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Traumatic lesions of male external genitalia are certainly less frequent than the other body sites and in the majority of cases they are caused by work accidents in the metalworking environment or by gunshot wounds. We present a rare case of traumatic degloving lesion of the male external genitalia with avulsion of the left testis caused by an accidental fall from the ladder. Reconstructive surgery was carried out in a single procedure, obtaining an excellent esthetic and functional result.
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In this work, we report on the small scale polycondensation and consecutive analysis of novel polyesters based on the potentially renewable 1,3-cyclopentanediol (CPdiol). To avoid evaporation of monomers during thin-film polymerization reactions, trimer pre-polyesters have been synthesized from the corresponding acid-chlorides with diol monomers. Polymerization of these trimers was explored by thermogravimetric analysis to identify potential side reactions, and to assess the ideal polymerization temperature. In general we observe that trans-1,3-cyclopentanediol exhibits good thermal stability up to 200 °C, whereas thermal dehydration of the alcohol end-groups occurs upon further heating. In contrast, for cis-1,3-cyclopentanediol, the ester bonds of the cyclopentane end-groups become labile, thereby generating carboxylic acid end-groups, and 3-cyclopentenol already at 180 °C. The thermal dehydration reactions yield double bond end-groups, which in turn facilitate cross-linking through cross-coupling and Diels-Alder reactions, leading to an increase in molecular weight. Despite the limited thermal stability of CPdiol, here we demonstrate that polymerization of CPdiol can successfully be achieved in thin-film polycondensation conditions at 180 °C, yielding molecular weights well above 10 kg mol-1.
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UNLABELLED: The prostate cancer became for two decades the most frequent cancer in men. We describe the evolution of its incidence and mortality from 1980 to 2011 for France. METHODS: Incidence data were collected from registries and national incidence estimates were based on the use of mortality as a correlate of incidence. RESULTS: After a very strong increase of incidence between 1980 (24.8/100,000) and 2005 (124.5/100,000), we observe a net decline since (97.7/100,000, in 2011). The reduction began earlier for the old patients. The evolution of mortality is very different. We observe a regular reduction since the end of 1990s (from 18.0/100,000 in 1990 to 10.5/100,000 in 2011). The reduction began earlier for the young patients. CONCLUSION: This pattern of evolution is observed in all the countries where the use of the PSA had caused an important increase of the diagnosis of prostate cancer. LEVEL OF EVIDENCE: 3.
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Neoplasias da Próstata/epidemiologia , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , França/epidemiologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Sistema de RegistrosRESUMO
Proximal humeral fractures are complex lesions with difficult management problems; therefore, they pose a challenge for orthopaedic surgeons. In the literature, numerous treatment techniques have been proposed for these kinds of fractures. In our study we reviewed 30 patients with a mean age of 75 years presenting a proximal humeral fracture (Neer 2-3) and treated at our clinic with a Polarus nail, with a mean follow-up of 7 years. We obtained 73.3% of good and excellent results in line with literature. Complications were recorded in 6 of the patients (20%) recruited in our study. In particular, 3 cases of proximal screw pull-out, 1 case of deep infection and 2 cases of acromio-clavicular joint impingement syndrome. The aim of our study was to review our case histories and compare them with the literature analysing this complex type fracture and treatment options.
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Pinos Ortopédicos , Fixação Intramedular de Fraturas/instrumentação , Fraturas do Ombro/diagnóstico por imagem , Fraturas do Ombro/cirurgia , Idoso , Idoso de 80 Anos ou mais , Desenho de Equipamento , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do TratamentoRESUMO
AIM: Functional dyspepsia, though benign, leads to deterioration of the quality of life and high costs for healthcare systems. The optimal therapy for functional dyspepsia is still to be defined because of its multifactorial pathogenesis. In an open multicentric study of patients with functional dyspepsia, we prospectively evaluated the benefit of treatment with a food supplement composed of sodium alginate, carbonate calcium, pineapple, papaya, ginger, α-galactosidase and fennel (Perdiges, Bioten Snc, Turin, Italy). METHODS: Ninety-one consecutive patients were included, suffering from functional dyspepsia, who had been previously submitted to therapy to eradicate the infection from Helicobacter pylori (H. pylori) and were waiting to perform the Urea Breath Test (UBT). The primary goal was to establish the percentage of patients who continued to abstain from proton pump inhibitors (PPI) as they waited to carry out the UBT, differentiating between patients who were treated (N.=55) with Perdiges and those who were not (N.=36). Our secondary goal was to document the differences within the 2 groups in terms of symptoms perceived between the start and end of the observation period. The wellness reported, during or in absence of treatment with Perdiges, was evaluated by the use of the VAS scale (Visual Analogical Scale) completed before the start of the treatment and after 30 days. RESULTS: All the patients treated with Perdiges (55/55, 100%) and 31/36 (86.1%) patients who were not (P=0.008) continued to abstain from PPI in the period awaiting the UBT. The VAS scale of those who took Perdiges improved on average by 1.78 points versus a worsening of 0.08 points of those who did not take it (P<0.0001). Furthermore, while among those who took Perdiges there was a statistically significant improvement (P<0.0001) in the VAS scale, between the baseline and the end of treatment, a worsening of 0.08 points (P=0.78) was noticed among the patients who did not take it. CONCLUSION: Perdiges is significantly effective in the period following treatment to eradicate the infection from H. pylori in patients with functional dyspepsia. This allows to reduce the need to use antisecretive drugs. Further randomised studies, with wide ranging case histories, must assess its long-term efficacy.
