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OBJECTIVE: Previous preliminary clinical trials have confirmed that edoxaban can be efficacious for venous thromboembolism (VTE). This meta-analysis was considered to evaluate edoxaban's short-term efficacy and safety for venous thromboembolism after arthroplasty. MATERIALS AND METHODS: A comprehensive search was performed in these databases: PubMed, MEDLINE, Web of Science, and EMBASE on March 2022. All eligible trials should be randomized controlled trials (RCTs) when evaluating short-term efficacy and safety outcomes of edoxaban for VTE after total hip or knee arthroplasty. RESULTS: Nine RCTs with 4274 patients were involved in this meta-analysis. Edoxaban in the VTE group prevented the incidence of VTE and indicated valuable clinical efficacy. The incidence of adverse events (AEs) and adverse drug reactions (ADRs) in the edoxaban group was decreased than that in other groups. Edoxaban increased the incidence of all bleeding events. However, in the edoxaban group and other groups, there was no statistical difference between major bleeding events and clinically relevant non-major or minor bleeding events. Edoxaban subgroups included edoxaban 15 mg, edoxaban 30 mg and edoxaban 60 mg prevented the incidence of VTE. Edoxaban 30 mg and 60 mg group increased the risk of all bleeding events. Edoxaban 30 mg can increase the incidence of major bleeding events. There was no difference in clinically relevant non-major or minor bleeding events. Edoxaban 30 mg can decrease the incidence of AEs. CONCLUSIONS: Edoxaban was an efficacious and safe option to prevent and treat VTE in patients undergoing arthroplasty. However, we need further trials to explore edoxaban's long-term efficacy and safety.
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Artroplastia do Joelho , Tromboembolia Venosa , Anticoagulantes/uso terapêutico , Artroplastia do Joelho/efeitos adversos , Hemorragia/etiologia , Humanos , Piridinas , Tiazóis , Tromboembolia Venosa/tratamento farmacológico , Tromboembolia Venosa/etiologia , Tromboembolia Venosa/prevenção & controleRESUMO
Objective: To investigate the clinical features of JAK2V617F gene mutation and non-mutation in patients with Budd-Chiari syndrome (BCS). Methods: 17 and 127 BCS cases with JAK2V617F gene mutation (mutation group) and non-gene mutation (non-mutation group) who were continuously treated with interventional therapy between January 2016 to December 2020 in the Affiliated Hospital of Xuzhou Medical University were selected as the research object for a comparative study. The hospitalization and follow-up data of the two groups were analyzed retrospectively, and the deadline for follow-up was June 2021. Quantitative data group differences were analyzed using the independent sample t-test and Wilcoxon rank sum test. Qualitative data group differences were analyzed with χ2 test or Fisher's exact test. Mann-Whitney U test was used to analyze the differences between groups in rank data. Kaplan-Meier method was used to calculate the patient survival and recurrence rate. Results: Age [(35.41±17.10) years vs. (50.09±14.16) years, t=3.915, P<0.001], time of onset (median duration: 3 months vs. 12 months), and the cumulative survival rate (65.5% vs 95.1%; χ2=5.21, P=0.022) were lower in mutation than non-mutation group. Aaspartate aminotransferase, alanine aminotransferase, prothrombin time, Child-Pugh score, Rotterdam score, Model for End-stage Liver Disease score, hepatic vein thrombosis incidence, and the cumulative recurrence rate after intervention were higher in mutation than non-mutation group. The above all indexes had statistically significant differences (P<0.05) between the groups. Conclusion: Younger age, acute onset, severe liver injury, high incidence of hepatic vein thrombosis, and poor prognosis are the features of patients with BCS with JAK2V617F gene mutation than non-mutation.
