RESUMO
Background: Alpha-fetoprotein (AFP) and carbohydrate antigen 19-9 (CA 19-9) are two tumor markers that are widely used in the differential diagnosis in patients with primary liver tumors. Very high levels of AFP are sporadically observed in patients with intrahepatic cholangiocarcinoma (ICC) and may cause an incorrect initial diagnosis of hepatocellular carcinoma (HCC). Methods: Two cases of tumors in cirrhotic livers were described, in which the initial diagnosis, based on very high AFP levels (Patient I: 10,464 ng/mL, Patient II: 2212 ng/mL, reference range: ≤8.04 ng/mL) was HCC. In addition, the PubMed database was searched for cases of ICC with elevated AFP. Discussion: In both individuals, liver cirrhosis was diagnosed, but there was no typical rapid "washout" in the contrast-enhanced computed tomography. Based on the histological assessment of samples obtained in the core biopsies, the initially assumed diagnosis of HCC was changed to ICC in both cases. Only nine cases of patients with ICC and high AFP levels were found in the PubMed database. The AFP levels ranged from slightly elevated to over 16,000 ng/mL. Conclusions: A very high AFP level does not necessarily correlate with the presence of HCC. Therefore, the diagnosis has to be verified histologically, when the radiological imaging is uncertain in patients with liver cirrhosis.
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Neoplasias dos Ductos Biliares , Biomarcadores Tumorais , Colangiocarcinoma , Erros de Diagnóstico , alfa-Fetoproteínas , Humanos , alfa-Fetoproteínas/análise , Colangiocarcinoma/sangue , Colangiocarcinoma/diagnóstico , Masculino , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/análise , Neoplasias dos Ductos Biliares/diagnóstico , Neoplasias dos Ductos Biliares/sangue , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/diagnóstico por imagem , Pessoa de Meia-Idade , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/diagnóstico , Diagnóstico Diferencial , Idoso , Cirrose Hepática/sangue , Cirrose Hepática/diagnóstico , Cirrose Hepática/complicações , Feminino , Tomografia Computadorizada por Raios X/métodosRESUMO
Breast cancer (BC) is a heterogeneous disease distinguished by four main subtypes based on the expression of estrogen, progesterone receptors, and human epidermal growth factor-2 on the cancer cells. Triple-negative breast cancer (TNBC) consists of approximately 10-20% of all BCs and is characterized by a poor prognosis. Adenoid cystic carcinoma (ACC) of the breast is a rare, special type of TNBC with low metastatic potential and usually favorable prognosis. There are no established recommendations concerning systemic therapy in advanced ACC. We present a case of a 70-year-old woman with locally advanced ACC with progression after radical mastectomy, and review the literature concerning the treatment of metastatic disease focused on systemic therapy.
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Neoplasias da Mama , Carcinoma Adenoide Cístico , Neoplasias de Mama Triplo Negativas , Feminino , Humanos , Idoso , Neoplasias da Mama/patologia , Mastectomia , Carcinoma Adenoide Cístico/cirurgia , Carcinoma Adenoide Cístico/metabolismo , Carcinoma Adenoide Cístico/patologia , Mama , PrognósticoAssuntos
Infecções Relacionadas a Cateter , Cateterismo Venoso Central , Cateteres Venosos Centrais , Hemofilia A , Criança , Humanos , Hemofilia A/complicações , Cateteres Venosos Centrais/efeitos adversos , Cateterismo Venoso Central/efeitos adversos , Fator VIII/uso terapêutico , Cateteres de DemoraRESUMO
BACKGROUND: Tetralogy of Fallot (ToF) is the most common cyanotic congenital heart disease and the population of ToF repair survivors is growing rapidly. Adults with repaired ToF develop late complications. The aim of this study was to describe and analyze long-term follow-up of patients with repaired ToF. METHODS: This is a retrospective cohort study. Consecutive 83 patients with repaired ToF who did not undergo pulmonary valve replacement were included. Mean age of all patients was 30.5 ± 10.7. There were 49 (59%) male. Patients were divided into two groups according to the time since the repair (< 25 years and ≥ 25 years). The electrocardiographic (ECG), cardiopulmonary exercise testing (CPET), echocardiographic and cardiac magnetic resonance (CMR) data were reviewed retrospectively. RESULTS: In CPET values were not significantly different in the two groups. In CMR volumes of left and right ventricles were not significantly different in the two groups. There were no differences between the groups in ventricular ejection fraction, mass of ventricles, or pulmonary regurgitation fraction. Among all the patients, ejection fraction and left and right ventricle mass, indexed pulmonary regurgitation volume measured by CMR did not correlate with the time since repair. In ECG among all the patients, ejection fraction of the RV, measured in CMR, negatively correlated with QRS duration (r = - 0.43; p < 0.001). There was a positive correlation between QRS duration and end diastolic volume of the RV (r = 0.30; p < 0.02), indexed end diastolic volume of the RV (r = 0.29; p = 0.04), RV mass (r = 0.36; p < 0.001) and left ventricle mass (r = 0.26; p = 0.04). CONCLUSION: Long-term survival and clinical condition after surgical correction of ToF in infancy is generally good and the late functional status in ToF - operated patients could be excellent up to 25 years after the repair. QRS duration could be an utility and easy factor to assessment of right ventricular function. TRIAL REGISTRATION: The study protocol was approved by the local Ethics Committee. Each participant provided informed consent to participate in the study (license number 122.6120.88.2016 from 28.04.2016).