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Suplementos Nutricionais , Dispepsia/tratamento farmacológico , Preparações de Plantas/uso terapêutico , Adulto , Antibacterianos/administração & dosagem , Antibacterianos/efeitos adversos , Biotina/uso terapêutico , Combinação de Medicamentos , Quimioterapia Combinada , Dispepsia/etiologia , Dispepsia/microbiologia , Feminino , Seguimentos , Infecções por Helicobacter/tratamento farmacológico , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Inibidores da Bomba de Prótons/administração & dosagem , Inibidores da Bomba de Prótons/efeitos adversos , Qualidade de Vida , Resultado do Tratamento , Escala Visual Analógica , Complexo Vitamínico B/uso terapêuticoRESUMO
The present study aims to assess the evolution of different proto-horizons as embryonic soils built by pedotechnologies for the reclamation and management of derelict and damaged lands, such as abandoned quarries. The model proto-horizons were assembled by utilizing coarse limestone gravel or zeolitized Phlegraean Yellow Tuff (PYT) as mineral components and commercial compost-amendments or a phosphorite-poultry manure mixture as organic matrices for growth of a pasture-grass under controlled conditions. The evolution of the model proto-horizons was followed by an evaluation of the stability and modification of the organic matter (OM) with reference to plant development. The results suggest that the natural carbonatic substrate occurring in limestone quarries was unable to sustain significant plant growth, while the PYT was suitable and efficient as a pedogenic substrate because it supported plant growth and induced a conspicuous accumulation of OM due to root activity. In particular, OM, including humic and non-humic components, greatly increased in the PYT treatment with the phosphorite-poultry manure mixture showing a concurrent trend toward humification. Conversely, an overall tendency toward degradation of OM was detected in the PYT model proto-horizon treated with commercial compost. Feasibility estimates show that quarry restoration costs appear reasonable where environmental impacts are high.
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Solo/análise , Substâncias Húmicas , Itália , Poluentes do Solo/análiseRESUMO
Combination therapies for cancer aim to exploit either additive or synergistic effects arising from the action of two species with the final goal to maximize the therapeutic efficacy. In this work, we develop multifunctional nanoparticles (NPs) for co-delivery of the conventional anticancer drug docetaxel (DTX) and the second generation photosensitizer zinc-phthalocyanine (ZnPc) as potential dual carrier system for the combination of chemotherapy and photodynamic therapy (PDT). Biodegradable and amphiphilic block copolymers based on poly(ε-caprolactone) (PCL=B) and poly(ethylene oxide) (PEO=A), with AB and ABA architectures, were assembled in "core-shell" NPs and loaded with both DTX and ZnPc employing the melting/sonication method. Hydrodynamic diameters within the range 60-100nm and low polydispersity indexes were obtained. Zeta potential was negative for all the formulations and unaffected by drug encapsulation. Concerning drug loading ability of NPs, the entrapment efficiency was related to initial ZnPc/DTX ratio. Steady-stationary and time-resolved emission fluorescence measurements pointed out the embedding of monomeric ZnPc in the NPs, excluding the presence of ZnPc self-supramolecular oligomers. The release of DTX was biphasic whereas ZnPc remained mainly associated with NPs. Singlet oxygen generation was observed when ZnPc-loaded NPs were irradiated at 610nm within a 45min time range, despite that ZnPc was not released in the medium. Stability of NPs in the presence of serum proteins and plasma was excellent and no toxicity toward red blood cells was found. NPs cytotoxicity was evaluated in HeLa cells irradiated for 30min with a halogen lamp. After 72h, viability of cells treated with ZnPc/DTX-loaded NPs strongly decreased as compared to NPs loaded only with DTX, thus showing a combined effect of both DTX and ZnPc. Superior antitumor activity of ZnPc/DTX-loaded NPs as compared to DTX-loaded NPs was confirmed in an animal model of orthotopic amelanotic melanoma, thus pointing to the application of PEO-PCL NPs in the combined chemo-photodynamic therapy of cancer.