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Síndrome de Budd-Chiari , Doença Hepática Terminal , Janus Quinase 2 , Adolescente , Adulto , Humanos , Pessoa de Meia-Idade , Adulto Jovem , Síndrome de Budd-Chiari/genética , Síndrome de Budd-Chiari/terapia , Estudos Retrospectivos , Índice de Gravidade de Doença , Janus Quinase 2/genética , MutaçãoRESUMO
Objective: To investigate the efficacy of transjugular intrahepatic portosystemic shunt (TIPS) using viabahn stent in patients with Budd-Chiari syndrome (BCS) with extensive hepatic vein occlusion. Methods: Technical success rates, portal pressure gradient (PPG), complications and shunt patency rate of 25 cases with BCS with extensive hepatic vein occlusion treated by TIPS using viabahn stent were retrospectively analyzed. Color Doppler ultrasound was used for postoperative follow-up. Patency rates were evaluated by Kaplan-Meier curve. Results: The technical success rate of TIPS was 100%. Mean PPG decreased from (22.7 ± 6.2) mmHg preoperatively to (9.7 ± 2.6) mmHg postoperatively (t = 9.58, P < 0.05). Hepatic encephalopathy incidence was 8.0% (2/25), and there were no complications such as intra-abdominal hemorrhage. Twenty-five cases were followed up for 1 to 39 ( mean 19.0 ± 11.9) months, and one patient died of liver failure three months after interventional treatment. The primary patency rates at 1, 2, and 3 years after interventional treatment were 91.3%, 91.3%, and 78.2%, respectively, while the repatency rates were 100%, 92.9%, and 92.9%, respectively. Conclusion: TIPS using viabahn stent can bring better short-term and mid-term curative efficacy in treatment of BCS with extensive hepatic vein occlusion.
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Síndrome de Budd-Chiari , Derivação Portossistêmica Transjugular Intra-Hepática , Síndrome de Budd-Chiari/cirurgia , Veias Hepáticas , Humanos , Estudos Retrospectivos , Stents , Resultado do TratamentoRESUMO
IgG4-related sclerosing cholangitis (IgG4-SC) is characterized by biliary strictures and obstructive jaundice.Elevated levels of serum IgG4 and a multifocal IgG4-rich lymphoplasmacytic infiltration of affected organs are also the characteristics of IgG4-SC. Prednisone is recommended in the initial treatment of IgG4-SC. The differential diagnosis between IgG4-SC and cholangiocarcinoma is not easy. Comprehensively collection of medical history, paying attention to other organs involvement, and getting the pathologic diagnosis are important for diagnosis of this disease. In order to prevent misdiagnosis we should learn more about IgG4-SC. On the other hand, if we can not differentiate IgG4-SC and cholangiocarcinoma, operation may be recommended.
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Colangite Esclerosante/diagnóstico , Colangite Esclerosante/terapia , Doença Relacionada a Imunoglobulina G4/diagnóstico , Doença Relacionada a Imunoglobulina G4/terapia , Adulto , Neoplasias dos Ductos Biliares/diagnóstico , Colangiocarcinoma/diagnóstico , Colangite Esclerosante/sangue , Colangite Esclerosante/imunologia , Diagnóstico Diferencial , Humanos , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Doença Relacionada a Imunoglobulina G4/sangue , Doença Relacionada a Imunoglobulina G4/imunologiaRESUMO
We systematically investigate the wave propagation, plasticity and void collapse, as well as the effects of porosity, specific surface area and impact velocity, in a set of open-cell nanoporous Ta, during shock compression, via performing large-scale non-equilibrium molecular dynamics simulations. The shock wave propagation presents an impedance, sensitive to porosity, but not to specific surface area. Such surprising phenomena are due to the similar sensitivities in density and stress variations to porosity or specific surface area. Upon impact, shock front shapes change from ramped to steep ones, with increasing porosity, specific surface area or impact velocity, owing to the transition from the heterogeneous to homogeneous plasticity along transverse directions. This transition of plasticity arises by (i) the strong impedance on large deformation bands as porosity increases; and (ii) the transition from deformation twinning to dislocation slips, and to amorphization, as the specific surface area or impact velocity increases. Shock-induced plasticity, including their nucleation, growth and interactions, also facilitates the collapse of voids.
