RESUMEN
BACKGROUND: The Patient Reported Outcome for Fighting FInancial Toxicity (PROFFIT) questionnaire was developed to measure financial toxicity (FT) and identify its determinants. The aim of the present study was to confirm its validity in a prospective cohort of patients receiving anticancer treatment. PATIENTS AND METHODS: From March 2021 to July 2022, 221 patients were enrolled at 10 Italian centres. Selected items of the EORTC-QLQ-C30 questionnaire represented the anchors, specifically, question 28 (Q-28) on financial difficulties, and questions 29-30 measuring global health status/quality of life (HR-QOL). The study had 80% power to detect a 0.20 correlation coefficient (r) between anchors and PROFFIT-score (items 1-7, range 0-100, 100 indicating maximum FT) with bilateral alpha 0.05 and 80% power. Confirmatory factor analysis was conducted. FT determinants (items 8-16) were described. RESULTS: Median age of patients was 65 years, 116 (52.5%) were females, 96 (43.4%) had low education level. Confirmatory factor analysis confirmed goodness of fit of the PROFFIT-score. Significant partial correlation of PROFFIT-score was found with Q-28 (r = 0.51) and HR-QOL (r = -0.23). Mean (SD) PROFFIT-score at baseline was 36.5 (24.9); it was statistically significantly higher for patients living in South Italy, those with lower education level, those who were freelancer/unemployed at diagnosis and those who reported significant economic impact from the COVID-19 pandemic. Mean (SD) scores of determinants ranged from 17.6 (27.1) for item 14 (support from medical staff) to 49.0 (36.3) for item 10 (expenses for medicines or supplements). PROFFIT-score significantly increased with worsening response to determinants. CONCLUSIONS: External validation of PROFFIT-score in an independent sample of patients was successful. The instrument is now being used in clinical studies.
Asunto(s)
Neoplasias , Calidad de Vida , Femenino , Humanos , Anciano , Masculino , Estudios Prospectivos , Estrés Financiero , Pandemias , Neoplasias/terapia , Encuestas y Cuestionarios , Medición de Resultados Informados por el PacienteRESUMEN
Dendritic cells (DCs) are able to orchestrate innate and acquired immunity and can activate and sustain a long-lasting anti-tumor immune response in vivo when used as anti-tumor cell therapy. The selection of the antigen and the choice of its formulation are key points in designing anti-cancer DC-based vaccines. Cell released vesicles/exosomes have been shown to transfer antigens, HLAI/peptide complexes and co-stimulatory molecules to recipient cells. In this study we describe the generation of an allogenic microvesicle cell factory in which the expression of a specific tumor antigen was combined to the expression of co-stimulatory and allogeneic molecules. The DG75 lymphoblastoid cell line was selected as microvesicle producer and transfected with ErbB2, as tumor antigen prototype. The shed microvesicles transferred antigenic components to recipient DCs, increasing their immunogenicity. DC pulsing resulted in cross-presentation of ErbB2 both in HLAI and HLAII compartments, and ErbB2-specific CD8+ T cells from cancer patients were activated by DCs pulsed with vesicle-bound ErbB2. The microvesicle cell factory proposed may represent a source of cell free immunogen to be used for DC-based cancer therapy.