Assuntos
Procedimentos Cirúrgicos Cardíacos/métodos , Teste de Esforço/métodos , Imagem Multimodal/métodos , Tetralogia de Fallot/diagnóstico por imagem , Tetralogia de Fallot/cirurgia , Adulto , Estudos de Coortes , Ecocardiografia Doppler/métodos , Eletrocardiografia/métodos , Eletrocardiografia Ambulatorial/métodos , Feminino , Seguimentos , Humanos , Imagem Cinética por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Medição de Risco , Estatísticas não Paramétricas , Sobreviventes/estatística & dados numéricos , Tempo , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Second-stage palliation with hemi-Fontan or bidirectional Glenn procedures has improved the outcomes of patients treated for single-ventricle heart disease. The aim of this study was to retrospectively analyze risk factors for death after second-stage palliation of single-ventricle heart and to compare therapeutic results achieved with the hemi-Fontan and bidirectional Glenn procedures. MATERIAL AND METHODS: We analyzed 60 patients who had undergone second-stage palliation for single-ventricle heart. Group HF consisted of 23 (38.3%) children who had been operated with the hemi-Fontan method; Group BDG consisted of 37 (61.7%) who had been operated with the bidirectional Glenn method. The analysis focused on 30-day postoperative mortality rates, clinical and echocardiographic data, and early complications. RESULTS: The patients' ages at the time of repair was 33 ± 11.2 weeks; weight was 6.7 ± 1.2 kg. The most common anatomic subtype was hypoplastic left heart syndrome, in 36 (60%) patients. The early mortality rate was 13.3%. Significant preoperative atrioventricular valve regurgitation, single-ventricle heart dysfunction, pneumonia/sepsis, and arrhythmias were associated with higher mortality rates after second-stage palliation. Multivariate analysis identified significant preoperative single-ventricle heart dysfunction as an independent predictor of early death after second-stage palliation. No differences were found in the analyzed variables after bidirectional Glenn compared with hemi-Fontan procedures. CONCLUSION: Significant preoperative atrioventricular valve regurgitation, arrhythmias and pneumonia/sepsis are closely correlated with mortality in patients with single-ventricle heart after second-stage palliation. Preoperative significant single-ventricle heart dysfunction is an independent mortality predictor in this group of patients. There are no differences in clinical, echocardiographic data, or outcomes in patients treated with the hemi-Fontan compared with bidirectional Glenn procedures.
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Técnica de Fontan/métodos , Ventrículos do Coração/fisiopatologia , Síndrome do Coração Esquerdo Hipoplásico/fisiopatologia , Cuidados Paliativos/métodos , Ecocardiografia , Feminino , Seguimentos , Ventrículos do Coração/anormalidades , Ventrículos do Coração/cirurgia , Humanos , Síndrome do Coração Esquerdo Hipoplásico/diagnóstico , Síndrome do Coração Esquerdo Hipoplásico/cirurgia , Lactente , Masculino , Período Pré-Operatório , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do TratamentoRESUMO
Mastocytosis is a disease resulting from a proliferation of clonal, abnormal mast cells in tissues and organs, defined as Philadelphia-negative myeloproliferative neoplasm. We present a male patient with clinically, morphologically and immunohistochemically confirmed mastocytosis with preceding myelodysplastic syndrome, occurred after wasp bite in the course of anaphylactic reaction. The propensity to hymenoptera venom-induced anaphylaxis and the presence of an increased population of atypical mast cells in bone marrow found after anaphylactic shock may suggest the possible relationship between hymenoptera venom allergy and anaphylaxis and the development of mastocytosis of unusual course in a predisposed person.
