts (r > 0.69 and p < 0.002) and IgG index (r > 0.55, p < 0.037). CSF NF-L levels were increased in ON patients compared to those in HC (q = 0.0077). In MS-ON, a progressive increase in NF-L levels was observed at 7 to 14 days after disease onset (r = 0.73, p < 0.0065). Receiver-operating characteristic (ROC) curves for two multivariable prediction models were generated, with IL-10, CXCL13, and NF-L in one ("candidate") and IgG index, OCB, and leukocytes in another ("routine"). Area under the curve was 0.89 [95% CI 0.77-1] and 0.86 [0.74-0.98], respectively. Predictions of the risk of MS diagnosis were illustrated by two nomograms. CONCLUSIONS: CSF TNF-α, IL-10, CXCL13, and NF-L levels were associated with the development of MS, suggesting that the inflammatory and neurodegenerative processes occurred early. Based on subsequent diagnosis, we observed a high predictive value of routine and candidate biomarkers in CSF for the development of MS in acute ON. The nomogram predictions may be useful in the diagnostic work-up of MS.


Assuntos
Citocinas/líquido cefalorraquidiano , Progressão da Doença , Esclerose Múltipla/líquido cefalorraquidiano , Esclerose Múltipla/etiologia , Neurite Óptica/complicações , Adolescente , Adulto , Idoso , Quimiocinas CXC/líquido cefalorraquidiano , Estudos de Coortes , Planejamento em Saúde Comunitária , Feminino , Humanos , Interleucina-10/líquido cefalorraquidiano , Leucócitos/patologia , Masculino , Pessoa de Meia-Idade , Bandas Oligoclonais/líquido cefalorraquidiano , Valor Preditivo dos Testes , Curva ROC , Estatísticas não Paramétricas , Fator de Necrose Tumoral alfa/líquido cefalorraquidiano , Adulto Jovem
11.
Fish Shellfish Immunol ; 88: 259-265, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30716521

RESUMO

The pathogenesis of sepsis involves complex systems and multiple interrelationships between the host and pathogen producing high mortality rates in various animal species. In this study, hematological disturbances, innate immunity and survival during the septic process in Piaractus mesopotamicus inoculated with Aeromonas hydrophila were studied. For this aim, fish blood samples were taken from control and infected groups 1, 3, 6, and 9 h post-inoculation (HPI). Leukogram showed reduction in the number of leukocytes and thrombocytes, followed by cessation of leukocyte chemotaxis 6 HPI and severe morphological changes in leukocytes and erythrocytes. At 3 HPI production of reactive oxygen species increased and at 6 HPI decreased. There was no change in serum lysozyme concentration and lytic activity of the complement system, despite the progressive increase in serum lytic activity and bacterial agglutination. Finally, the changes in clinical signs due to aeromonosis and increasing septicemia resulted in a reduction in survival to 57.14% after 36 HPI. It was possible concluded that these hematological and immune are crucial event in the worsening of sepsis in P. mesopotamicus, and these findings are utility for diagnosing and understanding the pathophysiology sepsis in pacu induced by A. hydrophila.


Assuntos
Aeromonas hydrophila/fisiologia , Caraciformes/imunologia , Doenças dos Peixes/imunologia , Infecções por Bactérias Gram-Negativas/veterinária , Sepse/veterinária , Animais , Caraciformes/sangue , Caraciformes/microbiologia , Eritrócitos/patologia , Doenças dos Peixes/microbiologia , Infecções por Bactérias Gram-Negativas/imunologia , Infecções por Bactérias Gram-Negativas/mortalidade , Imunidade Inata , Leucócitos/patologia , Sepse/imunologia , Sepse/microbiologia , Sepse/mortalidade
12.
J Orthop Surg Res ; 14(1): 58, 2019 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-30782193