Asunto(s)
Antígenos de Neoplasias/inmunología , Neoplasias de la Mama/terapia , Linfocitos T CD8-positivos/inmunología , Células Dendríticas/trasplante , Inmunoterapia Adoptiva , Activación de Linfocitos , Receptor ErbB-2/inmunología , Vesículas Transportadoras/trasplante , Antígenos de Neoplasias/genética , Neoplasias de la Mama/inmunología , Línea Celular , Células Dendríticas/inmunología , Femenino , Antígenos HLA/inmunología , Humanos , Inmunofenotipificación , Interferón gamma/metabolismo , Receptor ErbB-2/genética , Transfección , Vesículas Transportadoras/inmunologíaRESUMEN
Human immunodeficiency virus (HIV)-infected patients are at a significantly higher risk from coronary heart diseases (CHD) and myocardial infarction (MI) compared to gender- and age-matched non-infected individuals. Combination antiretroviral therapy (cART) has transformed a fatal illness into a chronic stable condition. However, cART induces metabolic abnormalities in HIV-infected patients, while its role in vascular atherosclerosis is still under investigation. The use of cART is linked to inflammation - a key mechanism in atherosclerotic progression and destabilisation that precedes clinical events like MI. There is evidence of visceral fat abnormal distribution in HIV infected patients, and inflammatory changes in HIV infected patients drive the initiation, progression and, ultimately, thrombotic clinical complications induced by atherosclerosis. Visceral adipose tissue, a virtual factory for manufacturing pro-inflammatory mediators, affects the liver function. The inflamed liver promotes the development of pro-atherogenic dyslipidaemia. Pro-inflammatory cytokines released by adipocytes travel to the skeletal muscles and other peripheral tissues, worsening insulin sensitivity and leading to hyperglycaemia. Increased high sensitivity C-reactive protein (hs-CRP) inflammatory marker is associated with endothelial dysfunction in HIV-infected patients. Increased levels of monocytic nuclear factor kappa-B (NFkappa-B), a master switch in the inflammatory cascade, are documented in patients with elevated hs-CRP levels. It can be assumed that, as a result of NFkappa-B activation, hs-CRP up-regulates cytokines that contribute to MI by recruiting leukocytes and promoting thrombosis. This review focuses on the association of HIV-infection, metabolic abnormalities and known mechanisms involved in inducing accelerated atherosclerosis and inflammation in HIV-infected patients, as well as the role of lipid lowering agents in potentially preventing CHD.
Asunto(s)
Aterosclerosis/complicaciones , Aterosclerosis/prevención & control , Regulación de la Expresión Génica , Infecciones por VIH/complicaciones , Animales , Proteína C-Reactiva/metabolismo , Química Farmacéutica/métodos , Comorbilidad , Enfermedad Coronaria/complicaciones , Enfermedad Coronaria/prevención & control , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/metabolismo , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Hiperlipidemias/complicaciones , Hiperlipidemias/prevención & control , Inflamación/complicaciones , Inflamación/tratamiento farmacológico , Lipodistrofia/complicaciones , Lipodistrofia/prevención & control , Macrófagos/efectos de los fármacos , Resultado del TratamientoRESUMEN
In an investigation of the mutagenic properties of 20 carbamate herbicides and fungicides by use of the Salmonella/microsome mutagenicity test as developed by Ames et al. (Mutation Res., 31: 347-364, 1975), we have found that three thiocarbamate compounds, diallate, sulfallate and triallate, are mutagenic in the presence of a liver microsomal fraction on strains TA1535 and TA100. This indicates that the metabolic products of these thiocarbamates are causing base-pair substitutions. Since the 2-chloro-allyl group is common to the three mutagenic compounds but is not common to the 17 nonmutagenic compounds, a metabolic derivative of this group is probably responsible for the mutagenic activity.
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Fungicidas Industriales/farmacología , Herbicidas/farmacología , Mutágenos , Tiocarbamatos/farmacología , Trialato/farmacología , Animales , Ditiocarba/análogos & derivados , Evaluación Preclínica de Medicamentos , Técnicas In Vitro , Microsomas Hepáticos/metabolismo , Ratas , Salmonella typhimurium/efectos de los fármacos , Relación Estructura-ActividadRESUMEN
In a systematic study of the mutagenic effect of chemical compounds used as pesticides, we found that D. D. soil fumigant and Telone are mutagenic. The test was performed using the bacterial tester strains following the procedure developed by Ames. The active principle of D. D. soil fumigant and Telone is a mixture of the cis and trans isomers of 1,3-dichloropropene. Both isomers are mutagenic in Salmonella strains TA 1535 and TA 100. 2,3-Dichloro-1-propene, a minor component (5%) of the commercial preparation Telone, was also found to be mutagenic in strains TA 1535 and TA 100. Mutagenesis of these tester strains is an indication of a base-pair substitution event causing a missense mutation. 1,3-Dichloropropene is widely used in agriculture all over the world. In Italy 2,187,100 kg were produced in 1972. In California over 1,000,000 kg of 1,3-dichloropropene-containing pesticides were used in 1971.
