RESUMEN
UNLABELLED: This study investigated the efficacy of 131iodine-labeled lipiodol (131I-lipiodol) as a palliative therapy, evaluated overall survival (OS) across Barcelona Clinic Liver Cancer (BCLC) stages, and determined the main prognostic factors influencing OS in patients with hepatocellular carcinoma (HCC). PATIENTS, METHODS: We retrospectively analyzed 57 (44 men; mean age, 65.7 years; mean activity per session, 1.6 GBq; mean cumulative activity in patients with >1 sessions, 3.9 GBq) HCC patients who underwent 131I-lipiodol therapy. A majority of patients exhibited Child-Pugh class B (53.6%) disease and a good Eastern Cooperative Oncology Group performance status (0-1; 72%). Multinodular disease was observed in 87.7% patients, bilobar disease in 73%, and portal vein occlusion (PVO) in 54%. Furthermore, 21.1% patients were staged as BCLC B and 59.6 % as BCLC C. All patients were followed until death. RESULTS: The median OS was 6.4 months, which varied significantly with disease stage (median OS for BCLC A, B, C, and D was 29.4, 12.0, 4.6, and 2.7 months, respectively; p = 0.009); Child-Pugh score and class; presence of ascites, PVO, or extrahepatic disease; largest lesion size; favourable treatment response; international normalized ratio, baseline albumin and alpha-fetoprotein levels. Patients with a Child-Pugh A liver disease had a longer OS. CONCLUSION: Currently, different treatment modalities for HCC include radioembolization, transarterial chemoembolization, and systemic therapy with sorafenib; however, 131I-lipiodol therapy remains a feasible alternative for patients without a favourable response to other therapies, particularly for patients with Child-Pugh A liver cirrhosis.
Asunto(s)
Carcinoma Hepatocelular/radioterapia , Aceite Etiodizado/uso terapéutico , Neoplasias Hepáticas/radioterapia , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma Hepatocelular/diagnóstico por imagen , Quimioradioterapia , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Hepáticas/diagnóstico por imagen , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Cintigrafía , Radiofármacos/uso terapéutico , Estudios Retrospectivos , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
Spontaneous bacterial peritonitis (SBP) is a life-threatening complication of liver cirrhosis. Recently, rifaximin, a non-absorbable antibiotic which is used to prevent recurrent hepatic encephalopathy, has been proposed as effective prophylaxis for SBP. Here, we present an unusual case of SBP under treatment with rifaximin. A 50-year-old woman with liver cirrhosis was admitted because of tense ascites and abdominal pain. She was under long-term oral prophylaxis with rifaximin due to hepatic encephalopathy. Paracentesis revealed SBP caused by Pasteurella multocida, which was sensitive to multiple antibiotics, including rifaximin. Treatment with ceftriaxone resulted in rapid resolution of the peritonitis and restoration of the patient. Since P. multocida is usually transmitted from pets, the patient's cat was tested and could be identified as the most likely source of infection. This case should elicit our awareness that uncommon pathogens and unusual routes of transmission may lead to SBP, despite antibacterial prophylaxis with non-absorbable antibiotics. Nevertheless, such infections may still remain sensitive to systemic therapy with conventional antibiotics.