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Objective: To study the application of intravoxel incoherent motion (IVIM) quantitative index combined with time-signal intensity curve (TIC) of dynamic contrast enhanced 3.0T magnetic resonance in the early precise diagnosis of residual lesions in non-small cell lung cancer (NSCLC) after argon-helium cryosurgery. Methods: One hundred NSCLC patients who underwent argon-helium cryosurgery were collected and divided into the residual group (21 cases) and non-residual group (79 cases) according to the result of needle biopsy and follow-up. The apparent diffusion coefficient (ADC), slow apparent diffusion coefficient (sADC), fast apparent diffusion coefficient (fADC), fraction of fast apparent diffusion coefficient (ffADC) and TIC type of IVIM quantitative index between the two groups were compared at 7 days and 1 month after argon-helium cryosurgery, respectively. The diagnosis performance of each quantitative index was analyzed by receiver operating characteristic (ROC) curve and the best cut-off value was computed. The specificity and sensitivity of TIC types were calculated as diagnostic criteria. The diagnosis performance of IVIM quantitative index combined with TIC type was evaluated and compared with the conventional MRI and DWI. Results: The differences of ADC, sADC and ffADC at 7 days and 1 month after argon-helium cryosurgery between the residual group and non-residual group were statistically significant (all P<0.05), in which the diagnosis performance of sADC and ffADC were better. The AUC of sADC and ffADC at 7 days after argon-helium cryosurgery were 0.861 and 0.895, the sensitivity were 81.0% and 90.5%, and the specificity were 77.2% and 73.4%, respectively. The AUC of sADC and ffADC at 1 month after argon-helium cryosurgery were 0.836 and 0.883, the sensitivity were 100.0% and 76.2%, and the specificity were 58.2% and 89.9%, respectively. The diagnosis performance of TIC type â ¡&â ¢ was best. The sensitivity and specificity were 80.9% and 58.2% at 7 days after treatment, 85.7% and 62.0% at 1 month after treatment, respectively. At 7 days after treatment, the sensitivity and specificity of IVIM combined with TIC were 97.5% and 85.7%, while at 1 month after treatment, the sensitivity and specificity of IVIM combined with TIC were 97.5% and 90.5%, respectively. The diagnosis performance of IVIM quantitative index combined with TIC type was better than conventional MRI and DWI. Conclusion: The combination of IVIM quantitative index and TIC type can be used in the early diagnosis of residual lesions after argon-helium cryosurgery for NSCLC, whose effect is better than conventional MRI and DWI.
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Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Criocirurgia/métodos , Imagem de Difusão por Ressonância Magnética/métodos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/cirurgia , Argônio , Meios de Contraste , Detecção Precoce de Câncer/métodos , Hélio , Humanos , Neoplasia Residual/diagnóstico por imagem , Curva ROC , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
Objective: To investigate the prognostic factors of primary liver cancer treated with transcatheter arterial chemoembolization (TACE) combined with radiofrequency ablation (RFA), and then to establish a prognostic model. Methods: Clinicopathological and follow-up data of 145 patients who underwent TACE combined with RFA from January 2010 to December 2012 were retrospectively analyzed. Univariate and multivariate survival analyses were performed using the Cox proportional hazards model, and the prognostic model was established. Results: The 1, 2, and 3-year survival rates were 92.6%, 81.4% and 66.2%, respectively. The 3-year recurrence and metastasis rate was 64.8%.Multivariate analysis showed that female cases and higher serum albumin levels were the protective factors for the 3-year overall and relapse-free survival of patients(P<0.05 for all). High levels of alpha-fetoprotein (AFP), alanine aminotransferase (ALT), total bilirubin (TBIL), portal vein thrombosis and higher Child Pugh stages were the independent risk factors for the 3-year overall survival(P<0.05 for all). High levels of AFP, TBIL, portal vein thrombosis and advanced stages of BCLC staging (B and C) were the independent risk factors for tumor recurrence and metastasis(P<0.05 for all). The predictive model established based on the multivariate analysis showed good sensitivity and specificity. The area under ROC curve were higher than 0.90. Conclusions: The prognosis of liver cancer patients treated with TACE combined with RFA is affected by various clinicopathological factors. The systematic evaluation of the relevant factors before treatment may help to select proper patients and improve prognosis.