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Compuestos Alílicos/farmacología , Hidrocarburos Clorados/farmacología , Mutágenos , Plaguicidas/farmacología , Compuestos Alílicos/metabolismo , Animales , Hidrocarburos Clorados/metabolismo , Técnicas In Vitro , Microsomas Hepáticos/metabolismo , Mutación/efectos de los fármacos , Plaguicidas/metabolismo , Salmonella typhimurium/efectos de los fármacosRESUMEN
Heart failure is commonly associated with vascular diseases and a high rate of athero-thrombotic events, but the risks and benefits of antithrombotic therapy are unknown. The incidence of thromboembolism in heart failure patients (which may include stroke, peripheral embolism, pulmonary embolism) seems to be around 2%, based on the data available from several small studies. However, the incidence of thromboembolism should greatly depend upon what is being looked at in each of these studies, as it will (generally) not be individually categorised. There is very little true epidemiological data to base this figure. The pathophysiology of heart failure is complex. There are many well- recognised factors, which are associated with thrombosis in heart failure patients, such as vascular abnormalities, increased coagulability and impaired blood flow. In the past 50 years, many studies have been performed to find out if oral anticoagulation is of benefit for the prevention of thromboembolism in patients with heart failure. Expert therapeutic guidelines in the Europe and North America agree that there is insufficient evidence to recommend that antithrombotic therapy should be given to patients with heart failure, unless they have atrial fibrillation or, perhaps, a previous thrombo-embolic episode. There is a lack of evidence for any antithrombotic agent that is effective in patients with heart failure; therefore, randomised clinical trials need to be designed to test the hypothesis that patients with chronic heart failure would have benefit from anticoagulant therapy. This review summarises the incidence, potential mechanism and therapeutic approaches for the management of thromboembolism in heart failure.
Asunto(s)
Anticoagulantes/uso terapéutico , Insuficiencia Cardíaca/tratamiento farmacológico , Heparina/uso terapéutico , Warfarina/uso terapéutico , Enfermedad Crónica , Insuficiencia Cardíaca/complicaciones , Insuficiencia Cardíaca/fisiopatología , Humanos , Peso Molecular , Tasa de Supervivencia , Tromboembolia/etiología , Tromboembolia/fisiopatología , Tromboembolia/prevención & control , Trombosis/etiología , Trombosis/prevención & controlRESUMEN
Cardiovascular diseases are the major cause of morbidity and mortality in the Western countries and their prevalence is increasing in developing world. The final biological evolution of atherosclerotic process, supporting development and progression of cardiovascular diseases, is thrombosis. In the most recent years several clinical trails have established that low molecular weight heparins play a major role in the area of prevention and treatment of arterial and venous thrombosis. It is now established, that low molecular weight heparins are efficacious and safe anticoagulant options for patients with deep vein thrombosis, pulmonary embolism, unstable angina and non-ST-segment elevation myocardial infarction. In addition, low molecular weight heparins play a major role to prevent thromboembolic events in patients with chronic diseases (e.g. due to cerebrovascular ischemic events, cancer) and in patients undergoing surgical interventions. Clinical trials have also shown that low molecular weight heparins might play a role in the treatment of patients with ST-segment elevation acute myocardial infarction, in the prevention of thrombotic events in patients with congestive heart failure, and in patients undergoing percutaneous coronary interventions. The combined use of low molecular weight heparins with fibrinolysis and other antithrombotic agents has been also studies in a number of clinical trials. This review summarises the results of the most recent clinical studies regarding the use of low molecular weight heparins in prevention and treatment of cardiovascular diseases.