Asunto(s)
Antiinfecciosos/uso terapéutico , Profilaxis Antibiótica/métodos , Cirrosis Hepática/complicaciones , Infecciones por Pasteurella/diagnóstico , Pasteurella multocida/aislamiento & purificación , Peritonitis/diagnóstico , Rifamicinas/uso terapéutico , Ceftriaxona/uso terapéutico , Femenino , Humanos , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Infecciones por Pasteurella/microbiología , Infecciones por Pasteurella/patología , Infecciones por Pasteurella/prevención & control , Pasteurella multocida/efectos de los fármacos , Peritonitis/microbiología , Peritonitis/patología , Peritonitis/prevención & control , Rifaximina , Resultado del TratamientoRESUMEN
OBJECTIVE: We investigated whether ingestion of polyphenols from fruit juices or a fruit-vegetable-concentrate affects lymphocyte proliferation and apoptosis in human immunodeficiency virus (HIV)-seropositive (HIV(+)) and HIV-seronegative (HIV(-)) subjects. DESIGN: Randomized, prospective pilot intervention study. SETTING: University of Bonn, Department of General Internal Medicine. SUBJECTS: A total of 23 HIV(+) subjects from the HIV outpatient clinic, 18 HIV(-) controls. INTERVENTIONS: Subjects ingested either 1 l of fruit juice or 30 ml of fruit-vegetable-concentrate daily for 16 weeks in addition to their regular diet. Lymphocyte proliferation and apoptosis were investigated in peripheral blood mononuclear cells at baseline, during 16-weeks of intervention, and after a 6-week washout. Proliferation was assessed by (3)H-thymidine incorporation and apoptosis by nuclear content as measured by flow cytometry. RESULTS: Supplementation of fruit juices increased phytohemagglutinin-induced lymphocyte proliferation (mitotic index) in HIV(+) patients from 18+/-16 to 40+/-34 (P=0.004) and in healthy controls from 27+/-16 to 51+/-21 (P=0.016). Apoptosis was not affected in HIV(+) patients, but rose in healthy controls from 9+/-10 to 34+/-11 (apoptotic index; P=0.001). Intervention with concentrate did not significantly alter proliferation and apoptosis in HIV(+) and HIV(-) subjects. CONCLUSIONS: Even though apoptosis did not change in HIV(+) subjects, ingestion of polyphenol-rich fruit juices might be favorable to HIV(+) patients due to enhanced proliferation, which could restore disturbances in T-cell homeostasis. In healthy controls, increased lymphocyte proliferation during juice consumption was counterbalanced by increased apoptosis.
Asunto(s)
Antioxidantes/administración & dosificación , Apoptosis , Frutas/química , Seropositividad para VIH/sangre , Verduras/química , Vitaminas/administración & dosificación , Adulto , Antirretrovirales/uso terapéutico , Bebidas/análisis , Recuento de Linfocito CD4 , Registros de Dieta , Femenino , Flavonoides/administración & dosificación , Flavonoides/análisis , Alemania , Seropositividad para VIH/tratamiento farmacológico , Humanos , Masculino , Persona de Mediana Edad , Fenoles/administración & dosificación , Proyectos Piloto , Polifenoles , TiempoRESUMEN
The effects of two forms of antioxidative co-therapy were analyzed in 24 interferon-alpha (IFN)-naive patients with chronic hepatitis C who were randomized to either receive IFN monotherapy (3 x 4.5 million units IFN-alpha 2a per week), (group A), or IFN and N-acetylcysteine (N-acetylcysteine (NAC) 1.800 mg/day) plus sodium selenite (400 microg/day) supplementation (group B), or treatment as in group B plus vitamin E (544 IU/day) (group C), over 24 weeks. Changes in histology, normalization of ALT, reduction of viral RNA, serum levels of glutathione, selenium, vitamin E, erythrocyte glutathione peroxidase, trolox equivalent antioxidative capacity (TEAC), thiobarbituric acid reactive substances (TBARS) and protein carbonyl groups were measured. Low baseline TEAC and elevated TBARS indicated increased oxidative stress before therapy, which was not affected by antioxidant supplementation. At the end of treatment complete responses were found in 3/8, 2/8 and 6/8 patients in groups A, B and C, respectively, but liver histology had not significantly improved. Vitamin E treated patients had a 2.4 greater chance (95% CI: 1.05-5.5) of obtaining a complete response and had significantly greater reduction in viral load (P = 0.028) than patients without vitamin E. Relapses, i.e. re-appearance of detectable hepatitis C virus (HCV) RNA and/or re-elevation of ALT-activity occurred in 7 out of the 11 responders within 6 months after termination of therapy (group A: 2/3, group B: 1/2 and group C: 4/6). Thus, no overall beneficial effect of antioxidant/IFN therapy was detected. However, the apparent trend towards a more favorable outcome with vitamin E supplementation warrants to further study this substance as an adjuvant to IFN therapy in chronic hepatitis C.