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Anafilaxia/complicações , Mordeduras e Picadas de Insetos/complicações , Mastocitose/etiologia , Síndromes Mielodisplásicas/complicações , Animais , Humanos , Masculino , Pessoa de Meia-Idade , VespasRESUMO
BACKGROUND: New paclitaxel coated balloons (PCB) developments have been proposed to maintain therapeutic levels of drug in the tissue while decreasing particle release. In this series of studies, we evaluated the pharmacokinetic profile and biological effects after paclitaxel delivery via novel microcrystalline PCB coating (mcPCB, Pax®, Balton) in porcine iliofemoral arteries. METHODS: Ten domestic swine were enrolled yielding 24 iliofemoral segments for evaluation. In the pharmacokinetic study, nine mcPCBs were dilated for 60 sec and animals sacrificed after 1 hr, 3 and 7 days. Studied segments were harvested and tissue paclitaxel concentration was analyzed utilizing HPLC. In the biological response evaluation, self-expandable stents were implanted followed by post dilation with either mcPCB (n = 10) or POBA (n = 5). After 28 days, angiography was performed, animals were sacrificed and stented segments harvested for histopathological evaluation. RESULTS: The 1-hr, 3 and 7 days vessel paclitaxel concentrations were 152.9 ± 154.5, 36.5 ± 49.5, and 0.9 ± 0.7 ng/mg respectively. In the biological response study, stents in the mcPCB group presented lower angiographic measures of neointimal hyperplasia as expressed by late loss when compared to POBA (-0.43 ± 0.9 vs. 0.23 ± 1.2; P = 0.24) at 28 days. In the histopathological evaluation, percent area of stenosis (%AS) was reduced by 42% in the mcPCB group (P < 0.05). The healing process in mcPCB group was comparable to POBA with regard to fibrin deposition (0.7 vs. 0.7; P = ns), neointimal maturity (1.97 vs. 1.93; P = ns), inflammation score (0.92 vs. 1; P = ns) and endothelialization score (1.77 vs. 1.73; P = ns). The mcPCB group did however display a greater tendency of medial cell loss and mineralization (60% vs. 0; P = 0.08). CONCLUSIONS: Delivery of paclitaxel via a novel mcPCB resulted in low long-term tissue retention of paclitaxel. However, this technological approach displayed reduced neointimal proliferation and favorable healing profile.
Assuntos
Angioplastia com Balão/instrumentação , Fármacos Cardiovasculares/administração & dosagem , Fármacos Cardiovasculares/farmacocinética , Materiais Revestidos Biocompatíveis , Stents Farmacológicos , Artéria Femoral/efeitos dos fármacos , Artéria Ilíaca/efeitos dos fármacos , Paclitaxel/administração & dosagem , Paclitaxel/farmacocinética , Animais , Fármacos Cardiovasculares/química , Proliferação de Células/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão , Cristalização , Feminino , Artéria Femoral/diagnóstico por imagem , Artéria Femoral/metabolismo , Artéria Femoral/patologia , Hiperplasia , Artéria Ilíaca/diagnóstico por imagem , Artéria Ilíaca/metabolismo , Artéria Ilíaca/patologia , Masculino , Teste de Materiais , Modelos Animais , Neointima , Paclitaxel/química , Desenho de Prótese , Radiografia , Sus scrofa , Cicatrização/efeitos dos fármacosRESUMO
BACKGROUND: The aim of this study was to investigate the distribution of different types of primary orbital tumors, histopathological diagnosis, and postoperative complications. MATERIAL AND METHODS: We analyzed 122 patients (68 women and 54 men) with orbital tumors, hospitalized in the ENT Department of the Medical University of Silesia in Katowice during 1990-2013. The patients were characterized in terms of anatomic, topographical, histopathological, and clinical parameters. The role of diagnostic imagining such as CT, NMR, and fine-needle aspiration (FNB) in preoperative diagnostics is discussed. RESULTS: of FNB, cytological, and histopathological examination of the postoperative specimens were compared. Results There were 56 (46%) patients with malignant tumors, 42 (34%) with benign tumors, 19 (16%) with inflammatory tumors, and 5 patients (4%) had other tumors. In cases of malignant tumors, local recurrence up to 5 years was found in 36 (64.3%) cases. In the other 20 (35.7%) cases of malignant tumors, the patients remained under close follow-up in the outpatient clinic, without signs of local recurrence (follow-up 1-17 years). According to histopathological examination, malignant tumors were detected in 45.9% of patients and non-malignant tumor in 34.4% of patients. In 19.7% of patients, inflammatory and other types of tumors were diagnosed. CONCLUSIONS: We characterized the occurrence and pathological profiles of orbital tumors. The tumor location, histopathological diagnosis, and postoperative complications give us important information for the diagnosis of tumor prior to biopsy or tumor resection and for the determination of the treatment strategy and possible complications after surgery.