Asunto(s)
Anticoagulantes/uso terapéutico , Enfermedades Cardiovasculares/tratamiento farmacológico , Heparina de Bajo-Peso-Molecular/uso terapéutico , Aterosclerosis/tratamiento farmacológico , Ensayos Clínicos como Asunto , Enfermedad Coronaria/tratamiento farmacológico , Humanos , Infarto del Miocardio/tratamiento farmacológico , Tromboembolia/tratamiento farmacológico , Tromboembolia/prevención & control , Resultado del TratamientoRESUMEN
The association between obesity and risk of coronary artery disease is well established. The distribution of body fat was shown to be related to serum lipids and lipoproteins in a group of healthy men, but the association between body fat and haemostatic factors is less clear. The aim of the present study was to determine the association of overall adiposity (OVRAD, percent total fat mass contributing to body weight) and body mass index (BMI, weight/height2) with lipids and haemostatic factors in order to evaluate which of these was more associated with circulating procoagulant factors. The total fat mass was estimated by dual-energy X-ray absorptiometry (DEXA) and OVRAD computed for 28 male and 36 healthy female subjects, whose median age were 44.2 years and 48.4 years respectively. In addition, the BMI was computed for each of them from their weight and height measurements. Fasting samples were analysed for serum lipids (total, HDL- and LDL-cholesterol and triglyceride) and plasma fibrinogen, factor VII coagulant (FVII:C) activity, tissue plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) activities. The men and women had similar median BMI (23.9 kg/m2 and 23.1 kg/m2 respectively), but the median fat mass of women (19.6 kg) was higher than that of men (16.9 kg). Age, BMI and OVRAD exhibited statistically significant correlations with lipids and haemostatic factors in both men and women. However, when BMI was adjusted for age and OVRAD, the statistically significant associations were no longer apparent in men or women. In contrast, OVRAD adjusted for age and BMI still exhibited statistically significant associations with FVII:C activity (R = 0.38, p = 0.05), triglyceride (R = 0.51, p = 0.008), LDL-cholesterol (R = 0.45, p = 0.02) and HDL/Total cholesterol ratio (R = -0.63, p <0.001). It is concluded that OVRAD, a fat mass-based index, rather than BMI, a weight-height based index, is better associated with circulating coronary risk factors.
Asunto(s)
Factores de Coagulación Sanguínea , Índice de Masa Corporal , Enfermedad Coronaria/etiología , Lípidos/sangre , Obesidad , Adulto , Enfermedad Coronaria/sangre , Femenino , Humanos , Masculino , Persona de Mediana Edad , Factores de RiesgoRESUMEN
We investigated whether chronic fatigue syndrome (CFS) patients have physical and/or cardiovascular de-conditioning, in 273 CFS patients and 72 healthy controls. We used laboratory tests to assess haematological, biochemical, endocrinological and immunological systems. The cardiovascular system was assessed by echocardiography and carotid echography. Body composition was determined by dual energy X-ray absorptiometry (DEXA). CFS patients had smaller left ventricular end systolic (p < 0.001) and diastolic (p = 0.008) dimensions but thinner posterior walls (p = 0.02) than corresponding values in healthy controls. Left ventricular mass was also reduced in CFS patients (p = 0.006). Both maximum (p < 0.001) and minimum (p < 0.008) diameter of the carotid artery were smaller in CFS patients. The laboratory screening tests showed significant differences in serum albumin (p = 0.05), phosphate (p = 0.02), HDL-cholesterol (p = 0.03), HDL:total cholesterol ratio (p = 0.01), triglycerides (p = 0.02), neutrophils (p = 0.01) and thyroid-stimulating hormone (p = 0.04) between CFS patients and controls. Male CFS patients had an increased percentage of fat mass compared with healthy male subjects (p = 0.02). This large group of CFS patients had evidence of physical and cardiovascular de-conditioning, suggesting that in these patients a graded exercise programme could lead to physical reconditioning and could increase their ability to perform physical activities.