Asunto(s)
Antioxidantes/uso terapéutico , Hepatitis C Crónica/tratamiento farmacológico , Interferón-alfa/uso terapéutico , Acetilcisteína/uso terapéutico , Adulto , Quimioterapia Combinada , Femenino , Glutatión/sangre , Hepacivirus/genética , Hepacivirus/aislamiento & purificación , Hepatitis C Crónica/virología , Humanos , Interferón alfa-2 , Masculino , Persona de Mediana Edad , Estrés Oxidativo , Peroxidasa/sangre , Proyectos Piloto , ARN Viral/sangre , Proteínas Recombinantes , Selenito de Sodio/sangre , Selenito de Sodio/uso terapéutico , Sustancias Reactivas al Ácido Tiobarbitúrico/análisis , Resultado del Tratamiento , Vitamina E/sangre , Vitamina E/uso terapéuticoRESUMEN
BACKGROUND: The aim of this work was to study the effects of combined oral administration of N-acetylcysteine (NAC) and sodium selenite (Se) on plasma glutathione (GSH), lymphocyte subpopulations and viral load in asymptomatic human immunodeficiency virus (HIV)-infected patients. METHODS: We used a prospective, randomized and controlled therapy trial with partial crossover. Twenty-four antiretroviral-naive HIV-infected outpatients at Centers for Disease Control (CDC)'93 stages I and II were randomized to receive the antioxidant combination NAC 600 mg t.i.d. and Se 500 micrograms per day for either 24 weeks (group A, n = 13) or from the end of week 12 (group B, n = 11) until the end of week 24. Thus, group B served as untreated control during the first 12 weeks. RESULTS: There was (a) a trend towards an increase in the percentage of CD4+ lymphocytes after 6 weeks (P = 0.08); (b) an increase in the CD4/CD8 ratio after 6 and 12 weeks (P = 0.02 and P = 0.04 respectively); and (c) a decrease in the absolute CD8/CD38 count and percentage of lymphocytes after 6 weeks (P = 0.002 and P = 0.033 respectively) and 12 weeks (P = 0.033, P = 0.1 respectively) in group A compared with the control period of group B. The effects observed in group A were, however, not paralleled to the same extent by group B after crossing-over to treatment after 12 weeks. In addition, erythrocyte glutathione peroxidase (GSH-Px) activity and GSH, glutathionedisulphide (GSSG) concentrations and the reduced/total GSH ratio were not affected by the treatment. Serum selenium levels increased significantly (P < 0.001) upon treatment. Viral load was not altered. CONCLUSIONS: The changes in lymphocyte subsets after NAC/Se treatment were not comparable to those after standard antiretroviral drug therapy. This, however, does not preclude per se possible benefits of antioxidant supplementation in HIV disease.