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Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Portadores de Fármacos/administração & dosagem , Nanopartículas/administração & dosagem , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/química , Protocolos de Quimioterapia Combinada Antineoplásica/química , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Docetaxel , Portadores de Fármacos/química , Estabilidade de Medicamentos , Feminino , Hemólise/efeitos dos fármacos , Humanos , Indóis/administração & dosagem , Indóis/química , Isoindóis , Melanoma Amelanótico/tratamento farmacológico , Melanoma Amelanótico/patologia , Camundongos , Camundongos Nus , Nanopartículas/química , Compostos Organometálicos/administração & dosagem , Compostos Organometálicos/química , Fotoquimioterapia , Fármacos Fotossensibilizantes/administração & dosagem , Fármacos Fotossensibilizantes/química , Plasma/química , Oxigênio Singlete/química , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/patologia , Taxoides/administração & dosagem , Taxoides/química , Carga Tumoral/efeitos dos fármacos , Compostos de ZincoRESUMO
OBJECTIVES: Present national estimations of the incidence and mortality trends in urological cancers in France between 1980 and 2012. MATERIAL AND METHODS: Francim database and French Register of Cancers. RESULTS: Analysis of the current data shows a regular increase of the incidence of renal cancer in men and women (7,781 cases in men and 3,792 in women in 2012). For bladder cancer, trends are divergent. There is a small reduction in incidence for men and an increase for women (9,549 cases in men and 2,416 in women in 2012). Testicular cancer is still increasing slightly (2,317 incidental cases in 2012). The incidence of prostate cancer experienced a huge increase up until 2005, and thereafter it decreased sharply, though it is difficult to discern whether this drop (which was observed up until 2008) continued at the same rate after that point (56,841 incidences in 2012 based on the rates calculated for 2009). CONCLUSION: The analyses by organ database show that there are significant variations in the incidence of urological cancers, particularly for prostate cancer, which shows that both the natural history of urological tumours and the methods of detection have an impact on incidence.
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Neoplasias da Próstata/epidemiologia , Neoplasias Testiculares/epidemiologia , Neoplasias Urológicas/epidemiologia , Feminino , França/epidemiologia , Humanos , Incidência , Masculino , Neoplasias da Próstata/mortalidade , Neoplasias Testiculares/mortalidade , Neoplasias Urológicas/mortalidadeRESUMO
AIM: Since the major established risk factors explain the pathogenesis of ischemic heart disease (IHD) in a proportion of cases, it is crucial to search for other causal mechanisms. The possible link between IHD and Helicobacter pylori (H.pylori) infection has been reported. However, the precise mechanism of this potential relationship, by a proinflammatory activity or metabolic disorder, is unclear. In order to investigate this issue, the authors assessed changes in clinical and biochemical parameters related to IHD after bacterial eradication. METHODS: A total of 496 patients (281 males; mean age 59.7+/-2.3) with H.pylori-positive dyspepsia and/or peptic ulcer were studied after cure of the bacterium. H.pylori status was determined by histology or 13C-urea breath testing. Examinations for body mass index, diastolic blood pressure and blood testing (C-reactive protein, fibrinogen, triglycerides, total cholesterol, high-density and low-density lipoprotein cholesterol, fasting glucose) were performed before eradication and annually for up to five years thereafter. For statistical analyses, the Student's t test was performed. RESULTS: HDL-C increased (P=0.02) while C-reactive protein and fibrinogen levels diminished (P<0.0001) significantly. BMI and diastolic blood pressure increased in a significant (P=0.032 and P=0.039 respectively) manner compared to baseline. CONCLUSIONS: H.pylori eradication is associated with modification of some clinical and biochemical parameters related to IHD during a follow-up of five years. There is a need for large interventional randomized studies in order to prove a causal association.