Asunto(s)
Sistema Cardiovascular/fisiopatología , Síndrome de Fatiga Crónica/fisiopatología , Aptitud Física , Adulto , Composición Corporal , Arterias Carótidas/diagnóstico por imagen , Colesterol/sangre , HDL-Colesterol/sangre , Ecocardiografía , Síndrome de Fatiga Crónica/diagnóstico , Síndrome de Fatiga Crónica/metabolismo , Femenino , Ventrículos Cardíacos , Humanos , Masculino , Persona de Mediana Edad , Neutrófilos/patología , Fosfatos/metabolismo , Estudios Prospectivos , Albúmina Sérica/análisis , Volumen Sistólico , Tirotropina/sangre , Triglicéridos/metabolismoRESUMEN
Epidemiological studies have shown an increase in acute myocardial infarctions or deaths due to myocardial infarction in colder weather; the mechanisms most likely involve increased blood levels of haemostatic risk factors, and increases in arterial blood pressure and heart rate. We studied the relationship between cold adaptation, haemostatic risk factors and haemodynamic variables. Cold adaptation was obtained by a programme of immersion of the whole body up to the neck in a water-filled bath, the temperature of which was gradually decreased from 22 degrees C to 14 degrees C, time of exposure being increased from 5 to 20 min over a period of 90 days. We studied 428 patients (44% men) and measured blood levels of fibrinogen, plasminogen activator inhibitor 1 (PAI-1), tissue plasminogen activator antigen (t-PA), plasma viscosity, von Willebrand factor, D-dimer and platelet count, both at baseline and after 90 days of daily immersion. There were significant reductions in von Willebrand factor (-3%; p < 0.001), and plasma viscosity (-3.0 s; p < 0.001), and a mild but significant increase in PAI-1 (+0.3 IU/ml; p = 0.02). The pressure rate product (systolic blood pressure x heart rate) was also significantly lower after cold adaptation (-310; p = 0.004). Cold adaptation, compared with exposure to cold weather, induces different haemodynamic responses and changes of blood levels of haemostatic risk factors.
Asunto(s)
Aclimatación/fisiología , Frío , Hemodinámica/fisiología , Hemostasis , Interleucina-6 , Adulto , Anciano , Presión Sanguínea , Viscosidad Sanguínea , Femenino , Fibrinógeno/análisis , Inhibidores de Crecimiento/análisis , Frecuencia Cardíaca , Humanos , Factor Inhibidor de Leucemia , Linfocinas/análisis , Masculino , Persona de Mediana Edad , Inhibidor 1 de Activador Plasminogénico/análisis , Recuento de Plaquetas , Factores de Riesgo , Factores de Tiempo , Activador de Tejido Plasminógeno/análisis , Factor de von Willebrand/análisisRESUMEN
We measured the response of HepG2 cells to the classic cytochrome (cyt.) P-450 inducers 3-methylcholanthrene (3-MC) and phenobarbital (PB), by evaluating oxidative and/or reductive metabolism of the nitroarenes, 1-NP and 1,6-dinitropyrene (1,6-DNP), in control and induced cells. In HepG2 cells, 3-MC induces ring-hydroxylation of 1-NP, whereas PB stimulates its nitroreduction. PB induces NADPH-cyt. c reductase, but does not affect other cytosolic and microsomal enzymes which contribute to 1-NP nitroreduction in these cells. However, PB-inducible nitroreductase activity seems to be associated primarily with cyt. P-450 isoenzymatic form(s), as indicated by the requirement for NADPH and the response to specific inhibitors such as alpha-naphthoflavone and CO.