Asunto(s)
Acetilcisteína/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , VIH-1/efectos de los fármacos , Selenito de Sodio/uso terapéutico , Administración Oral , Adulto , Eritrocitos/enzimología , Femenino , Glutatión/sangre , Disulfuro de Glutatión/sangre , Glutatión Peroxidasa/sangre , Infecciones por VIH/sangre , Infecciones por VIH/virología , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Estudios Prospectivos , Valores de Referencia , Selenio/sangre , Subgrupos de Linfocitos T/efectos de los fármacos , Carga ViralRESUMEN
Experimental and clinical studies have led to the hypothesis that the phosphodiester signal obtained by 31P magnetic resonance (MR) spectroscopy may be a specific marker for the hepatic induction of oxidative metabolism (P450 induction) by phenobarbitone or ethanol. Systematic studies in humans are lacking. Therefore, we studied 10 volunteers who received rifampin (600 mg/d) for 6 days, resulting in a documented induction of oxidative metabolism as measured by an increase in urinary 6-beta-hydroxycortisol output in all volunteers (P = .0004). 31P-MR spectroscopy and 1H-MR relaxometry were performed before and after hepatic P450 induction. As shown by 31P-MR spectroscopy, the median phosphomonoester concentration (PME) relative to nucleoside triphosphate (NTP) increased by 21% from 0.63 (range, 0.40-0.89) before induction to 0.76 (0.49-1.67) after induction (P = .0451). The median level of phosphodiesters (PDE) relative to NTP increased by 28% from 4.82 (3.41-6.67) before induction to 6.18 (4.63-11.63) after induction (P = .0091). An increase in the level of inorganic phosphates (Pi) relative to NTP was observed, but changes were not significant. As shown by 1H-MR relaxometry, a nonsignificant trend of the liver parenchyma to shorter relaxation times was observed after P-450 induction. In conclusion, both PME/NTP and PDE/NTP ratios (measured by in vivo 31P-MR spectroscopy) increased significantly after hepatic induction with rifampin. Further clinical studies with 31P-MR spectroscopy must take into account the potential effects of P450-inducing agents.
Asunto(s)
Sistema Enzimático del Citocromo P-450/biosíntesis , Hígado/enzimología , Fósforo/metabolismo , Adulto , Antibióticos Antituberculosos/farmacología , Inducción Enzimática , Humanos , Hidrocortisona/análogos & derivados , Hidrocortisona/orina , Hígado/efectos de los fármacos , Imagen por Resonancia Magnética/métodos , Espectroscopía de Resonancia Magnética , Masculino , Radioisótopos de Fósforo/análisis , Rifampin/farmacologíaRESUMEN
OBJECTIVES: Antioxidant defense status was investigated in HIV-infected patients by measuring serum selenium, erythrocyte glutathione peroxidase (GSH-Px) activity, plasma thiol (-SH) and glutathione (GSH) concentrations along with the assessment of the clinical stage and surrogate markers of HIV-disease. DESIGN, SETTING AND SUBJECTS: Serum selenium levels were determined cross-sectionally in 104 sequentially selected HIV-infected patients (83 outpatients and 21 patients with ongoing AIDS defining events). The patients were classified into three stages of the disease, I, II and III according to the 1993 Centers For Disease Control (CDC) classification system for HIV-infection. GSH-Px activities, plasma SH and plasma GSH concentrations were determined in a subset of 24 patients at stage I and 12 patients at stage III with an active AIDS-defining disease. RESULTS: Mean serum selenium levels were lower in CDC stage II (68.7 +/- 20.9 micrograms/l; P < 0.01; n = 34) and stage III (51.4 +/- 14.7 micrograms/l; P < 0.01; n = 37) HIV-infected patients than in healthy subjects (89.2 +/- 20.9 micrograms/l; n = 72) and stage I patients (82.3 +/- 20.5; microgram/l; n = 33). Serum selenium levels were positively correlated with CD4-count (r = 0.42; P < 0.001; n = 104) and inversely with levels of soluble tumor necrosis factor receptors type II (r = -0.58; P < 0.01; n = 35), neopterin (r = -0.5; P < 0.001; n = 80) and beta 2-microglobulin (r = -0.4; P < 0.001; n = 94). Hepatitis C virus (HCV) and HIV-coinfected patients at CDC stages I and II showed markedly lower selenium concentrations compared to HIV-infected patients without concomitant HCV-infection. Serum selenium and GSH-Px activity in hospitalized AIDS patients was significantly lower as compared to asymptomatic patients and healthy subjects, whereas plasma SH and GSH concentrations were lower in both, asymptomatic -and AIDS-patients, than in the controls. CONCLUSION: The results show that stages I-III of HIV-disease are characterized by significant impairments of antioxidative defenses provided by selenium, GSH-Px, SH-groups and GSH.