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Centros Médicos Acadêmicos , Departamentos Hospitalares , Neoplasias Orbitárias/patologia , Adulto , Idoso , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Oftalmológicos/efeitos adversos , Órbita/diagnóstico por imagem , Órbita/patologia , Neoplasias Orbitárias/classificação , Neoplasias Orbitárias/diagnóstico por imagem , Neoplasias Orbitárias/cirurgia , Polônia , Complicações Pós-Operatórias/etiologia , Tomografia Computadorizada por Raios X , Adulto JovemRESUMO
OBJECTIVES: Increased arterial stiffness is a risk factor of atherosclerosis and cardio-vascular complications. The aim of the study was to determine whether peripheral vascular function might be an early marker of impaired health status in patients with a single ventricle after Fontan procedure. METHODS AND RESULTS: Twenty five consecutive adults (11 women and 14 men) aged 24.7 ± 6.2 years after the Fontan procedure and 25 sex, age and BMI match healthy volunteers underwent physical examination, blood analysis, transthoracic echocardiography and noninvasive assessment of aortic stiffness. Augmented pressure and Augmentation Index (AIx) were both significantly elevated in Fontan when compared to the controls (6,08 ± 0,7 vs. 2,0 ± 3,7; p = 0.002 and 17,01 ± 3,3 vs. 6,05 ± 11; p < 0.001, respectively). There were no differences in pulse wave velocity (PWV), mean blood pressure (BP), brachial pulse pressure (PP), central: systolic BP, diastolic BP and PP. In Fontan group we find negative correlation between PWV and SatO2 (r = -0.68; p = 0.04) and positive correlation with WBC (0.72; p = 0.72; p = 0.013), INR (0.81; p = 0.008), TNFα (r = 0.45; p = 0.04), and postoperative time (r = 0.77; p = 0.02). AIx correlates positively only with age at surgery (r = 0.45; p = 0.04). Bilirubin level correlates positively with brachial PP (r = 0.71; p = 0.02) and central PP (r = 0.68; p = 0.03).The multivariate model showed that SatO2 (ß = -0.44, p = 0.04) was the only independent predictor of PWV (R² = 0.32, p = 0.03). CONCLUSION: Adult Fontan patients have an increased arterial stiffness assessed by a noninvasive technique. Low arterial oxygen saturation postoperative time, age at surgery, white blood cells, TNFα and bilirubin level are associated with arterial stiffening in these patients. The combination of blood parameters of the hepatic function and noninvasive measurements of arterial stiffness could be helpful in comprehensive care of patients with Fontan circulation.
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Aterosclerose/diagnóstico por imagem , Aterosclerose/etiologia , Ecocardiografia/métodos , Técnica de Fontan/efeitos adversos , Rigidez Vascular/fisiologia , Adolescente , Adulto , Aorta/fisiologia , Aterosclerose/fisiopatologia , Diagnóstico Precoce , Feminino , Humanos , Masculino , Análise Multivariada , Oxigênio/sangue , Fluxo Pulsátil/fisiologia , Volume Sistólico/fisiologia , Adulto JovemRESUMO
BACKGROUND: Patients who have undergone a Fontan operation (FO) may suffer from both systolic and diastolic single ventricle (SV) dysfunction. AIM: The aim of the study was to quantify non-invasively the systolic and diastolic single ventricle function in adult FO patients and to assess its effect on exercise tolerance. METHODS: We investigated 21 patients (12F; 9M) after FO with morphological left ventricle with a mean age of 26 +/- 6 years, and 17 age-matched, healthy people (control group). Pulse-wave Doppler signals from the mitral inflow, aortic flow and tissue Doppler imaging of the mitral annulus were obtained. A cardiopulmonary exercise test (CPET) was performed. RESULTS: The Fontan patients, as compared to the controls, had a lower value of SV ejection fraction (SVEF), E velocity, E/A ratio, aortic valve velocity time integral, exercise time, SatO2, VO(2peak) and significantly higher E/E' ratio, VE/VCO(2peak) and VE/VO(2peak'). We found negative correlations between E/E' and exercise time and VO(2peak). Positive correlations were found between E/E' and VE/VCO(2peak) and age at surgery. S' velocity correlated positively with SVEF, VO(2peak) and negatively with E/E' ratio. Patients after FO with E/E' ratio > or = 12 had a significantly lower oxygen uptake when compared to those with E/E' ratio < 12. CONCLUSION: Adult patients after Fontan operations are characterized by both systolic and diastolic dysfunction of the single ventricle, associated with severe exercise intolerance reflected by shorter duration of exercise with decreased oxygen uptake and increased ventilatory response. E/E' ratio assessed by Tissue Doppler echocardiography can be a powerful predictor of oxygen uptake and ventilatory response.
