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Aerosol-generating procedures are medical interventions considered high risk for transmission of airborne pathogens. Tracheal intubation of anaesthetised patients is not high risk for aerosol generation; however, patients often perform respiratory manoeuvres during awake tracheal intubation which may generate aerosol. To assess the risk, we undertook aerosol monitoring during a series of awake tracheal intubations and nasendoscopies in healthy participants. Sampling was undertaken within an ultraclean operating theatre. Procedures were performed and received by 12 anaesthetic trainees. The upper airway was topically anaesthetised with lidocaine and participants were not sedated. An optical particle sizer continuously sampled aerosol. Passage of the bronchoscope through the vocal cords generated similar peak median (IQR [range]) aerosol concentrations to coughing, 1020 (645-1245 [120-48,948]) vs. 1460 (390-2506 [40-12,280]) particles.l-1 respectively, p = 0.266. Coughs evoked when lidocaine was sprayed on the vocal cords generated 91,700 (41,907-166,774 [390-557,817]) particles.l-1 which was significantly greater than volitional coughs (p < 0.001). For 38 nasendoscopies in 12 participants, the aerosol concentrations were relatively low, 180 (120-525 [0-9552]) particles.l-1 , however, five nasendoscopies generated peak aerosol concentrations greater than a volitional cough. Awake tracheal intubation and nasendoscopy can generate high concentrations of respiratory aerosol. Specific risks are associated with lidocaine spray of the larynx, instrumentation of the vocal cords, procedural coughing and deep breaths. Given the proximity of practitioners to patient-generated aerosol, airborne infection control precautions are appropriate when undertaking awake upper airway endoscopy (including awake tracheal intubation, nasendoscopy and bronchoscopy) if respirable pathogens cannot be confidently excluded.
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Tos , Vigilia , Humanos , Tos/etiología , Aerosoles y Gotitas Respiratorias , Intubación Intratraqueal/métodos , LidocaínaRESUMEN
Despite advances in antiviral therapy, molecular drivers of Hepatitis C Virus (HCV)-related liver disease remain poorly characterised. Chronic infection with HCV genotypes (1 and 3) differ in presentation of liver steatosis and virological response to therapies, both to interferon and direct acting antivirals. To understand what drives these clinically important differences, liver expression profiles of patients with HCV Genotype 1 or 3 infection (n = 26 and 33), alcoholic liver disease (n = 8), and no liver disease (n = 10) were analysed using transcriptome-wide microarrays. In progressive liver disease, HCV genotype was the major contributor to altered liver gene expression with 2151 genes differentially expressed >1.5-fold between HCV Genotype 1 and 3. In contrast, only 6 genes were altered between the HCV genotypes in advanced liver disease. Induction of lipogenic, lipolytic, and interferon stimulated gene pathways were enriched in Genotype 1 injury whilst a broad range of immune-associated pathways were associated with Genotype 3 injury. The results are consistent with greater lipid turnover in HCV Genotype 1 patients. Moreover, the lower activity in inflammatory pathways associated with HCV genotype 1 is consistent with relative resistance to interferon-based therapy. This data provides a molecular framework to explain the clinical manifestations of HCV-associated liver disease.
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Regulación Viral de la Expresión Génica/genética , Hepacivirus/genética , Hepatitis C/metabolismo , Inflamación/metabolismo , Metabolismo de los Lípidos , Hígado/virología , Adolescente , Adulto , Femenino , Perfilación de la Expresión Génica , Genotipo , Humanos , Hígado/metabolismo , Cirrosis Hepática/metabolismo , Hepatopatías Alcohólicas/metabolismo , Masculino , Redes y Vías Metabólicas , Persona de Mediana Edad , Transcripción Genética , Adulto JovenRESUMEN
A simple, compact, and high-sensitivity optical sensor for salinity measurement is reported based on an optical microfiber coil resonator (MCR). The MCR is manufactured by initially wrapping microfiber on a polymethylmethacrylate (PMMA) rod, which is dissolved to leave a hollow cylindrical fluidic channel within the coil for measurement. Based on the light propagation through the MCR, the device's spectrum moves to long wavelengths with increased salinity in the fluid. The MCR device's sensitivity can reach up to 15.587 nm/% with a resolution of 1.28 × 10-3%. It is also confirmed that the temperature dependence is 79.87 pm/°C, which results from the strong thermal-expansion coefficient of the low refractive index epoxy. The experimental results indicate that the device can be widely used as a high sensitivity salinity sensor in water and other liquids due to its stability, compactness, electromagnetic immunity, and high sensitivity.