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Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/cirurgia , Ablação por Cateter , Quimioembolização Terapêutica , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/cirurgia , Idoso , Alanina Transaminase/sangue , Artérias , Bilirrubina/sangue , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/mortalidade , Terapia Combinada/métodos , Feminino , Humanos , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Albumina Sérica/análise , Taxa de Sobrevida , Fatores de Tempo , Trombose Venosa/mortalidade , alfa-Fetoproteínas/análiseRESUMO
Objective: To initially explore MRI features and its changing trends including of lung tumors after Argon-Helium cryoablation therapy, and enhance the recognition of MR findings of lung tumors postcryoablation. Methods: Twenty-three cases of patients with twenty six nodules of pulmonary malignance who received Argon-Helium cryoablation therapy in Henan Cancer Hospital from July 2014 to January 2016 were enrolled.All patients underwent unenhanced and dynamic contrast-enhanced MRI scans at pre-and 1-day, 1-week, 1-, 3-, 6-, 12-month postcryoablation. Two radiologists independently reviewed MRI images, signal intensity in the ablated zone on T1WI and T2WI were assessed by a 5-point scale.The changing trends of size and signal intensity with time were showed by time-maximum diameter and time-score curve.Time-signal intensity curves based on dynamic enhanced sequence were also performed. Results: Typical MRI findings includes: heterogeneous signal intensity on both T1WI and T2WI at 1-day postcryoablation(26/26, 100%). Hyper-intense on T1WI(22/26, 84.6%) and T2WI(17/26, 65.4%) with a hypo-intense rim at 1-week postcryoablation.Decreasing signal intensity on T1WI(17/26, 65.4%) and increasing signal intensity on T2WI(22/26, 84.6%) at 1-month.Signal intensity declined to the level of muscle on both T1WI(18/26, 69.2%) and T2WI(19/26, 73.1%) at 3-month, nineteen ablated zone turned into patchy shape(19/26, 73.1%). The maximum diameter was largest at 1-day and gradually shrunk with time. The mean score value toped at 1-week and gradually decreased. A straight line type without definite enhancement was found from 1-day to 1-month postcryoablation, an inflow curve with a mild delayed enhancement was seen from 3- to 12- month. Totally 4 recurrence (4/26, 15.4%) all occurred at 3-month and were lack of a complete hypo-intense rim at 1-week postcryoablation. Conclusion: MRI findings of lung tumors postcryoablation are characteristic, a complete hypo-intense rim at 1-week is helpful to determine further recurrence, 1-week to 3-month is an important period to observe significant change of the ablation zone, MRI is valuable in identifying the ablation zone and can reflect its evolution with time.
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Neoplasias Pulmonares , Imageamento por Ressonância Magnética , Criocirurgia , Humanos , RecidivaRESUMO
AIM: To determinate the RPA1 expression in esophageal carcinoma and the paired tumor-adjacent tissue, and to explore the influence of RPA1 on radiosensitivity of esophageal carcinoma TE-1 cells. METHODS: Firstly, the RPA1 expression of 40 cases esophageal carcinoma and their adjacent tissues were detected by immunohistochemistry. Secondly, The esophageal carcinoma cell subline-radiation resistance model (TE-1R) was constructed by radiation-induction, the RPA1 expression and proliferation activity of TE-1 and TE-1R cells were detected by Western blot and MTT assay respectively. After radiation, the expression of RPA1 and cell apoptosis were detected by Western blot and FACS respectively. Cell clone formation and survival rate were detected by clonogenic assay. Thirdly, Inhibiting RPA1 expression by siRNA in TE-1 cells, the expression of RPA1 was detected by RT-PCR and Western blot, Cell proliferation inhibition ratio and cell apoptosis after radiation were detected by MTT assay and FACS respectively. RESULTS: The RPA1 expression in esophageal carcinoma was significantly higher than that in the tumor-adjacent tissues, which was associated with tumor invasion and lymph node metastasis. The RPA1 expression in TE-1R cells was higher than that in TE-1 cells, while the proliferation activity of TE-1R cells was lower than that of TE-1 cells, and the apoptosis rate of TE-1R cells after radiation was less than that of TE-1 cells. In addtion, the clone formation and survival rate of TE-1R cells were higher than that of TE-1 cells. Moreover, inhibiting RPA1 expression by siRNA-RPA1 could promoted proliferation inhibition ratio and apoptosis rate of TE-1 cells after radiation. CONCLUSION: The over-expression of RPA1 in esophageal carcinoma was related with progression and metastasis. Moreover, radiation induced the excessive expression RPA1 in TE-1 cells, and the radiosensitivity of TE-1R cells was less than that of TE-1 cells. Furthermore, inhibiting RPA1 expression could increase radiosensitivity of TE-1 cells. Overall, RPA1 could influence radiosensitivity and might be one important mechanism of radiation resistance in TE-1 cells.