RESUMO

BACKGROUND: Singular traumatic insults, such as bone fracture, typically initiate an appropriate immune response necessary to restore the host to pre-insult homeostasis with limited damage to self. However, multiple concurrent insults, such as a combination of fracture, blunt force trauma, and burns (polytrauma), are clinically perceived to result in abnormal immune response leading to inadequate healing and resolution. To investigate this phenomenon, we created a model rat model of polytrauma. METHODS: To investigate relationship between polytrauma and delayed healing, we created a novel model of polytrauma in a rat which encompassed a 3-mm osteotomy, blunt chest trauma, and full-thickness scald burn. Healing outcomes were determined at 5 weeks where the degree of bone formation at the osteotomy site of polytrauma animals was compared to osteotomy only animals (OST). RESULTS: We observed significant differences in the bone volume fraction between polytrauma and OST animals indicating that polytrauma negatively effects wound healing. Polytrauma animals also displayed a significant decrease in their ability to return to pre-injury weight compared to osteotomy animals. Polytrauma animals also exhibited significantly altered gene expression in osteogenic pathways as well as the innate and adaptive immune response. Perturbed inflammation was observed in the polytrauma group compared to the osteotomy group as evidenced by significantly altered white blood cell (WBC) profiles and significantly elevated plasma high-mobility group box 1 protein (HMGB1) at 6 and 24 h post-trauma. Conversely, polytrauma animals exhibited significantly lower concentrations of plasma TNF-alpha (TNF-α) and interleukin 6 (IL-6) at 72 h post-injury compared to OST. CONCLUSIONS: Following polytrauma with burn injury, the local and systemic immune response is divergent from the immune response following a less severe singular injury (osteotomy). This altered immune response that follows was associated with a reduced capacity for wound healing.


Assuntos
Queimaduras/imunologia , Modelos Animais de Doenças , Consolidação da Fratura/imunologia , Leucócitos/imunologia , Traumatismo Múltiplo/imunologia , Traumatismos Torácicos/imunologia , Animais , Queimaduras/diagnóstico por imagem , Queimaduras/patologia , Inflamação/diagnóstico por imagem , Inflamação/imunologia , Inflamação/patologia , Cinética , Leucócitos/patologia , Masculino , Traumatismo Múltiplo/diagnóstico por imagem , Traumatismo Múltiplo/patologia , Ratos , Ratos Sprague-Dawley , Traumatismos Torácicos/diagnóstico por imagem , Traumatismos Torácicos/patologia , Ferimentos não Penetrantes/diagnóstico por imagem , Ferimentos não Penetrantes/imunologia , Ferimentos não Penetrantes/patologia
13.
J Neuroinflammation ; 16(1): 37, 2019 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-30764852

RESUMO

BACKGROUND: High white blood cell (WBC) count and high blood glucose level are risk factors for mortality and pneumonia after acute ischemic stroke (AIS). We investigated the combined effect of high WBC count and high blood glucose level on hospital admission and in-hospital mortality and pneumonia in acute AIS patients. METHODS: A total of 3124 AIS patients enrolled from December 2013 to May 2014 across 22 hospitals in Suzhou city were included in the present study. We divided patients into four groups according to their level of WBC count and blood glucose: NWNG (normal WBC count and normal glucose), NWHG (normal WBC count and higher glucose), HWNG (higher WBC count and normal glucose), and HWHG (higher WBC count and higher glucose). Cox proportional hazard model and logistic regression model were used to estimate the combined effect of WBC count and blood glucose on all-cause in-hospital mortality and pneumonia in AIS patients. RESULTS: HWHG was associated with a 2.22-fold increase in the risk of in-hospital mortality in comparison to NWNG (adjusted hazard ratio [HR] 2.22; 95% confidence interval [CI], 1.21-4.07; P trend = 0.003). The risk of pneumonia was significantly higher in patients with HWHG compared to those with NWNG (adjusted odds ratio [OR] 2.61; 95% CI, 1.66-4.10; P trend < 0.001). The C-statistic for the combined WBC count and blood glucose was higher than WBC count or blood glucose alone for prediction of in-hospital mortality and pneumonia (all p < 0.01). CONCLUSIONS: High WBC count combined with high blood glucose level at admission was independently associated with in-hospital mortality and pneumonia in AIS patients. Moreover, the combination of WBC count and blood glucose level appeared to be a better predictor than WBC count or blood glucose alone.


Assuntos
Glicemia/metabolismo , Hospitalização , Contagem de Leucócitos/métodos , Leucócitos/patologia , Acidente Vascular Cerebral/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Isquemia Encefálica/sangue , Isquemia Encefálica/complicações , Feminino , Seguimentos , Mortalidade Hospitalar , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Curva ROC , Estudos Retrospectivos , Fatores de Risco , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/mortalidade , Acidente Vascular Cerebral/terapia
14.
Radiat Oncol ; 14(1): 23, 2019 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-30700317