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Adipose tissue plays a significant role in whole body energy homeostasis. Obesity-associated diabetes, fatty liver and metabolic syndrome are closely linked to adipose stress and dysfunction. Genetic predisposition, overeating and physical inactivity influence the expansion of adipose tissues. Under conditions of constant energy surplus, adipocytes become hypertrophic and adipose tissues undergo hyperplasia so as to increase their lipid storage capacity, thereby keeping circulating blood glucose and fatty acids below toxic levels. Nonetheless, adipocytes have a saturation point where they lose capacity to store more lipids. At this stage, when adipocytes are fully lipid-engorged, they express stress signals. Adipose depots (particularly visceral compartments) from obese individuals with a severe metabolic phenotype are characterized by the high proportion of hypertrophic adipocytes. This review focuses on the mechanisms of adipocyte enlargement in relation to adipose fatty acid and cholesterol metabolism, and considers how this may be related to adipose dysfunction.
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Adipocitos/patología , Adipocitos/fisiología , Ácidos Grasos/metabolismo , Metabolismo de los Lípidos/fisiología , Obesidad/fisiopatología , Hipernutrición/fisiopatología , Adipocitos/citología , Adiposidad , Humanos , Mediadores de Inflamación/metabolismo , Obesidad/metabolismo , Hipernutrición/complicaciones , Hipernutrición/metabolismo , Estrés FisiológicoRESUMEN
BACKGROUND: Entecavir and tenofovir potently suppress hepatitis B virus (HBV) replication so that serum HBV DNA levels <20 IU/mL can be achieved after 2 years. Despite this, inadequate suppression is reported in >20% of cases for unclear reasons. AIM: We tested whether 4-week viral load (VL) assessment could improve 96-week treatment outcome. METHODS: Data on all chronic hepatitis B patients treated with entecavir or tenofovir between 2005 and 2014 were entered prospectively. Full data capture included pre-treatment, weeks 4, 24, 48 and 96 HBV DNA titre, HBeAg, age, gender, antiviral agent and dose escalation. Compliance data were compiled from pharmacy records, doctors' letters and clinic bookings/attendance. Time to achieve complete viral suppression (HBV DNA < 20 IU/mL) was graphed using Kaplan-Meier curves. Factors affecting this were examined using a multivariate Cox Proportional Hazard model. RESULTS: Among 156 patients treated, 72 received entecavir and 84 tenofovir. Pre-treatment HBV DNA titre, 4-week assessment and compliance impacted significantly on time to complete viral suppression. At 96 weeks, 90% of those assessed as compliant by 4-week HBV DNA had complete viral suppression versus 50% followed by 6-month VL estimation. Continuing care by the same physician was related to 4-week VL testing and optimal compliance. CONCLUSIONS: Medium-term outcomes of HBV antiviral therapy are improved by early on-treatment VL testing, facilitating patient engagement and improved compliance. The observation that 90% complete viral suppression after 2 years monotherapy is achievable in a routine clinic setting questions the need for combination therapy in HBV cases with suboptimal response.