Assuntos
Neoplasias Esofágicas/metabolismo , Tolerância a Radiação , Proteína de Replicação A/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Apoptose , Linhagem Celular Tumoral , Proliferação de Células , Sobrevivência Celular , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/radioterapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , RNA Interferente Pequeno/genéticaRESUMO
OBJECTIVE: This study analyzed a relationship between prenatal mood states and serologic evidence of immune response to Toxoplasma gondii. A secondary aim was to determine whether thyroid peroxidase autoantibody status was related to T gondii status. STUDY DESIGN: Pregnant women (n = 414) were measured at 16-25 weeks' gestation with demographic and mood questionnaires and a blood draw. All plasma samples were analyzed for thyroid peroxidase and T gondii immunoglobulin G, tryptophan, kynurenine, and neopterin. T gondii serotypes were also measured in the women who were T gondii positive. Cytokines were available on a subset (n = 142). RESULTS: Women with serologic evidence of exposure to T gondii (n = 44) showed positive correlations between immunoglobulin G levels and the Profile of Mood States depression and anxiety subscales. Plasma tumor necrosis factor-α was higher in women who were positive for T gondii. Serotypes were type I (27%), type II (31%), and unclassified (42%, which shows intermediate levels of reactivity). The depression and anxiety scores were highest in type I, but this was not significant. The Profile of Mood States vigor score was lowest in type II, compared with the type I or unclassified groups. CONCLUSION: Higher T gondii immunoglobulin G titers in infected women were related to anxiety and depression during pregnancy. Subclinical reactivation of T gondii or immune responses to T gondii may worsen mood in pregnant women.
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Anticorpos Antiprotozoários/sangue , Ansiedade/psicologia , Depressão/psicologia , Complicações Parasitárias na Gravidez/psicologia , Complicações na Gravidez/psicologia , Toxoplasma/imunologia , Toxoplasmose/psicologia , Adulto , Ansiedade/sangue , Ansiedade/imunologia , Depressão/sangue , Depressão/imunologia , Feminino , Humanos , Gravidez , Complicações na Gravidez/sangue , Complicações na Gravidez/imunologia , Complicações Parasitárias na Gravidez/sangue , Complicações Parasitárias na Gravidez/imunologia , Inquéritos e Questionários , Toxoplasmose/sangue , Toxoplasmose/imunologiaRESUMO
The genetic characterization of Trichomonas vaginalis (Protista: Trichomonadidae), the causative agent of trichomoniasis in humans, is central to understanding the epidemiology, treatment, drug resistance, and virulence as well as the diagnosis and control of this parasite. Various molecular approaches, including DNA fingerprinting, have been employed for this purpose, and random amplification of polymorphic DNA (RAPD) continues to be utilized. However, little attention has been paid to the fact that some T. vaginalis populations can harbor symbiotic Mycoplasma hominis and/or other agents, which could cause artifacts in the RAPD results. In the present study, we demonstrate clearly that the presence of M. hominis from T. vaginalis isolates impacts significantly on RAPD results and on the subsequent analyses and interpretation of data sets. Moreover, symbiotic M. hominis displays an isolate-to-isolate variability in RAPD profile before elimination, suggesting a variability of M. hominis infection.
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Impressões Digitais de DNA/métodos , Erros de Diagnóstico , Mycoplasma hominis/isolamento & purificação , Simbiose , Trichomonas vaginalis/genética , Trichomonas vaginalis/microbiologia , Animais , DNA de Protozoário/análise , Mycoplasma hominis/classificação , Mycoplasma hominis/genética , Reação em Cadeia da Polimerase , Técnica de Amplificação ao Acaso de DNA Polimórfico , Trichomonas vaginalis/classificação , Trichomonas vaginalis/isolamento & purificaçãoRESUMO
Fourteen of 28 Trichomonas vaginalis isolates collected from patients in Guangzhou, China from 2003 to 2004 were found to be naturally infected with Mycoplasma hominis, as determined by PCR using specific primers. In vitro metronidazole sensitivity assay of the 28 isolates revealed four displaying low susceptibility [minimum lethal concentration (MLC)= approximately 13-25 microg/ml] and another four displaying high resistance (MLC=50-100 microg/ml). The overwhelming majority of these resistant isolates (7/8) were mycoplasma-infected. The mean of MLCs of mycoplasma-infected isolates is approximately 10-fold higher than the mean of noninfected isolates (p=0.029). Sequence analyses of PCR-amplified small subunit-large subunit rRNA interspacer regions (ITS1/5.8S/ITS2) revealed that 23 of the 28 samples are identical, the remaining five being separable into two groups, each with a single point mutation. These internal transcribed spacer sequence variants are associated neither with mycoplasma infection nor with drug resistance. In contrast, random amplified polymorphic DNA analyses of DNAs using 10 different primers showed that the drug-resistant isolates are clustered together in association with mycoplasma infection, albeit more loosely. Taken together, the results obtained from this study suggest that in vitro metronidazole resistance of T. vaginalis is related to mycoplasma infection of this protozoan.