Assuntos
Diástole , Tolerância ao Exercício , Técnica de Fontan , Cardiopatias Congênitas/fisiopatologia , Ventrículos do Coração/fisiopatologia , Ventrículos do Coração/cirurgia , Sístole , Adulto , Estudos de Casos e Controles , Ecocardiografia Doppler , Teste de Esforço , Feminino , Seguimentos , Técnica de Fontan/métodos , Cardiopatias Congênitas/cirurgia , Ventrículos do Coração/anormalidades , Ventrículos do Coração/diagnóstico por imagem , Humanos , MasculinoRESUMO
BACKGROUND: Glycoprotein-2 (GP2) IgA is a predictor of disease severity in primary sclerosing cholangitis (PSC). We examined GP2's occurrence in the biliary tract, the site of inflammation. METHODS: GP2 was analyzed using ELISA, immunoblotting, mass spectrometry, and immunohistochemistry. The samples included: 20 bile and 30 serum samples from PSC patients, 23 bile and 11 serum samples from patients with gallstone disease (GD), 15 bile samples from healthy individuals undergoing liver-donation surgery (HILD), 20 extracts of gallstones (GE) obtained during cholecystectomy, and 101 blood-donor sera. RESULTS: Biliary GP2 concentrations were significantly higher in patients with PSC and GD than in HILD (p < 0.0001). Serum GP2 levels were similar in PSC and GD patients, and controls, but lower than in bile (p < 0.0001). GP2 was detected in all 20 GEs. Mass spectrometry identified GP2 in the bile of 2 randomly selected GD and 2 PSC patients, and in none of 2 HILD samples. GP2 was found in peribiliary glands in 8 out of 12 PSC patients, showing morphological changes in acinar cells, but not in GD-gallbladders. CONCLUSIONS: GP2 is present in bile of PSC and GD patients. It is synthesized in the peribiliary glands of PSC patients, supporting a pathogenic role for biliary GP2 in PSC.
Assuntos
Bile , Colangite Esclerosante , Cálculos Biliares , Humanos , Colangite Esclerosante/metabolismo , Colangite Esclerosante/patologia , Cálculos Biliares/metabolismo , Cálculos Biliares/química , Cálculos Biliares/patologia , Bile/química , Bile/metabolismo , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Idoso , Adulto Jovem , Proteínas Ligadas por GPIRESUMO
A 19-years old, previously healthy male, ingested the higher amount of rifampicin, isoniazyd, pyrazinamide, ketoprofene and alcohol. Within less than 20 hours he developed dyspnoe, pruritus, red man syndrome, and ECG changes suggesting acute coronary syndrome appeared - ST interval elevation. In the next few hours chest pain appeared and troponin I concentration was elevated (13.54 ng/ml). The performed echocardiography revealed global hypokinesis with the decreased left ventricular ejection fraction (approx. 30%). There was no significant pathological changes in coronarography, except for slowed blood flow. Further patient developed cardiogenic shock, pulmonary oedema and died within 32 hours from medication overdose.
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Síndrome Coronariana Aguda/induzido quimicamente , Síndrome Coronariana Aguda/diagnóstico , Antituberculosos/intoxicação , Overdose de Drogas/complicações , Overdose de Drogas/diagnóstico , Suicídio , Ecocardiografia , Etanol/intoxicação , Evolução Fatal , Humanos , Isoniazida/intoxicação , Cetoprofeno/intoxicação , Masculino , Pirazinamida/intoxicação , Rifampina/intoxicação , Choque Cardiogênico/induzido quimicamente , Choque Cardiogênico/diagnóstico , Adulto JovemRESUMO
BACKGROUND: Morbidity and mortality following Fontan (FO) surgery are primarily thromboembolic in nature. However, follow-up data regarding thromboembolic complications (TECs) in adult patients after FO procedure are inconsistent. In this multicenter study, we investigated the incidence of TECs in FO patients. METHODS: We studied 91 patients who underwent FO procedure. Clinical data, laboratory, and imaging investigations were collected prospectively during the scheduled medical appointments in 3 Adult Congenital Heart Disease Departments in Poland. TECs were recorded during a median follow-up of 31 months. RESULTS: Four patients (4.4%) were lost to follow-up. The mean age of patients was 25.3 (±6.0) years at enrollment, and the mean time between FO operation and investigation was 22.1 (±5.1) years. A total of 21 out of 91 patients (23.1%) had a history of 24 TECs since an FO procedure, mainly pulmonary embolism (PE; n = 12, 13.2%), including 4 (33.3%) silent PE. The mean time since FO operation to the first TEC was 17.8 (±5.1) years. During follow-up, we documented 9 TECs in 7 (8.0%) patients, mainly PE (n = 5, 5.5%). Most patients with TEC had a left type of systemic ventricle (57.1%). Three patients (42.9%) were treated with aspirin, 3 (3.4%) with Vitamin K antagonists or novel oral anticoagulants, and 1 patient had no antithrombotic treatment at the time of TEC occurrence. Supraventricular tachyarrhythmias were present in 3 patients (42.9%). CONCLUSIONS: This prospective study shows that TECs are common in FO patients, and a significant number of these events occur during adolescence and young adulthood. We also indicated how much TECs are underestimated in the growing adult FO population. The complexity of the problem requires more studies, especially to standardize the prevention of TECs in the whole FO population.