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Antivirales/uso terapéutico , Guanina/análogos & derivados , Hepatitis B Crónica/tratamiento farmacológico , Tenofovir/uso terapéutico , Carga Viral , Adulto , Anciano , Anciano de 80 o más Años , Australia , ADN Viral/sangre , Quimioterapia Combinada , Femenino , Guanina/uso terapéutico , Virus de la Hepatitis B/efectos de los fármacos , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Resultado del TratamientoRESUMEN
BACKGROUND: We have previously demonstrated that peroxisome proliferator-activated receptor (PPARγ) activation inhibits hepatocarcinogenesis. We aim to investigate the effect of PPARγ on hepatocellular carcinoma (HCC) metastatic potential and explore its underlying mechanisms. METHODS: Human HCC cells (MHCC97L, BEL-7404) were infected with adenovirus-expressing PPARγ (Ad-PPARγ) or Ad-lacZ and treated with or without PPARγ agonist (rosiglitazone). The effects of PPARγ on cell migration and invasive activity were determined by wound healing assay and Matrigel invasive model in vitro, and in an orthotopic liver tumour metastatic model in mice. RESULTS: Pronounced expression of PPARγ was demonstrated in HCC cells (MHCC97L, BEL-7404) treated with Ad-PPARγ, rosiglitazone or Ad-PPARγ plus rosiglitazone, compared with control (Ad-LacZ). Such induction markedly suppressed HCC cell migration. Moreover, the invasiveness of MHCC97L and BEL-7404 cells infected with Ad-PPARγ, or treated with rosiglitazone was significantly diminished up to 60%. Combination of Ad-PPARγ and rosiglitazone showed an additive effect. Activation of PPARγ by rosiglitazone significantly reduced the incidence and severity of lung metastasis in an orthotopic HCC mouse model. Key mechanisms underlying the effect of PPARγ in HCC include upregulation of cell adhesion genes, E-cadherin and SYK (spleen tyrosine kinase), extracellular matrix regulator tissue inhibitors of metalloproteinase (TIMP) 3, tumour suppressor gene retinoblastoma 1, and downregulation of pro-metastatic genes MMP9 (matrix metallopeptidase 9), MMP13, HPSE (heparanase), and Hepatocyte growth factor (HGF). Direct transcriptional regulation of TIMP3, MMP9, MMP13, and HPSE by PPARγ was shown by ChIP-PCR. CONCLUSION: Peroxisome proliferator-activated receptor-gamma exerts an inhibitory effect on the invasive and metastatic potential of HCC in vitro and in vivo, and is thus, a target for the prevention and treatment of HCC metastases.
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Carcinoma Hepatocelular/tratamiento farmacológico , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , PPAR gamma/agonistas , PPAR gamma/metabolismo , Tiazolidinedionas/farmacología , Animales , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Western Blotting , Cadherinas , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patología , Adhesión Celular/efectos de los fármacos , Movimiento Celular/efectos de los fármacos , Inmunoprecipitación de Cromatina , Perfilación de la Expresión Génica , Humanos , Hipoglucemiantes/farmacología , Técnicas In Vitro , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/secundario , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Análisis de Secuencia por Matrices de Oligonucleótidos , ARN Mensajero/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Rosiglitazona , Células Tumorales CultivadasRESUMEN
BACKGROUND: Liver disease is an increasing cause of morbidity and mortality in Human immunodeficiency virus (HIV) positive patients. AIM: To describe the first cases of organ transplantation in HIV positive patients in Ireland. METHOD: We report the Irish patients with HIV who received liver transplantation and performed a chart review. RESULT: Two patients received liver transplantation for end stage liver disease caused by Hepatitis C, with survival at 2 years of 100%. CONCLUSION: Liver transplantation is a feasible treatment for patients with HIV and end stage liver disease. The success of transplantation in the HIV positive population should encourage the provision of other medical and surgical interventions previously not offered to patients with HIV.
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Enfermedad Hepática en Estado Terminal/cirugía , Infecciones por VIH/complicaciones , Hepatitis C Crónica/complicaciones , Cirrosis Hepática/complicaciones , Trasplante de Hígado , Enfermedad Hepática en Estado Terminal/etiología , Infecciones por VIH/tratamiento farmacológico , Humanos , Irlanda , MasculinoRESUMEN
Hepatitis C virus (HCV) is a major cause of liver disease in HIV-infected patients. The HCV treatment outcomes and barriers to HCV referral were examined in a centre with a HIV/HCV co-infection clinic. Patients who were antibody positive for both HIV and HCV between 1987 and January 2009 were identified. A retrospective chart review was undertaken. Multivariate analysis was performed to assess predictors of HCV clinic referral. Data were collected on 386 HIV/HCV patients; 202/386 had been referred to the co-infection clinic and 107/202 had HCV treatment. In addition, 29/202 were undergoing pretreatment work-up. Overall sustained virologic response (SVR) was 44%; SVR was equivalent in those who acquired HIV/HCV infection from intravenous drug use (IDU) and others. On multivariate analysis, patients who missed appointments, were younger, with active IDU and advanced HIV and who were not offered HCV treatment were less likely to be referred to the clinic. Patients attending the clinic were more likely to have been screened for hepatocellular carcinoma than those attending the general HIV service. Two-thirds of patients referred to the clinic had engaged with the HCV treatment programme. Dedicated co-infection clinics lower the threshold for treatment and improve management of liver disease in co-infected patients.