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Metronidazol/farmacologia , Mycoplasma hominis/fisiologia , Trichomonas vaginalis/microbiologia , Animais , China , Primers do DNA , DNA Bacteriano/genética , Farmacorresistência Bacteriana , Humanos , Testes de Sensibilidade Microbiana , Mycoplasma hominis/efeitos dos fármacos , Filogenia , Reação em Cadeia da Polimerase , Simbiose , Trichomonas vaginalis/classificação , Trichomonas vaginalis/isolamento & purificaçãoRESUMO
AIMS: It is still not clear whether oval cells demonstrate diverse morphology, immunophenotype or quantity in different human liver diseases. The aim of this study was to investigate these differences in hepatitis B virus (HBV)-positive and hepatitis C virus (HCV)-positive human liver cirrhosis (HLC). METHODS AND RESULTS: Thirty-eight cases of HBV+ HLC and 32 cases of HCV+ HLC were investigated by light microscopy and immunohistochemistry for Hepatocyte, CK19, stem cell factor (SCF) and CD34. Five cases were also examined by transmission electron microscopy. Oval cells of similar morphology could be found in proliferating bile ductules in both groups. These cells coexpressed CK19 and Hepatocyte, but did not express SCF or CD34. Some of these cells exhibited a trend towards differentiation. There was no difference in the amount of oval cells between the two groups. The oval cell number was found to increase significantly with the progression of inflammation. A similar stem-like cell was not seen in the normal liver. CONCLUSIONS: There are bipotential oval cells in both HBV+ and HCV+ HLC. The lack of difference in oval cells between the two groups suggests that they might play a similar biological role in the histogenesis of different liver diseases.
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Hepatite B/complicações , Hepatite C/complicações , Cirrose Hepática/patologia , Fígado/patologia , Adulto , Idoso , Antígenos CD34/análise , DNA Viral/genética , Feminino , Hepacivirus/genética , Hepatite B/virologia , Vírus da Hepatite B/genética , Hepatite C/virologia , Hepatócitos/química , Hepatócitos/ultraestrutura , Hepatócitos/virologia , Humanos , Imuno-Histoquímica , Queratinas/análise , Fígado/química , Fígado/virologia , Cirrose Hepática/complicações , Cirrose Hepática/metabolismo , Masculino , Microscopia Eletrônica de Transmissão , Pessoa de Meia-Idade , RNA Viral/genética , Fator de Células-Tronco/análiseRESUMO
AIMS: To investigate whether cells with features similar to those of the oval cells of rodents and the small epithelial cells (SEC) recently described in certain human liver diseases, i.e. hepatic progenitor cells, also occur in human liver cirrhosis. METHODS AND RESULTS: Surgical specimens from 35 cases of hepatitis B virus-positive cirrhosis (30 cases containing hepatocellular carcinoma) were investigated by immunohistochemical staining for cytokeratin 7 and albumin. Electron microscopic investigations, and immunoelectron microscopic investigations using the same antibodies and a double-labelling technique were performed in 15 and seven cases, respectively. SEC were observed in proliferated bile ductules, at the margins of regenerating nodules and in the fibrous septa in all cases of cirrhosis. The SEC were morphologically similar to the SEC described previously, and to the oval cells seen in experimental hepatocarcinogenesis. They were characterized by their small size, oval shape, scanty electron-dense or electron-lucent cytoplasm, a high nucleo-cytoplasmic ratio, tonofilaments and intercellular junctions. Immunoelectron microscopy revealed that the SEC co-expressed cytokeratin 7 and albumin. Both relatively undifferentiated SEC and SEC with morphological and immunophenotypical signs of differentiation towards biliary epithelial cells and hepatocytes were found. CONCLUSIONS: SEC that exhibit morphological and immunophenotypical features of the SEC seen in certain other liver diseases are found in cirrhosis. These findings further support the hypothesis that a bipotent hepatic stem cell that may give rise to biliary epithelial cells and hepatocytes exists in the human liver.