Asunto(s)
Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/metabolismo , Metilcolantreno/farmacología , Fenobarbital/farmacología , Pirenos/metabolismo , Carcinoma Hepatocelular/enzimología , Inducción Enzimática , Humanos , Neoplasias Hepáticas/enzimología , Mutágenos/metabolismo , Fracciones Subcelulares/enzimología , Células Tumorales CultivadasRESUMEN
Preparations of two new beta-adrenergic blocking drugs, Zami 1305 [1-(2-nitro-3-methyl-phenoxy)-3-tert-butylaminopropan-2-ol] and Zami 1327 [1-(6-nitro-3-methyl-phenoxy)-3-tert-butylaminopropan-2-ol], were found to be contaminated by expoxides which are direct acting mutagens on TA 100 and TA 1535 in the Salmonella/microsome mutagenicity test. Because of the suggested correlation between mutagenicity and carcinogenicity of a chemical [10,11], beta-adrenergic blocking agents contaminated by mutagenic expoxide impurities may be a health hazard.
Asunto(s)
Antagonistas Adrenérgicos beta/análisis , Contaminación de Medicamentos , Compuestos Epoxi/farmacología , Éteres Cíclicos/farmacología , Propanolaminas/análisis , Compuestos Epoxi/análisis , Pruebas de Mutagenicidad , Salmonella typhimurium/efectos de los fármacosRESUMEN
Diesel particles were collected from the exhaust of a VW Golf diesel car by electrostatic precipitation. The particulate and its DCM extract were highly mutagenic in the Salmonella/microsome test in the presence and absence of metabolic activation; the highest response was observed with TA98 and TA1538 tester strains. The biological availability of particulate-associated mutagenic compounds was demonstrated by administering powder to rats and assaying, in vitro, the urine excreted within 24 h after treatment. The highest activity was obtained with TA98 in the presence of metabolic activation. Typical dose-effect responses were evident in urine of animals treated by all the administration routes tested (i.p., s.c. and per os), both in the presence and absence of a suspending vehicle. Concentration of mutagenic compounds present in urine of treated animals could be achieved by chromatography on Amberlite XAD-2 and XAD-7 resins. This study provides direct evidence for bioavailability to animal tissues of mutagens adsorbed onto diesel particulate, although part of the activity might be ascribed to nitroaromatic compounds formed during the collection of the powder. The present study is part of a more comprehensive work on diesel exhaust particulate, and results have to be considered in this light before any final conclusion can be drawn.
Asunto(s)
Mutágenos/aislamiento & purificación , Mutación , Emisiones de Vehículos/toxicidad , Adsorción , Animales , Disponibilidad Biológica , Microsomas Hepáticos/metabolismo , Pruebas de Mutagenicidad , Mutágenos/toxicidad , Mutágenos/orina , Ratas , Salmonella typhimurium/efectos de los fármacos , Especificidad de la EspecieRESUMEN
The use of therapeutic apheresis in very low weight patients is generally thought to have limitations, because of possible severe adverse reactions, potential risk related to the extracorporeal procedure, due to the low weight of the young patients. A careful therapeutic approach using appropriate precautions, and also introducing modifications to the standard procedure, can minimise the risk without compromising the efficacy of the plasmapheresis. The aim of the study was to evaluate apheresis tolerance and acceptability in children [Artif. Organs. 21 (1997) 1126] and infants [J. Clin. Apheresis 5 (1989) 21] with inherited lipid metabolism disorder, familial hypercholesterolemia (FH), primary hyperlipoproteinemia (lipoprotein phenotype I), and acute leukemia, weighing on average 20.55 kg. One thousand one hundred twenty three aphereses were completed. Three types of apheresis were performed: leukapheresis, plasma exchange, dextran sulphate cellulose (DSC) low density lipoprotein (LDL)-apheresis. Three different types of continuous flow systems were used. Technical adaptation depending on patients blood volume, body mass index, hematocrit, type of system used, permitted us to perform complete aphereses, obtaining a high degree of tolerance and acceptability of the treatment. The use of plasmapheresis is regarded to be an extreme therapeutic measure in children. However, when the need for such treatment is undebatable, plasmapheresis must be done. A well-trained and experienced team can overcome the technical difficulties in order to complete the procedures without complications. The most frequently observed adverse effects are vascular relative access insufficiency (2.0%), and mild hypotension (2.0%).
Asunto(s)
Eliminación de Componentes Sanguíneos/métodos , Discapacidades del Desarrollo/terapia , Delgadez/terapia , Adolescente , Eliminación de Componentes Sanguíneos/efectos adversos , Peso Corporal , Niño , Preescolar , Femenino , Humanos , Lactante , Recién Nacido de Bajo Peso , Recién Nacido , Masculino , Cooperación del Paciente , Aumento de Peso/fisiologíaRESUMEN
In this short-term open label clinical pilot study, conducted at one center, the immune complex dextran sulphate adsorber (Selesorb) was used to treat four female patients aged 59-69 with HCV-related cryoglobulinaemia, vasculitis and/or neuropathy. The primary trial objective was to assess the clinical efficacy of the immunoadsorber. The secondary objective of the trial was to determine the safety of the adsorber and to investigate the adsorption capacity, measured as the adsorption of cryoglobulin-related immune complexes and the resulting influence on plasma components of the immune system. The patients have been submitted to treatment with the immunoadsorber, at approximately 1-3 days intervals, completing six sessions. The follow-up was one month. In the patients treated with Selesorb, we observed a statistically significant decrease in plasma of all classes of immunoglobulins (IgA: 5-28%; IgG: 14-44%; IgM: 8-38%). In two patients with peripheral neuropathy secondary to cryoglobulinemia, the symptomatology was improved. In a third patient the neurological involvement was substantially unchanged, and the same unsuccessful outcome was observed for Sjögren syndrome is concerned. Nevertheless, the two patients with lower extremity vasculitis showed an appreciable improvement. We failed to observe significant side effects directly related to the use of this immunoadsorbent.
Asunto(s)
Eliminación de Componentes Sanguíneos/métodos , Crioglobulinemia/terapia , Hepatitis C Crónica/complicaciones , Inmunoadsorbentes/uso terapéutico , Anciano , Eliminación de Componentes Sanguíneos/normas , Crioglobulinemia/etiología , Sulfato de Dextran/normas , Sulfato de Dextran/uso terapéutico , Femenino , Hepatitis C Crónica/inmunología , Hepatitis C Crónica/terapia , Humanos , Inmunoglobulinas/sangre , Inmunoglobulinas/efectos de los fármacos , Técnicas de Inmunoadsorción , Inmunoadsorbentes/normas , Persona de Mediana Edad , Enfermedades del Sistema Nervioso Periférico/etiología , Enfermedades del Sistema Nervioso Periférico/terapia , Proyectos Piloto , Resultado del Tratamiento , Vasculitis/etiología , Vasculitis/terapiaRESUMEN
Hyperlipidemia is a major risk factor for atherosclerosis. Early signs of cardiovascular disease can be detected also in asymptomatic patients with hyperlipidemia. Forty-four patients with serum cholesterol greater than 300 mg/dl (7.8 mmol/l) and/or serum triglycerides greater than 500 mg/dl (5.6 mmol/l) and 35 healthy controls had their carotid and iliac arteries examined by echo-Doppler with spectral analysis. Systolic ankle pressure was also measured. A vascular score was calculated: a 0 score was assigned to normal findings and a 1 score for each artery with abnormality at echo-Doppler or Winsor index less than 0.97. The XbaI Restriction Fragment Length Polymorphism of Apo B gene was investigated in all hyperlipidemic patients. Arterial lesions, especially those of internal carotid and iliac arteries, were more frequent (p less than 0.01) in patients with high serum lipids, compared to controls. Patients with lesions were older and had higher serum triglyceride concentrations compared to those without lesions. When divided according to serum triglycerides, patients with concentrations exceeding 200 mg/dl had higher vascular score (p less than 0.02) compared to those with serum triglycerides less than 200 mg/dl. No difference in restriction fragment length polymorphism (XbaI) of Apo B gene was demonstrated in patients with arterial lesions compared to those without lesions. Non-invasive echo-Doppler examination gives useful information on the arterial involvement of hyperlipidemic patients and its use should therefore be implemented, especially when high triglyceride concentrations are present.