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Instituciones de Atención Ambulatoria/estadística & datos numéricos , Antivirales/uso terapéutico , Infecciones por VIH/complicaciones , Hepacivirus/efectos de los fármacos , Hepatitis C/complicaciones , Hepatitis C/tratamiento farmacológico , Interferón-alfa/uso terapéutico , Polietilenglicoles/uso terapéutico , Ribavirina/uso terapéutico , Adulto , Estudios de Cohortes , Coinfección , Quimioterapia Combinada , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/prevención & control , Infecciones por VIH/virología , Hepatitis C/prevención & control , Hepatitis C/virología , Humanos , Interferón alfa-2 , Persona de Mediana Edad , Evaluación de Programas y Proyectos de Salud , Proteínas Recombinantes/uso terapéutico , Derivación y Consulta/estadística & datos numéricos , Abuso de Sustancias por Vía Intravenosa/complicaciones , Resultado del Tratamiento , Adulto JovenRESUMEN
OBJECTIVE: Fat Aussie mice (foz/foz) are morbidly obese, glucose intolerant and have liver steatosis that develops into steatohepatitis on a high-fat diet. The cannabinoid 1 receptor (CB1) antagonist SR141716 has been shown to improve obesity-associated metabolic complications in humans and rodent models. The aim of this study was to assess the effect of SR141716 in foz/foz mice. DESIGN: Male wildtype (WT) and foz/foz mice were fed a chow or high-fat diet (45% saturated fat). Vehicle or SR141716 (10 mg kg(-1) per day) was administered in jelly once daily for 4 weeks from 4 months of age. RESULTS: Foz/foz mice were obese but had less epididymal adipose tissue mass than fat-fed WT mice despite being significantly heavier. Liver weight was increased by twofold in foz/foz compared with WT mice and showed significant steatogenesis associated with impaired liver function. Foz/foz and fat-fed WT mice were glucose intolerant as determined by oral glucose tolerance test. In chow-fed foz/foz mice, SR141716 reduced body weight, liver weight, reversed hepatosteatosis and glucose intolerance. Subcutaneous white adipose tissue gene expression of the macrophage-specific marker Cd68 reflected the improvements in the metabolic status by SR141716 in these mice. CONCLUSION: The results are consistent with the hypothesis that foz/foz mice have defective lipid metabolism, are unable to adequately store fat in adipose tissue but instead sequester fat ectopically in other metabolic tissues (liver) leading to insulin resistance and hepatic steatosis associated with inflammation. Our findings suggest that SR141716 can improve liver lipid metabolism in foz/foz mice in line with improved insulin sensitivity and adipose tissue inflammation.
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Tejido Adiposo/metabolismo , Hígado Graso/tratamiento farmacológico , Inflamación/tratamiento farmacológico , Metabolismo de los Lípidos/efectos de los fármacos , Hígado/metabolismo , Obesidad Mórbida/tratamiento farmacológico , Obesidad Mórbida/metabolismo , Piperidinas/farmacología , Pirazoles/farmacología , Receptor Cannabinoide CB1/antagonistas & inhibidores , Tejido Adiposo/efectos de los fármacos , Tejido Adiposo/patología , Animales , Dieta Alta en Grasa , Modelos Animales de Enfermedad , Hígado Graso/metabolismo , Hígado Graso/patología , Intolerancia a la Glucosa/metabolismo , Prueba de Tolerancia a la Glucosa , Inflamación/etiología , Inflamación/metabolismo , Inflamación/patología , Resistencia a la Insulina , Hígado/efectos de los fármacos , Hígado/patología , Masculino , Ratones , Obesidad Mórbida/complicaciones , RimonabantRESUMEN
Although the number of mental health presentations to emergency departments is increasing as a result of the integration of psychiatric services with general services, few studies have explored the characteristics of mental health patients presenting to emergency departments in Australia. This study investigated the characteristics of, and outcomes in relation to, people presenting with a mental health problem to one large metropolitan emergency department. Data were collected from the emergency department's electronic records system for adult patients aged 18-65 years old with an emergency department discharge diagnosis of a mental health disorder, including substance abuse and psychosocial crisis, for two months. Mental health patients totalled 5.3% (n= 290) of adult presentations to the emergency department. Over half were male; mean age 37.4 years; 49% were allocated triage category 3/urgent; 45% arrived by ambulance; 39% were overdosed/intoxicated and 55% received one or more diagnostic investigations. Patients who were intoxicated, those who arrived after hours, or patients admitted to a mental health ward were more likely to wait longer than 8h. Findings are broadly in line with that reported for other Australian studies, although the present findings suggest that patients had significantly more routine investigations and there were higher rates of presentations for 'intoxication'.