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Ductos Biliares Intra-Hepáticos/patologia , Hepatócitos/ultraestrutura , Cirrose Hepática/patologia , Células-Tronco/patologia , Albuminas/metabolismo , Ductos Biliares Intra-Hepáticos/metabolismo , Carcinoma Hepatocelular/complicações , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Técnica Indireta de Fluorescência para Anticorpo , Hepatite B/complicações , Hepatite B/patologia , Hepatócitos/metabolismo , Humanos , Queratina-7 , Queratinas/metabolismo , Cirrose Hepática/metabolismo , Cirrose Hepática/virologia , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Microscopia Imunoeletrônica , Células-Tronco/metabolismoRESUMO
AIMS: It is still unclear whether hepatic stem cells that give rise to both biliary epithelial cells and hepatocytes exist in the human liver. The aim of this study was to investigate whether cells with ultrastructural and immunophenotypical features similar to those of the oval cells of rodents or the small epithelial cells (SEC) described recently in hepatoblastoma, i.e. putative hepatic progenitor cells, are found in the liver of patients with extrahepatic biliary atresia. METHODS AND RESULTS: Liver biopsies from 10 infants with extrahepatic biliary atresia were investigated by transmission electron microscopy. Single and double immunolabelling for cytokeratin 7, a marker of biliary differentiation, and albumin, a marker of hepatocytic differentiation, was investigated by immunoelectron microscopy. Electron microscopy revealed SEC that were ultrastructurally similar to the oval cells and coexpressed albumin and cytokeratin 7. The SEC exhibited a spectrum of differentiation that, in addition to relatively undifferentiated cells, included cells that exhibited morphological and immunophenotypical signs of differentiation towards biliary epithelial cells and hepatocytes. CONCLUSIONS: The findings demonstrate that SEC with morphological and immunophenotypical features of the oval cells of rodents and the SEC described in hepatoblastoma are found in the liver of patients with extrahepatic biliary atresia. The data further support the hypothesis that the SEC represent possible candidates for hepatic progenitor cells.
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Ductos Biliares Extra-Hepáticos/patologia , Atresia Biliar/patologia , Células Epiteliais/ultraestrutura , Fígado/patologia , Células-Tronco/patologia , Albuminas/metabolismo , Ductos Biliares Extra-Hepáticos/metabolismo , Atresia Biliar/metabolismo , Biomarcadores/análise , Núcleo Celular/ultraestrutura , Células Epiteliais/metabolismo , Técnica Indireta de Fluorescência para Anticorpo , Humanos , Recém-Nascido , Queratina-7 , Queratinas/metabolismo , Fígado/metabolismo , Microscopia Imunoeletrônica , Células-Tronco/metabolismoRESUMO
Investigation of the human glomerulus in health and disease shows that the human glomerulus comprises seven lobule-like structures with numerous anastomoses. The total length of the capillaries in a single glomerulus is 0.95 cm, making a total of 19 km for all 2-million glomeruli. The total surface area of all glomerular capillaries is 6,000 cm2. The total filtration surface area is 516.1 cm2. Severe isolated disease of the glomerulus, as seen in acute endocapillary glomerulonephritis, membranoproliferative glomerulonephritis types I and II, membranoproliferative glomerulonephritis plus chronic membranous glomerulonephritis, diabetic glomerulosclerosis, and glomerular amyloidosis, does not lead to elevation of serum creatinine concentration, even if the filtration area is reduced to about 20% (as in diabetes) of the normal value. It is concluded that isolated glomerular disease does not lead to elevation of the serum creatinine concentration. Glomerulopathies in which there is acute or chronic elevation of the serum creatinine concentration are accompanied by acute renal failure or involvement of the renal cortical interstitium, respectively.