RESUMO

BACKGROUND: To compare WBC counts during treatment of localized prostate cancer with either conventionally fractionated (CF) or moderately hypofractionated (HYPO) radiotherapy. METHODS: Weekly blood test results were extracted from the charts of patients treated within a phase III study comparing HYPO to CF. In order to compare WBC counts at the same nominal dose in both arms and thus to tease out the effect of fractionation, for each recorded WBC value the corresponding cumulative total dose was extracted as well. WBC counts were binned according to percentiles of the delivered dose and three dose levels were identified at median doses of 16, 34.1 and 52 Gy, respectively. A General Linear Model based on mixed design Analysis Of Variance (ANOVA) was used to test variation of WBC counts between the two treatment arms. RESULTS: Out of 168 randomized patients, 140 (83.3%) had at least one observation for each one of the selected dose levels and were included in the analysis. Mean counts were lower in the CF than the HYPO arm at all selected dose levels, reaching a statistically significant difference at dose level #3 (5397/mm3 vs 6038/mm3 for CF and HYPO, respectively, p = 0.004). The GLM model confirms that the impact of dose on WBC counts is significantly lower in the HYPO arm over the CF one (Greenhouse-Geisser test, p = 0.04). Interestingly, while WBC counts tend to drop throughout all dose levels in the CF arm, this is the case only in the earlier part of treatment in the HYPO arm. CONCLUSION: This secondary analysis of a phase III study shows that dose fractionation is correlated to WBC drop during treatment of localized prostate cancer, favoring HYPO over CF.


Assuntos
Leucócitos/patologia , Neoplasias da Próstata/radioterapia , Hipofracionamento da Dose de Radiação , Lesões por Radiação/patologia , Radioterapia/efeitos adversos , Humanos , Leucócitos/efeitos da radiação , Masculino , Prognóstico , Neoplasias da Próstata/sangue , Neoplasias da Próstata/patologia , Lesões por Radiação/etiologia
15.
Cells ; 8(2)2019 02 18.
Artigo em Inglês | MEDLINE | ID: mdl-30781683

RESUMO

According to estimates from the International Agency for Research on Cancer, by the year 2030 there will be 22 million new cancer cases and 13 million deaths per year. The main cause of cancer mortality is not the primary tumor itself but metastasis to distant organs and tissues, yet the mechanisms of this process remain poorly understood. Leukocyte⁻cancer cell fusion and hybrid formation as an initiator of metastasis was proposed more than a century ago by the German pathologist Prof. Otto Aichel. This proposal has since been confirmed in more than 50 animal models and more recently in one patient with renal cell carcinoma and two patients with malignant melanoma. Leukocyte⁻tumor cell fusion provides a unifying explanation for metastasis. While primary tumors arise in a wide variety of tissues representing not a single disease but many different diseases, metastatic cancer may be only one disease arising from a common, nonmutational event: Fusion of primary tumor cells with leukocytes. From the findings to date, it would appear that such hybrid formation is a major pathway for metastasis. Studies on the mechanisms involved could uncover new targets for therapeutic intervention.


Assuntos
Leucócitos/patologia , Neoplasias/patologia , Animais , Fusão Celular , Humanos , Macrófagos/patologia , Repetições de Microssatélites/genética , Modelos Biológicos
16.
PLoS One ; 14(2): e0211745, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30730943

RESUMO

BACKGROUND: Prior studies have shown that AHRR (cg05575921) hypomethylation may be a marker of smoking, lung cancer risk and potentially lung cancer survival (in some lung cancer subtypes). It is unknown if AHRR (cg05575921) hypomethylation is associated with reduced survival among lung cancer patients. METHODS: In bisulfite treated leukocyte DNA from 465 lung cancer patients from the Copenhagen prospective lung cancer study, we measured AHRR (cg05575921) methylation. 380 died during max follow-up of 4.4 years. Cox proportional hazard models were used to analyze survival as a function of AHRR (cg05575921) methylation. RESULTS: We observed the expected inverse correlation between cumulative smoking and AHRR methylation, as methylation (%) decreased (Coefficient -0.03; 95% confidence interval, -0.04- -0.02, p = 8.6x10-15) for every pack-year. Cumulative smoking > 60 pack-years was associated with reduced survival (hazard ratio and 95% confidence interval 1.48; 1.05-2.09), however, AHRR (cg05575921) methylation was not associated with survival when adjusted for sex, body mass index, smoking status, ethnicity, performance status, TNM Classification, and histology type of lung cancer. CONCLUSION: AHRR (cg05575921) methylation is linked to smoking but does not provide independent prognostic information in lung cancer patients.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/sangue , Biomarcadores Tumorais/sangue , Metilação de DNA , DNA de Neoplasias/sangue , Leucócitos/metabolismo , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/mortalidade , Proteínas de Neoplasias/sangue , Proteínas Repressoras/sangue , Idoso , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Biomarcadores Tumorais/genética , DNA de Neoplasias/genética , Intervalo Livre de Doença , Feminino , Humanos , Leucócitos/patologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Proteínas de Neoplasias/genética , Estudos Prospectivos , Proteínas Repressoras/genética , Fumar/sangue , Fumar/genética , Fumar/mortalidade , Taxa de Sobrevida
17.
Int J Lab Hematol ; 41(3): 338-344, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30742354