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Servicios de Urgencia Psiquiátrica/estadística & datos numéricos , Adolescente , Adulto , Anciano , Servicio de Urgencia en Hospital/estadística & datos numéricos , Femenino , Hospitalización/estadística & datos numéricos , Humanos , Tiempo de Internación , Masculino , Trastornos Mentales/epidemiología , Trastornos Mentales/terapia , Persona de Mediana Edad , Alta del Paciente/estadística & datos numéricos , Servicio de Psiquiatría en Hospital/estadística & datos numéricos , Victoria/epidemiología , Adulto JovenRESUMEN
SUMMARY: The impact of mutations in the precore and basal core promoter (BCP) regions of the hepatitis B virus on the course of chronic liver disease is not well established. We sought to examine the relationship of these characteristics to the clinical expression of liver disease in patients infected with genotype D chronic hepatitis B (CHB). BCP and precore mutations in 110 patients with genotype D1 CHB were determined and correlated with clinical phenotype. Of 110 patients, 95 (86.5%) were HBeAg-negative. Compared with HBeAg-positive subjects, HBeAg-negative patients were over a decade older and had lower viral loads (3.70 +/- 0.98 vs 5.77 +/- 0.69 log copies/ml, P < 0.001). The double mutation A1762T-G1764A was more prevalent in patients with advanced liver disease (AdLD) and was associated with higher alanine aminotransferase and viral load. After adjusting for age, there was a more than fourfold increase in the risk of AdLD with this mutation (OR = 4.4; 95% CI: 1.13-16.92, P < 0.03). Conversely, the G1757A substitution was associated with protection, being 90% less frequent among patients with AdLD (P = 0.001). The results indicate that in genotype D CHB, the presence of the A1762T-G1764A mutation was associated with more aggressive liver disease while the G1757A substitution was associated with protection from advanced disease.
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Virus de la Hepatitis B , Hepatitis B Crónica , Mutación , Regiones Promotoras Genéticas/genética , Precursores de Proteínas/genética , Proteínas del Núcleo Viral/genética , Adulto , Anciano , ADN Viral/análisis , ADN Viral/aislamiento & purificación , Femenino , Genotipo , Antígenos del Núcleo de la Hepatitis B/genética , Virus de la Hepatitis B/clasificación , Virus de la Hepatitis B/genética , Virus de la Hepatitis B/patogenicidad , Hepatitis B Crónica/genética , Hepatitis B Crónica/fisiopatología , Hepatitis B Crónica/virología , Humanos , Irán , Masculino , Persona de Mediana Edad , FilogeniaRESUMEN
The objective of the study was to evaluate the role of rapid virological response (RVR) in predicting sustained virological response (SVR) rates to hepatitis C virus (HCV) therapy. 65 HIV / HCV co-infected patients commenced HCV treatment per protocol. HIV / HCV patients with a mean CD4 count of 502 were treated for 24-48 weeks depending on genotype. Virological response was assessed at weeks 4 (RVR), 12 [early virological response (EVR)], 24, at end of treatment (EOTR) and 24 weeks post-completion of treatment (SVR). Primary end-point was defined as undetectable HCV RNA at 24 weeks post-treatment completion. Fifty-five per cent of co-infected patients were on highly active anti-retroviral therapy. A majority of patient group were male. 60% of HIV / HCV patients achieved SVR (35% genotype 1 / 4; 77% genotype 2 / 3). 24 HIV / HCV patients achieved undetectable HCV levels compared with baseline by week 4. The positive predictive value (PPV) of RVR at week 4 for subsequent SVR in HIV-HCV co-infected patients was 100%; the negative predictive value (NPV) was 57%. Significant variables associated with SVR were: (i) lower median pre-treatment HCV viral load, (ii) genotype 2 / 3 disease and (iii) achievement of RVR. Independent variables associated with RVR were low pre-treatment HCV viral load and genotype 2 / 3 disease. Achievement of RVR, a negative HCV-PCR, at week 4 of treatment is predictive of SVR in this cohort of patients. This may be used to guide optimal treatment duration in patient groups. More significantly, the data serve to highlight the subgroup of patients who, on achieving RVR, should be actively supported to complete HCV treatment with full dose therapy, especially patients co-infected with G2 / 3 disease for whom 6 months' full dose therapy may be sufficient to obtain a SVR.