RESUMO
BACKGROUND: In humans, chronic liver disease (CLD) is a serious clinical condition with many life-threatening complications. Currently, there is no therapy to stop or slow down the progression of liver fibrosis. Experimental mouse models of CLD, induced by repeated intraperitoneal injections of carbon tetrachloride (CCL4) and D-galactosamine (D-GalN), can be used to evaluate therapies that cannot be performed in humans. A major drawback of these animal models is the different dynamics of liver fibrosis progression depending on the animal strain, administered hepatotoxin, its dose, duration of intoxication, and frequency of injections. The aim of this study was to describe and compare the dynamics of progression of pathological changes in the BALB/c mouse and Sprague Dawley rat models of CLD induced by CCl4 and D-GalN. We defined the onset and duration of these changes and suggested the optimal time for therapeutic intervention in the analyzed CLD models. METHODS: CLD was induced by repeated intraperitoneal injection of CCl4 in mice (12.5 µL/100 g bw every 5 days) and rats (25-100 µL/100 g bw twice a week) and D-GalN in mice (75 mg/100 g bw twice a week) and rats (25 mg/100 g bw twice a week). Blood and liver samples were collected at weeks 2, 4, 6, 8, 10, and 12 of intoxication. Liver injury and its progression were assessed by using complete blood count and liver function blood tests as well as by analyzing histopathological changes, including fibrosis, proliferation activity, apoptosis, stellate cell activation, and gene expression. RESULTS: In mice and rats treated with CCl4, early fibrosis was observed in most pericentral areas from week 2 to 4 of intoxication. Established fibrosis developed in both rats and mice at week 6 of intoxication. Incomplete cirrhosis, defined as the presence of occasional cirrhotic nodules, was observed in rats at week 12 of intoxication. The dynamics of liver fibrosis in CCl4-treated animals were greater than in the D-GalN groups. In D-GalN-intoxicated rats and mice, the first signs of liver fibrosis were observed at weeks 4 and 10 of intoxication, respectively. The rats developed early fibrosis after 8 weeks of D-GalN intoxication. The progression of collagen deposition was accompanied by histological changes and alteration of certain genes and blood liver parameters. CONCLUSIONS: The dynamics of liver fibrosis in CCl4 treated rodents is greater than in the D-GalN treated ones. In the CCl4 models, two appropriate times for therapeutic intervention are indicated, which to varying degrees reflect the real clinical situation and may potentially differ in the obtained results: early intervention before week 4 of intoxication (early fibrosis) and late intervention after week 8 of intoxication (when signs of established fibrosis are present). Rodent models of D-GalN-induced fibrosis are not recommended due to the long incubation period and weak toxic effect.
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Doença Hepática Induzida por Substâncias e Drogas , Fígado , Humanos , Ratos , Camundongos , Animais , Ratos Sprague-Dawley , Fígado/metabolismo , Cirrose Hepática/tratamento farmacológico , Tetracloreto de Carbono/toxicidade , Tetracloreto de Carbono/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/patologia , Modelos Animais de DoençasRESUMO
BACKGROUND: Long-term treatment with gonadoliberin analogs is used to block the hypothalamic-pituitary-gonadal axis. The use of these agents is generally considered to be safe; however, some observations suggest the possibility of adverse effects. MATERIAL/METHODS: We investigated whether a 3-months administration of a low dose (6 µg/kg b.w.) of dalarelin - a new agonist, and cetrorelix - a known antagonist of GnRH to female rats causes morphological changes in pituitary gland, ovaries, uterus and liver (HE and VG staining); effects on pituitary, hepatic and blood enzyme activities (histochemical and kinetic methods, respectively), and on the blood lipid profile (colorimetric methods); and to what extent these changes are reversible. RESULTS: Applying analogs effectively inhibited ovulation, affected the uterine endometrium and changed histological appearance of the liver (e.g., steatosis). They altered activities of marker enzymes of cellular respiration, gluconeogenesis and intracellular digestion in the liver and, partially in the pituitary gland, caused undesirable changes in the activities of aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, and creatine kinase, and a concentration of cholesterol HDL fraction and triglycerides in the blood. Both morphological and enzymatic effects were more evident after antagonist administration; changes in the blood lipid profile were more evident after agonist administration. In both analogs histological and enzymatic changes persisted a relatively long time after the discontinuation of the treatment. CONCLUSIONS: The low dose of dalarelin and cetrorelix is sufficient to cause limited damage of hepatic cells and may modify the function of pituitary, ovaries, uterus and liver as well as other organs, even after discontinuation of the treatment.