Asunto(s)
Arteriosclerosis/etiología , Enfermedades de las Arterias Carótidas/etiología , Hiperlipoproteinemias/complicaciones , Arteria Ilíaca , Apolipoproteínas B/genética , Arteriosclerosis/diagnóstico por imagen , Arteriosclerosis/epidemiología , Arteriosclerosis/genética , Enfermedades de las Arterias Carótidas/diagnóstico por imagen , Enfermedades de las Arterias Carótidas/epidemiología , Arteria Carótida Común , Arteria Carótida Interna , Femenino , Humanos , Hiperlipoproteinemias/genética , Arteria Ilíaca/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Polimorfismo de Longitud del Fragmento de Restricción , Prevalencia , Factores de Riesgo , Triglicéridos/sangre , UltrasonografíaRESUMEN
The possible associations between coronary heart disease (CHD) and peripheral arterial disease (PAD), detected by echo-Doppler analysis, with restriction fragment length polymorphism (RFLP) of apo AI/CIII cluster and apo B gene were investigated in a group of men with premature CHD (n = 39) and in a control group of men without evidence of CHD (n = 40). The genetic analysis of SstI RFLP of apo AI/CIII cluster showed a significantly higher frequency of the rare SstI allele (S2) in CHD patients (0.16) as compared with controls (0.06). No significant differences were found in the frequencies of XbaI RFLP for the apo B gene between CHD patients and controls. Moreover, patients with PAD showed no significant differences in the frequencies of XbaI RFLP for the apo B gene and of SstI RFLP for the apo AI/CIII cluster as compared with patients without evidence of peripheral arterial disease detected by echo-Doppler analysis.
Asunto(s)
Apolipoproteína A-I/genética , Apolipoproteínas B/genética , Apolipoproteínas C/genética , Enfermedad Coronaria/genética , ADN/genética , Enfermedades Vasculares Periféricas/genética , Alelos , Apolipoproteína C-III , Secuencia de Bases , Enfermedad Coronaria/patología , Ecocardiografía Doppler , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , Familia de Multigenes , Enfermedades Vasculares Periféricas/patología , Polimorfismo de Longitud del Fragmento de RestricciónRESUMEN
The benefit of using subcutaneous low molecular weight heparin for the treatment of acute myocardial infarction is not known. The aim of this study was to determine the efficacy of a low molecular weight heparin (dalteparin sodium) for the treatment of acute myocardial infarction in patients not treated with thrombolytic therapy. Twenty-nine cardiological centres from leading hospitals in India participated in this prospective, multicentre, double-blind, placebo-controlled study in two phases which included 1128 patients with acute myocardial infarction. In the acute phase (between day 1 and 3 of admission) all the patients received a weight-adjusted dose of subcutaneous dalteparin (120 IU/kg twice daily). In the second, double-blind phase of acute myocardial infarction, patients were randomised to receive a fixed dose of dalteparin (7,500 IU) or an identical placebo injection for 30 days. A composite primary endpoint of death, reinfarction, recurrence of angina and emergency revascularisation was used. All the 1128 patients with acute myocardial infarction were included in the trial. In the acute phase, the composite primary endpoint was observed in 58 (5.1%) patients. Of 1037 paients who were randomly assigned to receive a fixed dose of dalteparin (n=519) or placebo (n=518), the composite primary event rate was 6.7 percent and 7.0 percent, respectively (RR 0.97; 95% CI 0.62-1.52; p=0.90). To conclude, treatment with dalteparin administered subcutaneously in a weight-adjusted dose of 120 IU/kg twice daily resulted in a lower than expected mortality during the acute phase of myocardial infarction. A lower fixed once daily dose of 7,500 IU during the chronic phase did not confer additional protection.