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Antivirales/uso terapéutico , Infecciones por VIH/complicaciones , Hepacivirus/genética , Hepatitis C/complicaciones , Interferón-alfa/uso terapéutico , Ribavirina/uso terapéutico , Viremia , Adulto , Femenino , Genotipo , Hepacivirus/efectos de los fármacos , Humanos , Interferón alfa-2 , Masculino , Polietilenglicoles/uso terapéutico , ARN Viral/sangre , Proteínas Recombinantes , Estudios Retrospectivos , Resultado del TratamientoAsunto(s)
Hígado Graso/complicaciones , Hepatitis A/inmunología , Cirrosis Hepática/patología , Adulto , Factores de Edad , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Inmunoglobulina G/sangre , Cirrosis Hepática/etiología , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Análisis de Regresión , Factores Sexuales , Sri LankaRESUMEN
Hepatitis C virus-infected haemophiliacs are traditionally under represented in international treatment studies thus data assessing response to pegylated-interferon (peg-IFN) and ribavirin (RBV) in HCV mono-infected or HCV/HIV co-infected haemophiliacs are few. Since 2001, 37 haemophiliac patients have received peg-IFN and RBV according to centre-based investigator initiated protocols. Primary end points were: early virological response (EVR); end of treatment response (EOTR) and sustained virological response (SVR). An intention-to-treat analysis was used. Secondary end points were adverse events, haemopoietic stem cell growth factor use, therapy discontinuations and dose reductions. Hepatitis C virus mono-infection group (Mono-I) numbered 20 (60% genotype 1). HCV/HIV co-infected group (Co-I) numbered 17 (59% genotype 1/4). Primary end points were: EVR 76%, EOTR 70% and SVR 43%. Comparison of Mono-I to Co-I demonstrated: EVR rates of 70% and 82%, respectively; EOTR rates of 65% and 76%, respectively, and SVR rates of 35% and 53%, respectively. SVR rates genotype 1/4 group - 17% (Mono-I) vs. 30% (Co-I); SVR rates genotype 2/3 group - 63% (Mono-I) vs. 86% (Co-I). Therapy discontinuations: six of 20 (30%) Mono-I vs. three of 17 (18%) Co-I. Dose reductions: two of 20 (10%) Mono-I vs. zero of 17 Co-I. Haematological support factor use: one of 20 (5%) Mono-I vs. four of 17 (23.5%) Co-I. Virological outcomes to peg-IFN and RBV in HCV-infected haemophiliacs are comparable to published data relating to other HCV-infected cohorts. Good virological outcomes can be achieved in HIV co-infected haemophiliacs particularly when growth factors are used to facilitate full dosing of peg-IFN and RBV.