Assuntos
Enzimas/metabolismo , Hormônio Liberador de Gonadotropina/análogos & derivados , Hormônio Liberador de Gonadotropina/agonistas , Hormônio Liberador de Gonadotropina/antagonistas & inibidores , Especificidade de Órgãos/efeitos dos fármacos , Animais , Peso Corporal/efeitos dos fármacos , Densitometria , Relação Dose-Resposta a Droga , Enzimas/sangue , Feminino , Hormônio Liberador de Gonadotropina/administração & dosagem , Hormônio Liberador de Gonadotropina/farmacologia , Imuno-Histoquímica , Fígado/citologia , Fígado/efeitos dos fármacos , Fígado/enzimologia , Tamanho do Órgão/efeitos dos fármacos , Ovário/citologia , Ovário/efeitos dos fármacos , Ovário/enzimologia , Hipófise/efeitos dos fármacos , Hipófise/enzimologia , Ratos , Ratos Sprague-Dawley , Fatores de Tempo , Útero/citologia , Útero/efeitos dos fármacos , Útero/enzimologiaRESUMO
BACKGROUND: Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms located in the alimentary tract. Our aim was to assess the influence of prognostic factors on survival in patients surgically treated for GISTs. STUDY: One hundred and five patients treated between January 1989 and December 2008 were available for study. A retrospective analysis of prognostic factors (age, gender, mitotic index, tumor location, tumor size, risk of malignant behavior, and coexisting other neoplasm) was performed. Univariate and multivariate survival analyses were undertaken. RESULTS: Univariate analyses revealed the importance of patient gender (p = 0.007), disease location (p = 0.055), mitotic index (p = 0.054) and coexistence with other neoplasms (p = 0.004). However, multivariate analysis showed 3 independently statistically significant factors: coexistence with other neoplasm (RR = 3.53, p = 0.004), male gender (RR = 2.60, p = 0.011) and mitotic index ≥10/50 HPF, (RR = 2.60, p = 0.042). CONCLUSIONS: Our study has shown that male gender, a high mitotic index ≥10/50 HPF, and coexistence with other malignant neoplasms were independent poor prognostic factors in patients with GIST. The presence of middle or lower gut disease location leads to an increased risk of mortality when compared with the upper gut.
Assuntos
Neoplasias Gastrointestinais/mortalidade , Neoplasias Gastrointestinais/cirurgia , Tumores do Estroma Gastrointestinal/mortalidade , Tumores do Estroma Gastrointestinal/cirurgia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Análise de Sobrevida , Adulto JovemRESUMO
OBJECTIVES: The Fontan procedure is the treatment of choice in congenital cardiac malformations defined as the single ventricle. Fontan patients are at high risk of thromboembolism, but the exact mechanism of this is poorly understood. The aim of this study was to evaluate an involvement of thrombin generations and microparticles (MPs) in prothrombotic state in adults with Fontan circulation. METHODS: This study included hospitalized patients after Fontan procedure and healthy volunteers. We assessed laboratory tests including thrombin generation by calibrated automated thrombography in three variants [platelet-poor plasma (impact of coagulation factors), platelet-rich plasma (PRP) (influence of platelets) and related with MPs]. The technique allows for a comprehensive evaluation of the coagulation system. RESULTS: The study groups consisted of 81 adult Fontan patients [41 females (50.6%); median age 22 interquartile range [20-27] years] and 54 control subjects. In patients with Fontan circulation, higher values of endogenous thrombin potential and peak values were observed for both platelet-poor plasma (+17% and +33%) and MPs (+29% and 41%) compared to controls (all P < 0.05). Moreover, in the Fontan group, we found a 64.9% shorter lag time and a 70.4% time to peak for MP variant (both P < 0.001). Contrarily, analysis in the PRP showed 17.1% of reduced endogenous thrombin potential in Fontan. Furthermore, there were no differences in thrombin synthesis in PRP in Fontan patients receiving aspirin or those with thrombocytopaenia (all P > 0.05). CONCLUSIONS: This study for the first time showed that thrombin generation associated with MPs may be an important contributor to the prothrombotic state in the Fontan population.