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Antibacterianos/uso terapêutico , Doenças Cardiovasculares/etiologia , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori/patogenicidade , Biomarcadores/sangue , Pressão Sanguínea , Índice de Massa Corporal , Testes Respiratórios , Proteína C-Reativa/metabolismo , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/fisiopatologia , HDL-Colesterol/sangue , Feminino , Fibrinogênio/metabolismo , Infecções por Helicobacter/complicações , Infecções por Helicobacter/diagnóstico , Infecções por Helicobacter/microbiologia , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Indução de Remissão , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do TratamentoRESUMO
AIM: Triple therapy consisting of a proton pump inhibitor (PPI) and two antibiotics is used as first choice in treating Helicobacter pylori (H. pylori) infection. Since in the North Italian population, metronidazole resistance is less than 40%, this antibiotic would be preferable as first approach. The aim of this randomized study was to assess the efficacy of a metronidazole-based versus a tinidazole-based treatment, in naïve patients with H. pylori infection. METHODS: Diagnosis and eradication of H. pylori infection were assessed by 13C-urea breath test, and by histology when an endoscopic examination was necessary. A total of 171 patients was treated: 91 (47 males, mean age 50+/-3 years) with metronidazole 250 mg q.i.d., amoxicilline 1 gr b.i.d. and PPI standard dose (MAO), and 80 (36 males, mean age 52+/-3.8 years) with tinidazole 500 mg b.i.d., amoxicilline 1 gr b.i.d. and PPI standard dose (TAO) regimen for 7, 10 or 14 days. RESULTS: Three patients suspended MAO treatment due to side effects. H. pylori eradication was obtained as follow indicated. After 7 days, in 23/30 (76.6%) patients in MAO versus 20/27 (74.0%) in TAO regimen. After 10 days, in 20/26 (76.9%) patients in MAO versus 20/26 (76.9%) in TAO regimen. After 14 days, in 25/32 subjects (78.1%) in MAO versus 21/27 (77.7%) in TAO treatment. The differences among durations or between metronidazole-versus tinidazole-based triple therapy were not statistically different. CONCLUSION: Treatment with metronidazole is as effective as that with tinidazole in terms of efficacy. Moreover, duration did not influence efficacy of treatment.
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Anti-Infecciosos/uso terapêutico , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori , Metronidazol/uso terapêutico , Tinidazol/uso terapêutico , Feminino , Humanos , Itália , Masculino , Pessoa de Meia-IdadeRESUMO
Helicobacter pylori (H.pylori), causal agent of several gastroduodenal diseases, has been involved in diverse aspects of many extragastric manifestations, including ischemic heart disease (IHD). The present paper focuses on the potential pathogenic mechanisms relating H. pylori to IHD. Since H. pylori DNA has been detected in the coronary arteries only in sporadic occasions, and considering that long-term inflammation might raise cytokine levels in the bloodstream, an indirect pathway is more plausible. Moreover, the evidence that some strains of H. pylori induce platelet aggregation supports a role in the acute phase of IHD. In conclusion, because IHD is a multifactorial disease, it is evident that H. pylori is not the only cause. Thus, the definition of H. pylori or other infectious agents as culprits requires a multidisciplinary approach.
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Infecções por Helicobacter/complicações , Helicobacter pylori , Isquemia Miocárdica/microbiologia , Doença Aguda , Animais , Modelos Animais de Doenças , HumanosRESUMO
Patients with chronic liver disease (CLD) respond poorly to standard hepatitis B (HBV) vaccine given as sequential 20 microg IM shots because of an overall impaired immune response. Many of these patients go on to liver transplantation and are at risk of acquiring recurrent or de novo HBV infection. To evaluate the efficacy and safety of high-dose (80 microg) IM HBV vaccination in patients with CLD who had previously failed to respond to a standard three-dose schedule of 40 microg IM vaccine given monthly. A retrospective review was undertaken at our institution of 79 patients with CLD who were treated with high-dose (80 microg) HBV vaccinations. All had previously failed a three-dose course of 40 microg HBV vaccine. An HBV vaccine response was defined as an anti-HBs titer greater than 100 mIU/ml. Liver enzymes, creatinine, age, prothrombin time, total vaccine dose, and MELD score were recorded. No adverse events were reported. Seventy-two per cent (57/79) of the subjects had an adequate response after receiving a mean total dose of 220 mug vaccine (range 80-800 microg). Twenty-eight per cent (22/79) of the subjects did not respond after receiving a mean total dose of 420 microg vaccine (range 240-720 microg). Non-responders had more severe hepatic disease defined as a higher mean total bilirubin level (p = 0.003) and a lower mean albumin level (p < 0.05). Age, prothrombin time, MELD score, and creatinine were not statistically significant between the responders and non-responders. Repeated high-dose (80 microg) HBV vaccination, in patients who do not respond to standard HBV vaccine doses, is safe and effective in the majority of patients with CLD.