RESUMO

INTRODUCTION: The aim of the present study was to evaluate the diagnostic ability of blast flags generated by Sysmex instruments (XE/XN) by comparing with immunophenotyping by flow cytometry (IFCM). Additionally, the ability of manual microscopy and CellaVision DM96 (pre- and reclassification) to predict the presence of "true" blasts was investigated. METHODS: Blood samples (n = 240) with suspect pathology flags reported by the XE were collected from the daily workload and examined by the XN, by manual microscopy, by CellaVision DM96 and by IFCM (CytoDiff Panel). RESULTS: The ROC analysis for blasts showed an area under the curve of 0.64 ("Blasts?") (XE), 0.57 ("Blasts/Abn Lympho?") (XN), 0.75 (CellaVision preclassification procedure), 0.78 (CellaVision reclassification procedure), and 0.81 (manual microscopy). The sensitivity of blast detection varied between the methods from 0.41 (XE) to 0.90 (XN), and the specificity varied from 0.17 (XN) to 0.95 (CellaVision reclassification). CONCLUSIONS: The CellaVision reclassification procedure has a diagnostic ability for predicting blasts close to that of manual microscopy. The blood smear methods show a notable number of false negative results. The Sysmex XN reported a higher rate of true positive blast flags than the XE. Taken together, the CytoDiff method could be a useful alternative to smear examination to correctly identify blasts.


Assuntos
Células Sanguíneas/patologia , Citometria de Fluxo , Microscopia , Contagem de Células Sanguíneas/métodos , Contagem de Células Sanguíneas/normas , Citometria de Fluxo/métodos , Citometria de Fluxo/normas , Humanos , Imunofenotipagem , Leucócitos/patologia , Microscopia/métodos , Microscopia/normas , Curva ROC
18.
J Neurooncol ; 142(3): 479-487, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30796745

RESUMO

PURPOSE: Telomere length-associated SNPs have been associated with incidence and survival rates for malignant brain tumors such as glioma. Here, we study the influence of genetically determined lymphocyte telomere length (LTL) by comparing telomerase associated SNPs between the most common non-malignant brain tumor, i.e. meningioma, and healthy controls. METHODS/PATIENTS: One thousand fifty-three (1053) surgically treated meningioma patients and 4437 controls of Western European ancestry were included. Germline DNA was genotyped for 8 SNPs previously significantly associated with LTL. Genotypically-estimated LTL was then calculated by summing each SNP's genotypically-specified telomere length increase in base pairs (bp) for each person. Odds ratios for genotypically-estimated LTL in meningioma cases and controls were evaluated using logistic regression with the first two ancestral principal components and sex as covariates. RESULTS: Three out of the eight evaluated LTL SNPs were significantly associated with increased meningioma risk (rs10936599: OR 1.14, 95% CI 1.01-1.28, rs2736100: OR 1.13, 95% CI 1.03-1.25, rs9420907: OR 1.22, 95% CI 1.07-1.39). Only rs9420907 remained significant after correction for multiple testing. Average genotypically-estimated LTL was significantly longer for those with meningioma compared to controls [mean cases: 560.2 bp (standard error (SE): 4.05 bp), mean controls: 541.5 bp (SE: 2.02 bp), logistic regression p value = 2.13 × 10-5]. CONCLUSION: Increased genotypically-estimated LTL was significantly associated with increased meningioma risk. A role for telomere length in the pathophysiology of meningioma is novel, and could lead to new insights on the etiology of meningioma.