Assuntos
Injúria Renal Aguda/patologia , Nefropatias Diabéticas/patologia , Glomerulonefrite Membranoproliferativa/patologia , Glomérulos Renais/citologia , Injúria Renal Aguda/fisiopatologia , Capilares/fisiologia , Creatinina/análise , Nefropatias Diabéticas/fisiopatologia , Glomerulonefrite Membranoproliferativa/fisiopatologia , Humanos , Glomérulos Renais/irrigação sanguínea , Glomérulos Renais/química , Circulação Renal/fisiologiaRESUMO
AIMS: In a recent study we described a population of small epithelial cells (SEC) in human hepatoblastoma that exhibit ultrastructural features of the oval cell of rodents. Both SEC and oval cells are immunoreactive for cytokeratin 7, a marker of biliary differentiation, and it was postulated that SEC, like oval cells, are closely related to hepatic stem cells. This study was undertaken to investigate whether SEC also exhibit immunolabelling for albumin, a marker of hepatocytic differentiation, and to determine whether other antigens typical of oval cells are detectable in hepatoblastoma. METHODS AND RESULTS: Hepatoblastomas of various subtypes were investigated by electron microscopy, and by immunohistochemistry with the monoclonal antibodies OV-1 and OV-6, which recognize antigens associated with oval cells. Double-labelling for cytokeratin 7 and albumin was carried out by immuno-electron microscopy. OV-1 stained scattered cells in seven of 12 tumours investigated and OV-6 in nine. On immunoelectron-microscopic investigation, SEC exhibited labelling for both cytokeratin 7 and albumin. CONCLUSIONS: The results demonstrate that antigens associated with oval cells are found in certain cells in hepatoblastoma. SEC, like oval cells, co-express markers for hepatocytic and biliary differentiation. The findings further support the hypothesis that SEC are closely related to the putative bipotent hepatic stem cell, which, by definition, gives rise to both hepatocytes and biliary epithelial cells.
Assuntos
Albuminas/metabolismo , Hepatoblastoma/metabolismo , Queratinas/metabolismo , Neoplasias Hepáticas/metabolismo , Células-Tronco/metabolismo , Antígenos de Diferenciação/metabolismo , Epitélio/metabolismo , Epitélio/patologia , Epitélio/ultraestrutura , Hepatoblastoma/patologia , Hepatoblastoma/ultraestrutura , Humanos , Imuno-Histoquímica , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/ultraestrutura , Microscopia Eletrônica , Microscopia ImunoeletrônicaRESUMO
A considerable proportion of cases of myeloproliferative and lymphoproliferative disorders exhibit renal involvement. However, it is unclear whether the cytologic features, immunophenotype or grade of malignancy of the cells infiltrating the kidney differ from those of the primary tumor. This study was performed on 120 autopsy cases with the following diagnoses: acute myelogenous leukemia (AML, n = 22; subtypes M1 + M2, n = 12, subtype M4, n = 10), chronic myelogenous leukemia (CML, n = 7), agnogenic myeloid metaplasia/myelofibrosis (AMM/MF, n = 6), acute lymphocytic leukemia (ALL, n = 6), chronic lymphocytic leukemia (CLL, n = 9), other low-grade non-Hodgkin's lymphomas (low-grade NHL, n = 24), high-grade NHL (n = 21) and multiple myeloma (MM, n = 25). Renal involvement was investigated by light microscopy and immunohistochemistry. It was found in 34% of the cases, and was most common in ALL (83%) and low-grade NHL (50%) and least common in high-grade NHL (10%) and MM (12%). Dense infiltration of almost the entire kidney was most commonly seen in AML, low-grade NHL and ALL. Infiltration was bilateral and involved both the cortex and medulla in the majority of cases. When involvement of other organs was compared with that of the kidney, the lung was found to be involved in approximately the same number of cases, but liver involvement was more common and heart involvement less common. Reactive lymphocytic infiltration of the kidney was found in 18 of the 120 cases (15%), and was distinguished from scanty tumorous infiltration by immunohistochemical staining. No major phenotypical differences were found between the tumor cells infiltrating the kidney and those of the primary tumors in the bone marrow or lymph nodes. However, in one case of CML, the cells infiltrating the kidney were negative for KP1 and chloroacetate esterase, but could be identified by reactivity for CD34. The grade of malignancy in NHL was similar in both the nodal and renal manifestations.