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Vacinas contra Hepatite B/administração & dosagem , Vírus da Hepatite B/imunologia , Hepatite B Crônica/imunologia , Hepatite B Crônica/terapia , Imunoterapia/métodos , Adulto , Idoso , Bilirrubina/sangue , Creatinina/sangue , Relação Dose-Resposta Imunológica , Feminino , Anticorpos Anti-Hepatite B/sangue , Hepatite B Crônica/sangue , Hepatite B Crônica/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Tempo de Protrombina , Estudos Retrospectivos , Albumina Sérica/metabolismoRESUMO
Catheter probe endoscopic sonography is a relatively rapid and safe procedure, carried out during standard endoscopy, capable of distinguishing solid from cystic lesions and vascular from avascular masses. Herein we discuss the role of catheter probe endoscopic sonography in the emergency assessment of a patient with recent and severe bleeding from an ulcerated polyp, arising from the papilla. During the endoscopy, catheter probe endoscopic sonography showed the solid and submucosal nature of the lesion, suggesting its localised and benign nature and, most importantly, demonstrating the high risk of rebleeding from vascular structures communicating with the ulcer. Because of this finding three metallic endoclips were positioned. The lesion was not removed endoscopically because of its difficult position and the high risk of haemorrhage. The mass, removed through a duodenotomy, was shown to be a gangliocytic paraganglioma, an uncommon tumour, frequently resulting in surgery because of abdominal pain and gastrointestinal bleeding.
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Neoplasias Duodenais/diagnóstico por imagem , Endossonografia , Paraganglioma/diagnóstico por imagem , Adulto , Neoplasias Duodenais/complicações , Emergências , Hemorragia Gastrointestinal/etiologia , Humanos , Masculino , Paraganglioma/complicações , Tomografia Computadorizada por Raios XRESUMO
Patients with the clinical syndrome of visceral larva migrans as a result of Toxocara species, have typical lesions in the liver consisting of granulomas that contain numerous eosinophils and often Charcot-Leyden crystals. This syndrome is rarely taken into account in patients with cholestatic syndrome, especially when hypereosinophilic reaction is absent. We report the case of a 47-year-old immunocompetent woman who presented with abdominal pain, in whom multiple focal liver lesions were discovered. She had come in contact with dogs. Diagnosis of toxocariasi was done. A good clinical response has been obtained by treating with thiabendazole. We present the findings of various imaging studies of the patient. This report shows that visceral larva migrans may be the cause of a chronic liver disease and should be suspected also in patients without fever and hypereosinophilia with cryptogenic cholestatic and focal liver lesions.
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Larva Migrans/patologia , Larva Migrans/parasitologia , Hepatopatias Parasitárias/patologia , Hepatopatias Parasitárias/parasitologia , Toxocara canis/fisiologia , Toxocaríase/patologia , Toxocaríase/parasitologia , Animais , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Larva Migrans/diagnóstico por imagem , Hepatopatias Parasitárias/diagnóstico por imagem , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Radiografia , Cintilografia , Toxocaríase/diagnóstico por imagemRESUMO
Hepatocellular carcinoma (HCC) is common throughout the world. The incidence of HCC is higher in cirrhotic patients and, among these patients, the incidence rate is 3% in Europe. The overall survival rate of HCC ranges between 20 and 30 months, and is influenced by the local stage of the neoplasm and by the liver function. The literature reports several serological, urinary and radiological markers used for the early detection of HCC. Currently, it is highly recommended to periodically screen cirrhotic patients and hepatitis B virus carriers older than 35 by serum alpha-fetoprotein (AFP) and liver ultrasound (US) every 6 months. The concomitant determination of des-g-carboxy prothrombin and AFP allows a 23% increase in sensibility of the diagnosis for HCC avoiding the need for invasive diagnostic procedures.