Assuntos
Leucócitos/patologia , Neoplasias Meníngeas/etiologia , Meningioma/etiologia , Polimorfismo de Nucleotídeo Único , Homeostase do Telômero , Estudos de Casos e Controles , Feminino , Seguimentos , Genótipo , Humanos , Leucócitos/metabolismo , Masculino , Neoplasias Meníngeas/patologia , Meningioma/patologia , Prognóstico , Fatores de Risco
19.
BMC Med ; 17(1): 27, 2019 02 06.
Artigo em Inglês | MEDLINE | ID: mdl-30722777

RESUMO

BACKGROUND: Newborn telomere length (TL) is considered a potential marker for future disease and lifelong health, but few epidemiological studies have examined the determinants of TL in early life. The study aim was to investigate whether there is an association between prenatal cadmium exposure and relative cord blood TL in Chinese newborns. METHODS: Participants were 410 mother-newborn pairs drawn from a prospective birth cohort study conducted in Wuhan, China, between November 2013 and March 2015. Urine samples were collected from pregnant women during their period of institutional delivery. Urinary cadmium concentrations were measured by inductively coupled plasma mass spectrometry. The real-time quantitative polymerase chain reaction detection was used to measure relative TL using genomic DNA isolated from umbilical cord blood leukocytes. Multivariate linear regression models were used to estimate the effect of prenatal urinary cadmium concentration on relative cord blood TL. RESULTS: The geometric mean of maternal urinary cadmium concentration was 0.68 µg/g creatinine. In the multivariate-adjusted linear regression model, per doubling of maternal urinary cadmium concentration was associated with 6.83% (95% CI - 11.44%, - 1.97%; P = 0.006) shorter relative cord blood TL. Stratified analyses indicated that the inverse association between prenatal urinary cadmium and newborn relative TL was more pronounced among female infants and mothers < 29 years, while there were no significant effect modification according to infant sex (P for interaction = 0.907) and maternal age (P for interaction = 0.797). CONCLUSIONS: The findings indicated that increased maternal urinary cadmium was associated with shortened relative cord blood TL. The results provide more evidence of the negative effects of environmental cadmium exposure and suggest that accelerated aging or cadmium-related diseases may begin in early life.


Assuntos
Cádmio/efeitos adversos , Efeitos Tardios da Exposição Pré-Natal/patologia , Telômero/efeitos dos fármacos , Telômero/patologia , Adulto , Cádmio/urina , China , Estudos de Coortes , Feminino , Sangue Fetal/efeitos dos fármacos , Humanos , Recém-Nascido , Leucócitos/patologia , Modelos Lineares , Masculino , Mães , Gravidez , Efeitos Tardios da Exposição Pré-Natal/sangue , Estudos Prospectivos
20.
Artigo em Inglês | MEDLINE | ID: mdl-30595207

RESUMO

Bromide (Br-) is a bromine atom with a negative charge which is released mainly in the production of pesticides and flame retardants. It is also found naturally in seawater. Br¯ has been associated with many detrimental effects such as respiratory problems, gastric hemorrhages, and dermal burns. The aim of the study was to monitor serum bromide in humans and to correlate its level with genotoxicity and apoptosis in human. The study utilized comet assay, to measure DNA damage in peripheral leukocytes (i.e. T%DNA), enzyme-linked immunosorbent assay were used to determine fortilin level as an apoptosis marker, and spectrophotometry to measure serum Br¯ in two populations at the Dead Sea area, which are located close to and far from a local bromine factory: Ghor As-safi and Deir Alla, respectively. The biomarkers were compared with the correlating serum Br¯. A total of 397 individuals were involved in the study. The serum Br- and the genotoxicity biomarker were significantly higher (p < 0.001) in Ghor As-safi than in Deir Alla. In contrast, serum fortilin did not differ significantly between the two regions (p > 0.05). T%DNA was significantly correlated (r = 0.867, p < 0.01) to serum Br¯. In conclusion, residing near a bromide source site is increasing the bromide body burden, and enhancing genotoxicity with no detectible apoptosis. Furthermore, the selected biomarkers could serve as tools to assess the toxicity of bromide as a consequence of environmental exposure.


Assuntos
Apoptose/efeitos dos fármacos , Biomarcadores Tumorais/genética , Brometos/sangue , Dano ao DNA/efeitos dos fármacos , Exposição Ambiental/efeitos adversos , Leucócitos/patologia , Poluentes Químicos da Água/sangue , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/análise , Brometos/efeitos adversos , Criança , Pré-Escolar , Ensaio Cometa , Feminino , Humanos , Jordânia , Leucócitos/citologia , Masculino , Pessoa de Meia-Idade , Testes de Mutagenicidade , Água do Mar/química , Poluentes Químicos da Água/efeitos adversos , Adulto Jovem
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA