RESUMO
BACKGROUND: Suboptimal response to ursodeoxycholic acid occurs in 40% of primary biliary cholangitis (PBC) patients, affecting survival. Achieving a deep response (normalisation of alkaline phosphatase [ALP] and bilirubin ≤0.6 upper limit of normal) improves survival. Yet, the long-term effectiveness of second-line treatments remains uncertain. AIMS: To evaluate the long-term effectiveness of obeticholic acid (OCA) ± fibrates. Focusing on biochemical response (ALP ≤1.67 times the upper limit of normal, with a decrease of at least 15% from baseline and normal bilirubin levels), normalisation of ALP, deep response and biochemical remission (deep response plus aminotransferase normalisation). METHODS: We conducted a longitudinal, observational, multicentre study involving ursodeoxyccholic acid non-responsive PBC patients (Paris-II criteria) from Spain and Portugal who received OCA ± fibrates. RESULTS: Of 255 patients, median follow-up was 35.1 months (IQR: 20.2-53). The biochemical response in the whole cohort was 47.2%, 61.4% and 68.6% at 12, 24 and 36 months. GLOBE-PBC and 5-year UK-PBC scores improved (p < 0.001). Triple therapy (ursodeoxycholic acid plus OCA plus fibrates) had significantly higher response rates than dual therapy (p = 0.001), including ALP normalisation, deep response and biochemical remission (p < 0.001). In multivariate analysis, triple therapy remained independently associated with biochemical response (p = 0.024), alkaline phosphatase normalisation, deep response and biochemical remission (p < 0.001). Adverse effects occurred in 41.2% of cases, leading to 18.8% discontinuing OCA. Out of 55 patients with cirrhosis, 12 developed decompensation. All with baseline portal hypertension. CONCLUSION: Triple therapy was superior in achieving therapeutic goals in UDCA-nonresponsive PBC. Decompensation was linked to pre-existing portal hypertension.
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Fosfatase Alcalina , Ácido Quenodesoxicólico , Colagogos e Coleréticos , Quimioterapia Combinada , Cirrose Hepática Biliar , Ácido Ursodesoxicólico , Humanos , Ácido Quenodesoxicólico/análogos & derivados , Ácido Quenodesoxicólico/uso terapêutico , Masculino , Feminino , Pessoa de Meia-Idade , Ácido Ursodesoxicólico/uso terapêutico , Estudos Longitudinais , Cirrose Hepática Biliar/tratamento farmacológico , Idoso , Resultado do Tratamento , Fosfatase Alcalina/sangue , Colagogos e Coleréticos/uso terapêutico , Ácidos Fíbricos/uso terapêutico , Espanha , Bilirrubina/sangue , AdultoRESUMO
BACKGROUND AND PURPOSE: Spain has been one of the countries more heavily stricken by SARS-CoV-2, which has had huge implications for stroke care. The aim was to analyse the impact of the COVID-19 epidemic outbreak on reperfusion therapies for acute ischaemic stroke in the northwest of Spain. METHODS: This was a Spanish multicentre retrospective observational study based on data from tertiary hospitals of the NORDICTUS network. All patients receiving reperfusion therapy for ischaemic stroke between 30 December 2019 and 3 May 2020 were recorded, and their baseline, clinical and radiological characteristics, extra- and intra-hospital times of action, Code Stroke activation pathway, COVID-19 status, reperfusion rate, and short-term outcome before and after the setting of the emergency state were analysed. RESULTS: A total of 796 patients received reperfusion therapies for ischaemic stroke. There was a decrease in the number of patients treated per week (46.5 patients per week vs. 39.0 patients per week, P = 0.043) and a delay in out-of-hospital (95.0 vs. 110.0 min, P = 0.001) and door-to-needle times (51.0 vs. 55.0, P = 0.038). Patients receiving endovascular therapy obtained less successful reperfusion rates (92.9% vs. 86.6%, P = 0.016). COVID-19 patients had more in-hospital mortality. CONCLUSION: A decrease in the number of patients benefiting from reperfusion therapies was found, with a delay in out-of-hospital and door-to-needle times and worse reperfusion rates in northwest Spain. COVID-19 patients had more in-hospital mortality.
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COVID-19 , AVC Isquêmico/terapia , Pandemias , Reperfusão , Adulto , Idoso , Idoso de 80 Anos ou mais , Serviços Médicos de Emergência/estatística & dados numéricos , Procedimentos Endovasculares/estatística & dados numéricos , Feminino , Humanos , AVC Isquêmico/epidemiologia , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Admissão do Paciente/estatística & dados numéricos , Sistema de Registros , Estudos Retrospectivos , Espanha/epidemiologia , Terapia Trombolítica/estatística & dados numéricos , Resultado do TratamentoRESUMO
Tetraspanins are a family of transmembrane proteins that form membrane microdomains. They play important roles in migration, adhesion and other cellular processes. TspanC8, a subfamily of tetraspanins, was found to associate and promote ADAM10 trafficking and cell surface localization. One of its members, Tspan33, is expressed in activated B cells. Using RT-PCR and flow cytometry, we analysed the pattern of expression of Tspan33 in B cells from healthy donors. We found Tspan33 expression in early and late stages of B cell development. However, Tspan33 expression did not correlate with ADAM10 surface expression. We also found expression of Tspan33 early in the activation process. Given its predominant expression in activated B cells and in several lymphomas, but not in naive B cells, we hypothesize that Tspan33 could be a potential target for therapeutic purposes.
Assuntos
Proteína ADAM10/imunologia , Linfócitos B/imunologia , Memória Imunológica/imunologia , Tetraspaninas/imunologia , Proteína ADAM10/genética , Antígenos CD/imunologia , Antígenos CD/metabolismo , Antígenos CD19/imunologia , Antígenos CD19/metabolismo , Antígenos de Diferenciação de Linfócitos T/imunologia , Antígenos de Diferenciação de Linfócitos T/metabolismo , Linfócitos B/metabolismo , Linhagem Celular Tumoral , Células Cultivadas , Citometria de Fluxo , Expressão Gênica/imunologia , Humanos , Lectinas Tipo C/imunologia , Lectinas Tipo C/metabolismo , Ativação Linfocitária/genética , Ativação Linfocitária/imunologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Tetraspaninas/genética , Fatores de TempoRESUMO
Patients with HCV genotype 3 (GT3) infection and cirrhosis are currently the most difficult to cure. We report our experience with sofosbuvir+daclatasvir (SOF+DCV) or sofosbuvir/ledipasvir (SOF/LDV), with or without ribavirin (RBV) in clinical practice in this population. This was a multicenter observational study including cirrhotic patients infected by HCV GT3, treated with sofosbuvir plus an NS5A inhibitor (May 2014-October 2015). In total, 208 patients were included: 98 (47%) treatment-experienced, 42 (20%) decompensated and 55 (27%) MELD score >10. In 131 (63%), treatment was SOF+DCV and in 77 (37%), SOF/LDV. Overall, 86% received RBV. RBV addition and extension to 24 weeks was higher in the SOF/LDV group (95% vs 80%, P=.002 and 83% vs 72%, P=.044, respectively). A higher percentage of decompensated patients were treated with DCV than LDV (25% vs 12%, P=.013). Overall, SVR12 was 93.8% (195/208): 94% with SOF+DCV and 93.5% with SOF/LDV. SVR12 was achieved in 90.5% of decompensated patients. Eleven treatment failures: 10 relapses and one breakthrough. RBV addition did not improve SVR (RR: 1.08; P=.919). The single factor associated with failure to achieve SVR was platelet count <75×10E9/mL (RR: 3.50, P=.019). In patients with MELD <10, type of NS5A inhibitor did not impact on SVR12 (94% vs 97%; adjusted RR: 0.49). Thirteen patients (6.3%) had serious adverse events, including three deaths (1.4%) and one therapy discontinuation (0.5%), higher in decompensated patients (16.7% vs 3.6%, P<.006). In patients with GT3 infection and cirrhosis, SVR12 rates were high with both SOF+DCV and SOF/LDV, with few serious adverse events.
Assuntos
Antivirais/uso terapêutico , Genótipo , Hepacivirus/classificação , Hepatite C Crônica/tratamento farmacológico , Cirrose Hepática/tratamento farmacológico , Ribavirina/uso terapêutico , Sofosbuvir/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antivirais/efeitos adversos , Feminino , Hepacivirus/genética , Hepacivirus/isolamento & purificação , Hepatite C Crônica/complicações , Hepatite C Crônica/virologia , Humanos , Cirrose Hepática/etiologia , Cirrose Hepática/virologia , Masculino , Pessoa de Meia-Idade , Ribavirina/efeitos adversos , Sofosbuvir/efeitos adversos , Resultado do Tratamento , Proteínas não Estruturais Virais/antagonistas & inibidores , Adulto JovemRESUMO
OBJECTIVE: To analyse the impact of liver resection (LR) in patients with Hepatocellular Carcinoma (HCC) within the Barcelona-Clinic-Liver-Cancer (BCLC)-B stage. METHODS: Analysis of patients with BCLC-B HCC treated with LR or transarterial chemoembolization (TACE) between 2007 and 2012 in our hospital. Survival/recurrence analyses were performed by log-rank tests and Cox multivariate models. Further analyses were specifically obtained for the HCC subclassification (B1-2-3-4) proposed recently. RESULTS: Eighty patients were treated (44-TACE/36-LR). Number of nodules was [1.8(1.1)], being multinodular in 50% of cases. Although resected patients had a higher hospital stay than those who underwent TACE (14 ± 13 vs 7 ± 6; P = 0.004), the rate and severity of complications was lower measured by Dindo-Clavien scale (P < 0.05). Overall survival was 40% with a median follow-up of 29.5 months (0.07-96.9). Five-years survival rates were 62.9%, 28.1% and 15.4%, respectively (P = 0.004) for B1, B2 and B3-4 stages. Cox model showed that only total bilirubin [OR = 2.055(1.23-3.44)] and BCLC subclassification B3-4 [OR = 2.439(1.04-5.7)] and B2 [OR = 2.79(1.35-5.77)] vs B1 were independent predictors of 5-years-survival. In B1 patients, surgical approach led a significant decrease in 5-years recurrence-rate (25% vs 60%; P = 0.018). In the surgical subgroup analysis, better results were observed if well/moderate differentiation combined with no microvascular-invasion (VI) in 5-years-survival (84.6%; P = 0.001) and -recurrence (23.1%; P = 0.041), respectively. These survival and recurrence trends were remarkable in B1 stages. CONCLUSIONS: Management of Intermediate BCLC-B HCC stage should be more complex and include updated criteria regarding B-stage subclassifications, VI and tumour differentiation. Modern surgical resection would offer improved survival benefit with acceptable safety in selected BCLC-B stage patients.
Assuntos
Antibióticos Antineoplásicos/uso terapêutico , Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica/métodos , Doxorrubicina/uso terapêutico , Hepatectomia/métodos , Neoplasias Hepáticas/terapia , Neoplasias Primárias Múltiplas/terapia , Idoso , Carcinoma Hepatocelular/patologia , Estudos de Casos e Controles , Intervalo Livre de Doença , Feminino , Humanos , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Resultado do TratamentoRESUMO
OBJECTIVE: To determine the degree of tumor necrosis in surgical specimens of hepatocellular carcinomas treated with microspheres preloaded with doxorubicin and to analyze the relationship between the degree of necrosis and a) morphologic factors and b) imaging biomarkers. MATERIAL AND METHODS: We studied the livers of 21 patients who had undergone selective arterial chemoembolization with DC beads (Biocompatibles, UK) before receiving liver transplants. RESULTS: Imaging techniques detected 43 nodules (mean size, 25 mm). Angiography showed 25 hypervascularized nodules, 12 slightly vascularized nodules, and 6 avascular nodules. A total of 81 hepatocellular carcinomas (mean size, 15 mm) were detected in the specimens: two were capsular and two had vascular infiltration. The mean degree of necrosis after chemoembolization was 39%; necrosis was greater than 60% in 28 hepatocellular carcinomas and less than 60% in 52. The degree of necrosis correlated significantly with the time elapsed between the last chemoembolization treatment and liver transplantation (the degree of necrosis decreased as time increased), with the number of nodules in the specimen, and with capsular infiltration. When imaging techniques detected 1 or 2 nodules, there was a greater probability of achieving greater than 90% necrosis. No relation with the degree of necrosis achieved was found for the size of the nodules detected at imaging, the enhancement pattern, or the number of chemoembolization treatments. CONCLUSION: The degree of necrosis achieved depends on the time spent on the waiting list, on the number of nodules in the specimen, and on whether capsular infiltration is present.
Assuntos
Antibióticos Antineoplásicos/administração & dosagem , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica/métodos , Doxorrubicina/administração & dosagem , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/terapia , Adulto , Idoso , Carcinoma Hepatocelular/cirurgia , Portadores de Fármacos , Feminino , Humanos , Neoplasias Hepáticas/cirurgia , Transplante de Fígado , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
INTRODUCTION: The Spanish Health System's stroke care strategy (EISNS) is a consensus statement that was drawn up by various government bodies and scientific societies with the aim of improving quality throughout the care process and ensuring equality among regions. Our objective is to analyse existing healthcare resources and establish whether they have met EISNS targets. MATERIAL AND METHODS: The survey on available resources was conducted by a committee of neurologists representing each of Spain's regions; the same committee also conducted the survey of 2008. The items included were the number of stroke units (SU), their resources (monitoring, neurologists on call 24h/7d, nurse ratio, protocols), SU bed ratio/100,000 inhabitants, diagnostic resources (cardiac and cerebral arterial ultrasound, advanced neuroimaging), performing iv thrombolysis, neurovascular interventional radiology (neuro VIR), surgery for malignant middle cerebral artery (MCA) infarctions and telemedicine availability. RESULTS: We included data from 136 hospitals and found 45 Stroke Units distributed unequally among regions. The ratio of SU beds to residents ranged from 1/74,000 to 1/1,037,000 inhabitants; only the regions of Cantabria and Navarre met the target. Neurologists performed 3,237 intravenous thrombolysis procedures in 83 hospitals; thrombolysis procedures compared to the total of ischaemic strokes yielded percentages ranging from 0.3 to 33.7%. Hospitals without SUs showed varying levels of available resources. Neuro VIR is performed in every region except La Rioja, and VIR is only available on a 24h/7 d basis in 17 cities. Surgery for malignant MCA infarction is performed in 46 hospitals, and 5 have telemedicine. CONCLUSION: Stroke care has improved in terms of numbers of participating hospitals, the increased use of intravenous thrombolysis and endovascular procedures, and surgery for malignant MCA infarction. Implementation of SUs and telemedicine remain insufficient. The availability of diagnostic resources is good in most SUs and irregular in other hospitals. Regional governments should strive to ensure better care and territorial equality, which would achieve the EISNS objectives.
Assuntos
Recursos em Saúde/provisão & distribuição , Disparidades em Assistência à Saúde/organização & administração , Acidente Vascular Cerebral/terapia , Procedimentos Endovasculares/métodos , Hospitais , Humanos , Neurologia , Qualidade da Assistência à Saúde , Espanha , Inquéritos e Questionários , Terapia Trombolítica/métodos , Recursos HumanosRESUMO
INTRODUCTION: Lobar intracerebral haemorrhage (LIH), is a rare cause of stroke which accounts for about 20% of primary intracerebral haemorrhages. The most common causes are cerebral amyloid angiopathy (CAA), high blood pressure and others, such as using anti-platelet or anticoagulation agents. We analysed a series of patients with LIH and compared it with subgroups of patients with LIH who were previously receiving anti-platelet or anticoagulation agents. We determined the volume of the bleeding and its predictive value for mortality. PATIENTS AND METHODS: We consecutively and retrospectively included 162 patients diagnosed with LIH and cared for in the Neurology Department of Hospital Meixoeiro in Vigo between 1991 and 2009. We collected demographic characteristics, risk factors, aetiologies and symptoms, and conducted a comparative analysis between the general series and the subgroups of patients receiving anticoagulation and anti-platelet agents. RESULTS: In the general series, the most common cause was possible or probable CAA followed by hypertension. In the subgroup of patients receiving anti-platelet or anticoagulation agents there were no differences in the variables studied, except for the frequency of heart disease. Nonetheless, there were differences with respect to age, heart disease and bleeding volume between the general series (patients not treated with anti-platelet or anticoagulation agents) when compared with the subgroups of patients receiving anti-platelet and anticoagulation agents. CONCLUSIONS: We provide new information regarding the clinical behaviour of LIH and its differences in patients receiving anti-platelet or anticoagulation agents. Mortality is higher in cases of LIH on anticoagulants. LIH. Female sex and the volume of bleeding are predictors of mortality.
Assuntos
Anticoagulantes/uso terapêutico , Hemorragia Cerebral/tratamento farmacológico , Inibidores da Agregação Plaquetária/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Hemorragia Cerebral/etiologia , Hemorragia Cerebral/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Acidente Vascular Cerebral/complicações , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
INTRODUCTION: Stroke is currently a major social health problem. For this reason, the Spanish Ministry of Health approved the Stroke National Strategy (SNS) in 2008 to improve the prevention, treatment and rehabilitation of stroke patients. This plan intends to guarantee 24-hour, 365-days neurological assistance in the whole country by the end of 2010. Our aim was to analyse the situation of stroke assistance in Spain in 2009. MATERIAL AND METHODS: A committee of neurologists practicing in the different autonomous communities (AC), and who had not participated in the preparation of the SNS, was created. A national survey was performed including the number of stroke units (SU) and their characteristics (monitoring, 24-h/7-day on-call neurology service, nursing staff ratio and the use of protocols), bed ratio of SU/100,000 people, availability of intravenous thrombolysis therapy, neurovascular intervention (NI) and telemedicine. RESULTS: We included data from 145 hospitals. There are 39 SU in Spain, unevenly distributed. The ratio between SU bed/number of people/AC varied from 1/75,000 to 1/1,037,000 inhabitants; Navarra and Cantabria met the goal. Intravenous thrombolysis therapy is used in 80 hospitals; the number of treatments per AC was between 7 and 536 in 2008. NI was performed in the 63% of the AC, with a total of 28 qualified hospitals (although only 1 hospital performed it 24h, 7 days a week in 2009). There were 3 hospitals offering clinical telemedicine services. CONCLUSIONS: Assistance for stroke patients has improved in Spain compared to previous years, but there are still some important differences between the AC that must be eliminated to achieve the objectives of the SNS.
Assuntos
Transtornos Cerebrovasculares , Atenção à Saúde , Recursos em Saúde , Acidente Vascular Cerebral/terapia , Coleta de Dados , Fibrinolíticos/uso terapêutico , Hospitais , Humanos , Infusões Intravenosas , Neurologia , Sociedades , Espanha , Telemedicina , Terapia Trombolítica/métodos , Recursos HumanosRESUMO
INTRODUCTION: Lobar intracerebral haemorrhage (LH) is an uncommon cause of stroke. Many LH are caused by cerebral amyloid angiopathy (CAA). The aim of the present study is to analyse the clinical signs, risk factors, lesion volume and development, of a consecutive series of patients suffering from LH and to compare the various characteristics between haemorrhages which comply with the Boston criteria for CAA and those which do not comply with these inclusion criteria. METHODS: A consecutive series of 106 patients suffering from LH and admitted to the neurological service in the Meixoeiro Hospital of Vigo between 1991 and 2005 is described. The Boston criteria were applied to all patients suffering from LH associated with possible, probable and confirmed CAA. The clinical signs, risk factors, haemorrhage sizes, evolution and complications of the patients complying with the CAA inclusion criteria were compared to those who did not comply with the inclusion criteria. RESULTS: The 106 patients from the series, represent 14.4% of intracerebral haemorrhages and 3.7% of all strokes. Fifty-four percent (54 %) of the patients were female and arterial hypertension was an important risk factor. Twenty point eight percent (20.8%) of the patients were admitted in coma and 60% with hemiparesis. Of these LH patients 28.3% died. The haemorrhage volume and the female gender were the only predictive factors for death. No significant variables were observed to differentiate the groups in the comparative analysis of the subgroups of patients with CAA inclusion criteria and those without. CONCLUSIONS: The series studied showed similar risk factors and clinical characteristics to other published series. No predictive clinical variables were found to differentiate between LH which complied with CAA inclusion criteria and those that did not comply.
Assuntos
Angiopatia Amiloide Cerebral/complicações , Hemorragia Cerebral/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Hemorragia Cerebral/complicações , Hemorragia Cerebral/fisiopatologia , Feminino , Humanos , Pessoa de Meia-Idade , Fatores de Risco , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/fisiopatologiaRESUMO
OBJECTIVES: the postoperative evolution of patients submitted to orthotopic liver transplant (OLT) is frequently associated with the appearance of different types of complications such as renal failure, graft rejection, infections, and neurological disorders. These complications are the most significant causes of early morbidity and mortality in patients undergoing OLT. The purpose of the present study was the identification of factors related to the different postoperative complications after OLT. EXPERIMENTAL DESIGN: a prospective study was carried out. PATIENTS: seventy-eight variables were analyzed in 32 consecutive patients undergoing OLT. The factors independently associated with the appearance of postoperative complications were identified using a stepwise logistic regression analysis. RESULTS: the multivariate analysis showed that malondialdehyde and creatinine pretransplant serum levels were associated with the development of renal dysfunction. The pretransplant levels of haemoglobin and the units of platelets administered during surgery were prognostic factors of infections. Acute graft rejection was predicted by ?-glutamyl transpeptidase and total bilirubin serum levels. The pretransplant sodium and glutaredoxin levels in serum were associated with neurological complications. CONCLUSIONS: we propose these markers for the identification of high-risk patients allowing an early surveillance and/or treatment to improve morbidity and survival in patients submitted to OLT.
Assuntos
Transplante de Fígado/efeitos adversos , Feminino , Humanos , Masculino , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Prognóstico , Estudos Prospectivos , Fatores de RiscoRESUMO
UNLABELLED: Orthotopic liver transplantation (OLT) is the best treatment for nonresectable hepatocellular carcinoma (HCC), but tumor recurrence reduces long-term and medium-term survival. The effectiveness of adjuvant chemotherapy to prevent tumor recurrence has not been fully established. METHODS: Three hundred eighty-seven consecutive patients, including 43 with HCC superimposed on liver cirrhosis, underwent OLT. Twelve patients with one or more prognostic criteria for HCC recurrence were entered into a prospective prophylaxis protocol with monthly cycles of cisplatin (60 mg/m(2)) and adriamycin (30 mg/m(2)), beginning the fourth week post-OLT for a maximum of seven sessions. RESULTS: The 5-year survival of the non-HCC patients was 65.7% and that of the HCC patients was 60.46% (P = NS). Chemotherapy was reasonably well tolerated, but the 9 patients with hepatitis C- or B-associated cirrhosis showed viral and histological recurrence of the primary disease. A high proportion of patients (7 of 12) developed tumor recurrence during the first year after OLT. Six of these patients died, all but one due to HCC relapse. Five patients remain healthy and tumor free at 58 to 130 months. Post-OLT adjuvant chemotherapy does not avoid tumor recurrence and its fatal consequences but may contribute to prolonged tumor-free survival among a significant proportion of patients with high-risk HCC. However, the uncertain implications on viral recurrence and the lack of control groups do not allow post-OLT chemotherapy to be recommended outside controlled clinical trials, which are clearly warranted.
Assuntos
Carcinoma Hepatocelular/cirurgia , Quimioterapia Adjuvante , Neoplasias Hepáticas/cirurgia , Adulto , Carcinoma Hepatocelular/mortalidade , Feminino , Humanos , Neoplasias Hepáticas/mortalidade , Pessoa de Meia-Idade , Prognóstico , Recidiva , Estudos Retrospectivos , Análise de Sobrevida , Fatores de TempoRESUMO
UNLABELLED: Pruritus is a common complication of cholestatic liver diseases or liver graft dysfunction. Current medical therapies lack efficacy. The molecular adsorbent recirculating system (MARS) represents an interesting therapeutic option. Our objective was to report our experience in the management of four patients with intractable pruritus with MARS. PATIENTS AND METHODS: The MARS treatment cycle included three consecutive treatments, each of 8 hours duration. The four patients with intractable pruritus who were treated had primary biliary cirrhosis/autoimmune hepatitis overlap syndrome (n = 1), ductopenic allograft rejection (n = 2), or posttransplant cholestatic HCV recurrence (n = 1). Intensity of pruritus was documented 24 hours before as well as 24 hours, 7 and 30 days after MARS therapy, and at the end of follow-up. We measured complete blood cell counts, glucose, BUN, creatinine, sodium, potassium, AST, ALT, GGT, alkaline phosphatase, bilirubin, prothrombin activity, and activated partial thromboplastin time. RESULTS: MARS therapy was well tolerated. Patient 1 experienced temporal relief of pruritus, but needed another MARS cycle because of relapse. Patient 2 experienced partial and temporary relief of pruritus, was listed for retransplantation, and received a liver graft 2 months later. Patient 3 showed a dramatic reduction in the degree of pruritus with MARS. Pruritus in patient 4 decreased promptly with MARS therapy and conversion of immunosuppression to tacrolimus, thereby avoiding retransplantation. CONCLUSION: MARS therapy is a promising, safe therapeutic option to treat refractory pruritus caused by cholestatic liver disorders.
Assuntos
Colestase/terapia , Soluções para Hemodiálise , Hepatopatias/cirurgia , Transplante de Fígado/efeitos adversos , Prurido/terapia , Desintoxicação por Sorção , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/terapiaRESUMO
Middle-age Down's syndrome patients develop dementia with antomicopathological changes that are characteristic for Alzheimer's disease. Cerebral amyolid angiopathy (CAA) most commonly manifests itself as a lobar intracerebral haemorrhage that tends to recur. Multiple haemorrhages may occur simultaneously. CAA is frequently associated with Alzheimer's disease, however the relationship between CCA and Down's syndrome is poorly know. Although there are established clinical criteria for the diagnosis of CAA related to lobar intracerebral haemorrhage, definitive CAA needs anatomicopathologial confirmation. This paper presents the case of a male with Down's syndrome and recurrent lobar intracerebral haemorrhage. An autopsy showed lesions in leptomeningeal and cortical arteries which are characteristic of CAA in addition to anatomicopathological changes of Alzheimer s disease that were mostly seen in entorhinal cortex and hippocampus. The paper also discusses the pathological association between beta-amyloid protein, apolipoprotein alleles, CAA, Alzheimer's disease and Down's syndrome.
Assuntos
Angiopatia Amiloide Cerebral/etiologia , Hemorragia Cerebral/etiologia , Síndrome de Down/complicações , Angiopatia Amiloide Cerebral/diagnóstico , Hemorragia Cerebral/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , RecidivaAssuntos
Rejeição de Enxerto/imunologia , Terapia de Imunossupressão/métodos , Transplante de Fígado , Soro Antilinfocitário/uso terapêutico , Carcinoma Hepatocelular/cirurgia , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Administração de Caso , Rejeição de Enxerto/prevenção & controle , Infecções por HIV/complicações , Hepatite C/complicações , Humanos , Imunossupressores/classificação , Imunossupressores/farmacologia , Imunossupressores/uso terapêutico , Falência Renal Crônica/complicações , Neoplasias Hepáticas/cirurgia , Risco , Linfócitos TRESUMO
D-galactosamine (D-GalN) toxicity is a useful experimental model of liver failure in human. It has been previously observed that PGE1 treatment reduced necrosis and apoptosis induced by D-GalN in rats. Primary cultured rat hepatocytes were used to evaluate if intracellular oxidative stress was involved during the induction of apoptosis and necrosis by D-GalN (0-40mM). Also, the present study investigated if PGE1 (1 microM) was equally potent reducing both types of cell death. The presence of hypodiploid cells, DNA fragmentation and caspase-3 activation were used as a marker of hepatocyte apoptosis. Necrosis was measured by lactate dehydrogenase (LDH) release. Oxidative stress was evaluated by the intracellular production of hydrogen peroxide (H2O2), the disturbances on the mitochondrial transmembrane potential (MTP), thiobarbituric-reacting substances (TBARS) release and the GSH/GSSG ratio. Data showed that intermediate range of D-GalN concentrations (2.5-10mM) induced apoptosis in association with a moderate oxidative stress. High D-GalN concentration (40 mM) induced a reduction of all parameters associated with apoptosis and enhanced all those related to necrosis and intracellular oxidative stress, including a reduction of GSH/GSSG ratio and MTP in comparison with D-GalN (2.5-10 mM)-treated cells. Although PGE1 reduced apoptosis induced by D-GalN, it was not able to reduce the oxidative stress and cell necrosis induced by the hepatotoxin in spite to its ability to abolish the GSH depletion.