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Biomarcadores Tumorais/sangue , Carcinoma Hepatocelular/diagnóstico , Neoplasias Hepáticas/diagnóstico , Biomarcadores/sangue , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/etiologia , Hepatite B/complicações , Hepatite C/complicações , Humanos , Cirrose Hepática/sangue , Cirrose Hepática/complicações , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/etiologia , Programas de Rastreamento , Precursores de Proteínas/sangue , Protrombina , Fatores de Risco , alfa-Fetoproteínas/análiseRESUMO
Hepatitis C is a heterogeneous disease and is responsible for considerable mortality and morbidity. The hepatitis C virus (HCV) infects nearly 170 million people world-wide. More than 80% of infected individuals develop chronic infection; the remaining 10-20% develop spontaneous clearance with natural immunity. Acute hepatitis is icteric in only 20% of patients and is rarely severe. The majority of patients who develop chronic HCV infection are asymptomatic; but 60-80% develop chronic hepatitis as indicated by elevated alanine aminotransferase (ALT), around 30% maintain persistently normal ALT levels despite having detectable HCV-RNA in serum. One-third of chronically infected patients develop progressive liver injury, fibrosis and cirrhosis over a period of 20-30 years. The relationship between virus load, HCV genotype, quasi-species variability and progression of liver disease is controversial. Acquired infection after age 40, male sex, excessive alcohol-consumption, hepatitis B virus (HBV) or HIV co-infection, steatosis, and immunosuppressed state have been identified as co-factors associated with progression of fibrosis and development of cirrhosis. In patients with cirrhosis, the incidence of hepatocellular carcinoma is 2-5% per year. At present, HCV-related end-stage cirrhosis is the first cause of liver transplantation.
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Carcinoma Hepatocelular/etiologia , Hepatite C Crônica/complicações , Hepatite C/complicações , Cirrose Hepática/etiologia , Neoplasias Hepáticas/etiologia , Infecções Oportunistas Relacionadas com a AIDS , Adulto , Ensaios Enzimáticos Clínicos , Progressão da Doença , Feminino , Seguimentos , Genótipo , Hepacivirus/genética , Hepatite C/diagnóstico , Hepatite C/imunologia , Hepatite C Crônica/diagnóstico , Hepatite C Crônica/imunologia , Humanos , Hospedeiro Imunocomprometido , Cirrose Hepática/cirurgia , Transplante de Fígado , Masculino , RNA Viral/análise , Fatores de Tempo , Carga ViralRESUMO
Individuals with chronic hepatitis C (CHC) progress to cirrhosis and hepatic cancer. Individuals with advanced CHC are coagulopathic and can manifest fibrinolysis. The coagulopathy is a consequence of hepatocytic dysfunction. The fibrinolysis represents a response to local endothelial cell injury, and is of a low-grade. Based upon this hypothesis, the effect of the infusion of recombinant human factor VIIa (rh-FVIIa) on endothelial cell inflammatory integrins and measures of endothelial stress were determined in 17 individuals with advanced CHC. Immediately prior to the infusion of rh-FVIIa, the plasma levels of tissue factor (TF), Thrombomodulin (TM), human soluble ICAM-1 (hs-ICAM-1), human soluble VCAM-1 (hs-VCAM-1), human soluble L-Selectin (hs-L-Selectin), the prothrombin time and the activated partial thromboplastin time were determined. The same parameters were assayed at 5, 10, 30, 120, 240 and 360 min after infusion. TF and TM levels were very high at baseline consistent with a vascular endothelial stress response. Similarly hs-ICAM-1, hs-VCAM-1 as well as L-Selectin levels were increased. Thirty minutes after the infusion, a marked reduction in ICAM-1 and VCAM-1 and to a lesser degree L-Selectin levels was observed. This reduction persisted for 360 min. No change in measures of fibrinolysis [plasminogen activator inhibitor-1 (PAI-1), total tissue factor pathway inhibitor (t-TFPI), activated tissue factor pathway inhibitor (TFPIa), d-dimers (DD), FSP and fibrinogen levels] occurred. In addition, no change in plasma Annexin-V was observed. Based upon these data it can be concluded that: (1) rh-FVIIa corrects the coagulopathy seen in advanced CHC; (2) reduces endothelial cell injury and/or stress as evidenced by the TF, TM, hs-ICAM-1 and hs-VCAM-1 levels in plasma; (3) these changes in coagulation occurred without inducing a propagated vascular thrombosis.