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Antivirales/uso terapéutico , Hemofilia A/tratamiento farmacológico , Hepatitis C Crónica/tratamiento farmacológico , Interferón-alfa/uso terapéutico , Polietilenglicoles/uso terapéutico , Ribavirina/uso terapéutico , Adulto , Estudios de Cohortes , Quimioterapia Combinada , Femenino , Genotipo , Hemofilia A/complicaciones , Hepatitis C Crónica/complicaciones , Humanos , Interferón alfa-2 , Masculino , ARN Viral/sangre , Proteínas Recombinantes , Estudios Retrospectivos , Carga ViralRESUMEN
Temperature-dependent (TD) Raman measurements at laser excitation 514.5 nm were performed at different concentrations. The spectral profile of the radial breathing modes were investigated up to a polymer concentration of 1 g/L and were found to be dominated by approximately 1.2-1.4 nm diameter tubes at room temperature. Upon heating above the glass transition of the polymer (60 degrees C) the smaller tubes around approximately 0.9 nm increased significantly in relative intensity. This suggests that below the glass transition of the polymer (60 degrees C) RBMs within the composite are damped and spectral changes cannot be interpreted as diameter selective solubilization. The observed RBM damping at room temperature only occurred up to a concentration of approximately 1.2 x 10(-4) g/L and below this no damping was observed. Photoluminescence intensity (PL) measurements were taken for a range of PmPV concentrations, in which HiPco single walled carbon nanotubes (SWNTs) at 100%, 10%, 1%, 0.1%, 0.01%, and 0% mass fractions were added. Fitting of the concentration dependence to a dynamic absorption/desorption model indicates that the polymer interacts with nanotube bundles until a critical concentration of approximately 1.2 x 10(-4) g/L is reached, below which the nanotubes are isolated. The polymer and or solvent has a significant effect on the debundling and aggregation within these systems. Aggregation and/or interaction with the polymer at higher concentrations can effect the RBM profile in the composite at ambient temperatures, providing an incomplete representation of the selection of diameters present within composites at a particular wavelength.
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The aim of this study was to determine whether hepatobiliary scintigraphy using (99m)technetium based di-isopropryl-imino-diacetic acid correlated to clinical or laboratory status of patients with primary sclerosing cholangitis (PSC). We carried out a retrospective case-control study involving 15 patients with proven PSC. Fifty-seven hepatobiliary scintigraphic studies were reviewed by consensus of two experienced observers using a semiquantitative scheme to score liver size and degree of radiopharmaceutical uptake, intrahepatic or extrahepatic biliary stasis, segmental liver clearance half-times and gall bladder visualization. The results were compared with age; disease duration; weight loss; serum bilirubin, alkaline phosphatase and albumin levels; antipyrine clearance; number of biliary stents and episodes of cholangitis and history of transplantation. Sixteen age-matched and sex-matched individuals with PSC, who did not undergo hepatobiliary scans, were selected for comparison. Among the scintigraphic variables, right lateral and superior liver clearance half-time values showed a significant linear correlation with disease duration and serum alkaline phosphatase levels (P < 0.05) but not with other clinical or biochemical indices. Other scintigraphic variables showed no correlation. An abnormal, hepatobiliary scan liver clearance half-time in patients with PSC correlates to disease duration and increased serum alkaline phosphatase levels, and this variable may be used to identify some subjects with more advanced disease.
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Colangitis Esclerosante/diagnóstico por imagen , Disofenina de Tecnecio Tc 99m/farmacocinética , Adulto , Estudios de Casos y Controles , Distribución de Chi-Cuadrado , Femenino , Humanos , Masculino , Persona de Mediana Edad , Cintigrafía , Radiofármacos/farmacocinética , Estudios Retrospectivos , Estadísticas no ParamétricasRESUMEN
OBJECTIVE: The aim of this study was to assess the efficacy, safety and tolerability of pegylated interferon and ribavirin in HIV/hepatitis C virus (HCV)-coinfected patients, prescribed for the same duration and at the same dosage as that used in HCV monoinfection studies. DESIGN: It was an open-label, single-centre, prospective study. METHODS: Forty-five patients coinfected with HIV and HCV with CD4 counts >200 cells/microL were treated with pegylated interferon-alpha2b 1.5 microg/kg/week and ribavirin 1000-1200 mg/day for 24-48 weeks depending on HCV genotype. Safety and tolerability were assessed weekly for the first month and monthly thereafter. Virological response was assessed at weeks 4, 12 and 24 and at the end of treatment and 12 and 24 weeks post completion of treatment. The primary endpoint was defined as undetectable HCV RNA at 24 weeks post completion of treatment [sustained virological response (SVR)]. RESULTS: The majority of patients were male and had been injecting drug users. Sixty per cent were on antiretroviral therapy. In an intention-to-treat analysis, 53% had an SVR (genotype 1, 19% and genotype 2/3, 75%). All patients who had undetectable HCV RNA at week 4 of HCV treatment [very early virological response (VEVR)] had a SVR. On multivariate analysis only HCV genotype predicted SVR. Adverse events occurred frequently. CONCLUSIONS: These results indicate that 24 weeks of HCV treatment may be adequate for HIV-infected individuals coinfected with HCV genotype 2 or 3. VEVR can predict SVR in this group and may be used to guide the subgroup of genotype 2/3 individuals who will respond to 24 weeks of treatment.