Assuntos
Alprostadil/farmacologia , Apoptose/efeitos dos fármacos , Doença Hepática Induzida por Substâncias e Drogas/patologia , Galactosamina , Hepatócitos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Inibidores da Agregação Plaquetária/farmacologia , Animais , Caspase 3 , Caspases/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Fragmentação do DNA , Citometria de Fluxo , Radicais Livres , Glutationa/metabolismo , Hepatócitos/patologia , L-Lactato Desidrogenase/metabolismo , Peroxidação de Lipídeos , Fígado/patologia , Masculino , Potenciais da Membrana , Mitocôndrias/metabolismo , Necrose , Ploidias , Ratos , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismo , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismoRESUMO
OBJECTIVE: To evaluate the characteristics of flutamide induced hepatotoxicity. MATERIAL AND METHODS: In this retrospective study we have analyzed all cases of flutamide hepatotoxicity submitted to the Andalucian Registry of drug-induced liver disease. Data were collected using a structured reporting form. Causality assessment was performed using two clinical scales: the standard CIOMS scale and the recently developed María and Victorino scale. RESULTS: Nine of 185 patients (4.9%) were identified. In 8 male patients, mean age 75 years (range 65-83), flutamide was indicated for palliative therapy of disseminated prostatic carcinoma, and in one young female (14 years) was given for the treatment of facial hirsutism. The mean duration of the flutamide therapy was 151 days (range 4-443). All patients presented with overt liver injury, the most frequent features being asthenia, anorexia, weight loss, nausea, vomiting and jaundice. No patient showed hypersensitivity features. In two patients (22%) the hepatic damage evolved to fulminant liver failure, one of them undergoing a liver transplantation and the other subsequently died. An additional patient died of a non-hepatic related cause when his liver function was improving. Causality assessment by the two clinical scales did not exclude any case, but the two patients who died where classified as unlikely by the María and Victorino scale. CONCLUSIONS: Flutamide can induce severe acute hepatitis, probably due to an idiosyncratic metabolic mechanism. Liver tests monitoring should probably be mandatory during the first months of flutamide therapy and the drug withdrawn if transaminases began to increase.
Assuntos
Antineoplásicos Hormonais/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas , Flutamida/efeitos adversos , Fígado/efeitos dos fármacos , Adolescente , Idoso , Idoso de 80 Anos ou mais , Feminino , Hirsutismo/tratamento farmacológico , Humanos , Masculino , Neoplasias da Próstata/tratamento farmacológico , Estudos RetrospectivosRESUMO
[structure: see text] Synthesis, structure, and reactivity toward amines of the new sulfamoylating reagent 2 are described. Compound 2 allowed sulfamoylation of amines under very mild conditions to give sulfamide derivatives in good yields.
Assuntos
Aminas/química , Di-Hidropiridinas/química , Sulfonamidas/química , Catálise , Cristalografia por Raios X , Espectroscopia de Ressonância Magnética , Conformação Molecular , Estrutura Molecular , Relação Estrutura-AtividadeRESUMO
Three glycosyl (glucosyl, galactosyl, mannosyl) conjugates of 4-hydroxyphenylretinamide have been synthesized and tested on a broad variety of tumor cells. All three compounds are active on promyelocytic leukemia cell lines HL60 but less than the parent compound 4-HPR. Among them, the mannosyl analog stands out by its very low toxicity.