Asunto(s)
Eritrocitos/enzimología , Glutatión Peroxidasa/sangre , Glutatión/sangre , Infecciones por VIH/sangre , VIH-1 , Selenio/sangre , Adulto , Anciano , Antioxidantes/análisis , Antioxidantes/metabolismo , Femenino , Glutatión Peroxidasa/análisis , Humanos , Masculino , Persona de Mediana Edad , Espectrofotometría Atómica , Compuestos de Sulfhidrilo/sangreRESUMEN
Serum selenium levels were determined cross-sectionally in 57 HIV-infected patients who were classified according to the Centers for Disease Control (CDC) 1993 classification system. Mean serum selenium levels were lower in CDC stage II (58.7 +/- 12.2 micrograms/L; p < 0.01; n = 18) and stage III (47.6 +/- 11.3 micrograms/L; p < 0.01; n = 19) HIV-infected patients, than in healthy subjects (80.6 +/- 9.6 micrograms/L; n = 48) and stage I patients (73.6 +/- 16.5 micrograms/L; n = 20). Serum selenium levels were positively correlated with CD4 count, CD4/8 ratio, hematocrit, and serum albumin (r = 0.42; r = 0.39; r = 0.48; and r = 0.45; p < 0.01, respectively) and inversely with serum levels of thymidine kinase (r = -0.49; p < 0.01; n = 49) and beta 2-microglobulin (r = -0.46; p < 0.001; n = 49). In addition, serum selenium levels in 20 randomly selected AIDS-free individuals (CDC I: n = 10; CDC II: n = 10) were inversely correlated with serum concentrations of interleukin-8 (IL-8) and soluble tumor necrosis factor receptors (sTNFR) types I and II. There was no correlation with serum immuneglobulin A and total serum protein levels. The results show that the progressive deprivation of serum selenium in HIV-infection is associated with loss of CD(4+)-cells and with increased levels of markers of disease progression and inflammatory response.
Asunto(s)
Recuento de Linfocito CD4 , Infecciones por VIH/sangre , Infecciones por VIH/inmunología , VIH-1 , Selenio/sangre , Selenio/deficiencia , Adulto , Biomarcadores , Relación CD4-CD8 , Estudios de Casos y Controles , Femenino , Infecciones por VIH/etiología , Humanos , Inflamación/etiología , Interleucina-8/sangre , Masculino , Persona de Mediana Edad , Receptores del Factor de Necrosis Tumoral/metabolismo , Timidina Quinasa/sangre , Microglobulina beta-2/metabolismoRESUMEN
Epidemiologic and experimental data suggest an antiatherothrombotic potential of omega-3 polyunsaturated fatty acids. Therefore, the Western diet, which supplies predominantly omega-6 polyunsaturated fatty acids, was supplemented with 40 ml/day of cod liver oil, which provides about 10 g of omega-3 polyunsaturated fatty acids daily, for 25 days in eight volunteers. The omega-3 polyunsaturated fatty acids were incorporated in platelet and erythrocyte membrane phospholipids at the expense of omega-6 polyunsaturated fatty acids. Bleeding time increased (p less than 0.01) and platelet count (p less than 0.05), platelet aggregation upon ADP and collagen (p less than 0.01-0.05), and associated thromboxane B2 formation (p less than 0.01) decreased. Blood pressure (p less than 0.05) and blood pressure response to norepinephrine (p less than 0.01) and angiotensin II (NS) fell, without major changes in plasma catecholamines, renin, urinary aldosterone, kallikrein, prostaglandins E2 and F2 alpha and red cell cation fluxes. Biochemical and functional changes were reversed 4 weeks after cod liver oil was discontinued. Formation of prostaglandins derived from eicosapentaenoic acid and interference of eicosapentaenoic acid with formation and action of prostaglandins derived from arachidonic acid were evident in vitro. Whatever the mechanism, this moderate supplement of omega-3 polyunsaturated fatty acids markedly changed membrane phospholipids, which was associated with a shift toward less reactive platelets and a blunted circulatory response to pressure hormones.