Assuntos
Técnica de Fontan , Tromboembolia , Feminino , Humanos , Adulto , Adulto Jovem , Trombina , Técnica de Fontan/efeitos adversos , Coagulação Sanguínea , Plaquetas , Testes de Coagulação SanguíneaRESUMO
Structural, hemodynamic, and morphological cardiac changes following Fontan operation (FO) can contribute to the development of arrhythmias and conduction disorders. Sinus node dysfunction, junction rhythms, tachyarrhythmias, and ventricular arrhythmias (VAs) are some of the commonly reported arrhythmias. Only a few studies have analyzed this condition in adults after FO. This study aimed to determine the type and prevalence of arrhythmias and conduction disorders among patients who underwent FO and were under the medical surveillance of the John Paul II Hospital in Krakow. Data for the study were obtained from 50 FO patients (mean age 24 ± 5.7 years; 28 men (56%)). The median follow-up time was 4 (2-9) years. Each patient received a physical examination, an echocardiographic assessment, and a 24 h electrocardiogram assessment. Bradyarrhythmia was diagnosed in 22 patients (44%), supraventricular tachyarrhythmias in 14 patients (28%), and VAs in 6 patients (12%). Six patients required pacemaker implantation, and three required radiofrequency catheter ablation (6%). Arrythmias is a widespread clinical problem in adults after FO. It can lead to serious haemodynamic impairment, and therefore requires early diagnosis and effective treatment with the use of modern approaches, including electrotherapy methods.
RESUMO
BACKGROUND AND AIMS: Experimental models using carbon tetrachloride (CCl4) and D-galactosamine (D-GalN) can be used in preclinical assessment of acute liver failure (ALF) therapies. Unfortunately, these models are characterized by different dynamics of liver injury depending on the animal strain, administered hepatotoxin, and its dose. The aim of this study was to compare known rat and mouse models of ALF with a view to their future introduction into preclinical cell therapy experiments. In particular, based on histopathological and molecular changes, we suggested experimental time cut-off points for an effective stem cell therapeutic intervention. METHODS: ALF was induced by a single intraperitoneal injection of CCl4 in mice (50 µL/100 g b.w.) and rats (200 µL/100 g b.w.) and D-GalN in mice (150 mg/100 g b.w.) and rats (50 mg/100 g b.w.). Blood and liver samples were collected 12 h, 24 h, 48 h and 7 days after intoxication. Blood morphology, liver function blood tests, histopathological changes, proliferation activity, apoptosis, fibrosis, and gene expression were analysed to assess liver damage. RESULTS: At 12 h, 24 h, and 48 h after CCl4 injection, mouse livers showed moderate inflammatory infiltration and massive pericentral necrosis. In rats treated with CCl4, minor lymphocytic infiltration in the liver parenchyma was seen at 12 h, followed by necrosis that appeared around central veins at 24 h and persisted to 48 h. In D-GalN-injected mice, the first histopathological signs of liver injury appeared at 48 h. In the livers of D-GalN-treated rats, moderate pericentral inflammatory infiltration occurred after 12 h, 24 h, and 48 h, accompanied by increased proliferation and apoptosis. All histological changes were accompanied by decreasing expression of certain genes. In most experimental groups of rats and mice, both histological and molecular parameters returned to the baseline values between 48 h and 7 days after intoxication. CONCLUSIONS: In mice and rats with CCl4-induced ALF, signs of liver failure can be seen as early as 12 h and develop to 48 h. In the D-GalN-induced model, mice are more resistant to the hepatotoxic effect than rats (after 12 h), and the early hepatitis phase can be observed much later, after 48 h. These cut-off points seem to be optimal for suppressing inflammation and applying effective stem cell therapy for acute liver injury.
Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Falência Hepática Aguda , Animais , Terapia Baseada em Transplante de Células e Tecidos , Doença Hepática Induzida por Substâncias e Drogas/patologia , Doença Hepática Induzida por Substâncias e Drogas/terapia , Modelos Animais de Doenças , Galactosamina/toxicidade , Lipopolissacarídeos/farmacologia , Fígado/metabolismo , Falência Hepática Aguda/induzido quimicamente , Falência Hepática Aguda/metabolismo , Falência Hepática Aguda/terapia , Camundongos , Necrose/patologia , RatosRESUMO
Serous neoplasms (SN) of the pancreas account for 1-2% of all pancreatic tumours. Six morphological variants of SN were previously recognized: serous microcystic (cyst)adenoma, serous macrocystic (cyst)adenoma, von Hippel-Lindau-associated serous cystic neoplasm, solid serous adenoma/neoplasm, mixed serous-neuroendocrine neoplasm and serous cystadenocarcinoma. It was recently postulated that SN shows a continuous spectrum of morphological patterns rather than distinct clinico-pathological subtypes. To address this issue, we performed a detailed review of 40 SN cases diagnosed at our institution between 1989 and 2011. We found 11 cases of serous microcystic (cyst)adenoma, 5 cases of serous macrocystic (cyst)adenoma, and a single case of von Hippel-Lindau-associated serous cystic neoplasm. Apart from that, we found 20 cases of SN which showed features of both microcystic and macrocystic (cyst)adenomas, 2 cases of small 'incipient' SN and a single case of a mixed microcystic and solid adenoma. In conclusion, we showed that 'borderline' lesions among SNs truly exist and are not rare. The reason for such a wide diversity of morphological patterns of SN remains unknown.