Asunto(s)
Antivirales/administración & dosificación , Infecciones por VIH/complicaciones , Hepatitis C/tratamiento farmacológico , Interferón-alfa/administración & dosificación , Polietilenglicoles/administración & dosificación , Ribavirina/administración & dosificación , Adulto , Terapia Antirretroviral Altamente Activa , Antivirales/efectos adversos , Recuento de Células Sanguíneas , Recuento de Linfocito CD4 , Esquema de Medicación , Portadores de Fármacos , Quimioterapia Combinada , Femenino , Genotipo , Infecciones por VIH/sangre , Infecciones por VIH/tratamiento farmacológico , Hepacivirus/aislamiento & purificación , Hepatitis C/sangre , Hepatitis C/complicaciones , Humanos , Interferón alfa-2 , Interferón-alfa/efectos adversos , Masculino , Trastornos Mentales/inducido químicamente , Polietilenglicoles/efectos adversos , Estudios Prospectivos , ARN Viral/análisis , Proteínas Recombinantes , Ribavirina/efectos adversos , Resultado del Tratamiento , Carga ViralRESUMEN
When assessing patients with chronic hepatitis B virus (HBV) infection, consider the state of viral replication, the immune response and whether viral mutations could be present, as well as evidence for liver disease or extrahepatic manifestations. In wild-type infections, loss of hepatitis B e antigen (HBeAg), gain of anti-HBe and disappearance of HBV DNA from serum indicate immunosuppression of viral replication, or 'nonreplicative chronic HBV infection'. This 'healthy carrier' state must be distinguished from HBeAg-negative chronic hepatitis B (CHB) resulting from precore and core promoter mutations. HBeAg-negative CHB is common with genotypes D (Mediterranean region, south Asia) and C (north Asia) infections. Age, disease activity (alanine aminotransferase level) and severity (fibrosis stage, cirrhosis) influence treatment decisions. Following the marginal effectiveness of interferon and often temporary effectiveness of lamivudine due to drug resistance, treatment of CHB is entering a new era. Adefovir, entecavir, tenofovir, telbivudine and clevudine have equal or superior antiviral efficacy to lamivudine, whereas several agents are effective against lamivudine-resistant HBV. Pegylated-interferon (peginterferon) is superior to conventional interferon for obtaining sustained immunosuppression of HBV without drug resistance. Antiviral suppression of HBV replication for 2-5 years reverses hepatic fibrosis, prevents cirrhosis and, when cirrhosis is established, improves liver function, prevents hepatic decompensation and lowers the risk of liver cancer. Before embarking on immunosuppressive chemotherapy or organ transplantation in patients with chronic HBV infection, it is important to start antiviral therapy to prevent hepatitis flares. Antiviral therapy can be effective against membranous glomerulonephritis and polyarteritis nodosa caused by HBV. Further improvements in treatment of CHB are needed to prevent drug resistance and permanently suppress viral replication by eradicating viral templates or stimulating host immune responsiveness to HBV.
Asunto(s)
Antivirales/uso terapéutico , Hepatitis B Crónica/tratamiento farmacológico , Humanos , Resultado del TratamientoRESUMEN
Hepatocellular carcinoma (HCC) is a leading cause of cancer death worldwide, and incidence rates in Western countries are on the rise. Despite many options, no ideal treatment yet exists for this highly malignant tumour, and management strategies have varied accordingly. This review summarises current strategies for the diagnosis and management of HCC.